Early antenatal prediction of gestational diabetes in obese women: development of prediction tools for targeted intervention

All obese women are categorised as being of equally high risk of gestational diabetes (GDM) whereas the majority do not develop the disorder. Lifestyle and pharmacological interventions in unselected obese pregnant women have been unsuccessful in preventing GDM. Our aim was to develop a prediction tool for early identification of obese women at high risk of GDM to facilitate targeted interventions in those most likely to benefit. Clinical and anthropometric data and non-fasting blood samples were obtained at 15+0–18+6 weeks’ gestation in 1303 obese pregnant women from UPBEAT, a randomised controlled trial of a behavioural intervention. Twenty one candidate biomarkers associated with insulin resistance, and a targeted nuclear magnetic resonance (NMR) metabolome were measured. Prediction models were constructed using stepwise logistic regression. Twenty six percent of women (n = 337) developed GDM (International Association of Diabetes and Pregnancy Study Groups criteria). A model based on clinical and anthropometric variables (age, previous GDM, family history of type 2 diabetes, systolic blood pressure, sum of skinfold thicknesses, waist:height and neck:thigh ratios) provided an area under the curve of 0.71 (95%CI 0.68–0.74). This increased to 0.77 (95%CI 0.73–0.80) with addition of candidate biomarkers (random glucose, haemoglobin A1c (HbA1c), fructosamine, adiponectin, sex hormone binding globulin, triglycerides), but was not improved by addition of NMR metabolites (0.77; 95%CI 0.74–0.81). Clinically translatable models for GDM prediction including readily measurable variables e.g. mid-arm circumference, age, systolic blood pressure, HbA1c and adiponectin are described. Using a ≥35% risk threshold, all models identified a group of high risk obese women of whom approximately 50% (positive predictive value) later developed GDM, with a negative predictive value of 80%. Tools for early pregnancy identification of obese women at risk of GDM are described which could enable targeted interventions for GDM prevention in women who will benefit the most

Biocontrol of Chromolaena odorata in Timor Leste

Chromolaena odorata (L.) King and Robinson (Asteraceae) is a major weed in Timor Leste, affecting grazing lands and subsistence farms, reducing productivity and food security. It was the focus of a biocontrol project funded by the Australian Government from 2005-2009. During this period, the gall fly Cecidochares connexa (Macquart) (Diptera: Tephritidae) was introduced from Papua New Guinea and Indonesia, where it is widespread. From these initial releases, the gall fly established at seven sites and was subsequently re-distributed to most areas in Timor Leste where chromolaena was a problem. It established at most of the release sites that were revisited and caused a visible reduction in plant density and height. Overall, control of chromolaena by the gall fly in Timor Leste is limited by the severe dry season and the widespread use of fire in clearing lands for agriculture, both of which reduce the ability of gall fly populations to persist at damaging levels. Thus additional agents that can tolerate prolonged dry periods are required to increase the level of control of chromolaena

Mechanisms of action of inhaled fibers, particles and nanoparticles in lung and cardiovascular diseases

<p>Abstract</p> <p>Background</p> <p>A symposium on the mechanisms of action of inhaled airborne particulate matter (PM), pathogenic particles and fibers such as silica and asbestos, and nanomaterials, defined as synthetic particles or fibers less than 100 nm in diameter, was held on October 27 and 28, 2005, at the Environmental Protection Agency (EPA) Conference Center in Research Triangle Park, North Carolina. The meeting was the eighth in a series of transatlantic conferences first held in Penarth, Wales, at the Medical Research Council Pneumoconiosis Unit (1979), that have fostered long-standing collaborations between researchers in the fields of mineralogy, cell and molecular biology, pathology, toxicology, and environmental/occupational health.</p> <p>Results</p> <p>The goal of this meeting, which was largely supported by a conference grant from the NHLBI, was to assemble a group of clinical and basic research scientists who presented and discussed new data on the mechanistic effects of inhaled particulates on the onset and development of morbidity and mortality in the lung and cardiovascular system. Another outcome of the meeting was the elucidation of a number of host susceptibility factors implicated in adverse health effects associated with inhaled pathogenic particulates.</p> <p>Conclusion</p> <p>New models and data presented supported the paradigm that both genetic and environmental (and occupational) factors affect disease outcomes from inhaled particulates as well as cardiopulmonary responses. These future studies are encouraged to allow the design of appropriate strategies for prevention and treatment of particulate-associated morbidity and mortality, especially in susceptible populations.</p

A Comment on the Topological Phase for Anti-Particles in a Lorentz-violating environment

Recently, a scheme to analyse topological phases in Quantum Mechanics by means of the non-relativistic limit of fermions non-minimally coupled to a Lorentz-breaking background has been proposed. In this letter, we show that the fixed background, responsible for the Lorentz-symmetry violation, may induce opposite Aharonov-Casher phases for a particle and its corresponding antiparticle. We then argue that such a difference may be used to investigate the asymmetry for particle/anti-particle as well as to propose bounds on the associated Lorentz-symmetry violating parameters.Comment: 4 pages - A published versio

Predicting, Preparing for, and Creating the Future: What Will Happen to Internal Medicine?

