The sensory shark: high-quality morphological, genomic and transcriptomic data for the small-spotted catshark Scyliorhinus canicula reveal the molecular bases of sensory organ evolution in jawed vertebrates.

Cartilaginous fishes (chimaeras and elasmobranchs -sharks, skates and rays) hold a key phylogenetic position to explore the origin and diversifications of jawed vertebrates. Here, we report and integrate reference genomic, transcriptomic and morphological data in the small-spotted catshark Scyliorhinus canicula to shed light on the evolution of sensory organs. We first characterise general aspects of the catshark genome, confirming the high conservation of genome organisation across cartilaginous fishes, and investigate population genomic signatures. Taking advantage of a dense sampling of transcriptomic data, we also identify gene signatures for all major organs, including chondrichthyan specializations, and evaluate expression diversifications between paralogs within major gene families involved in sensory functions. Finally, we combine these data with 3D synchrotron imaging and in situ gene expression analyses to explore chondrichthyan-specific traits and more general evolutionary trends of sensory systems. This approach brings to light, among others, novel markers of the ampullae of Lorenzini electro-sensory cells, a duplication hotspot for crystallin genes conserved in jawed vertebrates, and a new metazoan clade of the Transient-receptor potential (TRP) family. These resources and results, obtained in an experimentally tractable chondrichthyan model, open new avenues to integrate multiomics analyses for the study of elasmobranchs and jawed vertebrates.

Cardiac 123I-MIBG normal uptake values are population-specific: Results from a cohort of controls over 60 years of age.

PURPOSE: Cardiac 123I-MIBG image interpretation is affected by population differences and technical factors. We recruited older adults without cognitive decline and compared their cardiac MIBG uptake with results from the literature. METHODS: Phantom calibration confirmed that cardiac uptake results from Japan could be applied to our center. We recruited 31 controls, 17 individuals with dementia with Lewy bodies (DLB) and 15 with Alzheimer's disease (AD). Images were acquired 20 minutes and four hours after injection using Siemens cameras with medium-energy low-penetration (MELP) collimators. Local normal heart-to-mediastinum (HMR) ratios were compared to Japanese results. RESULTS: Siemens gamma cameras with MELP collimators should give HMRs very close to the calibrated values used in Japan. However, our cut-offs with controls were lower at 2.07 for early and 1.86 for delayed images. Applying our lower cut-off to the dementia patients may increase the specificity of cardiac MIBG imaging for DLB diagnosis in a UK population without reducing sensitivity. CONCLUSIONS: Our local HMR cut-off values are lower than in Japan, higher than in a large US study but similar to those found in another UK center. UK centers using other cameras and collimators may need to use different cut-offs to apply our results.

The allocation of resources for animal health.

Economics is too important to be left to the experts. This paper is therefore mainly for animal health policy-makers who are not economists but want a better appreciation of how economics can contribute to resource allocation decisions. First, the methodology of economic analysis is outlined with the objective of dispelling criticisms of its simplifying assumption of rationality. Then, unusual in economics but more familiar to biological and veterinary scientists, the technical aspects of transforming resources into products are discussed. Economics' unique contribution is to establish criteria enabling society to obtain maximum value from the production and distribution of goods and services (products) from scarce resources. Animal disease reduces the efficiency of this process. Value is intangible, but people reveal how much they value (i.e. feel a want or need for) products by what they actually consume, in quality and quantity. Animal products, and so implicitly animals themselves, are an example. The strength of people's preferences is reflected both in the prices they pay for market goods and services, and by their political votes where markets do not exist. Importantly, there is a difference between financial value (what the consumer pays for a good or service) and economic value (the maximum amount of money they would be prepared to pay for it). Allocating resources for animal health creates both costs and benefits, financial and economic. Moreover, costs and benefits are both private and social because of externalities, a major consideration in infectious diseases. Where production decisions with animal health implications are made exclusively for private benefit, government has a role in providing incentives for animal sectors to act in ways that result in socially efficient outcomes.

