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

Peer reviewedPublisher PD

Environmental drivers of population-level variation in the migratory and diving ontogeny of an Arctic top predator

This work is an output of the ARISE project (NE/P006035/1 and NE/P00623X/1), part of the Changing Arctic Ocean programme jointly funded by the UKRI Natural Environment Research Council (NERC) and the German Federal Ministry of Education and Research (BMBF). Fieldwork in Canada was carried out under a Canadian Council on Animal Care permit no. NAFC2017–2 and funded by Fisheries and Oceans Canada and a bursary from Department for Business, Energy and Industrial Strategy (BEIS) administered by the NERC Arctic Office. Fieldwork in the Greenland Sea was approved by the Greenland Ministry of Fisheries, Hunting and Agriculture and the Norwegian Food Safety Authority (permit no. 11546) as part of the Northeast Greenland Environmental Study Program 2017–2018 (by the Danish Centre for Environment and Energy at Aarhus University, The Greenland Institute of Natural Resources and the Environmental Agency for Mineral Resource Activities of the Government of Greenland) and financed by oil licence holders in the area.The development of migratory strategies that enable juveniles to survive to sexual maturity is critical for species that exploit seasonal niches. For animals that forage via breath-hold diving, this requires a combination of both physiological and foraging skill development. Here, we assess how migratory and dive behaviour develop over the first year of life for a migratory Arctic top predator, the harp seal Pagophilus groenlandicus, tracked using animal-borne satellite relay data loggers. We reveal similarities in migratory movements and differences in diving behaviour between 38 juveniles tracked from the Greenland Sea and Northwest Atlantic breeding populations. In both regions, periods of resident and transitory behaviour during migration were associated with proxies for food availability: sea ice concentration and bathymetric depth. However, while ontogenetic development of dive behaviour was similar for both populations of juveniles over the first 25 days, after this time Greenland Sea animals performed shorter and shallower dives and were more closely associated with sea ice than Northwest Atlantic animals. Together, these results highlight the role of both intrinsic and extrinsic factors in shaping early life behaviour. Variation in the environmental conditions experienced during early life may shape how different populations respond to the rapid changes occurring in the Arctic ocean ecosystem.Publisher PDFPeer reviewe

Polypyridylruthenium(II) complexes exert anti-schistosome activity and inhibit parasite acetylcholinesterases

Background: Schistosomiasis affects over 200 million people and there are concerns whether the current chemotherapeutic control strategy (periodic mass drug administration with praziquantel (PZQ)—the only licenced anti-schistosome compound) is sustainable, necessitating the development of new drugs. Methodology/Principal findings: We investigated the anti-schistosome efficacy of polypyridylruthenium(II) complexes and showed they were active against all intra-mammalian stages of S. mansoni. Two compounds, Rubb12-tri and Rubb7-tnl, which were among the most potent in their ability to kill schistosomula and adult worms and inhibit egg hatching in vitro, were assessed for their efficacy in a mouse model of schistosomiasis using 5 consecutive daily i.v. doses of 2 mg/kg (Rubb12-tri) and 10 mg/kg (Rubb7-tnl). Mice treated with Rubb12-tri showed an average 42% reduction (P = 0.009), over two independent trials, in adult worm burden. Liver egg burdens were not significantly decreased in either drug-treated group but ova from both of these groups showed significant decreases in hatching ability (Rubb12-tri—68%, Rubb7-tnl—56%) and were significantly morphologically altered (Rubb12-tri—62% abnormal, Rubb7-tnl—35% abnormal). We hypothesize that the drugs exerted their activity, at least partially, through inhibition of both neuronal and tegumental acetylcholinesterases (AChEs), as worms treated in vitro showed significant decreases in activity of these enzymes. Further, treated parasites exhibited a significantly decreased ability to uptake glucose, significantly depleted glycogen stores and withered tubercules (a site of glycogen storage), implying drug-mediated interference in this nutrient acquisition pathway. Conclusions/Significance: Our data provide compelling evidence that ruthenium complexes are effective against all intra-mammalian stages of schistosomes, including schistosomula (refractory to PZQ) and eggs (agents of disease transmissibility). Further, the results of this study suggest that schistosome AChE is a target of ruthenium drugs, a finding that can inform modification of current compounds to identify analogues which are even more effective and selective against schistosomes. Author summary: Schistosomiasis is a neglected tropical disease which affects over 200 million people and there is only one licensed drug, praziquantel, currently available for treatment. In a search for new drugs to control schistosomiasis, we tested the anti-schistosome efficacy of a series of ruthenium compounds and found that a number of them were able to inhibit parasite eggs from hatching and kill adult worms and praziquantel-refractory juvenile worms in vitro. We demonstrated that the compounds inhibit schistosome acetylcholinesterase (the enzyme that breaks down the neurotransmitter acetylcholine), which could potentially result in paralysis of the parasite, likely due to uncontrolled neuromuscular function caused by acetylcholine excess. Moreover, we showed that drug-treated worms had a significantly reduced ability to uptake exogenous glucose and markedly depleted glycogen stores, presumably through inhibition of the acetylcholinesterase-mediated glucose scavenging pathway. Lastly, we found that two of the drugs—Rubb12-tri and Rubb7-tnl—when used to treat schistosome-infected mice, were able to reduce worm burdens and significantly affect the viability of parasite eggs in vivo, which would have a marked impact on disease transmission. We believe that these complexes are desirable drug lead scaffolds which could be used to develop effective and selective compounds to control and treat schistosomiasis and, potentially, other parasitic diseases.Madhu K. Sundaraneedi, Bemnet A. Tedla, Ramon M. Eichenberger, Luke Becker, Darren Pickering, Michael J. Smout, Siji Rajan, Phurpa Wangchuk, F. Richard Keene, Alex Loukas, J. Grant Collins, Mark S. Pearso

First High-Speed Video Camera Observations of a Lightning Flash Associated With a Downward Terrestrial Gamma-Ray Flash

In this paper, we present the first high-speed video observation of a cloud-to-ground lightning flash and its associated downward-directed Terrestrial Gamma-ray Flash (TGF). The optical emission of the event was observed by a high-speed video camera running at 40,000 frames per second in conjunction with the Telescope Array Surface Detector, Lightning Mapping Array, interferometer, electric-field fast antenna, and the National Lightning Detection Network. The cloud-to-ground flash associated with the observed TGF was formed by a fast downward leader followed by a very intense return stroke peak current of −154 kA. The TGF occurred while the downward leader was below cloud base, and even when it was halfway in its propagation to ground. The suite of gamma-ray and lightning instruments, timing resolution, and source proximity offer us detailed information and therefore a unique look at the TGF phenomena

WormAssay: A Novel Computer Application for Whole-Plate Motion-based Screening of Macroscopic Parasites

Lymphatic filariasis is caused by filarial nematode parasites, including Brugia malayi. Adult worms live in the lymphatic system and cause a strong immune reaction that leads to the obstruction of lymph vessels and swelling of the extremities. Chronic disease leads to the painful and disfiguring condition known as elephantiasis. Current drug therapy is effective against the microfilariae (larval stage) of the parasite, but no drugs are effective against the adult worms. One of the major stumbling blocks toward developing effective macrofilaricides to kill the adult worms is the lack of a high throughput screening method for candidate drugs. Current methods utilize systems that measure one well at a time and are time consuming and often expensive. We have developed a low-cost and simple visual imaging system to automate and quantify screening entire plates based on parasite movement. This system can be applied to the study of many macroparasites as well as other macroscopic organisms

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

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