FEASIBILITY STUDY
FEASIBILITY STUDY
THE SECTORAL OPERATIVE PROGRAMME – THE DEVELOPEMENT OF ECONOMIC COMPETITIVITY
PRIORITY AXE II: RDI INFRASTRUCTURE INVESTMENT
- TARGET -
CENTRE FOR TREATMENT AND RESEARCH IN GASTROENTEROLOGY BASED ON IMAGING METHODS AND MOLECULAR TECHNIQUES
CONTENT:
CONTENT: .....................................................................................................................................3
Acronyms: .....................................................................................................................................5
1 GENERAL DATA .............................................................................................................6
1.a Name of investment objective .....................................................................................6
1.b The location (county, city, street, number) .........................................................................6
1.c The investment titular .............................................................................................................6
1.d The investment beneficiary .................................................................................................6
1.e The study elaborator .............................................................................................................6
2 GENERAL INFORMATION CONCERNING THE PROJECT .....................................6
2.a The actual situation and information about the responsible entity
of project implementation .......................................................................................................6
2.b Investment description ................................................................................................12
2.b.1 The conclusions of pre-feasibility study or of detailed investment plan
(if it was elaborated) regarding actual situation, the necessity and opportunity of investment promotion and technico-economic selected script as well ................................................12
2.b.2 Technical-economic scenarios ....................................................................................39
2.b.3 Constructive, functional and technological description, in any case ....................................42
2.c Technical data of investment ................................................................................................98
2.c.1 Area and location ............................................................................................................98
2.c.2 Judicial status of the ground .............................................................................................98
2.c.3 Situation of definite ground occupations ........................................................................98
2.c.4 Ground studies ............................................................................................................98
2.c.5 Main characteristics of constructions inside investments objective and the constructive variants of investment’s achievement ...............................................................................98
2.c.6 Existent situation of utility and consumption analysis ..............................................111
2.c.7 Conclusions of evaluation impact over environment .........................................................111
2.d Achievement duration and principal stages, graphic of investment’s achievement ..........112
3 ESTIMATED COST OF THE INVESTMENT ..................................................................114
3.a Total value with detail on the structure of general list ..............................................114
3.b The space out of corroborated costs with the achievement graphic of the investment .......117
4 ANALYSIS OF COST-BENEFIT ......................................................................................120
4.a Identification of the investment and defining of the objectives ..................................120
4.b Analysis of options ..........................................................................................................121
4.c Financial analysis ..........................................................................................................122
4.d Economic analysis ..........................................................................................................123
4.e Sensitivity analysis ..........................................................................................................123
4.f Risk analysis ......................................................................................................................123
5 FINANCE SOURCES OF THE INVESTMENT ...............................................................125
6 ESTIMATIONS REGARDING LABOUR EMPLOYERS THROUGH THE ACHIEVEMENT OF INVESTMENT ......................................................................126
6.a Number of labor places created in the execution place ..............................................126
6.b Number of places created in the operation place ..........................................................126
7 THE PRINCIPAL TECHNICO-ECONOMIC INDEXES OF INVESTMENT ................127
8 APROVALS AND AGREEMENTS .................................................................................131
8.a Notice of investment beneficiary regarding the necessity
and the opportunity of investment ..................................................................................131
8.b The city planning certificate ..........................................................................................131
8.c The principle approvals regarding the utilities availability (thermal and electric energy, methane gas, communications, water-sewerage etc) .........................................................131
8.d The environmental approval ..............................................................................................131
8.e Other specific approvals and principle agreements ..........................................................131
Appendix 1 A – 1P
Appendix 2
Appendix 3
Appendix 4
Appendix 5
Appendix 6
Appendix 7
Appendix 8
Appendix 9
Acronyms:
MP Master Plan
FS Feasibility study
R/D Research – Development
SOP-ECD Sectoral Operation Program – Economic Competitively Development
SOP-ECD/RDI Sectoral Operation Program – Economic Competitively Development/ Research – Development – Innovation
SOP-HRD Sectoral Operation Program – Human Resources Development
FP7 7th Framework Program
PET Positron Emission Tomography
CT Computer Tomography
MRI Magnetic Resonance Imaging
MRCP Magnetic Resonance Colangio-Pacreatography
MRS Magnetic Resonance Spectroscopy Module
ERCP Endoscopic Cholangiopancreatography
AFI Autofluorescence Endoscopy
LIFS Laser-Induced Fluorescence Spectroscopy
CLE Confocal Laser Endomicroscopy (CLE)
MCE Magnification Chromoendoscopy
NBI Narrow Band Imaging
EUS Endoscopic Ultrasound
NOTES Natural Orifice Transluminal Endoscopic Surgery
LS Laparoscopic Surgery
ICC Immunocytochemistry
IHC Immunohistochemistry
ISH In Situ Hybridization
LCM Laser Capture Microdissection
CGH Comparative Genome Hybridization Technique
MSI Microsatelitic Instability
SNP Single Nucleotide Polymorphism
LOH Loss of Heterozygosity State
RT-PCR Real-time Polymerase Chain Reaction
MALDI-TOF-MS Matrix Array Laser/Desorption Ionization Time of Flight Mass Spectrometry
AFM Atomic Force Microscopy
LSCM Laser Scanner Confocal Microscopy
AI Artificial Intelligence
GENERAL DATA
1 Name of investment objective
TARGET – CENTRE FOR TREATMENT AND RESEARCH IN GASTROENTEROLOGY BASED ON IMAGING METHODS AND MOLECULAR TECHNIQUES
2 The location (county, city, street, number)
LOCATION A
The old building of UMF Craiova, Dolj, Craiova, Petru Rares Street, No 2 (200349)
LOCATION B
The new building of UMF Craiova, Dolj, Craiova, 1 Mai Boulevard, No 66-68 (200638)
3 The investment titular
UNIVERSITY OF MEDICINE AND PHARMACY CRAIOVA
4 The investment beneficiary
UNIVERSITY OF MEDICINE AND PHARMACY CRAIOVA
5 The study elaborator
S.C. INTERGROUP ENGINEERING S.R.L.
GENERAL INFORMATION CONCERNING THE PROJECT
1 The actual situation and information about the responsible entity of project implementation
Situation of research and research infrastructure at national, international and institutional level
The use of technology innovation in medicine has lead to a constant growth of expenses in the international healthcare system. This trend will continue to increase the mean expectancy of life, which will subsequently lead to the desire of new treatments and better medications. Parallel with this development, a new discipline appeared, the sanitary economy, orienting the resources for a more efficient use. A part of this concept is the early diagnosis which will allow an optimal allocation of human resources and materials by the achievement of an individual tailored therapy. In the same time, the modern diagnosis, based on imaging methods and molecular techniques, represents a source of innovative exploration pertinent to the acknowledgement of fundamental mechanisms of diseases.
State-of-the-art imaging methods used for the assessment of digestive diseases currently include PET-CT (Positron Emission Tomography combined with Computed Tomography), MRI (Magnetic Resonance Imaging), as well as several endoscopic methods: Autofluorescence Endoscopy Imaging (AFI), Laser-Induced Fluorescence Spectroscopy (LIFS) and Confocal Laser Endomicroscopy (CLE). Modern diagnosis based on cell biology and biochemistry methods is oriented to elucidate the molecular mechanisms of clinical pathology, with the aim of identifying new molecular targets for testing new drugs. Laser microdissection and confocal laser microscopy are two new techniques used for this approach. In the analytical field several techniques recently became routine in the molecular investigation laboratory. These include the identification of tumor markers (Matrix Array Laser/Desorption Ionization Time of Flight Mass Spectrometry (MALDI-TOF-MS) and Atomic Force Microscopy (AFM)), as well as the identification of gene groups which can characterize a cancer type collectively (DNA microarrays, Genomics). The actual research focus is placed also in the field of information technologies in order to create human-machine interfaces. The best example is the recent creation of artificial neural networks controlled by bio-currents derived from human brain.
Nowadays, digestive pathology and especially digestive cancers are a major health problem in the world. These cancers are in the first place in the tumor pathology, with over 3 million patients and 2.2 million death people every year. Thus, digestive tract cancers are a major cause of death, having an incomplete response to chemotherapy in advanced stages and usually a very poor prognosis. The most frequent cancers in Romania are: colo-rectal cancer, gastric cancer, esophageal cancer, liver and pancreatic cancer, all being curable if diagnosed in early stages. These types of cancer are presently treated by multimodal treatment, including surgery and radio-chemotherapy, while new therapeutic strategies are still under evaluation. The latest discoveries in the tumor biology have identified some vulnerable therapeutic targets and created new therapeutic agents. The treatment strategies of advanced digestive cancer patients recently involved therapeutic combinations between cytotoxic and anti-angiogenesis agents, as a new and attractive target in the tumor therapy, which can keep under control the tumor progression for a long time.
The use of several modern imaging techniques in the gastroenterology field has revolutionized the management of patients suffering from digestive diseases, as well as the early detection of digestive cancers through screening programs oriented to high-risk group patients. Several imaging procedures (mainly PET-CT and MRI) have also developed strongly, leading to an increased accuracy of the diagnosis, as well as the precise staging of the digestive cancers, in order to improve the therapeutic protocols. Gastrointestinal endoscopy has also benefited strongly from new image processing methods (AFI, CLE, etc.) in the past 2 years, yielding higher diagnosis accuracy, a better detection rate of the structural changes and improved techniques which allow the detection and quantification of vascularization and neoangiogenesis.
Currently, the diseases are defined through the identification of morphologic characteristics detected by imaging and/or microscopy. Although the diagnosis precision and accuracy can be improved by a better training in pattern recognition, the future target would certainly be represented by the development of “optical biopsies”, that means recognition systems which can detect cancers in real-time. Moreover, by identifying new characteristics and prognosis markers it will be easier to stratify patients according to the disease stage. The high-performance and high-resolution imaging methods mentioned above will help to improve image quality, with a subsequent progressive “computerization” of medicine, while several IT methods will surely help doctors to improve the diagnosis precision. Computer simulations will thus become essential in the learning process and in the evaluation of competencies. The research efforts of this project will make possible the creation of “intelligent imaging systems” with large memory databases which will automate many aspects of the non-invasive diagnosis techniques. Establishing an early diagnosis through complex genomic and proteomic techniques that are able to detect the molecular changes (such as the DNA mutations and the genetic expressions, as well as the codified protein expression), will certainly support the progress of therapeutic management, especially in the case of digestive cancer patients.
In conclusion, early cancer diagnosis will become more accurate and more efficient through the use of these new imaging systems. The amount and type of services that the medical system offers to the population depends on the refunding system, while both of them are showing a significant deficit in Romania by comparison with the European Union. This difference is certainly more striking in Oltenia region, where the resources are restricted as compared with other regions of our country. This is the main reason why a series of new techniques which are strictly necessary for research, development and innovation, but also for improvement of the population health status have not been introduced in Romania yet.
Romania lacks the infrastructure necessary to initiate high-performance imaging examinations. Thus, both research and development, but also current medical practice will progress significantly by introducing early detection and screening programs, as well as recent diagnosis methods which use imaging, pathology, immunology or molecular biology techniques. The final objective will be to lower the morbidity and mortality induced by the late diagnosis of advanced digestive cancers.
We are talking about the imaging techniques recently introduced in most of the important centers from abroad, including “state-of-the-art” imaging, endoscopic and interventional methods. By the introduction in Romania of a high-tech system based on positron emission tomography (PET) combined with spiral computer tomography (CT), it will be possible to establish a location through PET, while CT will enhance the correct anatomic diagnosis. A 3 Tesla magnetic resonance imaging (MRI) system will be also used to obtain high-resolution images of the digestive organs, including MR virtual colonoscopy and MRCP (Magnetic Resonance Cholangio-Pancreatography), as well as through the inclusion of magnetic resonance spectroscopy. Among the recent endoscopic methods, we can mention: AFI, LIFS, magnification chromoendoscopy (including NBI mode) and CLE. Endoscopic ultrasound (EUS) allows supplementary the staging of malignant lesions identified through some of the “red-flag” techniques mentioned above. Development of EUS examinations using several techniques (contrast-enhanced EUS, elastography, 3D reconstructions, etc.), as well as improvement of hybrid imaging systems (CT-EUS and possibly MR-EUS), will push forward the medical research, as well as the medical system to a level comparable to those of other EU countries. By combining these endoscopic techniques and by making comparative studies with other imaging techniques, it will become obvious that they are very important in analyzing the structure and the vascularization of the pre-malignant and malignant lesions. The introduction of these early diagnosis techniques will also benefit from the introduction of mini-invasive experimental therapeutic procedures of natural orifice transluminal endoscopic surgery (NOTES). Moreover, the concentration of these imaging methods in the same center will certainly allow the development of diagnostic and therapeutic hybrid methods (PET-CT, EUS-CT, EUS-MR, etc.), in combination with other complex methods of image analysis, based on artificial intelligence techniques (AI). This will highlight the decision making process based on precise diagnosis algorithms supported by evidence-based medicine. Several “state-of-the-art” endoscopic methods will be combined in Romania for the first time with PET-CT and the 3T-MRI, allowing interdisciplinary research in digestive tract cancers. Also, the PET-CT system as a gold-standard of gastroenterological oncology imaging will be unique in Romania. Several other endoscopic procedures (AFI, LIFS, etc.) will also be performed for the first time in Romania.
The techniques and the systems necessary for an early diagnosis based on pathology (immunohistochemistry and imunocytochemistry, in situ hybridization, laser capture microdissection, two-photons laser microscopy), molecular biology (real-time PCR, high density microarrays, CGH, etc.), and biochemistry (MALDI-TOF-MS, AFM, etc.) are scarcely available in Romania or they do not exist at all in the Oltenia region. For example laser capture microdissection (LCM) and confocal laser microscopy will be used for the first time in Romania. The introduction of modern pathology (including the immunological investigation) at the level of an integrated module, which subsequently offers the necessary material and integration with the genomic and proteomic modules, has an absolute priority, because it is not currently utilized properly in Romania.
The modern pathology diagnosis has registered great progress toward specific cellular identification through the use of dedicated antibodies for research and diagnosis. In particular, the panel of antibodies used for cancer diagnosis is continuously growing. The cancerous tissue is heterogeneous and the latest research results have shown that a correct diagnosis entails the simultaneous visualization of 3-4 antibodies. Great progress has been reached by the introduction of the two-photon laser microscopy, which, apart from the simultaneous detection of several antibodies, allows the observation of the dynamics of tumor markers in the native tissue during a considerable period of time (3-4 weeks). The confocal laser microscopy facilitates three-dimensional reconstructions and this offers a spatial image which corresponds to the native tissue morphology. For instance, the laser microscopy offers three-dimensional images of the recently formed vessels (neoangiogenesis), this being an essential process in the malignant tissue evolution. The two-photon laser microscope will be unique in our country.
A lot of contradictory results are obtained in medical research because of tumor tissue homogenization and biochemical analysis. This is because of the heterogeneity of the tumor tissue which gives a different weight at the final result. This is why it is necessary to use a cryomicrotome to cut the tissue and a laser capture microscope for the microdissection. The isolated cells are then taken and analyzed by real-time PCR and the gene expression platform. Another approach is the molecular analysis through biochemical methods of the material obtained from cancerous cells. The last 5-years of research have shown that each cancer type is characterized by the expression of 200-300 genes. These genes have led to the current “genetic signature” concept, which is particular to each type of cancer. These genes are likely to constitute very soon the basis of the molecular diagnosis, which will probably entail a new classification of the cancers. The Genomic platform (DNA microarrays) will be used in order to identify these groups of genes which together characterize a type of cancer. However, it is also necessary to validate and quantify the genes identified through “Genomics” by real-time PCR (RT-PCR). Again, the Genomics platform will be unique in Romania.
The genetic analysis has registered so great a progress, that it has been automatized. The automatization of separation and identification of processes allowed the human genome to be sequenced and this is a great achievement of this century. At the same time, we have to be aware of the fact that the gene is only one piece of information, while the protein is the effector. The automatization of the proteins’ separation and identification is extremely difficult, as proteins are very heterogeneous structures. Despite these difficulties, the proteome’s analysis has registered great progress, too. Apart from improvements made in the classical bi-dimensional electrophoresis domain, great progress has also been registered by the use of new Protein-Chip (by analogy with the DNA chips) for protein separation. The tumor markers can then be identified through MALDI-TOF-MS. This will be a unique technique in Oltenia.
Cells cultures will be used for in vitro caracterization of malignant tissue by sampling cells groups or individual cells. These cells are transferred for molecular study. In vitro cultures are very important models in the cellular, biochemical and molecular characterization of potential therapeutic targets. The laboratory model also offers us information on the evolution in molecular terms of the malignancy process. It represents the first step in creating new anti-cancerous medicines. To achieve these aims we will use techniques such as the two-photon scanning laser microscopy, which is highly recommended to phenotype and study cellular dynamics as it does not bleach the cells and it thus allows a long term observation, as well as AFM microscopy. Both techniques will be uniques in Oltenia.
The use of the information society technologies in the intelligent systems field (like artificial neuronal networks, evolutionary algorithms, vector based machines, clustering algorithms, classification and decision trees, etc.) is only at the beginning in the world, especially in the imaging data study domain for the automatic diagnosis. This is the consequence of the complex processing of the data afferent to the medical imaging by Artificial Intelligence means, as well as of the weak connection between the IT specialists and doctors. The purpose of this project can become a breaking ground if it is put into practice in real-time. Moreover, the financial costs of this component of the project are relatively low, referring to relatively cheap IT systems, bibliographic references (specialized books and articles) and software for the image processing. The role of the AI module is especially to optimize currently known algorithms, as well as to develop new types of algorithms for intelligent systems, especially designed to process digital images in this field. Consequently, the costs of procurement of highly specialized software will be significantly diminished.