L'économie est trop importante pour être laissée entre les seules mains des experts. C'est pourquoi cet article s'adresse principalement aux responsables des politiques de santé animale qui ne sont pas économistes mais qui souhaitent néanmoins évaluer l'apport de l'économie aux décisions relatives à l'affectation des ressources. L'auteur commence par rappeler la méthodologie de l'analyse économique afin de réfuter les critiques sur le caractère supposément simplificateur du postulat de rationalité. Il examine ensuite les aspects techniques liés à la transformation de ressources en produits, concept familier pour les biologistes et les chercheurs en médecine vétérinaire mais moins courant chez les économistes. La véritable contribution de l'économie consiste à déterminer les critères qui permettent à une société de valoriser le plus possible la production et la distribution de biens et de services (produits) à partir de ressources limitées. Les maladies animales compromettent l'efficacité de ce processus. La valeur est intangible par nature mais les individus expriment la valeur qu'ils attachent à un produit (c'est-à-dire le désir ou le besoin qu'ils ont de ce produit) à travers leur consommation, au plan qualitatif et quantitatif. Les produits d'origine animale et partant, implicitement, les animaux eux-mêmes illustrent parfaitement ce phénomène. L'influence des préférences des individus se manifeste par le prix qu'ils sont disposés à payer pour les biens et les services pour lesquels il existe un marché, et par le vote politique pour tout ce qui est extérieur au marché. La distinction entre la valeur financière (prix payé par le consommateur pour un bien ou un service) et la valeur économique (le montant le plus élevé qu'il serait disposé à payer pour ce même bien ou service) est un aspect important. Les ressources allouées à la santé animale génèrent à la fois des coûts et des bénéfices, financiers et économiques. De plus, du fait des externalités, ces coûts et bénéfices sont de nature tant privée que sociale, facteur essentiel à prendre en compte pour les maladies infectieuses. Dans les situations où les décisions en matière de production animale obéissent aux seuls impératifs du profit privé, sans tenir compte des répercussions sur la santé animale, les gouvernements ont un rôle incitatif à jouer pour que le secteur de l'élevage infléchisse son action en vue de résultats efficients pour la société.

La economía es demasiado importante para abandonarla a los expertos. Por ello este artículo va dirigido sobre todo a los planificadores de políticas zoosanitarias que no son economistas pero desean tener una idea más clara de cómo puede ayudar la economía a tomar decisiones sobre la asignación de los recursos. Ante todo el autor presenta sucintamente la metodología del análisis económico, a fin de refutar las críticas que achacan una excesiva simplificación al postulado de la racionalidad. Después aborda algo inusual en economía, pero más familiar para biólogos y veterinarios: los aspectos técnicos de la transformación de los recursos en productos. La singular aportación de la economía estriba en definir criterios que permiten a la sociedad extraer el máximo «valor¼ de la producción y distribución de bienes y servicios (productos) a partir de recursos escasos. Las enfermedades animales restan eficiencia a este proceso. El «valor¼ es algo intangible, pero las personas revelan cuánto valoran un producto (es decir, hasta qué punto sienten que lo desean o lo necesitan) por lo que en la práctica consumen, tanto cualitativa como cuantitativamente. Los productos animales, y por ende, implícitamente, los propios animales, son ejemplo de ello. La fuerza de las preferencias de la gente se manifiesta en el precio que paga por bienes y servicios, cuando hay un mercado para ellos, o por su voto político, cuando no lo hay. Es importante señalar que hay una diferencia entre el valor monetario (lo que pagan los consumidores por un bien o servicio) y el valor económico (la cantidad máxima de dinero que estarían dispuestos a pagar por él). La forma en que se distribuyen los recursos en sanidad animal genera costos y beneficios, tanto monetarios como económicos. Además, esos costos y beneficios son tanto privados como sociales debido a la existencia de externalidades, factor este de gran importancia en el caso de las enfermedades infecciosas. Allí donde las decisiones de producción que tienen consecuencias zoosanitarias se rijan únicamente por el criterio del beneficio privado, las administraciones públicas deben cumplir la función de ofrecer incentivos a los sectores ligados a la producción animal para que su proceder se traduzca en resultados socialmente eficientes.

A Framework for Categorization of the Economic Impacts of Outbreaks of Highly Contagious Livestock Diseases.

