Littérature scientifique sur le sujet « "bio-bank" »

Globally, the establishment of bio-banks began around 1990s when scientists felt need for collaborative researches in biomedical field. Bio-banks collect and preserve biological specimens which are provided to researchers to investigate about specific disease or treatment. In Nepal, eye bank and skin bank are only two types of bio-banks currently in existence. However, specimens collected in these bio-banks are used only for medical treatment, not for research. With this regard, there is urgent need to establish bio-banks in Nepal. In this article, we aim to provide insights on current status of bio-banking and its benefits for scientific development of Nepal. Keywords: Bio-bank; eye bank; Nepal; skin bank

The reduction of organic content through transformation processes in the Danube aquifer along a studied area, biodegradability of Danube bank filtrate and its enhancement by ozonation have all been examined in a study carried out in order to assess amenability of Danube bank filtrate for bio-filtration. As determined during the study period Dissolved Organic Carbon (DOC) varied from 4.6–6.5 mgC/L and from 2.8–3.7 mgC/L in Danube River and Danube bank filtrate respectively. As determined 11.2% of Danube bank filtrate DOC was bio-degradable. A substantial enhancement of biodegradability has been observed after the application of Ozone dosages ranging from 0.45 to 0.9 mgO3/ mgC. It was concluded that Danube bank filtrate itself is not amenable for bio-filtration but an enhancement of its bio-degradability by ozonation could make bio-filtration a reasonable and economical option for reducing of DOC content to the levels that provide low risk of excessive disinfection by-products formation and prevent bacterial re-growth in distribution networks of cities using Danube bank filtrate as the source water.

This paper presents an effective way to control the temperature of bio-reactors (fermenters) used in ethanol production and to reduce the volume of cooling water required per square meter of ethanol produced. This paper specifically focuses on the fermentation of cassava starch using Saccharomyces cerevisiae at 32ºC. The flow across tube banks model is employed as the cooling mechanism of the bio-reactor. Cooling water at 28°C enters a shell containing five rows of fifteen (15) bio-reactors in a square in-line arrangement and exits the shell at 31.84°C. The total working volume of all fifteen (15) bio-reactors in the bank equals 180m^3. Each bio-reactor in the bank is designed to have an effective heat transfer area to volume ratio of two (2) to enhance heat transfer. The total quantity of cooling water required per cubic meter of ethanol produced is found to be 97.833m^3. A total amount of 1.303kW is required to power anchor impellers placed in each bio-reactor to provide mixing. The rotation speed of the impeller in each bio-reactor is 0.2〖rev·s〗^(-1). A total of 3.453*10^(-6) W is required to move cooling water through the bio-reactor bank at a speed of 3.942*10^(-5) ms^(-1). An overall heat transfer coefficient of 11.345W·m-2°C-1 was found for the bio-reactor cooling system. Employing flow across tube banks model in cooling ethanol bio-reactors required significantly less amount of cooling water per cubic meter of ethanol produced compared to using internal cooling coils.

River management implies in many situation to control the river bank stability. Bio-engineering techniques are used as an alternative to rip-rap. These techniques are not new but a renewed interest was observed during the last decade. However the design of such bank protection is still largely based an expert evaluation of each situation, and we still crudely lack a real state of the art, based on mechanistic consideration of forces exerted by the river. We present the results of preliminary flume experiments aiming to study the resistance of river bank protections using bio-engineering techniques. The final applied objectives will be to propose a framework for a good use of such technique, accounting for the river morphodynamics context.

Bio specimen collection and storage and bio bank data have numerous ethical issues. Stakeholders' views on these ethical problems are essential because they may assist establish ethical standards for bio banking. Physicians are key stakeholders because they may contact prospective participants and become bio bank users. The aim of this research is to assess Pakistani doctors' views and knowledge regarding bio banking and willingness to donate. A cross-sectional online survey was conducted to poll Pakistani physicians’ attitudes and views regarding bio banks. Between January and April 2021.473 doctors completed the questionnaire. Participants had sufficient knowledge of bio banking. Of those, 74.2 stated that they had heard of the term "Human Genome Project," while 72.5% revealed that they were familiar with the term "bio banking." 61.5% of the participants showed their willingness to donate bio specimens. Marital status (0.001), faculty (0.001), involvement in research (0.038), blood and tissue testing in recent years (0.420) and demonstrated a significant relationship with willingness to donate. While general health status, recent hospitalization, family history of inherited diseases, incidence of chronic disease, and gender had no statistically significant associations with willingness to donate. Although65.8% agreed that bio banks should be able to exchange bio specimens with foreign research groups and only 49.5% agreed on collaboration with pharmaceutical companies. Although more than half of Pakistani doctors heard of bio banking, the presence of bio banks in Pakistan was restricted. They were concerned about marketing, widespread consent and confidentiality. There is a great gap of knowledge and awareness among stakeholders that should encompass several educational initiatives. Community conversations on the problems of marketing and the return of research findings should begin to achieve an agreement.

In this paper, a special type of IIR filter banks; that is the bireciprocal lattice wave digital filter (BLWDF) bank, is presented to simulate scaling and wavelet functions of six-level wavelet transform. 1st order all-pass sections are utilized for the realization of such filter banks in wave lattice structures. The resulting structures are a bireciprocal lattice wave discrete wavelet filter banks (BLW-DWFBs). Implementation of these BLW-DWFBs are accomplished on Spartan-3E FPGA kit. Implementation complexity and operating frequency characteristics of such discrete wavelet 5th order filter bank is proved to be comparable to the corresponding characteristics of the lifting scheme implementation of Bio. 5/3 wavelet filter bank. On the other hand, such IIR filter banks possess superior band discriminations and perfect roll-off frequency characteristics when compared to their Bio. 5/3 wavelet FIR counterparts.

