A cryptotephra record from the Lake Victoria sediment core record of holocene palaeoenvironmental change

The sediment record from Lake Victoria is an important archive of regional environmental and climatic conditions, reaching back more than 15,000 cal. years before present (15 ka BP). As the largest lake by area in East Africa, its evolution is key to understanding regional palaeohydrological change during the late Pleistocene and Holocene, including controls on the Nile River flow. As well as important palaeoenvironmental proxies, the lake contains a unique record of explosive volcanism from the central Kenyan Rift, in the form of fine-grained volcanic ash (tephra) layers, interpreted as airfall deposits. In the V95-1P core, collected from the central northern basin of the lake, tephra layers vary in concentration from 10s to 10s of 1000s of glass shards per gram of sediment. None of the tephra are visible to the naked eye, and have only been revealed through careful laboratory processing. Compositional analyses of tephra glass shards has allowed the tephra layers to be correlated to previously unrecognized eruptions of Eburru volcano around 1.2 and 3.8 ka, and Olkaria volcano, prior to 15 ka. These volcanoes lie ~300 km east of the core site in the Kenyan Rift. Our results highlight the potential for developing cryptotephra analysis as a key tool in East African palaeolimnological research. Tephra layers offer opportunities for precise correlation of palaeoenvironmental sequences, as well as windows into the eruption frequency of regional volcanoes and the dispersal of volcanic ash. Leverhulme Trust Early Career Fellowshi

Fatigue cracking in gamma titanium aluminide

Fatigue crack initiation and growth were examined in cast and HIP'ed \textgamma-TiAl 4522XD. It was found that fatigue crack growth rates were higher at 750\celsius than 400\celsius, but that $\Delta K_\mathrm{th}$ was also higher. Temperature excursions between $400$ and 750\celsius during fatigue crack growth resulted in retardation of the crack growth rate, both on heating and cooling; however heating from 400 to 750\celsius at a $\Delta K$ that would then be below threshold did not result in complete crack arrest. It was also found that for notches $0.6$~mm in length and smaller, initiation from the microstructure could instead be observed at stresses similar to the material failure stress; a microstructural initiation site exists. Secondary cracking around borides could also be observed. A change from trans- to mixed trans-, inter- and intra-lamellar cracking could be observed where the estimated size of the crack tip plastic zone exceeded the colony size. Changes in fracture surface morphology could not be related to the temperature of fatigue crack growth, although this could be observed from the oxide scale colouration. Compressive pre-loading of a crack results in retardation of the crack, which could also be observed from the oxide

Big data and data repurposing – using existing data to answer new questions in vascular dementia research

Introduction: Traditional approaches to clinical research have, as yet, failed to provide effective treatments for vascular dementia (VaD). Novel approaches to collation and synthesis of data may allow for time and cost efficient hypothesis generating and testing. These approaches may have particular utility in helping us understand and treat a complex condition such as VaD. Methods: We present an overview of new uses for existing data to progress VaD research. The overview is the result of consultation with various stakeholders, focused literature review and learning from the group’s experience of successful approaches to data repurposing. In particular, we benefitted from the expert discussion and input of delegates at the 9th International Congress on Vascular Dementia (Ljubljana, 16-18th October 2015). Results: We agreed on key areas that could be of relevance to VaD research: systematic review of existing studies; individual patient level analyses of existing trials and cohorts and linking electronic health record data to other datasets. We illustrated each theme with a case-study of an existing project that has utilised this approach. Conclusions: There are many opportunities for the VaD research community to make better use of existing data. The volume of potentially available data is increasing and the opportunities for using these resources to progress the VaD research agenda are exciting. Of course, these approaches come with inherent limitations and biases, as bigger datasets are not necessarily better datasets and maintaining rigour and critical analysis will be key to optimising data use

HCV reinfection incidence and spontaneous clearance rates in HIV-positive men who have sex with men in Western Europe