The early diagnosis of digestive cancers will consequently lead to a significant decrease of the morbidity and mortality, but also to a consequent decrease of futile surgical interventions, by the exact selection of the patients groups and also by the diminution of the high costs determined by the incomplete and deficient management of the patients. The quick identification of the presence or absence of the disease risk and of the preneoplastic or neoplastic lesions (in situ early cancer or invasive advanced cancer) will lead not only to the early diagnosis, but also to the potentially curative treatment of the lesions detected in real-time. The identification of the prognosis markers and the sub-division of patients by risk groups will allow an improvement of diagnosis algorithms, with a consequent increase of the efficiency of the medical decisions and the survival of oncological digestive patients.
This project comes to solve the problem of lack of equipment that is necessary for the research and development activities, by creating a new Excellence Center in Gastroenterology as basis for the improvement of the University of Medicine and Pharmacy of Craiova research and development (R&D) infrastructure by means of some very modern equipment and software. By putting this project into practice, the infrastructure of a reference regional cancer center will develop in the Oltenia region, having as a consequence the growth of the research activity’s quality and efficiency in the south-east of Romania. The research center TARGET will focus on finding new strategies in the early detection of cancers by analyzing various cost-efficiency models and by improving the present strategies through the selection of the best screening methodology in accordance with evidence based medicine principles.
By supplying this centre with equipment in accordance with the European Union standards, it will reduce the gap currently present in the south-west region of Romania, by developing the infrastructure of the University of Medicine and Pharmacy Craiova, in concordance with the 7th Framework Program’s thematic areas. This will clearly improve the programs used for the early detection and screening of cancer, this having direct implications in the community medical assistance which will become a priority for the medico-social sector. The necessary equipment that is to be obtained by the present project will complete the actual resources of the Gastroenterology and Hepatology Research Center (authorized by the National University Research Council) and integrated in the national and international research structures.
Data of the entity responsible with project implementation
Craiova is an old cultural and commercial centre, the most important city in south (after Bucharest) and offers an educational framework and cultural and historical also. The south-west area of Romania is one of economically under-privileged region. Thus, there are preoccupations and intensive efforts for the minimization of the existing gap. Over 2500 beds in 5 hospitals exists only in Craiova, thus the academic medical centre of Craiova assures medical assistance for the entire south-west region of Romania. In the framework of international research, UMF Craiova has a particular position having a direct frontier with two countries in Balkans – Serbia and Bulgaria, developing research programs in partnership with these countries universities and other Balkans or European countries as well.
The University of Medicine and Pharmacy Craiova represents the only medical university in south-west area of Romania. The corresponding area has over 2.5 million inhabitants. In the framework of the University of Medicine and Pharmacy Craiova there are 4 faculties: General Medicine Faculty, Dentistry Faculty, Pharmacy Faculty and Midwifes and Nurses Faculty, with three specializations. The academic body has over 400 teachers and researchers which are training yearly 3000 students and 700 residents in almost all specialties. The students and the residents of our university are originally from various regions of the country, including regions with similar medico-pharmaceutical institutes. The entire academic body is integrated in highly esteemed research activity in our country and abroad.
2 Investment description
1 The conclusions of pre-feasibility study or of detailed investment plan (if it was elaborated) regarding actual situation, the necessity and opportunity of investment promotion and technico-economic selected script as well
The scientific justification of investment
The scientific justification has the role to support the necessity of investment. Thus, the research theme has the role to be the main element which justifies the investment. The TARGET project is scientifically based on four major research themes. These themes are, in fact, major research directions and the researchers of the TARGET center want to approach them after the project implementation.
The research themes are related to the functional structure of the TARGET research center. Every theme will evolve within a precise module. Thus, the TARGET center will contain four modules (divided in submodules, while each submodule will be divided in individual laboratories and support spaces - you can see the next figure), every module with its own specific scientific destination.
NOTE!!! Each research theme will contain (after the project implementation) specific research activities. These could be mixed up with the specific activities needed to create the research & development infrastructure, so they are consequenly named as “researches”.
For developing of the proposed “researches” included in the major research themes, we need a research infrastructure. This infrastructure has 2 investment components:
• First investment component is due by equipments involved in the research flow. The technical specifications and characteristics of these equipments help us to find the optimal solution regarding to location (functional place).
• Thus, we arrive to the second investment component: the construction of a building in B location and improvement of existing laboratories in A and B locations, similar to technical specifications of the equipments.
o The construction will have special characteristics, ordered by technical specification of the research equipment and by the strict flow of research subjects.
o Two types of fitting out are available. First type, ordinary fitting out: wall painting, reconstruction of sanitation, lighting system, flooring. The second type, special fitting out. This fitting out is necessary for the protection of researchers life, because in some laboratories it will be develop researches at gene level and DNA. The special fitting out are controlled by SR EN 12128 / April 2003 standard regarding risk and biohazard situations.
NOTE!!! In order to emphasize the links between the themes-“researches”-equipment-utilities (necessary for the operation) of the equipment-laboratories-spaces (corresponding to laboratories), we have presented the “Equipment Table” which can be visualized at the subchapter 2.b.3 of the feasibility study.
In the following pages we present all four research themes, the modules that belong to the research themes (with submodules and laboratories), the specific researches which the researchers of the University of Medicine and Pharmacy Craiova want to extend and the research flows in the framework of themes as well.
THEME I. ESTABLISHING AN EARLY DIAGNOSIS IN REAL-TIME AND / OR ASSESSING THE PROGNOSIS MARKERS BY “STATE-OF-ART” IMAGING METHODS, IN AGREEMENT WITH MODERN PATHOLOGY AND MOLECULAR BIOLOGY TECHNIQUES
A series of complex imaging techniques will be introduced in Romania based on this project, including combined positron emission tomography and computer tomography (PET-CT), as well as 3T MRI, with MR virtual colonoscopy and MRCP. By including a magnetic resonance spectroscopy module (MRS), information about the tissue metabolites specific to some diseases will be further obtained. An important part of the project will be represented by the assessment of several hybrid imaging techniques resulted from the fusion of images obtained by different methods. Different PET-CT, EUS-CT and possibly EUS-MR hybrid imaging techniques will be explored, together with some complex image analysis methods, based on AI techniques (neural networks, evolutionary calculation, etc.), which will be very helpful for the decision making process based on medical diagnosis algorithms. By introducing in Romania a PET-CT system as the gold-standard used in oncological imaging, different types of cancer will be detected at the molecular level, while the post-treatment staging and re-staging of the patients will be possible with increased accuracy, in order to assess the efficiency of therapy.
The imaging methods will include recent endoscopy techniques which allow the visualization of the digestive tract, by means of high-resolution techniques such as AFI, LIFS, magnification chromo-endoscopy (MCE, NBI), EUS, OCT, CLE, etc. By introducing these latest endoscopic techniques, there will be a lot of research topics which aim at finding a real-time pathology diagnosis, as well as the molecular characterization of the digestive tract diseases, in the diagnosis of metaplasia, dysplasia, premalignant lesions, as well as early diagnosis of malignant lesions. By identifying the prognosis markers (such as the assessment of neoangiogenesis), patients will be divided by subgroups, in order to improve the decisional process and the therapeutic strategies.
The diagnosis and therapeutic endoscopic techniques will be experimentally improved by some transluminal endoscopic surgery procedures and by experimental laparoscopic surgery. The improvement of the NOTES experimental techniques (Natural Orifice Transluminal Endoscopic Surgery) will be extremely important to make some prospective studies and to develop some combined mini-invasive surgery techniques, which are useful especially to diminish the morbidity and the futile surgical interventions.
This research theme will be developed functionally within Digestive Imaging Module.
I. Digestive Imaging Module
This module has a powerful research, diagnosis and treatment character due to the acquisition of several advanced techniques (unique in Romania), in addition to the existing ones.
This module contains 3 submodules:
I.1. The Imaging and Radiology Submodule (Imaging Department building)
I.2. The Digestive Endoscopy Submodule
I.3. The Endoscopic Surgery Submodule.
I.1. The Imaging and Radiology Submodule
Complex imaging systems (unique in Romania) will be used in this submodule, such as the PET-CT or the 3T MRI systems, in combination with the conventional imaging systems, such as digital radiology. Positron emission tomography (PET) combined with spiral computerized tomography (CT), or the fusion imaging, is one of the most modern and powerful methods used to offer functional images with a clear medical purpose.
The traditional methods of image creation (US, CT, MRI) reveal the anatomic relationship between organs, the morphology of systems, with enhanced high-resolution, high-quality and three-dimensional images. The main disadvantage is that it is not possible to establish if the pathologic process is malignant or benign unless abnormalities appear in the organ’s structure, dimension or shape.
The exclusivity of the PET-CT investigation consists in the fact that it offers information on the organs’ anatomic structure, as well as on the tissue metabolism. The development of new radio-labelled substances with metabolic substrate and receptor ligands for the study of the cellular functions has extended the PET-CT molecular imaging clinical applications, by offering unique diagnosis information that cannot be obtained by the conventional CT or MRI imaging techniques. By developing the new positron radio-agents with single-photon emission, including labeling of some enzymes, peptides, drugs and other antibodies, the medicine is now in the unique position of using the molecular mechanisms which stand as the basis of the pathological processes. Consequently, the apoptosis and neoangiogenesis imaging has been thus translated form the laboratory to the clinical practice. The fusion PET-CT imaging is applied at a large scale in the developed EU countries, offering diagnosis priorities in the molecular detection of different types of cancer, in the staging and re-staging procedures, and in assessing the chemo-radiotherapy effects. The procedure is being unanimously accepted as a gold standard in the oncological imaging, including gastroenterological oncology.
MRI also has a growing role in the assessment of a large number of abdominal diseases, especially for pancreas, bile duct and digestive tube evaluation. The recent technical progresses regarding the magnetic field (including the large availability of 3Tesla MRI systems), but also improvement of the hardware and software systems allowed the acquisition of MR images which offer excellent anatomic details and do not present secondary artifacts determined by intestinal peristalsis or respiratory movements. The use of rapid sequences has reduced the acquisition time improving the patient’s acceptance and allowing the more efficient use of the system. The new three-dimensional sequences allow the rapid acquisition of images, reducing the defective registration of sections and movement artifacts, while the multiplane reconstruction is improved. The MRI which offers anatomic and functional details is continuously developing, with new techniques, such as the diffusion and perfusion imaging are being evaluated. Further technical progress will offer wide uses of the MRI in the abdominal pathology. The optimization of sequences (for instance RARE, FISP) has put into practice a high-quality MRCP and has become an important non-invasive method by which the pancreatico-billiary system is being assessed. The dynamic images obtained from a combination of intravenous contrast agents and gradient-echo or fast breath-hold three-dimensional acquisitions have assured a more precise diagnosis of the abdominal vascular diseases. The 3D breath-hold acquisitions offer a precise diagnosis of small liver tumors. Recent studies have proven that MRI can be used as an imaging method in virtual colonoscopy, instead of using CT, as it offers a more precise diagnosis in intestinal diseases, without increasing the irradiation risk.
Romania is one of the few East-European countries where PET-CT or 3T MRI equipment is not used for the current moment and, therefore, the Romanian patients suffering from digestive affections are deprived of an efficient diagnosis which allows the detection of the disease in early stages, therefore reducing the medical costs and increasing the life expectancy. Moreover, the medical research has not benefited fully of these state-of-the art imaging systems which allow the integration of clinical-applicative information with fundamental data. The Radiology and Imaging Submodule will include three laboratories, with the following ”researches” that could be developed in connection:
I.1.A. Fusion Imaging Laboratory (PET-CT)
• Research a.1: Assessment of the usefulness of the PET-CT for the detection of different digestive cancers at molecular level;
• Research a.2: Assessment of the usefulness of the PET-CT for the pre- and post-therapeutic staging and re-staging of digestive cancers;
• Research a.3: Testing of PET-CT feasibility for the assessment of tumor apoptosis and neoangiogenesis in patients with digestive cancers;
• Research a.4: Assessment of PET-CT as compared to 3T MRI for the assessment of digestive cancers;
I.1.B. Magnetic Resonance Imaging Laboratory (MRI)
• Research b.1: Assessment of the role of high intensity magnetic field (3T) MRI, combined with contrast agents and 3D reconstruction, for the early detection and characterization of the digestive diseases;
• Research b.2: Assessment of MRI accuracy for the implementation of modern imaging techniques, including MRCP, virtual colonoscopy, MR spectroscopy, with a role in the early diagnosis of malignant digestive diseases;
• Research b.3: Assessment of the feasibility of hybrid methods like EUS-MR, EUS-CT, for the early diagnosis and accurate staging of digestive cancers;
• Research b.4: Establishing of a multi-step protocol of modern diagnosis of digestive diseases, which will stand at the basis of the medical diagnosis algorithms;
I.1.C Digital Radiology Laboratory (DRX)
• Research c.1: Assessment of the utility of digital radiology for the detection and characterization of digestive diseases;
• Research c.2: Assessment of the utility of digital radiology for guiding ERCP and miniprobe EUS catethers inside the bile duct and pancreatic duct;
• Research c.3: Assessment of the utility of digital radiology in setting stents in malignant obstructive pathology of digestive tract;
• Research c.4: Comparative assessment of ERCP (endoscopic cholangio-pancreatography) and MRCP in the diagnosis of pancreatico-biliary pathology.
NOTE!!! Both the research themes and the main research categories justify the infrastructure and equipments needs.
The connection between equipment-utilities (needed for proper functioning), of equipments-laboratories-rooms (afferent to the laboratories), and “researches”, can be identified at point 2.b.3 in the feasibility study.
The researches will be identified by the above existing codes. For example: Research a.1: “Assessment of the usefulness of the PET-CT for the detection of different digestive cancers at molecular level” can be identified in the table by the code: ”R.a.1”
The following diagram plots the research flow which is planned in The Imaging and Radiology Submodule, as well as its connection to the other modules.
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I.2. Digestive Endoscopy Submodule
This submodule will translate into practice some advanced endoscopic techniques which complete the existing ones: autofluorescence endoscopy imaging (AFI), laser-induced fluorescence spectroscopy (LIFS), magnification chromoendoscopy (MCE), including narrow band imaging (NBI), endoscopic ultrasound (EUS), optical coherence tomography (OCT) and confocal laser endomicrosopy (CLE). Parts of the necessary systems for this submodule have been already obtained during the unfolding of a recently funded national research project entitled: Platform of Interdisciplinary Research for Advanced Microendoscopic Imaging Devices (PYRAMID). The project has been financed in the PNCDI II competition in the Capacities program (2007-2009). The necessary equipment for the TARGET project thus completes the existing research infrastructure, by creating the bases of high functionality in research, as well as for professional interdisciplinary diagnosis.
The interdisciplinary character of these techniques will be ensured due to the close connection with other techniques (complex pathology staining, including immunohistochemistry and immunocytochemistry examinations, as well as genomic and proteomic examinations of the biopsies and of the samples drawn through fine-needle aspiration – FNA biopsy). The possibilities of real-time pathology examinations of the endomicroscopic images will be assessed through advanced telepathology techniques.
The Digestive Endoscopy Submodule will include four laboratories:
I.2.A. Endoscopic Autofluorescence Imaging Laboratory (AFI)
• Research a.1: Assessment of autofluorescence endoscopy for the early detection of preneoplastic lesions (low or high-grade dysplasia), as well as esophageal or gastric adenocarcinoma;
• Research a.2: Assessment of autofluorescence endoscopy for the colonoscopic screening of moderate or high-risk patients for an early detection of preneoplastic lesions (colorectal polyps) and colon adenocarcinoma.
• Research a.3: Assessment of LIFS-type biopsy forceps for the real-time diagnosis of eso-gastric preneoplastic and neoplastic lesions;
I.2.B. Magnification Chromoendoscopy Laboratory (MCE) including NBI (narrow band imaging) mode
• Research b.1: Assessment of magnification chromoendoscopy and NBI mode for the screening of patients with Barrett esophagus for an early diagnosis of esophageal adenocarcinoma;
• Research b.2: Assessment of magnification gastroscopy and NBI mode for the screening of patients with preneoplastic gastric lesions and for detection of gastric adenocarcinoma;
• Research b.3: Assessment of magnification chromoendoscopy and NBI mode for the colonoscopic screening of moderate and high risk, for the early detection of colon adenocarcinoma;
• Research b.4: Assessment of accuracy of supervised intensive endoscopic training program;
I.2.C. Endoscopic Ultrasound Laboratory (EUS)
• Research c.1: Assessment of EUS accuracy (including contrast agents examinations and 3D reconstruction for neoangiogenesis assessment) for the preoperative diagnosis and staging of patients with eso-gastric cancers.
• Research c.2: Assessment of endoscopic ultrasound accuracy (including fine needle aspiration, contrast agents examination, EUS elastography, 3D examination) for the diagnosis and preoperative staging of patients with pancreatic cancer.
