Antibodies to Henipavirus or Henipa-Like Viruses in Domestic Pigs in Ghana, West Africa

Henipaviruses, Hendra virus (HeV) and Nipah virus (NiV), have Pteropid bats as their known natural reservoirs. Antibodies against henipaviruses have been found in Eidolon helvum, an old world fruit bat species, and henipavirus-like nucleic acid has been detected in faecal samples from E. helvum in Ghana. The initial outbreak of NiV in Malaysia led to over 265 human encephalitis cases, including 105 deaths, with infected pigs acting as amplifier hosts for NiV during the outbreak. We detected non-neutralizing antibodies against viruses of the genus Henipavirus in approximately 5% of pig sera (N = 97) tested in Ghana, but not in a small sample of other domestic species sampled under a E. helvum roost. Although we did not detect neutralizing antibody, our results suggest prior exposure of the Ghana pig population to henipavirus(es). Because a wide diversity of henipavirus-like nucleic acid sequences have been found in Ghanaian E. helvum, we hypothesise that these pigs might have been infected by henipavirus(es) sufficiently divergent enough from HeVor NiV to produce cross-reactive, but not cross-neutralizing antibodies to HeV or NiV

Connective tissue disease related interstitial lung diseases and idiopathic pulmonary fibrosis: provisional core sets of domains and instruments for use in clinical trials

Rationale Clinical trial design in interstitial lung diseases (ILDs) has been hampered by lack of consensus on appropriate outcome measures for reliably assessing treatment response. In the setting of connective tissue diseases (CTDs), some measures of ILD disease activity and severity may be confounded by non-pulmonary comorbidities. Methods The Connective Tissue Disease associated Interstitial Lung Disease (CTD-ILD) working group of Outcome Measures in Rheumatology—a non-profit international organisation dedicated to consensus methodology in identification of outcome measures—conducted a series of investigations which included a Delphi process including >248 ILD medical experts as well as patient focus groups culminating in a nominal group panel of ILD experts and patients. The goal was to define and develop a consensus on the status of outcome measure candidates for use in randomised controlled trials in CTD-ILD and idiopathic pulmonary fibrosis (IPF). Results A core set comprising specific measures in the domains of lung physiology, lung imaging, survival, dyspnoea, cough and health-related quality of life is proposed as appropriate for consideration for use in a hypothetical 1-year multicentre clinical trial for either CTD-ILD or IPF. As many widely used instruments were found to lack full validation, an agenda for future research is proposed. Conclusion Identification of consensus preliminary domains and instruments to measure them was attained and is a major advance anticipated to facilitate multicentre RCTs in the field

Salvage radiotherapy after radical prostatectomy: analysis of toxicity by dose-fractionation in the RADICALS-RT trial

ABSTRACT: Emerging data indicate comparable disease control and toxicity of postoperative normo-fractionation and moderate hypofractionation radiotherapy (RT) in prostate cancer. In RADICALS-RT, patients were planned for treatment with either 66Gy in 33 fractions over 6.5 weeks or 52.5Gy in 20 fractions over 4 weeks. In this non-randomized, exploratory analysis, we explore the toxicity of these two schedules in patients who had adjuvant RT. METHODS: Information on RT dose was collected in all patients. Radiation Therapy Oncology Group toxicity score was recorded every 4 months for 2 years, 6-monthly until 5 years, then annually until 15 years. Patient-reported data were collected at baseline, 1, 5, and 10 years with use of standard questionnaires including Vaizey (bowel) and International Continence Society Male Short-Form (urinary incontinence). The highest grade of event was recorded within the first 2 years, and beyond 2 years, and compared between treatment groups using the χ² test. RESULTS: 217/634 (34%) patients were planned for 52.5Gy/20f and 417/634 (66%) for 66Gy/33f. In the first two years, grade 1 - 2 cystitis was reported more frequently among the 66Gy/33f group (52.5Gy/20f: 20% vs 66Gy/33f: 30%, p=0.04). After two years, grade 1-2 cystitis was reported in 16% in the 66Gy group, and 9% in the 52.5Gy group (p=0.08). Other toxicities were similar in the two groups and very few patients had any grade 3 - 4 toxicity. Patients reported slightly higher urinary and faecal incontinence scores at one year than at baseline, but no clinically meaningful differences were reported between 52.5Gy/20f and 66Gy/33f groups. Patient reported health was similar at baseline and at one year, and similar between 52.5Gy/20f and 66Gy/33f groups. CONCLUSION: Severe toxicity is rare after prostate bed radiotherapy with either 52.5Gy/20f or 66Gy/33f. Only modest differences were recorded in toxicity or in patient reported outcomes between these two schedules

