Superconducting properties in heavily overdoped Ba(Fe0.86Co0.14)2As2 single crystals

We report the intrinsic superconducting parameters in a heavily overdoped Ba(Fe1-xCox)(2)As-2 (x=0.14) single crystal and their influence in the resulting vortex dynamics. We find a bulk superconducting critical temperature of 9.8 K, magnetic penetration depth lambda(ab) (0)=660 +/- 50 nm, coherence length xi(ab) (0)=6.4 +/- 0.2 nm, and the upper critical field anisotropy gamma(T -> Tc) approximate to 3.7. The vortex phase diagram, in comparison with the optimally doped compound, presents a narrow collective creep regime. The intrinsic pinning energy plays an important role in the resulting vortex dynamics as compared with similar pinning landscape and comparable intrinsic thermal fluctuations. (C) 2014 Elsevier Ltd. All rights reserved.X1111Ysciescopu

A composite serum biomarker index for the diagnosis of systemic sclerosis interstitial lung disease: a multicentre, observational, cohort study

OBJECTIVE: In patients with systemic sclerosis (SSc), we investigated composite serum biomarker panels for the diagnosis and risk-stratification of SSc-associated interstitial lung disease (SSc-ILD). METHODS: Twenty-eight biomarkers were analysed in 640 participants: 259 with SSc-ILD and 179 SSc-controls without ILD (Australian Scleroderma Cohort Study), 172 idiopathic pulmonary fibrosis (IPF)-controls (Australian IPF Registry), and 30 healthy controls. A composite index was developed from biomarkers associated with ILD in multivariable analysis derived at empirical thresholds. Performance of the index to identify ILD, and specifically SSc-ILD, and its association with lung function, radiological extent, health-related quality of life (HRQoL) were evaluated in derivation and validation cohorts. Biomarkers to distinguish SSc-ILD from IPF-controls were identified. RESULTS: A composite biomarker index, comprising SP-D, Ca15-3 and ICAM-1, was strongly associated with SSc-ILD diagnosis, independent of age, sex, smoking and lung function (index=3: pooled adjusted OR 12.72, 95%CI 4.59-35.21, p<0.001). The composite index strengthened the performance of individual biomarkers for SSc-ILD identification. In SSc patients, a higher index was associated with worse baseline disease severity (index=3 relative to index=0: adjusted absolute change in FVC% - 17.84% and DLCO% - 20.16%, both p<0.001). CONCLUSION: A composite serum biomarker index, comprising SP-D, Ca15-3 and ICAM-1 may improve the identification and risk-stratification of ILD in SSc patients at baseline

Hubble Space Telescope Discovery of a z = 3.9 Multiply Imaged Galaxy Behind the Complex Cluster Lens WARPS J1415.1+36 at z = 1.026

We report the discovery of a multiply lensed Ly Alpha (Lya) emitter at z = 3.90 behind the massive galaxy cluster WARPS J1415.1+3612 at z = 1.026. Images taken by the Hubble Space Telescope(HST) using ACS reveal a complex lensing system that produces a prominent, highly magnified arc and a triplet of smaller arcs grouped tightly around a spectroscopically confirmed cluster member. Spectroscopic observations using FOCAS on Subaru confirm strong Lya emission in the source galaxy and provide redshifts for more than 21 cluster members, from which we obtain a velocity dispersion of 807+/-185 km/s. Assuming a singular isothermal sphere profile, the mass within the Einstein ring (7.13+/-0.38 ) corresponds to a central velocity dispersion of 686+15-19 km/s for the cluster, consistent with the value estimated from cluster member redshifts. Our mass profile estimate from combining strong lensing and dynamical analyses is in good agreement with both X-ray and weak lensing results

Global, regional, and national comparative risk assessment of 79 behavioural, environmental and occupational, and metabolic risks or clusters of risks, 1990-2015: a systematic analysis for the Global Burden of Disease Study 2015