• Research c.3: Assessment of EUS accuracy for the diagnosis and preoperative staging of patients with lung cancer (including complementary examinations of endobronchial ultrasound);
• Research c.4: Assessment of the utility of hybrid methods, like ultrasound – computed tomography for the early diagnosis of hepatocellular cancer;
• Research c.5: Assessment of the utility of hybrid methods, like ultrasound – computed tomography for the early diagnosis of pancreatic cancer;
• Research c.6: Assessment of EUS-guided FNA for the early diagnosis of digestive cancers using immunocytochemical and molecular techniques (microarray, real-time PCR);
• Research c.7: Comparative assessment of EUS elastography and ultrasound real-time elastography utility for the assessment of tumoral hepatic masses;
• Research c.8: Assessment of accuracy of intensive training programs supervised by dedicated simulators. Development of the researchers diagnostic abilities through the use of simulators;
I.2.D. Confocal Laser Endomicroscopy Laboratory (CLE)
• Research d.1: Assessment of the utility of endomicroscopy for the in vivo and in real-time pathological diagnosis in patients with Barrett esophagus and early esophageal adenocarcinoma;
• Research d.2: Assessment of the utility of endomicroscopy for the in vivo and in real-time pathological diagnosis in patients with preneoplastic lesions and early gastric adenocarcinoma;
• Research d.3: Assessment of the utility of endomicroscopy for the in vivo and in real-time pathological diagnosis in patients with ulcerative colitis and early colorectal cancer;
• Research d.4: Assessment of the utility of endomicroscopy for the in vivo and in real-time pathological diagnosis in patients with Helicobacter pylori infection;
• Research d.5: Assessment of the utility of endomicroscopy for the in vivo and in real time pathological diagnosis in patients with celiac disease;
• Research d.6: Testing of the feasibility of endomicroscopy for distance transmission of in vivo and in real-time images for pathological examinations;
• Research d.7: Testing of the feasibility of endomicrosopy for the assessment of tumoral neoangiogenesis in patients with digestive cancers (esophageal, gastric, pancreatic cancer);
NOTE!!! Both the research themes and the main research categories justify the infrastructure and equipments needs.
The connection between equipment-utilities (needed for proper functioning), of equipments-laboratories-rooms (afferent to the laboratories), and “researches”, can be identified at point 2.b.3 in the feasibility study.
The researches will be identified by the above existing codes.
The following diagram plots the research flow which is planned in the Digestive Endoscopy Module, as well as its connection to the other modules.
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I.3. Endoscopic Surgery Submodule
This submodule will allow several “researches” for the development of mini-invasive surgery applications in the early diagnosis of malignant diseases. Endoscopic Surgery is a new surgery branch which aims at minimizing the ways of access in the peritoneal cavity in order to approach the abdominal organs. Wide incisions of the abdomen walls are thus avoided as they are unaesthetic, they extend the hospitalization post-operative recovery period and they induce the risk of post-operative infections or hernias.
The first step has been made by the Laparoscopic Surgery (LS) by which the access in the peritoneal cavity is realized by small 2 cm orifices in the anterior or lateral abdominal wall.
A more recent step has been made by the NOTES techniques (N.O.T.E.S. – Natural Orifice Transluminal Endoscopic Surgery). By this type of approach the access in the peritoneal cavity is not made by crossing the abdominal wall, but by the body’s natural orifices: oral orifice (transgastric), vaginal or anal (transrectal or transcolonic). The traumatisms of the abdominal wall, any parietal infection or subsequent hernias or aesthetic prejudices are thus avoided.
A great benefit of Endoscopic Surgery (ES) by comparison with traditional surgery is the significant decrease of the general post-operative immuno-suppression thanks to the minimization of the parietal and peritoneal aggression. This represents an important advantage for the patients with malignant diseases, because the consequences of exploratory surgery, diagnosis or staging interventions should be minimal. Laparoscopic Surgery has attained a high technological level, while NOTES is only at the beginning, although its perspectives are unlimited. Endoscopic Surgery allows a direct visual, but also imaging (ultrasound) exploration, while the biologic material drawn for biopsies has direct applications in the early diagnosis and staging of the malignant diseases of the digestive tract.
The Endoscopic Surgery Submodule will contain two interconnected laboratories, both both concerning the information flow, but also with the other modules (Digestive Endoscopy Submodule, Radiology and Imaging Submodule). Histopathological and immunohistochemical exams, cytological and immunocytochemical exams, but also complex genomic and proteomic exams of sampled biopsies or smears (sampled by fine needle aspiration) will be performed in the proximity of the submodule.
I.3.A. Experimental Surgery Laboratory (CEX)
• Research a.1: Assessment of the local immune response (peritoneal) modifications induced by laparoscopic surgery;
• Research a.2 Assessment of the systemic immune response modifications induced by laparoscopic surgery;
• Research a.3 Assessment of laparoscopic surgery influence on the biology of secondary peritoneal malignant tumors;
• Research a.4 Assessment of the possibilities of staging of digestive cancers by biopsy sampling and ultrasound examinations;
I.3.B. NOTES Laboratory - Natural Orifice Transluminal Endoscopic Surgery
• Research b.1 Assessment of the local immune response modifications induced by NOTES;
• Research b.2 Assessment of feasibility and safety of transgastric approach in NOTES;
• Research b.3 Assessment of feasibility and safety of transrectal approach in NOTES;
• Research b.4 Assessment of various methods like peritoneal exploration, biopsy, ultrasonography for diagnosis and staging of digestive cancers;
• Research b.5 Assessment of surgical oncologic resection in digestive cancers in NOTES;
NOTE!!! Both the research themes and the main research categories justify the infrastructure and equipments needs.
The connection between equipment-utilities (needed for proper functioning), of equipments-laboratories-rooms (afferent to the laboratories), and “researches”, can be identified at point 2.b.3 in the feasibility study.
The researches will be identified by the above existing codes.
The following diagram presents the predicted research flow in the Endoscopic Surgery Module and the connection to other modules.
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THEME II. IMPLEMENTATION OF PATHOLOGIC DIAGNOSIS BY CONVENTIONAL AND MODERN METHODS
The conventional investigation methods (common and special stains) are relevant to the primary identification of the malignant pre-neoplastic and neoplastic processes. The immunocytochemical (ICC) and immunohistochemical (IHC) techniques will make possible, in the second stage of the investigation, the correct classification of the neoplastic processes and the identification of some possible prognosis factors, as well as therapeutic targets. The in situ hybridization technique (ISH) is the first step to be taken in order to clarify the carcinogenesis mechanisms at the molecular level by detecting at the tissue level the cells which can express pro-cancerous genes. Pathology currently benefits from a variety of investigations and research techniques such as: computerized tissue and cell morphometry, laser capture microdissection and monolayer liquid cytology.
The laser capture microdissection method (LCM), represents an important pivot connecting the histopathologic investigation of the Pathology Module to the molecular investigation of the Molecular Biology and Biochemistry Module. The method aims at isolating cell groups which have homogenous morphology and are specific to the malignant tissue. Isolation of an homogenous group of cells is essential to establish morphological markers that are specific to pathological diagnosis. Moreover, specific cell isolation will offer the biologic material necessary to identify cell markers which will afterwards facilitate the development of some therapeutic molecular targets. In order to quickly determine the diagnosis, it is necessary to have a cryomicrotome with which to cut the native tissue into thin sections. At the same time, the cryomicrotome is essential as it provides working material for the LCM.
The morphologic investigation algorithm is completed by the immunologic evaluation based on modern techniques (flow-cytometry and ELISA). Thus, flow-cytometry proved to be efficient in the digestive diseases investigation by estimating the tumor proliferative activity in colorectal lesions (DNA’s polyploidy evaluation, DNA index), by estimating the cell proliferation in digestive cancers, by evaluating the percentage and the absolute value of the lymphocyte populations and as a therapeutic indicator in colorectal cancer patients or in determining carcinoembryonic antigen (CEA) in biopsies of suspect lesions.
The immunologic exam by the ELISA method will complete the assessment of malignant cells population behavior and the response of immunological defense by determination of a large palette of tumor markers, important viral markers and cytokines secreted by lymphocytes subgroups. This research theme will be developed in the Pathology and Immunology Module.
II. Pathology and Immunology Module
The Pathology and Immunology Module aims at creating the necessary conditions for the application of high-performance pathological, cytological and immunological diagnosis by means of modern techniques, as well as special stains. The techniques used will include: immunohistochemistry and immunocytochemistry, in situ hybridization (using the FISH and CISH techniques), computer analysis of microscopic images, flowcytometry and ELISA.
The modern research and investigation arsenal of Cytology and Pathology, includes a great variety of techniques such as: the immunohistochemical staining technique, in situ hybridization (with fluorescence - Fluorescence in Situ Hybridization – FISH or with chromogen - Chromogen in Situ Hybridization - CISH), computer analysis of microscopic images, laser capture microdissection and single-layer liquid cytology.
This variety of methods ensures a correct and complete evaluation of pathology diagnosis which will further allow:
- primary identification of non-tumoral, preneoplastic and neoplastic lesions;
- correct classification of neoplastic lesions;
- correct and complete assessment of the factors involved in oncogenesis;
- correct and complete assessment of tumor development;
- identification and evaluation of prognosis factors;
- identification of possible therapeutic targets efficient in the treatment of cancer;
- assessment of the response to therapy;
Major research objectives and activities of this module will include :
1. Investigation of transcription factors (nuclear proteins necessary for the transcription of certain genes, some of them being tissue specific). The advantages consists in the high degree of specificity and the absence of diffusion phenomenon, as compared with the classical cytoplasmic, nuclear membrane and extracellular space markers. Moreover, because the location of the marker is inside the nucleus, immunoreactions can be combined with different chromogens addressed to cytoplasm or cytoplasmic membrane markers.
2. Evaluation of prognosis factors in different digestive cancer types (ki67, p53, PCNA, bcl2, VEGF, etc.). In malignant digestive pathology, for example, it was recently found the association between the over-expression of stathmin (major protein involved in microtubule depolymerization) and mutation of the p53 gene, both being correlated with tumor progression, poor prognosis and recurrence in carcinomas originating at the level of the digestive tract. Other examples consist in the over-expression of bcl-2, associated with a favorable prognosis in colorectal carcinoma, as well as the correlation of VEGF expression with tumor progression (as an indicator of recurrence and metastasis) in hepatocellular carcinoma.
3. Assessment of DNA repair and apoptosis, as suppressor functions of tumor development. It is possible that the aberrant forms of certain genes controlling the apoptotic phenomenon (like BARD1 or p53), might not function correctly to suppress tumor development. Consequently, over-expression in the cancerous cells represents a marker of poor prognosis.
4. Assessment of angiogenesis allows the tumors to restructure their own vascular support. Cancer cells cannot grow larger than 1 mm3, because oxygen and nutrient diffusion is insufficient in larger cell conglomerates. Due to the hypoxic or trophic stress, or as a direct result of oncogenic alterations, tumor cells produce angiogenesis signals, leading to the overexpression of genes that control the angiogenesis pathways, leading to a disorganized angiogenesis response. This dependence of tumors from the vascular flow offered by the endothelial cells favored the hypothesis of potential therapeutic strategies based on angiogenesis inhibition, which might lead to destruction of the tumor vascularization. This would further lead to a decrease of intratumoral perfusion, without the side effects of conventional chemotherapy.
5. Detection of possible therapeutic targets in different types of malignant tumors. Thus, the receptor of tyrosinkinase, c-erb B2, is an important prognostic factor and an important therapeutic target in breast and gastric carcinoma. VEGF also represents an important therapeutic target in hepatocellular carcinoma. Detection of ciclo-oxygenase 1 and 2 receptors in the patients with colorectal polyps might initiate the treatment with NSAIDs to prevent the cancerous process and the possible evolution to colorectal carcinoma.
The algorithm of pathology investigation is completed through the integration of modern techniques of immunological assessment (flow-cytometry and ELISA). The major objectives and activities of this submodule include:
(1) Demonstration of the applicability and utility of flow-cytometry for the investigation of digestive diseases through the evaluation of tumor proliferating activity in colorectal carcinoma (assessment of DNA polyploidy – DNA index), assessment of cell proliferation in digestive tract cancers (for example detection of nuclear antigen p105), assessment of lymphocytes population as a marker of therapeutic monitoring.
(2) Evaluation of the immune response of the patients with digestive tract cancers will be completed by ELISA which allows the assessment of the activity of lymphocyte subpopulations involved in the humoral and cellular immune response through the serum detection of secreted cytokines (IL-1, IL-2, IL-6, IL-8, TNF-alpha, IL-10, IL-12, etc.), as well as through the detection of antibodies with different specificities.
NOTE!!! Due to the connections and research flows that exists between different laboratories, the ”researches” of the Pathology and Immunology Module will take place sequentially in the submodules, and not in distinct laboratories as the Digestive Imaging Module.
This module will include two submodules: the Pathology Submodule and the Immunology Submodule.
II.1. Pathology Submodule
II.2. Immunology Submodule
II.1. Pathology Submodule
Will contain the following laboratories and support rooms:
A. Histopathology Laboratory (HP)
B. Immunohistochemistry and immunocytochemistry laboratory (L-IHC/ICC)
C. Laser Capture Microdissection, in situ hybridization and cytology (MdL-CIT-HIS)
D. Computerized Image Analysis Laboratory (L-ACI)
E. Telepathology - Telemedicine Room (TELMED)
F. Laboratory for tissue preparation and documentation (PMDF)
G. Research and Diagnosis Rooms (CDD)
H. LAN Secretariat / Servers (SS LAN)
I. Materials and reactives storage rooms
The submodule aims to develop the following types of researches:
• Research p.1: The microscopic study of paraffin embedded samples and the diagnosis of nontumoral or tumoral lesions by usual or special stauining techniques;
• Research p.2: The qualitative microscopic study of paraffin embedded samples and the diagnosis of tumoral or nontumoral lesions using the immunofluorescence technique;
• Research p.3: The qualitative microscopic study of paraffin embedded samples and the diagnosis of tumoral or nontumoral lesions using immunohistochemistry staining techniques;
• Research p.4: The qualitative cytological microscopical study and the diagnosis of tumoral or nontumoral lesions by usual or special staining techniques;
• Research p.5: The qualitative histological microscopical study and the diagnosis of tumoral or nontumoral lesions using the immunohistochemistry marking techniques;
• Research p.6: Sampling of tissue and cellular material for study and diagnosis of tumoral or nontumoral lesions using histopathological and cytological techniques;
• Research p.7: Sampling of tissue and cellular material for study and diagnosis of tumoral or nontumoral lesions using molecular pathology techniques;
• Research p.8: The quantitative morphometric study of paraffin embedded samples or cytological samples and the diagnosis of tumoral or nontumoral lesions using computer analysis of imaging techniques;
NOTE!!! Both the research themes and the main research categories justify the infrastructure and equipments needs.
The connection between equipment-utilities (needed for proper functioning), of equipments-laboratories-rooms (afferent to the laboratories), and “researches”, can be identified at point 2.b.3 in the feasibility study.
The researches will be identified by the above existing codes.
The following diagram plots the research flow which is planned in the Pathology Submodule, as well as its connection to the other modules.
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II.2. Immunology Submodule
Will contain the following laboratories:
A. Flow-cytometry Laboratory (FLWC)
B. ELISA investigation Laboratory (ELISA)
C. The documentation, interpretation and data processing room (DIP)
D. The sample receiving room (CPP)
The following researches will be performed within these laboratories:
o Research i.1: The identification of characteristic nontumoral or tumoral serologic and cellular markers using flow-cytometry;
o Research i.2: The identification of characteristic nontumoral or tumoral markers using the ELISA technique;
NOTE!!! Both the research themes and the main research categories justify the infrastructure and equipments needs.
The connection between equipment-utilities (needed for proper functioning), of equipments-laboratories-rooms (afferent to the laboratories), and “researches”, can be identified at point 2.b.3 in the feasibility study.
The researches will be identified by the above existing codes.
The following diagram plots the research flow which is planned in the Immunology Submodule, as well as its connection to the other modules.
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THEME III. STANDARDIZATION OF THE GENE PROFILES IN THE DIGESTIVE PATHOLOGY, IDENTIFICATION AND CHARACTERIZATION OF MALIGNANT PROGRESSION MARKERS AND THERAPEUTIC TARGETS BY MOLECULAR BIOLOGY AND BIOCHEMISTRY TECHNIQUES
The development and the evolution of some malignant tumor processes are followed by complex changes of gene expression. Although the individual genes were proposed for the diagnosis and were sometimes used as therapeutic targets for treating cancer, the last 5-year of research have shown that each type of cancer is characterized by the expression of 200-300 genes. These genes have led to the current concept called “genetic signature” which is specific to each cancer type. These genes are likely to become the basis of the molecular diagnosis, which will probably entail a new classification of cancers. Moreover, each gene of the “genetic signature” can be present in several forms, called polymorphisms. These groups of genes and polymorphisms which together are associated with an increased risk for cancer will be identified by means of DNA microarrays (Genomics). The microarray technique is an efficient and feasible method for getting and comparing the profiles of the genes’ expression from cancer patients to healthy individuals and those with premalignant lesions, as well as to patients with digestive malignant pathology. Some pattern of gene expression can become criteria of early diagnosis and could be very useful in the digestive lesions’ management. However, since the analysis of transcriptional activity using DNA Arrays is associated with false-positive results some genes must be eliminated. This disadvantage is inherent to the technique, as it has a statistic value. This is the reason why the DNA chip evaluation needs a statistic processing by means of specialized software in the Telemedicine and Artificial Intelligence Module (the Artificial Intelligence and Statistic Processing Submodule). The validation and quantification of the genes identified by “Genomics” will be done by real-time PCR (RT-PCR).
Although the expression of genes offers a huge amount of information regarding the transcriptional activity of the cancerous cell, it doesn’t tell either what cells express that gene or any information referring to the genetic information translation in proteins at the cell level. Due to this reason three imaging and analytic platforms are necessary: LCM platform for the localization in the tissue of cancer related proteins, a platform for identification of relatively abundant proteins by MALDI-TOF-MS technique and AFM for analyzing of extremely low concentration proteins. The AFM technique can identify a large array of globular proteins (immunoglobulin, feritin, phosphorylase, phosphorylaskinase, member of P450 cytochrome, etc.) and complexes of these. Thus, in the framework of this project this method alongside complementary techniques as MALDI-TOF-MS and fluorescence methods (confocal microscopy) compiles the basis of a complete proteomic analysis platform for identification of biomarkers in malignant digestive diseases.
