Vitamin D time profile based on the contribution of non-genetic and genetic factors in HIV-infected individuals of European ancestry

BACKGROUND Vitamin D deficiency is prevalent in HIV-infected individuals and vitamin D supplementation is proposed according to standard care. This study aimed at characterizing the kinetics of 25(OH)D in a cohort of HIV-infected individuals of European ancestry to better define the influence of genetic and non-genetic factors on 25(OH)D levels. These data were used for the optimization of vitamin D supplementation in order to reach therapeutic targets. METHODS 1,397 25(OH)D plasma levels and relevant clinical information were collected in 664 participants during medical routine follow up visits. They were genotyped for 7 SNPs in 4 genes known to be associated with 25(OH)D levels. 25(OH)D concentrations were analyzed using a population pharmacokinetic approach. The percentage of individuals with 25(OH)D concentrations within the recommended range of 20-40ng/ml during 12 months of follow up and several dosage regimens were evaluated by simulation. RESULTS A one-compartment model with linear absorption and elimination was used to describe 25(OH)D pharmacokinetics, while integrating endogenous baseline plasma concentrations. Covariate analyses confirmed the effect of seasonality, body mass index, smoking habits, the analytical method, darunavir/r and the genetic variant in GC (rs2282679) on 25(OH)D concentrations. 11% of the interindividual variability in 25(OH)D levels was explained by seasonality and other non-genetic covariates and 1% by genetics. The optimal supplementation for severe vitamin D deficient patients was 300000 IU two times per year. CONCLUSIONS This analysis allowed identifying factors associated with 25(OH)D plasma levels in HIV-infected individuals. Improvement of dosage regimen and timing of vitamin D supplementation is proposed based on those results.

Analytical thinking under distrust - better not to know that one distrusts

It is widely known that people utter an untruth from time to time. Our ability to detect and recognize deception and lies and, in the next step, to respond appropriately is not very far-reaching. We were interested in finding out if distrust triggers non-routine, analytical thought processes and therefore improves the detection of lies without dismissing the truth. We conducted two experiments to investigate the influence of an unconscious form of distrust on our thought processes. In the first experiment, participants had to determine whether a report is truthful or false. The aim of this second experiment was to investigate if this enhanced ability to detect a falsified report correctly is based on analytical thinking taking place. To examine our assumptions, we applied the paradigm of belief bias. The results of the second experiments strongly point out the fact that an unconscious form of distrust triggers and fosters analytical thinking.

Measurement of the inclusive jet cross section in pp collisions at sqrt(s)=2.76 TeV and comparison to the inclusive jet cross section at sqrt(s)=7 TeV using the ATLAS detector

The inclusive jet cross-section has been measured in proton-proton collisions at root s = 2.76 TeV in a dataset corresponding to an integrated luminosity of 0.20 pb(-1) collected with the ATLAS detector at the Large Hadron Collider in 2011. Jets are identified using the anti-k(t) algorithm with two radius parameters of 0.4 and 0.6. The inclusive jet double-differential cross-section is presented as a function of the jet transverse momentum p(T) and jet rapidity y, covering a range of 20 <= p(T) < 430 GeV and vertical bar y vertical bar < 4.4. The ratio of the cross-section to the inclusive jet cross-section measurement at root s = 7 TeV, published by the ATLAS Collaboration, is calculated as a function of both transverse momentum and the dimensionless quantity x(T) = 2p(T)/root s, in bins of jet rapidity. The systematic uncertainties on the ratios are significantly reduced due to the cancellation of correlated uncertainties in the two measurements. Results are compared to the prediction from next-to-leading order perturbative QCD calculations corrected for non-perturbative effects, and next-to-leading order Monte Carlo simulation. Furthermore, the ATLAS jet cross-section measurements at root s = 2.76 TeV and root s = 7 TeV are analysed within a framework of next-to-leading order perturbative QCD calculations to determine parton distribution functions of the proton, taking into account the correlations between the measurements.

