Very high prevalence of 25-hydroxyvitamin D deficiency in 6433 UK South Asian adults : Analysis of the UK Biobank Cohort

Acknowledgements This research has been conducted using the UK Biobank Resource under application number 15168. This work was supported by in-house funds from the University of Surrey for payment of the UK Biobank access fee. The UK Biobank was established by the Wellcome Trust medical charity, Medical Research Council, Department of Health, Scottish Government and the Northwest Regional Development Agency. It has also had funding from the Welsh Assembly Government and the British Heart Foundation. UK Biobank is hosted by the University of Manchester and supported by the National Health Service (NHS). All the above funders had no role in the design, analysis or writing of the present study. Author contributions were as follows: Formulating the research question(s) (A. L. D., D. J. B., K. R. A., S. L. N.), designing the study (A. L. D., D. J. B., K. R. A., S. A. L.-N.), data collection (not applicable), analysing the data (A. L. D., D. J. B., K. R. A., S. A. L.-N.) and writing the article (A. L. D., D. J. B., K. R. A., S. L. N.). S. A. L.-N. discloses that she is Research Director of D3-TEX limited which holds the UK and Gulf Corporation Council (GCC) patents for the use of UVB transparent clothing to prevent vitamin D deficiency. S. A. L.-N.’s husband William Lanham-New is Managing Director of D3-TEX limited. S. A. L.-N. has received grants from (1) The UK Biotechnology and Biological Sciences Research Council (BBSRC) (project: Ergocalciferol (D2) v. Cholecalciferol (D3) Food Fortification: Comparative Efficiency in Raising 25OHD Status & Mechanisms of Action (D2–D3 Study), BB/I006192/1, £516 823); (2) The UK Food Standards Agency (Project: Vitamin D, Food Intake, Nutrition and Exposure to Sunlight in Southern England (D-FINES) Study, N05064, £600 000); (3) The European Union (Project: Food Based Solutions for optimal vitamin D nutrition and health through the life cycle, Lead Work Package; (4) nutritional requirements for vitamin D during pregnancy, childhood and adolescence using RCTs, FP7-613977-ODIN, Euro 6·2 million) and (5) The UK Ministry of Defence (MoD, £2·4 million). S. L. N. is a current member of the Scientific Advisory Committee for Nutrition (SACN) and a member of the panel who was responsible for the most recent revision of vitamin D recommended nutritional intake guidelines in the UK. She is a board member for the UK Royal Osteoporosis Society and the British Nutrition Foundation. She is Secretary of the Nutrition Society as well as Editor in Chief of the Nutrition Society textbook series. All other authors have no conflict of interest.Peer reviewedPublisher PD

An Interaction between KSHV ORF57 and UIF Provides mRNA-Adaptor Redundancy in Herpesvirus Intronless mRNA Export

The hTREX complex mediates cellular bulk mRNA nuclear export by recruiting the nuclear export factor, TAP, via a direct interaction with the export adaptor, Aly. Intriguingly however, depletion of Aly only leads to a modest reduction in cellular mRNA nuclear export, suggesting the existence of additional mRNA nuclear export adaptor proteins. In order to efficiently export Kaposi's sarcoma-associated herpesvirus (KSHV) intronless mRNAs from the nucleus, the KSHV ORF57 protein recruits hTREX onto viral intronless mRNAs allowing access to the TAP-mediated export pathway. Similarly however, depletion of Aly only leads to a modest reduction in the nuclear export of KSHV intronless mRNAs. Herein, we identify a novel interaction between ORF57 and the cellular protein, UIF. We provide the first evidence that the ORF57-UIF interaction enables the recruitment of hTREX and TAP to KSHV intronless mRNAs in Aly-depleted cells. Strikingly, depletion of both Aly and UIF inhibits the formation of an ORF57-mediated nuclear export competent ribonucleoprotein particle and consequently prevents ORF57-mediated mRNA nuclear export and KSHV protein production. Importantly, these findings highlight that redundancy exists in the eukaryotic system for certain hTREX components involved in the mRNA nuclear export of intronless KSHV mRNAs

THE MYTH OF SELF RELIANCE: Economic Lives Inside a Liberian Refugee Camp. Naohiko Omata. New York: Berghahn Books, 2017

THE MYTH OF SELF RELIANCE: Economic Lives Inside a Liberian Refugee Camp. Naohiko Omata. New York: Berghahn Books, 2017. 194 pages, ISBN 9781785335648 (hardback)

Vitamin D Status of the British African-Caribbean Residents : Analysis of the UK Biobank Cohort

Funding: This work is part of the PhD of R.M.V., which is funded by the Universities Global Part‐ nership Network, co‐supervised by the Universities of Surrey and Wollongong. Funders did not have a role in the study. The researchers are independent to the funders. All authors take responsibility for the integrity of the data and the accuracy of the data analysis.Peer reviewedPublisher PD

Strike-slip influenced stratigraphic and structural development of the Foula Sandstone Group, Shetland: implications for offshore Devonian basin development on the northern UK continental shelf

