Associations between reliable changes in depression and changes in BMI, total body fatness and visceral adiposity during a 12-month weight loss trial.

We investigated associations between changes in depression and body composition over a 12-month weight loss trial. Of the 298 adults (BMI > 27 m/kg2), 219 with complete depression and body composition data were included. A 10-item Center for Epidemiologic Studies Depression Scale measured depression; dual-energy X-ray absorptiometry measured body composition. Multinomial logistic regression predicted reliable changes in depression by BMI, body fat (BF) and visceral adiposity (VAT). Multiplicative interaction terms tested modification by sex and ethnicity. Participants with increases in body composition were less likely to experience improvements in depression (BMI: RRR = 0.79 (0.68-0.91), p < 0.01; BF: RRR = 0.97 (0.94 - 0.99), p = 0.01; VAT: RRR = 0.99 (0.98-1.00), p = 0.02), but not worsening of depression (BMI: RRR = 1.29 (0.96-1.73), p = 0.10; BF: RRR = 1.04 (0.99-1.09), p = 0.15; VAT: RRR = 1.01 (1.00-1.03), p = 0.18). Sex and ethnicity interaction terms were not significant. However, the relationship was only significant among females, among non-Latinos for BMI and BF, and among Latinos for VAT. Our study supports the association between depression and obesity and highlights the need for longitudinal studies investigating VAT and depression in diverse ethnic groups

The BIG 2.04 MRC/EORTC SUPREMO Trial: pathology quality assurance of a large phase 3 randomised international clinical trial of postmastectomy radiotherapy in intermediate-risk breast cancer

Introduction SUPREMO is a phase 3 randomised trial evaluating radiotherapy post-mastectomy for intermediate-risk breast cancer. 1688 patients were enrolled from 16 countries between 2006 and 2013. We report the results of central pathology review carried out for quality assurance. Patients and methods A single recut haematoxylin and eosin (H&E) tumour section was assessed by one of two reviewing pathologists, blinded to the originally reported pathology and patient data. Tumour type, grade and lymphovascular invasion were reviewed to assess if they met the inclusion criteria. Slides from potentially ineligible patients on central review were scanned and reviewed online together by the two pathologists and a consensus reached. A subset of 25 of these cases was double-reported independently by the pathologists prior to the online assessment. Results The major contributors to the trial were the UK (75%) and the Netherlands (10%). There is a striking difference in lymphovascular invasion (LVi) rates (41.6 vs. 15.1% (UK); p = <0.0001) and proportions of grade 3 carcinomas (54.0 vs. 42.0% (UK); p = <0.0001) on comparing local reporting with central review. There was no difference in the locally reported frequency of LVi rates in node-positive (N+) and node-negative (N−) subgroups (40.3 vs. 38.0%; p = 0.40) but a significant difference in the reviewed frequency (16.9 vs. 9.9%; p = 0.004). Of the N− cases, 104 (25.1%) would have been ineligible by initial central review by virtue of grade and/or lymphovascular invasion status. Following online consensus review, this fell to 70 cases (16.3% of N− cases, 4.1% of all cases). Conclusions These data have important implications for the design, powering and interpretation of outcomes from this and future clinical trials. If critical pathology criteria are determinants for trial entry, serious consideration should be given to up-front central pathology review

Urinary albumin/creatinine ratio tertiles predict risk of diabetic retinopathy progression: a natural history study from the Adolescent Cardio-Renal Intervention Trial (AdDIT) observational cohort

