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Biomedical subjects

K Knox

Publications and source records attributed to K Knox.

At least 19 recordsLinked to original sources

TuBaFrost 3: regulatory and ethical issues on the exchange of residual tissue for research across Europe.

The regulatory regimes for research with residual tissue and accompanying data differ widely between countries in the European Union (EU): from specific consent to opt-out or even no consent at all. This could greatly hamper research where the exchange of tissue and accompanying data has become the gold standard, like in TubaFrost. Instead of adhering to international guidelines, which have a democratic deficit, or an attempt for a new set of possible harmonising rules, TubaFrost chose to create a coordinating rule: if tissue may legitimately be used for a certain kind of research in the country where it was taken and under whose jurisdiction the patient falls, it may also be used for such research in the country where it is sent to in the context of a scientific program even if in that other country other regulations would apply for research with residual tissue taken from patients under their jurisdiction. This coordinating rule has a sound basis in EU law in general and will solve the problems related to diverging national regulatory regimes in the case of cross national research with residual tissue.

Ethics, Research↗

TuBaFrost 5: multifunctional central database application for a European tumor bank.

Developing a tissue bank database has become more than just logically arranging data in tables combined with a search engine. Current demand for high quality samples and data, and the ever-changing legal and ethical regulations mean that the application must reflect TuBaFrost rules and protocols for the collection, exchange and use of tissue. To ensure continuation and extension of the TuBaFrost European tissue bank, the custodianship of the samples, and hence the decision over whether to issue samples to requestors, remains with the local collecting centre. The database application described in this article has been developed to facilitate this open structure virtual tissue bank model serving a large group. It encompasses many key tasks, without the requirement for personnel, hence minimising operational costs. The Internet-accessible database application enables search, selection and request submission for requestors, whereas collectors can upload and edit their collection. Communication between requestor and involved collectors is started with automatically generated e-mails.

Computer Simulation↗

TuBaFrost 2: Standardising tissue collection and quality control procedures for a European virtual frozen tissue bank network.

Tumour Bank Networking presents a great challenge for oncological research as in order to carry out large-scale, multi-centre studies with minimal intrinsic bias, each tumour bank in the network must have some fundamental similarities and be using the same standardised and validated procedures. The European Human Frozen Tumour Tissue Bank (TuBaFrost) has responded to this need by the promotion of an integrated platform of tumour banks in Europe. The operational framework for TuBaFrost has drawn upon the best practice of standard workflows and operating procedures employed by members of the TuBaFrost project and key initiatives worldwide.

Biological Specimen Banks↗

TuBaFrost 4: access rules and incentives for a European tumour bank.

When designing infrastructure for a networked virtual tumour bank (samples remain at the collector institutes and sample data are collected in a searchable central database), it is apparent that this can only function properly after developing an adequate set of rules for use and access. These rules must include sufficient incentives for the tissue sample collectors to remain active within the network and maintain sufficient sample levels in the local bank. These requirements resulted in a key TuBaFrost rule, stating that the custodianship of the samples remains under the authority of the local collector. As a consequence, the samples and the decision to issue the samples to a requestor are not transferred to a large organisation but instead remain with the collector, thus allowing autonomous negotiation between collector and requestor, potential co-authorship in publications or compensation for collection and processing costs. Furthermore, it realises a streamlined cost effective network, ensuring tissue visibility and accessibility thereby improving the availability of large amounts of samples of highly specific or rare tumour types as well as providing contact opportunities for collaboration between scientists with cutting edge technology and tissue collectors. With this general purpose in mind, the rules and responsibilities for collectors, requestors and central office were generated.

Europe↗

TuBaFrost 1: Uniting local frozen tumour banks into a European network: an overview.