Studying changes in life circumstances and personality: It's about time

Most theories of personality development posit that changes in life circumstances (e.g. due to major life events) can lead to changes in personality, but few studies have examined the exact time course of these changes. In this article, we argue that time needs to be considered explicitly in theories and empirical studies on personality development. We discuss six notions on the role of time in personality development. First, people can differ before the event. Second, change can be non-linear and discontinuous. Third, change can be reversible. Fourth, change can occur before the event. Fifth, control groups are needed to disentangle age-related and event-related changes. Sixth, we need to move beyond examining single major life events and study the effects of non-normative events, non-events, multiple events, and minor events on personality. We conclude by summarizing the methodological and theoretical implications of these notions.

Suicide tourism: a pilot study on the swiss phenomenon

While assisted suicide (AS) is strictly restricted in many countries, it is not clearly regulated by law in Switzerland. This imbalance leads to an influx of people —‘suicide tourists’—coming to Switzerland, mainly to the Canton of Zurich, for the sole purpose of committing suicide. Political debate regarding ‘suicide tourism’ is taking place in many countries. Swiss medicolegal experts are confronted with these cases almost daily, which prompted our scientific investigation of the phenomenon. The present study has three aims: (1) to determine selected details about AS in the study group (age, gender and country of residence of the suicide tourists, the organisation involved, the ingested substance leading to death and any diseases that were the main reason for AS); (2) to find out the countries from which suicide tourists come and to review existing laws in the top three in order to test the hypothesis that suicide tourism leads to the amendment of existing regulations in foreign countries; and (3) to compare our results with those of earlier studies in Zurich. We did a retrospective data analysis of the Zurich Institute of Legal Medicine database on AS of on-Swiss residents in the last 5 years (2008–2012), and internet research for current legislation and political debate in the three foreign countries most concerned. We analysed 611 cases from 31 countries all over the world. Non-terminal conditions such as neurological and rheumatic diseases are increasing among suicide tourists. The unique phenomenon of suicide tourism in Switzerland may indeed result in the amendment or supplementary guidelines to existing regulations in foreign countries.

A new model construction by making a detour via intuitionistic theories I: Operational set theory without choice is Π1-equivalent to KP

We introduce a version of operational set theory, OST−, without a choice operation, which has a machinery for Δ0Δ0 separation based on truth functions and the separation operator, and a new kind of applicative set theory, so-called weak explicit set theory WEST, based on Gödel operations. We show that both the theories and Kripke–Platek set theory KPKP with infinity are pairwise Π1Π1 equivalent. We also show analogous assertions for subtheories with ∈-induction restricted in various ways and for supertheories extended by powerset, beta, limit and Mahlo operations. Whereas the upper bound is given by a refinement of inductive definition in KPKP, the lower bound is by a combination, in a specific way, of realisability, (intuitionistic) forcing and negative interpretations. Thus, despite interpretability between classical theories, we make “a detour via intuitionistic theories”. The combined interpretation, seen as a model construction in the sense of Visser's miniature model theory, is a new way of construction for classical theories and could be said the third kind of model construction ever used which is non-trivial on the logical connective level, after generic extension à la Cohen and Krivine's classical realisability model.

Imperialismustheorien und Geschichte: Eine empirische Annäherung

For decades, if not centuries, the term imperialism has been used in manifold and ambivalent ways. Some historians, such as William Hancock, therefore shied away from using it in their texts, while others set up theories to explain as much as possible with regard to the European expansion into the non-European world – and in some cases even beyond. Taking the three cases of German colonial policy before 1890, the granting of “responsible government” to the so-called British dominions and the expansion of British power in South Asia from the mid-eighteenth century to 1914, this article seeks to show to what extent a knowledge of both older and more recent theories of imperialism can still be useful for empirical research in the humanities and the social sciences.

