Age trajectories of glycaemic traits in non-diabetic South Asian and white individuals: the Whitehall II cohort study.

South Asian individuals have an increased prevalence of type 2 diabetes, but little is known about the development of glycaemic traits in this ethnic group. We compared age-related changes in glycaemic traits between non-diabetic South Asian and white participants

Dietary factors and Type 2 diabetes in the Middle East : what is the evidence for an association? - A systematic review.

This review aims to search and summarise the available evidence on the association between dietary factors and type 2 diabetes mellitus (T2DM) in Middle Eastern populations, where diabetes prevalence is among the highest in the world. Electronic databases were searched; authors, libraries, and research centres in the Middle East were contacted for further studies and unpublished literature. Included studies assessed potential dietary factors for T2DM in Middle Eastern adults. Two reviewers assessed studies independently. Extensive searching yielded 17 studies which met the inclusion criteria for this review. The findings showed that whole-grain intake reduces the risk of T2DM, and potato consumption was positively correlated with T2DM. Vegetables and vegetable oil may play a protective role against T2DM. Dietary patterns that are associated with diabetes were identified, such as Fast Food and Refined Grains patterns. Two studies demonstrated that lifestyle interventions decreased the risk of T2DM. In summary, the identified studies support an association between some dietary factors and T2DM; however, many of the included studies were of poor methodological quality so the findings should be interpreted with caution. The review draws attention to major gaps in current evidence and the need for well-designed studies in this area

Kondo effect in coupled quantum dots: a Non-crossing approximation study

The out-of-equilibrium transport properties of a double quantum dot system in the Kondo regime are studied theoretically by means of a two-impurity Anderson Hamiltonian with inter-impurity hopping. The Hamiltonian, formulated in slave-boson language, is solved by means of a generalization of the non-crossing approximation (NCA) to the present problem. We provide benchmark calculations of the predictions of the NCA for the linear and nonlinear transport properties of coupled quantum dots in the Kondo regime. We give a series of predictions that can be observed experimentally in linear and nonlinear transport measurements through coupled quantum dots. Importantly, it is demonstrated that measurements of the differential conductance ${\cal G}=dI/dV$, for the appropriate values of voltages and inter-dot tunneling couplings, can give a direct observation of the coherent superposition between the many-body Kondo states of each dot. This coherence can be also detected in the linear transport through the system: the curve linear conductance vs temperature is non-monotonic, with a maximum at a temperature $T^*$ characterizing quantum coherence between both Kondo states.Comment: 20 pages, 17 figure

Activity of a novel, dual PI3-kinase/mTor inhibitor NVP-BEZ235 against primary human pancreatic cancers grown as orthotopic xenografts

The phosphatidylinositol-3-kinase (PI3K)/Akt signalling pathway is frequently deregulated in pancreatic cancers, and is believed to be an important determinant of their biological aggression and drug resistance. NVP-BEZ235 is a novel, dual class I PI3K/mammalian target of rapamycin (mTor) inhibitor undergoing phase I human clinical trials. To simulate clinical testing, the effects of NVP-BEZ235 were studied in five early passage primary pancreatic cancer xenografts, grown orthotopically. These tumours showed activated PKB/Akt, and increased levels of at least one of the receptor tyrosine kinases that are commonly activated in pancreatic cancers. Pharmacodynamic effects were measured following acute single doses, and anticancer effects were determined in separate groups following chronic drug exposure. Acute oral dosing with NVP-BEZ235 strongly suppressed the phosphorylation of PKB/Akt, followed by recovery over 24 h. There was also inhibition of Ser235/236 S6 ribosomal protein and Thr37/46 4E-BP1, consistent with the effects of NVP-BEZ235 as a dual PI3K/mTor inhibitor. Chronic dosing with 45 mg kg−1 of NVP-BEZ235 was well tolerated, and produced significant tumour growth inhibition in three models. These results predict that agents targeting the PI3K/Akt/mTor pathway might have anticancer activity in pancreatic cancer patients, and support the testing of combination studies involving chemotherapy or other molecular targeted agents

Analyzing models of work addiction: single factor and bi-factor models of the Bergen Work Addiction Scale

Work addiction ('workaholism') has become an increasingly studied topic in the behavioral addictions literature and had led to the development of a number of instruments to assess it. One such instrument is the Bergen Work Addiction Scale (BWAS - Andreassen et al. 2012 Scandinavian Journal of Psychology, 53, 265-272). However, the BWAS has never been investigated in Eastern-European countries. The goal of the present study was to examine the factor structure, the reliability and cut-off scores of the BWAS in a comprehensive Hungarian sample. This study is a direct extension of the original validation of BWAS by providing results on the basis of representative data and the development of appropriate cut-off scores The study utilized an online questionnaire with a Hungarian representative sample including 500 respondents (F = 251; M age = 35.05 years) who completed the BWAS. A series of confirmatory factor analyses were carried out leading to a short, 7-item first-order factor structure and a longer 14-item seven-factor nested structure. Despite the good validity of the longer version, its reliability was not as high as it could have been. One-fifth (20.6 %) of the Hungarians who used the internet at least weekly were categorized as work addicts using the BWAS. It is recommended that researchers use the original seven items from the Norwegian scale in order to facilitate and stimulate cross-national research on addiction to work

Effective-Range Expansion of the Neutron-Deuteron Scattering Studied by a Quark-Model Nonlocal Gaussian Potential