TuBaFrost is the consortium responsible for the creation of a virtual European human frozen tumour tissue bank: a collection of high quality frozen residual, accurately classified tumour tissue samples, which are stored in European cancer centres and universities. This virtual tissue bank, searchable on the internet, has rules for access and use, and a code of conduct to comply with the various legal and ethical regulations in European countries. The easy accessibility and the European scale of the bank will result in the availability of a large number of samples even of rarer tumour types. Standardisation of collection, storage and quality control throughout the network is achieved minimising inter-institutional variability. A website providing access to upload, search and request samples is a key tool of the tissue bank. The search engine makes use of virtual microscopy. An overview of the development of the European virtual frozen tissue bank infrastructure is described in this paper. The various key aspects are described in more detail in a series of articles to appear in this Journal.

Biological Specimen Banks↗

TuBaFrost 6: virtual microscopy in virtual tumour banking.

Many systems have already been designed and successfully used for sharing histology images over large distances, without transfer of the original glass slides. Rapid evolution was seen when digital images could be transferred over the Internet. Nowadays, sophisticated Virtual Microscope systems can be acquired, with the capability to quickly scan large batches of glass slides at high magnification and compress and store the large images on disc, which subsequently can be consulted through the Internet. The images are stored on an image server, which can give simple, easy to transfer pictures to the user specifying a certain magnification on any position in the scan. This offers new opportunities in histology review, overcoming the necessity of the dynamic telepathology systems to have compatible software systems and microscopes and in addition, an adequate connection of sufficient bandwidth. Consulting the images now only requires an Internet connection and a computer with a high quality monitor. A system of complete pathology review supporting bio-repositories is described, based on the implementation of this technique in the European Human Frozen Tumor Tissue Bank (TuBaFrost).

Computer Simulation↗

TuBaFrost: European virtual tumor tissue banking.

TuBaFrost is a consortium responsible for the task to create a virtual European human frozen tumor tissue bank, composed of high quality frozen tumor tissue collections with corresponding accurate diagnosis stored in European cancer centers and universities, searchable on the Internet, providing rules for access and use and a code of conduct to comply with the various legal and ethical regulations in European countries. Such infrastructure would enlarge tissue availability and accessibility in large amounts of specified or even rare tumor samples. Design of an infrastructure for European residual tissue banking with the described characteristics, clear focus points emerge that can be broken down in dedicated subjects: (1) standardization and quality assurance (QA) to avoid inter-institute quality variation; (2) law and ethics enabling exchange of tissue samples possible between institutes in the different European countries, where law and ethics are characterized by a strong variability; (3) rules for access, with sufficient incentives for collectors; (4) central database application containing innovations on search and selection procedures; (5) support when needed with histology images; and (6) Internet access to search and upload, with in addition a solid website giving proper information on the procedures, intentions and activities not only to the scientific community, but also to the general public. One consortium decision, part of the incentives for collectors, had major impact on the infrastructure; custodianship over the tissues as well as the tissues stay with the collector institute. Resulting in specimens that are not given to an organization, taking decisions on participation of requests, but instead the local collected tissues stay very easy to access by the collector and allows autonomous negotiation between collector and requestor on cooperation, coauthorship in publication or compensation in costs. Thereby, improving availability of large amounts of high quality samples of a highly specified or rare tumor types and contact opportunities for cooperation with other institutes.

Databases, Factual↗

Virtual microscopy in virtual tumor banking.

Many systems have already been designed and successfully used for sharing histology images over large distances, without transfer of the original glass slides. Rapid evolution was seen when digital images could be transferred over the Internet. Nowadays, sophisticated virtual microscope systems can be acquired, with the capability to quickly scan large batches of glass slides at high magnification and compress and store the large images on disc, which subsequently can be consulted through the Internet. The images are stored on an image server, which can give simple, easy to transfer pictures to the user specifying a certain magnification on any position in the scan. This offers new opportunities in histology review, overcoming the necessity of the dynamic telepathology systems to have compatible software systems and microscopes and in addition, an adequate connection of sufficient bandwidth. Consulting the images now only requires an Internet connection and a computer with a high quality monitor. A system of complete pathology review supporting biorepositories is described, based on the implementation of this technique in the European Human Frozen Tumor Tissue Bank (TuBaFrost).