A framework for categorization of economic impacts of outbreaks of highly contagious livestock diseases (HCLD) is presented. This framework interprets veterinary measures to control HCLD outbreaks with reference to economic definitions of costs and benefits, and the implications for value losses both for different stakeholders affected and society as a whole. Four cost categories are identified, that is virus control-related direct costs (DC), spread prevention and zoning-related direct consequential costs (DCC), market and price disruption-related costs during (indirect consequential costs, ICC) and after the outbreak (aftermath costs, AC). The framework is used to review existing literature on cost estimation for different stakeholders. This review shows considerable differences between studies, making comparison of results difficult and susceptible to misunderstanding. It is concluded that the framework provides a logical basis for all future analyses of the economic impacts of HCLD.

Identification of a role for a mouse sperm surface aldo-keto reductase (AKR1B7) and its human analogue in the detoxification of the reactive aldehyde, acrolein.

Mouse vas deferens protein (AKR1B7), a member of the aldo-keto reductase family, was purified to homogeneity. Antibodies raised to AKR1B7 revealed an aldo-keto reductase on the human sperm surface, while confocal microscopy experiments demonstrated that this enzyme covered the entire human sperm surface and was concentrated on the mid-piece. Further functional characterisation of a recombinant form of AKR1B7 showed that the likely role of AKR1B7 is the reduction of the reactive aldehyde, acrolein, a by-product of spermine catabolism in the reproductive tract. A similar acrolein detoxification activity was displayed by human sperm membrane extracts but was not present in seminal plasma. These results indicate that human sperm possess an aldo-keto reductase on their membrane surface and are thus enzymatically protected against reactive aldehyde species both in the male and female reproductive tract.

Economic principles for resource allocation decisions at national level to mitigate the effects of disease in farm animal populations.

This paper originated in a project to develop a practical, generic tool for the economic evaluation of surveillance for farm animal diseases at national level by a state veterinary service. Fundamental to that process is integration of epidemiological and economic perspectives. Using a generalized example of epidemic disease, we show that an epidemic curve maps into its economic equivalent, a disease mitigation function, that traces the relationship between value losses avoided and mitigation resources expended. Crucially, elementary economic principles show that mitigation, defined as loss reduction achieved by surveillance and intervention, must be explicitly conceptualized as a three-variable process, and the relative contributions of surveillance and intervention resources investigated with regard to the substitution possibilities between them. Modelling the resultant mitigation surfaces for different diseases should become a standard approach to animal health policy analysis for economic efficiency, a contribution to the evolving agenda for animal health economics research.

Lack of T-cell responses following autologous tumour lysate pulsed dendritic cell vaccination, in patients with relapsed osteosarcoma.

BACKGROUND: Immunotherapy using autologous dendritic cell (DC) vaccination has not been systematically evaluated in osteosarcoma. We therefore conducted a phase I trial to assess feasibility, safety and tumour-specific immune responses in patients with relapsed disease. PATIENTS AND METHODS: Of 13 recruited patients with relapsed osteosarcoma, 12 received 3 weekly vaccines of autologous DCs matured with autologous tumour lysate and keyhole limpet haemocyanin (KLH), to a maximum of 6 vaccinations. An additional 3 paediatric patients afflicted with other tumour types and with relapsed disease received vaccines generated with identical methodology. Immune responses were assessed using an ELISpot assay for the detection of interferon gamma, whilst interleukin-2 and granzyme B were additionally assessed in cases where interferon-γ responses were induced. RESULTS: In total 61 vaccines, of homogeneous maturation phenotype and viability, were administered with no significant toxicity. Only in 2 out of 12 treated osteosarcoma cases was there an induction of specific T-cell immune response to the tumour, whilst a strong but non-specific immune response was induced in 1 further osteosarcoma patient. Immune response against KLH was induced in only 3 out of 12 osteosarcoma patients. In contrast, three additional non-osteosarcoma patients showed significant T-cell responses to vaccine. CONCLUSION: We have shown the strategy of DC vaccination in relapsed osteosarcoma is safe and feasible. However, significant anti-tumour responses were induced in only 2 out of 12 vaccinated patients with no evidence of clinical benefit. Comparison of results with identically treated control patients suggests that osteosarcoma patients might be relatively insensitive to DC-based vaccine treatments.