Cornea is the front transparent window of the eye which is responsible for optimal and clear vision. Transparency of this tissue is highly inevitable and cannot be compromised. Human cornea is made up of multiple layers out of which the posterior layer ‘endothelium’ is responsible for the transparency of the cornea. Endothelium is a monolayer of cells that allow the ions and solutes to transport from aqueous humour to the cornea and back which in turn maintains the transparency of the cornea by preserving the homeostasis between the anterior and posterior cornea. Earlier, it was observed that the endothelium had non regenerating capability however; recent studies have shown that these cells could be proliferated in vitro. Currently, the only method of treatment is the replacement of the diseased endothelium with the healthy donor endothelium. Penetrating keratoplasty which transplants a full thickness cornea was the only solution a decade ago. However, with the new advancements in the field of corneal transplants, specific surgical techniques like DMEK and DSAEK which replace only a part of the cornea have been identified. DSAEK replaces a part of the stroma along with the Descemet’s membrane and endothelium whereas DMEK only replaces the Descemet’s membrane and the endothelium and does not involve stroma. The results in terms of visual rehabilitation and outcomes have been found to be advantageous in these specific surgical procedures. However, DMEK is more challenging then DSAEK as DMEK is not yet a widespread technique, associated with steep learning curves and difficult donor tissue preparation. Despite DMEK is a challenging procedure it is becoming more popular because of the significant advantages in term of faster visual recovery, less postoperative astigmatism and reduced risk of transplant rejection, as compared to the other EK procedures. DMEK has several advantages in terms of rehabilitation rate and post-operative visual outcomes and therefore it is necessary to further refine this technique for a higher uptake of such surgeries and also considering that this is the only possible treatment for treating the patients suffering from endothelial dysfunctions. Although the corneal transplantation is well advanced, due to a limited supply of donor corneas for the transplantation purposes, alternative approaches like culturing corneal endothelium in vitro play an important role. Culturing the endothelium is not the only problem in EK but transplanting a 20 micron thick graft inside the recipient eye is another challenge. Moreover, the donor availability for culturing the corneal endothelium is less, making this strategy further more complicated. The thesis is therefore structured to highlight two significantly important issues in current scenario of endothelial keratoplasty, 1) posterior corneal transplantation or EK which is the on-going method of treatment for EK and 2) Human corneal endothelial cell culture which is the future of EK. Chapter 1 is an introduction to the world of eye banking, its current nature and development in the modern world and as a support to the surgeons not only in terms of new techniques but also devices for selective surgeries. It also highlights the preservation of the corneal tissues which is an important element in the field of eye banking. Eye banks play a significant role in the field of corneal transplants as they collect the human corneas and process them for transplantation. The corneas that are rejected for transplantation can be used for research and therefore development of eye banking and its research can change the field of corneal transplantation. Chapter 2 introduces the field of corneal cell culture and current techniques that are followed for culturing and possible transplantation of the cultured cells. To understand the reason and requirement of tissue engineering, it is important to study the human cornea, its extracellular matrix and its behaviour in different media. The biomechanical behaviour of the thin tissue i.e. the DM in different conditions becomes a relevant part of this study for future engineering which is studied in chapter 3. It is also important to standardize the currently available treatment options to reduce the burden of endothelial compromised patients in the future and avoid damages or tissue wastage that is currently occurring in the surgical theatres by providing standardized tissues in validated preservation medium which is studied in chapter 4. DMEK promises to become a more popular technique for the replacement of unhealthy corneal endothelium as it shows advantages like early rehabilitation rate and visual outcomes. Chapter 5 highlights the importance of new technique in rolling the DMEK tissue for easy insertion and unfolding in the recipient eye compared to the currently used technique with endothelium rolled in opposite direction. Presently, the DMEK tissues are either prepared in the surgical theatre or are stripped in the eye bank and shipped to the surgeons. However, there is no standardized procedure that could help validate a graft before surgery and provide a ready-to-use graft to the surgeons. Chapter 6 describes about a new technique of pre-loading a graft in a commercially available IOL cartridge which can be used as a preservation, transportation and transplantation device. This technique will further reduce graft wastage and will provide the surgeons a pre-validated graft further reducing the overall time in the surgical theatre and related costs. Thus different approaches for standardizing the DMEK technique were studied in the first phase of the thesis. HCECs are currently being cultured using young donor corneas. There are two major issues, firstly, the availability of the young donor corneas is less compared to the old donor corneas and secondly, there is no standard method of culturing the HCECs obtained so far. Therefore, to reduce the global tissue demand, there is a strong need to culture the HCECs from the old donor corneas which are less proliferative and less robust in nature but with high availability of the donor source. Chapter 7 is a study on isolation of HCECs and further culture of these cells from old donor corneas. Once the protocol was obtained, a full length study was performed with high sample size to prove the consistency of this technique which is highlighted in chapter 8. Meanwhile it was also noted that cells from old donors can be cultured using ROCK inhibitor in combination with Hyaluronic Acid (HA). HA induces mechanical force to the cells attaching them forcefully on the base and allows a higher proliferation of old donor cells which was studied in chapter 9. The second part of the thesis therefore investigates the culturing technique of HCECs from old donor corneas. However, once the cells are cultured, another challenge is to transplant them in the anterior chamber of the eye. This can be performed using two strategies, first, to implant the cells as suspension in the anterior chamber which is already been proposed, but the clinical evidence is still not confirmed yet, and second, to develop a carrier to transport the cultured cells. In chapter 10, we identified fish scales as a great source of collagen and therefore have investigated it as a potential scaffold to be used for HCECs culture and transplant in the future. It is also important to understand the regulations that govern the scientific studies and its use for clinical applications. Therefore, we also identified rHSA as a source to replace FCS for preserving human corneas in chapter 11. This will also help to create a synthetic media that could be used for GMP purposes for HCECs culture in the future. In conclusion, it was observed that pre-loading the tissues with endothelium-flapped inwards and preserved in dextran based medium could be a potential solution for providing a validated and standardized DMEK graft for the treatment of current endothelial dysfunction. Eye banks play a major role in the development of these surgical techniques and related devices which will change the face of corneal transplantation in the future. Alternatives like HCECs culture has a potential for the treatment of endothelial disorders and carriers like FSS could be used for culturing and transplanting these cells. However, the efficacy of these cells will only be validated after the clinical study. Considering the regulatory issues, synthetic medium would help both, the eye banks for preserving the corneas and its new products like pre-loaded DMEK and for cell culture in the future.
