Oral anticoagulants for nonvalvular atrial fibrillation in frail elderly patients: insights from the ARISTOPHANES study.

BACKGROUND: Patient frailty amongst patients with nonvalvular atrial fibrillation (NVAF) is associated with adverse health outcomes and increased risk of mortality. Additional evidence is needed to evaluate effective and safe NVAF treatment in this patient population. OBJECTIVES: This subgroup analysis of the ARISTOPHANES study compared the risk of stroke/systemic embolism (S/SE) and major bleeding (MB) amongst frail NVAF patients prescribed nonvitamin K antagonist oral anticoagulants (NOACs) or warfarin. METHODS: This comparative retrospective observational study of frail, older NVAF patients who initiated apixaban, dabigatran, rivaroxaban or warfarin from 01JAN2013-30SEP2015 was conducted using Medicare and 3 US commercial claims databases. To compare each drug, 6 propensity score-matched (PSM) cohorts were created. Patient cohorts were pooled from 4 databases after PSM. Cox models were used to estimate hazard ratios (HR) of S/SE and MB. RESULTS: Amongst NVAF patients, 34% (N = 150 487) met frailty criteria. Apixaban and rivaroxaban were associated with a lower risk of S/SE vs warfarin (apixaban: HR: 0.61, 95% CI: 0.55-0.69; rivaroxaban: HR: 0.79, 95% CI: 0.72-0.87). For MB, apixaban (HR: 0.62, 95% CI: 0.57-0.66) and dabigatran (HR: 0.79, 95% CI: 0.70-0.89) were associated with a lower risk and rivaroxaban (HR: 1.14, 95% CI: 1.08-1.21) was associated with a higher risk vs warfarin. CONCLUSION: Amongst this cohort of frail NVAF patients, NOACs were associated with varying rates of stroke/SE and MB compared with warfarin. Due to the lack of real-world data regarding OAC treatment in frail patients, these results may inform clinical practice in the treatment of this patient population.

Management and biosecurity practices by small to medium egg producers in Scotland.

1. Information about procedures and biosecurity practices used by small and medium egg producers (SMEPs) is scarce. Anecdotal evidence suggests that biosecurity in such enterprises may be poor, as personnel and equipment move freely between sites and this may be compounded by personnel working on commercial units who keep their own poultry.2. To fill this knowledge gap, a questionnaire was designed and implemented targeting SMEPs in Scotland. Small enterprises were defined as egg producers that have ≥50 laying hens but <350 laying hens; while medium enterprises were defined as egg producers that have ≥350 laying hens but ≤32 000 laying hens. The questionnaire consisted of a total of 56 questions divided into multiple sections, covering the characteristics of the primary keeper, location of the enterprise and size of the flocks, husbandry, marketing of products and health/biosecurity.3. The questionnaire was posted to 375 holdings at the beginning of March 2017 and the survey remained open until the end of May 2017. In total 90 questionnaires were received by the cut-off date of which 76 questionnaires were from SMEPs. Forty were small enterprises and 36 were medium enterprises. For three questionnaires, it was not possible to identify the enterprise type.4. Differences were observed between SMEPs in terms of reported biosecurity and management practices, with medium enterprises reporting the adoption of more biosecurity measures than small enterprises. Furthermore, SMEPs behave differently from backyard poultry keepers and large commercial companies in terms of disease risk.5. In conclusion, it is important to ensure that SMEPs are considered in contingency plans and disease control programmes and that engagement with them is promoted so that the uptake of relevant information, such as awareness of disease control programmes, is optimised.

AOtools: a Python package for adaptive optics modelling and analysis.

AOtools is a Python package that is open-source and aimed at providing tools for adaptive optics users and researchers. We present version 1.0, which contains tools for adaptive optics processing, including analysing data in the pupil plane, images and point spread functions in the focal plane, wavefront sensors, modelling of atmospheric turbulence, physical optical propagation of wavefronts, and conversion between frequently used adaptive optics and astronomical units. The main drivers behind AOtools is that it should be easy to install and use. To achieve this the project features extensive documentation, automated unit testing and is registered on the Python Package Index. AOtools is under continuous active development to expand the features available, and we encourage everyone involved in adaptive optics to become involved and contribute to the project.

Gender violence, poverty and HIV infection risk among persons engaged in the sex industry: cross-national analysis of the political economy of sex markets in 30 European and Central Asian countries.