The malignant tissue is extremely heterogeneous. In order to make a phenotypic and molecular cell analysis of the cancerous tissue, it is necessary to isolate phenotypic homogeneous cells by the LCM method. By means of the laser microdissection we will realize:
- (i) identification and quantification of important genes in the cancerous process, by isolating the messenger RNA and amplification by real-time PCR of cell groups specific to the malignant tissue;
- (ii) verification of the tissue location of messenger RNA specific to the cancerous cell, by the ISH technique;
- (iii) identification of the functional proteins by the MALDI-TOF-MS technique;
- (iv) investigation of the dynamics and of the topography of the proteins identified by proteomics at the cell substructure in native, physiologic state by using the AFM microscope whose resolution is comparable to the electronic one (nm / tens of nm).
In order to complete the study, we will realize:
- (v) analysis of structural and conformational changes of the tumor markers by luminescence and spectroscopic studies. The AFM is a non-destructive method, while the spectroscopic changes can be used as diagnosis and prognosis criteria useful in the digestive disease management.
- (vi) identification (phenotype) of the cells which express proteins specific to the malignant cells will be realized by two-photon laser scanner confocal microscopy (LSCM). This microscope can penetrate in the tissues even to 1-2 mm. Moreover, the bi-photon microscope can be used for observations of long time periods (weeks), so the cancerous process in an animal model can be kept under observation in vivo. The identification of these molecular and cellular markers will become the basis of new molecular therapeutic targets. For logistic reasons, the material used for the laser microdissection will be prepared by a cryomicrotome which allows cutting the native tissue into small sections. The cryomicrotome will be also used in the Pathology Module to establish a rapid diagnosis.
New molecular cytogenetic methods will be added to the previous investigations. They do not entirely replace the classical cytogenetic techniques, but they can identify chromosomal changes undetectable by standard techniques (banding G, T, C, R). The new FISH method makes easier to characterize complex reshuffling of some chromosome markers, especially in tumor cells (gastric, hepatic or colorectal cancers). The comparative genome hybridization technique (CGH) will be used to establish the gene dosage and will be done with the equipment that will be acquired. This method is particularly useful to investigate the chromosomal aberrations in solid tumors where it is difficult to identify the karyotype.
In order to further characterize the malignant tissue, cancerous cells will be cultured in vitro and used for molecular studies. Based on the model of cellular cultures, there will be studies on the intracellular activity, which will focus on the DNA replication and transcription, on the protein synthesis, on the cellular metabolism and on the cellular death (necrosis or apoptosis). It is important to establish relevant cellular lines for different tumors types in order to find therapeutic strategies to fight cancer.
This research theme will be extended within the Molecular Biology and Biochemistry Module. The activity of Molecular Biology and Biochemistry Module has mainly a fundamental research character.
By acquiring new equipment in the framework of this module, besides the existing one, it will be possible to make better research in order to detect new diagnosis markers, but also to develop new training programs to familiarize the resident doctors and the candidates for a doctor’s degree with the latest international techniques.
The techniques used in the framework of this module, together with the imaging and pathology techniques, will establish the interdisciplinary character of the research made within this center.
III. Molecular Biology and Biochemistry Module
The most important research activities will focus on:
1. identifying transcriptional genetic activity profiles (Transcriptome) in the malignant gastro-intestinal pathology in order to establish a genetic diagnosis;
2. quantifying of genes (gene dosage) which are specific to the cancerous cell by CGH;
3. identifying some genetic mutations specific to the malignancy process;
4. standardization of some biochemical tests for early diagnosis;
5. detecting some possible therapeutic targets at the cellular and molecular level;
6. determining some protein markers (tumor markers, cytokines, growth factors, fibrosis factors, oxidative stress markers) in biological liquids (serum, plasma);
7. evaluating the specificity of some genetic and biochemical marker panels – as non invasive diagnosis indexes in colon, pancreatic, gastric and liver cancer;
8. determining of proteic markers in tissue extract and the correlation to the obtained result by analysis of biologic liquid for the correct diagnosis of mentioned digestive cancers;
9. developing nanosystems for the separation of the proteins according to their biologic properties;
10. installing molecular detectors able to “measure” individual or complex molecules, as the AFM microscope or Raman microspectroscope;
11. phenotype characterization of the cancerous cells;
12. corroborating the results of the biochemical determinations with the clinical and imaging diagnosis and their use as indexes of prognostic and of monitoring the efficiency of therapy.
The aims of this module can be attained by means of new molecular technologies based on global analysis of the genetic expression: the microarray techniques doubled by real-time PCR, CGH and the DNA sequencing (the advanced optic system is currently being acquired), protein separation and analysis through advanced techniques (MALDI-TOF-MS, AFM and Raman).
For example, the AFM is used to visualize a wide spectrum of globular proteins (such as immunoglobulin, ferritin, phosphorylase, phosphorylase-kinase, members of the P450 cytochrome family, etc.) and their derivatives. This method, together with complementary techniques such as MALDI-TOF-MS or fluorescent techniques like confocal microscopy, represents the basis of a complete proteomic analysis platform, their purpose being to identify biomarkers for the digestive tumor pathology.
The activity of the Molecular Biology and Biochemistry Module will be aimed at:
• imaging, creating and introduction of some molecular diagnosis tests in digestive cancer by using latest technologies (based on genomics and proteomics) and transferring the results from the laboratory to the clinic, in the patient’s benefit;
• making studies in order to initiate a data basis of the proteins involved in cancer; the studies will refer to plasmatic and tissue proteome changes, in order to detect efficient biomarkers for an early diagnosis in digestive cancers, for prognosis and therapy monitoring, but also to establish optimum prevention and therapeutic targets;
• evaluating the efficiency of some protein marker panels (tumor markers, cytokines, growth factors, fibrosis markers, etc.) as diagnosis indexes in digestive cancers, their use as prognosis markers and monitoring of the efficiency of the selected therapy;
• establishing the identity of the malignant cells by phenotyping.
The researches will be performed in the following submodules:
III.1. Molecular Biology Submodule
III.2. Biochemistry Submodule
III.1. Molecular Biology Submodule
This submodule will include the following laboratories and support rooms:
A. Genomic Laboratory (LG)
B. Cytogenetics Laboratory (LCG);
C. Cellular Cultures Laboratory (LCC);
D. Secretariat – The Analysis and Documentation Centre (SCAD);
E. Sterilization Space (SS);
The following researches will be performed in the framework of these laboratories:
III.1.A. Genomic Laboratory (LG)
• Research g.1: Detection of microsatellite instability (MSI), single nucleotide polymorphism (SNP) and gene mutations involved in malignant pathology of digestive tract;
• Research g.2: Assessment of methylation state and loss of heterozygosity state (LOH) in malignant tissues;
• Research g.3: Simultaneous assessment of level activities of hundred of genes (microarray) followed by validation of results through Real-Time qPCR;
• Research g.4: Generation of several profiles of genetic status for healthy subjects with premalignant or malignant lesions. Detecting of genetic markers useful in digestive cancers screening;
III.1.B. Cytogenetics Laboratory (CGL)
• Research cg.1: Initiation of cellular cultures out of lymphocytes and tumors for chromosomal preparation;
• Research cg.2: Accomplishment of chromosomal preparations and the preparedness for exam (banding, denaturation, hybridization, etc.);
• Research cg.3: Microscopic exam and karyotyping, results interpretation;
III.1.C Cellular Cultures Laboratory (CCL)
• Research c.1: Initiation of primary cellular cultures from cells and tumor tissue sampling from patients;
• Research c.2: Stabilization of high-fidelity cellular lines reflecting tumor cells characteristics;
• Research c.3: In vitro testing of potential therapeutic substances;
• Research c.4: Accomplishment of genomic and proteomic experiments on cells cultures;
• Research c.5: Long and medium term storage of cell lines;
NOTE!!! Both the research themes and the main research categories justify the infrastructure and equipments needs.
The connection between equipment-utilities (needed for proper functioning), of equipments-laboratories-rooms (afferent to the laboratories), and “researches”, can be identified at point 2.b.3 in the feasibility study.
The researches will be identified by the above existing codes.
The following diagram plots the research flow which is planned in the Molecular Biology Submodule, as well as its connection to the other modules.
III.2. Biochemistry Submodule
It will include the following laboratories:
o MALDI-TOF Analysis Laboratory (MLD)
o Laboratory for Atomic Force Microscopy (AFM)
o Laboratory for Luminescent Measurements (LL)
o Laboratory for two-photon confocal microscopy (MCF)
o Sample Processing Laboratory (LPP)
This submodule will also benefit of some spaces used for the purpose of a Data Analysis Centre (CAD), and for depositing materials and reagents (SD), as well as of a server room (SS). The following researches will be performed in the framework of this submodule:
III.2.A MALDI-TOF Analysis Laboratory (MLD)
• Research p.1: Obtaining of SELDI-TOF mass spectrum of plasmatic proteins in healthy subjects;
• Research p.2: Obtaining of SELDI-TOF mass spectrum of plasmatic proteins in suspected or diagnosed subjects with malignant digestive pathology;
III.2.B Laboratory for Atomic Force Microscopy (AFM)
• Research p.3: Analysis of data obtained in various conditions for the assessment of the sensitivity and specificity of the method for the studied pathology as compared with other types of cancer;
• Research p.4: Cluster analysis will be used to identify the proteomic profile correlated to high-risk patients or already advanced malignant disease;
III.2.C Laboratory for Luminescent Measurements (LL)
• Research p.5: Characterization of plasmatic proteins properties in malignant digestive diseases by chemiluminescence measurement;
III.2.D III.2.D Laborator microscopie confocala cu doi fotoni (MCF)
• Research p.6: Research of dynamics and topography of the proteins identified thorugh proteomics techniques, oriented on substructural cellular level in native status.
NOTE!!! Both the research themes and the main research categories justify the infrastructure and equipments needs.
The connection between equipment-utilities (needed for proper functioning), of equipments-laboratories-rooms (afferent to the laboratories), and “researches”, can be identified at point 2.b.3 in the feasibility study.
The researches will be identified by the above existing codes.
The following diagram plots the research flow which is planned in the Biochemistry Submodule, as well as its connection to the other modules.
THEME IV. USAGE OF INTEGRATIVE TELEMEDICINE METHODS BASED ON ARTIFICIAL INTELLIGENCE AND STATISTIC PROCESSING TECHNIQUES
This complex objective will be realized through the development of telemedicine techniques, based on the creation of databases with public and private access, as well as through the use of modern artificial intelligence (AI) techniques in the automatic learning field (Machine Learning), in order to create real-time intelligent automatic diagnosis systems for the computerized surveillance of the medical decision. The AI technologies envisioned in the project include: artificial neural networks, evolutionary algorithms, vector machines, clustering algorithms, and classification and decision trees. Moreover, the use of modern multivariate analysis techniques, multiple linear regression, survival analysis and statistical inference, used for the deep statistical analysis of medical data, will get them closer for the use of the information technology in order to get a complete and accurate computer-assisted diagnosis.
This research theme will be developed in the framework of Telemedicine and Artificial Intelligence Module.
IV. Telemedicine and Artificial Intelligence Module
This module should represent the bridge which makes the connection between all the other modules of the project, in order to facilitate work and information exchange between the involved laboratories and disciplines, as well as with the whole world, by Internet and by other information integrative methods. The module is complex and includes a Telecommunication and Data Bases Submodule with public and private access, as well as an Artificial Intelligence and Statistic Processing Submodule which will function as an interface between the medical equipment and the data bases developed within the modules.
The information flow is mainly oriented form the medical data sources (text recordings, static and dynamic images, etc.) to the Telemedicine and Artificial Intelligence Module in the process of data collection and storage in a global data basis. The new data will be processed offline in the Video Processing Laboratory and stored as a set of analytical parameters which will be statistically analyzed in the Statistical Processing Laboratory. All the data will be finally analyzed in the AI Laboratory in order to reach to the right conclusions. The final aim of the activity of the AI and Statistical Processing Submodule is the creation of the on-line processing flow of information. Thus, the integrated software package built on software modules corresponding to each intelligent system will be able to provide a real-time automated diagnosis as soon it has been supplied with the corresponding medical information.
NOTE!!! Due to the connections and research flows that exists between different laboratories, the ”researches” of the Telemedicine and Artificial intelligence Module will take place sequentially in the submodules, and not in distinct laboratories as the Digestive Imaging Module.
The following two submodules will be included in The Telemedicine and Artificial Intelligence Module:
IV.1. Telecommunication and DataBase Submodule
IV.2. Artificial Intelligence and Statistical Processing Submodule
III.1. Telecommunication and DataBase Submodule
• Research t.1: Obtaining video images from the medical equipment (static and dynamic images) and storing them in a mega database with private access;
• Research t.2: Developing advanced algorithms and some automatic programs to process the video files in order to identify a set of utilizable parameters in the comparative and significant statistical tests, as well as in the intelligent systems;
• Research t.3: Results presenting, case reports and storage of research results;
III.2. Artificial Intelligence and Statistical Processing Submodule
• Research v.1: Interpretation and classification of the information according to specific statistic processing and to advanced AI techniques;
• Research v.2: Design of intelligent systems (neural networks, evolutionary algorithms, classification and decision trees, support vector machines, clustering analysis) and the implementation of intelligent systems in medical data processing;
• Research v.3: Creation of integrated software packages built from corresponding intelligent system which lead to the automated diagnosis by choosing the most accurate diagnosis based on the competition of component modules;
• Research v.4: Developing virtual modeling techniques (such as 3D-reconstruction and virtual palpation), as well as distance diagnosis (telemedicine);
NOTE!!! Both the research themes and the main research categories justify the infrastructure and equipments needs.
The connection between equipment-utilities (needed for proper functioning), of equipments-laboratories-rooms (afferent to the laboratories), and “researches”, can be identified at point 2.b.3 in the feasibility study.
The researches will be identified by the above existing codes.
The following diagram plots the research flow which is planned in The Telemedicine and Artificial Intelligence Module, as well as its connection to the other modules.
The current situation
In conclusion, digestive tract cancers are a major cause of death, having an incomplete response to chemotherapy in advanced stages and usually a very poor prognosis. However, the use of modern imaging techniques in gastroenterology has revolutionized the management of patients suffering from digestive diseases, as well as the early detection of digestive cancers through screening programs oriented to high-risk group patients.
State-of-the-art imaging procedures (mainly PET-CT and MRI) have developed strongly, leading to an increased accuracy of the diagnosis, as well as the precise staging of the digestive cancers, in order to improve the therapeutic protocols. Gastrointestinal endoscopy has benefited strongly from new image processing methods in the past 2 years, yielding higher diagnosis accuracy, a better detection rate of the structural changes and improved techniques which allow the detection and quantification of vascularization and neoangiogenesis.
Presently, the diseases are defined through the identification of morphologic characteristic detected by endoscopy and microscopy. Although the diagnosis precision and accuracy can be improved by a better training in recognizing the lesions’ pattern, the future target would certainly be represented by the development of “optic biopsies”, that means recognition systems which can detect cancers in real-time. By identifying new characteristics and prognosis markers it will be easier to divide patients according to the disease stage. The high performance imaging methods mentioned above will help to improve images, while the computer methods will surely help doctors to improve the diagnosis precision. The computerized simulation will thus become essential in the learning process and in the evaluation of competencies. The research efforts of this project will make possible the creation of “intelligent imaging systems” with large memory databases which will automate many aspects of the non-invasive diagnosis techniques. Establishing an early diagnosis through complex genomic and proteomic techniques that are able to detect the molecular changes (such as the DNA mutations and the genetic expressions, as well as the codified protein expression), will entail the change of the therapeutic management, especially in the case of digestive cancer patients.
The early cancer diagnosis will become more accurate and more efficient through the use of these new imaging systems. The amount and type of services that the medical system offers to the population depends on the refunding system, but both of them are showing a significant deficit in Romania by comparison with the European Union. This difference is certainly more striking in Oltenia region, where the resources are restricted as compared with other regions of our country. This is the reason why a series of new techniques which are strictly necessary for the improvement of the population health status have not been introduced in Romania (PET-CT, 3T MRI, endoscopic autofluorescence, etc) and Oltenia (confocal laser endomicroscopy, laser microdissection system, microarray platform, AFM, etc.). These techniques are strictly necessary to enhance the population health status, but also to increase the research capacity of the University of Medicine and Pharmacy Craiova.
The development of an interdisciplinary research center of this magnitude will help boost high-quality research in the region, by attaining and coagulating a critical mass of researchers able to develop different interdisciplinary and transdisciplinary research and development projects.
The current situation
In conclusion, digestive tract cancers are a major cause of death, having an incomplete response to chemotherapy in advanced stages and usually a very poor prognosis. However, the use of modern imaging techniques in gastroenterology has revolutionized the management of patients suffering from digestive diseases, as well as the early detection of digestive cancers through screening programs oriented to high-risk group patients.
State-of-the-art imaging procedures (mainly PET-CT and MRI) have developed strongly, leading to an increased accuracy of the diagnosis, as well as the precise staging of the digestive cancers, in order to improve the therapeutic protocols. Gastrointestinal endoscopy has benefited strongly from new image processing methods in the past 2 years, yielding higher diagnosis accuracy, a better detection rate of the structural changes and improved techniques which allow the detection and quantification of vascularization and neoangiogenesis.
Presently, the diseases are defined through the identification of morphologic characteristic detected by endoscopy and microscopy. Although the diagnosis precision and accuracy can be improved by a better training in recognizing the lesions’ pattern, the future target would certainly be represented by the development of “optic biopsies”, that means recognition systems which can detect cancers in real-time. By identifying new characteristics and prognosis markers it will be easier to divide patients according to the disease stage. The high performance imaging methods mentioned above will help to improve images, while the computer methods will surely help doctors to improve the diagnosis precision. The computerized simulation will thus become essential in the learning process and in the evaluation of competencies. The research efforts of this project will make possible the creation of “intelligent imaging systems” with large memory databases which will automate many aspects of the non-invasive diagnosis techniques. Establishing an early diagnosis through complex genomic and proteomic techniques that are able to detect the molecular changes (such as the DNA mutations and the genetic expressions, as well as the codified protein expression), will entail the change of the therapeutic management, especially in the case of digestive cancer patients.