La cornea è quel tessuto trasparente che riveste la superficie anteriore dell'occhio, e che consente di avere una visione ottimale e chiara. La trasparenza di questo tessuto è fondamentale e non può essere compromessa. La cornea umana è costituita da più strati,tra cui lo strato posteriore o “endotelio” è responsabile della trasparenza della cornea. L’ endotelio è un monostrato di cellule che permettono agli ioni ed ai soluti di essere trasportati dall’ umor acqueo alla cornea e viceversa, e che a sua volta mantiene la trasparenza della cornea conservando l'omeostasi tra la cornea anteriore e posteriore. L’endotelio non possiede capacità rigenerative. Attualmente, l'unico metodo di trattamento è la sostituzione dell'endotelio danneggiato con l'endotelio di un donatore sano. La cheratoplastica perforante, che prevede trapianti di cornea a tutto spessore,rappresentava l'unica soluzione terapeuticafino ad un decennio fa. Tuttavia, con i nuovi progressi nel campo dei trapianti di cornea, sono state identificate specifiche tecniche chirurgiche, come DMEK e DSAEK, che sostituiscono solo una parte (o uno strato) della cornea. Sono I risultati ottenuti, in termini di riabilitazione visiva, si sono rivelati vantaggiosi grazie all’utilizzo di queste procedure chirurgiche specifiche. Tuttavia, la DMEK è più impegnativarispetto alla DSAEK in quanto non è ancora completamente standardizzata. La DMEK ha diversi vantaggi in termini di tasso di riabilitazione e risultati visivi post-operatori e quindi è necessario standardizzare questa tecnica per una maggiore diffusione di tali interventi e anche considerando che questo è l'unico trattamento possibile per la cura di pazienti affetti da disfunzioni endoteliali. Sebbene il trapianto di cornea sia in fase avanzata, a causa di una quantità limitata di cornee da donatori ai fini di trapianto, approcci alternativi come la coltura di endotelio corneale in vitro svolgono un ruolo importante. La coltura di endotelio non è l'unico problema nel trapianto di endotelio (EK)dal momento che trapiantare un innesto di 20 micron di spessore all'interno dell'occhio destinatario rappresenta una sfida ulteriore. Inoltre, la disponibilità dei donatori per la coltura di endotelio corneale è inferiore, rendendo questa strategia ulteriormente più complicata. La tesi è quindi strutturata in modo da mettere in evidenza due questioni molto importanti nell’ attuale scenario della cheratoplastica endoteliale, 1) trapianto di cornea posteriore o EK, che è l'attuale metodo di trattamento per la cheratoplastica endoteliale e 2) coltura delle cellule endoteliali della cornea umana, che rappresenta il futuro della cheratoplastica endoteliale. Il Capitolo 1 è un'introduzione sul mondo dell’ Eye Banking, sulle sue caratteristiche attuali, sullo sviluppo nel mondo moderno e sul supporto per i chirurghi, non solo in termini di nuove tecniche, ma anche di dispositivi per interventi selettivi. Si evidenzia anche la conservazione dei tessuti corneali, che è un elemento importante nel campo dell’Eye Banking. Le banche degli occhi svolgono un ruolo significativo nel settore dei trapianti di cornea, dal momento cheraccolgono le cornee umane e le analizzano per ilsuccessivo trapianto. Le cornee non idonee per il trapianto possono essere utilizzate per la ricerca e quindi lo sviluppo dell’Eye Bankinge la ricerca possono influenzare il campo del trapianto di cornea. Il Capitolo 2 introduce l’argomento delle colture cellulari corneali e le tecniche attuali che sono utilizzate per la coltura ed il trapianto di cellule coltivate. Per capire il motivo e l'esigenza dell’ingegnerizzazione dei tessuti, è importante studiare la cornea umana, la sua matrice extracellulare ed il suo comportamento in diversi mezzi di coltura. Il comportamento biomeccanico di un tessuto sottile (DM) in condizioni diverse rappresenta una parte rilevante di questo studio per la futura ingegnerizzazione,che viene descritta nel Capitolo 3. E’ inoltre importante standardizzare il trattamento attualmente disponibile allo scopo di ridurre in futuro l’onere di pazienti con endotelio compromesso ed evitare danni o sprechi di tessuto, che attualmente avvengono nelle sale chirurgiche, fornendo tessuti standardizzati in terreni di conservazione validati, come descritto nel Capitolo 4. La DMEK è considerata il futuro della cheratoplastica endoteliale, dal momento che presenta vantaggi quali la velocità dei tempi di riabilitazione ed i risultati visivi. Il Capitolo 5 mette in evidenza l'importanza della nuova tecnica che consiste nell’arrotolare il tessuto DMEK per consentire un facile inserimento per poi dispiegarlo nell'occhio ricevente, rispetto alla tecnica attualmente utilizzata con endotelio arrotolato in senso opposto. Attualmente, i tessuti DMEK sono o preparati in sala operatoria o allestiti in Banca degli Occhi e spediti ai chirurghi. Tuttavia, non vi è alcuna procedura standardizzata che possa contribuire ad ottenereun lembo endoteliale validato prima dell'intervento e fornire un innesto ready-to-use ai chirurghi. Il Capitolo 6 descrive una nuova tecnica di pre-caricamento di un lembo endoteliale in una cartuccia IOL disponibile in commercio che può essere utilizzato come dispositivo di conservazione, trasporto e trapianto. Questa tecnica consentirà di ridurre ulteriormente gli sprechi nei trapianti e fornirà ai chirurghi un innesto pre-convalidato,riducendo ulteriormente il tempo complessivo in sala operatoria edi relativi costi. Quindi nella prima fase della tesi, sono stati analizzati i diversi approcci per standardizzare la tecnica DMEK. Le HCECs sono attualmente coltivate usando cornee di donatori giovani. Ci sono due aspetti importanti, in primo luogo la disponibilità di tessuti di donatori giovani è minore rispetto a quella di donatori anziani, ed in secondo luogo non vi è, ad oggi, alcun metodo standardizzato di coltura delle HCECs. Pertanto, per ridurre la domanda di tessuti a livello mondiale, vi è una forte necessità di coltivare leHCECsderivanti da cornee di donatori anziani, che sono meno proliferative e meno resistenti in natura, ma per le quali vi è una elevata disponibilità della fonte donatrice. Il Capitolo 7 descrivelo studio sull'isolamento delle HCECs e la successiva coltura di tali cellule ottenute da cornee di donatori anziani. Una volta stabilito il protocollo, è stato eseguito uno studio completocon un alto campionamento, per dimostrare la coerenza di questa tecnica,come evidenziato nel Capitolo 8. Nel frattempo si è anche osservato che le cellule da donatori anziani possono essere coltivate utilizzando l’inibitore ROCK in combinazione con acido ialuronico (HA). HA induce una forza meccanica alle cellule per far sì che siano saldamente attaccate alla base e consentire così una maggiore proliferazione,come descritto nel Capitolo 9. La seconda parte della tesi indaga quindi la tecnica di coltura delle HCECs da cornee di donatori anziani. Tuttavia, una volta che le cellule sono coltivate, un'altra sfida è trapiantarle nella camera anteriore dell'occhio. Ciò può essere eseguito utilizzando due strategie: la prima è quella di ad impiantare le cellule in forma di sospensione nella camera anteriore, tecnica che è già stata proposta, ma che non ha ancora fornito un’evidenza clinica; la secondaè quella di sviluppare un substrato per il trasporto delle cellule coltivate. Nel Capitolo 10, si identifica la colla di pesce (FSS)come una grande fonte di collagene e quindi come un potenziale scaffold da utilizzare per la cultura HCECs e successivo trapianto. E’ inoltre importante capire le norme che regolano gli studi scientifici ed il loro uso nelle applicazioni cliniche. Pertanto, nel Capitolo 11, viene descritta l’identificazione dell’ rHSA come sostitutodell’ FCS per la conservazione di cornee umane. Questo contribuirà anche a creare un terreno di coltura sintetico che potrebbe essere utilizzato per la cultura HCECs in condizioni GMP in futuro. In conclusione, si è osservato che il pre-caricamento di tessuti con endotelio rivolto verso l'interno e conservati in un terreno con destrano, potrebbe rappresentare una possibile soluzione per fornire un lembo per DMEK validato e standardizzato per il trattamento delle disfunzioni endoteliali. Le banche degli occhi svolgono un ruolo importante nello sviluppo di queste tecniche chirurgiche e relativi dispositivi, che potranno cambiarele modalità del trapianto di cornea in futuro. Una tecnica alternativa come la coltura di HCECs ha in sèil potenziale per il trattamento di disturbi endoteliali e substrati come FSS potrebbero essere utilizzati per la coltura edil trapianto di queste cellule. Tuttavia, l'efficacia di queste cellule potrà essere validata solo dopo uno studio clinico. Considerando le questioni regolatorie, il terreno sintetico potrebbe aiutare le banche degli occhi sia per la conservazione delle cornee e dei i nuovi prodotti come DMEK pre-caricati sia, in futuro, per le colture.