OBJECTIVES: Persons engaged in the sex industry are at greater risk of HIV and other sexually transmitted infections than the general population. One major factor is exposure to higher levels of risky sexual activity. Expanding condom use is a critical prevention strategy, but this requires negotiation with those buying sex, which takes place in the context of cultural and economic constraints. Impoverished individuals who fear violence are more likely to forego condoms. METHODS: Here we tested the hypotheses that poverty and fear of violence are two structural drivers of HIV infection risk in the sex industry. Using data from the European Centre for Disease Prevention and Control and the World Bank for 30 countries, we evaluated poverty, measured using the average income per day per person in the bottom 40% of the income distribution, and gender violence, measured using homicide rates in women and the proportion of women exposed to violence in the last 12 months and/or since age 16 years. RESULTS: We found that HIV prevalence among those in the sex industry was higher in countries where there were greater female homicide rates (ß = 0.86; P = 0.018) and there was some evidence that self-reported exposure to violence was also associated with higher HIV prevalence (ß = 1.37; P = 0.043). Conversely, HIV prevalence was lower in countries where average incomes among the poorest were greater (ß = -1.05; P = 0.046). CONCLUSIONS: Our results are consistent with the theory that reducing poverty and exposure to violence may help reduce HIV infection risk among persons engaged in the sex industry.

British Escherichia coli O157 in Cattle Study (BECS): to determine the prevalence of E. coli O157 in herds with cattle destined for the food chain.

Escherichia coli O157 are zoonotic bacteria for which cattle are an important reservoir. Prevalence estimates for E. coli O157 in British cattle for human consumption are over 10 years old. A new baseline is needed to inform current human health risk. The British E. coli O157 in Cattle Study (BECS) ran between September 2014 and November 2015 on 270 farms across Scotland and England & Wales. This is the first study to be conducted contemporaneously across Great Britain, thus enabling comparison between Scotland and England & Wales. Herd-level prevalence estimates for E. coli O157 did not differ significantly for Scotland (0·236, 95% CI 0·166-0·325) and England & Wales (0·213, 95% CI 0·156-0·283) (P = 0·65). The majority of isolates were verocytotoxin positive. A higher proportion of samples from Scotland were in the super-shedder category, though there was no difference between the surveys in the likelihood of a positive farm having at least one super-shedder sample. E. coli O157 continues to be common in British beef cattle, reaffirming public health policy that contact with cattle and their environments is a potential infection source.

An assessment of oral health promotion programmes in the United Kingdom.

BACKGROUND: Improving oral health and reducing tooth decay is a key area for action, both in the United Kingdom (UK) and overseas. The World Health Organization (WHO) has highlighted the unique advantage schools have in promoting oral health. AIM: We summarise current oral health promotion strategies in the United Kingdom and estimate the spread of their use as well as their impact on oral health and influence on the oral health-related knowledge and behaviour in a patient population. METHODS: A structured overview of published papers, government publications, official government websites and policy reports. A cross-sectional study of patients referred for a tooth extraction in one dental surgery in south-east London. Statistical methods consisted of logistic and ordinal regressions to model the likelihood of exposure to oral health promotion and of obtaining higher levels of knowledge of oral health issues, respectively. Linear regression was used to model the level of oral health and knowledge of oral health issues. RESULTS: We found three main promotion programmes, namely, National Healthy Schools (NHS), Sure Start and Brushing for life plus a small number of local initiatives. Sure Start targets disadvantaged areas, but is limited. In our observational study, 34% of the patients reported exposure to a settings-based oral health education programme: Sure Start (5%), NHS (7%) and other (22%). This exposure was not influenced by age or gender, but an association with education was detected. Although oral health promotion was not found to influence the actual knowledge of oral health issues, it was found to influence some oral health-related attitudes and perceptions. CONCLUSIONS: Participation in an oral health promotion programme was found to be significantly associated with the patients' education, their belief that they can prevent oral disease and the subjective perception of their own oral health. The WHO principles need to be embedded across all schools to achieve a true national oral health promotion programme for the United Kingdom. The National Healthy Schools programme provides the perfect platform.

Laparoscopic restorative proctocolectomy: a 10-year experience of an evolving technique.

