A proposed method of grading malaria chemoprevention efficacy

The efficacy and effectiveness of antimalarial drugs are threatened by increasing levels of resistance and therefore require continuous monitoring. Chemoprevention is increasingly deployed as a malaria control measure, but there are no generally accepted methods of assessment. We propose a simple method of grading the parasitological response to chemoprevention (focusing on seasonal malaria chemoprevention) that is based on pharmacometric assessment

Surface embedding, topology and dualization for spin networks

Spin networks are graphs derived from 3nj symbols of angular momentum. The surface embedding, the topology and dualization of these networks are considered. Embeddings into compact surfaces include the orientable sphere S^2 and the torus T, and the not orientable projective space P^2 and Klein's bottle K. Two families of 3nj graphs admit embeddings of minimal genus into S^2 and P^2. Their dual 2-skeletons are shown to be triangulations of these surfaces.Comment: LaTeX 17 pages, 6 eps figures (late submission to arxiv.org

Vanishing wildlife corridors and options for restoration: a case study from Tanzania

Conserving wildlife corridors is increasingly important for maintaining ecological and genetic connectivity in times of unprecedented habitat fragmentation. Documenting connectivity loss, assessing root causes, and exploring restoration options are therefore priority conservation goals. A 2009 nationwide assessment in Tanzania documented 31 major remaining corridors, the majority of which were described as threatened. The corridor between the Udzungwa Mountains and the Selous Game Reserve in south-central Tanzania, a major link between western and southern wildlife communities, especially for the African elephant Loxodonta africana, provides an illuminating case study. A preliminary assessment in 2005 found that connectivity was barely persisting via two remaining routes. Here we present assessments of these two corridors conducted from 2007-2010, using a combination of dung surveys, habitat mapping and questionnaires. We found that both corridor routes have become closed over the last five years. Increased farming and livestock keeping, associated with both local immigration and population growth, were the main reasons for corridor blockage. However, continued attempts by elephants to cross by both routes suggest that connectivity can be restored. This entails a process of harmonizing differing land owners and uses towards a common goal. We provide recommendations for restoring lost connectivity and discuss the prospects for preventing further loss of corridors across the country

Relative Roles of Grey Squirrels, Supplementary Feeding, and Habitat in Shaping Urban Bird Assemblages

Non-native species are frequently considered to influence urban assemblages. The grey squirrel Sciurus carolinensis is one such species that is widespread in the UK and is starting to spread across Europe; it predates birds’ nests and can compete with birds for supplementary food. Using distance sampling across the urbanisation intensity gradient in Sheffield (UK) we test whether urban grey squirrels influence avian species richness and density through nest predation and competition for supplementary food sources. We also assess how urban bird assemblages respond to supplementary feeding. We find that grey squirrels slightly reduced the abundance of breeding bird species most sensitive to squirrel nest predation by reducing the beneficial impact of woodland cover. There was no evidence that grey squirrel presence altered relationships between supplementary feeding and avian assemblage structure. This may be because, somewhat surprisingly, supplementary feeding was not associated with the richness or density of wintering bird assemblages. These associations were positive during the summer, supporting advocacy to feed birds during the breeding season and not just winter, but explanatory capacity was limited. The amount of green space and its quality, assessed as canopy cover, had a stronger influence on avian species richness and population size than the presence of grey squirrels and supplementary feeding stations. Urban bird populations are thus more likely to benefit from investment in improving the availability of high quality habitats than controlling squirrel populations or increased investment in supplementary feeding

Direct glia-to-neuron transdifferentiation gives rise to a pair of male-specific neurons that ensure nimble male mating

Sexually dimorphic behaviours require underlying differences in the nervous system between males and females. The extent to which nervous systems are sexually dimorphic and the cellular and molecular mechanisms that regulate these differences are only beginning to be understood. We reveal here a novel mechanism by which male-specific neurons are generated in Caenorhabditis elegans through the direct transdifferentiation of sex-shared glial cells. This glia-to-neuron cell fate switch occurs during male sexual maturation under the cell-autonomous control of the sex-determination pathway. We show that the neurons generated are cholinergic, peptidergic, and ciliated putative proprioceptors which integrate into male-specific circuits for copulation. These neurons ensure coordinated backward movement along the mate’s body during mating. One step of the mating sequence regulated by these neurons is an alternative readjustment movement performed when intromission becomes difficult to achieve. Our findings reveal programmed transdifferentiation as a developmental mechanism underlying flexibility in innate behaviour

Type III Nrg1 Back Signaling Enhances Functional TRPV1 along Sensory Axons Contributing to Basal and Inflammatory Thermal Pain Sensation