Résumé : Dans ce projet, un décodage neuronal bayésien est effectué sur le colliculus inférieur du cochon d'Inde. Premièrement, On lit les potentiels évoqués grâce aux électrodes et ensuite on en déduit les potentiels d'actions à l'aide de technique de classification des décharges des neurones. Ensuite, un modèle linéaire généralisé (GLM) est entraîné en associant un stimulus acoustique en même temps que les mesures de potentiel qui sont effectuées. Enfin, nous faisons le décodage neuronal de l'activité des neurones en utilisant une méthode d'estimation statistique par maximum à posteriori afin de reconstituer la représentation spectro-temporelle du signal acoustique qui correspond au stimulus acoustique. Dans ce projet, nous étudions l'impact de différents modèles de codage neuronal ainsi que de différentes représentations spectro-temporelles (qu'elles sont supposé représenter le stimulus acoustique équivalent) sur la précision du décodage bayésien de l'activité neuronale enregistrée par le système auditif central. En fait, le modèle va associer une représentation spectro-temporelle équivalente au stimulus acoustique à partir des mesures faites dans le cerveau. Deux modèles de codage sont comparés: un GLM et un modèle bilinéaire généralisé (GBM), chacun avec trois différentes représentations spectro-temporelles des stimuli d'entrée soit un spectrogramme ainsi que deux représentations bio-inspirées: un banc de filtres gammatones et un spikegramme. Les paramètres des GLM et GBM, soit le champ récepteur spectro-temporel, le filtre post décharge et l'entrée non linéaire (seulement pour le GBM) sont adaptés en utilisant un algorithme d'optimisation par maximum de vraisemblance (ML). Le rapport signal sur bruit entre la représentation reconstruite et la représentation originale est utilisé pour évaluer le décodage, c'est-à-dire la précision de la reconstruction. Nous montrons expérimentalement que la précision de la reconstruction est meilleure avec une représentation par spikegramme qu'avec une représentation par spectrogramme et, en outre, que l'utilisation d'un GBM au lieu d'un GLM augmente la précision de la reconstruction. En fait, nos résultats montrent que le rapport signal à bruit de la reconstruction d'un spikegramme avec le modèle GBM est supérieur de 3.3 dB au rapport signal à bruit de la reconstruction d'un spectrogramme avec le modèle GLM.
Abstract : In this project, Bayesian neural decoding is performed on the neural activity recorded from the inferior colliculus of the guinea pig following the presentation of a vocalization. In particular, we study the impact of different encoding models on the accuracy of reconstruction of different spectro-temporal representations of the input stimulus. First voltages recorded from the inferior colliculus of the guinea pig are read and the spike trains are obtained. Then, we fit an encoding model to the stimulus and associated spike trains. Finally, we do neural decoding on the pairs of stimuli and neural activities using the maximum a posteriori optimization method to obtain the reconstructed spectro-temporal representation of the signal. Two encoding models, a generalized linear model (GLM) and a generalized bilinear model (GBM), are compared along with three different spectro-temporal representations of the input stimuli: a spectrogram and two bio-inspired representations, i.e. a gammatone filter bank (GFB) and a spikegram. The parameters of the GLM and GBM including spectro-temporal receptive field, post spike filter and input non linearity (only for the GBM) are fitted using the maximum likelihood optimization (ML) algorithm. Signal to noise ratios between the reconstructed and original representations are used to evaluate the decoding, or reconstruction accuracy. We experimentally show that the reconstruction accuracy is better with the spikegram representation than with the spectrogram and GFB representation. Furthermore, using a GBM instead of a GLM significantly increases the reconstruction accuracy. In fact, our results show that the spikegram reconstruction accuracy with a GBM fitting yields an SNR that is 3.3 dB better than when using the standard decoding approach of reconstructing a spectrogram with GLM fitting.

