4,554 research outputs found

    Eyewitness identification evidence: procedural developments and the ends of adjudicative accuracy

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    This article provides critical analysis of some of the more notable procedural developments relating to eyewitness identification evidence over the past decade

    An economic analysis of a pneumococcal vaccine programme in people aged over 64 years in a developed country setting.

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    BACKGROUND: Polysaccharide pneumococcal vaccination for older adults is being introduced in developed country settings. Evidence of protection by this vaccine against pneumococcal pneumonia, or confirmation that illness and death from bacteraemia are prevented, is currently limited. Decisions are often made based on partial information. We examined the policy implications by exploring the potential economic benefit to society and the health sector of pneumococcal vaccination in older adults. METHODS: A model to estimate the potential cost savings and cost-effectiveness of a polysaccharide pneumococcal vaccine programme was based on costs collected from patients, the literature, and routine health-services data. The effect of a pneumococcal vaccine (compared with no vaccination) was examined in a hypothetical cohort aged over 64 years. The duration of protection was assumed to be 10 years, with or without a booster at 5 years. RESULTS: If it were effective against morbidity from pneumococcal pneumonia, the main burden from pneumococcal disease, the vaccine could be cost-neutral to society or the health sector at low efficacy (28 and 37.5%, respectively, without boosting and with 70% coverage). If it were effective against morbidity from bacteraemia only, the vaccine's efficacy would need to be 75 and 89%, respectively. If protection against both morbidity and mortality from pneumococcal bacteraemia was 50%, the net cost to society would be 2500 pounds per year of life saved ( 3365 pounds from the health-sector perspective). Results were sensitive to incidence, case-fatality rates, and costs of illness. CONCLUSIONS: A vaccine with moderate efficacy against bacteraemic illness and death would be cost-effective. If it also protected against pneumonia, it would be cost-effective even if its efficacy were low

    Retrograde transport pathways utilised by viruses and protein toxins

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    A model has been presented for retrograde transport of certain toxins and viruses from the cell surface to the ER that suggests an obligatory interaction with a glycolipid receptor at the cell surface. Here we review studies on the ER trafficking cholera toxin, Shiga and Shiga-like toxins, Pseudomonas exotoxin A and ricin, and compare the retrograde routes followed by these protein toxins to those of the ER trafficking SV40 and polyoma viruses. We conclude that there is in fact no obligatory requirement for a glycolipid receptor, nor even with a protein receptor in a lipid-rich environment. Emerging data suggests instead that there is no common pathway utilised for retrograde transport by all of these pathogens, the choice of route being determined by the particular receptor utilised

    A cohort study of the effectiveness of influenza vaccine in older people, performed using the United Kingdom general practice research database.

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    BACKGROUND: The effectiveness of influenza vaccination against hospitalization and death can only ethically be assessed in observational studies. A concern is that individuals who are vaccinated are healthier than individuals who are not vaccinated, potentially biasing estimates of effectiveness upward. METHODS: We conducted a historical cohort study of individuals >64 years of age, for whom there were data available in the General Practice Research Database for 1989 to 1999 in England and Wales. Rates of admissions for acute respiratory diseases and rates of death due to respiratory disease were compared over 692,819 person-years in vaccine recipients and 1,534,280 person-years in vaccine nonrecipients. RESULTS: The pooled effectiveness of vaccine against hospitalizations for acute respiratory disease was 21% (95% confidence interval [CI], 17%-26%). The rate reduction attributable to vaccination was 4.15 hospitalizations/100,000 person-weeks in the influenza season. Among vaccine recipients, no important reduction in the number of admissions to the hospital was seen outside influenza seasons. The pooled effectiveness of vaccine against deaths due to respiratory disease was 12% (95% CI, 8%-16%). A greater proportionate reduction was seen among people without medical disorders, but absolute rate reduction was higher in individuals with medical disorders, compared with individuals without such disorders (6.14 deaths due to respiratory disease/100,000 person-weeks vs. 3.12 deaths due to respiratory disease/100,000 person-weeks). Clear protection against death due to all causes was not seen. CONCLUSIONS: Influenza vaccination reduces the number of hospitalizations and deaths due to respiratory disease, after correction for confounding in individuals >64 years of age who had a high risk or a low risk for influenza. For elderly people, untargeted influenza vaccination is of confirmed benefit against serious outcomes