The recently development of new imaging systems tends to increase the acceptance and efficiency of cancers early diagnosis procedures. The amount and type of services that the medical system offers to the population depends on the refunding system, but both of them are showing a significant deficit in Romania by comparison with the European Union. This difference is certainly more striking in Oltenia region, where the resources are restricted as compared with other regions of our country. This is the reason why a series of new techniques which are strictly necessary for the improvement of the population health status have not been introduced in Romania (PET-CT, 3T MRI, endoscopic autofluorescence, etc) and Oltenia (confocal laser endomicroscopy, laser microdissection system, microarray platform, AFM, etc.). These techniques are strictly necessary to enhance the population health status, but also to increase the research capacity of the University of Medicine and Pharmacy Craiova.
The necessity and opportunity of investment promotion
The necessity
The proposed objectives of the Research and Treatment Centre are in accordance to the general objectives of research programs in Romania, because they allow the development of applicable essential researching to prevent a diseases group with major impact; the development of essential medical science, the usage of medical information network with optimal administration of information included in an academic network, and also implementation of telemedical modern techniques, which allow the end of differences against European medical services level.
According to expectations of this project implementation, it will be developed researching themes, whose results go firstly to acquiring an early diagnosis in malignant pathology, which would have direct influence over people’s health, especially in Oltenia, and generally in Romania.
A growth of life quality (people’s health) will also have implications on economic environment in Romania.
The project is emphasized because it puts the basis and creates an excellency centre in gastroenterology as a support to infrastructure CD development in UMF Craiova through endowment with the most modern equipments, instruments, software which contribute at the development of C-D existent infrastructure.
By infrastructure development of the excellency centre, it will be possible to expand the international partnership in C-D (especially in European planning) and to develop technological ideas with economic interest potential for Romania through endowment and modernization of existent laboratories. The creation of a new researching infrastructure which integrates the 4 Modules described (Imaging Modules, Pathology and Immunity Modules, Molecular Biology Modules and Biochemistry, Telemedical and Artificial Intelligence) belongs to major intervention area, which will allow the increasing of C-D ability and efficiency activity of UMF Craiova.
The opportunity
• The participation possibility at European researching programs
After the implementation of TARGET project, University of Medicine and Pharmacy Craiova will have the possibility, due to researching infrastructure, to develop the project in partnerships with other institutions and CD institutes in Europe, for example the current Framework Program 7, where UMF Craiova can apply CD projects for Cooperation Program-Health Area.
In the past there were international projects of UMF Craiova which, because of insufficient infrastructures, were rejected by the international assessors:
1. „Mini-invasive Evaluation of tumour angiogenesis” Project was evaluated in Framework Program7 -Ideas, Call ERC-2007-StG, obtaining a score of 6.5 from a total of 10. The main reason which didn’t obtain the subsidiary was that of resources deficiency (infrastructure and human resource. Although, the project was considered very interesting by the assessors, with an important practical impact, it wasn’t subsidized.
2. Researchers from Researching Gastroenterology and Hepatology Centre of UMF Craiova, tried to apply, in a consortium, for Framework Program 7 - Partnerships- the „Europhysione-Eu_Giome” project. Despite this, the consortium couldn’t be achieved because of insufficiency of resources and equipments (especially, because of the lack of some endowments like confocal laser endomicroscopy and endoscopic autofluorescence). It is desired that by achieving TARGET centre infrastructure, future projects would not be rejected because of infrastructure insufficiency.
• The possibility of subsidizing through POS-CCE, prior axis II: competition through researching, technological development and innovation, major area of intervention 2.2 - Investments in CDI infrastructure, Operation 2.2.1: The development of existent CD infrastructure and creation of new CD infrastructures
Area Operative Program-Increasing of Economic Competition, through major Area of Intervention
2.2. Operation 2.2.1. It is the only Area Operational Program which subsidizes the creation of CD infrastructures for institutions which develop CD activities.
Certainly, we can say that there are programs either national (National Plan of Researching, Development and Innovation II: Abilities and Partnerships Program), or international (Framework Program 7: Cooperation and Abilities) which subsidize in a certain measure the development of CD-I infrastructure of CD institution (acquisition of CD equipments), but none of them subsidize the creation of infrastructures (construction of buildings for CD).
In these terms we consider that it is convenient for the University of Medicine and Pharmacy Craiova, to apply for obtaining subsidizes from Structure Stocks in consideration of development of CD infrastructure.
• The uniqueness of infrastructure makes that researching as those of 2.b.1. „Science justification of project” be possible:
o detection of molecular modification (at ADN mutation level and gene expressions), respective of modified proteins’ expressions;
o achievement of integrated imaging system;
o initiation of screening programs and early detection with the following possible consequences: decreasing of mortality and morbidity induced by digestive cancers;
o usage of ultramodern endoscopy techniques: autofluorescence endoscopy, spectroscopy with laser fluorescence, magnification cromoendoscopy with NBI mood, optical coherence tomography and laser confocal endomicroscopy;
o characterization in situ of malignant texture through usage of microscopy techniques with 2 photons;
o usage of informatic technologies of intelligent systems area (artificial neuronal networks, evaluational algorithms, cars with vectorial support, cluster algorithms, tomography with optical coherence and decision)- incipient techniques at world wide level;
o fast absence and presence identification of sickness risk, respective of premalignant lesions.
• Creation of infrastructure can take to the following results:
o early identification of digestive cancers with direct result over mortality and morbidity
o fast identification of presence or absence of sickness risk;
o the integration in Researching European Program and the improvement of researching potential inside the project will be ensured by constant collaboration between project participants and other gastroenterology departments, medical imagistic and medical informatics: Laboratory of Endoscopy and Department of Gastroenterology and Hepatology, University Hospital Aarhus, Denmark; Laboratory of Gastrointestinal Endoscopy and Department of Surgical Endoscopy, Gentofte University Hospital, Copenhagen, Denmark; University Group for Healthcare Modeling, University of Westminster, London, United Kingdom;
o integration of ultrasound endoscopy and endomicroscopy laboratory in formation, the network of European Society of Digestive Endoscopy (ESGE) will allow the formation of Romanian and foreigners experts inside researching centre, respective formation of Romanian experts in high reputation centre in Europe under the care of NEEG and ESGE. We mention that Endoscopy Laboratory of UMF Craiova disposes of performant equipment, inclusive through the gain of 2 CEEX grants in 2006 on which basis will acquire performant equipment of ultrasound endoscopy elastrography, the only one in Romania in this moment. Activity of Ultrasound Endoscopy Lab can be reflected through creation of a CD and an interactive and dynamic website of linear ultrasound endoscopy, EUSAtlas.ro, which already has some registered users from Romania and abroad (USA, France, Netherlands, Denmark, Sweden, Germany, Hungary, Mexico, Taiwan, Thailand, Vietnam, India, China, Venezuela, Egypt etc) over 18000 individual visits permanently contributing at dissemination results of personal researches and increase of clinic prestige, respective centre. The CD and website has been awarded with The Biggest Prize Gheorghe Badea, every year prize of Romanian Society of Ultrasonography in medicine and Pharmacy Biology, awarded at the second national Congress of Ultrasound, Cluj Napoca, May 28th, 2005. Moreover, the extinction of site with pictures and films of some new endoscopy mastrography or Endomicroscopy techniques would allow increasing of popularity and dissemination through this activity:
o large spreading of information through articles which will be published in extenso in ISI and/or Medline index magazines, through works which will be presented at national and international meetings, respective through achievement of continuous medical education materials (CD, DVD, sites, web).
Taking into account the strategic directions of Area Operational Program for Economic Competition Increasing which are in concordance with guiding lines proposed by European Committee, it is necessary and convenient to introduce this project because stocks of investment allocated to this research area were insufficient, and own sources entirely missed.
Selected technical-economic scenario
It is proposed the implementation of TARGET project with the next components:
- Building construction
It is desired the achievement of a construction in Location B (1st, May Bdv, no. 66, Craiova) with S+P+3E characteristics, with Hmaxx14,15m (compared to ground quote), with built surface of 445mp and built developed surface 2250mp.
The construction will have a structural system made of BA: BA frames, BA beams and floors, and covering system with thermoisulating and hydroisulating terrace.
The construction will have branchings at:
- water feeding system;
- sewerage system, used and domestic waters;
- sewerage system, pluvial waters;
- electric energy/telephony/internet system;
- gas feeding system.
NOTE!!! You can find information about building at 2.b.3.+ Building Construction in Location B”
- Achievement of arrangements for existent Location A and B
It is wanted the achievement of 2 arrangemet types:
▪ special arrangement, for white rooms (in Location A, Petru Rares Street, no. 2, Craiova) regulated through standard SR EN 12128/2003, standard regarding security levels of microbiology labs, risk areas, situations and security demands. These arrangements will be achieved for labs of Molecular Biology Sub Module (SS, SR, SC, LLC, LCG, LG, CR) and for labs of Biochemistry Sub Module (MLD, LPP, SD, MCF).
▪ normal arrangements- these ones (paintings, replacement of electric and thermal installations, parquet replacement, isolation systems, doors and windows) are necessary regarding an ensuring of an optimal average both research development and optimal functioning of research devices.
The arrangements will be achieved in the project’s Location A and B
NOTE!!! You can find information about arrangements at 2.b.3.-„Arrangement of spaces in Location A and Location B”
- Acquisition of equipments and furniture
There are wanted acquisition equipments for the achievement of research -developing activities. Many of these equipments have „state of the arts’ character and they are the only ones in Romania. It will be acquired IT equipments too, necessary for achievement of integrated researches ( Telemedical and Artificial Intelligenge Equipments Modules).
Both Building of Location B and buildings of Location A will be endowed with special medical furniture and normal furniture.
NOTE!!! You can find information about CD equipmentsIt equipments and furniture at 2.b.3-„Endowment of CD equipments”; „Endowment with hardware and software”; „Endowment with furniture”
2 Technical-economic scenarios
Technical-economic proposed scenarios:
For the increasing of CD ability of UMF Craiova we can characterize the next scenarios:
Scenario 1: Renting of some labs completely endowed in which UMF Craiova searchers can develop researching themes which are at the basis of scientific justification of TARGET project.
Scenario operability
An informal survey of the market in early 2008 revealed that approximately 350 to 400 3T whole-body–capable MR systems are currently operational in the world, with roughly 25% used primarily for research.
Overall, the geographic distribution of cyclotrons throughout Europe, and thus the supply of 18F-FDG meant that development of PET/CT at the current rate could be sustained. While Germany, with 94 PET and PET/CT scanners, had the highest installed base of these modalities in Europe, the major markets of the UK and France which are late adopters of the technology, were lagging far behind.
Autofluorescence endoscopy and confocal laser microscopy systems represent the newest standard in gastroenterology. At the time, there is no autofluorescence endoscopy and only one confocal laser endomicroscopy in Romania. In Europe only 10 autofluorescence and 20 endomicroscopy systems are respectively functioned in highly ranking clinics.
Despite the fact that these techniques and devices are absolute necessary in order to establish an early diagnostic related to pathology investigations (immunohistochemistry, in-situ hybridization, laser microdisection, two-photon microscopy), molecular biology (real-time PCR, high density microarray, CGH, ETC) and biochemistry (MALDI-TOF-MS, AFM, etc) they are very few (or even none) places in Romania where one can find them. In Oltenia region none of these techniques and devices can be found. It should be mentioned that both laser-microdisection technique and confocal laser microscopy are completely new for Romania.
Scenario incompatibility:
a) The alternative of researches development in similar labs of study centers abroad is not viable because at this moment there are no study centers which broach only themes as those proposed.
b) Not many explorers are disposed to go abroad to develop these researches.
c) The costs of displacements are immense; University of Medicine and Pharmacy does not have the possibility of financial support of this type of scenario.
Scenario 2: The achievement of staged researching infrastructure, with help of internal and international subsidiaries.
SCENARIO OPERABILITY
Starting from premise that University of Medicine and Pharmacy Craiova can participate at PNCDI2 investigation national programs: abilities and partnerships, as well as investigation international programs, FP 7: abilities and cooperation, we estimate that, applying with smaller projects (from valuable point of view) for each o these programs, and obtaining maximum subsidies, it can be created an infrastructure similar to the one proposed through TARGET project approximately in 6 years and 9 months:
o PNCDI2:
- Abilities Program-it is estimated the obtaining of a subsidiary with maximum value, meaning 2.000.000 RON
- Partnerships Program- it is estimates the gain of at least 3 researching projects with maximum value of 600.000 RON, so a total value: 1.800.000 RON
o FP 7:
- Abilities Program- it is estimated a gain at least of an approximately subsidiary: 3.600.000 RON
- Cooperation Program- it is estimated a gain at least of an approximately subsidiary:1.260.000 RON
Calculating, we can reach at the achievement of staged proposed infrastructure: with total of 8660.000 RON/year, we can reach at maximum investment proposed by this project, approximately 60.000.000 RON- in 6 years and 9 months.
SCENARIO INCOMPATIBILITY:
a) None of these Programs (either national or international) subsidize construction of research infrastructure;
b) None of these programs finances the acquisition of equipments with values that overtake 2.000.000 RON (aproximatively 540.000 Euros)
c) Time period necessary for infrastructure achievement is too big (6 years and 9 months).There is the possibility that proposed studies can not be brought up to date.
Scenario 3: Development of infrastructure of TARGET Research Centre
The creation of infrastructure supposes the construction of a building with special constructive specifications, achievement of normal and special arrangements for spaces which will lodge Modules research components of TARGET infrastructure, acquisitions of research equipments.
From technical point of view, this scenario supposes the investment in:
• construction of a building with the next characteristics: S+P+3E, Hmax 14,15 m (against ground quote), built surface 445 mp, developed built surface 2250 mp.
NOTE!!! You can find information about building at 2.b.3.+ Building Construction in Location B”
• achievement of special and normal arrangements for Locations A and B- it is proposed the achievement of normal and special arrangements regulated through standard SR EN 12128/2003
NOTE!!! You can find information about arrangements at 2.b.3.-„Arrangement of spaces in Location A and Location B”
• acquisition of CD equipments and furniture- it is proposed the acquisition of CD equipments, necessary for the development of studies and acquisition of specialty furniture
NOTE!!! You can find information about CD equipments and furniture at 2.b.3-„Endowment of CD equipments”; „Endowment with hardware and software”; „Endowment with furniture”
Scenario recommended by the assessor
Scenario 3: Development of infrastructure of TARGET Research Centre
The scenario recommended by lab supposes the construction of a new building which corresponds to the characteristics of research equipments (Location B), the achievement of special fitting out (for the white room) in labs from Location A and the achievement of normal fitting out for labs from Locations A and B.
It is proposed the acquisition of CD equipments, IT and specialty furniture necessary for the endowment of a new construction in Location B, as well as the endowment of research labs existent in Locations A and B.
You will find information about construction (construction memorial) about equipments and furniture at 2.b.3. - where we detailed the following:
- for construction – technical memorial
- for equipments - minimum functioning characteristics, utilities necessary for good functioning of the equipments, physical spaces intended to equipments’ placing and utility of equipments in researching flow.
Advantages of recommended scenario
• period which we can achieve the infrastructure which doesn’t pass 3 years, against Scenario 2 where the achievement period of a similar infrastructure can start, if estimations remain inavariable, 6 years and 9 months.
• it can achieve all structure in terms of subsidiary of the project through POS-CCE, Axis 2, Area 2, Operation1; in maximum 3 years
• integrated development of propossed serching themes;
• creation of new working months in socio-economic unfavoured region Oltenia;
• the achievement of an infrastructure with „state of the art”, many of them unique in Romania and even if South-East Central part of Europe;
• the possibility of some investigations in partnership with abroad research centers;
• the possibility that after implemetation of the project and development of researches to obtain results with direct impact over the development of people’s healthcare and quality of poeple’s lives;
3 Constructuive, functional and technological description, in any case
Constructive description
• Buildings construction in Location B
I. GENERALITIES
I.1 THE PROJECT ‘S OBJECT
The present documentation, made according to provisions of Law 453/2001, contains the written and painted pieces for SF projection phase, and it refers to the achievement of construction works of Research and Imaging Centre UMF Craiova. According to P100/92, the building is framed in the second importance class. The importance category of construction is C.
I.2 THEME DATA
According to the projection theme, the documentation refers at the integral projection of the building. The functioning of the building is pavilion of labs for research activity.
- Construction regime: Individual construction
- Constructive system:
- Constructive system: frameworks in BA and floors in BA;
- Covering system: - covering thermoisolating and hydroisolating terrace.
I.3 DATA REGARDING THE SITE
The lot, is situated in Craiova, 1st May Bdv, no.66
- judicial regime: private property.
I.4 ACCESSES AND CIRCULATIONS
- auto access on lot: directly in the street
- pedestrian access: directly in the street
-stationary circulation: solved inside the lot (parking places on the lot)
I.5 HEIGHT REGIME
The existent building is framed in height regime of the area, being a construction: S+P+3E with maximum height at cornice: Hmax=14,50m (against ground quote).
II.THE DESCRIPTION OF ARCHITECTURAL SOLUTIONS
II.1 FUNCTIONAL ORGANIZATION
Major functioning scheme contents:
- spaces for research activities (labs),
- spaces for the administration of the building
II.2. SURFACES OF THE CONSTRUCTION
SC = 445 mp
SCD = 2250 mp
II.3 COVER CIVIL PROTECTION
According to the Ministry of Local Administration and Internal Order no. 602/2nd of December 2003, for the recommended construction is not necessary the precaution of a cover of civil protection.
