Modelling the functional connectivity of landscapes for greater horseshoe bats Rhinolophus ferrumequinum at a local scale

Context: The importance of habitat connectivity for wildlife is widely recognised. However, assessing the movement of species tends to rely on radio-tracking or GPS evidence, which is difficult and costly to gather. Objectives: To examine functional connectivity of greater horseshoe bats (GHS, Rhinolophus ferrumequinum) at a local scale using Circuitscape software; comparing our results against expert opinion ‘fly ways’. Methods: Expert opinions were used to rank and score five environmental layers influencing GHS movement, generating resistance scores. The slope and resistance scores of these layers were varied, and validated against independent ground truthed GHS activity data, until a unimodal peak in correlation was identified for each layer. The layers were combined into a multivariate model and re-evaluated. Radiotracking studies were used to further validate the model, and the transferability was tested at other roost locations. Results: Functional connectivity models could be created using bat activity data. Models had the ability to be transferred between roost locations, although site-specific validation is strongly recommended. For all other bat species recorded, markedly more (125%) bat passes occurred in the top quartile of functional connectivity compared to any of the lower three quartiles. Conclusion: The model predictions identify areas of key conservation importance to habitat connectivity for GHS that are not recognised by expert opinion. By highlighting landscape features that act as barriers to movement, this approach can be used by decision-makers as a tool to inform local management strategies

Ways Ahead: developing a supported self-management programme for people living with low- and intermediate-grade gliomas - a protocol for a multi-method study

INTRODUCTION: Living with and beyond a diagnosis of a low- and intermediate-grade glioma (LIGG) can adversely impact many aspects of people's lives and their quality of life (QoL). In people with chronic conditions, self-management can improve QoL. This is especially true if people are supported to self-manage. Supported self-management programmes have been developed for several cancers, but the unique challenges experienced by LIGG survivors mean these programmes may not be readily transferable to this group. The Ways Ahead study aims to address this gap by exploring the needs of LIGG survivors to develop a prototype for a supported self-management programme tailored to this group. METHODS AND ANALYSIS: Ways Ahead will follow three sequential phases, underpinned by a systematic review of self-management interventions in cancer. In phase 1, qualitative methods will be used to explore and understand the issues faced by LIGG survivors, as well as the barriers and facilitators to self-management. Three sets of interviews will be conducted with LIGG survivors, their informal carers and professionals. Thematic analysis will be conducted with reference to the Theoretical Domains Framework and Normalisation Process Theory. Phase 2 will involve co-production workshops to generate ideas for the design of a supported self-management programme. Workshop outputs will be translated into a design specification for a prototype programme. Finally, phase 3 will involve a health economic assessment to examine the feasibility and benefits of incorporating the proposed programme into the current survivorship care pathway. This prototype will then be ready for testing in a subsequent trial. ETHICS AND DISSEMINATION: The study has been reviewed and approved by an National Health Service Research Ethics Committee (REC ref: 20/WA/0118). The findings will be disseminated through peer-reviewed journals, conference presentations, broadcast media, the study website, The Brain Tumour Charity and stakeholder engagement activities

Making Sense of Family Deaths in Urban Senegal: Diversities, Contexts, and Comparisons

Despite calls for cross-cultural research, Minority world perspectives still dominate death and bereavement studies, emphasizing individualized emotions and neglecting contextual diversities. In research concerned with contemporary African societies, on the other hand, death and loss are generally subsumed within concerns about AIDS or poverty, with little attention paid to the emotional and personal significance of a death. Here, we draw on interactionist sociology to present major themes from a qualitative study of family deaths in urban Senegal, theoretically framed through the duality of meanings-in-context. Such themes included family and community as support and motivation; religious beliefs and practices as frameworks for solace and (regulatory) meaning; and material circumstances as these are intrinsically bound up with emotions. Although we identify the experience of (embodied, emotional) pain as a common response across Minority and Majority worlds, we also explore significant divergencies, varying according to localized contexts and broader power dynamics

Clinical evaluation of iron treatment efficiency among non-anemic but iron-deficient female blood donors: a randomized controlled trial