Climate change promotes parasitism in a coral symbiosis.

Coastal oceans are increasingly eutrophic, warm and acidic through the addition of anthropogenic nitrogen and carbon, respectively. Among the most sensitive taxa to these changes are scleractinian corals, which engineer the most biodiverse ecosystems on Earth. Corals' sensitivity is a consequence of their evolutionary investment in symbiosis with the dinoflagellate alga, Symbiodinium. Together, the coral holobiont has dominated oligotrophic tropical marine habitats. However, warming destabilizes this association and reduces coral fitness. It has been theorized that, when reefs become warm and eutrophic, mutualistic Symbiodinium sequester more resources for their own growth, thus parasitizing their hosts of nutrition. Here, we tested the hypothesis that sub-bleaching temperature and excess nitrogen promotes symbiont parasitism by measuring respiration (costs) and the assimilation and translocation of both carbon (energy) and nitrogen (growth; both benefits) within Orbicella faveolata hosting one of two Symbiodinium phylotypes using a dual stable isotope tracer incubation at ambient (26 °C) and sub-bleaching (31 °C) temperatures under elevated nitrate. Warming to 31 °C reduced holobiont net primary productivity (NPP) by 60% due to increased respiration which decreased host %carbon by 15% with no apparent cost to the symbiont. Concurrently, Symbiodinium carbon and nitrogen assimilation increased by 14 and 32%, respectively while increasing their mitotic index by 15%, whereas hosts did not gain a proportional increase in translocated photosynthates. We conclude that the disparity in benefits and costs to both partners is evidence of symbiont parasitism in the coral symbiosis and has major implications for the resilience of coral reefs under threat of global change

‘Trial and error…’, ‘…happy patients’ and ‘…an old toy in the cupboard’: a qualitative investigation of factors that influence practitioners in their prescription of foot orthoses

Background: Foot orthoses are used to manage of a plethora of lower limb conditions. However, whilst the theoretical foundations might be relatively consistent, actual practices and therefore the experience of patients is likely to be less so. The factors that affect the prescription decisions that practitioners make about individual patients is unknown and hence the way in which clinical experience interacts with knowledge from training is not understood. Further, other influences on orthotic practice may include the adoption (or not) of technology. Hence the aim of this study was to explore, for the first time, the influences on orthotic practice. Methods: A qualitative approach was adopted utilising two focus groups (16 consenting participants in total; 15 podiatrists and 1 orthotist) in order to collect the data. An opening question “What factors influence your orthotic practice?” was followed with trigger questions, which were used to maintain focus. The dialogue was recorded digitally, transcribed verbatim and a thematic framework was used to analyse the data. Results: There were five themes: (i) influences on current practice, (ii) components of current practice, (iii) barriers to technology being used in clinical practice, (iv) how technology could enhance foot orthoses prescription and measurement of outcomes, and (v) how technology could provide information for practitioners and patients. A final global theme was agreed by the researchers and the participants: ‘Current orthotic practice is variable and does not embrace technology as it is perceived as being not fit for purpose in the clinical environment. However, practitioners do have a desire for technology that is usable and enhances patient focussed assessment, the interventions, the clinical outcomes and the patient’s engagement throughout these processes’. Conclusions: In relation to prescribing foot orthoses, practice varies considerably due to multiple influences. Measurement of outcomes from orthotic practice is a priority but there are no current norms for achieving this. There have been attempts by practitioners to integrate technology into their practice, but with largely negative experiences. The process of technology development needs to improve and have a more practice, rather than technology focus

