Entropy of chains placed on the square lattice

We obtain the entropy of flexible linear chains composed of M monomers placed on the square lattice using a transfer matrix approach. An excluded volume interaction is included by considering the chains to be self-and mutually avoiding, and a fraction rho of the sites are occupied by monomers. We solve the problem exactly on stripes of increasing width m and then extrapolate our results to the two-dimensional limit to infinity using finite-size scaling. The extrapolated results for several finite values of M and in the polymer limit M to infinity for the cases where all lattice sites are occupied (rho=1) and for the partially filled case rho<1 are compared with earlier results. These results are exact for dimers (M=2) and full occupation (\rho=1) and derived from series expansions, mean-field like approximations, and transfer matrix calculations for some other cases. For small values of M, as well as for the polymer limit M to infinity, rather precise estimates of the entropy are obtained.Comment: 6 pages, 7 figure

Promoting Mental Health and Preventing Mental Illness in General Practice

This paper calls for the routine integration of mental health promotion and prevention into UK General Practice in order to reduce the burden of mental and physical disorders and the ensuing pressure on General Practice. The proposals & the resulting document (https://ethicscharity.files.wordpress.com/2015/09/rcgp_keymsg_150925_v5.pdf) arise from an expert ‘Think Tank’ convened by the London Journal of Primary Care, Educational Trust for Health Improvement through Cognitive Strategies (ETHICS Foundation) and the Royal College of General Practitioners. It makes 12 recommendations for General Practice: (1) Mental health promotion and prevention are too important to wait. (2) Work with your community to map risk factors, resources and assets. (3) Good health care, medicine and best practice are biopsychosocial rather than purely physical. (4) Integrate mental health promotion and prevention into your daily work. (5) Boost resilience in your community through approaches such as community development. (6) Identify people at increased risk of mental disorder for support and screening. (7) Support early intervention for people of all ages with signs of illness. (8) Maintain your biopsychosocial skills. (9) Ensure good communication, interdisciplinary team working and inter-sectoral working with other staff, teams and agencies. (10) Lead by example, taking action to promote the resilience of the general practice workforce. (11) Ensure mental health is appropriately included in the strategic agenda for your ‘cluster’ of General Practices, at the Clinical Commissioning Groups, and the Health and Wellbeing Board. (12) Be aware of national mental health strategies and localise them, including action to destigmatise mental illness within the context of community development

Impact of an adherence intervention on the effectiveness of tenofovir gel in the CAPRISA 004 trial.

CAPRISA, 2014.Abstract not available in pdf

Lake isotope records of the 8200-year cooling event in western Ireland: Comparison with model simulations

The early Holocene cooling, which occurred around 8200 calendar years before present, was a prominent abrupt event around the north Atlantic region. Here, we investigate the timing, duration, magnitude and regional coherence of the event as expressed in carbonate oxygen-isotope records from three lakes on northwest Europe's Atlantic margin in western Ireland, namely Loch Avolla, Loch Gealáin and Lough Corrib. An abrupt negative oxygen-isotope excursion lasted about 200 years. Comparison of records from three sites suggests that the excursion was primarily the result of a reduction of the oxygen-isotope values of precipitation, which was likely caused by lowered air temperatures, possibly coupled with a change in atmospheric circulation. Comparison of records from two of the lakes (Loch Avolla and Loch Gealáin), which have differing bathymetries, further suggests a reduction in evaporative loss of lake water during the cooling episode. Comparison of climate model experiments with lake-sediment isotope data indicates that effective moisture may have increased along this part of the northeast Atlantic seaboard during the 8200-year climatic event, as lower evaporation compensated for reduced precipitation

Optimizing Staining Protocols for Laser Microdissection of Specific Cell Types from the Testis Including Carcinoma In Situ

Microarray and RT-PCR based methods are important tools for analysis of gene expression; however, in tissues containing many different cells types, such as the testis, characterization of gene expression in specific cell types can be severely hampered by noise from other cells. The laser microdissection technology allows for enrichment of specific cell types. However, when the cells are not morphologically distinguishable, it is necessary to use a specific staining method for the target cells. In this study we have tested different fixatives, storage conditions for frozen sections and staining protocols, and present two staining protocols for frozen sections, one for fast and specific staining of fetal germ cells, testicular carcinoma in situ cells, and other cells with embryonic stem cell-like properties that express the alkaline phosphatase, and one for specific staining of lipid droplet-containing cells, which is useful for isolation of the androgen-producing Leydig cells. Both protocols retain a morphology that is compatible with laser microdissection and yield RNA of a quality suitable for PCR and microarray analysis

