Reduction of radiation pneumonitis by V20-constraints in breast cancer

<p>Abstract</p> <p>Introduction</p> <p>Adjuvant local-regional radiotherapy (LRRT) is routinely recommended for breast cancer patients. It is well known being related to pulmonary side-effects. We studied post-RT radiological changes on X-ray and CT, and correlated the findings with Quality of Life (QoL), common dosimetric factors and co-variates. The results were compared with a previously reported cohort of 137 irradiated women.</p> <p>Methods</p> <p>88 women underwent chest X-ray and CT pre-and 4-5 months after 3-D planned LRRT, minimizing the dose to the ipsilateral lung to V₂₀< 30%. The lung field was divided into 3 regions and the development of post-RT density changes were graded (0-3). Patients with radiological changes were compared with non-responders. Clinical symptoms were registered and data on patient and treatment related co-variates were gathered prospectively. The ipsilateral lung dosimetric factors V₁₃, V₂₀, V₃₀and mean dose were calculated and QoL was assessed before and 4 months after RT.</p> <p>Results</p> <p>The use of dose-volume constraints significally reduced moderate-severe radiological changes on chest X-ray compared with our earlier study (Chi square trend test: p < 0.001). Symptomatic pneumonitis was also rare in the present study. No agreement was found between CT and chest X-ray as diagnostic tools for post-RT pneumonitis. V₁₃correlated independently with radiological changes on CT (logistic regression: p = 0.04; ROC area: 0.7). The Co-variates smoking habits, age, chemotherapy, endocrine or trastuzumab therapy did not influence the outcome on multivariate analysis. QoL changes in physical function, i.e. fatigue, dyspnoea were not detected but there was a trend for a worse recovery after chemotherapy in patients with high V₁₃(Spearman Rank Correlation: p < 0.05).</p> <p>Conclusions</p> <p>The use of dose-volume constraints significantly reduced post-RT radiological changes on chest X-ray in LRRT for BC. The lung changes on CT were also generally limited when we used this strategy and was not always picked up on chest X-ray. Variation in V₁₃alone was correlated with occurrence of lung changes on CT.</p

Genderforschung - zwischen disziplinärer Marginalisierung und institutioneller Etablierung: zum aktuellen Stand des Institutionalisierungsprozesses von Genderprofessuren an deutschsprachigen Hochschulen

"Die Schaffung von Genderprofessuren ist ein wichtiger Aspekt im Prozess einer nachhaltigen Institutionalisierung von Frauen- und Geschlechterforschung/Gender Studies an den Hochschulen. Der Beitrag basiert auf einer Auswertung der Datenbank Genderprofessuren an deutschsprachigen Hochschulen (Stand Juli 2010) zur Gesamtzahl der Genderprofessuren, deren Verteilung auf Bundesländer (Deutschland), Hochschultypen und Disziplinen, zu den Besoldungsgruppen und der Vertragsdauer. Zudem werden Aussagen zur Entwicklung der Denominationen getroffen. Im Ergebnis zeigt sich ein mehrschichtiges Bild: einerseits eine Zunahme der Anzahl der Genderprofessuren im Laufe der letzten Jahre sowie eine Verteilung auf ein großes Fächerspektrum, andererseits jedoch eine andauernde, quantitativ marginale Bedeutung im Vergleich zur Gesamtzahl aller Professuren an den Hochschulen." (Autorenreferat)"The creation of Gender Studies professorships is one important aspect in the process of the long-term institutionalization of Women's Studies/Gender Studies at universities. The article is based on an analysis of the database 'Gender Studies professorships at Germanlanguage universities' (as of July 2010) regarding the total number of Gender Studies professorships, their distribution among the federal states (Germany), types of universities and disciplines, as well as regarding pay grade and duration of appointment. Furthermore, the article addresses the development of denominations. The resulting picture is multilayered: on the one hand, there are increasing numbers of Gender Studies professorships in the course of the last number of years as well as their distribution and a broad range of subjects; on the other hand, however, they continue to have little relevance (quantitatively) compared to the total number of professorships at the universities." (author's abstract

New genetic loci implicated in fasting glucose homeostasis and their impact on type 2 diabetes risk.

