Deaths, late deaths, and role of infecting dose in Ebola virus disease in Sierra Leone: retrospective cohort study.

OBJECTIVES:  To assess the frequency of fatal recrudescence from Ebola virus disease after discharge from treatment centres, and explore the influence of infecting dose on case fatality rates. DESIGN:  Retrospective cohort study. SETTING:  Western Area, Sierra Leone. PARTICIPANTS:  151 survivors treated for Ebola virus disease at the Kerry Town treatment centre and discharged. Survivors were followed up for a vital status check at four to nine months after discharge, and again at six to 13 months after discharge. Verbal autopsies were conducted for four survivors who had died since discharge (that is, late deaths). Survivors still living in Western Area were interviewed together with their household members. Exposure level to Ebola virus disease was ascertained as a proxy of infecting dose, including for those who died. MAIN OUTCOME MEASURES:  Risks and causes of late death; case fatality rates; odds ratios of death from Ebola virus disease by age, sex, exposure level, date, occupation, and household risk factors. RESULTS:  Follow-up information was obtained on all 151 survivors of Ebola virus disease, a mean of 10 months after discharge. Four deaths occurred after discharge, all within six weeks: two probably due to late complications, one to prior tuberculosis, and only one after apparent full recovery, giving a maximum estimate of recrudescence leading to death of 0.7%. In these households, 395 people were reported to have had Ebola virus disease, of whom 227 died. A further 53 people fulfilled the case definition for probable disease, of whom 11 died. Therefore, the case fatality rate was 57.5% (227/395) for reported Ebola virus disease, or 53.1% (238/448) including probable disease. Case fatality rates were higher in children aged under 2 years and adults older than 30 years, in larger households, and in infections occurring earlier in the epidemic in Sierra Leone. There was no consistent trend of case fatality rate with exposure level, although increasing exposure increased the risk of Ebola virus disease. CONCLUSIONS:  In this study of survivors in Western Area, Sierra Leone, late recrudescence of severe Ebola virus disease appears to be rare. There was no evidence for an effect of infecting dose (as measured by exposure level) on the severity of disease

Traumatic Brain Injury-Practice Based Evidence Study: Design and Patients, Centers, Treatments, and Outcomes

OBJECTIVES: To describe study design, patients, centers, treatments, and outcomes of a traumatic brain injury (TBI) practice-based evidence (PBE) study and to evaluate the generalizability of the findings to the U.S. TBI inpatient rehabilitation population. DESIGN: Prospective, longitudinal, observational study. SETTING: Ten inpatient rehabilitation centers. PARTICIPANTS: Patients (N=2130) enrolled between October 2008 and September 2011 and admitted for inpatient rehabilitation after an index TBI injury. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Return to acute care during rehabilitation, rehabilitation length of stay, FIM at discharge, residence at discharge, and 9 months postdischarge rehospitalization, FIM, participation, and subjective well-being. RESULTS: The level of admission FIM cognitive score was found to create relatively homogeneous subgroups for the subsequent analysis of best treatment combinations. There were significant differences in patient and injury characteristics, treatments, rehabilitation course, and outcomes by admission FIM cognitive subgroups. TBI-PBE study patients were overall similar to U.S. national TBI inpatient rehabilitation populations. CONCLUSIONS: This TBI-PBE study succeeded in capturing naturally occurring variation in patients and treatments, offering opportunities to study best treatments for specific patient impairments. Subsequent articles in this issue report differences between patients and treatments and associations with outcomes in greater detail

The functional response of a generalist predator

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Body density of humpback whales (Megaptera novaengliae) in feeding aggregations estimated from hydrodynamic gliding performance