Introduzione: Numerosi studi hanno accertato il ruolo dei markers molecolari e citogenetici, specialmente in pazienti con carcinoma renale a cellule chiare (ccRCC) , allo scopo di aumentare l’accuratezza diagnostica raggiungibile con le classiche caratteristiche clinico patologiche del tumore. Obiettivo: Il principale scopo del presente studio era quello di valutare il potenziale ruolo della perdita del cromosoma 9p e del 14q come predittori di rischio di recidiva in una coorte di pazienti andati incontro a nefrectomia parziale (PN) o radicale (RN) per carcinoma renale a cellule chiare (ccRCC) non metastatico. Materiali: Abbiamo identificato la perdita del cromosoma 9p e 14q in 175 pazienti che erano stati sottoposti a nefrectomia parziale o radicale tra il 1990 e il 2000 per carcinoma renale a cellule chiare non metastatico. Nessun paziente aveva ricevuto trattamento adiuvante dopo la chirurgia. Metodi: Abbiamo eseguito un’analisi citogenetica in interfase, (F.I.S.H:fluorescence in situ hybridization ) utilizzando una specifica sonda telomerica (115 kb) che mappa sui telomeri del cromosoma 9p e 14q (SpectrumGreen LSI, Abbott) e una sonda centromerica (alpha-satellite DNA) che mappa sul cromosoma 9p11-q11. Per ogni paziente abbiamo estratto dall’archivio tutte le piu’ rilevanti caratteristiche cliniche. Abbiamo identificato nella sopravvivenza libera da malattia (DFS: disease-free serviva) il nostro principale parametro di valutazione prognostico. Abbiamo generato differenti modelli di analisi statistica multivariata allo scopo di dimostrare il valore predittivo indipendente delle anomalie citogenetiche analizzate, quando aggiustate in base agli effetti dei principali parametri usati per stratificare i pazienti in categorie di rischio durante le prove di fase 3 di valutazione di efficacia di nuove terapie adiuvanti. Risultati e limiti: In 135 casi (77.1%) non abbiamo osservato alterazioni citogenetiche, in 14 casi (8%) e in 9 casi (5.1%) abbiamo osservato la perdita del cromosoma 9p o 14q rispettivamente. In 17 casi (9.7%) si è osservata la contemporanea presenza delle due alterazioni citogenetiche. La durata del follow-up medio era di 36 mesi (interquartile range: 21–78). La simultanea perdita del cromosoma 9p and 14q è risultato essere un fattore predittivo indipendente di DFS, una volta aggiustato in base agli effetti della dimensione tumorale (pT) e del grado di differenziazione (G) (hazard ratio [HR]: 4.579; 95% confidence interval [CI], 1.767 11.868), del Leibovich score (HR: 3.704; 95% CI, 1.565–8.768), o dell’ UCLA Integrated Staging System (UISS; HR: 3.194; 95% CI, 1.351–7.553). Il piu’ rilevante limite del nostro studio è il campione di analisi relativamente piccolo. Conclusioni: la perdita del cromosoma 9p e 14q è un parametro predittivo indipendente di sopravvivenza libera da malattia (DFS) in pazienti andati incontro a nefrectomia parziale (PN) o radicale (RN) per carcinoma renale a cellule chiare (ccRCC) non metastatico , una volta aggiustato in base ai parametri o del Leibovich score o del sistema UISS. Questo studio dimostra che la sopravvivenza libera da recidiva in pazienti candidabili a protocolli di terapia adiuvante potrebbe essere fortemente influenzata dalle caratteristiche citogenetiche del tumore.
Background: Several studies have assessed the role of molecular and cytogenetic markers, especially in patients with clear cell renal cell carcinoma (ccRCC), with the intent of increasing the prognostic accuracy that is achievable with the classic clinical and pathologic features. Objective: The main purpose of the present study was to evaluate the potential role of loss of chromosomes 9p and 14q as predictors of the risk of recurrence in a cohort of patients who underwent partial nephrectomy (PN) or radical nephrectomy (RN) for nonmetastatic ccRCC. Design, setting, and participants: We evaluated the loss of chromosomes 9p and 14q in 175 patients who underwent PN or RN between 1990 and 2000 for nonmetastatic ccRCC. None of the patients received adjuvant treatment after surgery. Intervention: We performed an interphase cytogenetic fluorescence in situ hybridization analysis using a telomeric-specific probe (115 kb) mapping on the chromosome 9p and 14q telomeres (SpectrumGreen LSI, Abbott) and a centromeric (alpha-satellite DNA) probe mapping on chromosome 9p11-q11. Measurements: For each patient, we extracted from the database all of the most relevant clinical records. Disease-free survival (DFS) was the main outcome of the study. We generated different multivariable models with the intent of demonstrating the independent predictive role of cytogenetic abnormalities once adjusted for the effects of the most common tools used to stratify patients in ongoing phase 3 trials evaluating the efficacy of adjuvant therapies Results and limitations: No cytogenetic abnormalities were observed in 135 cases (77.1%), and loss of chromosome 9p or 14q was detected in 14 cases (8%) and 9 cases (5.1%), respectively. The contemporary presence of both cytogenetic alterations was reported in 17 cases (9.7%). The median follow-up duration was 36 months (interquartile range: 21–78). The simultaneous loss of both chromosomes 9p and 14q turned out to be an independent predictor of DFS, once adjusted for the effects of pT and nuclear grade (hazard ratio [HR]: 4.579; 95% confidence interval [CI], 1.767 11.868), Leibovich score (HR: 3.704; 95% CI, 1.565–8.768), or UCLA Integrated Staging System (UISS; HR: 3.194; 95% CI, 1.351–7.553). The most relevant limitation is the relatively small sample of evaluated patients. Conclusions: Loss of chromosomes 9p and 14q was an independent predictor of DFS in patients who underwent PN or RN for nonmetastatic ccRCC, once adjusted for the effects of either Leibovich score or UISS. This study demonstrates that the recurrence-free survival of patients suitable for adjuvant protocols could be strongly influenced by the cytogenetic characteristics of the tumor.