An economic model to evaluate the mitigation programme for bovine viral diarrhoea in Switzerland.

Economic analyses are indispensable as sources of information to help policy makers make decisions about mitigation resource use. The aim of this study was to conduct an economic evaluation of the Swiss national mitigation programme for bovine viral diarrhoea virus (BVDV), which was implemented in 2008 and concludes in 2017. The eradication phase of the mitigation programme comprised testing and slaughtering of all persistently infected (PI) animals found. First, the whole population was antigen tested and all PI cattle removed. Since October 2008, all newborn calves have been subject to antigen testing to identify and slaughter PI calves. All mothers of PI calves were retested and slaughtered if the test was positive. Antigen testing in calves and elimination of virus-carriers was envisaged to be conducted until the end of 2011. Subsequently, a surveillance programme will document disease freedom or detect disease if it recurs. Four alternative surveillance strategies based on antibody testing in blood from newborn calves and/or milk from primiparous cows were proposed by Federal Veterinary Office servants in charge of the BVDV mitigation programme. A simple economic spreadsheet model was developed to estimate and compare the costs and benefits of the BVDV mitigation programme. In an independent project, the impact of the mitigation programme on the disease dynamics in the population was simulated using a stochastic compartment model. Mitigation costs accrued from materials, labour, and processes such as handling and testing samples, and recording results. Benefits were disease costs avoided by having the mitigation programme in place compared to a baseline of endemic disease equilibrium. Cumulative eradication costs and benefits were estimated to determine the break-even point for the eradication component of the programme. The margin over eradication cost therefore equalled the maximum expenditure potentially available for surveillance without the net benefit from the mitigation programme overall becoming zero. Costs of the four surveillance strategies and the net benefit of the mitigation programme were estimated. Simulations were run for the years 2008-2017 with 20,000 iterations in @Risk for Excel. The mean baseline disease costs were estimated to be 16.04 m CHF (1 Swiss Franc, CHF=0.73 € at the time of analysis) (90% central range, CR: 14.71-17.39 m CHF) in 2008 and 14.89 m CHF (90% CR: 13.72-16.08 m CHF) in 2009. The break-even point was estimated to be reached in 2012 and the margin over eradication cost 63.15m CHF (90% CR: 53.72-72.82 m CHF). The discounted cost for each surveillance strategy was found to be smaller than the margin, so the mitigation programme overall is expected to have a positive net economic benefit irrespective of the strategy adopted. For economic efficiency, the least cost surveillance alternative must be selected.

A qualitative approach to measure the effectiveness of active avian influenza virus surveillance with respect to its cost: a case study from Switzerland.

The aim of the project was to apply cost-effectiveness analysis to the economic appraisal of avian influenza virus (AIV) surveillance, using the implemented surveillance programme in Switzerland as a case study. First a qualitative risk assessment approach was used to assess the expected impact of surveillance on the transmission and spread of AIV. The effectiveness of surveillance was expressed as the difference in defined probabilities between a scenario with surveillance and a scenario without surveillance. The following probabilities were modelled (i) transmission of highly pathogenic AIV (HPAIV) from wild birds to poultry, (ii) mutation from low pathogenic AIV (LPAIV) into HPAIV in poultry, and (iii) transmission of HPAIV to other poultry holdings given a primary outbreak. The cost-effectiveness ratio was defined conventionally as the difference in surveillance costs (ΔC) divided by the change in probability (ΔP), the technical objective, on the presumption that surveillance diminishes the respective probabilities. However, results indicated that surveillance in both wild birds and poultry was not expected to change the probabilities of primary and secondary AIV outbreaks in Switzerland. The overall surveillance costs incurred were estimated at 31,000 €/year, which, to be a rational investment of resources, must still reflect the value policy makers attribute to other benefits from having surveillance (e.g. peace of mind). The advantage of the approach adopted is that it is practical, transparent, and thus able to clarify for policy makers the key variables to be taken into account when evaluating the economic efficiency of resources invested in surveillance, prevention and intervention to exclude AIV.