Type III Nrg1, a member of the Nrg1 family of signaling proteins, is expressed in sensory neurons, where it can signal in a bi-directional manner via interactions with the ErbB family of receptor tyrosine kinases (ErbB RTKs) [1]. Type III Nrg1 signaling as a receptor (Type III Nrg1 back signaling) can acutely activate phosphatidylinositol-3-kinase (PtdIns3K) signaling, as well as regulate levels of α7* nicotinic acetylcholine receptors, along sensory axons [2]. Transient receptor potential vanilloid 1 (TRPV1) is a cation-permeable ion channel found in primary sensory neurons that is necessary for the detection of thermal pain and for the development of thermal hypersensitivity to pain under inflammatory conditions [3]. Cell surface expression of TRPV1 can be enhanced by activation of PtdIns3K [4], [5], [6], making it a potential target for regulation by Type III Nrg1. We now show that Type III Nrg1 signaling in sensory neurons affects functional axonal TRPV1 in a PtdIns3K-dependent manner. Furthermore, mice heterozygous for Type III Nrg1 have specific deficits in their ability to respond to noxious thermal stimuli and to develop capsaicin-induced thermal hypersensitivity to pain. Cumulatively, these results implicate Type III Nrg1 as a novel regulator of TRPV1 and a molecular mediator of nociceptive function

Patient-reported outcomes in the ProtecT randomized trial of clinically localized prostate cancer treatments: Study design, and baseline urinary, bowel and sexual function and quality of life

Objectives: To present the baseline patient-reported outcome measures (PROMs) in the Prostate Testing for Cancer and Treatment (ProtecT) randomized trial comparing active monitoring, radical prostatectomy and external-beam conformal radiotherapy for localized prostate cancer and to compare results with other populations. Materials and Methods: A total of 1643 randomized men, aged 50-69 years and diagnosed with clinically localized disease identified by prostate-specific antigen (PSA) testing, in nine UK cities in the period 1999-2009 were included. Validated PROMs for disease-specific (urinary, bowel and sexual function) and condition-specific impact on quality of life (Expanded Prostate Index Composite [EPIC], 2005 onwards; International Consultation on Incontinence Questionnaire-Urinary Incontinence [ICIQ-UI], 2001 onwards; the International Continence Society short-form male survey [ICSmaleSF]; anxiety and depression (Hospital Anxiety and Depression Scale [HADS]), generic mental and physical health (12-item short-form health survey [SF-12]; EuroQol quality-of-life survey, the EQ-5D-3L) were assessed at prostate biopsy clinics before randomization. Descriptive statistics are presented by treatment allocation and by men's age at biopsy and PSA testing time points for selected measures. Results: A total of 1438 participants completed biopsy questionnaires (88%) and 77-88% of these were analysed for individual PROMs. Fewer than 1% of participants were using pads daily (5/754). Storage lower urinary tract symptoms were frequent (e.g. nocturia 22%, 312/1423). Bowel symptoms were rare, except for loose stools (16%, 118/754). One third of participants reported erectile dysfunction (241/735) and for 16% (118/731) this was a moderate or large problem. Depression was infrequent (80/1399, 6%) but 20% of participants (278/1403) reported anxiety. Sexual function and bother were markedly worse in older men (65-70 years), whilst urinary bother and physical health were somewhat worse than in younger men (49-54 years, all P < 0.001). Bowel health, urinary function and depression were unaltered by age, whilst mental health and anxiety were better in older men (P < 0.001). Only minor differences existed in mental or physical health, anxiety and depression between PSA testing and biopsy assessments. Conclusion: The ProtecT trial baseline PROMs response rates were high. Symptom frequencies and generic quality of life were similar to those observed in populations screened for prostate cancer and control subjects without cancer

A bird’s eye view: using circuit theory to study urban landscape connectivity for birds

Context Connectivity is fundamental to understanding how landscape form influences ecological function. However, uncertainties persist due to the difficulty and expense of gathering empirical data to drive or to validate connectivity models, especially in urban areas, where relationships are multifaceted and the habitat matrix cannot be considered to be binary. Objectives This research used circuit theory to model urban bird flows (i.e. ‘current’), and compared results to observed abundance. The aims were to explore the ability of this approach to predict wildlife flows and to test relationships between modelled connectivity and variation in abundance. Methods Circuitscape was used to model functional connectivity in Bedford, Luton/Dunstable, and Milton Keynes, UK, for great tits (Parus major) and blue tits (Cyanistes caeruleus), drawing parameters from published studies of woodland bird flows in urban environments. Model performance was then tested against observed abundance data. Results Modelled current showed a weak yet positive agreement with combined abundance for P. major and C. caeruleus. Weaker correlations were found for other woodland species, suggesting the approach may be expandable if re-parameterised. Conclusions Trees provide suitable habitat for urban woodland bird species, but their location in large, contiguous patches and corridors along barriers also facilitates connectivity networks throughout the urban matrix. Urban connectivity studies are well-served by the advantages of circuit theory approaches, and benefit from the empirical study of wildlife flows in these landscapes to parameterise this type of modelling more explicitly. Such results can prove informative and beneficial in designing urban green space and new developments