The corticocortical connections of the areas of the dorsal bank of the intraparietal sulcus (IPS) of macaque monkeys were studied by means of retrograde tracers injections in order to provide histological basis for the tractography analysis. The combined approach of these two techniques allows direct comparison of the results and a cross-validation of both methodological approaches. However, only preliminary results and perspectives from tractography analysis were included in the present thesis. Instead, tangential and laminar distribution and topographical aspects of the projections to the dorsal bank of the IPS were discussed, together with the relationships between parieto-frontal connectivity and corticospinal systems.

AbstractPathology and its laboratories are central in support of every facet of cancer care in a CCC center, from diagnosis, to patient support during treatment, research, therapeutic drug manufacture and development and bio-banking.We have approached this discussion from the perspective of the timeline of a patient’s journey through cancer care. We begin with screening programs, high quality diagnostics and then maintaining quality supportive cancer care. Specialised services such as cellular therapies and haematopoietic stem cell transplantation with their unique requirements are considered and lastly we discuss the vital role of clinical trials and research in comprehensive cancer care with a focus on biobanks.We also examine the role of the diagnostic laboratories and their clinical and scientific staff in shaping an integrated cancer diagnostic report, as an integral part of a cancer Multidisciplinary Team (MDT) or “Tumour Board”. Increasingly, integration of a large amount of clinical data, laboratory results and interpretation of complex molecular and genomic datasets is required to underpin the role of CCC’s as centres of clinical excellence and to collaborate with partners in local, national and international research protocols.