Many baleen whales undertake annual fasting and feeding cycles, resulting in substantial changes in their body condition, an important factor affecting fitness. As a measure of lipid store body condition, tissue density of a few deep diving marine mammals has been estimated using a hydrodynamic glide model of drag and buoyancy forces. Here, we applied the method to shallow-diving humpback whales (Megaptera novaeangliae) in North Atlantic and Antarctic feeding aggregations. High-resolution 3-axis acceleration, depth and speed data were collected from 24 whales. Measured values of acceleration during 5 s glides were fitted to a hydrodynamic glide model to estimate unknown parameters (tissue density, drag term and diving gas volume) in a Bayesian framework. Estimated species-average tissue density (1031.6 ± 2.1 kg m-3, ±95% credible interval) indicates that humpback whale tissue is typically negatively buoyant although there was a large inter-individual variation ranging from 1025.2 to 1043.1 kg m-3. The precision of the individual estimates was substantially finer than the variation across different individual whales, demonstrating a progressive decrease in tissue density throughout the feeding season and comparably high lipid-store in pregnant females. The drag term (CDAm-1) was estimated to be relatively high, indicating a large effect of lift-related induced drag for humpback whales. Our results show that tissue density of shallow diving baleen whales can be estimated using the hydrodynamic gliding model, although cross-validation with other techniques is an essential next step. This method for estimating body condition is likely to be broadly applicable across a range of aquatic animals and environments

Carcinogenic Liver Fluke Secretes Extracellular Vesicles That Promote Cholangiocytes to Adopt a Tumorigenic Phenotype.

BACKGROUND: Throughout Asia, there is an unprecedented link between cholangiocarcinoma and infection with the liver fluke Opisthorchis viverrini. Multiple processes, including chronic inflammation and secretion of parasite proteins into the biliary epithelium, drive infection toward cancer. Until now, the mechanism and effects of parasite protein entry into cholangiocytes was unknown. METHODS: Various microscopy techniques were used to identify O. viverrini extracellular vesicles (EVs) and their internalization by human cholangiocytes. Using mass spectrometry we characterized the EV proteome and associated changes in cholangiocytes after EV uptake, and we detected EV proteins in bile of infected hamsters and humans. Cholangiocyte proliferation and interleukin 6 (IL-6) secretion was measured to assess the impact of EV internalization. RESULTS: EVs were identified in fluke culture medium and bile specimens from infected hosts. EVs internalized by cholangiocytes drove cell proliferation and IL-6 secretion and induced changes in protein expression associated with endocytosis, wound repair, and cancer. Antibodies to an O. viverrini tetraspanin blocked EV uptake and IL-6 secretion by cholangiocytes. CONCLUSIONS: This is the first time that EVs from a multicellular pathogen have been identified in host tissues. Our findings imply a role for O. viverrini EVs in pathogenesis and highlight an approach to vaccine development for this infectious cancer.This work was supported by a Project Grant (APP1085309) from the National Health and Medical Research Council of Australia (NHMRC). AL is supported by a NHMRC principal research fellowship. SC was supported by the Thailand Research Fund (TRF)-the Royal Golden Jubilee PhD scholarship (RGJ) through Dr. Banchob Sripa.This is the final version. It was first published by OUP at http://dx.doi.org/10.1093/infdis/jiv29

Interaction of convective organisation with monsoon precipitation, atmosphere, surface and sea: the 2016 INCOMPASS field campaign in India

The INCOMPASS field campaign combines airborne and ground measurements of the 2016 Indian monsoon, towards the ultimate goal of better predicting monsoon rainfall. The monsoon supplies the majority of water in South Asia, but forecasting from days to the season ahead is limited by large, rapidly developing errors in model parametrizations. The lack of detailed observations prevents thorough understanding of the monsoon circulation and its interaction with the land surface: a process governed by boundary-layer and convective-cloud dynamics. INCOMPASS used the UK Facility for Airborne Atmospheric Measurements (FAAM) BAe-146 aircraft for the first project of this scale in India, to accrue almost 100 hours of observations in June and July 2016. Flights from Lucknow in the northern plains sampled the dramatic contrast in surface and boundary layer structures between dry desert air in the west and the humid environment over the northern Bay of Bengal. These flights were repeated in pre-monsoon and monsoon conditions. Flights from a second base at Bengaluru in southern India measured atmospheric contrasts from the Arabian Sea, over the Western Ghats mountains, to the rain shadow of southeast India and the south Bay of Bengal. Flight planning was aided by forecasts from bespoke 4km convection-permitting limited-area models at the Met Office and India's NCMRWF. On the ground, INCOMPASS installed eddy-covariance flux towers on a range of surface types, to provide detailed measurements of surface fluxes and their modulation by diurnal and seasonal cycles. These data will be used to better quantify the impacts of the atmosphere on the land surface, and vice versa. INCOMPASS also installed ground instrumentation supersites at Kanpur and Bhubaneswar. Here we motivate and describe the INCOMPASS field campaign. We use examples from two flights to illustrate contrasts in atmospheric structure, in particular the retreating mid-level dry intrusion during the monsoon onset

