Trait-Based Vaccination of Individual Meerkats (Suricata suricatta) against Tuberculosis Provides Evidence to Support Targeted Disease Control.

Individuals vary in their potential to acquire and transmit infections, but this fact is currently underexploited in disease control strategies. We trialled a trait-based vaccination strategy to reduce tuberculosis in free-living meerkats by targeting high-contact meerkats (socially dominant individuals) in one study arm, and high-susceptibility individuals (young subordinates) in a second arm. We monitored infection within vaccinated groups over two years comparing the results with untreated control groups. Being a member of a high-contact group had a protective effect on individuals' survival times (Hazard Ratio = 0.5, 95% Confidence Interval, CI: 0.29-0.88, p = 0.02) compared to control groups. Over the study, odds of testing positive for tuberculosis increased more than five-fold in control groups (Odds Ratio = 5.40, 95% CI = 0.94-30.98, p = 0.058); however, no increases were observed in either of the treatment arms. Targeted disease control approaches, such as the one described in this study, allow for reduced numbers of interventions. Here, trait-based vaccination was associated with reduced infection rates and thus has the potential to offer more efficient alternatives to traditional mass-vaccination policies. Such improvements in efficiency warrant further study and could make infectious disease control more practically achievable in both animal (particularly wildlife) and human populations

Prioritization of Managed Pork Supply Movements during a FMD Outbreak in the US

In the event of a Foot and Mouth Disease (FMD) outbreak in the U.S., local, state, and federal authorities will implement a foreign animal disease emergency response plan restricting the pork supply chain movements and likely disrupting the continuity of the swine industry business. To minimize disruptions of the food supply while providing an effective response in an outbreak, it is necessary to have proactive measures in place to ensure minimal disease spread and maximum continuation of business. Therefore, it is critical to identify candidate movements for proactive risk assessments: those that are both most likely to contribute to disease spread and most necessary for business continuity. To do this, experts from production, harvest, retail, and allied pork industries assessed 30 common pork supply movements for risk of disease spread and industry criticality. The highest priority movements for conducting a risk assessment included the movement of weaned pigs originating from multiple sow farm sources to an offsite nursery or wean to finish facility, the movement of employees or commercial crews, the movement of vaccination crews, the movement of dedicated livestock hauling trucks, and the movement of commercial crews such as manure haulers and feed trucks onto, off, or between sites. These critical movements, along with several others identified in this study, will provide an initial guide for prioritization of risk management efforts and resources to be better prepared in the event of a FMD outbreak in the United States. By specifically and proactively targeting movements that experts agree are likely to spread the disease and are critical to the continuity of business operations, potentially catastrophic consequences in the event of an outbreak can be limited

Bringing UMAP Closer to the Speed of Light with GPU Acceleration

The Uniform Manifold Approximation and Projection (UMAP) algorithm has become widely popular for its ease of use, quality of results, and support for exploratory, unsupervised, supervised, and semi-supervised learning. While many algorithms can be ported to a GPU in a simple and direct fashion, such efforts have resulted in inefficient and inaccurate versions of UMAP. We show a number of techniques that can be used to make a faster and more faithful GPU version of UMAP, and obtain speedups of up to 100x in practice. Many of these design choices/lessons are general purpose and may inform the conversion of other graph and manifold learning algorithms to use GPUs. Our implementation has been made publicly available as part of the open source RAPIDS cuML library (https://github.com/rapidsai/cuml)

The use of error-category mapping in pharmacokinetic model analysis of dynamic contrast-enhanced MRI data.

This study introduces the use of 'error-category mapping' in the interpretation of pharmacokinetic (PK) model parameter results derived from dynamic contrast-enhanced (DCE-) MRI data. Eleven patients with metastatic renal cell carcinoma were enrolled in a multiparametric study of the treatment effects of bevacizumab. For the purposes of the present analysis, DCE-MRI data from two identical pre-treatment examinations were analysed by application of the extended Tofts model (eTM), using in turn a model arterial input function (AIF), an individually-measured AIF and a sample-average AIF. PK model parameter maps were calculated. Errors in the signal-to-gadolinium concentration ([Gd]) conversion process and the model-fitting process itself were assigned to category codes on a voxel-by-voxel basis, thereby forming a colour-coded 'error-category map' for each imaged slice. These maps were found to be repeatable between patient visits and showed that the eTM converged adequately in the majority of voxels in all the tumours studied. However, the maps also clearly indicated sub-regions of low Gd uptake and of non-convergence of the model in nearly all tumours. The non-physical condition ve ≥ 1 was the most frequently indicated error category and appeared sensitive to the form of AIF used. This simple method for visualisation of errors in DCE-MRI could be used as a routine quality-control technique and also has the potential to reveal otherwise hidden patterns of failure in PK model applications.This work was supported by GlaxoSmithKline UK, Wellcome Trust, Cambridge NIHR Biomedical Research Centre, Cambridge Experimental Cancer Medicine Centre, Cancer Research UKThis is the published version. It first appeared at http://www.sciencedirect.com/science/article/pii/S0730725X1400321X

Can a clinical placement influence stigma? An analysis of measures of social distance