Economic evaluation of the surveillance and intervention programme for bluetongue virus serotype 8 in Switzerland.

Empirical analyses founded on sound economic principles are essential in advising policy makers on the efficiency of resource use for disease mitigation. Surveillance and intervention are resource-using activities directed at mitigation. Surveillance helps to offset negative disease effects by promoting successful intervention. Intervention is the process of implementing measures (e.g. vaccination or medication) to reduce or remove a hazard in a population. The scale and ratios in which the two are combined affect the efficiency of mitigation, its costs, benefits, and thus net effect on society's well-being. The Swiss national mitigation programme for bluetongue virus serotype 8 was used as case study to investigate the economic efficiency of mitigation. In 2008, Switzerland implemented a vaccination programme to avoid and reduce disease and infection in its ruminant population. To monitor the vaccination programme and the vector dynamics, a surveillance system consisting of serological and entomological surveillance was established. Retrospective analyses for the years 2008-2009 and prospective analyses for the years 2010-2012 were conducted to investigate if the mitigation programme was economically beneficial. In the retrospective analysis, the implemented programme (=comparative scenario) was compared to a hypothesised baseline scenario of voluntary vaccination and surveillance. In the prospective analysis, the comparative scenario assumed to continue was compared to two baseline scenarios: one of voluntary vaccination combined with surveillance and one of no vaccination combined with surveillance. For each scenario, monetary surveillance, intervention and disease costs were calculated. The comparison of baseline and comparative scenarios yielded estimates for the total benefit (=disease costs avoided), margin over intervention cost and the net value of the programme. For 2008-2009, in aggregate, the mean biannual total benefit was 17.46 m Swiss francs (CHF) (1CHF=0.66€ at the time of analysis) and the mean net benefit after subtraction of the intervention and surveillance cost was 3.95 m CHF. For the three years 2010-2012, overall net costs were estimated at 12.93 m and 8.11 m CHF, respectively, for comparison of the implemented mitigation programme with the two baseline scenarios. It was concluded that the surveillance and intervention programme implemented in 2008-2009 was economically beneficial, while its continuation in the same form in 2010-2012 would produce net costs. These costs were due to the mean intervention cost remaining constant at a level of approximately 11 m CHF per year while the mean total benefit would be gradually reduced in 2010-2012 due to the reduced occurrence of disease in a fully vaccinated population.

Evaluation of enrichment media for improved PCR-based detection of V. cholerae and V. vulnificus from estuarine water and plankton.

AIMS: Pathogenic Vibrio spp., including V. cholerae and V. vulnificus, are commonly found along the estuaries of the south-east United States; however, it is often difficult to recover these species directly from environmental samples. Pre-enrichment assays are commonly used to improve the detection of pathogenic vibrios from environmental sources. Here, we evaluated a novel enrichment procedure using freshly collected and autoclaved natural estuarine water amended with 1% peptone (designated as estuarine peptone water, EPW) and compared it to traditional alkaline peptone water (APW) for detection by PCR of V. cholerae and V. vulnificus. METHODS AND RESULTS: Of the 50 samples collected in total, V. cholerae DNA was detected in APW 10% of the time and in EPW 40% of the time. Likewise, the cholera toxin gene (ctxA) was detected in 4 vs 18% of the samples using APW and EPW, respectively. Conversely, APW showed improved recovery for V. vulnificus relative to EPW with respective detection frequencies of 46 and 20%. Results showed similar patterns across different sample types (water and plankton). CONCLUSIONS: While enrichment in traditional APW was adequate for the recovery of Vibrio vulnificius, use of sterile estuarine water amended with peptone significantly improved the detection of V. cholerae and the virulence gene ctxA from estuarine sources.

The effects of low dose parathyroid hormone on lumbar vertebrae in a rat model for chronic alcohol abuse.