A dusty, normal galaxy in the epoch of reionization

Candidates for the modest galaxies that formed most of the stars in the early universe, at redshifts $z > 7$, have been found in large numbers with extremely deep restframe-UV imaging. But it has proved difficult for existing spectrographs to characterise them in the UV. The detailed properties of these galaxies could be measured from dust and cool gas emission at far-infrared wavelengths if the galaxies have become sufficiently enriched in dust and metals. So far, however, the most distant UV-selected galaxy detected in dust emission is only at $z = 3.25$, and recent results have cast doubt on whether dust and molecules can be found in typical galaxies at this early epoch. Here we report thermal dust emission from an archetypal early universe star-forming galaxy, A1689-zD1. We detect its stellar continuum in spectroscopy and determine its redshift to be $z = 7.5\pm0.2$ from a spectroscopic detection of the Ly{\alpha} break. A1689-zD1 is representative of the star-forming population during reionisation, with a total star-formation rate of about 12M$_\odot$ yr$^{-1}$. The galaxy is highly evolved: it has a large stellar mass, and is heavily enriched in dust, with a dust-to-gas ratio close to that of the Milky Way. Dusty, evolved galaxies are thus present among the fainter star-forming population at $z > 7$, in spite of the very short time since they first appeared.Comment: Nature in press. 14 pages, 10 figures, including methods sectio

Chronic Consumption of Farmed Salmon Containing Persistent Organic Pollutants Causes Insulin Resistance and Obesity in Mice

Background: Dietary interventions are critical in the prevention of metabolic diseases. Yet, the effects of fatty fish consumption on type 2 diabetes remain unclear. The aim of this study was to investigate whether a diet containing farmed salmon prevents or contributes to insulin resistance in mice. Methodology/Principal Findings: Adult male C57BL/6J mice were fed control diet (C), a very high-fat diet without or with farmed Atlantic salmon fillet (VHF and VHF/S, respectively), and Western diet without or with farmed Atlantic salmon fillet (WD and WD/S, respectively). Other mice were fed VHF containing farmed salmon fillet with reduced concentrations of persistent organic pollutants (VHF/S-POPs). We assessed body weight gain, fat mass, insulin sensitivity, glucose tolerance, ex vivo muscle glucose uptake, performed histology and immunohistochemistry analysis, and investigated gene and protein expression. In comparison with animals fed VHF and WD, consumption of both VHF/S and WD/S exaggerated insulin resistance, visceral obesity, and glucose intolerance. In addition, the ability of insulin to stimulate Akt phosphorylation and muscle glucose uptake was impaired in mice fed farmed salmon. Relative to VHF/S-fed mice, animals fed VHF/S-POPs had less body burdens of POPs, accumulated less visceral fat, and had reduced mRNA levels of TNFa as well as macrophage infiltration in adipose tissue. VHF/S-POPs-fed mice further exhibited better insulin sensitivity and glucose tolerance than mice fed VHF/S. Conclusions/Significance: Our data indicate that intake of farmed salmon fillet contributes to several metabolic disorders linked to type 2 diabetes and obesity, and suggest a role of POPs in these deleterious effects. Overall, these findings may participate to improve nutritional strategies for the prevention and therapy of insulin resistance

Changing genetic architecture of body mass index from infancy to early adulthood : an individual based pooled analysis of 25 twin cohorts