An initiative for participatory monitoring of large scale acquisitions: Opportunities and results thus far

Increasing commercial pressures on land are provoking fundamental and far-reaching changes in the relationships between people and land. Much knowledge on land-oriented investments projects currently comes from the media. Although this provides a good starting point, lack of transparency and rapidly changing contexts mean that this is often unreliable. The International Land Coalition, in partnership with Oxfam Novib, Centre de coopération internationale en recherche agronomique pour le développement (CIRAD), University of Pretoria, Centre for Development and Environment of the University of Bern (CDE), and GIZ, started to compile an inventory of land-related investments. This project aims to better understand the extent, trends and impacts of land-related investments by supporting an ongoing and systematic stocktaking exercise of the various investment projects currently taking place worldwide. It involves a large number of organizations and individuals working in areas where land transactions are being made, and able to provide details of such investments. The project monitors land transactions in rural areas that imply a transformation of land use rights from communities and smallholders to commercial use, and are made both by domestic and foreign investors (private actors, governments, government-back private investors). The focus is on investments for food or agrofuel production, timber extraction, carbon trading, mineral extraction, conservation and tourism. A novel way of using ITC to document land acquisitions in a spatially explicit way and by using an approach called “crowdsourcing” is being developed. This approach will allow actors to share information and knowledge directly and at any time on a public platform, where it will be scrutinized in terms of reliability and cross checked with other sources. Up to now, over 1200 deals have been recorded across 96 countries. Details of such transactions have been classified in a matrix and distributed to over 350 contacts worldwide for verification. The verified information has been geo-referenced and represented in two global maps. This is an open database enabling a continued monitoring exercise and the improvement of data accuracy. More information will be released over time. The opportunities arise from overcoming constraints by incomplete information by proposing a new way of collecting, enhancing and sharing information and knowledge in a more democratic and transparent manner. The intention is to develop interactive knowledge platform where any interested person can share and access information on land deals, their link to involved stakeholders, and their embedding into a geographical context. By making use of new ICT technologies that are more and more in the reach of local stakeholders, as well as open access and web-based spatial information systems, it will become possible to create a dynamic database containing spatial explicit data. Feeding in data by a large number of stakeholders, increasingly also by means of new mobile ITC technologies, will open up new opportunities to analyse, monitor and assess highly dynamic trends of land acquisition and rural transformation.

Conceptual design and simulation of a water Cherenkov muon veto for the XENON1T experiment

XENON is a dark matter direct detection project, consisting of a time projection chamber (TPC) filled with liquid xenon as detection medium. The construction of the next generation detector, XENON1T, is presently taking place at the Laboratori Nazionali del Gran Sasso (LNGS) in Italy. It aims at a sensitivity to spin-independent cross sections of 2 10-47 c 2 for WIMP masses around 50 GeV2, which requires a background reduction by two orders of magnitude compared to XENON100, the current generation detector. An active system that is able to tag muons and muon-induced backgrounds is critical for this goal. A water Cherenkov detector of ~ 10 m height and diameter has been therefore developed, equipped with 8 inch photomultipliers and cladded by a reflective foil. We present the design and optimization study for this detector, which has been carried out with a series of Monte Carlo simulations. The muon veto will reach very high detection efficiencies for muons (>99.5%) and showers of secondary particles from muon interactions in the rock (>70%). Similar efficiencies will be obtained for XENONnT, the upgrade of XENON1T, which will later improve the WIMP sensitivity by another order of magnitude. With the Cherenkov water shield studied here, the background from muon-induced neutrons in XENON1T is negligible.

Ego depletion and action initiation

Optimal sprint start performance requires the self-control of responses. Therefore, start performance should depend on self-control strength. It was expected that momentary depletion of self-control strength (ego depletion) would slow down the initiation of a sprint start, resulting in impaired reaction times. N = 37 participants performed three sprint starts at T1 and the average reaction times were measured with a foot-pressure release system attached under the starting block (in ms). Next, participants were randomly assigned to a depletion or a non-depletion condition and self-control strength was experimentally manipulated by applying the transcription task. Following the depletion manipulation, participants performed another series of three sprints (T2). The results of a mixed between (ego depletion: yes vs. no) within (T1 vs. T2) ANOVA supported the hypothesis as average reaction times in the depletion condition significantly increased from T1 (M = 0.35, SD = 0.03) to T2 (M = 0.38, SD = 0.04), F(1, 35) = 6.77, p = .01, η2p = .16. Average reaction times in the non-depletion condition did not differ significantly between T1 (M = 0.36, SD = 0.03) and T2 (M = 0.35, SD = 0.04), F(1, 35) = 0.47, p = .50, η2p = .01. In line with the hypothesis, higher levels of self-control strength were associated with quicker movement initiations. Therefore, improving self-control strength may serve as a buffer against the negative effects of ego depletion on performance.