II.4 STRUCTURAL SYSTEM
- constructive system: foundations in BA, frameworks in BA, beams and floors in BA;
- covering system: thermoisolating and hydroisolating terrace.
II.5 CLOSINGS AND DIVISIONS
II.5.1 Closings
- Curtain facade on aluminum structure
- Opaque closings with veneering on ventilated structure
II.5.2 Divisions
Internal divisions are made of walls with unstructured role of 12,5-25cm brick and easy gyps-cardboard partition walls with acoustic treatment of 15 cm.
II.6 EXTERNAL AND INETRNAL FINISHINGS
II.6.1 External finishing
Base: decorative plaster and veneering with natural stone;
Walls: Baumit type waterproof plaster, curtain wall on aluminum structure and veneering on ventilated structure;
Joiner’s trade: aluminum doors and windows with termoisolating glass, provided with tearing of thermal bridge;
Covering: termoisolating and hydrisolating.
II.6.2. Internal finishing
Floors: intense traffic moquette for offices, ceramics or natural stone for walls, sanitary groups and stairs, PVC floor-antistatic and antibacterial in labs.
Walls: washable painting on gyps cardboard veneering and false divided ceiling.
Joinery: wooden joinery (cellular plate doors (massive wood-furnishings), aluminum joinery with termoisolating glass).
II.7 INSTALLATIONS ADHERENT TO CONSTRUCTION
The construction is provided with elastic, sanitary installations, sewerage system, gas detached at town networks. The heating of internal spaces of construction will be ensured through own thermal station. The thermal station is placed at subsoil level and benefits of explosion surface according to P-118/1999.
Installations:
- feeding with water-branching;
- sewerage system with used domestic waters- branching;
- sewerage system with pluvial waters- branching;
- electric/telephony/energy- branching;
- gas feeding- branching.
II.8 EXTERNAL ARRANGEMENTS
They are as following:
- free spaces: sward and trees;
- spaces for circulation: Ferro-concrete veneering;
- spaces for pedestrian circulations: concrete pavements;
- spaces for gathering domestic garbage and residues resulted from technological flows: concreted ceiling etc.
-surroundings: will be used those which exist.
III. CONSTRUCTION SITE ORGANIZATION
CONSTRUCTION SITE ORGANIZATION will be made in „flows in chain” system- the development of technological flows being the following:
- construction works of infrastructure;
- construction works of over structure
- mounting workings of curtain facades, execution works of hydroisolatings;
- execution workings of internal divisions;
-joinery and finishing works.
The waste resulted of construction works will be conveyed to the closest renting pit indicated by authorities (with written agreement of these).
All construction site organization will develop on the lot, without being necessary other ground surfaces (neighborhoods and public area).
MINIMAL TERMS FOR QUALITY ENSURANCE
IV. ENSURANCE OF QUALITY DEMANDS ACCORDING TO LAW NO. 10/1995
IV.1 CONTROOL MINIMAL LIST
IV.1.1 CLASSIFICATION OF JUDICIAL REGIME (GROUND, EXISTENT CONSTRUCTIONS)
- GROUND: PRIVATE PROPERTY.
IV.1.2 INVESTOR, INVESTMENT BENEFICIARY (USER), DESTINATION
- investor: UMF CRAIOVA.
- destination: RESEARCHING AND IMAGING CENTRE
IV.1.3. TECHNIQUE REGIME
IV.1.3.a. Accesses, circulation (auto), own parking insurance for visitors;
- own parking for visitors too, are solved on the lot.
IV.1.3.b. Alignment, retiring, height (number of floors)
-there are respected the alignments provided in urbanism certificate
IV.1.3.c. Utility insurance (electric, water, sewerage system, telephone etc)
- the building will benefit of all utilities connected to technical edilitary networks existent into the area
IV.1.3.d. Integrated expressivity of the ensemble
-all ensembles are framed in neighborhoods’ character
IV.1.3.e. Construction influence over environment (natural and arranged)
- aren’t necessary major interventions over natural or arranged framework.
- sunny/shadowing: there are respected provisions of Local Urbanism regulation.
IV.1.3.f. Measures for protection against external pollutions
- there is no external pollutions; the construction does not have pollution functions.
IV.1.3.g. Radiation climate:
- there is no radioactive emanation, electric, magnetic fields etc.
IV.1.4 Modifications in flora, fauna
- there are not necessary clearings, release of biologic agents.
IV.1.5 Modifications in soil and subsoil (soil quality, slopes)
- the soil doesn’t take place of fertility class I and II, in addiction, it is the situation within the built up area and it was definitive taken out of agricultural circuit;
- release of natural ground is arranged for evacuation of pluvial waters to swearing system network existent in the framework of the lot.
IV.1.6. Collecting evacuation mood
- solid waste: town sanitation service;
- liquid waste: at swearing network which the area uses it.
Through this project ensures quality demands provided in Law no. 10/1995 regarding the quality of constructions. In execution will be respected the solutions which are in the project as well as legislation and technical robustness prescription which regulates the execution of constructions- mounting works.
IV.2 SAFETY DEMAND IN EXPLOITATION
IV.2.1. Users’ safety
Documentation provides floors (according to c37 normative), safety heights (according to STAS 6131) and utile heights (according to General Norms of labor Protection 1996)
IV.2.1.a. External circulation
- Concrete premanufactures with striation floors
IV.2.1.b. Horizontal internal circulation
- provided floors are antifire and non-skidding
IV.2.1.c. Vertical internal circulation:
- stair in 2 steps according to 2h+1=62:64, approximately slope of 57%, width grade 1,20 m
rail 90 cm
- walking surface: steps are provided with striations
IV.2.1.d. Safety regarding aggressions from installations
- electric installation: all under plaster, plugs and St switches
IV.2.1.e. Safety regarding maintaining workings
-non-skidding floors (see internal finishing)
IV.2.2. Construction security
It is provided „The present purchasing of the construction’, according to Regulation approved through HGR 766/1997 and P130-88 Normative.
Resistance and stability
- structure insurance (frameworks in BA)
- spatial organization is subordinated to structural trauma
Fire security demand
Protection against neighborhoods:
- distance between buildings: min. 10.00m
Protection against fire conduction:
-there are insured evacuations and saving ways: minimum width 1.50 m horizontal circulation, evacuation doors 1.00m etc.
Intervention teams’ access:
- firemen cars can intervene on existent road network and inside the building;
IV.3 Hygiene and people’s health demand, remaking and environmental protection
IV.3.1. Possibilities for hygiene maintaining
- internal finishing is washable;
- evacuation of used waters to sewerage proposed network;
- evacuation of domestic waste: outside the building in boxes for garbage disposed in some household platforms.
IV.3.2. Hygiene and people’s health
All microclimate terms are ensured: temperature, humidity, natural and artificial lightning, natural and mechanical ventilation.
Lightning, ventilation terms
- lightning spaces: for all rooms are ensured the necessary terms of natural lightning (norm min. of 2h/day in winter solstice is more than satisfied) (and ventilation); spaces’ orientation respects RGU.
- spaces’ ventilation: for all rooms are ensured the terms necessary of natural lightning; air volume computed: 2m3air/hour for 1 person.
IV.3.3. Remarks and environmental protection
There are no pollution sources: water, air, soil. There aren’t pollutions. The local microclimate will improve itself through plantation of trees, bushes and grass on unoccupied construction grounds.
IV.4 DEMAND OF THERMIC, WATERPROOF PREOTCTION AND ENERGY ECONOMY
IV.4.1. THERMIC ISULATION:
Climate terms:
- temperature in winter: -15°
- temperature in summer: +25°
Constructive solutions and provided material ensure the thermal isolation
- thermal bridges: avoidance (veneering with compact politer 5 cm).
IV.4.2. Waterproof isolation
- it is ensured with covers and closings (guaranteed by builder)
IV.5 DEMAND OF NOISE PROTECTION
IV.5.1. Acoustic protection measures against the noise of building exterior
IV.5.1.a Spaces orientation:
- spaces for research activities are oriented to sunny part.
Insurance of air change in isolation terms against external noise is ensured through deficiencies (joineries).
IV.5.1.b. Acoustic protection measures inside the building
- division walls between functions on the same floor: brick joinery and cardboard gyps=mineral wadding cardboard gyps=15cm.
IV.5.1.c. Spaces proposed to non-sound effects
- spaces proposed to non-sound effects: offices and meetings and protocol rooms
- spatial organization insures optimal terms for „isolation” of protected spaces
- protected spaces: sound effect level computed max. 35 Db.
The existent constructive structures are corresponding to building destination.
Activities developed in exploitation do not impose special phonoisolating measures of closings and divisions.
V. OBSEVATIONS
At closing elements projection were respected the provisions of P118/1999 Normative.
The necessary works to be executed and proposed technologies are useful to any contactor, for which reason they weren’t provided through special measures to necessitate additional charges.
The builder, through service or representative with labor protection, will insure the execution staff by the terms which are necessary for the avoidance of working accidents or professional sickness. It will respect the norms of special labor protection of working place and operation which it executes in a certain moment respective workers, as well as Regulation regarding labor protection approved by MLPAT with Order 9/N/15.03.1999 according to Constructions Bulletin no.5/1993.It will be respected provisions of Law no.90 of July 1996.
We mention that employed materials should have the characteristics provided in robustness standards, for which the bidder will present the technical arguments emitted by MLPAT-INCERC.
The control of works’ quality will be made according to control program on finished phases.
VI. GUARD MEASURES AGIANST FIRES
The documentation was made according to robustness PSI norms.
The building is framed in the degree of fire resistance according to P118/1999 Normative.
There will be respected the next norms:
- projection and achievement of technical norms of constructions regarding protection at fire action, P118/1999 Indicative;
- general norms of prevention and fire extinction approved by MI no. 381/1994
- technical norms regarding the fireproof of the materials, wood and textile products used in constructions C58/1996 Indicative, approved by Order MLPAT no.24/N
VII. MEASURES OF LABOR PROTECTION
During works’ execution will respect the provisions contented in robustness normative:
– Law of labor protection no. 90/1996,
– general norms of labor protection– 1996,
NDPM 1968, NSPM 1969, NRPM 1975, NPM 1980 i.e.
– Regulation regarding labor protection in constructions-MLPAT 9/N/1993
For the insurance of lab protection during exploitation will provide protection rails against falling according to STAS 6131/73.
This instructions are not limited, the builder at execution and the robustness beneficiary will take protection to additional measures of workers when they will be necessary, such as to avoid the production of accidents.
• Spaces arrangement in Locations A and B
➢ Special arrangements
For Molecular Biology Modules, which proposes to develop researching at gene and ADN level are necessary for the achievement of special arrangements (clean room), according to SR EN 12128/April 2003 Standard, the standard regarding the insuring levels of microbiology labs, risk areas, safety situations and demands, arrangements to insure both researchers’ life protection and optimal working average from the development of researching point of view.
The next table presents the main arrangement operations and characteristics of arranged equipments.
|Special arrangements |
|I. Demolition of existent infrastructure |
|II. Rearrangement of existent infrastructure and the endowment with: |
|a. Equipment for acclimation ensuring parameters |
|Nr. Crt |Equipment |Characteristics |
|1. |Modular air – CTA treating central |-self-carrying structure, with missing surface; |
| | |- air treated air: D=2, 7.000m³/h, available pressure dP=500Pa; |
| | |- heating ability Qinc=30Kw for each primary agent T=65/55ºC; |
| | |- cooling ability Qrac=16,30Kw |
|2. |Double aspirate ventilator for evacuation |650m³/h; available pressune: dP=200 |
| |and air recycling D=2 | |
|3. |Absolute filters | HEPA filter, efficiency class H13; 610x610x150 mm; 650x305x150 mm |
|4. |Air introduction device of anode aluminum |Air conditioner on 4 directions, inclusive regenerating individual system; |
| | |-450x450 mm |
|5 |Aspiration and air recycling device |Bulk prefilter G4, inclusive regenerating individual system 300x600 mm |
|6 |Humid air |Adherent Air treating modular Central CTA; ensuring of humidity level imposed at room level |
| | |M=5,00kg/h; distribution degree of tubular system |
|b. Linoleum |
|1 |Antistatic |Particles of 5µm/ft³: 650-100.000; 65-10.000 |
|2 |Bacteriostatic | |
|3 |Fungicide | |
This way they will need special arrangements for white room labs noticed in Spaces Schemata of Molecular Biology Sub Modules) visualization of the emphasized can be made at the following point „Endowment with CD equipments” with (SS, SR, SC, LCG, LCC, LG, CR, and in Spaces Schemata of Biology Sub Modules, with MLD, LPP, SD, MCF.
➢ Normal arrangements
In the frame of normal arrangements will achieve paintings, the replacement of the floor, windows and doors, replacement of electric and thermal equipment.
• Endowment with CD equipments
In the tables below (1st column) are presented the equipments of the 4 modules of TARGET research centre with submodules and labs.
In the second column are presented characteristics of minimum functioning which have to execute the equipments. These characteristics correspond to the best researching need.
The third column presents the utilities necessary for equipments’ functioning.
The forth presents the link between equipments and functional spaces where they will be placed. In fact, after each table we will place relays to the functional spaces.
The fifth column presents the link between equipments and their implication in researches. To visualize the researching types which are implied the equipments, please see 2.b.1. (the scientific justification) of feasibility study. It was wanted, through the achievement of this table, the demonstration of research need through correlation between researches (written below as „n Searching”), equipments necessary to research, utilities necessary for equipments to function, as well as functional spaces for equipments. We defined them like utility elements which an equipment/equipments system needs to function (e.g. number of people, electric energy type, natural gas, internet, soft and special programs etc).
The creation of TARGET Researching Centre infrastructure, equipment acquisition and device for the labs proposed in this project, can determine the initiation of research themes proposed to be studied. The results of research activities can contribute certainly to diminishing financial losses, material and especially human. In the same time researching results can go to an increasing mood of output in many practical activities, they can be accounted. These researching themes propose them, respond the basis objective’s demand at Area Operational Program for Increasing of Economic Competition.
The educational system in Romania is a great beneficiary of this project, such as students, masters and doctors can finish their studies in TARGET Researching Centre. After youth’s implication in researching we can provide an increasing of preparing and knowledge degree of young people in malignant digestive pathology area.
Social exchange average is the biggest beneficiary; people in Unfavorable Area Oltenia can have access at diagnosis services and treatment in decent terms and with maximum efficiency.
I Digestive Imaging Module
I.1 Radiology-Imaging Submodule
|I. DIGESTIVE IMAGING MODULE |
|Device/Equipment/System |Specific requirements |Utilities |Location |Area of research |
|I.1 RADIOLOGY-IMAGING SUBMODULE |
|A. FUSION IMAGING LABORATORY (PET-CT) |
|1. PET-CT System with integrated positron|a) PET system with multi-LSO-detector,| - energy supply (220 V) |PET-CT |C a.1, C a.2, C a.3, |
|emission tomography and computed |crystal dimensions 4.0 x 4.0 mm, 70 cm|- tap water | |C a.4 |
|tomography |gantry aperture, axial FOV 21.6 cm, 3D|- evacuation of | | |
| |data acquisition and image |biological and | | |
| |reconstruction |radioactive waste | | |
| | |- air conditioning system| | |
| |b) Multislice CT system (6 slices), 70|- energy supply (220 V) |PET-CT | |
| |cm gantry aperture, adaptive array |- tap water | | |
| |detector, 130 kV, 345 mA x-ray tube, |- evacuation of | | |
| |extended 70 cm FOV, 3D image |biological waste | | |
| |reconstruction, virtual colonoscopy |- air conditioning system| | |
| |software | | | |
|2. Cyclotron System |An automated, compact negative ion |- energy supply (220 V) |PET-CT |C a.1, C a.2, C a.3 |
| |accelerator, optimized for production |- tap water | | |
| |and delivery of positron emitting |- evacuation of | | |
| |radionuclides, self-shielding |radioactive waste | | |
| |cyclotron |evacuation | | |
| | |- air conditioning system| | |
|3. Color Printer |Thermal dye sublimation print |- energy supply (220 V) |PET-CT |C a.1, C a.2 |
| |technique, 320 dpi resolution, output |- air conditioning system| | |
| |grayscale resolution 12 bits (4096 | | | |
| |shades of gray), color resolution 16.t| | | |
| |millions, maximum print sizes 24 x 30 | | | |
| |cm, print throughput 100 films/hour, | | | |
| |DICOM support and compatibility with | | | |
| |PET-CT system | | | |
| | | | | |
|B. MAGNETIC RESONANCE IMAGING LABORATORY (MRI) |
|1. Magnetic Resonance System (MRI) |Superconductive 3T closed bore - long |- energy supply (220 V) |MRI |C b.1, C b.2, C b.3, |
| |(198 cm) magnet, 70 cm gantry |- tap water | |C b.4 |
| |aperture,102 integrated coil elements |- waste | | |
| |with 18 independent RF channels, 181 |evacuation | | |
| |cm FOV, gradient field strength up to |- air conditioning system| | |
| |45 mT/m, parallel image aquisition, | | | |
| |total imaging matrix, virtual | | | |
| |colonoscopy, MRCP and vascular | | | |
| |analysis softwares | | | |
|2. Dry Laser Printer |325 dpi resolution, grayscale |- energy supply (220 V) |MRI |C b.1, C b.2 |
| |resolution 4096, dual scan, 70 |- air conditioning system| | |
| |films/hour, print sizes 35x43 cm, | | | |
| |28x35 cm, 35x35 cm, integrated DICOM | | | |
| |interface, MRI compatibility | | | |
|3. Self-acting MR Injector for Contrast |Compatibility with 3T magnetic field |- energy supply (220 V) |MRI |C b.1 |
|Media |strenght, multiphase programmable | | | |
| |injection, flow rates 0.01-10 ml/s, | | | |
| |dual syringe holder, 65/115 ml | | | |
| |syringe disposables (Contrast | | | |
| |Media/Saline),function prevents | | | |
| |vascular occlusions (KVO) | | | |
| | | | | |
|C. DIGITAL X-RAY LABORATORY (DRX) |
|1. Digital X-RAY System |65-100 kW x-ray generator, dual focus | - energy supply (220 V) |DRX |C c.1, C c.2, C c.3, |
| |rotating anode tube with high heat |- tap water | |C c.4 |
| |storage capacity and high thermal load|- waste | | |
| |capacity for small focal spots, |evacuation | | |
| |40-150kV tube voltage, exposing time 1|- air conditioning system| | |
| |ms, tiltable from +90°/-17°, swivable | | | |
| |tube assembly stand with rotation | | | |
| |±90°/-180°, storage digital system | | | |
| |(2000 images), real-time acquisition | | | |
| |and image postprocessing, integated | | | |
| |DICOM interface | | | |
|2. Dry Laser Printer |325 dpi resolution, grayscale |- energy supply (220 V) |DRX |C c.1, C c.2 |
| |resolution 4096, dual scan, 70 |- air conditioning system| | |
| |films/hour, print sizes 35x43 cm, | | | |
| |28x35 cm, 35x35 cm, integrated DICOM | | | |
| |interface, MRI compatibility | | | |
You can find the plan with laboratories location in annex 8.
