Effect of Body Mass Index on pregnancy outcomes in nulliparous women delivering singleton babies

Peer reviewedPublisher PD

Wet Granular Materials

Most studies on granular physics have focused on dry granular media, with no liquids between the grains. However, in geology and many real world applications (e.g., food processing, pharmaceuticals, ceramics, civil engineering, constructions, and many industrial applications), liquid is present between the grains. This produces inter-grain cohesion and drastically modifies the mechanical properties of the granular media (e.g., the surface angle can be larger than 90 degrees). Here we present a review of the mechanical properties of wet granular media, with particular emphasis on the effect of cohesion. We also list several open problems that might motivate future studies in this exciting but mostly unexplored field.Comment: review article, accepted for publication in Advances in Physics; tex-style change

Quantitative cross-species extrapolation between humans and fish: The case of the anti-depressant fluoxetine

This article has been made available through the Brunel Open Access Publishing Fund.Fish are an important model for the pharmacological and toxicological characterization of human pharmaceuticals in drug discovery, drug safety assessment and environmental toxicology. However, do fish respond to pharmaceuticals as humans do? To address this question, we provide a novel quantitative cross-species extrapolation approach (qCSE) based on the hypothesis that similar plasma concentrations of pharmaceuticals cause comparable target-mediated effects in both humans and fish at similar level of biological organization (Read-Across Hypothesis). To validate this hypothesis, the behavioural effects of the anti-depressant drug fluoxetine on the fish model fathead minnow (Pimephales promelas) were used as test case. Fish were exposed for 28 days to a range of measured water concentrations of fluoxetine (0.1, 1.0, 8.0, 16, 32, 64 μg/L) to produce plasma concentrations below, equal and above the range of Human Therapeutic Plasma Concentrations (HTPCs). Fluoxetine and its metabolite, norfluoxetine, were quantified in the plasma of individual fish and linked to behavioural anxiety-related endpoints. The minimum drug plasma concentrations that elicited anxiolytic responses in fish were above the upper value of the HTPC range, whereas no effects were observed at plasma concentrations below the HTPCs. In vivo metabolism of fluoxetine in humans and fish was similar, and displayed bi-phasic concentration-dependent kinetics driven by the auto-inhibitory dynamics and saturation of the enzymes that convert fluoxetine into norfluoxetine. The sensitivity of fish to fluoxetine was not so dissimilar from that of patients affected by general anxiety disorders. These results represent the first direct evidence of measured internal dose response effect of a pharmaceutical in fish, hence validating the Read-Across hypothesis applied to fluoxetine. Overall, this study demonstrates that the qCSE approach, anchored to internal drug concentrations, is a powerful tool to guide the assessment of the sensitivity of fish to pharmaceuticals, and strengthens the translational power of the cross-species extrapolation

Breast cancer risk variants at 6q25 display different phenotype associations and regulate ESR1, RMND1 and CCDC170.

We analyzed 3,872 common genetic variants across the ESR1 locus (encoding estrogen receptor α) in 118,816 subjects from three international consortia. We found evidence for at least five independent causal variants, each associated with different phenotype sets, including estrogen receptor (ER(+) or ER(-)) and human ERBB2 (HER2(+) or HER2(-)) tumor subtypes, mammographic density and tumor grade. The best candidate causal variants for ER(-) tumors lie in four separate enhancer elements, and their risk alleles reduce expression of ESR1, RMND1 and CCDC170, whereas the risk alleles of the strongest candidates for the remaining independent causal variant disrupt a silencer element and putatively increase ESR1 and RMND1 expression.This is the author accepted manuscript. The final version is available from Nature Publishing Group via http://dx.doi.org/10.1038/ng.352

Is the meiofauna a good indicator for climate change and anthropogenic impacts?

Our planet is changing, and one of the most pressing challenges facing the scientific community revolves around understanding how ecological communities respond to global changes. From coastal to deep-sea ecosystems, ecologists are exploring new areas of research to find model organisms that help predict the future of life on our planet. Among the different categories of organisms, meiofauna offer several advantages for the study of marine benthic ecosystems. This paper reviews the advances in the study of meiofauna with regard to climate change and anthropogenic impacts. Four taxonomic groups are valuable for predicting global changes: foraminifers (especially calcareous forms), nematodes, copepods and ostracods. Environmental variables are fundamental in the interpretation of meiofaunal patterns and multistressor experiments are more informative than single stressor ones, revealing complex ecological and biological interactions. Global change has a general negative effect on meiofauna, with important consequences on benthic food webs. However, some meiofaunal species can be favoured by the extreme conditions induced by global change, as they can exhibit remarkable physiological adaptations. This review highlights the need to incorporate studies on taxonomy, genetics and function of meiofaunal taxa into global change impact research