Publisher Copyright: © 2022, The Author(s).Background: Body mass index (BMI) shows strong continuity over childhood and adolescence and high childhood BMI is the strongest predictor of adult obesity. Genetic factors strongly contribute to this continuity, but it is still poorly known how their contribution changes over childhood and adolescence. Thus, we used the genetic twin design to estimate the genetic correlations of BMI from infancy to adulthood and compared them to the genetic correlations of height. Methods: We pooled individual level data from 25 longitudinal twin cohorts including 38,530 complete twin pairs and having 283,766 longitudinal height and weight measures. The data were analyzed using Cholesky decomposition offering genetic and environmental correlations of BMI and height between all age combinations from 1 to 19 years of age. Results: The genetic correlations of BMI and height were stronger than the trait correlations. For BMI, we found that genetic correlations decreased as the age between the assessments increased, a trend that was especially visible from early to middle childhood. In contrast, for height, the genetic correlations were strong between all ages. Age-to-age correlations between environmental factors shared by co-twins were found for BMI in early childhood but disappeared altogether by middle childhood. For height, shared environmental correlations persisted from infancy to adulthood. Conclusions: Our results suggest that the genes affecting BMI change over childhood and adolescence leading to decreasing age-to-age genetic correlations. This change is especially visible from early to middle childhood indicating that new genetic factors start to affect BMI in middle childhood. Identifying mediating pathways of these genetic factors can open possibilities for interventions, especially for those children with high genetic predisposition to adult obesity.Peer reviewe

Changing genetic architecture of body mass index from infancy to early adulthood: an individual based pooled analysis of 25 twin cohorts

BACKGROUND: Body mass index (BMI) shows strong continuity over childhood and adolescence and high childhood BMI is the strongest predictor of adult obesity. Genetic factors strongly contribute to this continuity, but it is still poorly known how their contribution changes over childhood and adolescence. Thus, we used the genetic twin design to estimate the genetic correlations of BMI from infancy to adulthood and compared them to the genetic correlations of height. METHODS: We pooled individual level data from 25 longitudinal twin cohorts including 38,530 complete twin pairs and having 283,766 longitudinal height and weight measures. The data were analyzed using Cholesky decomposition offering genetic and environmental correlations of BMI and height between all age combinations from 1 to 19 years of age. RESULTS: The genetic correlations of BMI and height were stronger than the trait correlations. For BMI, we found that genetic correlations decreased as the age between the assessments increased, a trend that was especially visible from early to middle childhood. In contrast, for height, the genetic correlations were strong between all ages. Age-to-age correlations between environmental factors shared by co-twins were found for BMI in early childhood but disappeared altogether by middle childhood. For height, shared environmental correlations persisted from infancy to adulthood. CONCLUSIONS: Our results suggest that the genes affecting BMI change over childhood and adolescence leading to decreasing age-to-age genetic correlations. This change is especially visible from early to middle childhood indicating that new genetic factors start to affect BMI in middle childhood. Identifying mediating pathways of these genetic factors can open possibilities for interventions, especially for those children with high genetic predisposition to adult obesity

Amplified Loci on Chromosomes 8 and 17 Predict Early Relapse in ER-Positive Breast Cancers

Adjuvant hormonal therapy is administered to all early stage ER+ breast cancers, and has led to significantly improved survival. Unfortunately, a subset of ER+ breast cancers suffer early relapse despite hormonal therapy. To identify molecular markers associated with early relapse in ER+ breast cancer, an outlier analysis method was applied to a published gene expression dataset of 268 ER+ early-stage breast cancers treated with tamoxifen alone. Increased expression of sets of genes that clustered in chromosomal locations consistent with the presence of amplicons at 8q24.3, 8p11.2, 17q12 (HER2 locus) and 17q21.33-q25.1 were each found to be independent markers for early disease recurrence. Distant metastasis free survival (DMFS) after 10 years for cases with any amplicon (DMFS  = 56.1%, 95% CI  = 48.3–63.9%) was significantly lower (P  = 0.0016) than cases without any of the amplicons (DMFS  = 87%, 95% CI  = 76.3% –97.7%). The association between presence of chromosomal amplifications in these regions and poor outcome in ER+ breast cancers was independent of histologic grade and was confirmed in independent clinical datasets. A separate validation using a FISH-based assay to detect the amplicons at 8q24.3, 8p11.2, and 17q21.33-q25.1 in a set of 36 early stage ER+/HER2- breast cancers treated with tamoxifen suggests that the presence of these amplicons are indeed predictive of early recurrence. We conclude that these amplicons may serve as prognostic markers of early relapse in ER+ breast cancer, and may identify novel therapeutic targets for poor prognosis ER+ breast cancers