UNLABELLED: This study evaluated the hypothesis that increased bone marrow adipogenesis is coupled to decreased bone formation in rats consuming alcohol. Parathyroid hormone (PTH) increased bone formation but had no effect on marrow adiposity. We conclude that increased adiposity does not prevent the bone anabolic response to PTH. INTRODUCTION: Alcoholism results in decreased bone formation and increased bone marrow adiposity. The present study tested the hypothesis that these reciprocal changes are coupled by evaluating the effect of intermittent PTH on bone formation and bone marrow adiposity in a rat model for chronic alcohol abuse. METHODS: Three-month-old male Sprague Dawley rats (n = 10-11/group) were fed the Lieber-DeCarli liquid diet with 35% of the calories derived from ethanol. Control rats were pair-fed an isocaloric alcohol-free diet. The rats were administered low dose PTH (1 µg/kg/day sc, 5 d/week) or vehicle for 6 weeks. Cancellous bone architecture in lumbar vertebrae was evaluated by micro-computed tomography followed by histomorphometric assessment of bone formation and marrow adiposity. RESULTS: Alcohol increased bone marrow adiposity but reduced bone formation. The latter was due to decreases in mineralizing perimeter/bone perimeter, a surrogate measure of osteoblast number, and mineral apposition rate, a measure of osteoblast activity. PTH increased bone formation by increasing mineralizing perimeter/bone perimeter. In contrast, PTH had no effect on mineral apposition rate or bone marrow adiposity. Interactions between alcohol consumption and PTH treatment were not detected for any endpoints evaluated. CONCLUSIONS: PTH treatment blunted the decrease in mineralizing perimeter/bone perimeter in alcohol-fed rats but was ineffective in preventing the increase in bone marrow adiposity. These findings suggest that the alcohol-induced increase in adipocytes is not directly responsible for the accompanying reduction in bone formation.

Genetics coupled to quantitative intact proteomics links heritable aphid and endosymbiont protein expression to circulative polerovirus transmission.

Yellow dwarf viruses in the family Luteoviridae, which are the causal agents of yellow dwarf disease in cereal crops, are each transmitted most efficiently by different species of aphids in a circulative manner that requires the virus to interact with a multitude of aphid proteins. Aphid proteins differentially expressed in F2 Schizaphis graminum genotypes segregating for the ability to transmit Cereal yellow dwarf virus-RPV (CYDV-RPV) were identified using two-dimensional difference gel electrophoresis (DIGE) coupled to either matrix-assisted laser desorption ionization-tandem mass spectrometry or online nanoscale liquid chromatography coupled to electrospray tandem mass spectrometry. A total of 50 protein spots, containing aphid proteins and proteins from the aphid's obligate and maternally inherited bacterial endosymbiont, Buchnera, were identified as differentially expressed between transmission-competent and refractive aphids. Surprisingly, in virus transmission-competent F2 genotypes, the isoelectric points of the Buchnera proteins did not match those in the maternal Buchnera proteome as expected, but instead they aligned with the Buchnera proteome of the transmission-competent paternal parent. Among the aphid proteins identified, many were involved in energy metabolism, membrane trafficking, lipid signaling, and the cytoskeleton. At least eight aphid proteins were expressed as heritable, isoelectric point isoform pairs, one derived from each parental lineage. In the F2 genotypes, the expression of aphid protein isoforms derived from the competent parental lineage aligned with the virus transmission phenotype with high precision. Thus, these isoforms are candidate biomarkers for CYDV-RPV transmission in S. graminum. Our combined genetic and DIGE approach also made it possible to predict where several of the proteins may be expressed in refractive aphids with different barriers to transmission. Twelve proteins were predicted to act in the hindgut of the aphid, while six proteins were predicted to be associated with the accessory salivary glands or hemolymph. Knowledge of the proteins that regulate virus transmission and their predicted locations will aid in understanding the biochemical mechanisms regulating circulative virus transmission in aphids, as well as in identifying new targets to block transmission.

Tangible benefits of the aphid Acyrthosiphon pisum genome sequencing for aphid proteomics: Enhancements in protein identification and data validation for homology-based proteomics.