SummaryBackground The Global Burden of Diseases, Injuries, and Risk Factors Study 2015 provides an up-to-date synthesis of the evidence for risk factor exposure and the attributable burden of disease. By providing national and subnational assessments spanning the past 25 years, this study can inform debates on the importance of addressing risks in context. Methods We used the comparative risk assessment framework developed for previous iterations of the Global Burden of Disease Study to estimate attributable deaths, disability-adjusted life-years (DALYs), and trends in exposure by age group, sex, year, and geography for 79 behavioural, environmental and occupational, and metabolic risks or clusters of risks from 1990 to 2015. This study included 388 risk-outcome pairs that met World Cancer Research Fund-defined criteria for convincing or probable evidence. We extracted relative risk and exposure estimates from randomised controlled trials, cohorts, pooled cohorts, household surveys, census data, satellite data, and other sources. We used statistical models to pool data, adjust for bias, and incorporate covariates. We developed a metric that allows comparisons of exposure across risk factors—the summary exposure value. Using the counterfactual scenario of theoretical minimum risk level, we estimated the portion of deaths and DALYs that could be attributed to a given risk. We decomposed trends in attributable burden into contributions from population growth, population age structure, risk exposure, and risk-deleted cause-specific DALY rates. We characterised risk exposure in relation to a Socio-demographic Index (SDI). Findings Between 1990 and 2015, global exposure to unsafe sanitation, household air pollution, childhood underweight, childhood stunting, and smoking each decreased by more than 25%. Global exposure for several occupational risks, high body-mass index (BMI), and drug use increased by more than 25% over the same period. All risks jointly evaluated in 2015 accounted for 57·8% (95% CI 56·6–58·8) of global deaths and 41·2% (39·8–42·8) of DALYs. In 2015, the ten largest contributors to global DALYs among Level 3 risks were high systolic blood pressure (211·8 million [192·7 million to 231·1 million] global DALYs), smoking (148·6 million [134·2 million to 163·1 million]), high fasting plasma glucose (143·1 million [125·1 million to 163·5 million]), high BMI (120·1 million [83·8 million to 158·4 million]), childhood undernutrition (113·3 million [103·9 million to 123·4 million]), ambient particulate matter (103·1 million [90·8 million to 115·1 million]), high total cholesterol (88·7 million [74·6 million to 105·7 million]), household air pollution (85·6 million [66·7 million to 106·1 million]), alcohol use (85·0 million [77·2 million to 93·0 million]), and diets high in sodium (83·0 million [49·3 million to 127·5 million]). From 1990 to 2015, attributable DALYs declined for micronutrient deficiencies, childhood undernutrition, unsafe sanitation and water, and household air pollution; reductions in risk-deleted DALY rates rather than reductions in exposure drove these declines. Rising exposure contributed to notable increases in attributable DALYs from high BMI, high fasting plasma glucose, occupational carcinogens, and drug use. Environmental risks and childhood undernutrition declined steadily with SDI; low physical activity, high BMI, and high fasting plasma glucose increased with SDI. In 119 countries, metabolic risks, such as high BMI and fasting plasma glucose, contributed the most attributable DALYs in 2015. Regionally, smoking still ranked among the leading five risk factors for attributable DALYs in 109 countries; childhood underweight and unsafe sex remained primary drivers of early death and disability in much of sub-Saharan Africa. Interpretation Declines in some key environmental risks have contributed to declines in critical infectious diseases. Some risks appear to be invariant to SDI. Increasing risks, including high BMI, high fasting plasma glucose, drug use, and some occupational exposures, contribute to rising burden from some conditions, but also provide opportunities for intervention. Some highly preventable risks, such as smoking, remain major causes of attributable DALYs, even as exposure is declining. Public policy makers need to pay attention to the risks that are increasingly major contributors to global burden. Funding Bill & Melinda Gates Foundation

The expression of FHIT, PCNA and EGFR in benign and malignant breast lesions

Immunohistochemical staining for FHIT and PCNA proteins was carried out in 451 breast lesions showing nonproliferative benign breast disease (BBD) (n=263), proliferative BBD without atypia (n=128), proliferative BBD with atypia (n=11), carcinoma in situ (n=15) or invasive carcinoma (n=34) and for EGFR protein in a subset of 71 of these cases. FHIT underexpression was not detected in nonproliferative lesions, but occurred in 2% of proliferative BBD without atypia, 10% proliferative BBD with atypia, 27% of carcinoma in situ and 41% of invasive carcinoma, which suggests that it could be useful in assessing those carcinoma in situ lesions (ductal, DCIS and lobular, LCIS) that are more likely to progress to malignancy. Preliminary microarray comparisons on DCIS and invasive carcinoma samples dissected from formalin-fixed paraffin sections showed a consistent downregulation of two previously identified FHIT-related genes, caspase 1 and BRCA1 in lesions underexpressing FHIT

An integrative multi-dimensional genetic and epigenetic strategy to identify aberrant genes and pathways in cancer

<p>Abstract</p> <p>Background</p> <p>Genomics has substantially changed our approach to cancer research. Gene expression profiling, for example, has been utilized to delineate subtypes of cancer, and facilitated derivation of predictive and prognostic signatures. The emergence of technologies for the high resolution and genome-wide description of genetic and epigenetic features has enabled the identification of a multitude of causal DNA events in tumors. This has afforded the potential for large scale integration of genome and transcriptome data generated from a variety of technology platforms to acquire a better understanding of cancer.</p> <p>Results</p> <p>Here we show how multi-dimensional genomics data analysis would enable the deciphering of mechanisms that disrupt regulatory/signaling cascades and downstream effects. Since not all gene expression changes observed in a tumor are causal to cancer development, we demonstrate an approach based on multiple concerted disruption (MCD) analysis of genes that facilitates the rational deduction of aberrant genes and pathways, which otherwise would be overlooked in single genomic dimension investigations.</p> <p>Conclusions</p> <p>Notably, this is the first comprehensive study of breast cancer cells by parallel integrative genome wide analyses of DNA copy number, LOH, and DNA methylation status to interpret changes in gene expression pattern. Our findings demonstrate the power of a multi-dimensional approach to elucidate events which would escape conventional single dimensional analysis and as such, reduce the cohort sample size for cancer gene discovery.</p