I.2 Digestive Endoscopy Submodule
|I. DIGESTIVE IMAGING MODULE |
|Device/Equipment/System |Specific requirements |Utilities |Location |Area of research |
|I.2 DIGESTIVE ENDOSCOPY SUBMODULE |
|A. ENDOSCOPIC AUTOFLUORESCENCE LABORATORY (AFI) |
|1.Autofluorescence gastroscope + |Autofluorescence and magnification |- power supply (220V) |AFI |C a.1, C a.2 |
|colonoscope |capabilities (AFI, NBI, HDTV), |- tap water | | |
| |compatible with the already acquired |- evacuation of biological| | |
| |autofluorescence system |waste | | |
| | |- air conditioning system | | |
|2. LIFS- optic biopsy forceps (life induced|System console, with: laser, |- power supply (220V) |AFI |C a.3 |
|fluorescence) |electronic fluorescent signal |- tap water | | |
| |reception components, computer for |- evacuation of biological| | |
| |analysis of tissue signal + biopsy |waste | | |
| |forceps with built-in optic fiber, |- air conditioning system | | |
| |compatible with usage through the | | | |
| |endoscope’s biopsy channel | | | |
|3. Endobase - software and hardware for |Image & video recording, DICOM + HL7 |- power supply (220V) |AFI |C1, C2, C3 |
|medical imaging integration |format, statistics, browser based |- air conditioning system | | |
| |application | | | |
| | | | | |
|B. MAGNIFICATION CHROMOENDOSCOPY LABORATORY (MCE) |
|1. High-resolution (HDTV) videoendoscopic |HDTV and NBI modes; 1.5x |- power supply (220V) |MCE |C b.1, C b.2, C b.3|
|system with NBI capabilities |magnification gastroscope and |- tap water | | |
| |colonoscope, NBI compatible (narrow |- evacuation of biological| | |
| |band imaging) and magnetic |waste | | |
| |positioning system compatible |- air conditioning system | | |
|2. Plasma argon coagulation system |Superior and inferior endoscopy |- power supply (220V) |MCE |C b.1, C b.2, C b.3|
| |system compatible |- tap water | | |
| | |- evacuation of biological| | |
| | |waste | | |
| | |- air conditioning system | | |
|3. 3D magnetic positioning system for |Central unit for the detection of the|- power supply (220V) |MCE |C b.3, C b.4 |
|colonoscope |colonoscope position, compatible with|- air conditioning system | | |
| |the colonoscope of the NBI system; | | | |
| |real-time visualization of the | | | |
| |colonoscope’s position | | | |
|4. Integrative Software and Hardware for |Image & video recording, DICOM + HL7 |- power supply (220V) |MCE |C1, C2, C3, C4 |
|medical images – Endobase type |format, statistics, browser based |- air conditioning system | | |
| |application | | | |
| | | | | |
|C. ULTRASOUND ENDOSCOPY LABORATORY (EUS) |
|1. Radial and liniar ultrasound endoscopy |Compatibility with the dedicated |- power supply (220V) |EUS |C c.1, C c.2, C |
|system, with contrast-enhanced EUS |ultrasound system, with |- tap water | |c.3, C c.4, C c.5, |
|capabilities |contrast-enhanced capabilities; 360 |- evacuation of biological| |C c.6 |
| |degrees radial ultrasound endoscope; |waste | | |
| |therapeutic liniar ultrasound |- air conditioning system | | |
| |endoscope, with contrast enhanced | | | |
| |harmonic EUS possibility | | | |
| |(contrast-enhanced harmonic EUS) | | | |
|2. Dedicated ultrasound system with |Compatible with the dedicated radial |- power supply (220V) |EUS |C c.1, C c.2, C |
|contrast-enhanced capabilities |and liniar ultrasound endoscopy |- tap water | |c.3, C c.4, C c.5, |
| |system; 3D real-time; harmonic |- evacuation of biological| |C c.6 |
| |contrast low; extended field of view |waste | | |
| | |- air conditioning system | | |
|3. Radial and liniar ultrasound endoscope |Compatibility with the already |- power supply (220V) |EUS |C c.1, C c.2, C c.3|
|with elastography capabilities |acquired endoscopic ultrasound |- tap water | | |
| |elastography system, 360 degrees |- evacuation of biological| | |
| |radial ultrasound endoscope, liniar |waste | | |
| |therapeutic ultrasound endoscope with|- air conditioning system | | |
| |elastography and contrast-enhancement| | | |
| |capabilities | | | |
|4. Dedicated ultrasound system with |Real-time 3D imaging, advanced 4D |- power supply (220V) |EUS |C c.4, C c.7 |
|elastography and panoramic view |ultrasound imaging technology, 2D and|- tap water | | |
|capabilities |Spectral ultrasound technology, B/W |- evacuation of biological| | |
| |and color panoramic imaging, Touch |waste | | |
| |Elasticity imaging, contrast pulse |- air conditioning system | | |
| |sequencing technology, direct | | | |
| |ultrasound research interface, full | | | |
| |suite of array transducers, Hanafy | | | |
| |Lens transducer technology | | | |
|5. Endoscopy and ultrasound endoscopy |GI Mentor II, simulator for |- power supply (220V) |EUS |C c.8 |
|examination simulator |endoscopic gastro-intestinal |- air conditioning system | | |
| |investigations, ERCP, ultrasound | | | |
| |endoscopy | | | |
|6. Integrative Software and Hardware for |image & video recording, DICOM + HL7 |- power supply (220V) |EUS |C c.1, C c.2, C |
|medical images – Endobase type |format, statistics, browser based |- air conditioning system | |c.3, C c.4, C c.5 |
| |application | | | |
| | | | | |
|D. CONFOCAL LASER ENDOMICROSCOPY LABORATORY (CLE) |
|1. Dedicated endomicroscopy system (HD |Confocal in vivo laser endomicroscopy|- power supply (220V) |CLE |C d.1, C d.2, C |
|digital video processor + gastroscope + |with x1000 magnification, with |- tap water | |d.3, C d.4, C d.5, |
|colonoscope), in completion of already |identification of tissue structures |- evacuation of biological| |C d.6 |
|acquired system |observed through conventional |waste | | |
| |histology |- air conditioning system | | |
|2. Endomicroscopy miniprobe system, |Laser scanning unit (488 nm), micro |- power supply (220V) |CLE |C1, C2, C3, C4, C5,|
|compatible with the gastroscope, |and miniprobe (300 µm - 2.8 mm), |- tap water | |C6 |
|colonoscope and eneteroscope |variable length (2-6m), image |- evacuation of biological| | |
| |processing software (Cellvizio GI) |waste | | |
| | |- air conditioning system | | |
|3. Integrative Software and Hardware for |Image & video recording, DICOM + HL7 |- power supply (220V) |CLE |C d.1, C d.2, C |
|medical images – Endobase type |format, statistics, browser based |- air conditioning system | |d.3, C d.4, C d.5 |
| |application | | | |
Hereby, in red, on the plan, are depicted the locations for the laboratories and accessory spaces for the Digestive Endoscopy Submodule
[pic]
The Digestive Endoscopy Submodule locations include:
AFI = Autofluorescence Endoscopy laboratory (area 30 sqm)
MCE = Magnification Chromoendoscopy laboratory (area 45 sqm)
CLE = Confocal Laser Endomicroscopy laboratory (area 30 sqm)
EUS = Endoscopic Ultrasound laboratory (area 30 mp)
MON AFI MCE = AFI and MCE monitoring room (area 34 sqm)
MON CLE EUS = CLE and EUS monitoring room (area 34 sqm)
SS = Sterilization room (area 6 sqm)
SA = Waiting room (area 21 sqm)
SEDIU = Gastroenterology and Hepatology Research Center, main quarters (area 63 sqm)
TMED = Telemedicine and Imaging room (area 21 sqm)
DBSLAN = Database server and LAN room (area 16 sqm)
ARHIVA = Multimedia archive (area 10 sqm)
DEPOZIT = Imaging module storage space for media (area 7 sqm)
MAGAZIE = imaging module storage (area 7 sqm)
SECR = Logistics (area 43 sqm)
WC = Toilet (area 26 sqm)
Hallways (area 40 sqm)
I.3 Endoscopic Surgery Submodule
|I. DIGESTIVE IMAGING MODULE |
|Device/Equipment/System |
|A. LABORATORY FOR EXPERIMENTAL SURGERY (EXS) |
|1. Surgical lighting |surgical lighting system 150.000 lux,|- power supply (220 V) |CEX |C a.1, C a.2, C |
| |single spot, mount-ceiling |- air conditioning system | |a.3, C a.4, C a.5 |
|2. Anesthesia Machine |Anesthesia machine – with closed |- power supply (220 V) |CEX |C a.1, C a.2, C |
| |breathing circuit |- air conditioning system | |a.3, C a.4, C a.5 |
| | |- oxygen supply | | |
|3. Monitor |Device to monitor the pulse and the |- power supply (220 V) |CEX |C a.1, C a.2, C |
| |blood pressure | | |a.3, C a.4, C a.5 |
|4. Pulse Oximeter |Device for measuring the blood gases |- power supply (220 V) |CEX |C a.1, C a.2, C |
| |(O2, CO2) portable | | |a.3, C a.4, C a.5 |
|5. Video-laparoscopy system |TV monitor |- power supply (220V) |CEX |C a.1, C a.2, C |
| |High-definition video camera |- tap water | |a.3, C a.4, C a.5 |
| |Cold light source |- evacuation of biologic | | |
| |Insufflator – automatic |waste | | |
| |Electrosurgery unit – monopolar and |- air conditioning system | | |
| |bipolar | | | |
| |Aspiration/Irrigation system | | | |
|6. Instruments for laparoscopic surgery |Laparoscope 0 degree |- power supply (220V) |CEX |C a.1, C a.2, C |
| |Laparoscope, 30 degree, |- tap water | |a.3, C a.4, C a.5 |
| |Suction/Irrigation cannula |- evacuation of biologic | | |
| |Monopolar dissection hook; Unipolar |waste | | |
| |scissors Metzenbaum; Bipolar |- air conditioning system | | |
| |scissors; Metzenbaum; | | | |
| |Rotating hook scissors; | | | |
| |Grasping forceps fenestrated 24 mm; | | | |
| |Grasping forceps serrated 24 mm; | | | |
| |Maryland dissector; Bipolar forceps | | | |
|7. Vessel sealing system |System for vascular sealing |- power supply (220V) |CEX |C a.1, C a.2, C |
| | |- tap water | |a.3, C a.4, C a.5 |
| | |- evacuation of biologic | | |
| | |waste | | |
| | |- air conditioning system | | |
|8. Argon beam coagulator |Argon beam coagulator |- power supply (220V) |CEX |C a.1, C a.2, C |
| | |- tap water | |a.3, C a.4, C a.5 |
| | |- evacuation of biologic | | |
| | |waste | | |
| | |- air conditioning system | | |
|9. Ultrasonic morcelator |Ultrasonic device for cutting tissue |- power supply (220V) |CEX | |
| |in pieces |- tap water | | |
| | |- evacuation of biologic | | |
| | |waste | | |
| | |- air conditioning system | | |
| | | | | |
|B. NOTES LABORATORY |
|1. Surgical lightning |Surgical lightning 150.000 lux, |- power supply (220 V) |NOTES |C b.1, C b.2, C |
| |single spot, mount-ceiling |- air conditioning system | |b.3, C b.4, C b.5 |
|2. Anesthesia machine |Anesthesia machine with closed |- power supply (220 V) |NOTES |C b.1, C b.2, C |
| |breathing circuit |- air conditioning system | |b.3, C b.4, C b.5 |
| | |- tap water | | |
| | |- oxygen supply | | |
|3. Monitor |Device for monitoring the pulse and |- power supply (220 V) |NOTES |C b.1, C b.2, C |
| |the blood pressure | | |b.3, C b.4, C b.5 |
|4. Puls Oximeter |Device for monitoring the SpO2l |- power supply (220 V) |NOTES |C b.1, C b.2, C |
| | | | |b.3, C b.4, C b.5 |
|5. System for videolaparoscopy |TV Monitor |- power supply (220 V) |NOTES |C b.1, C b.2, C |
| |High-definition video-camera |- air conditioning system | |b.3, C b.4, C b.5 |
| |Cold light source |- tap water | | |
| |Automatic insufflator with automatic |- evacuation of biologic | | |
| |control of pressure |waste | | |
| |Electrosurgery unit- monopolar and | | | |
| |bipolar | | | |
| |Aspiration/Irrigation system | | | |
|6. System for videoendoscopy |Trolly, Irrigation/aspiration system,|- power supply (220 V) |NOTES |C b.1, C b.2, C |
| |cold light source, video processor, |- air conditioning system | |b.3, C b.4, C b.5 |
| |therapeutic gastroscope with ½ |- tap water | | |
| |channels, therapeutc duodenoscope and|- evacuation of biologic | | |
| |colonoscope |waste | | |
|7. Argon beam coagulator |Compatible with systems for upper and|- power supply (220 V) |NOTES |C b.1, C b.2, C |
| |lower endoscopy |- air conditioning system | |b.3, C b.4, C b.5 |
| | |- tap water | | |
| | |- evacuation of biologic | | |
| | |waste | | |
|8. Integrative Software and Hardware for |Image & video recording, DICOM + HL7 |- power supply (220 V) |NOTES |C b.1, C b.2, C |
|medical images – Endobase type |format, statistics, browser based |- air conditioning system | |b.3, C b.4, C b.5 |
| |application | | | |
Hereby, in violet, on the plan, are depicted the locations for the laboratories and accessory spaces for the Endoscopic Surgery Submodule
[pic]
Endoscopic Surgery Submodule:
PA = Reception, preparation of the animal (27 sqm)
BPS = Room for biopsies ( 8 sqm)
DS = Room for instruments disinfection, cleaning (17 sqm)
SS = Sterilization room (17 sqm)
V = Dressing room (17 sqm)
CP = Lounge (35 sqm)
WC = Sanitary closets, showers (17 sqm)
NOTES ( 35 sqm)
S = Surgical lavatory (17 sqm)
CEX = Laboratory for experimental surgery (35 sqm)
MAGAZIE - (cloak room – 17 sqm)
HOL (hall – 88 sqm)
TB. EL = Electric panel - (7 sqm)
II Pathology and Immunology Module
II.1 Pathology Submodule
|II. PATHOLOGY AND IMMUNOLOGY MODULE |
|Device/Equipment/ |Specific requirements |Utilities |Location |Area of research |
|System | | | | |
|II.1 PATHOLOGY SUBMODULE |
|A. HISTOPATHOLOGY LABORATORY (HP) |
|1. Manual rotational microtome |• sectionning range 0,5-60 µm; |- power supply (220 |HP |C p.1, C p.2, C |
|(Equipment for tissue and cells from |• specimen retraction more than 100 µm |V) | |p.3, C p.4 |
|fluids embedded in paraffin bloks |- specimen orientation on 3 axis |- tap water | | |
|sectionning) |• trimming advance in 2 steps |- biological waste | | |
| |• standard specimen clamp and universal cassetes |drain | | |
| |specimen holder |- air conditioning | | |
| | |system | | |
|2. Cryostat |• cutting range: 0 - 60 µm |- power supply (220 |HP |C p.1, C p.2, C |
|(Equipment for tissue sectionning at low|• cooling down to –40ºC in steps of 1ºC |V) | |p.3 |
|temperature) |• shock freezing system for cooling down to -60ºC |- tap water | | |
| |• multiple cooling stations |- biological waste | | |
| |• automatic sterilyzing system, containing one |drain | | |
| |formalin container, one waste container one pump |- air conditioning | | |
| |and two injectors |system | | |
| |• specimen holder orientation on X,Y axis 15º min. | | | |
| |and 360º on Z | | | |
| |• vertical advance of the specimen holder min. 55 | | | |
| |mm | | | |
| |• horizontal advanceof the specimen holder min. 40 | | | |
| |mm | | | |
| |• Cutting with knifes and microtome blades | | | |
| |• adjustable knife angle 0 – 30º | | | |
| |• anti-roll system, operator protection against the| | | |
| |knife sharp edge | | | |
| |• 2-speed motorized coarse advance/retraction | | | |
| |• microtome mechanism should allow specimen | | | |
| |retraction at each stroke The microtome mechanism | | | |
| |located on the oustside of the working chamber | | | |
| |• fluorescent lamp illumination | | | |
| |• window protection against condensate | | | |
| |• cooling system located inside the cryostat base | | | |
| |• automatic defrost at preset time or at user | | | |
| |command | | | |
| | | | | |
|B. IMMUNOHISTOCHEMISTRY AND IMMUNOCYTOCHEMISTRY LABORATORY |
|1. Immunohistocemistry automatic stainer|Similar characteristics with those of the automatic|- power supply (220 |IHCICC |C p.3, C p.6 |
| |stainer for standard staining |V) | | |
|(equipment for automatic staining of | |- tap water | | |
|histo-pathology slides through the | |- biological waste | | |
|immunohistochemistry techniques) | |drain | | |
| | |- air conditioning | | |
| | |system | | |
| | | | | |
|C. IMAGE ANALYSIS LABORATORY |
|1. Microscopy system with halogen and UV|a) Erect microscope for transmitted light |- power supply (220 |ACI |C p.1, C p.2, C |
|illumination |brightfield observation and epi-fluorescence |V) | |p.3, C p.4, C |