Aims/hypothesis: We hypothesised that adolescents with type 1 diabetes with a urinary albumin/creatinine ratio (ACR) in the upper tertile of the normal range (high ACR) are at greater risk of three-step diabetic retinopathy progression (3DR) independent of glycaemic control. Methods: This was a prospective observational study in 710 normoalbuminuric adolescents with type 1 diabetes from the non-intervention cohorts of the Adolescent Cardio-Renal Intervention Trial (AdDIT). Participants were classified as ‘high ACR’ or ‘low ACR’ (lowest and middle ACR tertiles) using baseline standardised log10 ACR. The primary outcome, 3DR, was determined from centrally graded, standardised two-field retinal photographs. 3DR risk was determined using multivariable Cox regression for the effect of high ACR, with HbA1c, BP, LDL-cholesterol and BMI as covariates; diabetes duration was the time-dependent variable. Results: At baseline mean ± SD age was 14.3 ± 1.6 years and mean ± SD diabetes duration was 7.2 ± 3.3 years. After a median of 3.2 years, 83/710 (12%) had developed 3DR. In multivariable analysis, high ACR (HR 2.1 [1.3, 3.3], p=0.001), higher mean IFCC HbA1c (HR 1.03 [1.01, 1.04], p=0.001) and higher baseline diastolic BP SD score (HR 1.43 [1.08, 1.89], p=0.01) were independently associated with 3DR risk. Conclusions/interpretation: High ACR is associated with greater risk of 3DR in adolescents, providing a target for future intervention studies

Regular symmetry patterns

Symmetry reduction is a well-known approach for alleviating the state explosion problem in model checking. Automatically identifying symmetries in concurrent systems, however, is computationally expensive. We propose a symbolic framework for capturing symmetry patterns in parameterised systems (i.e. an infinite family of finite-state systems): two regular word transducers to represent, respectively, parameterised systems and symmetry patterns. The framework subsumes various types of "symmetry relations" ranging from weaker notions (e.g. simulation preorders) to the strongest notion (i.e. isomorphisms). Our framework enjoys two algorithmic properties: (1) symmetry verification: given a transducer, we can automatically check whether it is a symmetry pattern of a given system, and (2) symmetry synthesis: we can automatically generate a symmetry pattern for a given system in the form of a transducer. Furthermore, our symbolic language allows additional constraints that the symmetry patterns need to satisfy to be easily incorporated in the verification/synthesis. We show how these properties can help identify symmetry patterns in examples like dining philosopher protocols, self-stabilising protocols, and prioritised resource-allocator protocol. In some cases (e.g. Gries's coffee can problem), our technique automatically synthesises a safety-preserving finite approximant, which can then be verified for safety solely using a finite-state model checker.UPMAR

A diplexer with direct coupled resonant junction

Conventionally, diplexers are designed by connecting two filters of different frequencies using a transmission T‐line junction which acts as a distribution network serving the individual filters. Here, a novel diplexer has been proposed and designed to utilize a directly coupled resonator as the distribution network. The directly coupled resonator is designed using two square open‐loop resonators of the same resonant frequency of 1.95 GHz. Coupling of the two resonators is achieved using a λ/4 transmission line to directly couple them. This process made the resonator pair to possess a dual‐mode resonator function, resonating at 1.85 and 2.05 GHz. Two bandpass filters are then designed in the corresponding modes of the resonator pair with 5% fractional bandwidth and coupled accordingly. This technique allowed the resonator pair to contribute to the resonant poles of the diplexer while functioning as the distribution network

Vascular Effects of ACE (Angiotensin-Converting Enzyme) Inhibitors and Statins in Adolescents With Type 1 Diabetes

An increased albumin-creatinine ratio within the normal range can identify adolescents at higher risk of developing adverse cardio-renal outcomes as they progress into adulthood. Utilizing a parallel randomized controlled trial and observational cohort study, we characterized the progression of vascular phenotypes throughout this important period and investigated the effect of ACE (angiotensin-converting enzyme) inhibitors and statins in high-risk adolescents. Endothelial function (flow-mediated dilation and reactive hyperemia index) and arterial stiffness (carotid-femoral pulse wave velocity) were assessed in 158 high-risk participants recruited to a randomized, double-blind placebo-controlled 2×2 factorial trial (randomized, placebo-controlled trial) of ACE inhibitors and/or statins in adolescents with type 1 diabetes (AdDIT [Adolescent Type 1 Diabetes cardio-renal Intervention Trial]). Identical measures were also assessed in 215 lower-risk individuals recruited to a parallel observational study. In the randomized, placebo-controlled trial, high-risk patients randomized to ACE inhibitors had improved flow-mediated dilation after 2 to 4 years of follow-up (mean [95% CI]: 6.6% [6.0-7.2] versus 5.3% [4.7-5.9]; P=0.005), whereas no effect was observed following statin use (6.2% [5.5-6.8] versus 5.8% [5.1-6.4]; P=0.358). In the observational study, patients classed as high-risk based on albumin-creatinine ratio showed evidence of endothelial dysfunction at the end of follow-up (flow-mediated dilation=4.8% [3.8-5.9] versus 6.3% [5.8-6.7] for high-risk versus low-risk groups; P=0.015). Neither reactive hyperemia index nor pulse wave velocity were affected by either treatment (P>0.05 for both), but both were found to increase over the duration of follow-up (0.07 [0.03-0.12]; P=0.001 and 0.5 m/s [0.4-0.6]; P<0.001 for reactive hyperemia index and pulse wave velocity, respectively). ACE inhibitors improve endothelial function in high-risk adolescents as they transition through puberty. The longer-term protective effects of this intervention at this early age remain to be determined. Registration- URL: https://www.clinicaltrials.gov; Unique identifier NCT01581476

