Quantifying the differences in avian attack rates on reptiles between an infrastructure and a control site

Acknowledgements We would like to thank Professor Bob Furness for his comments on an earlier draft of this manuscript, and the staff of Camster Wind Farm for their cooperation. Two anonymous reviewers provided comments that greatly improved the text.Peer reviewedPostprin

Adrenal suppression following intralesional corticosteroids for periocular haemangiomas

Background/aims Treatment with intralesional triamcinolone/betamethasone is recommended for infantile sight-threatening periocular haemangiomas. This study investigates the endocrine and weight changes in 15 infants undergoing therapy over 12 years. Methods 15 infants, median age 19 weeks (range 10–56) receiving intra/perilesional triamcinolone/betamethasone underwent serial measurement of weight, early morning serum cortisol and adrenocorticotropic hormone (ACTH) before and after injection. Results Cortisol fell from a median (range) of 383 (112–594) to 28 (<10–506) nmol/l (p=0.005) and ACTH from 26 (14–134) to 9 (5–20) ng/l (p=0.05) from before injection to 4 weeks after treatment. Prolonged adrenal suppression occurred in 13 out of 15 cases with time to recovery being 19.5 (4–65) weeks. Failure to gain weight appropriately was observed in 14 infants but recovered once normal adrenal function was re-established. Conclusion Prolonged adrenal suppression following triamcinolone/betamethasone injection for periocular haemangiomas is common and associated with faltering weight gain

A dyad of lymphoblastic lysosomal cysteine proteases degrades the antileukemic drug L-asparaginase

l-Asparaginase is a key therapeutic agent for treatment of childhood acute lymphoblastic leukemia (ALL). There is wide individual variation in pharmacokinetics, and little is known about its metabolism. The mechanisms of therapeutic failure with l-asparaginase remain speculative. Here, we now report that 2 lysosomal cysteine proteases present in lymphoblasts are able to degrade l-asparaginase. Cathepsin B (CTSB), which is produced constitutively by normal and leukemic cells, degraded asparaginase produced by Escherichia coli (ASNase) and Erwinia chrysanthemi. Asparaginyl endopeptidase (AEP), which is overexpressed predominantly in high-risk subsets of ALL, specifically degraded ASNase. AEP thereby destroys ASNase activity and may also potentiate antigen processing, leading to allergic reactions. Using AEP-mediated cleavage sequences, we modeled the effects of the protease on ASNase and created a number of recombinant ASNase products. The N24 residue on the flexible active loop was identified as the primary AEP cleavage site. Sole modification at this site rendered ASNase resistant to AEP cleavage and suggested a key role for the flexible active loop in determining ASNase activity. We therefore propose what we believe to be a novel mechanism of drug resistance to ASNase. Our results may help to identify alternative therapeutic strategies with the potential of further improving outcome in childhood ALL

Microwave dielectric sensing of free-flowing, single, living cells in aqueous suspension

Dielectric measurements offer the possibility of highly sensitive detection of physical cell properties, and are of interest for clinical applications due to their non-destructive nature and the lack of need for cell labelling. Here we report sensitive measurements on single, living, free-flowing cells (not electrostatically or dielectrophoretically trapped, cultured or fixed directly on sensing elements) in aqueous medium at ~9.8 GHz taken using a coupled dielectric-split ring resonator assembly. Inductive coupling between the two resonators enabled separation of microfluidic chips from RF connectors and allowed for time-resolved continuous-wave measurements on flowing single cells via the coaxial ports of a dielectric-loaded microwave cavity. Analysis via an equivalent circuit model showed that the novel resonator assembly maintained the permittivity-dependent sensitivity of a split ring resonator while operating at quality factors >1000 with lossy aqueous media (typically ~1900). Using a microfluidic channel with a 300 x 300 μm cross section, at a water-loaded resonant amplitude of ~-22 dB at 0 dBm input power level, shifts in amplitude due to individual cells passing through the sensing region of up to -0.0015 dB were observed. Correlations between averaged amplitude shifts and cell size as well as material properties demonstrate the diagnostic potential of this technique

Final Protocol and Statistical Analysis Plan for the SNAP Trial - a randomised, double-blind, placebo-controlled trial of nicotine replacement therapy in pregnancy

This NIHR HTA-funded smoking, nicotine and pregnancy (SNAP) trial investigated whether or not nicotine replacement therapy (NRT) is effective, cost-effective and safe when used for smoking cessation by pregnant women. We randomised 1050 women who were between 12 and 24 weeks pregnant as they attended hospital for ante-natal ultrasound scans. Women received either nicotine or placebo transdermal patches with behavioural support. The primary outcome measure was biochemically-validated, self-reported, prolonged and total abstinence from smoking between a quit date (defined before randomisation and set within 2 weeks of this) and delivery. At 6 months after childbirth self-reported maternal smoking status was ascertained and 2 years after childbirth, self-reported maternal smoking status and the behaviour, cognitive development and respiratory symptoms of children born in the trial were compared in both groups. This repository contains the final approved version of the protocol plus the statistical analysis plan (SAP) for both outcomes at delivery and following the 2 year follow up period after birth

Cost and cost-effectiveness analysis of mass drug administration compared to school-based targeted preventive chemotherapy for hookworm control in Dak Lak province, Vietnam