BACKGROUND & AIMS: Moderate cure rates of acute hepatitis C virus (HCV) infections with pegylated interferon and ribavirin have been described in the last decade in men who have sex with men (MSM), who are also coinfected with the human immunodeficiency virus (HIV). However, a subsequent high incidence of HCV reinfections has been reported regionally in men who both clear the infection spontaneously or who respond to treatment. METHODS: Retrospective analysis of reinfections in HIV infected MSM in eight centers from Austria, France, Germany, and the UK within the NEAT network between May 2002 and June 2014. RESULTS: Of 606 individuals who cleared HCV spontaneously or were successfully treated, 149 (24.6%) presented with a subsequent HCV reinfection. Thirty out of 70 (43%) who cleared again or were successfully treated, presented with a second reinfection, 5 with a third, and one with a fourth reinfection. The reinfection incidence was 7.3/100 person-years (95% CI 6.2-8.6). We found a trend for lower incidence among individuals who had spontaneously cleared their incident infection than among individuals who were treated (Hazard ratio 0.62, 95% CI 0.38-1.02, p=0.06). Spontaneous clearance of reinfection was associated with ALT levels >1000IU/ml and spontaneous clearance of a prior infection. CONCLUSIONS: HCV reinfection is an issue of major concern in HIV-positive MSM. Prevention strategies are needed for high risk groups to reduce morbidity and treatment costs. HIV-positive MSM with a prior HCV infection should be tested every 3 to 6months for reinfection. Those who had achieved a reinfection should be tested every 3months. LAY SUMMARY: We evaluated the occurrence of HCV reinfection in HIV-positive men who have sex with men. We found an alarming incidence of 7.3/100 person-years. Prevention measures need to address this specific subgroup of patients at high risk for HCV

A Single-Arm, Proof-Of-Concept Trial of Lopimune (Lopinavir/Ritonavir) as a Treatment for HPV-Related Pre-Invasive Cervical Disease

BACKGROUND: Cervical cancer is the most common female malignancy in the developing nations and the third most common cancer in women globally. An effective, inexpensive and self-applied topical treatment would be an ideal solution for treatment of screen-detected, pre-invasive cervical disease in low resource settings. METHODS: Between 01/03/2013 and 01/08/2013, women attending Kenyatta National Hospital's Family Planning and Gynaecology Outpatients clinics were tested for HIV, HPV (Cervista®) and liquid based cervical cytology (LBC -ThinPrep®). HIV negative women diagnosed as high-risk HPV positive with high grade squamous intraepithelial lesions (HSIL) were examined by colposcopy and given a 2 week course of 1 capsule of Lopimune (CIPLA) twice daily, to be self-applied as a vaginal pessary. Colposcopy, HPV testing and LBC were repeated at 4 and 12 weeks post-start of treatment with a final punch biopsy at 3 months for histology. Primary outcome measures were acceptability of treatment with efficacy as a secondary consideration. RESULTS: A total of 23 women with HSIL were treated with Lopimune during which time no adverse reactions were reported. A maximum concentration of 10 ng/ml of lopinavir was detected in patient plasma 1 week after starting treatment. HPV was no longer detected in 12/23 (52.2%, 95%CI: 30.6-73.2%). Post-treatment cytology at 12 weeks on women with HSIL, showed 14/22 (63.6%, 95%CI: 40.6-82.8%) had no dysplasia and 4/22 (18.2%, 95%CI: 9.9-65.1%) were now low grade demonstrating a combined positive response in 81.8% of women of which 77.8% was confirmed by histology. These data are supported by colposcopic images, which show regression of cervical lesions. CONCLUSIONS: These results demonstrate the potential of Lopimune as a self-applied therapy for HPV infection and related cervical lesions. Since there were no serious adverse events or detectable post-treatment morbidity, this study indicates that further trials are clearly justified to define optimal regimes and the overall benefit of this therapy. TRIAL REGISTRATION: ISRCTN Registry 48776874

Can ground-based assessments of forest biodiversity reflect the biological condition of canopy assemblages?