Homology-driven proteomics promises to reveal functional biology in insects with sparse genome sequence information. A proteomics study comparing plant virus transmission competent and refractive genotypes of the aphid Schizaphis graminum isolated numerous candidate proteins involved in virus transmission, but limited genome sequence information hampered their identification. The complete genome of the pea aphid, Acyrthosiphon pisum, released in 2008, enabled us to double the number of protein identifications beyond what was possible using available EST libraries and other insect sequences. This was concomitant with a dramatic increase of the number of MS and MS/MS peptide spectra matching the genome-derived protein sequence. LC-MS/MS proved to be the most robust method of peptide detection. Cross-matching spectral data to multiple EST sequences and error tolerant searching to identify amino acid substitutions enhanced the percent coverage of the Schizaphis graminum proteins. 2-D electrophoresis provided the protein pI and MW which enabled the refinement of the candidate protein selection and provided a measure of protein abundance when coupled to the spectral data. Thus, the homology-based proteomics pipeline for insects should include efforts to maximize the number of peptide matches to the protein to increase certainty in protein identification and relative protein abundance.

Histologically confirmed hippocampal structural features revealed by 3T MR imaging: potential to increase diagnostic specificity of mesial temporal sclerosis.

BACKGROUND AND PURPOSE: With appropriate selection, temporal lobe epilepsy is potentially curable with surgical intervention achieving seizure freedom in ~80% of individuals. MR imaging-based identification of MTS remains central to the selection process but currently relies on qualitative visual analysis. We sought to determine if new ultrastructural hippocampal details seen on 3T MR imaging had histopathologic correlates and whether these could serve as a useful tool in MTS identification. MATERIALS AND METHODS: Patients undergoing selective anterior temporal lobectomy (n = 5) were scanned using 3T MR imaging preoperatively. En bloc resections were rescanned and subsequently prepared for histopathologic analysis of all hippocampal layers in the CA1-3 regions. Using a newly identified landmark from 3T FSTIR coronal images in 20 patients with histologically confirmed MTS, blinded studies compared ipsilateral and contralateral sides to generate threshold measurements for application in a fast quantitative analysis tool. RESULTS: Histopathologic analysis and correlation with 3T imaging of en bloc resections identified the low-intensity signal as the stratum lacunosum. MTS was associated with extensive gliosis throughout the CA1-3 regions, with loss of tissue thickness in the stratum pyramidale most pronounced in CA1. Fast quantitative analysis by using the stratum lacunosum as a landmark provided a test that identifies MTS with a SN of 70% and SP of 85%. CONCLUSIONS: Here we delineated ultrastructural hippocampal details seen on 3T MR imaging in both the in vivo and ex vivo setting, correlating these with histopathologic features consistent with MTS, and provided preliminary data suggesting their utility in the development of a quantitative analysis assessment tool for application in surgical-candidate selection.

Alcohol alters whole body composition, inhibits bone formation, and increases bone marrow adiposity in rats.

UNLABELLED: Chronic alcohol abuse is a risk factor for osteoporosis and sarcopenia, but the long-term effects of alcohol on the immature musculoskeletal system are less clear. The present investigation in growing rats was designed to determine the effects of alcohol consumption on body composition, muscle mass, and bone mass, architecture, and turnover. INTRODUCTION: Few studies have focused on the long-term effects of drinking on bone and muscle during skeletal maturation. METHODS: Alcohol was included in the diet of 4-week-old male Sprague-Dawley rats (35% caloric intake) for 3 months. The controls were fed an isocaloric alcohol-free liquid diet ad libitum. A second study was performed in which the controls were pair-fed to the alcohol-fed animals. RESULTS: Compared to ad libitum-fed age-matched controls, alcohol-fed rats weighed less and had lower lean mass, fat mass, and percent body fat. In addition, they had lower slow- and fast-twitch muscle mass, lower total body bone mineral content and bone mineral density, and lower cancellous bone volume in the lumbar vertebra and proximal tibia. The effects of alcohol consumption on body composition were reduced when compared to the pair-fed control diet, indicating that caloric restriction was a comorbidity factor. In contrast, the effects of alcohol to decrease bone formation and serum leptin and IGF-I levels and to increase bone marrow adiposity appeared independent of caloric restriction. CONCLUSIONS: The skeletal abnormalities in growing alcohol-fed rats were due to a combination of effects specific to alcohol consumption and alcohol-induced caloric restriction.