AMPK Regulates Circadian Rhythms in a Tissue- and Isoform-Specific Manner

AMP protein kinase (AMPK) plays an important role in food intake and energy metabolism, which are synchronized to the light-dark cycle. In vitro, AMPK affects the circadian rhythm by regulating at least two clock components, CKIα and CRY1, via direct phosphorylation. However, it is not known whether the catalytic activity of AMPK actually regulates circadian rhythm in vivo.THE CATALYTIC SUBUNIT OF AMPK HAS TWO ISOFORMS: α1 and α2. We investigate the circadian rhythm of behavior, physiology and gene expression in AMPKα1-/- and AMPKα2-/- mice. We found that both α1-/- and α2-/- mice are able to maintain a circadian rhythm of activity in dark-dark (DD) cycle, but α1-/- mice have a shorter circadian period whereas α2-/- mice showed a tendency toward a slightly longer circadian period. Furthermore, the circadian rhythm of body temperature was dampened in α1-/- mice, but not in α2-/- mice. The circadian pattern of core clock gene expression was severely disrupted in fat in α1-/- mice, but it was severely disrupted in the heart and skeletal muscle of α2-/- mice. Interestingly, other genes that showed circadian pattern of expression were dysreguated in both α1-/- and α2-/- mice. The circadian rhythm of nicotinamide phosphoryl-transferase (NAMPT) activity, which converts nicotinamide (NAM) to NAD+, is an important regulator of the circadian clock. We found that the NAMPT rhythm was absent in AMPK-deficient tissues and cells.This study demonstrates that the catalytic activity of AMPK regulates circadian rhythm of behavior, energy metabolism and gene expression in isoform- and tissue-specific manners

Polymorphisms of TP53 codon 72 with breast carcinoma risk: evidence from 12226 cases and 10782 controls

<p>Abstract</p> <p>Background</p> <p>Previously, TP53 codon 72 polymorphisms have been implicated as risk factors for various cancers. A number of studies have conducted on the association of TP53 codon 72 polymorphisms with susceptibility to breast carcinoma and have yielded inconclusive results. The aim of the present study was to derive a more precise estimation of the relationship.</p> <p>Methods</p> <p>We conducted a search in the Medline, EMBASE, OVID, Sciencedirect, and Chinese National Knowledge Infrastructure (CNKI) without a language limitation, covering all papers published up to Jan 2009. The associated literature was acquired through deliberate searching and selected based on the established inclusion criteria for publications.</p> <p>Results</p> <p>A total of seventeen case-control studies, including 12226 cases and 10782 controls, met the included criteria and thus were selected. Ultimately, the relevant data were extracted and further analyzed using systematic meta-analyses. Overall, no associations of TP53 codon 72 polymorphisms with breast carcinoma were observed (for Arg/Arg vs Pro/Pro: OR = 1.20; 95%CI = 0.96–1.50; for dominant model: OR = 1.12; 95%CI = 0.96–1.32; for recessive model: OR = 1.13; 95%CI = 0.98–1.31). In the subgroup analysis by ethnicity, statistically similar results were obtained when the data were stratified as Asians, Caucasians and Africans.</p> <p>Conclusion</p> <p>Collectively, the results of the present study suggest that <it>TP53 codon 72 </it>polymorphisms might not be a low-penetrant risk factor for developing breast carcinoma.</p

A Bovine Model of Respiratory Chlamydia psittaci Infection: Challenge Dose Titration

This study aimed to establish and evaluate a bovine respiratory model of experimentally induced acute C. psittaci infection. Calves are natural hosts and pathogenesis may resemble the situation in humans. Intrabronchial inoculation of C. psittaci strain DC15 was performed in calves aged 2–3 months via bronchoscope at four different challenge doses from 106 to 109 inclusion-forming units (ifu) per animal. Control groups received either UV-inactivated C. psittaci or cell culture medium. While 106 ifu/calf resulted in a mild respiratory infection only, the doses of 107 and 108 induced fever, tachypnea, dry cough, and tachycardia that became apparent 2–3 days post inoculation (dpi) and lasted for about one week. In calves exposed to 109 ifu C. psittaci, the respiratory disease was accompanied by severe systemic illness (apathy, tremor, markedly reduced appetite). At the time point of most pronounced clinical signs (3 dpi) the extent of lung lesions was below 10% of pulmonary tissue in calves inoculated with 106 and 107 ifu, about 15% in calves inoculated with 108 and more than 30% in calves inoculated with 109 ifu C. psittaci. Beside clinical signs and pathologic lesions, the bacterial load of lung tissue and markers of pulmonary inflammation (i.e., cell counts, concentration of proteins and eicosanoids in broncho-alveolar lavage fluid) were positively associated with ifu of viable C. psittaci. While any effect of endotoxin has been ruled out, all effects could be attributed to infection by the replicating bacteria. In conclusion, the calf represents a suitable model of respiratory chlamydial infection. Dose titration revealed that both clinically latent and clinically manifest infection can be reproduced experimentally by either 106 or 108 ifu/calf of C. psittaci DC15 while doses above 108 ifu C. psittaci cannot be recommended for further studies for ethical reasons. This defined model of different clinical expressions of chlamydial infection allows studying host-pathogen interactions