Natural outbreaks of multidrug-resistant microorganisms can cause widespread devastation, and several can be utilized or engineered as agents of bio-terrorism (emergent strains). From a bio-security standpoint, the capacity to detect and then efficiently control, within hours, the spread and the potential pathological effects of an emergent outbreak, without recourse to either antibiotics or vaccines, become key challenges that must be met. We turned to phage engineering as a potentially highly flexible and effective means to both detect and eradicate threats originating from emergent (uncharacterized) bacterial strains. To this effect, we developed technologies allowing us to 1) concurrently modify multiple regions within the coding sequence of a gene while conserving intact the remainder of the gene, 2) reversibly interrupt the lytic cycle of an obligate virulent phage (T4) within its host, 3) carry out efficient insertion, by homologous recombination, of any number of engineered genes into the deactivated genomes of a T4 wild-type phage population and 4) reactivate the lytic cycle, leading to the production of engineered infective virulent recombinant progeny. This allows the production of very large, genetically engineered lytic phage banks containing, in an E. coli host, a very wide spectrum of variants for any chosen phage-associated function, including host-range. Rapid screening of such a bank allowed the isolation of recombinant T4 particles capable of detecting (diagnosis), infecting and destroying hosts belonging to gram-negative bacterial species evolutionarily close (Yersinia ruckeri) as well as far removed (Pseudomonas aeruginosa) from the original E.coli host (DK8).

<i>Abstract</i>.—Conventional wisdom, based on observations spanning two and a half decades (1975–2000), asserts that inflow to the Gulf of Maine (GoM) occurs primarily in two areas: inshore on the Scotian Shelf off Cape Sable, Nova Scotia and on the eastern side of the Northeast Channel (NEC). In particular, the monthly mean currents in the eastern NEC have shown persistent inflow at all depths and in all seasons, except for the occasional, but brief, reversals near the bottom (~200 m). Conversely, the flow on the western side of the NEC is normally directed out of the gulf in the surface layer and at mid-depth, consistent with the clockwise gyre over Georges Bank, but those currents do show relatively frequent reversals to inflow in the deeper layers (150–200 m), in sympathy with the flow on the eastern side. At some point between the year 2000, when the last Bedford Institute of Oceanography (BIO)/U.S. GLOBEC mooring was removed from the eastern NEC, and 2004, when a new mooring was placed there as part of the U.S. ocean observing array, a transformation occurred. The recent data, collected from a representative location in the eastern NEC, show a strongly seasonal current signal marked by persistent periods of outflow in the deep layers (>100 m), particularly in winter. This observation was first reported by Pettigrew et al. (2008), where the outflow currents occasionally extend to the surface layers as well, most notably in the winters of 2004–2005 and 2006–2007. Additional data and analyses reported here suggest that this new mode of behavior in the NEC currents could have important consequences for the GoM ecosystem. Possible causes for this “regime shift” in the NEC circulation and implications for the GoM deepwater nutrient fields and ecosystem are discussed.

This paper describes the results of an on going development program aimed at determining the technical feasibility of utilizing alternative fuels such as bio-mass derived BioOil, Ethanol, Bio-Diesel and bituminous Crude Oil in a 2.5 MW GT2500 industrial Gas Turbine Engine. This gas turbine engine was designed and manufactured by “Zorya-Mashproekt” in the Ukraine and further modified for the alternative fuels application through a join development program between “Zorya-Mashproekt” and Orenda Aerospace Corporation in Canada. The modification of the GT2500 Gas Turbine Engine hot section and combustion system to operate on liquid alternative fuels are described. Also described is an engine hot section online cleaning system and features of the fuel-handling module, which carries out fuel preheating and preprocessing. A test rig equipped with a load bank was designed and built to test the modified GT2500 Gas turbine Engine on different alternative fuels (full speed/full power). Results of the modified GT2500 gas turbine engine operation along with the emissions data are presented. The tests proved the technical feasibility of operating this gas turbine engine on the alternative fuels mentioned above. Based on these results a power generation package with the engine and fuel handling module have been accepted for commercial operation in a pilot plant under construction in West Lorne, Ontario, Canada.

Since the early 1980’s TransCanada PipeLines Ltd. (TransCanada) has employed a number of stream bank stabilization measures in an effort to minimize the loss of fish habitat and to reduce the risk of long term erosion and sedimentation. Traditional stream crossing stabilization involved the re-contouring of streambanks to a stable slope (generally 2:1) and then lining the banks with rock armour and seeding. TransCanada began using alternate techniques, primarily log-walls in 1981. Since 1981 TransCanada has evolved the use stream bank stabilization techniques to include bio-stabilization techniques such as live log-walls, fascines, live staking, and brush layering in combination with more traditional structures. In 2004, TransCanada initiated a two year project to assess the success of biostabilization techniques used on a number of watercrossing throughout the its’ Alberta System. A total of 22 stream crossings were assessed in 2004 and 24 in 2005. Sites assessed were located the foothills and boreal forest areas of Alberta. In the majority of cases the biostabilization methods utilized were still intact and functioning as planned by providing stable streambanks and fish habitat. Several factors appeared to be influencing the value of the measures employed. Cattle grazing on sites where fencing did not exclude cattle from the crossing site resulted in destruction or reduced value of the measures employed. Uncontrolled All Terrain Vehicle activity resulted in a reduced value of the measure employed. Implementation of biostabilization techniques in the winter months (frozen ground conditions) created challenges in implementation of biostabilization measures resulting in less favorable results compared to other sites constructed in early and late fall. Seeding to control surface erosion also appeared to affect overall success of woody vegetation used as part of the biostabilization techniques. Biostabilization techniques employed by TransCanad have been effective in stabilizing watercrossings and providing fish habitat. In designing biostabilization systems for watercrossings consideration should be given to overall stabilization objectives, stream flow information, fish and fish habitat values, and likelihood of success given the geographic region, timing of construction, and surrounding land-use pressures.