Background: School-based targeted preventive chemotherapy (PC), the main strategy for soil-transmitted helminths (STH) control, excludes other at-risk populations including adults and preschool children. Mass drug administration (MDA), covering all age groups, would bring additional health benefits but also requires greater investment. This cost survey and cost-effectiveness analysis compared MDA with school-based targeted PC for STH control in Dak Lak, Vietnam, where STH are endemic. Methods: A cost survey was conducted in 2020 to estimate the total and per person economic and financial cost of each strategy. Monte Carlo simulation accounted for uncertainty in cost estimates. The primary effectiveness measure was hookworm-related disability-adjusted life years (DALYs) averted, and secondary measures were hookworm infection-years averted and moderate-to-heavy intensity hookworm infection-years averted. A Markov model was used to determine the incremental cost-effectiveness ratio (ICER) of MDA compared to school-based targeted PC using a government payer perspective and a ten-year time horizon. One-way and probabilistic sensitivity analyses (PSA) were performed. Costs are reported in 2020 USD ($). Findings: The economic cost per person was$0.27 for MDA and $0.43 for school-based targeted PC. MDA in Dak Lak will cost$472,000 per year, while school-based targeted PC will cost $117,000. Over 10 years, MDA is estimated to avert an additional 121,465 DALYs; 4,019,262 hookworm infection-years, and 765,844 moderate-to-heavy intensity hookworm infection-years compared to school-based targeted PC. The ICER was$28.55 per DALY averted; $0.87 per hookworm infection-years averted, and$4.54 per moderate-to-heavy intensity hookworm infection-years averted. MDA was cost-effective in all PSA iterations. Interpretation: In areas where hookworm predominates and adults suffer a significant burden of infection, MDA is cost effective compared to school based targeted PC and is the best strategy to achieve global targets. \</p

High-throughput sequencing offers insight into mechanisms of resource partitioning in cryptic bat species

Sympatric cryptic species, characterized by low morphological differentiation, pose a challenge to understanding the role of interspecific competition in structuring ecological communities. We used traditional (morphological) and novel molecular methods of diet analysis to study the diet of two cryptic bat species that are sympatric in southern England (Plecotus austriacus and P. auritus) (Fig. 1). Using Roche FLX 454 (Roche, Basel, CH) high-throughput sequencing (HTS) and uniquely tagged generic arthropod primers, we identified 142 prey Molecular Operational Taxonomic Units (MOTUs) in the diet of the cryptic bats, 60% of which were assigned to a likely species or genus. The findings from the molecular study supported the results of microscopic analyses in showing that the diets of both species were dominated by lepidopterans. However, HTS provided a sufficiently high resolution of prey identification to determine fine-scale differences in resource use. Although both bat species appeared to have a generalist diet, eared-moths from the family Noctuidae were the main prey consumed. Interspecific niche overlap was greater than expected by chance (Ojk= 0.72, P &lt; 0.001) due to overlap in the consumption of the more common prey species. Yet, habitat associations of nongeneralist prey species found in the diets corresponded to those of their respective bat predator (grasslands for P. austriacus, and woodland for P. auritus). Overlap in common dietary resource use combined with differential specialist prey habitat associations suggests that habitat partitioning is the primary mechanism of coexistence. The performance of HTS is discussed in relation to previous methods of molecular and morphological diet analysis. By enabling species-level identification of dietary components, the application of DNA sequencing to diet analysis allows a more comprehensive comparison of the diet of sympatric cryptic species, and therefore can be an important tool for determining fine-scale mechanisms of coexistence

A multi-disciplinary investigation of the AFEN Slide: The relationship between contourites and submarine landslides

Contourite drifts are sediment deposits formed by ocean bottom currents on continental slopes worldwide. Although it has become increasingly apparent that contourites are often prone to slope failure, the physical controls on slope instability remain unclear. This study presents high-resolution sedimentological, geochemical and geotechnical analyses of sediments to better understand the physical controls on slope failure that occurred within a sheeted contourite drift within the Faroe-Shetland Channel. We aim to identify and characterize the failure plane of the late Quaternary landslide (the AFEN Slide), and explain its location within the sheeted drift stratigraphy. The analyses reveal abrupt lithological contrasts characterized by distinct changes in physical, geochemical and geotechnical properties. Our findings indicate that the AFEN Slide likely initiated along a distinct lithological interface, between overlying sandy contouritic sediments and softer underlying mud-rich sediments. These lithological contrasts are interpreted to relate to climatically-controlled variations in sediment input and bottom current intensity. Similar lithological contrasts are likely to be common within contourite drifts at many other oceanic gateways worldwide; hence our findings are likely to apply more widely. As we demonstrate here, recognition of such contrasts requires multi-disciplinary data over the depth range of stratigraphy that is potentially prone to slope failure

Protocol for the Smoking, Nicotine and Pregnancy (SNAP) trial: double-blind, placebo-randomised, controlled trial of nicotine replacement therapy in pregnancy

Background: Smoking in pregnancy remains a public health challenge. Nicotine replacement therapy (NRT) is effective for smoking cessation in non-pregnant people, but because women metabolise nicotine and cotinine much faster in pregnancy, it is unclear whether this will be effective for smoking cessation in pregnancy. The NHS Health Technology Assessment Programme (HTA)-funded smoking, nicotine and pregnancy ( SNAP) trial will investigate whether or not nicotine replacement therapy ( NRT) is effective, cost-effective and safe when used for smoking cessation by pregnant women. Methods/Design: Over two years, in 5 trial centres, 1050 pregnant women who are between 12 and 24 weeks pregnant will be randomised as they attend hospital for ante-natal ultrasound scans. Women will receive either nicotine or placebo transdermal patches with behavioural support. The primary outcome measure is biochemically-validated, self-reported, prolonged and total abstinence from smoking between a quit date ( defined before randomisation and set within two weeks of this) and delivery. At six months after childbirth self-reported maternal smoking status will be ascertained and two years after childbirth, self-reported maternal smoking status and the behaviour, cognitive development and respiratory symptoms of children born in the trial will be compared in both groups. Discussion: This trial is designed to ascertain whether or not standard doses of NRT ( as transdermal patches) are effective and safe when used for smoking cessation during pregnancy