© 2015 . Biological assessments of forest systems often involve a single ground-invertebrate sampling method that may ignore the biological component of the non-sampled canopy. Pitfall trapping for ground-active arthropods is a widely implemented technique for biological assessment in forested and open habitats. Although much evidence highlights the biases of pitfall trapping, this evidence typically comes from open-habitat crop and grassland systems. In forest systems where much of the biodiversity is found within the above-ground structure, management recommendations based solely on ground sampling may not represent the diversity within the three dimensional forest habitat. We provide evidence from combined ground and canopy sampling of three major forest types within the study region. We use canopy insecticide fogging to compare with more traditional ground-based pitfall trapping, and use spiders as a comparative species-rich biota that is able to colonise most terrestrial habitats and is strongly affected by changes in environmental condition.We identified 3933 spiders from 109 species from the 18 forest patches sampled. Both types of sampling defined differences in community composition between forest types in a similar manner; hence, either method could be used to evaluate differences or test management regimes in well-replicated experiments of forest type. However, the association in community composition between ground and canopy assemblages at the individual site-based level was weak; we found low correlation between the two data sets indicating that surrogacy between methods was not supported at this level. Furthermore, disparities in spider habitat association, body size, hunting guild and vertical stratification of spider families indicates that where detailed species and family-based information is required, or if inventorying is necessary, then multiple targeted surveys are essential

Anthropometric indices of Gambian children after one or three annual rounds of mass drug administration with azithromycin for trachoma control.

BACKGROUND: Mass drug administration (MDA) with azithromycin, carried out for the control of blinding trachoma, has been linked to reduced mortality in children. While the mechanism behind this reduction is unclear, it may be due, in part, to improved nutritional status via a potential reduction in the community burden of infectious disease. To determine whether MDA with azithromycin improves anthropometric indices at the community level, we measured the heights and weights of children aged 1 to 4 years in communities where one (single MDA arm) or three annual rounds (annual MDA arm) of azithromycin had been distributed. METHODS: Data collection took place three years after treatment in the single MDA arm and one year after the final round of treatment in the annual MDA arm. Mean height-for-age, weight-for-age and weight-for-height z scores were compared between treatment arms. RESULTS: No significant differences in mean height-for-age, weight-for-age or weight-for-height z scores were found between the annual MDA and single MDA arms, nor was there a significant reduction in prevalence of stunting, wasting or underweight between arms. CONCLUSIONS: Our data do not provide evidence that community MDA with azithromycin improved anthropometric outcomes of children in The Gambia. This may suggest reductions in mortality associated with azithromycin MDA are due to a mechanism other than improved nutritional status

Gene set of nuclear-encoded mitochondrial regulators is enriched for common inherited variation in obesity

There are hints of an altered mitochondrial function in obesity. Nuclear-encoded genes are relevant for mitochondrial function (3 gene sets of known relevant pathways: (1) 16 nuclear regulators of mitochondrial genes, (2) 91 genes for oxidative phosphorylation and (3) 966 nuclear-encoded mitochondrial genes). Gene set enrichment analysis (GSEA) showed no association with type 2 diabetes mellitus in these gene sets. Here we performed a GSEA for the same gene sets for obesity. Genome wide association study (GWAS) data from a case-control approach on 453 extremely obese children and adolescents and 435 lean adult controls were used for GSEA. For independent confirmation, we analyzed 705 obesity GWAS trios (extremely obese child and both biological parents) and a population-based GWAS sample (KORA F4, n = 1,743). A meta-analysis was performed on all three samples. In each sample, the distribution of significance levels between the respective gene set and those of all genes was compared using the leading-edge-fraction-comparison test (cut-offs between the 50(th) and 95(th) percentile of the set of all gene-wise corrected p-values) as implemented in the MAGENTA software. In the case-control sample, significant enrichment of associations with obesity was observed above the 50(th) percentile for the set of the 16 nuclear regulators of mitochondrial genes (p(GSEA,50) = 0.0103). This finding was not confirmed in the trios (p(GSEA,50) = 0.5991), but in KORA (p(GSEA,50) = 0.0398). The meta-analysis again indicated a trend for enrichment (p(MAGENTA,50) = 0.1052, p(MAGENTA,75) = 0.0251). The GSEA revealed that weak association signals for obesity might be enriched in the gene set of 16 nuclear regulators of mitochondrial genes