ABSTRACT: Iron deficiency without anemia (IDWA) is related to adverse symptoms that can be relieved by supplementation. Since a blood donation can induce such an iron deficiency, we investigated the clinical impact of an iron treatment after blood donation. METHODS: One week after donation, we randomly assigned 154 female donors with IDWA aged <50 years to a 4-week oral treatment of ferrous sulfate vs. placebo. The main outcome was the change in the level of fatigue before and after the intervention. Also evaluated were aerobic capacity, mood disorder, quality of life, compliance and adverse events. Biological markers were hemoglobin and ferritin. RESULTS: Treatment effect from baseline to 4 weeks for hemoglobin and ferritin were 5.2 g/L (p < 0.01) and 14.8 ng/mL (p < 0.01) respectively. No significant clinical effect was observed for fatigue (-0.15 points, 95% confidence interval -0.9 to 0.6, p = 0.697) or for other outcomes. Compliance and interruption for side effects was similar in both groups. Additionally, blood donation did not induce overt symptoms of fatigue in spite of the significant biological changes it produces. CONCLUSIONS: These data are valuable as they enable us to conclude that donors with IDWA after a blood donation would not clinically benefit from iron supplementation. Trial registration: NCT00689793

Rest-Mediated Regulation of Extracellular Matrix Is Crucial for Neural Development

Neural development from blastocysts is strictly controlled by intricate transcriptional programmes that initiate the down-regulation of pluripotent genes, Oct4, Nanog and Rex1 in blastocysts followed by up-regulation of lineage-specific genes as neural development proceeds. Here, we demonstrate that the expression pattern of the transcription factor Rest mirrors those of pluripotent genes during neural development from embryonic stem (ES) cells and an early abrogation of Rest in ES cells using a combination of gene targeting and RNAi approaches causes defects in this process. Specifically, Rest ablation does not alter ES cell pluripotency, but impedes the production of Nestin+ neural stem cells, neural progenitor cells and neurons, and results in defective adhesion, decrease in cell proliferation, increase in cell death and neuronal phenotypic defects typified by a reduction in migration and neurite elaboration. We also show that these Rest-null phenotypes are due to the dysregulation of its direct or indirect target genes, Lama1, Lamb1, Lamc1 and Lama2 and that these aberrant phenotypes can be rescued by laminins

Therapeutic and Prognostic Implications of BRAF V600E in Pediatric Low-Grade Gliomas.

Purpose BRAF V600E is a potentially highly targetable mutation detected in a subset of pediatric low-grade gliomas (PLGGs). Its biologic and clinical effect within this diverse group of tumors remains unknown. Patients and Methods A combined clinical and genetic institutional study of patients with PLGGs with long-term follow-up was performed (N = 510). Clinical and treatment data of patients with BRAF V600E mutated PLGG (n = 99) were compared with a large international independent cohort of patients with BRAF V600E mutated-PLGG (n = 180). Results BRAF V600E mutation was detected in 69 of 405 patients (17%) with PLGG across a broad spectrum of histologies and sites, including midline locations, which are not often routinely biopsied in clinical practice. Patients with BRAF V600E PLGG exhibited poor outcomes after chemotherapy and radiation therapies that resulted in a 10-year progression-free survival of 27% (95% CI, 12.1% to 41.9%) and 60.2% (95% CI, 53.3% to 67.1%) for BRAF V600E and wild-type PLGG, respectively ( P \u3c .001). Additional multivariable clinical and molecular stratification revealed that the extent of resection and CDKN2A deletion contributed independently to poor outcome in BRAF V600E PLGG. A similar independent role for CDKN2A and resection on outcome were observed in the independent cohort. Quantitative imaging analysis revealed progressive disease and a lack of response to conventional chemotherapy in most patients with BRAF V600E PLGG. Conclusion BRAF V600E PLGG constitutes a distinct entity with poor prognosis when treated with current adjuvant therapy

Therapeutic and Prognostic Implications of BRAF V600E in Pediatric Low-Grade Gliomas