    Admissibility Compared: The Reception of Incriminating Expert Evidence (i.e., Forensic Science) in Four Adversarial Jurisdictions

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    There is an epistemic crisis in many areas of forensic science. This crisis emerged largely in response both to the mobilization of a range of academic commentators and critics and the rise and influence of DNA typing. It gained popular and authoritative support through the influence of the National Academy of Science (NAS) and a surprisingly critical report produced under its auspices by a committee of the National Research Council (NRC). Interestingly, as this article endeavors to explain, the courts themselves seem to have played a rather indirect, inconsistent and ultimately ineffective role in the supervision and evaluation of forensic science evidence. Indeed, in the aftermath of recent criticism of the forensic sciences, this essay considers the effect of the dominant admissibility standards that operate in four common law jurisdictions. The revealing result seems to be that although admissibility standards vary across these jurisdictions, actual admissibility practices are remarkably consistent. In this article we will question the extent to which courts (and legal personnel) are able to meaningfully invigilate the use of forensic science evidence in criminal proceedings and consider some of the ideological commitments and institutional pressures that might lead judges in all jurisdictions to prefer inclusive approaches to incriminating expert opinions. In the first part of the article, we compare rules, jurisprudence and practices, across four jurisdictions: the United States, England and Wales, Canada, and Australia. All profoundly shaped by the English common law, these jurisdictions (and their sub- jurisdictions) tend to use a mixture of common law (e.g. England and Wales and Canada), judge-made rules (e.g. the U.S. Federal Rules of Evidence) and statutory schemes (e.g. the Australian Evidence Act 1995 Cth and many states in the United States) to regulate the admission of evidence, including expert opinion. These jurisdictions tend to maintain criminal trial processes that remain reasonably similar and facilitate broad brush comparisons. Our findings suggest that admissibility standards, including the first generation of reliability-based standards, seem to make little, if any, difference to (traditional) admissibility decision-making and practice. Allowing for some variation, the same sorts of forensic science evidence are admitted across all jurisdictions, even where the techniques are not demonstrably reliable and the jurisdiction in question has explicit reliability standards and other rules regulating the admission of expert opinion evidence. Moreover, it is our contention that the legal accommodation of the techniques considered in this article exemplifies a more general response to admissibility and the regulation of forensic science and medicine evidence. In the second part of the article we will consider possible explanations and some of the implications of our findings

    Genetic and environmental influences on eating behavior - a study of twin pairs reared apart or reared together

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    This study examined the relative influence of genetic versus environmental factors on specific aspects of eating behavior. Adult monozygotic twins (22 pairs and 3 singleton reared apart, 38 pairs and 9 singleton reared together, age 18-76 years, BMI 17-43 kg/m2) completed the Three Factor Eating Questionnaire. Genetic and environmental variance components were determined for the three eating behavior constructs and their subscales using model-fitting univariate and multivariate analyses. Unique environmental factors had a substantial influence on all eating behavior variables (explaining 45-71% of variance), and most strongly influenced external locus for hunger and strategic dieting behavior of restraint (explaining 71% and 69% of variance, respectively). Genetic factors had a statistically significant influence on only 4 variables: restraint, emotional susceptibility to disinhibition, situational susceptibility to disinhibition, and internal locus for hunger (heritabilities were 52%, 55%, 38% and 50%, respectively). Common environmental factors did not statistically significantly influence any variable assessed in this study. In addition, multivariate analyses showed that disinhibition and hunger share a common influence, while restraint appears to be a distinct construct. These findings suggest that the majority of variation in eating behavior variables is associated with unique environmental factors, and highlights the importance of the environment in facilitating specific eating behaviors that may promote excess weight gain.R01 AR046124 - NIAMS NIH HHS; R01 MH065322 - NIMH NIH HHS; T32 HL069772 - NHLBI NIH HHS; R37 DA018673 - NIDA NIH HHS; R01 DK073321 - NIDDK NIH HHS; R01 DA018673 - NIDA NIH HH

    Palmitoylation of Desmoglein 2 Is a Regulator of Assembly Dynamics and Protein Turnover.

