Prolonged Influenza Virus Shedding and Emergence of Antiviral Resistance in Immunocompromised Patients and Ferrets

Immunocompromised individuals tend to suffer from influenza longer with more serious complications than otherwise healthy patients. Little is known about the impact of prolonged infection and the efficacy of antiviral therapy in these patients. Among all 189 influenza A virus infected immunocompromised patients admitted to ErasmusMC, 71 were hospitalized, since the start of the 2009 H1N1 pandemic. We identified 11 (15%) cases with prolonged 2009 pandemic virus replication (longer than 14 days), despite antiviral therapy. In 5 out of these 11 (45%) cases oseltamivir resistant H275Y viruses emerged. Given the inherent difficulties in studying antiviral efficacy in immunocompromised patients, we have infected immunocompromised ferrets with either wild-type, or oseltamivir-resistant (H275Y) 2009 pandemic virus. All ferrets showed prolonged virus shedding. In wild-type virus infected animals treated with oseltamivir, H275Y resistant variants emerged within a week after infection. Unexpectedly, oseltamivir therapy still proved to be partially protective in animals infected with resistant virus. Immunocompromised ferrets offer an attractive alternative to study efficacy of novel antiviral therapies

Where are we now with European forest multi-taxon biodiversity and where can we head to?

The European biodiversity and forest strategies rely on forest sustainable management (SFM) to conserve forest biodiversity. However, current sustainability assessments hardly account for direct biodiversity indicators. We focused on forest multi-taxon biodiversity to: i) gather and map the existing information; ii) identify knowledge and research gaps; iii) discuss its research potential. We established a research network to fit data on species, standing trees, lying deadwood and sampling unit description from 34 local datasets across 3591 sampling units. A total of 8724 species were represented, with the share of common and rare species varying across taxonomic classes: some included many species with several rare ones (e.g., Insecta); others (e.g., Bryopsida) were represented by few common species. Tree-related structural attributes were sampled in a subset of sampling units (2889; 2356; 2309 and 1388 respectively for diameter, height, deadwood and microhabitats). Overall, multitaxon studies are biased towards mature forests and may underrepresent the species related to other developmental phases. European forest compositional categories were all represented, but beech forests were overrepresented as compared to thermophilous and boreal forests. Most sampling units (94%) were referred to a habitat type of conservation concern. Existing information may support European conservation and SFM strategies in: (i) methodological harmonization and coordinated monitoring; (ii) definition and testing of SFM indicators and thresholds; (iii) data-driven assessment of the effects of environmental and management drivers on multi-taxon forest biological and functional diversity, (iv) multi-scale forest monitoring integrating in-situ and remotely sensed information. Forest biodiversity Multi-taxon Sustainable management Biodiversity conservation Forest stand structurepublishedVersio

Improving our understanding of the in vivo modelling of psychotic disorders: a systematic review and meta-analysis

Psychotic disorders represent a severe category of mental disorders affecting about one percent of the population. Individuals experience a loss or distortion of contact with reality alongside other symptoms, many of which are still not adequately managed using existing treatments. While animal models of these disorders could offer insights into these disorders and potential new treatments, translation of this knowledge has so far been poor in terms of informing clinical trials and practice. The aim of this project was to improve our understanding of these pre-clinical studies and identify potential weaknesses underlying translational failure. I carried out a systematic search of the literature to provide an unbiased summary of publications reporting animal models of schizophrenia and other psychotic disorders. From these publications, data were extracted to quantify aspects of the field including reported quality of studies, study characteristics and behavioural outcome data. The latter of these data were then used to calculate estimates of efficacy using random-effects meta-analysis. Having identified 3847 publications of relevance, including 852 different methods used to induce the model, over 359 different outcomes tested in them and almost 946 different treatments reported to be administered. I show that a large proportion of studies use simple pharmacological interventions to induce their models of these disorders, despite the availability of models using other interventions that are arguably of higher translational relevance. I also show that the reported quality of these studies is low, and only 22% of studies report taking measures to reduce the risk of biases such as randomisation and blinding, which has been shown to affect the reliability of results drawn. Through this work it becomes apparent that the literature is incredibly vast for studies looking at animal models of psychotic disorders and that some of the relevant work potentially overlaps with studies describing other conditions. This means that drawing reliable conclusions from these data is affected by what is made available in the literature, how it is reported and identified in a search and the time that it takes to reach these conclusions. I introduce the idea of using computer-assisted tools to overcome one of these problems in the long term. Translation of results from studies looking at animals modelling uniquely-human psychotic disorders to clinical successes might be improved by better reporting of studies including publishing of all work carried out, labelling of studies more uniformly so that it is identifiable, better reporting of study design including improving on reporting of measures taken to reduce the risk of bias and focusing on models with greater validity to the human condition

Search for dark matter produced in association with bottom or top quarks in √s = 13 TeV pp collisions with the ATLAS detector

A search for weakly interacting massive particle dark matter produced in association with bottom or top quarks is presented. Final states containing third-generation quarks and miss- ing transverse momentum are considered. The analysis uses 36.1 fb−1 of proton–proton collision data recorded by the ATLAS experiment at √s = 13 TeV in 2015 and 2016. No significant excess of events above the estimated backgrounds is observed. The results are in- terpreted in the framework of simplified models of spin-0 dark-matter mediators. For colour- neutral spin-0 mediators produced in association with top quarks and decaying into a pair of dark-matter particles, mediator masses below 50 GeV are excluded assuming a dark-matter candidate mass of 1 GeV and unitary couplings. For scalar and pseudoscalar mediators produced in association with bottom quarks, the search sets limits on the production cross- section of 300 times the predicted rate for mediators with masses between 10 and 50 GeV and assuming a dark-matter mass of 1 GeV and unitary coupling. Constraints on colour- charged scalar simplified models are also presented. Assuming a dark-matter particle mass of 35 GeV, mediator particles with mass below 1.1 TeV are excluded for couplings yielding a dark-matter relic density consistent with measurements

Initial experiences in the photoacoustic detection of melanoma metastases in resected lymph nodes

Accurate lymph node analysis is essential to determine the prognosis and treatment of patients suffering from melanoma. The initial results of a tomographic photoacoustic modality to detect melanoma metastases in resected lymph nodes are presented based on phantom models and a human lymph node. The results show melanoma metastases detection is feasible and the setup is capable of distinguishing absorbing structures down to 1 mm. In addition, the use of longer laser wavelengths could result in an image containing a higher contrast ratio. Future research shall be focused on using the melanin characteristics to improve contrast and detection possibilities