Infectious disease testing of UK-bound refugees: a population-based, cross-sectional study

Background: The UK, like a number of other countries, has a refugee resettlement programme. External factors, such as higher prevalence of infectious diseases in the country of origin and circumstances of travel, are likely to increase the infectious disease risk of refugees, but published data is scarce. The International Organization for Migration carries out and collates data on standardised pre-entry health assessments (HA), including testing for infectious diseases, on all UK refugee applicants as part of the resettlement programme. From this data, we report the yield of selected infectious diseases (tuberculosis (TB), HIV, syphilis, hepatitis B and hepatitis C) and key risk factors with the aim of informing public health policy. Methods: We examined a large cohort of refugees (n = 18,418) who underwent a comprehensive pre-entry HA between March 2013 and August 2017. We calculated yields of infectious diseases stratified by nationality and compared these with published (mostly WHO) estimates. We assessed factors associated with case positivity in univariable and multivariable logistic regression analysis. Results: The number of refugees included in the analysis varied by disease (range 8506–9759). Overall yields were notably high for hepatitis B (188 cases; 2.04%, 95% CI 1.77–2.35%), while yields were below 1% for active TB (9 cases; 92 per 100,000, 48–177), HIV (31 cases; 0.4%, 0.3–0.5%), syphilis (23 cases; 0.24%, 0.15–0.36%) and hepatitis C (38 cases; 0.41%, 0.30–0.57%), and varied widely by nationality. In multivariable analysis, sub-Saharan African nationality was a risk factor for several infections (HIV: OR 51.72, 20.67–129.39; syphilis: OR 4.24, 1.21–24.82; hepatitis B: OR 4.37, 2.91–6.41). Hepatitis B (OR 2.23, 1.05–4.76) and hepatitis C (OR 5.19, 1.70–15.88) were associated with history of blood transfusion. Syphilis (OR 3.27, 1.07–9.95) was associated with history of torture, whereas HIV (OR 1521.54, 342.76–6754.23) and hepatitis B (OR 7.65, 2.33–25.18) were associated with sexually transmitted infection. Syphilis was associated with HIV (OR 10.27, 1.30–81.40). Conclusions: Testing refugees in an overseas setting through a systematic HA identified patients with a range of infectious diseases. Our results reflect similar patterns found in other programmes and indicate that the yields for infectious diseases vary by region and nationality. This information may help in designing a more targeted approach to testing, which has already started in the UK programme. Further work is needed to refine how best to identify infections in refugees, taking these factors into account

TRAIL regulatory receptors constrain human hepatic stellate cell apoptosis

This work was funded by UCLH NIHR BRC (sample collection), Wellcome Trust Investigator award (MKM) and Clinical Research Training Fellowship (USG); Medical Research Council grant (MKM) and Clinician Scientist Fellowship (DP); EASL fellowship (IO); National Health and Medical Research Council Australia (KPS)

Polycation-π Interactions Are a Driving Force for Molecular Recognition by an Intrinsically Disordered Oncoprotein Family

Molecular recognition by intrinsically disordered proteins (IDPs) commonly involves specific localized contacts and target-induced disorder to order transitions. However, some IDPs remain disordered in the bound state, a phenomenon coined "fuzziness", often characterized by IDP polyvalency, sequence-insensitivity and a dynamic ensemble of disordered bound-state conformations. Besides the above general features, specific biophysical models for fuzzy interactions are mostly lacking. The transcriptional activation domain of the Ewing's Sarcoma oncoprotein family (EAD) is an IDP that exhibits many features of fuzziness, with multiple EAD aromatic side chains driving molecular recognition. Considering the prevalent role of cation-π interactions at various protein-protein interfaces, we hypothesized that EAD-target binding involves polycation- π contacts between a disordered EAD and basic residues on the target. Herein we evaluated the polycation-π hypothesis via functional and theoretical interrogation of EAD variants. The experimental effects of a range of EAD sequence variations, including aromatic number, aromatic density and charge perturbations, all support the cation-π model. Moreover, the activity trends observed are well captured by a coarse-grained EAD chain model and a corresponding analytical model based on interaction between EAD aromatics and surface cations of a generic globular target. EAD-target binding, in the context of pathological Ewing's Sarcoma oncoproteins, is thus seen to be driven by a balance between EAD conformational entropy and favorable EAD-target cation-π contacts. Such a highly versatile mode of molecular recognition offers a general conceptual framework for promiscuous target recognition by polyvalent IDPs. © 2013 Song et al