Ensembl 2009.

The Ensembl project (http://www.ensembl.org) is a comprehensive genome information system featuring an integrated set of genome annotation, databases, and other information for chordate, selected model organism and disease vector genomes. As of release 51 (November 2008), Ensembl fully supports 45 species, and three additional species have preliminary support. New species in the past year include orangutan and six additional low coverage mammalian genomes. Major additions and improvements to Ensembl since our previous report include a major redesign of our website; generation of multiple genome alignments and ancestral sequences using the new Enredo-Pecan-Ortheus pipeline and development of our software infrastructure, particularly to support the Ensembl Genomes project (http://www.ensemblgenomes.org/).

Control of a hospital-wide vancomycin-resistant Enterococci outbreak.

BACKGROUND: To analyze control measures used to eradicate a large vancomycin-resistant Enterococci (VRE) outbreak in a nonendemic 1600-bed tertiary care institution. METHODS: In mid-March 2005, VRE Van B was isolated from 2 clinical samples from different wards. Despite such measures as screening patients sharing rooms with index cases and isolating VRE patients, 43 isolates from different wards were detected by the end of March 2005. To eradicate a hospital-wide outbreak, a coordinated strategy between March and June 2005 comprised (1) formation of a VRE task force, (2) hospital-wide screening, (3) isolation of carriers, (4) physical segregation of contacts, (5) surveillance of high-risk groups, (6) increased cleaning, (7) electronic tagging of VRE status, and (8) education and audits. This is a retrospective study of this multipronged approach to containing VRE. The adequacy of rectal swab sampling for VRE was assessed in a substudy of 111 patients. The prevalence of methicillin-resistant Staphylococcus aureus (MRSA)/VRE co-colonization or co-infection also was determined. RESULTS: A total of 19,574 contacts were identified. Between April and June 2005, 5095 patients were screened, yielding 104 VRE carriers, 54 of whom (52%) were detected in the first 2 weeks of hospital-wide screening. The initial positive yield of 11.4% of persons actively screened declined to 4.2% by the end of June 2005. Pulsed-field typing revealed 1 major clone and several minor clones among the 151 total VRE cases, including 4 clinical cases. Hospital-wide physical segregation of contacts from other patients was difficult to achieve in communal wards. Co-colonization or co-infection with MRSA, which was present in 52 of 151 cases (34%) and the indefinite electronic tagging of positive VRE status strained limited isolation beds. Analysis of 2 fecal or rectal specimens collected 1 day apart may detect at least 83% of VRE carriers. CONCLUSION: A multipronged strategy orchestrated by a central task force curbed but could not eradicate VRE. Control measures were confounded by hospital infrastructure and high MRSA endemicity.

Ensembl 2008.

The Ensembl project (http://www.ensembl.org) is a comprehensive genome information system featuring an integrated set of genome annotation, databases and other information for chordate and selected model organism and disease vector genomes. As of release 47 (October 2007), Ensembl fully supports 35 species, with preliminary support for six additional species. New species in the past year include platypus and horse. Major additions and improvements to Ensembl since our previous report include extensive support for functional genomics data in the form of a specialized functional genomics database, genome-wide maps of protein-DNA interactions and the Ensembl regulatory build; support for customization of the Ensembl web interface through the addition of user accounts and user groups; and increased support for genome resequencing. We have also introduced new comparative genomics-based data mining options and report on the continued development of our software infrastructure.

The vertebrate genome annotation (Vega) database.

The Vertebrate Genome Annotation (Vega) database (http://vega.sanger.ac.uk) was first made public in 2004 and has been designed to view manual annotation of human, mouse and zebrafish genomic sequences produced at the Wellcome Trust Sanger Institute. Since its initial release, the number of human annotated loci has more than doubled to close to 33 000 and now contains comprehensive annotation on 20 of the 24 human chromosomes, four whole mouse chromosomes and around 40% of the zebrafish Danio rerio genome. In addition, we offer manual annotation of a number of haplotype regions in mouse and human and regions of comparative interest in pig and dog that are unique to Vega.