Impact of Tanzania's Wildlife Management Areas on household wealth

Large-scale area-based conservation measures affect millions of people globally. Understanding their social impacts is necessary to improve effectiveness and minimize negative consequences. However, quantifying the impacts of conservation measures that affect large geographic areas and diverse peoples is expensive and methodologically challenging, particularly because such evaluations should capture locally defined conceptions of well-being while permitting policy-relevant comparisons. Here, we measure the impact of Tanzania’s Wildlife Management Areas (WMAs), a national community-based conservation and poverty reduction initiative. We use a novel, cost-effective impact evaluation method based on participatory wealth ranking and Bayesian multilevel modelling. We find that from 2007 to 2015 the impacts of WMAs on wealth were small and variable, with no clear evidence of widespread poverty reduction. Accompanying qualitative data suggest that apparently positive effects in one WMA cannot be directly attributed to WMA activities. Our results suggest that current WMA policy needs to be revisited if it is to promote positive local development

Fractional branes, warped compactifications and backreacted orientifold planes

The standard extremal p-brane solutions in supergravity are known to allow for a generalisation which consists of adding a linear dependence on the world-volume coordinates to the usual harmonic function. In this note we demonstrate that remarkably this generalisation goes through in exactly the same way for p-branes with fluxes added to it that correspond to fractional p-branes. We relate this to warped orientifold compactifications by trading the Dp-branes for Op-planes that solve the RR tadpole condition. This allows us to interpret the worldvolume dependence as due to lower-dimensional scalars that flow along the massless directions in the no-scale potential. Depending on the details of the fluxes these flows can be supersymmetric domain wall flows. Our solutions provide explicit examples of backreacted orientifold planes in compactifications with non-constant moduli.Comment: 20 pages, incl. references. v2: small changes required for JHEP publication. v3: few equation typos correcte

Genome-wide distribution of 5-formylcytosine in embryonic stem cells is associated with transcription and depends on thymine DNA glycosylase

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.EAR is a Herchel Smith Fellow. MB and HB are supported by the Centre for Trophoblast Research, MB is a Next Generation Research Fellow. MJB is supported by a BBSRC studentship. The WR lab is supported by BBSRC, MRC, the Wellcome Trust, EU EpiGeneSys and BLUEPRINT. The SB lab is supported by core funding from Cancer Research UK

The problematic backreaction of SUSY-breaking branes

In this paper we investigate the localisation of SUSY-breaking branes which, in the smeared approximation, support specific non-BPS vacua. We show, for a wide class of boundary conditions, that there is no flux vacuum when the branes are described by a genuine delta-function. Even more, we find that the smeared solution is the unique solution with a regular brane profile. Our setup consists of a non-BPS AdS_7 solution in massive IIA supergravity with smeared anti-D6-branes and fluxes T-dual to ISD fluxes in IIB supergravity.Comment: 27 pages, Latex2e, 5 figure

Management of imatinib-resistant CML patients

Imatinib has had marked impact on outcomes in chronic myelogenous leukemia (CML) patients for all stages of the disease and is endorsed by international treatment guidelines as the first line option. Although imatinib is highly effective and well tolerated, the development of resistance represents a clinical challenge. Since the most frequently identified mechanism of acquired imatinib resistance is bcr-abl kinase domain point mutations, periodic hematologic, cytogenetic, and molecular monitoring is critical throughout imatinib therapy. Once cytogenetic remission is achieved, residual disease can be monitored by bcr-abl transcript levels as assayed by reverse transcription polymerase chain reaction (RT-PCR). Detection of bcr-abl mutants prior to and during imatinib therapy can aid in risk stratification as well as in determining therapeutic strategies. Thus, mutation screening is indicated in patients lacking or losing hematologic response. Moreover, search for mutations should also be performed when a 3-log reduction of bcr-abl transcripts is not achieved or there is a reproducible increase of transcript levels. In patients harboring mutations which confer imatinib resistance, novel second line tyrosine kinase inhibitors have demonstrated encouraging efficacy with low toxicity. Only the T315I bcr-abl mutant has proved totally resistant to all clinically available bcr-abl inhibitors. Strategies to further increase the rates of complete molecular remissions represent the next frontier in the targeted therapy of CML patients

(Anti-)Brane backreaction beyond perturbation theory

We improve on the understanding of the backreaction of anti-D6-branes in a flux background that is mutually BPS with D6-branes. This setup is analogous to the study of the backreaction of anti-D3-branes inserted in the KS throat, but does not require us to smear the anti-branes or do a perturbative analysis around the BPS background. We solve the full equations of motion near the anti-D6-branes and show that only two boundary conditions are consistent with the equations of motion. Upon invoking a topological argument we eliminate the boundary condition with regular H flux since it cannot lead to a solution that approaches the right kind of flux away from the anti-D6-brane. This leaves us with a boundary condition which has singular, but integrable, H flux energy density.Comment: 12 pages + appendices, 1 figure; v2: minor changes, version published in JHE

Fluoroquinolones and isoniazid-resistant tuberculosis: implications for the 2018 WHO guidance.