It is the year 2025. During the past 20 years, internal medicine as a discipline continued to become less prestigious, less respected, and more fragmented. As fewer medical students chose internal medicine as a career, residency programs began to close. Those that remained open filled with fewer graduates of US medical schools but filled with more US citizens who graduated from international medical schools, more graduates of osteopathic medical schools, and more foreign graduates of international medical schools. Due to lack of adequate remuneration and a shift of primary care provision from generalist physicians to nurse practitioners and physician assistants, training in general internal medicine as a patient care specialty ceased. Generalist internal medicine careers have been replaced by tracks designed to foster health services research or academic careers; internal medicine training graduates subspecialty physicians. Although the projected collapse of Medicare in 2019 was avoided, severe cuts in federal funding for undergraduate and graduate medical education programs forced medical schools and residency programs to compete for federal funds. As a result, medical school tuition became prohibitive, for-profit health care systems viewed medical education as a significant cost center and chose to limit the size of their residency programs, and community-based training programs could not withstand the financial pressures and closed. The result was a reduced supply of internists. Furthermore, compliance with the regulatory burden imposed by accrediting organizations—such as the Accreditation Council for Graduate Medical Education—drove individuals from sustained careers in education, further impacting the viability of training programs

Mitochondrial Protein Lipoylation and the 2-Oxoglutarate Dehydrogenase Complex Controls HIF1α Stability in Aerobic Conditions.

Hypoxia-inducible transcription factors (HIFs) control adaptation to low oxygen environments by activating genes involved in metabolism, angiogenesis, and redox homeostasis. The finding that HIFs are also regulated by small molecule metabolites highlights the need to understand the complexity of their cellular regulation. Here we use a forward genetic screen in near-haploid human cells to identify genes that stabilize HIFs under aerobic conditions. We identify two mitochondrial genes, oxoglutarate dehydrogenase (OGDH) and lipoic acid synthase (LIAS), which when mutated stabilize HIF1α in a non-hydroxylated form. Disruption of OGDH complex activity in OGDH or LIAS mutants promotes L-2-hydroxyglutarate formation, which inhibits the activity of the HIFα prolyl hydroxylases (PHDs) and TET 2-oxoglutarate dependent dioxygenases. We also find that PHD activity is decreased in patients with homozygous germline mutations in lipoic acid synthesis, leading to HIF1 activation. Thus, mutations affecting OGDHC activity may have broad implications for epigenetic regulation and tumorigenesis.This work was supported by a Wellcome Trust Senior Clinical Research Fellowship to J.A.N. (102770/Z/13/Z), Wellcome Trust Principal Research Fellowship to P.J.L. (084957/Z/08/Z), and the Medical Research Council (A.S.H.C. and C.F.). The Cambridge Institute for Medical Research is in receipt of a Wellcome Trust Strategic Award (100140).This is the final version of the article. It first appeared from Elsevier (Cell Press) via https://doi.org/10.1016/j.cmet.2016.09.01

Cosmic Concordance and Quintessence

We present a comprehensive study of the observational constraints on spatially flat cosmological models containing a mixture of matter and quintessence --- a time varying, spatially inhomogeneous component of the energy density of the universe with negative pressure. Our study also includes the limiting case of a cosmological constant. Low red shift constraints include the Hubble parameter, baryon fraction, cluster abundance, age of the universe, bulk velocity and shape of the mass power spectrum; intermediate red shift constraints are due to type 1a supernovae, gravitational lensing, the Ly-a forest, and the evolution of large scale structure; high red shift constraints are based on cosmic microwave background temperature anisotropy. Mindful of systematic errors, we adopt a conservative approach in applying these constraints. We determine that quintessence models in which the matter density parameter is 0.2 \ls \Omega_m \ls 0.5 and the effective, density-averaged equation of state is -1 \le w \ls -0.2, are consistent with the most reliable, current low red shift and CMB observations at the $2\sigma$ level. Factoring in the constraint due to type 1a SNe, the range for the equation of state is reduced to -1 \le w \ls -0.4, where this range represents models consistent with each observational constraint at the 2$\sigma$ level or better (concordance analysis). A combined maximum likelihood analysis suggests a smaller range, -1 \le w \ls -0.6. We find that the best-fit and best-motivated quintessence models lie near $\Omega_m \approx 0.33$, $h \approx 0.65$, and spectral index $n_s=1$, with an effective equation of state $w \approx -0.65$ for ``tracker'' quintessence and $w=-1$ for ``creeper'' quintessence. (abstract shortened)Comment: revised to match ApJ version; 33 pages; 20 figures, 4 in color; uses emulateapj.st

Making Maps Of The Cosmic Microwave Background: The MAXIMA Example

This work describes Cosmic Microwave Background (CMB) data analysis algorithms and their implementations, developed to produce a pixelized map of the sky and a corresponding pixel-pixel noise correlation matrix from time ordered data for a CMB mapping experiment. We discuss in turn algorithms for estimating noise properties from the time ordered data, techniques for manipulating the time ordered data, and a number of variants of the maximum likelihood map-making procedure. We pay particular attention to issues pertinent to real CMB data, and present ways of incorporating them within the framework of maximum likelihood map-making. Making a map of the sky is shown to be not only an intermediate step rendering an image of the sky, but also an important diagnostic stage, when tests for and/or removal of systematic effects can efficiently be performed. The case under study is the MAXIMA data set. However, the methods discussed are expected to be applicable to the analysis of other current and forthcoming CMB experiments.Comment: Replaced to match the published version, only minor change