|for the observation, aquisition, |• infinity corrected universal plan apochromate |- tap water | |p.5, C p.6, C p.9|
|analysis of the histopathological images|objectives 2x, 4x/0.16, 10x/0.40, 20x/0.75, |- biological waste | | |
| |40x/0,95 and 100x/1.40, |drain | | |
| |• field of view min. 22 mm, |- air conditioning | | |
| |• trinocular head with light path changer |system | | |
| |• swing-out front lens condenser with adjustable | | | |
| |aperture diaphragm | | | |
| |• built-in daylight and neutral density filters | | | |
| |• halogen 100W transmitted light illumination and | | | |
| |HBO 100W lamp for epi-fluorescence | | | |
| |• epi-fluorescence condenser with motorized filter | | | |
| |turret and UV protective shield | | | |
| |• adjustable field and aperture diaphragms | | | |
| |• filter sets for blue, green and UV excitations | | | |
| |b) Aquisition system |- power supply (220 |ACI | |
| |• color digital photo/video camera with min. 5 Mpxl|V) | | |
| |resolution |- air conditioning | | |
| |• signal conversion board |system | | |
| |c) Image analysis module: |- power supply (220 |ACI | |
| |• Pentium 4 PC, updated configuration |V) | | |
| |• image analysis and camera control software, |- air conditioning | | |
| |including morphometry functions for automatic |system | | |
| |analysis | | | |
|2. Laser microdissection system |a) Motorized inverted microscope |- power supply (220 |ACI |C p.7, C p.8, C |
|(Equipment for the precise selection of |• infinity corrected objectives with plan corection|V) | |p.9 |
|tissue and cell areas, through the |4x, 10x, 20x and 40x, |- tap water | | |
|Microarray and molecular pathology |• motorized stage, |- biological waste | | |
|techniques) |• motorized focus |drain | | |
| |• 10x eyepieces with wide field of view, min. 22 mm|- air conditioning | | |
| |• epi-fluorescence accessories |system | | |
| |b) Dissection Module with UV-A 355 nm laser beam, |- power supply (220 |ACI | |
| |picosecond impuls rate |V) | | |
| |• precise and fast cutting, repetition rate bigger |- tap water | | |
| |than 5 KHz, |- biological waste | | |
| |• laser beam diameter 99.999% for 0.1 to 0.3 | | | |
| |micron particles, better than HEPA filters. | | | |
| |- Exclusive dual exhaust filters provide | | | |
| |>100,000 times better protection than | | | |
| |single-stage designs. | | | |
| |- Microprocessor-based Esco Sentinel™ Silver | | | |
| |control system provides visual / audible | | | |
| |alarms for airflow. | | | |
| |- Magnehelic pressure gauge* is mounted in | | | |
| |the rear of the work zone for at-a-glance | | | |
| |monitoring of operating pressure. | | | |
| |- Arm-length Neoprene™ gloves are chemical | | | |
| |and flame resistant. | | | |
| |- An integrated pass-through with interlocking| | | |
| |doors permits materials transfer without risk | | | |
| |of environmental contamination. | | | |
| |- An angled cabinet front ensures an ergonomic| | | |
| |working posture. | | | |
| |- Cabinet operates at negative pressure | | | |
| |relative to the laboratory in order to prevent| | | |
| |migration of pathogenic materials out of the | | | |
| |work area. | | | |
|5. Vacuum concentrator for DNA, RNA and|- Chemical-resistant PTFE diaphragm pump; |- power supply (220V)|LG |C g.1, C g.2, C |
|proteins |- Chemical-resistant stainless steel chamber; |- tap water | |g.3, C g.4, C g.5 |
| |- Choice of three application modes (aqueous, |- evacuation of | | |
| |alcohol or high vapour pressure) to correspond|biologic waste | | |
| |with sample solvent → reduction of processing |- air conditioning | | |
| |time up to 20%; |system | | |
| |- Choice of four heating levels (room | | | |
| |temperature, 30 °C, 45° C, 60 °C) allows safe | | | |
| |and efficient concentration of various | | | |
| |samples; | | | |
| |- Centrifugation and Desiccator function; | | | |
| |- with built-in diaphragm pump and 48 x | | | |
| |1.5/2.0 ml fixed-angle rotor; | | | |
| |-max. 144 tubes | | | |
| |2 microplates | | | |
| | | | | |
|B. CYTOGENETICS LABORATORY |
|1. Complete system for karyotyping, |- Motorized microscope, Sextuple Nosepiece, |- power supply (220V)|LCG |C cg.1 |
|FISH, MFISH, CGH and epi-fluorescence |Trinocular Tube, Eyepiece, Abbe Condenser, 30W|- tap water | | |
|examination |illuminator, 6-position fluorescence turret, |- evacuation of | | |
| |fluorescence filter, fluorescence Lamp -130W,|biologic waste | | |
| |Optical fiber transmission , Plan Achromat X4,|- air conditioning | | |
| |20, 4- and Plan Fluor x10 and X100, digital |system | | |
| |cooled camera 2MPx, Digital Camera Control, | | | |
| |C-mount, Adapter, UnitTV tube for C-mount | | | |
| |adapter, software for automatic karyotyping, | | | |
| |FISH, MFISH and CGH (comparative genomic | | | |
| |Hybridization) , computer and LCD monitor | | | |
|2.Automatic Denaturation/Hybridization |- 12 slide capacity for fast throughput - |- power supply (220V)|LCG |C cg.2 |
|System |- Precise control of heating and cooling for |- tap water | | |
| |more consistent FISH results |- evacuation of | | |
| |-Programmable Temperature Controlled Slide |biologic waste | | |
| |-Automatic Denaturation/Hybridization |- air conditioning | | |
| |Programable system |system | | |
|3. Automatic Karyotyping System |-Microscope with trinocular tube, Plan |- power supply (220V)|LCG |C cg.3 |
| |Achromate 4x, 20x, 40x, 90x, 100x, LED |- tap water | | |
| |illuminator, 2MPx digital camera, software |- evacuation of | | |
| |for automatic karyotyping, computer |biologic waste | | |
| | |- air conditioning | | |
| | |system | | |
|4. VP 2000 Processor for slide Sistem |-Automatic pretreatment and staining, special |- power supply (220V)|LCG |C cg.1, C cg.2 |
|procesare automata a lamelor |stains (G-banding and other), and routine |- tap water | | |
| |slide washing with a single system. The VP |- evacuation of | | |
| |2000 Processor -easily processes slides using |biologic waste | | |
| |pre-programmed protocols for fluorescence in |- air conditioning | | |
| |situ hybridization (FISH) - solid tumor. |system | | |
| |Contain:PC computer, UPS, VP 200 software si | | | |
| |VP 2000 procesor | | | |
|5. Flow Hood class II |-Samples protection, vertical and horizontal |- power supply (220V)|LCG |C cg.1, C cg.2 |
| |windows movement mechanism, safety system for | | | |
| |air flow speed, air filter, air clean LCD | | | |
| |display | | | |
|6.Termostat Incubator/Thermostat |-Temperature range of 7 °C (13 °F) above |- power supply (220V)|LCG |C cg.1, C cg.2 |
|Cell culture |abient temperature up to 60 °C (140 °F), |- air conditioning | | |
| |Temperature variation at 37 °C : ± 0.3, |system | | |
| |interface for communication , Electronic | | | |
| |self-diagnostic system for errors with optical| | | |
| |and acoustic alarm, Perforated shelves, | | | |
| |stainless steel, controller for temperature | | | |
| |and CO2 concentration. | | | |
|7.Centrifuge |-Speed: 5.000 rpm, Programmable RPM and RCF , |- power supply (220V)|LCG |C cg.2 |
| |Digital display:time and RPM |- air conditioning | | |
| | |system | | |
|8. Heating Magnetic stirrer |-Speed range 0 - 1500 1it/min , Heating rate |- power supply (220V)|LCG |C cg.1, C cg.2 |
| |7°C /min , Heating temperature range room |- air conditioning | | |
| |temp. - 340°C, Heat control accuracy 10 ±°C, |system | | |
| |Connection for ext. temperature sensor ETS-D 4| | | |
| |fuzzy, Control accuracy with sensor 1± °C | | | |
|9. Thermostatic water multiple baths- |-Independent temperature regulation of every |- power supply (220V)|LCG |C cg.1, C cg.2 |
| |bath. Tank for every bath, Bath :4, Tempt |- tap water | | |
| |range:Amb.+120, Precision at base °C:± 1,5; |- air conditioning | | |
| |Heating power W:1600 |system | | |
| | | | | |
|C. CELL CULTURES LABORATORY |
|1. Incubator with CO2 |Lampa UV lamp; Perforated shelves, stainless |- power supply (220V)|LCC |C c.1, C c.2, C |
| |steel, air flow system computer assited, |- air conditioning | |c.3, C c.4 |
| |sensor CO2; |system | | |
|2. Flow Hood class II |Samples protection, vertical and horizontal |- power supply (220V)|LCC |C c.1, C c.2, C |
| |windows movement mechanism, safety system for |- air conditioning | |c.3, C c.4 |
| |air flow speed, air filter, air clean LCD |system | | |
| |display | | | |
|3. Refrigerated centrifuge with |Microprocessor and digital display, induction|- power supply (220V)|LCC |C c.1, C c.2, C |
|interchangeable-rotor |motor, Programmable RPM and RCF Increments of |- air conditioning | |c.3, C c.4 |
| |10; stainless steel, 9 level of preselection, |system | | |
| |protection of centrifuge motor, Automatic | | | |
| |rotor recognition, | | | |
|4.Laboratory microcentrifuge |Microprocessor and digital display, automatic|- power supply (220V)|LCC |C c.3, C c.4 |
| |sensor blocks centrifuge door, stainless |- air conditioning | | |
| |steel, Programmable RPM and RCF Increments of |system | | |
| |10, max. speed/RCF: 1800 rpm/23.907; volume | | | |
| |6*50 ml; timer 1....99 min | | | |
|5. Inverted fluorecence microscope for |For examination cell cultures and the changes |- power supply (220V)|LCC |C c.1, C c.2, C |
|cell cultures examination with PC camera|appeared in flasks (numer and morphology of |- tap water | |c.3, C c.4 |
| |cells), digital camera connected at PC for |- evacuation of | | |
| |analysis |biologic waste | | |
| | |- air conditioning | | |
| | |system | | |
|6. Analytical |internal calibration , adjustable and time |- power supply (220V)|LCC |C c.1, C c.2, C |
|Balance |control, detrmination of the fluids density | | |c.3, C c.4 |
Hereby, in green on the plan, are depicted the locations for the laboratories and accessory spaces for the Molecular Biology Submodule
[pic]
Spaces in the Molecular Biology Submodule include:
SS = sterilization area (15 sqm)
SR = sample collecting area (12 sqm)
SV = cloakroom (12 sqm)
SC = sample storage area (16 sqm)
SCAD = Secretariat, documentation and analysis area (24 sqm)
LCG = Cytogenetics area (68 sqm)
LCG1 = sample processing area (16 sqm)
LCG2 = standard karyotyping area (17 sqm)
LCG3 = FISH analysis area (12 sqm)
LCG4 = CGH analysis area (12 sqm)
Lobby = (11 sqm)
LCC = Cell cultures laboratory (52 sqm)
LCC1 = sample processing area (17 sqm)
LCC2 = incubating area (12 sqm)
LCC3 = microscopy area (12 sqm)
Lobby = (11 sqm)
LG = Genomics laboratory (79 sqm)
LG1D = DNA Pre-amplification area (6 sqm)
LG2D = DNA amplification area (8 sqm)
LG3 = post PCR area (28 sqm)
LG1R = RNA Pre-amplification area (6 sqm)
LG2R = DNA amplification area (9 sqm)
CR = Reagents area (5 sqm)
Lobby = (17 sqm)
III.2 Biochemistry Submodule
|III. MOLECULAR BIOLOGY AND BIOCHEMISTRY MODULE |
|Device/Equipment/System |Specific requirements |Utilities |Location |Area of research |
|III.2 BIOCHEMISTRY SUBMODULE |
|1. 2D electrophoresis system |Isoelectric focusing system with: power source | - energy supply (220 |MLD |C p.1, C p.2, C |
| |(10000 V, 2.4 mA); platform for up to 24 strips|V) | |p.3, C p.4 |
| |of 7, 12 strips of 11, 17, 24 cm with a precise |- tap water | | |
| |temperature control at 10-25oC (Peltier system);|- evacuation of | | |
| |rehydration and equilibration trays for 12 |biological waste | | |
| |strips; isoeletric focusing tank including |- air conditioning | | |
| |platinium electrodes assuring sample integrity; |system | | |
| |collecting data via RS-232 serial port; | | | |
| |interface for method programmation and providing| | | |
| |continuous information on the migration process;| | | |
| |IPG strips with different pH gradient (3–6, 5–8,| | | |
| |7–10), labeled for rapid identification of | | | |
| |polarity and pH range | | | |
| |compact vertical electrophoresis system for 12 | | | |
| |gels simultaneous processing; cooling system, | | | |
| |buffer recycling vacuum; plate electrodes making| | | |
| |an equal electric field; versatility for | | | |
| |different gel sizes (18,3x19,3 cm, 18,5x20 cm, | | | |
| |20x20,5 cm, 25x20,5 cm) and different thickness | | | |
| |(1-3 mm); spacers; accessory for stabilizing | | | |
| |loaded gels;appropriate power source (250 V, 3 | | | |
| |A, 300 W) | | | |
| |scanner with high resolution for quantitative | | | |
| |evaluation of spots and appropriate software for| | | |
| |protein analysis | | | |
|2. MALDI -TOF-MS system |microScout Ion Source with state-of-the-art | - energy supply (220 |MLD |C p.1, C p.2, C |
| |pulsed ion extraction (PIE™); target area |V) | |p.3, C p.4 |
| |exactly ¼ of industry standard microtiter |- tap water | | |
| |plates; various 96-spot target types available |- evacuation of | | |
| |for specific applications; nitrogen laser with |biological waste | | |
| |variable repetition rate up to 20 Hz; TOF |- air conditioning | | |
| |analyzer: high resolution reflectron |system | | |
| |configuration or optional linear only version; | | | |
| |optional MS/MS capability with auto PSD | | | |
| |(automated post-source decay) including | | | |
| |precursor ion selection device; modular design | | | |
| |allows for future upgrades; WhisperMode™ erases | | | |
| |noise pollution; software for data analysis | | | |
|3.Homogenising system |Sonication system; homogenising system with | - energy supply (220 |MLD |C p.1, C p.2, C |
| |liquid nitrogen |V) | |p.3, C p.4 |
| | |- tap water | | |
| | |- evacuation of | | |
| | |biological waste | | |
| | |- air conditioning | | |
| | |system | | |
|4. Luminiscence spectrophotometer |Analysis of luminescence, excitation, | - energy supply (220 |RL |C p.5 |
| |phosphorescence spectra in (200-800nm) range, |V) | | |
| |photomultiplier detection, automatic correction |- tap water | | |
| |of spectra, polarized light measurements, |- evacuation of | | |
| |bio-luminescence measurements, sample |biological waste | | |
| |temperature control, variable gate and delay of |- air conditioning | | |
| |excitation, flow-cytometry option, plate reader |system | | |
| |option for chemiluminescence, CCD detection, | | | |
| |software for data analysis | | | |
|5. Chemiluminiscence detection system|Dual system of excitation and emission for | - energy supply (220 |MCF |C p.1, C p.2, C |
|for Western blots |protein detection on Western blots; emission |V) | |p.3, C p.4 |
| |wavelenght:488 si 560 nm; 2D imaging; CCD |- tap water | | |
| |detection; detector temperature control; UV |- evacuation of | | |
| |filter; real time working; transiluminator, |biological waste | | |
| |EPI-iluminator; software for image analysis and |- air conditioning | | |
| |processing |system | | |
|6. Atomic Force Microscope AFM |Atomic force microscope with operating modes: | - energy supply (220 |AFM |C p.6 |
| |contact and true non-contact Atomic Force |V) | | |
| |Microscopy, Lateral Force Mode, AFM-SPM mode for|- tap water | | |
| |operation in liquid environment, intermittent |- evacuation of | | |
| |contact mode, phase imaging force modulation |biological waste | | |
| |mode, Force Mode, nanolithography, EFM – |- air conditioning | | |
| |Electrostatic Force Microscopy, Adhesion Force |system | | |
| |Imaging, software for 3D analyses, inverted | | | |
| |optical, microscope, XY scan > 90 (m, active and| | | |
| |passive devices for damping of vibrations, | | | |
| |computer, noise Z ................
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