INTRODUCTION: 2018 World Health Organization (WHO) guidelines for the treatment of isoniazid (H)-resistant (Hr) tuberculosis recommend a four-drug regimen: rifampicin (R), ethambutol (E), pyrazinamide (Z) and levofloxacin (Lfx), with or without H ([H]RZE-Lfx). This is used once Hr is known, such that patients complete 6 months of Lfx (≥6[H]RZE-6Lfx). This cohort study assessed the impact of fluoroquinolones (Fq) on treatment effectiveness, accounting for Hr mutations and degree of phenotypic resistance. METHODS: This was a retrospective cohort study of 626 Hr tuberculosis patients notified in London, 2009-2013. Regimens were described and logistic regression undertaken of the association between regimen and negative regimen-specific outcomes (broadly, death due to tuberculosis, treatment failure or disease recurrence). RESULTS: Of 594 individuals with regimen information, 330 (55.6%) were treated with (H)RfZE (Rf=rifamycins) and 211 (35.5%) with (H)RfZE-Fq. The median overall treatment period was 11.9 months and median Z duration 2.1 months. In a univariable logistic regression model comparing (H)RfZE with and without Fqs, there was no difference in the odds of a negative regimen-specific outcome (baseline (H)RfZE, cluster-specific odds ratio 1.05 (95% CI 0.60-1.82), p=0.87; cluster NHS trust). Results varied minimally in a multivariable model. This odds ratio dropped (0.57, 95% CI 0.14-2.28) when Hr genotype was included, but this analysis lacked power (p=0.42). CONCLUSIONS: In a high-income setting, we found a 12-month (H)RfZE regimen with a short Z duration to be similarly effective for Hr tuberculosis with or without a Fq. This regimen may result in fewer adverse events than the WHO recommendations

Ovarian cancer symptom awareness and anticipated delayed presentation in a population sample

Background: While ovarian cancer is recognised as having identifiable early symptoms, understanding of the key determinants of symptom awareness and early presentation is limited. A population-based survey of ovarian cancer awareness and anticipated delayed presentation with symptoms was conducted as part of the International Cancer Benchmarking Partnership (ICBP). Methods: Women aged over 50 years were recruited using random probability sampling (n = 1043). Computer-assisted telephone interviews were used to administer measures including ovarian cancer symptom recognition, anticipated time to presentation with ovarian symptoms, health beliefs (perceived risk, perceived benefits/barriers to early presentation, confidence in symptom detection, ovarian cancer worry), and demographic variables. Logistic regression analysis was used to identify the contribution of independent variables to anticipated presentation (categorised as < 3 weeks or ≥ 3 weeks). Results: The most well-recognised symptoms of ovarian cancer were post-menopausal bleeding (87.4%), and persistent pelvic (79.0%) and abdominal (85.0%) pain. Symptoms associated with eating difficulties and changes in bladder/bowel habits were recognised by less than half the sample. Lower symptom awareness was significantly associated with older age (p ≤ 0.001), being single (p ≤ 0.001), lower education (p ≤ 0.01), and lack of personal experience of ovarian cancer (p ≤ 0.01). The odds of anticipating a delay in time to presentation of ≥ 3 weeks were significantly increased in women educated to degree level (OR = 2.64, 95% CI 1.61 – 4.33, p ≤ 0.001), women who reported more practical barriers (OR = 1.60, 95% CI 1.34 – 1.91, p ≤ 0.001) and more emotional barriers (OR = 1.21, 95% CI 1.06 – 1.40, p ≤ 0.01), and those less confident in symptom detection (OR = 0.56, 95% CI 0.42 – 0.73, p ≤ 0.001), but not in those who reported lower symptom awareness (OR = 0.99, 95% CI 0.91 – 1.07, p = 0.74). Conclusions: Many symptoms of ovarian cancer are not well-recognised by women in the general population. Evidence-based interventions are needed not only to improve public awareness but also to overcome the barriers to recognising and acting on ovarian symptoms, if delays in presentation are to be minimised

Investigating causality in associations between smoking initiation and schizophrenia using Mendelian randomization

Smoking is strongly associated with schizophrenia. Although it has been widely assumed that this reflects self-medication, recent studies suggest that smoking may be a risk factor for schizophrenia. We performed two-sample bi-directional Mendelian randomization using summary level genomewide association data from the Tobacco And Genetics Consortium and Psychiatric Genomics Consortium. Variants associated with smoking initiation and schizophrenia were combined using an inverse-variance weighted fixed-effects approach. We found evidence consistent with a causal effect of smoking initiation on schizophrenia risk (OR 1.73, 95% CI 1.30-2.25, p < 0.001). However, after relaxing the p-value threshold to include variants from more than one gene and minimize the potential impact of pleiotropy, the association was attenuated (OR 1.03, 95% CI 0.97-1.09, p = 0.32). There was little evidence in support of a causal effect of schizophrenia on smoking initiation (OR 1.01, 95% CI 0.98-1.04, p = 0.32). MR Egger regression sensitivity analysis indicated no evidence for pleiotropy in the effect of schizophrenia on smoking initiation (intercept OR 1.01, 95% CI 0.99-1.02, p = 0.49). Our findings provide little evidence of a causal association between smoking initiation and schizophrenia, in either direction. However, we cannot rule out a causal effect of smoking on schizophrenia related to heavier, lifetime exposure, rather than initiation.Funding from British Heart Foundation, Cancer Research UK, Economic and Social Research Council, Medical Research Council, and the National Institute for Health Research, under the auspices of the UK Clinical Research Collaboration, is gratefully acknowledged. Support from the Medical Research Council (MC_UU_12013/6, MR/M006727/1) is also gratefully acknowledged. Stephen Burgess is supported by a fellowship from the Wellcome Trust (100114)