The influence of students' prior clinical skills and context characteristics on mini-CEX scores in clerkships - a multilevel analysis.

BACKGROUND In contrast to objective structured clinical examinations (OSCEs), mini-clinical evaluation exercises (mini-CEXs) take place at the clinical workplace. As both mini-CEXs and OSCEs assess clinical skills, but within different contexts, this study aims at analyzing to which degree students' mini-CEX scores can be predicted by their recent OSCE scores and/or context characteristics. METHODS Medical students participated in an end of Year 3 OSCE and in 11 mini-CEXs during 5 different clerkships of Year 4. The students' mean scores of 9 clinical skills OSCE stations and mean 'overall' and 'domain' mini-CEX scores, averaged over all mini-CEXs of each student were computed. Linear regression analyses including random effects were used to predict mini-CEX scores by OSCE performance and characteristics of clinics, trainers, students and assessments. RESULTS A total of 512 trainers in 45 clinics provided 1783 mini-CEX ratings for 165 students; OSCE results were available for 144 students (87 %). Most influential for the prediction of 'overall' mini-CEX scores was the trainers' clinical position with a regression coefficient of 0.55 (95 %-CI: 0.26-0.84; p < .001) for residents compared to heads of department. Highly complex tasks and assessments taking place in large clinics significantly enhanced 'overall' mini-CEX scores, too. In contrast, high OSCE performance did not significantly increase 'overall' mini-CEX scores. CONCLUSION In our study, Mini-CEX scores depended rather on context characteristics than on students' clinical skills as demonstrated in an OSCE. Ways are discussed which focus on either to enhance the scores' validity or to use narrative comments only.

The promoting effect of water on the electroreduction of CO2 in acetonitrile

The promoting effect of water on the electrochemical reduction of carbon dioxide (CO2) from non-aqueous solvents has been studied by means of cyclic voltammetry and in-situ surface-enhanced infrared absorption spectroscopy (SEIRAS). CO2 electroreduction on gold is known to be highly selective towards CO formation in aqueous and in non-aqueous media. The use of non-aqueous solvents is advantageous due to the significantly increased solubility of CO2 compared to aqueous systems. However, in the absence of any proton source, extremely high overpotentials are required for the CO2 electroreduction. In this work, we demonstrate for the first time a tremendous accelerating effect of water additives on the electroreduction of CO2 taking place at gold/acetonitrile interfaces. Already moderate amounts of water, in the concentration range of 0.5 to 0.7 M, are sufficient to decrease significantly the overpotential of CO2 reduction while keeping the CO2 concentration as high as in the pure acetonitrile. The effect of water additives on the mechanism of CO2 electroreduction on gold is discussed on the basis of electrochemical and IR spectroscopic data. The results obtained from gold are compared to analogue experiments carried out on platinum.

Selenium isotope analysis by N-TIMS: Potential and challenges

The isotope composition of selenium (Se) can provide important constraints on biological, geochemical, and cosmochemical processes taking place in different reservoirs on Earth and during planet formation. To provide precise qualitative and quantitative information on these processes, accurate and highly precise isotope data need to be obtained. The currently applied ICP-MS methods for Se isotope measurements are compromised by the necessity to perform a large number of interference corrections. Differences in these correction methods can lead to discrepancies in published Se isotope values of rock standards which are significantly higher than the acclaimed precision. An independent analytical approach applying a double spike (DS) and state-of-the-art TIMS may yield better precision due to its smaller number of interferences and could test the accuracy of data obtained by ICP-MS approaches. This study shows that the precision of Se isotope measurements performed with two different Thermo Scientific™ Triton™ Plus TIMS is distinctly deteriorated by about ±1‰ (2 s.d.) due to δ80/78Se by a memory Se signal of up to several millivolts and additional minor residual mass bias which could not be corrected for with the common isotope fractionation laws. This memory Se has a variable isotope composition with a DS fraction of up to 20% and accumulates with increasing number of measurements. Thus it represents an accumulation of Se from previous Se measurements with a potential addition from a sample or machine blank. Several cleaning techniques of the MS parts were tried to decrease the memory signal, but were not sufficient to perform precise Se isotope analysis. If these serious memory problems can be overcome in the future, the precision and accuracy of Se isotope analysis with TIMS should be significantly better than those of the current ICP-MS approaches.