Development of an Acute and Highly Pathogenic Nonhuman Primate Model of Nipah Virus Infection

Nipah virus (NiV) is an enigmatic emerging pathogen that causes severe and often fatal neurologic and/or respiratory disease in both animals and humans. Amongst people, case fatality rates range between 40 and 75 percent and there are no vaccines or treatments approved for human use. Guinea pigs, hamsters, cats, ferrets, pigs and most recently squirrel monkeys (New World monkey) have been evaluated as animal models of human NiV infection, and with the exception of the ferret, no model recapitulates all aspects of NiV-mediated disease seen in humans. To identify a more viable nonhuman primate (NHP) model, we examined the pathogenesis of NiV in African green monkeys (AGM). Exposure of eight monkeys to NiV produced a severe systemic infection in all eight animals with seven of the animals succumbing to infection. Viral RNA was detected in the plasma of challenged animals and occurred in two of three subjects as a peak between days 7 and 21, providing the first clear demonstration of plasma-associated viremia in NiV experimentally infected animals and suggested a progressive infection that seeded multiple organs simultaneously from the initial site of virus replication. Unlike the cat, hamster and squirrel monkey models of NiV infection, severe respiratory pathology, neurological disease and generalized vasculitis all manifested in NiV-infected AGMs, providing an accurate reflection of what is observed in NiV-infected humans. Our findings demonstrate the first consistent and highly pathogenic NHP model of NiV infection, providing a new and critical platform in the evaluation and licensure of either passive and active immunization or therapeutic strategies for human use

Computer-Based Interventions for Problematic Alcohol Use:a Review of Systematic Reviews

PURPOSE: The aim of this review is to provide an overview of knowledge and knowledge gaps in the field of computer-based alcohol interventions by (1) collating evidence on the effectiveness of computer-based alcohol interventions in different populations and (2) exploring the impact of four specified moderators of effectiveness: therapeutic orientation, length of intervention, guidance and trial engagement.  METHODS: A review of systematic reviews of randomized trials reporting on effectiveness of computer-based alcohol interventions published between 2005 and 2015.  RESULTS: Fourteen reviews met the inclusion criteria. Across the included reviews, it was generally reported that computer-based alcohol interventions were effective in reducing alcohol consumption, with mostly small effect sizes. There were indications that longer, multisession interventions are more effective than shorter or single session interventions. Evidence on the association between therapeutic orientation of an intervention, guidance or trial engagement and reductions in alcohol consumption is limited, as the number of reviews addressing these themes is low. None of the included reviews addressed the association between therapeutic orientation, length of intervention or guidance and trial engagement.  CONCLUSIONS: This review of systematic reviews highlights the mostly positive evidence supporting computer-based alcohol interventions as well as reveals a number of knowledge gaps that could guide future research in this field

Multiphysics simulation of a microfluidic perfusion chamber for brain slice physiology

Understanding and optimizing fluid flows through in vitro microfluidic perfusion systems is essential in mimicking in vivo conditions for biological research. In a previous study a microfluidic brain slice device (μBSD) was developed for microscale electrophysiology investigations. The device consisted of a standard perfusion chamber bonded to a polydimethylsiloxane (PDMS) microchannel substrate. Our objective in this study is to characterize the flows through the μBSD by using multiphysics simulations of injections into a pourous matrix to identify optimal spacing of ports. Three-dimensional computational fluid dynamic (CFD) simulations are performed with CFD-ACE + software to model, simulate, and assess the transport of soluble factors through the perfusion bath, the microchannels, and a material that mimics the porosity, permeability and tortuosity of brain tissue. Additionally, experimental soluble factor transport through a brain slice is predicted by and compared to simulated fluid flow in a volume that represents a porous matrix material. The computational results are validated with fluorescent dye experiments