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    Desmosomes are prominent adhesive junctions present between many epithelial cells as well as cardiomyocytes. The mechanisms controlling desmosome assembly and remodeling in epithelial and cardiac tissue are poorly understood. We recently identified protein palmitoylation as a mechanism regulating desmosome dynamics. In this study, we have focused on the palmitoylation of the desmosomal cadherin desmoglein-2 (Dsg2) and characterized the role that palmitoylation of Dsg2 plays in its localization and stability in cultured cells. We identified two cysteine residues in the juxtamembrane (intracellular anchor) domain of Dsg2 that, when mutated, eliminate its palmitoylation. These cysteine residues are conserved in all four desmoglein family members. Although mutant Dsg2 localizes to endogenous desmosomes, there is a significant delay in its incorporation into junctions, and the mutant is also present in a cytoplasmic pool. Triton X-100 solubility assays demonstrate that mutant Dsg2 is more soluble than wild-type protein. Interestingly, trafficking of the mutant Dsg2 to the cell surface was delayed, and a pool of the non-palmitoylated Dsg2 co-localized with lysosomal markers. Taken together, these data suggest that palmitoylation of Dsg2 regulates protein transport to the plasma membrane. Modulation of the palmitoylation status of desmosomal cadherins can affect desmosome dynamics

    Antibiotic dosing in the 'at risk' critically ill patient: Linking pathophysiology with pharmacokinetics/pharmacodynamics in sepsis and trauma patients

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    Background: Critical illness, mediated by trauma or sepsis, can lead to physiological changes that alter the pharmacokinetics of antibiotics and may result in sub-therapeutic concentrations at the sites of infection. The first aim of this project is to identify the clinical characteristics of critically ill patients with significant trauma that have been recently admitted to ICU that may predict the dosing requirements for the antibiotic, cefazolin. The second aim of this is to identify the clinical characteristics of critically ill patients with sepsis that may predict the dosing requirements for the combination antibiotic, piperacillin-tazobactam

    Exploring the costs and outcomes of sexually transmitted infection (STI) screening interventions targeting men in football club settings: preliminary cost-consequence analysis of the SPORTSMART pilot randomised controlled trial

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    Background: The objective of this study was to compare the costs and outcomes of two sexually transmitted infection (STI) screening interventions targeted at men in football club settings in England, including screening promoted by team captains. Methods: A comparison of costs and outcomes was undertaken alongside a pilot cluster randomised control trial involving three trial arms: (1) captain-led and poster STI screening promotion; (2) sexual health advisor-led and poster STI screening promotion and (3) poster-only STI screening promotion (control/comparator). For all study arms, resource use and cost data were collected prospectively. Results: There was considerable variation in uptake rates between clubs, but results were broadly comparable across study arms with 50% of men accepting the screening offer in the captain-led arm, 67% in the sexual health advisor-led arm and 61% in the poster-only control arm. The overall costs associated with the intervention arms were similar. The average cost per player tested was comparable, with the average cost per player tested for the captain-led promotion estimated to be £88.99 compared with £88.33 for the sexual health advisor-led promotion and £81.87 for the poster-only (control) arm. Conclusions: Costs and outcomes were similar across intervention arms. The target sample size was not achieved, and we found a greater than anticipated variability between clubs in the acceptability of screening, which limited our ability to estimate acceptability for intervention arms. Further evidence is needed about the public health benefits associated with screening interventions in non-clinical settings so that their cost-effectiveness can be fully evaluated
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