AIM: Restorative proctocolectomy is the definitive procedure for ulcerative colitis. The potential benefits of a minimal invasive approach make it appropriate to consider this approach provided that there are no adverse effects. The aim of the present study was to report our experience of laparoscopic assisted and 'total' laparoscopic restorative proctocolectomy (LRPC) and to highlight the difficulties encountered and the functional results obtained. METHOD: Electronic data were prospectively collected from all patients who underwent laparoscopic restorative proctocolectomy (LRPC) from October 1999 to April 2010. RESULTS: Seventy-two (40 male) patients [median body mass index 24 (19-48) kg/m(2) ] underwent LRPC over 10 years. Three had cancer. Forty-two had undergone a previous colectomy (laparoscopic in 38). There were 40 W- and 32 J-pouch reconstructions; seven were single-port procedures. The median operation time was 210 (75-330) min. There were five (7%) conversions, one of which resulted in immediate pouch failure. The median time to full diet was 36 (4-168) h, with a median hospital stay of 7 (2-64) days. There were seven (10%) readmissions. Complications were immediate (3%), early (22%) and long term (11%). The incidence of failure (excision or indefinite diversion) was 2.7%. The stoma has been closed in 67 patients. Median frequency of defaecation was 4/24 h, with normal continence in 90% and the ability to defer during the day in 98%. There was no new case of impotence or dyspareunia. CONCLUSION: Laparoscopic restorative proctocolectomy is safe and gives good results when performed by an experienced laparoscopic surgeon.

FloSeal hemostatic matrix use for intraventricular hemorrhage during a neuroendoscopic procedure.

INTRODUCTION: Neuroendoscopy is a rapidly growing field, but the risk of intraventricular hemorrhage is signficant. There are few novel ways of obtaining hemostasis for major hemorrhage described in the literature. PATIENT: A 5-year-old boy with a history of intraventricular hemorrhage and multi-cystic hydrocephalus presented with worsening brainstem compression from dilation of a 4 (th) ventricle cyst. RESULTS: During endoscopic surgery to fenestrate the cyst, arterial hemorrhage was emergently controlled with the hemostatic agent, FloSeal. CONCLUSION: To the best of the authors' knowledge, this is the first report of a patient with intraoperative intraventricular hemorrhage controlled with FloSeal.

Approaches for evaluating veterinary epidemiological models: verification, validation and limitations.

The evaluation of models of the spread and control of animal diseases is crucial if these models are to be used to inform decisions about the control or management of such diseases. Two key steps in the evaluation of epidemiological models are model verification and model validation. Verification is the demonstration that a computer-driven model is operating correctly, and conforms to its intended design. Validation refers to the process of determining how well a model corresponds to the system that it is intended to represent. For a veterinary epidemiological model, validation would address such issues as how well the model represents the dynamics of the disease in question in the population to which this model is applied, and how well the model represents the application of different measures for disease control. Just as the development of epidemiological models is a subjective, continuous process, subject to change and refinement, so too is the evaluation of models. The purpose of model evaluation is not to demonstrate that a model is a 'true' or accurate' representation of a system, but to subject it to sufficient scrutiny so that it may be used with an appropriate degree of confidence to aid decision-making. To facilitate model verification and validation, epidemiological modellers should clearly state the purpose, assumptions and limitations of a model; provide a detailed description of the conceptual model; document those steps already taken to test the model; and thoroughly describe the data sources and the process used to produce model input parameters from those data.

Adapting existing models of highly contagious diseases to countries other than their country of origin.

Many countries do not have the resources to develop epidemiological models of animal diseases. As a result, it is tempting to use models developed in other countries. However, an existing model may need to be adapted in order for it to be appropriately applied in a country, region, or situation other than that for which it was originally developed. The process of adapting a model has a number of benefits for both model builders and model users. For model builders, it provides insight into the applicability of their model and potentially the opportunity to obtain data for operational validation of components of their model. For users, it is a chance to think about the infection transmission process in detail, to review the data available for modelling, and to learn the principles of epidemiological modelling. Various issues must be addressed when considering adapting a model. Most critically, the assumptions and purpose behind the model must be thoroughly understood, so that new users can determine its suitability for their situation. The process of adapting a model might simply involve changing existing model parameter values (for example, to better represent livestock demographics in a country or region), or might require more substantial (and more labour-intensive) changes to the model code and conceptual model. Adapting a model is easier if the model has a user-friendly interface and easy-to-read user documentation. In addition, models built as frameworks within which disease processes and livestock demographics and contacts are flexible are good candidates for technology transfer projects, which lead to long-term collaborations.

Data sets for the qualification of volumetric CT as a quantitative imaging biomarker in lung cancer.