Databases, Factual↗

Rapid prototyping to create vascular replicas from CT scan data: making tools to teach, rehearse, and choose treatment strategies.

Our goal was to develop and prove the accuracy of a system that would allow us to re-create live patient arterial pathology. Anatomically accurate replicas of blood vessels could allow physicians to teach and practice dangerous interventional techniques and might also be used to gather basic physiologic information. The preparation of replicas has, until now, depended on acquisition of fresh cadaver material. Using rapid prototyping, it should be able to replicate vascular pathology in a live patient. We obtained CT angiographic scan data from two patients with known arterial abnormalities. We took such data and, using proprietary software, created a 3D replica using a commercially available rapid prototyping machine. From the prototypes, using a lost wax technique, we created vessel replicas, placed those replicas in the CT scanner, then compared those images with the original scans. Comparison of the images made directly from the patient and from the replica showed that with each step, the relationships were maintained, remaining within 3% of the original, but some smoothing occurred in the final computer manipulation. From routinely obtainable CT angiographic data, it is possible to create accurate replicas of human vascular pathology with the aid of commercially available stereolithography equipment. Visual analysis of the images appeared to be as important as the measurements. With 64 and 128 slice detector scanners becoming available, acquisition times fall enough that we should be able to model rapidly moving structures such as the aortic root.

Angiography↗

Leachate quality from landfilled MBT waste.

A research project recently completed on behalf of the UK Environment Agency, has collected data and sampled leachates from EU landfills that have received imports of MSOR and MBT wastes. Results are presented for sanitary analyses, heavy metals, and an extensive range of trace organic substances, from sites containing MBT wastes that have received different degrees of composting pre-treatment. Leachates produced from MSOR wastes have a very high polluting potential, but biological pre-treatment of these wastes can avoid the peak acetogenic phase of decomposition, and produce leachates similar to, or weaker than, those from conventional methanogenic landfills. Effective MBT processes can also significantly reduce concentrations of trace organics, and of ammoniacal-N in leachates. However, further research is needed to examine the relative importance of nitrification/denitrification processes, generation of stable, organically based nitrogen forms, and other routes during MBT processing, in order that appropriate reactions to remove nitrogen can be encouraged and optimised.

Biodegradation, Environmental↗

Multidisciplinary antimicrobial management and the role of the infectious diseases pharmacist--a UK perspective.

Improved clinical outcome, patient safety, cost savings and a reduction in the burden of antimicrobial resistance are outcomes associated with optimizing antimicrobial use. Despite this, the misuse of antimicrobials in the hospital setting remains a huge problem. The development of antimicrobial management teams and the promotion of the role of the clinical pharmacist in antimicrobial prescribing are recommended strategies for improving prescribing practice. It is recognized that there is a lack of published evidence-based research looking at the effects of antimicrobial control programmes and there is a need for more data. In the UK, the role of the hospital pharmacist in promoting responsible antimicrobial prescribing has been largely undervalued and needs to be encouraged and formalized in line with current directives. Managerial structures within hospitals need to endorse multidisciplinary antimicrobial management schemes with appropriate authoritative, administrative and information technology support.

Drug Resistance↗

The influence of psychosocial difficulties on women's attrition in an HIV/STD prevention program.

We examined attrition from an HIV/STD group counselling intervention in two ways: quantitative analyses of the entire sample (n=287) and structured interviews of a subset of 30 women with low attendance. In the interviews, the most common reasons for low attendance were time conflicts and enrolling primarily to obtain the monetary incentives given for completing research questionnaires. Latent class statistical analysis of the full sample identified two subgroups that differed from each other in the number of psychosocial problems recently experienced. Relative to the 'non-distressed' class, the 'distressed' class members had higher probabilities of psychological distress, low incomes, heavy substance use, sex for trade, relationship violence, and unstable housing. This group had higher HIV/STD risk, but lower intervention attendance. Members also had less education and less knowledge about HIV/STD. A higher proportion of the distressed group was African-American. Study findings suggest that in interventions for women at HIV/STD risk, it is not necessarily enough to ensure cultural relevance and to provide food, childcare, and transportation. To increase retention, interventionists should consider (1) the use of strategies to support attendance (such as monetary incentives and attention to group process factors) and (2) intervention formats that are brief, matched to participants' stage of change, population-specific, and/or maximally accessible.