The geographical distribution of lymphatic filariasis infection in Malawi

Mapping distribution of lymphatic filariasis (LF) is a prerequisite for planning national elimination programmes. Results from a nation wide mapping survey for lymphatic filariasis (LF) in Malawi are presented. Thirty-five villages were sampled from 23 districts excluding three districts (Karonga, Chikwawa and Nsanje) that had already been mapped and Likoma, an Island, where access was not possible in the time frame of the survey. Antigenaemia prevalence [based on immunochromatographic card tests (ICT)] ranged from 0% to 35.9%. Villages from the western side of the country and distant from the lake tended to be of lower prevalence. The exception was a village in Mchinji district on the Malawi-Zambia border where a prevalence of 18.2% was found. In contrast villages from lake shore districts [Salima, Mangochi, Balaka and Ntcheu (Bwanje valley)] and Phalombe had prevalences of over 20%

Concepts for risk-based surveillance in the field of veterinary medicine and veterinary public health: Review of current approaches

BACKGROUND: Emerging animal and zoonotic diseases and increasing international trade have resulted in an increased demand for veterinary surveillance systems. However, human and financial resources available to support government veterinary services are becoming more and more limited in many countries world-wide. Intuitively, issues that present higher risks merit higher priority for surveillance resources as investments will yield higher benefit-cost ratios. The rapid rate of acceptance of this core concept of risk-based surveillance has outpaced the development of its theoretical and practical bases. DISCUSSION: The principal objectives of risk-based veterinary surveillance are to identify surveillance needs to protect the health of livestock and consumers, to set priorities, and to allocate resources effectively and efficiently. An important goal is to achieve a higher benefit-cost ratio with existing or reduced resources. We propose to define risk-based surveillance systems as those that apply risk assessment methods in different steps of traditional surveillance design for early detection and management of diseases or hazards. In risk-based designs, public health, economic and trade consequences of diseases play an important role in selection of diseases or hazards. Furthermore, certain strata of the population of interest have a higher probability to be sampled for detection of diseases or hazards. Evaluation of risk-based surveillance systems shall prove that the efficacy of risk-based systems is equal or higher than traditional systems; however, the efficiency (benefit-cost ratio) shall be higher in risk-based surveillance systems. SUMMARY: Risk-based surveillance considerations are useful to support both strategic and operational decision making. This article highlights applications of risk-based surveillance systems in the veterinary field including food safety. Examples are provided for risk-based hazard selection, risk-based selection of sampling strata as well as sample size calculation based on risk considerations

Mission impossible? The paradoxes of stretch goal setting

© 2016, © The Author(s) 2016. Stretch goal setting is a process involving multiple and nested paradoxes. The paradoxical side of stretch is attractive because it holds great promise yet dangerous because it triggers processes that are hard to control. Paradoxes are not readily managed by assuming a linear relation between the here and now and the intended future perfect. Before adopting stretch goal setting, managers should thus be prepared for the tensions and contradictions created by nested or interwoven paradoxes. Achieving stretch goals can be as difficult for the managers seeking to direct the process as for designated delegates. While the increasing popularity of stretch goal setting is understandable, its unexpected consequences must be taken into account. The inadequate use of stretch goals can jeopardize the social sustainability of organizations as well as their societal support systems