The drug development industry is faced with increasing costs and decreasing success rates. New ways to understand biology as well as the increasing interest in personalized treatments for smaller patient segments requires new capabilities for the rapid assessment of treatment responses. Deployment of qualified imaging biomarkers lags apparent technology capabilities. The lack of consensus methods and qualification evidence needed for large-scale multi-center trials, as well as the standardization that allows them, are widely acknowledged to be the limiting factors. The current fragmentation in imaging vendor offerings, coupled with the independent activities of individual biopharmaceutical companies and their contract research organizations (CROs), may stand in the way of the greater opportunity were these efforts to be drawn together. A preliminary report, "Volumetric CT: a potential biomarker of response," of the Quantitative Imaging Biomarkers Alliance (QIBA) activity was presented at the Medical Imaging Continuum: Path Forward for Advancing the Uses of Medical Imaging in the Development of New Biopharmaceutical Products meeting of the Extended Pharmaceutical Research and Manufacturers of America (PhRMA) Imaging Group sponsored by the Drug Information Agency (DIA) in October 2008. The clinical context in Lung Cancer and a methodology for approaching the qualification of volumetric CT as a biomarker has since been reported [Acad. Radiol. 17, 100-106, 107-115 (2010)]. This report reviews the effort to collect and utilize publicly available data sets to provide a transparent environment in which to pursue the qualification activities in such a way as to allow independent peer review and verification of results. This article focuses specifically on our role as stewards of image sets for developing new tools.

Intracellular olfactory response of hippocampal neurons in awake, sitting squirrel monkeys.

Intracellular recordings of archicortical neurons in a primate have been made and the responses of these neurons in awake, sitting animals have been observed. Electrical stimulation of the olfactory bulbs elicits excitatory postsynaptic potentials in these neurons, which unlike those evoked by septal stimulation, are subliminal for generating spikes. The olfactory and septal pathways may be considered representative of inputs from exteroceptive and interoceptive systems. The findings are discussed in relation to a paradigm for archicortical conditioning.

Neurogenesis in the neocortex of adult primates.

In primates, prefrontal, inferior temporal, and posterior parietal cortex are important for cognitive function. It is shown that in adult macaques, new neurons are added to these three neocortical association areas, but not to a primary sensory area (striate cortex). The new neurons appeared to originate in the subventricular zone and to migrate through the white matter to the neocortex, where they extended axons. These new neurons, which are continually added in adulthood, may play a role in the functions of association neocortex.

Expression of the murine Duchenne muscular dystrophy gene in muscle and brain.

Complementary DNA clones were isolated that represent the 5' terminal 2.5 kilobases of the murine Duchenne muscular dystrophy (Dmd) messenger RNA (mRNA). Mouse Dmd mRNA was detectable in skeletal and cardiac muscle and at a level approximately 90 percent lower in brain. Dmd mRNA is also present, but at much lower than normal levels, in both the muscle and brain of three different strains of dystrophic mdx mice. The identification of Dmd mRNA in brain raises the possibility of a relation between human Duchenne muscular dystrophy (DMD) gene expression and the mental retardation found in some DMD males. These results also provide evidence that the mdx mutations are allelic variants of mouse Dmd gene mutations.

The Reference Image Database to Evaluate Response to therapy in lung cancer (RIDER) project: a resource for the development of change-analysis software.

Critical to the clinical evaluation of effective novel therapies for lung cancer is the early and accurate determination of tumor response, which requires an understanding of the sources of uncertainty in tumor measurement and subsequent attempts to minimize their effects on the assessment of the therapeutic agent. The Reference Image Database to Evaluate Response (RIDER) project seeks to develop a consensus approach to the optimization and benchmarking of software tools for the assessment of tumor response to therapy and to provide a publicly available database of serial images acquired during lung cancer drug and radiation therapy trials. Images of phantoms and patient images acquired under situations in which tumor size or biology is known to be unchanged also will be provided. The RIDER project will create standardized methods for benchmarking software tools to reduce sources of uncertainty in vital clinical assessments such as whether a specific tumor is responding to therapy.

Learning enhances adult neurogenesis in the hippocampal formation.

Thousands of hippocampal neurons are born in adulthood, suggesting that new cells could be important for hippocampal function. To determine whether hippocampus-dependent learning affects adult-generated neurons, we examined the fate of new cells labeled with the thymidine analog bromodeoxyuridine following specific behavioral tasks. Here we report that the number of adult-generated neurons doubles in the rat dentate gyrus in response to training on associative learning tasks that require the hippocampus. In contrast, training on associative learning tasks that do not require the hippocampus did not alter the number of new cells. These findings indicate that adult-generated hippocampal neurons are specifically affected by, and potentially involved in, associative memory formation.

Strategies for screening young stock for antibodies - optimising numbers to test, cut-points, & predictive values for bovine viral diarrhoea virus.