Superluminal motion of a relativistic jet in the neutron star merger GW170817

The binary neutron star merger GW170817 was accompanied by radiation across the electromagnetic spectrum and localized to the galaxy NGC 4993 at a distance of 41+/-3 Mpc. The radio and X-ray afterglows of GW170817 exhibited delayed onset, a gradual rise in the emission with time as t^0.8, a peak at about 150 days post-merger, followed by a relatively rapid decline. To date, various models have been proposed to explain the afterglow emission, including a choked-jet cocoon and a successful-jet cocoon (a.k.a. structured jet). However, the observational data have remained inconclusive as to whether GW170817 launched a successful relativistic jet. Here we show, through Very Long Baseline Interferometry, that the compact radio source associated with GW170817 exhibits superluminal motion between two epochs at 75 and 230 days post-merger. This measurement breaks the degeneracy between the models and indicates that, while the early-time radio emission was powered by a wider-angle outflow (cocoon), the late-time emission was most likely dominated by an energetic and narrowly-collimated jet, with an opening angle of <5 degrees, and observed from a viewing angle of about 20 degrees. The imaging of a collimated relativistic outflow emerging from GW170817 adds substantial weight to the growing evidence linking binary neutron star mergers and short gamma-ray bursts.Comment: 42 pages, 4 figures (main text), 2 figures (supplementary text), 2 tables. Referee and editor comments incorporate

Environmental factors shaping the distribution of common wintering waterbirds in a lake ecosystem with developed shoreline

In this study, we tested whether the spatial distribution of waterbirds is influenced by shoreline urbanization or other habitat characteristics. We conducted monthly censuses along shoreline sections of a continental lake (Lake Balaton, Hungary) to assess the abundance of 11 common species that use this lake as a feeding and staging area during migration and winter. We estimated the degree of urbanization of the same shoreline sections and also measured other habitat characteristics (water depth, extent of reed cover, biomass of zebra mussels, distances to waste dumps and to other wetlands). We applied linear models and model averaging to identify habitat variables with high relative importance for predicting bird distributions. Bird abundance and urbanization were strongly related only in one species. Other habitat variables exhibited stronger relationships with bird distribution: (1) diving ducks and coots preferred shoreline sections with high zebra mussel biomass, (2) gulls preferred sites close to waste dumps, and (3) the abundances of several species were higher on shoreline sections close to other wetlands. Our findings suggest that the distribution of waterbirds on Lake Balaton is largely independent of shoreline urbanization and influenced by food availability and connectivity between wetlands

Chronic non-specific low back pain - sub-groups or a single mechanism?

Copyright 2008 Wand and O'Connell; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.Background: Low back pain is a substantial health problem and has subsequently attracted a considerable amount of research. Clinical trials evaluating the efficacy of a variety of interventions for chronic non-specific low back pain indicate limited effectiveness for most commonly applied interventions and approaches. Discussion: Many clinicians challenge the results of clinical trials as they feel that this lack of effectiveness is at odds with their clinical experience of managing patients with back pain. A common explanation for this discrepancy is the perceived heterogeneity of patients with chronic non-specific low back pain. It is felt that the effects of treatment may be diluted by the application of a single intervention to a complex, heterogeneous group with diverse treatment needs. This argument presupposes that current treatment is effective when applied to the correct patient. An alternative perspective is that the clinical trials are correct and current treatments have limited efficacy. Preoccupation with sub-grouping may stifle engagement with this view and it is important that the sub-grouping paradigm is closely examined. This paper argues that there are numerous problems with the sub-grouping approach and that it may not be an important reason for the disappointing results of clinical trials. We propose instead that current treatment may be ineffective because it has been misdirected. Recent evidence that demonstrates changes within the brain in chronic low back pain sufferers raises the possibility that persistent back pain may be a problem of cortical reorganisation and degeneration. This perspective offers interesting insights into the chronic low back pain experience and suggests alternative models of intervention. Summary: The disappointing results of clinical research are commonly explained by the failure of researchers to adequately attend to sub-grouping of the chronic non-specific low back pain population. Alternatively, current approaches may be ineffective and clinicians and researchers may need to radically rethink the nature of the problem and how it should best be managed

Inter-rater reliability of three standardized functional tests in patients with low back pain