Purpose BRAF V600E is a potentially highly targetable mutation detected in a subset of pediatric low-grade gliomas (PLGGs). Its biologic and clinical effect within this diverse group of tumors remains unknown. Patients and Methods A combined clinical and genetic institutional study of patients with PLGGs with long-term follow-up was performed (N = 510). Clinical and treatment data of patients with BRAF V600E mutated PLGG (n = 99) were compared with a large international independent cohort of patients with BRAF V600E mutated-PLGG (n = 180). Results BRAF V600E mutation was detected in 69 of 405 patients (17%) with PLGG across a broad spectrum of histologies and sites, including midline locations, which are not often routinely biopsied in clinical practice. Patients with BRAF V600E PLGG exhibited poor outcomes after chemotherapy and radiation therapies that resulted in a 10-year progression-free survival of 27% (95% CI, 12.1% to 41.9%) and 60.2% (95% CI, 53.3% to 67.1%) for BRAF V600E and wild-type PLGG, respectively (P < .001). Additional multivariable clinical and molecular stratification revealed that the extent of resection and CDKN2A deletion contributed independently to poor outcome in BRAF V600E PLGG. A similar independent role for CDKN2A and resection on outcome were observed in the independent cohort. Quantitative imaging analysis revealed progressive disease and a lack of response to conventional chemotherapy in most patients with BRAF V600E PLGG. Conclusion BRAF V600E PLGG constitutes a distinct entity with poor prognosis when treated with current adjuvant therapy. (C) 2017 by American Society of Clinical Oncolog

Evaluation of eight lateral flow tests for the detection of anti-SARS-CoV-2 antibodies in a vaccinated population

Background: Rapid determination of an individual's antibody status can be beneficial in understanding an individual's immune response to SARS-CoV-2 and for initiation of therapies that are only deemed effective in sero-negative individuals. Antibody lateral flow tests (LFTs) have potential to address this need as a rapid, point of care test. Methods: Here we present a proof-of-concept evaluation of eight LFT brands using sera from 95 vaccinated individuals to determine sensitivity for detecting vaccination generated antibodies. Samples were analysed on eight different brands of antibody LFT and an automated chemiluminescent microparticle immunoassay (CMIA) that identifies anti-spike antibodies which was used as our reference standard. Results: All 95 (100%) participants tested positive for anti-spike antibodies by the chemiluminescent microparticle immunoassay (CMIA) reference standard post-dose two of their SARS-CoV-2 vaccine: BNT162b2 (Pfizer/BioNTech, n = 60), AZD1222 (AstraZeneca, n = 31), mRNA-1273 (Moderna, n = 2) and Undeclared Vaccine Brand (n = 2). Sensitivity increased from dose one to dose two in six out of eight LFTs with three tests achieving 100% sensitivity at dose two in detecting anti-spike antibodies. Conclusions: These tests are demonstrated to be highly sensitive to detect raised antibody levels in vaccinated individuals. RDTs are low cost and rapid alternatives to ELISA based systems

Proceedings of Patient Reported Outcome Measure’s (PROMs) Conference Oxford 2017: Advances in Patient Reported Outcomes Research

A33-Effects of Out-of-Pocket (OOP) Payments and Financial Distress on Quality of Life (QoL) of People with Parkinson’s (PwP) and their Carer

Adrenal gland tumorigenesis after gonadectomy in mice is a complex genetic trait driven by epistatic loci

Postgonadectomy adrenocortical tumorigenesis is a strain-specific phenomenon in inbred mice, assumed to be caused by elevated LH secretion and subsequent ectopic LH receptor (LHR) overexpression in adrenal gland. However, the molecular mechanisms of this cascade of events remain unknown. In this study, we took advantage of the mouse strain dependency of the phenotype to unravel its genetic basis. Our results present the first genome-wide screening related to this pathology in two independent F2 and backcross populations generated between the neoplastic DBA/2J and the nonsusceptible C57BL/6J strains. Surprisingly, the postgonadectomy elevation of serum LH was followed by similar up-regulation of adrenal LHR expression in both parental strains and their crosses, irrespective of their tumor status, indicating that it is not the immediate cause of the tumorigenesis. Linkage analysis revealed one major significant locus for the tumorigenesis on chromosome 8, modulated by epistasis with another quantitative trait locus on chromosome 18. Weight gain, a secondary phenotype after gonadectomy, showed a significant but separate quantitative trait locus on chromosome 7. Altogether, postgonadectomy adrenocortical tumorigenesis in DBA/2J mice is a dominant trait that is not a direct consequence of adrenal LHR expression but is driven by a complex genetic architecture. Analysis of candidate genes in the tumorigenesis linkage region showed that Sfrp1 (secreted frizzled-related protein 1), a tumor suppressor gene, is differentially expressed in the neoplastic areas. These findings may have relevance to the human pathogenesis of macronodular adrenal hyperplasia and adrenocortical tumors in postmenopausal women and why some of them develop obesity