The Heart Failure Overweight/Obesity Survival Paradox : The Missing Sex Link

Objectives: This study sought to determine whether body mass index (BMI) has a differential impact on survival for females versus males with advanced systolic heart failure (HF). Background: Females have a survival advantage in HF, the mechanisms of which are unclear. There is also a proposed “obesity survival paradox” in which excess adiposity promotes HF survival. Methods: We reviewed 3,811 patients with left ventricular ejection fraction ≤40% who had undergone cardiopulmonary exercise testing between 1995 and 2011. The endpoint was all-cause mortality. Multivariable analysis was performed using a Cox proportional hazards model. Because of the nonlinearity of BMI, a restricted cubic spline was used. An interaction term was added to investigate the impact of BMI on mortality by sex. Results: The unadjusted data demonstrated an overall obesity survival paradox in HF. This survival paradox disappeared for males after adjustment for potential confounders, with overweight and obese males showing higher adjusted mortality hazard ratios compared with normal weight males. Conversely, females in the overweight BMI range (25.0 to 29.9 kg/m2) had the lowest adjusted mortality (hazard ratio: 0.84; 95% confidence interval: 0.77 to 0.93; p = 0.0005 compared with normal weight females) with a nadir in mortality hazard just below BMI 30 kg/m2. The multivariable model supported a differential impact of BMI on mortality in males versus females (p for interaction \u3c0.0001). Conclusions: In this advanced HF cohort, an unadjusted obesity survival paradox disappeared after adjustment for confounders. Overweight and obese males had higher adjusted mortality than normal weight males, whereas a BMI in the overweight range was associated with a significant survival benefit in females

Note and Comment

The Completion of a Contract by Posting of Acceptance - In the recent case of Kennedy Mcrcantile Co. v. Western Union Telegraph Co., the court says, It is well settled law in this state that,where an offer is submitted by letter, an acceptance is conclusive and binding when a letter is deposited in the post-office accepting the same. The delivery to the one making the offer is not the test; for when the offer is submitted in that way it is equivalent to an invitation to accept by the same means, and when the acceptance is delivered to the agency chosen by the one making the offer the contract is complete

The Radio Continuum of the Metal-Deficient Blue Compact Dwarf Galaxy SBS0335-052

We present new Very Large Array observations at five frequencies, from 1.4 to 22GHz, of the extremely low-metallicity blue compact dwarf SBS0335-052. The radio spectrum shows considerable absorption at 1.49GHz, and a composite thermal+non-thermal slope. After fitting the data with a variety of models, we find the best-fitting geometry to be one with free-free absorption homogeneously intermixed with the emission of both thermal and non-thermal components. The best-fitting model gives an an emission measure EM ~ 8x10^7pc cm^{-6} and a diameter of the radio-emitting region D ~17pc. The inferred density is n_e ~ 2000 cm^{-3}. The thermal emission comes from an ensemble of \~9000 O7 stars, with a massive star-formation rate (>=5Msun) of 0.13-0.15 yr^{-1}, and a supernova rate of 0.006 yr^{-1}. We find evidence for ionized gas emission from stellar winds, since the observed Bralpha line flux significantly exceeds that inferred from the thermal radio emission. The non-thermal fraction at 5GHz is ~0.7, corresponding to a non-thermal luminosity of ~2x10^{20} W Hz^{-1}. We attribute the non-thermal radio emission to an ensemble of compact SN remnants expanding in a dense interstellar medium, and derive an equipartition magnetic field of ~0.6-1 mG, and a pressure of \~3x10^{-8}-1x10^{-7} dyne cm^{-2}. If the radio properties of SBS0335-052 are representative of star formation in extremely low-metallicity environments, derivations of the star formation rate from the radio continuum in high redshift primordial galaxies need to be reconsidered. Moreover, photometric redshifts inferred from ``standard'' spectral energy distributions could be incorrect.Comment: 25 pages, including 3 figures, accepted for publication in Ap

An Integrative, Multilevel, and Transdisciplinary Research Approach to Challenges of Work, Family, and Health

Recognizing a need for rigorous, experimental research to support the efforts of workplaces and policymakers in improving the health and wellbeing of employees and their families, the National Institutes of Health and the Centers for Disease Control and Prevention formed the Work, Family & Health Network (WFHN). The WFHN is implementing an innovative multisite study with a rigorous experimental design (adaptive randomization, control groups), comprehensive multilevel measures, a novel and theoretically based intervention targeting the psychosocial work environment, and translational activities. This paper describes challenges and benefits of designing a multilevel and transdisciplinary research network that includes an effectiveness study to assess intervention effects on employees, families, and managers; a daily diary study to examine effects on family functioning and daily stress; a process study to understand intervention implementation; and translational research to understand and inform diffusion of innovation. Challenges were both conceptual and logistical, spanning all aspects of study design and implementation. In dealing with these challenges, however, the WFHN developed innovative, transdisciplinary, multi-method approaches to conducting workplace research that will benefit both the research and business communities

Prenatal nicotine sex-dependently alters adolescent dopamine system development.