<p>Abstract</p> <p>Background</p> <p>Of all patients with low back pain, 85% are diagnosed as "non-specific lumbar pain". Lumbar instability has been described as one specific diagnosis which several authors have described as delayed muscular responses, impaired postural control as well as impaired muscular coordination among these patients. This has mostly been measured and evaluated in a laboratory setting. There are few standardized and evaluated functional tests, examining functional muscular coordination which are also applicable in the non-laboratory setting. In ordinary clinical work, tests of functional muscular coordination should be easy to apply. The aim of this present study was to therefore standardize and examine the inter-rater reliability of three functional tests of muscular functional coordination of the lumbar spine in patients with low back pain.</p> <p>Methods</p> <p>Nineteen consecutive individuals, ten men and nine women were included. (Mean age 42 years, SD ± 12 yrs). Two independent examiners assessed three tests: "single limb stance", "sitting on a Bobath ball with one leg lifted" and "unilateral pelvic lift" on the same occasion. The standardization procedure took altered positions of the spine or pelvis and compensatory movements of the free extremities into account. The inter-rater reliability was analyzed by Cohen's kappa coefficient (κ) and by percentage agreement.</p> <p>Results</p> <p>The inter-rater reliability for the right and the left leg respectively was: for the single limb stance very good (κ: 0.88–1.0), for sitting on a Bobath ball good (κ: 0.79) and very good (κ: 0.88) and for the unilateral pelvic lift: good (κ: 0.61) and moderate (κ: 0.47).</p> <p>Conclusion</p> <p>The present study showed good to very good inter-rater reliability for two standardized tests, that is, the single-limb stance and sitting on a Bobath-ball with one leg lifted. Inter-rater reliability for the unilateral pelvic lift test was moderate to good. Validation of the tests in their ability to evaluate lumbar stability is required.</p

Ten Years of Surveillance for Invasive Streptococcus pneumoniae during the Era of Antiretroviral Scale-Up and Cotrimoxazole Prophylaxis in Malawi

OBJECTIVE: To document trends in invasive pneumococcal disease (IPD) in a central hospital in Malawi during the period of national scale-up of antiretroviral therapy (ART) and cotrimoxazole prophylaxis. METHODS: Between 1 January 2000 and 31 December 2009 almost 100,000 blood cultures and 40,000 cerebrospinal fluid (CSF) cultures were obtained from adults and children admitted to the Queen Elizabeth Central Hospital, Blantyre, Malawi with suspected severe bacterial infection. RESULTS: 4,445 pneumococcal isolates were obtained over the 10 year period. 1,837 were from children: 885 (19.9%) from blood and 952 (21.4%) from CSF. 2,608 were from adults: 1,813 (40.8%) from blood and 795 (17.9%) from CSF. At the start of the surveillance period cotrimoxazole resistance was 73.8% and at the end was 92.6%. Multidrug resistance (MDR) was present in almost one third of isolates and was constant over time. Free ART was introduced in Malawi in 2004. From 2005 onwards there was a decline in invasive pneumococcal infections with a negative correlation between ART scale-up and the decline in IPD (Pearson's correlation r = -0.91; p<0.001). CONCLUSION: During 2004-2009, national ART scale-up in Malawi was associated with a downward trend in IPD at QECH. The introduction of cotrimoxazole prophylaxis in HIV-infected groups has not coincided with a further increase in pneumococcal cotrimoxazole or multidrug resistance. These data highlight the importance of surveillance for high disease burden infections such as IPD in the region, which will be vital for monitoring pneumococcal conjugate vaccine introduction into national immunisation programmes

3D extracellular matrix microenvironment in bioengineered tissue models of primary pediatric and adult brain tumors.

Dynamic alterations in the unique brain extracellular matrix (ECM) are involved in malignant brain tumors. Yet studies of brain ECM roles in tumor cell behavior have been difficult due to lack of access to the human brain. We present a tunable 3D bioengineered brain tissue platform by integrating microenvironmental cues of native brain-derived ECMs and live imaging to systematically evaluate patient-derived brain tumor responses. Using pediatric ependymoma and adult glioblastoma as examples, the 3D brain ECM-containing microenvironment with a balance of cell-cell and cell-matrix interactions supports distinctive phenotypes associated with tumor type-specific and ECM-dependent patterns in the tumor cells\u27 transcriptomic and release profiles. Label-free metabolic imaging of the composite model structure identifies metabolically distinct sub-populations within a tumor type and captures extracellular lipid-containing droplets with potential implications in drug response. The versatile bioengineered 3D tumor tissue system sets the stage for mechanistic studies deciphering microenvironmental role in brain tumor progression