Background The way people who experience mental illness are perceived by health care professionals, which often includes stigmatising attitudes, can have a significant impact on treatment outcomes and on their quality of life. Objective To determine whether stigma towards people with mental illness varied for undergraduate nursing students who attended a non-traditional clinical placement called Recovery Camp compared to students who attended a \u27typical\u27 mental health clinical placement. Design Quasi-experimental. Participants Seventy-nine third-year nursing students were surveyed; n = 40 attended Recovery Camp (intervention), n = 39 (comparison group) attended a \u27typical\u27 mental health clinical placement. Methods All students completed the Social Distance Scale (SDS) pre- and post-placement and at three-month follow-up. Data analysis consisted of a one-way repeated measures analysis of variance (ANOVA) exploring parameter estimates between group scores across three time points. Two secondary repeated measures ANOVAs were performed to demonstrate the differences in SDS scores for each group across time. Pairwise comparisons demonstrated the differences between time intervals. Results A statistically significant difference in ratings of stigma between the intervention group and the comparison group existed. Parameter estimates revealed that stigma ratings for the intervention group were significantly reduced post-placement and remained consistently low at three-month follow-up. There was no significant difference in ratings of stigma for the comparison group over time. Conclusions Students who attended Recovery Camp reported significant decreases in stigma towards people with a mental illness over time, compared to the typical placement group. Findings suggest that a therapeutic recreation based clinical placement was more successful in reducing stigma regarding mental illness in undergraduate nursing students compared to those who attended typical mental health clinical placements

Influences on recruitment to randomised controlled trials in mental health settings in England: a national cross-sectional survey of researchers working for the Mental Health Research Network

Background: Recruitment to trials is complex and often protracted; selection bias may compromise generalisability. In the mental health field (as elsewhere), diverse factors have been described as hindering researcher access to potential participants and various strategies have been proposed to overcome barriers. However, the extent to which various influences identified in the literature are operational across mental health settings in England has not been systematically examined. Methods: A cross-sectional, online survey of clinical studies officers employed by the Mental Health Research Network in England to recruit to trials from National Health Service mental health services. The bespoke questionnaire invited participants to report exposure to specified influences on recruitment, the perceived impact of these on access to potential participants, and to describe additional positive or negative influences on recruitment. Analysis employed descriptive statistics, the framework approach and triangulation of data. Results: Questionnaires were returned by 98 (58%) of 170 clinical studies officers who reported diverse experience. Data demonstrated a disjunction between policy and practice. While the particulars of trial design and various marketing and dommunication strategies could influence recruitment, consensus was that the culture of NHS mental health services is not donducive to research. Since financial rewards for recruitment paid to Trusts and feedback about studies seldom reaching frontline services, clinicians were described as distanced from research. Facing continual service change and demanding clinical workloads, clinicians generally did not prioritise recruitment activities. Incentives to trial participants had variable impact on access but recruitment could be enhanced by engagement of senior investigators and integrating referral with routine practice. Comprehensive, robust feasibility studies and reciprocity between researchers and clinicians were considered crucial to successful recruitment. Conclusions: In the mental health context, researcher access to potential trial participants is multiply influenced. Gatekeeping clinicians are faced with competing priorities and resources constrain research activity. It seems that environmental adjustment predicated on equitable resource allocation is needed if clinicians in NHS mental health services are to fully support the conduct of randomised controlled trials. Whilst cultural transformation, requiring changes in assumptions and values, is complex, our findings suggest that attention to practical matters can support this and highlight issues requiring careful consideration

Academic Medicine as a Bridge to Peace: Building Arab and Israeli Cooperation

Can you imagine Canadian, Israeli, Jordanian, and Palestinian medical students singing, volunteering, and working together to develop programs to address issues related to global pediatric emergency medicine? Such a program was first held in Toronto in 2003 and continues annually. Can you imagine Canadians, Israelis, Jordanians, and Palestinians jointly teaching and developing solutions, via video teleconference, to address behavioral neurological problems affecting elderly populations? Such an initiative began in 2006 and continues to expand today. Can you imagine senior Jordanian and Israeli ear surgeons operating together, successfully carrying out pioneering cochlear implant surgery on deaf infants, on Jordanian national television? Such a surgery was performed in Amman in December 2003. Can you imagine every newborn baby in Jordan having her or his hearing tested? Such a program began in January 2005 as a result of Canadian, Israeli, Palestinian, and Jordanian service, educational, and scientific research cooperation, becoming national health policy in Jordan in 2007. All of this and much more are the result of the Canada International Scientific Exchange Program (CISEPO) and its cooperation network of knowledge

TRPV4-Mediated Calcium Influx into Human Bronchial Epithelia upon Exposure to Diesel Exhaust Particles

BACKGROUND: Human respiratory epithelia function in airway mucociliary clearance and barrier function and have recently been implicated in sensory functions. OBJECTIVE: We investigated a link between chronic obstructive pulmonary disease (COPD) pathogenesis and molecular mechanisms underlying Ca2+ influx into human airway epithelia elicited by diesel exhaust particles (DEP). METHODS AND RESULTS: Using primary cultures of human respiratory epithelial (HRE) cells, we determined that these cells possess proteolytic signaling machinery, whereby proteinase-activated receptor-2 (PAR-2) activates Ca2+-permeable TRPV4, which leads to activation of human respiratory disease-enhancing matrix metalloproteinase-1 (MMP-1), a signaling cascade initiated by diesel exhaust particles (DEP), a globally relevant air pollutant. Moreover, we observed ciliary expression of PAR-2, TRPV4, and phospholipase-Cβ3 in human airway epithelia and their DEP-enhanced protein-protein complex formation. We also found that the chronic obstructive pulmonary disease (COPD)-predisposing TRPV4P19S variant enhances Ca2+ influx and MMP 1 activation, providing mechanistic linkage between man-made air pollution and human airway disease. CONCLUSION: DEP evoked protracted Ca2+ influx via TRPV4, enhanced by the COPD-predisposing human genetic polymorphism TRPV4P19S. This mechanism reprograms maladaptive inflammatory and extracellular-matrix-remodeling responses in human airways. The novel concept of air pollution-responsive ciliary signal transduction from PAR-2 to TRPV4 in human respiratory epithelia will accelerate rationally targeted therapies, possibly via the inhalatory route