Despite persistent public health initiatives, many women continue to smoke during pregnancy. Since maternal smoking has been linked to persisting sex-dependent neurobehavioral deficits in offspring, some consider nicotine to be a safer alternative to tobacco during pregnancy, and the use of electronic nicotine delivery systems is on the rise. We presently show, however, that sustained exposure to low doses of nicotine during fetal development, approximating plasma levels seen clinically with the nicotine patch, produces substantial changes in developing corticostriatal dopamine systems in adolescence. Briefly, pregnant dams were implanted on gestational day 4 with an osmotic minipump that delivered either saline (GS) or nicotine (3 mg/kg/day) (GN) for two weeks. At birth, pups were cross-fostered with treatment naïve dams and were handled daily. Biochemical analyses, signaling assays, and behavioral responses to cocaine were assessed on postnatal day 32, representative of adolescence in the rodent. GN treatment had both sex-dependent and sex-independent effects on prefrontal dopamine systems, altering Catechol-O-methyl transferase (COMT)-dependent dopamine turnover in males and norepinephrine transporter (NET) binding expression in both sexes. GN enhanced cocaine-induced locomotor activity in females, concomitant with GN-induced reductions in striatal dopamine transporter (DAT) binding. GN enhanced ventral striatal D2-like receptor expression and G-protein coupling, while altering the roles of D2 and D3 receptors in cocaine-induced behaviors. These data show that low-dose prenatal nicotine treatment sex-dependently alters corticostriatal dopamine system development, which may underlie clinical deficits seen in adolescents exposed to tobacco or nicotine in utero

The Mini-Addenbrooke's Cognitive Examination: a new assessment tool for dementia.

BACKGROUND/AIMS: We developed and validated the Mini-Addenbrooke's Cognitive Examination (M-ACE) in dementia patients. Comparisons were also made with the Mini Mental State Examination (MMSE). METHOD: The M-ACE was developed using Mokken scaling analysis in 117 dementia patients [behavioural variant frontotemporal dementia (bvFTD), n = 25; primary progressive aphasia (PPA), n = 49; Alzheimer's disease (AD), n = 34; corticobasal syndrome (CBS), n = 9] and validated in an independent sample of 164 dementia patients (bvFTD, n = 23; PPA, n = 82; AD, n = 38; CBS, n = 21) and 78 controls, who also completed the MMSE. RESULTS: The M-ACE consists of 5 items with a maximum score of 30. Two cut-offs were identified: (1) ≤25/30 has both high sensitivity and specificity, and (2) ≤21/30 is almost certainly a score to have come from a dementia patient regardless of the clinical setting. The M-ACE is more sensitive than the MMSE and is less likely to have ceiling effects. CONCLUSION: The M-ACE is a brief and sensitive cognitive screening tool for dementia. Two cut-offs (25 or 21) are recommended.This work was supported by funding to Forefront, a collaborative research group dedicated to the study of frontotemporal dementia and motor neurone disease, by the National Health and Medical Research council (NHMRC) of Australia program grant (1037746) and the Australian Research Council (ARC) Centre of Excellence in Cognition and Its Disorders Memory Node (CE110001021). S.H. is supported by the Graham Linford Fellowship from the Motor Neurone Disease Research Institute of Australia. S.M. is supported by Alzheimer Scotland (PhD Studentship). F.L. is supported by an Australian Postgraduate Award (PhD Scholarship). K.D. is supported by NIHR Cambridge Biomedical Research Centre. S.A. is supported by the NIHR Biomedical Research Centre, Oxford. C.R.B. is supported by a Clinician Scientist Fellowship from the Medical Research Council (MR/K010395/1). J.B.R. is supported by the Wellcome Trust (088324), Medical Research Council, McDonnell Foundation and the NIHR (Cambridge Biomedical Research Centre and Biomedical Research Unit in Dementia). E.M. is supported by the NHMRC Early Career Fellowship (1016399) and Alzheimer Association USA. J.R.H. is supported by an ARC Federation Fellowship (FF0776229).This is the final version of the article. It first appeared from Karger via http://dx.doi.org/10.1159/00036604

Colouring cryo-cooled crystals: online microspectrophotometry

A portable and readily aligned online microspectrophotometer that can be easily installed on macromolecular crystallography beamlines is described. It allows measurement of the spectral characteristics of macromolecular crystals prior, during, and after the X-ray diffraction experiment

Progress in marine geoconservation in Scotland’s seas : assessment of key interests and their contribution to Marine Protected Area network planning

This study was part-funded by Marine Scotland and was undertaken as part of the Scottish Marine Protected Areas (MPA) Programme, a joint initiative between Marine Scotland, Historic Scotland, Scottish Natural Heritage (SNH) and the Joint Nature Conservation Committee (JNCC).Geoconservation in the marine environment has been largely overlooked, despite a wealth of accumulated information on marine geology and geomorphology and clear links between many terrestrial and marine features. As part of the wider characterisation of Scotland’s seas, this study developed criteria and a methodology that follow the established principles of the terrestrial, Great Britain-wide geoconservation audit, the Geological Conservation Review, to assess geodiversity key areas on the seabed. Using an expert judgement approach, eight geodiversity feature categories were identified to represent the geological and geomorphological processes that have influenced the evolution and present-day morphology of the Scottish seabed: Quaternary of Scotland; Submarine Mass Movement; Marine Geomorphology of the Scottish Deep-Ocean Seabed; Seabed Fluid and Gas Seep; Cenozoic Structures of the Atlantic Margin; Marine Geomorphology of the Scottish Shelf Seabed; Coastal Geomorphology of Scotland; and Biogenic Structures of the Scottish Seabed. Within these categories, 35 key areas were prioritised for their scientific value. Specific interests range from large-scale landforms (e.g. submarine landslides, sea-mounts and trenches) to fine-scale dynamic features (e.g. sand waves). Although these geodiversity interests provided supporting evidence for the identification and selection of a suite of Nature Conservation Marine Protected Areas (MPAs) containing important marine natural features, they are only partially represented in these MPAs and existing protected areas. Nevertheless, a pragmatic approach is emerging to integrate as far as possible the conservation management of marine geodiversity with that of biodiversity and based on evidence of the sensitivity and vulnerability geological and geomorphological features on the seabed.PostprintPeer reviewe