Adolescent↗

Invasive pneumococcal disease in Oxford, 1985-2001: a retrospective case series.

AIMS: To describe a series of children with invasive pneumococcal disease (IPD). METHODS: A review of patient records for children aged 0-18 years admitted to the John Radcliffe Hospital with IPD from 1985 to 2001. Social deprivation was measured by the Jarman index. The proportion of children with congenital abnormalities was compared with national data. RESULTS: We identified 140 children with IPD; complete data were available for 136 children. The median age at diagnosis was 1.5 years. The social deprivation score of households of children with IPD was higher than that of the average Oxfordshire household (-2.5 v -7.3, p < 0.001). Forty four per cent of cases had at least one preceding health problem. The children with preceding health problems were significantly older than those with no preceding problems (median age 2.67 years, interquartile range 1.21 to 6.20 versus 1.11 years, interquartile range 0.51 to 2.21; p < 0.001). There was an increased risk of IPD for children with central nervous system malformations (OR = 99, 95% CI 31 to 236), congenital heart disease (OR = 62, 95% CI 24 to 131), and chromosomal abnormalities (OR = 32, 95% CI 6.6 to 96). CONCLUSIONS: There is an increased risk of IPD associated with increased social deprivation; and also with central nervous system malformations, congenital heart disease, and chromosomal abnormalities.

Adolescent↗

Serum alpha-tocopherol concentrations in German shepherd dogs with chronic degenerative radiculomyelopathy.

The concentration of serum alpha-tocopherol was measured in German shepherd dogs with chronic degenerative radiculomyopathy, and in German shepherd dogs and dogs of other breeds unaffected by the condition. The mean concentration was significantly higher in German shepherd dogs with the condition than in other breeds of dog unaffected by it, but it was not significantly higher than in unaffected German shepherd dogs. Estimates of components of variance indicated that the concentration varied more widely in individual affected dogs than in unaffected dogs, irrespective of breed. These results suggest that chronic degenerative radiculomyopathy in German shepherd dogs is unlikely to be due to uncomplicated vitamin E deficiency.

Animals↗

Predictive validity of the Strain Index in turkey processing.

The Strain Index is a job analysis method for determining if workers are exposed to increased risk of developing distal upper extremity disorders. Its predictive and external validity was initially demonstrated in a pork processing plant. The purpose of this study was to evaluate the predictive validity of the Strain Index in one turkey processing plant. While blinded to health outcomes, investigators analyzed the right and left sides of workers in 28 jobs using the Strain Index and classified them as "hazardous" or "safe" based on the Strain Index score. Subsequently, OSHA 200 logs were used to ascertain the occurrence of distal upper extremity disorders retrospectively. If at least one such disorder had occurred on the right or left side during the previous 3 years, that side was classified as "positive." If no such disorder was reported during the previous 3 years, that side was classified as "negative." When comparing sides, symmetry between morbidity and hazard classification was required. When comparing jobs, such symmetry was not required. Evidence of association between the hazard classifications and the morbidity classifications for the 56 sides and the 28 jobs was evaluated using 2 x 2 contingency tables. For the sides, the association between hazard classification and morbidity classification was statistically significant, with an odds ratio of 22.0. The sensitivity, specificity, positive predictive value, and negative predictive value were 0.86, 0.79, 0.92, and 0.65, respectively. Similar results were noted for the jobs--the odds ratio was 50.0, and the sensitivity, specificity, positive predictive value, and negative predictive value were 0.91, 0.83, 0.95, and 0.71. These results provide additional evidence of the external validity and predictive validity of the Strain Index.

Animals↗