The antibody seroprevalence of young stock can be a useful indicator of recent or current infection in a herd. We examine the factors that contribute to the assessment of herd exposure to disease, via spot testing for antibody, using bovine viral diarrhoea virus (BVDv) as an example. A statistical distribution of seroprevalences for BVDv in beef herds identified three groups of herds: low, intermediate and high within-herd BVDv antibody seroprevalence. We tested two assumptions -the intermediate seroprevalence group of herds is assumed to be negative for BVDv at the herd level and alternatively if this group is assumed to be positive. We found that: The herd-level sensitivity and specificity are sensitive to the assumption regarding the herds with intermediate seroprevalence. If an appropriate cut-point is chosen, reducing the sample size from ten to five does not produce a large drop in herd-level test performance. Increasing the cut-point may be valuable at the outset of an eradication programme. Increasing the sample size and decreasing the cut-point is advantageous towards the end of an eradication programme, to minimise the risk of positive herds being misclassified. The framework presented here illustrates how seroprevalence screening may be understood and assessed.

Imaging Acetaldehyde Formation During Ethanol Metabolism in Living Cells using a Hydrazinyl Naphthalimide Fluorescent Probe.

The metabolism of ethanol to acetaldehyde has been visualized in living lung epithelial cells using a hydrazinyl naphthalimide fluorescent probe. Utilizing a condensation reaction between carbonyls and a hydrazine moeity, we demonstrate that the fluorescent probe (Aldehydefluor-1) AF1 reacts with a range of reactive carbonyl species including formaldehyde, acetaldehyde, glyoxylic acid, and methyl glyoxal. With AF1, it is possible to directly visualize endogenous carbonyl metabolites. Here, we have applied it towards the visualization of acetaldehyde generated from alcohol dehydrogenase mediated ethanol metabolism, validating it as a useful tool to study the roles of alcohol in respiratory disease and other pathological mechanisms.

'First, do no harm': are disability assessments associated with adverse trends in mental health? A longitudinal ecological study.

BACKGROUND: In England between 2010 and 2013, just over one million recipients of the main out-of-work disability benefit had their eligibility reassessed using a new functional checklist-the Work Capability Assessment. Doctors and disability rights organisations have raised concerns that this has had an adverse effect on the mental health of claimants, but there are no population level studies exploring the health effects of this or similar policies. METHOD: We used multivariable regression to investigate whether variation in the trend in reassessments in each of 149 local authorities in England was associated with differences in local trends in suicides, self-reported mental health problems and antidepressant prescribing rates, while adjusting for baseline conditions and trends in other factors known to influence mental ill-health. RESULTS: Each additional 10,000 people reassessed in each area was associated with an additional 6 suicides (95% CI 2 to 9), 2700 cases of reported mental health problems (95% CI 548 to 4840), and the prescribing of an additional 7020 antidepressant items (95% CI 3930 to 10100). The reassessment process was associated with the greatest increases in these adverse mental health outcomes in the most deprived areas of the country, widening health inequalities. CONCLUSIONS: The programme of reassessing people on disability benefits using the Work Capability Assessment was independently associated with an increase in suicides, self-reported mental health problems and antidepressant prescribing. This policy may have had serious adverse consequences for mental health in England, which could outweigh any benefits that arise from moving people off disability benefits.

Fit-for-work or fit-for-unemployment? Does the reassessment of disability benefit claimants using a tougher work capability assessment help people into work?

BACKGROUND: Many governments have introduced tougher eligibility assessments for out-of-work disability benefits, to reduce rising benefit caseloads. The UK government initiated a programme in 2010 to reassess all existing disability benefit claimants using a new functional checklist. We investigated whether this policy led to more people out-of-work with long-standing health problems entering employment. METHOD: We use longitudinal data from the Labour Force Survey linked to data indicating the proportion of the population experiencing a reassessment in each of 149 upper tier local authorities in England between 2010 and 2013. Regression models were used to investigate whether the proportion of the population undergoing reassessment in each area was independently associated with the chances that people out-of-work with a long-standing health problem entered employment and transitions between inactivity and unemployment. We analysed whether any effects differed between people whose main health problem was mental rather than physical. RESULTS: There was no significant association between the reassessment process and the chances that people out-of-work with a long-standing illness entered employment. The process was significantly associated with an increase in the chances that people with mental illnesses moved from inactivity into unemployment (HR=1.22, 95% CI 1.03 to 1.45). CONCLUSIONS: The reassessment policy appears to have shifted people with mental health problems from inactivity into unemployment, but there was no evidence that it had increased their chances of employment. There is an urgent need for services that can support the increasing number of people with mental health problems on unemployment benefits.