Interaction of convective organisation with monsoon precipitation, atmosphere, surface and sea: the 2016 INCOMPASS field campaign in India

The INCOMPASS field campaign combines airborne and ground measurements of the 2016 Indian monsoon, towards the ultimate goal of better predicting monsoon rainfall. The monsoon supplies the majority of water in South Asia, but forecasting from days to the season ahead is limited by large, rapidly developing errors in model parametrizations. The lack of detailed observations prevents thorough understanding of the monsoon circulation and its interaction with the land surface: a process governed by boundary‐layer and convective‐cloud dynamics. INCOMPASS used the UK Facility for Airborne Atmospheric Measurements (FAAM) BAe‐146 aircraft for the first project of this scale in India, to accrue almost 100 h of observations in June and July 2016. Flights from Lucknow in the northern plains sampled the dramatic contrast in surface and boundary‐layer structures between dry desert air in the west and the humid environment over the northern Bay of Bengal. These flights were repeated in pre‐monsoon and monsoon conditions. Flights from a second base at Bengaluru in southern India measured atmospheric contrasts from the Arabian Sea, over the Western Ghats mountains, to the rain shadow of southeast India and the south Bay of Bengal. Flight planning was aided by forecasts from bespoke 4 km convection‐permitting limited‐area models at the Met Office and India's NCMRWF. On the ground, INCOMPASS installed eddy‐covariance flux towers on a range of surface types, to provide detailed measurements of surface fluxes and their modulation by diurnal and seasonal cycles. These data will be used to better quantify the impacts of the atmosphere on the land surface, and vice versa. INCOMPASS also installed ground instrumentation supersites at Kanpur and Bhubaneswar. Here we motivate and describe the INCOMPASS field campaign. We use examples from two flights to illustrate contrasts in atmospheric structure, in particular the retreating mid‐level dry intrusion during the monsoon onset

Environment-sensitive mass changes influence breeding frequency in a capital breeding marine top predator

UK Natural Environment Research Council funding to the Sea Mammal Research Unit enabled this work. NERC grant no. NE/G008930/1 and Esmée Fairbairn Foundation (PP). SCS was supported as a EPSRC postdoctoral fellow (RK, PP).1. The trade‐off between survival and reproduction in resource‐limited iteroparous animals can result in some individuals missing some breeding opportunities. In practice, even with the best observation regimes, deciding whether ‘missed’ years represent real pauses in breeding or failures to detect breeding can be difficult, posing problems for the estimation of individual reproductive output and overall population fecundity. 2. We corrected fecundity estimates by determining whether breeding had occurred in skipped years, using long‐term capture–recapture observation datasets with parallel longitudinal mass measurements, based on informative underlying relationships between individuals’ mass, breeding status and environmental drivers in a capital breeding phocid, the grey seal. 3. Bayesian modelling considered interacting processes jointly: temporal changes in a phenotypic covariate (mass); relationship of mass to breeding probability; effects of maternal breeding state and mark type on resighting. Full reproductive histories were imputed, with the status of unobserved animals estimated as breeding or non‐breeding, accounting for local environmental variation. Overall fecundity was then derived for Scottish breeding colonies with contrasting pup production trends. 4. Maternal mass affected breeding likelihood. Mothers with low body mass at the end of breeding were less likely to bear a pup the following year. Successive breeding episodes incurred a cost in reduced body mass which was more pronounced for North Rona, Outer Hebrides (NR) mothers. Skipping breeding increased subsequent pupping probability substantially for low mass females. Poor environmental conditions were associated with declines in breeding probability at both colonies. Seal mass gain between breeding seasons was (a) negatively associated with lagged North Atlantic Oscillation for seals at NR and (b) positively associated with an index of seal prey (Ammodytes spp) abundance at Isle of May, Firth of Forth (IM). Overall fecundity was marginally greater at IM (increasing/stable pup production) than at NR (decreasing). No effects of mass were detected on maternal survival. 5. Skipping breeding in female grey seals appears to be an individual mass‐dependent constraint moderated by previous reproductive output and local environmental conditions. Different demographic trends at breeding colonies were consistent with the fecundities estimated using this method, which is general and adaptable to other situations.PostprintPeer reviewe