The S-wave effective range parameters of the neutron-deuteron (nd) scattering are derived in the Faddeev formalism, using a nonlocal Gaussian potential based on the quark-model baryon-baryon interaction fss2. The spin-doublet low-energy eigenphase shift is sufficiently attractive to reproduce predictions by the AV18 plus Urbana three-nucleon force, yielding the observed value of the doublet scattering length and the correct differential cross sections below the deuteron breakup threshold. This conclusion is consistent with the previous result for the triton binding energy, which is nearly reproduced by fss2 without reinforcing it with the three-nucleon force.Comment: 21 pages, 6 figures and 6 tables, submitted to Prog. Theor. Phy

Somatostatin-based radiopeptide therapy with [177Lu-DOTA]-TOC versus [90Y-DOTA]-TOC in neuroendocrine tumours

Purpose: Somatostatin-based radiopeptide treatment is generally performed using the β-emitting radionuclides 90Y or 177Lu. The present study aimed at comparing benefits and harms of both therapeutic approaches. Methods: In a comparative cohort study, patients with advanced neuroendocrine tumours underwent repeated cycles of [90Y-DOTA]-TOC or [177Lu-DOTA]-TOC until progression of disease or permanent adverse events. Multivariable Cox regression and competing risks regression were employed to examine predictors of survival and adverse events for both treatment groups. Results: Overall, 910 patients underwent 1,804cycles of [90Y-DOTA]-TOC and 141 patients underwent 259cycles of [177Lu-DOTA]-TOC. The median survival after [177Lu-DOTA]-TOC and after [90Y-DOTA]-TOC was comparable (45.5months versus 35.9months, hazard ratio 0.91, 95% confidence interval 0.63-1.30, p = 0.49). Subgroup analyses revealed a significantly longer survival for [177Lu-DOTA]-TOC over [90Y-DOTA]-TOC in patients with low tumour uptake, solitary lesions and extra-hepatic lesions. The rate of severe transient haematotoxicities was lower after [177Lu-DOTA]-TOC treatment (1.4 vs 10.1%, p = 0.001), while the rate of severe permanent renal toxicities was similar in both treatment groups (9.2 vs 7.8%, p = 0.32). Conclusion: The present results revealed no difference in median overall survival after [177Lu-DOTA]-TOC and [90Y-DOTA]-TOC. Furthermore, [177Lu-DOTA]-TOC was less haematotoxic than [90Y-DOTA]-TOC

A gap between rational annuitization price for producer and price for customer

The paper studies pricing of insurance products focusing on the pricing of annuities under uncertainty. This pricing problem is crucial for financial decision making and was studied intensively; however, many open questions still remain. In particular, there is a so-called ``annuity puzzle" related to certain inconsistency of existing financial theory with the empirical observations for the annuities market. The paper suggests a pricing method based on the risk minimization such that both producer and customer seek to minimize the mean square hedging error accepted as a measure of risk. This leads to two different versions of the pricing problem: the selection of the annuity price given the rate of regular payments, and the selection of the rate of payments given the annuity price. It appears that solutions of these two problems are different. This can contribute to explanation for the "annuity puzzle"

Job strain and risk of obesity: systematic review and meta-analysis of cohort studies

Job strain, the most widely used indicator of work stress, is a risk factor for obesity-related disorders such as cardiovascular disease and type 2 diabetes. However, the extent to which job strain is related to the development of obesity itself has not been systematically evaluated. We carried out a systematic review (PubMed and Embase until May 2014) and meta-analysis of cohort studies to address this issue. Eight studies that fulfilled inclusion criteria showed no overall association between job strain and the risk of weight gain (pooled odds ratio for job strain compared with no job strain 1.04, 95% confidence interval (CI) 0.99-1.09, NTotal=18 240) or becoming obese (1.00, 95% CI 0.89-1.13, NTotal=42 222). In addition, a reduction in job strain over time was not associated with lower obesity risk (1.13, 95% CI 0.90-1.41, NTotal=6507). These longitudinal findings do not support the hypothesis that job strain is an important risk factor for obesity or a promising target for obesity prevention.International Journal of Obesity advance online publication, 30 June 2015; doi:10.1038/ijo.2015.103

hERG1a N-terminal eag domain–containing polypeptides regulate homomeric hERG1b and heteromeric hERG1a/hERG1b channels: A possible mechanism for long QT syndrome

Human ether-á-go-go–related gene (hERG) potassium channels are critical for cardiac action potential repolarization. Cardiac hERG channels comprise two primary isoforms: hERG1a, which has a regulatory N-terminal Per-Arnt-Sim (PAS) domain, and hERG1b, which does not. Isolated, PAS-containing hERG1a N-terminal regions (NTRs) directly regulate NTR-deleted hERG1a channels; however, it is unclear whether hERG1b isoforms contain sufficient machinery to support regulation by hERG1a NTRs. To test this, we constructed a series of PAS domain–containing hERG1a NTRs (encoding amino acids 1–181, 1–228, 1–319, and 1–365). The NTRs were also predicted to form from truncation mutations that were linked to type 2 long QT syndrome (LQTS), a cardiac arrhythmia disorder associated with mutations in the hERG gene. All of the hERG1a NTRs markedly regulated heteromeric hERG1a/hERG1b channels and homomeric hERG1b channels by decreasing the magnitude of the current–voltage relationship and slowing the kinetics of channel closing (deactivation). In contrast, NTRs did not measurably regulate hERG1a channels. A short NTR (encoding amino acids 1–135) composed primarily of the PAS domain was sufficient to regulate hERG1b. These results suggest that isolated hERG1a NTRs directly interact with hERG1b subunits. Our results demonstrate that deactivation is faster in hERG1a/hERG1b channels compared to hERG1a channels because of fewer PAS domains, not because of an inhibitory effect of the unique hERG1b NTR. A decrease in outward current density of hERG1a/hERG1b channels by hERG1a NTRs may be a mechanism for LQTS