The island of Foula, located 25 km SW of Shetland, preserves a gently folded, 1.6 km thick sequence of Middle Devonian sandstones spectacularly exposed in kilometre-long cliff sections >350 m high. These rocks unconformably overlie likely Precambrian-age amphibolite facies basement rocks that are intruded by sheeted granites. The onshore succession is similar in age to the nearby Lower Clair Group offshore to the west. New mapping, incorporating the use of drone imagery in the inaccessible cliff sections, uses down-plunge projections to show that growth folding and faulting on Foula were contemporaneous with sedimentation during basin filling. The large-scale structural geometry is consistent with the regional constrictional strain due to the sinistral transtension associated with movements along the Walls Boundary–Great Glen fault zone system during the Mid-Devonian. Detrital zircon provenance studies indicate that the Devonian sequences of Foula (and nearby Melby in western Shetland) show similarities with the Clair Group and Orkney successions. We suggest that NE–SW transtensional fold development contemporaneous with regional subsidence in the Devonian basins of Scotland may be more widespread than previously realized. Large, kilometre-scale folds previously interpreted to be related to Permo-Carboniferous inversion may therefore have initiated earlier in the basin evolution sequence than previously realized

The effect of dapagliflozin on glycaemic control and other cardiovascular disease risk factors in type 2 diabetes mellitus:a real-world observational study

Aims/hypothesis: Dapagliflozin, a sodium–glucose cotransporter 2 (SGLT2) inhibitor, is indicated for improving glycaemic control in type 2 diabetes mellitus. Whether its effects on HbA1c and other variables, including safety outcomes, in clinical trials are obtained in real-world practice needs to be established. Methods: We used data from the comprehensive national diabetes register, the Scottish Care Information-Diabetes (SCI-Diabetes) collaboration database, available from 2004 to mid-2016. Data within this database were linked to mortality data from the General Registrar, available from the Information Services Division (ISD) of the National Health Service in Scotland. We calculated crude within-person differences between pre- and post-drug-initiation values of HbA1c, BMI, body weight, systolic blood pressure (SBP) and eGFR. We used mixed-effects regression models to adjust for within-person time trajectories in these measures. For completeness, we evaluated safety outcomes, cardiovascular disease events, lower-limb amputation and diabetic ketoacidosis, focusing on cumulative exposure effects, using Cox proportional hazard models, though power to detect such effects was limited. Results: Among 8566 people exposed to dapagliflozin over a median of 210 days the crude within-person change in HbA1c was −10.41 mmol/mol (−0.95%) after 3 months’ exposure. The crude change after 12 months was −12.99 mmol/mol (−1.19%) but considering the expected rise over time in HbA1c gave a dapagliflozin-exposure-effect estimate of −15.14 mmol/mol (95% CI −15.87, −14.41) (−1.39% [95% CI −1.45, −1.32]) at 12 months that was maintained thereafter. A drop in SBP of −4.32 mmHg (95% CI −4.84, −3.79) on exposure within the first 3 months was also maintained thereafter. Reductions in BMI and body weight stabilised by 6 months at −0.82 kg/m2 (95% CI −0.87, −0.77) and −2.20 kg (95% CI −2.34, −2.06) and were maintained thereafter. eGFR declined initially by −1.81 ml min−1 [1.73 m]−2 (95% CI −2.10, −1.52) at 3 months but varied thereafter. There were no significant effects of cumulative drug exposure on safety outcomes. Conclusions/interpretation: Dapagliflozin exposure was associated with reductions in HbA1c, SBP, body weight and BMI that were at least as large as in clinical trials. Dapagliflozin also prevented the expected rise in HbA1c and SBP over the period of study

Effect of serum sample storage temperature on metabolomic and proteomic biomarkers

Prospective biomarker studies can be used to identify biomarkers predictive of disease onset. However, if serum biomarkers are measured years after their collection, the storage conditions might affect analyte concentrations. Few data exists concerning which metabolites and proteins are affected by storage at - 20 degrees C vs - 80 degrees C. Our objectives were to document analytes affected by storage of serum samples at - 20 degrees C vs - 80 degrees C, and to identify those indicative of the storage temperature. We utilized liquid chromatography tandem mass spectrometry and Luminex to quantify 300 analytes from serum samples of 16 Finnish individuals with type 1 diabetes, with split-aliquot samples stored at - 80 degrees C and - 20 degrees C for a median of 4.2 years. Results were validated in 315 Finnish and 916 Scottish individuals with type 1 diabetes, stored at -20 degrees C and at - 80 degrees C, respectively. After quality control, we analysed 193 metabolites and proteins of which 120 were apparently unaffected and 15 clearly susceptible to storage at - 20 degrees C vs - 80 degrees C. Further, we identified serum glutamate/glutamine ratio greater than 0.20 as a biomarker of storage at - 20 degrees C vs - 80 degrees C. The results provide a catalogue of analytes unaffected and affected by storage at - 20 degrees C vs - 80 degrees C and biomarkers indicative of suboptimal storage.Peer reviewe

Diaspora Policies, Consular Services and Social Protection for German Citizens Abroad

This chapter presents an overview of German policies vis-à-vis German nationals living abroad. For the most part, the German Government does not reach out to or encourage engagement from or with German nationals living abroad. This is in contrast to a concerted cultural outreach to ethno-national German minorities in Central and Eastern Europe. Rights in Germany are largely residence-based, and access to rights is thus associated with (legal) residence in Germany, rather than with holding German citizenship. There are two clear exceptions: one is a robust system that enables voting from abroad for German citizens, and the other is facilitated access from abroad to pensions for years worked in Germany. With respect to other measures of social protections, no clear policy can be said to exist. Access to other forms of social protection is on the basis of exception, with consular officials exercising discretion in such cases