Low risk of thromboembolic complications after fast-track hip and knee arthroplasty

BACKGROUND AND PURPOSE: Pharmacological prophylaxis can reduce the risk of deep venous thrombosis (DVT), pulmonary embolism (PE), and death, and it is recommended 10–35 days after total hip arthroplasty (THA) and at least 10 days after total knee arthroplasty (TKA). However, early mobilization might also reduce the risk of DVT and thereby the need for prolonged prophylaxis, but this has not been considered in the previous literature. Here we report our results with short-duration pharmacological prophylaxis combined with early mobilization and reduced hospitalization.PATIENTS AND METHODS: 1,977 consecutive, unselected patients were operated with primary THA, TKA, or bilateral simultaneous TKA (BSTKA) in a well-described standardized fast-track set-up from 2004–2008. Patients received DVT prophylaxis with low-molecular-weight heparin starting 6–8 h after surgery until discharge. All re-admissions and deaths within 30 and 90 days were analyzed using the national health register, concentrating especially on clinical DVT (confirmed by ultrasound and elevated D-dimer), PE, or sudden death. Numbers were correlated to days of prophylaxis (LOS).RESULTS: The mean LOS decreased from 7.3 days in 2004 to 3.1 days in 2008. 3 deaths (0.15%) were associated with clotting episodes and overall, 11 clinical DVTs (0.56%) and 6 PEs (0.30%) were found. The vast majority of events took place within 30 days; only 1 death and 2 DVTs occurred between 30 and 90 days. During the last 2 years (854 patients), when patients were mobilized within 4 h postoperatively and the duration of DVT prophylaxis was shortest (1–4 days), the mortality was 0% (95% CI: 0–0.5). Incident cases of DVT in TKA was 0.60% (CI: 0.2–2.2), in THA it was 0.51% (CI: 0.1–1.8), and in BSTKA it was 0% (CI: 0–2.9). Incident cases of PE in TKA was 0.30% (CI: 0.1–1.7), in THA it was 0% (CI: 0–1.0), and in BSTKA it was 0% (CI: 0–2.9).INTERPRETATION: The risk of clinical DVT, and of fatal and non-fatal PE after THA and TKA following a fast-track set-up with early mobilization, short hospitalization, and short duration of DVT prophylaxis compares favorably with published regimens with extended prophylaxis (up to 36 days) and hospitalization up to 11 days. This calls for a reconsideration of optimal duration of chemical thromboprophylaxis.</p

A Longitudinal Test of the Demand–Control Model Using Specific Job Demands and Specific Job Control

# The Author(s) 2010. This article is published with open access at Springerlink.com Background Supportive studies of the demand–control (DC) model were more likely to measure specific demands combined with a corresponding aspect of control. Purpose A longitudinal test of Karasek’s (Adm Sci Q. 24:285–308, 1) job strain hypothesis including specific measures of job demands and job control, and both selfreport and objectively recorded well-being. Method Job strain hypothesis was tested among 267 health care employees from a two-wave Dutch panel survey with a 2-year time lag. Results Significant demand/control interactions were found for mental and emotional demands, but not for physical demands. The association between job demands and job satisfaction was positive in case of high job control, whereas this association was negative in case of low job control. In addition, the relation between job demands and J. de Jonge (*

A Model of Ischemia-Induced Neuroblast Activation in the Adult Subventricular Zone

We have developed a rat brain organotypic culture model, in which tissue slices contain cortex-subventricular zone-striatum regions, to model neuroblast activity in response to in vitro ischemia. Neuroblast activation has been described in terms of two main parameters, proliferation and migration from the subventricular zone into the injured cortex. We observed distinct phases of neuroblast activation as is known to occur after in vivo ischemia. Thus, immediately after oxygen/glucose deprivation (6–24 hours), neuroblasts reduce their proliferative and migratory activity, whereas, at longer time points after the insult (2 to 5 days), they start to proliferate and migrate into the damaged cortex. Antagonism of ionotropic receptors for extracellular ATP during and after the insult unmasks an early activation of neuroblasts in the subventricular zone, which responded with a rapid and intense migration of neuroblasts into the damaged cortex (within 24 hours). The process is further enhanced by elevating the production of the chemoattractant SDf-1α and may also be boosted by blocking the activation of microglia. This organotypic model which we have developed is an excellent in vitro system to study neurogenesis after ischemia and other neurodegenerative diseases. Its application has revealed a SOS response to oxygen/glucose deprivation, which is inhibited by unfavorable conditions due to the ischemic environment. Finally, experimental quantifications have allowed us to elaborate a mathematical model to describe neuroblast activation and to develop a computer simulation which should have promising applications for the screening of drug candidates for novel therapies of ischemia-related pathologies