Banco de la República provides a comprehensive overview of Colombia’s finan¬cial infrastructure in its Payment Systems Report, which is an important product of the work it does to oversee that infrastructure. The figures published in this edition of the report are for the year 2020, a pandemic period in which the con¬tainment measures designed and adopted to alleviate the strain on the health system led to a sharp reduction in economic activity and consumption in Colom¬bia, as was the case in most countries. At the start of the pandemic, the Board of Directors of Banco de la República adopted decisions that were necessary to supply the market with ample liquid¬ity in pesos and US dollars to guarantee market stability, protect the payment system and preserve the supply of credit. The pronounced growth in mone¬tary aggregates reflected an increased preference for liquidity, which Banco de la República addressed at the right time. These decisions were implemented through operations that were cleared and settled via the financial infrastructure. The second section of this report, following the introduction, offers an analysis of how the various financial infrastructures in Colombia have evolved and per¬formed. One of the highlights is the large-value payment system (CUD), which registered more momentum in 2020 than during the previous year, mainly be¬cause of an increase in average daily remunerated deposits made with Banco de la República by the General Directorate of Public Credit and the National Treasury (DGCPTN), as well as more activity in the sell/buy-back market with sovereign debt. Consequently, with more activity in the CUD, the Central Securi¬ties Depository (DCV) experienced an added impetus sparked by an increase in the money market for bonds and securities placed on the primary market by the national government. The value of operations cleared and settled through the Colombian Central Counterparty (CRCC) continues to grow, propelled largely by peso/dollar non-deliverable forward (NDF) contracts. With respect to the CRCC, it is important to note this clearing house has been in charge of managing risks and clearing and settling operations in the peso/dollar spot market since the end of last year, following its merger with the Foreign Exchange Clearing House of Colombia (CCDC). Since the final quarter of 2020, the CRCC has also been re¬sponsible for clearing and settlement in the equities market, which was former¬ly done by the Colombian Stock Exchange (BVC). The third section of this report provides an all-inclusive view of payments in the market for goods and services; namely, transactions carried out by members of the public and non-financial institutions. During the pandemic, inter- and intra-bank electronic funds transfers, which originate mostly with companies, increased in both the number and value of transactions with respect to 2019. However, debit and credit card payments, which are made largely by private citizens, declined compared to 2019. The incidence of payment by check contin¬ue to drop, exhibiting quite a pronounced downward trend during the past last year. To supplement to the information on electronic funds transfers, section three includes a segment (Box 4) characterizing the population with savings and checking accounts, based on data from a survey by Banco de la República con-cerning the perception of the use of payment instruments in 2019. There also is segment (Box 2) on the growth in transactions with a mobile wallet provided by a company specialized in electronic deposits and payments (Sedpe). It shows the number of users and the value of their transactions have increased since the wallet was introduced in late 2017, particularly during the pandemic. In addition, there is a diagnosis of the effects of the pandemic on the payment patterns of the population, based on data related to the use of cash in circu¬lation, payments with electronic instruments, and consumption and consumer confidence. The conclusion is that the collapse in the consumer confidence in¬dex and the drop in private consumption led to changes in the public’s pay¬ment patterns. Credit and debit card purchases were down, while payments for goods and services through electronic funds transfers increased. These findings, coupled with the considerable increase in cash in circulation, might indicate a possible precautionary cash hoarding by individuals and more use of cash as a payment instrument. There is also a segment (in Focus 3) on the major changes introduced in regulations on the retail-value payment system in Colombia, as provided for in Decree 1692 of December 2020. The fourth section of this report refers to the important innovations and tech¬nological changes that have occurred in the retail-value payment system. Four themes are highlighted in this respect. The first is a key point in building the financial infrastructure for instant payments. It involves of the design and im¬plementation of overlay schemes, a technological development that allows the various participants in the payment chain to communicate openly. The result is a high degree of interoperability among the different payment service providers. The second topic explores developments in the international debate on central bank digital currency (CBDC). The purpose is to understand how it could impact the retail-value payment system and the use of cash if it were to be issued. The third topic is related to new forms of payment initiation, such as QR codes, bio¬metrics or near field communication (NFC) technology. These seemingly small changes can have a major impact on the user’s experience with the retail-value payment system. The fourth theme is the growth in payments via mobile tele¬phone and the internet. The report ends in section five with a review of two papers on applied research done at Banco de la República in 2020. The first analyzes the extent of the CRCC’s capital, acknowledging the relevant role this infrastructure has acquired in pro¬viding clearing and settlement services for various financial markets in Colom¬bia. The capital requirements defined for central counterparties in some jurisdic¬tions are explored, and the risks to be hedged are identified from the standpoint of the service these type of institutions offer to the market and those associated with their corporate activity. The CRCC’s capital levels are analyzed in light of what has been observed in the European Union’s regulations, and the conclusion is that the CRCC has a scheme of security rings very similar to those applied internationally and the extent of its capital exceeds what is stipulated in Colombian regulations, being sufficient to hedge other risks. The second study presents an algorithm used to identify and quantify the liquidity sources that CUD’s participants use under normal conditions to meet their daily obligations in the local financial market. This algorithm can be used as a tool to monitor intraday liquidity. Leonardo Villar Gómez Governor