A systematic review of selected birth outcomes in diabetic women who received preconception care and/or used multivitamins prior to pregnancy

Objective. To conduct a systematic review of published literature on preconception care in pre-existing diabetic women looking at the effect of glycemic control and multivitamin usage on the frequency of spontaneous abortion and birth defects.^ Methods. Articles were retrieved from Medline (1950–Dec 2007), Cochrane Library (1800–Dec 2007), Academic Search Complete (Ebsco) (Jan 1800–Dec 2007) and Maternal and Child Health Library (1965–Dec 2007). Studies included women with pre-existing, non-gestational diabetes and a comparison group. Participants must have either received preconception care and/or consumed a multivitamin as part of the study.^ Results. Overall, seven studies met the study criteria and applicability to the study objectives. Four of these reported the frequency of spontaneous abortion. Only one found a statistically significant increased risk of spontaneous abortion among pregnant women who did not receive preconception care compared with those who did receive care, odds ratio 4.32; 95% CI 1.34 to 13.9. Of the seven studies, six reported the frequency of birth defects. Five of these six studies found a significantly increased rate of birth defects among pregnant women who did not receive preconception care compared with those who did receive care, with odds ratios ranging from 1.53 to 10.16. All seven studies based their preconception care intervention on glycemic control. One study also used multivitamins as part of the preconception care.^ Conclusion. Glycemic control was shown to be useful in reducing the prevalence of birth defects, but not as useful in reducing the prevalence of spontaneous abortion. Insulin regimen options vary widely for the diabetic woman. No author excluded or controlled for women who may have been taking a multivitamin on their own. Due to the small amount of literature available, it is still not known which preconception care option, glucose control and/or multivitamin usage, provides better protection from birth defects and spontaneous abortion for the diabetic woman. An area for future investigation would be glycemic control and the use of folic acid started before pregnancy and the effects on birth defects and spontaneous abortion.^

Factors that affect non-adherence to first line antiretroviral medications among HIV infected children and adolescents in Botswana

The aims of the study were to determine the prevalence of and factors that affect non-adherence to first line antiretroviral (ARV) medications among HIV infected children and adolescents in Botswana. The study used secondary data from Botswana-Baylor Children's Clinical Center of Excellence for the period of June 2008 to February 10th, 2010. The study design was cross-sectional and case-comparison between non-adherent and adherent participants was used to examine the effects of socio-demographic and medication factors on non-adherence to ARV medications. A case was defined as non-adherent child with adherence level < 95% based on pill count and measurement of liquid formulations. The comparison group consisted of children with adherence levels ≥95%.^ A total of 842 participants met the eligibility criteria for determination of the prevalence of non-adherence and 338 participants (169 cases and 169 individuals) were used in the analysis to estimate the effects of factors on non-adherence. ^ Univariate and multivariable logistic regression were used to estimate the association between non-adherence (outcome) and socio-demographic and medication factors (exposures). The prevalence of non-adherence for participants on first line ARV medications was 20.0% (169/842).^ Increase in age (OR (95% CI): 1.10 (1.04–1.17) p = 0.001) was associated with nonadherence, while increase in number of caregivers (OR (95% CI): 0.72 (0.56–0.93) p = 0.01) and increase in number of monthly visits (OR (95% CI): 0.92 (0.86–0.99) p = 0.02), were associated with good adherence in both the unadjusted and the adjusted models. For the categorical variables, having more than two caregivers (OR (95% CI): 0.66 (0.28–0.84), p = 0.002) was associated with good adherence even in the adjusted model. ^ Conclusion. The prevalence of non-adherence to antiretroviral medicines among the study population was estimated to be 20.0%. In previous studies, adherence levels of ≥ 95% have been associated with better clinical outcomes and suppression of virus to prevent development of resistance. Older age, fewer numbers of caregivers and fewer monthly visits were associated with non-adherence. Strategies to improve and sustain adherence especially among older children are needed. The role of caregivers and social support should be investigated further.^