Levels of circulating glucose are tightly regulated. To identify new loci influencing glycemic traits, we performed meta-analyses of 21 genome-wide association studies informative for fasting glucose, fasting insulin and indices of beta-cell function (HOMA-B) and insulin resistance (HOMA-IR) in up to 46,186 nondiabetic participants. Follow-up of 25 loci in up to 76,558 additional subjects identified 16 loci associated with fasting glucose and HOMA-B and two loci associated with fasting insulin and HOMA-IR. These include nine loci newly associated with fasting glucose (in or near ADCY5, MADD, ADRA2A, CRY2, FADS1, GLIS3, SLC2A2, PROX1 and C2CD4B) and one influencing fasting insulin and HOMA-IR (near IGF1). We also demonstrated association of ADCY5, PROX1, GCK, GCKR and DGKB-TMEM195 with type 2 diabetes. Within these loci, likely biological candidate genes influence signal transduction, cell proliferation, development, glucose-sensing and circadian regulation. Our results demonstrate that genetic studies of glycemic traits can identify type 2 diabetes risk loci, as well as loci containing gene variants that are associated with a modest elevation in glucose levels but are not associated with overt diabetes

A haplotype of polymorphisms in ASE-1, RAI and ERCC1 and the effects of tobacco smoking and alcohol consumption on risk of colorectal cancer: a danish prospective case-cohort study

<p>Abstract</p> <p>Background</p> <p>Single nucleotide polymorphisms (SNPs) are the most frequent type of genetic variation in the human genome, and are of interest for the study of susceptibility to and protection from diseases. The haplotype at chromosome 19q13.2-3 encompassing the three SNPs <it>ASE-1 </it>G-21A, <it>RAI </it>IVS1 A4364G and <it>ERCC1 </it>Asn118Asn have been associated with risk of breast cancer and lung cancer. Haplotype carriers are defined as the homozygous carriers of <it>RAI </it>IVS1 A4364G^A, <it>ERCC1 </it>Asn118Asn^Tand <it>ASE-1 </it>G-21A^G. We aimed to evaluate whether the three polymorphisms and the haplotype are associated to risk of colorectal cancer, and investigated gene-environment associations between the polymorphisms and the haplotype and smoking status at enrolment, smoking duration, average smoking intensity and alcohol consumption, respectively, in relation to risk of colorectal cancer.</p> <p>Methods</p> <p>Associations between the three individual polymorphisms, the haplotype and risk of colorectal cancer were examined, as well as gene-environment interaction, in a Danish case-cohort study including 405 cases and a comparison group of 810 persons. Incidence rate ratio (IRR) were estimated by the Cox proportional hazards model stratified according to gender, and two-sided 95% confidence intervals (CI) and p-values were calculated based on robust estimates of the variance-covariance matrix and Wald's test of the Cox regression parameter.</p> <p>Results</p> <p>No consistent associations between the three individual polymorphisms, the haplotype and risk of colorectal cancer were found. No statistically significant interactions between the genotypes and the lifestyle exposures smoking or alcohol consumption were observed.</p> <p>Conclusion</p> <p>Our results suggest that the <it>ASE-1 </it>G-21A, <it>RAI </it>IVS1 A4364G and <it>ERCC1 </it>Asn118Asn polymorphisms and the previously identified haplotype are not associated with risk of colorectal cancer. We found no evidence of gene-environment interaction between the three polymorphisms and the haplotype and smoking intensity and alcohol consumption, respectively, in relation to the risk of colorectal cancer.</p

Still Arctic? — The changing Barents Sea

The Barents Sea is one of the Polar regions where current climate and ecosystem change is most pronounced. Here we review the current state of knowledge of the physical, chemical and biological systems in the Barents Sea. Physical conditions in this area are characterized by large seasonal contrasts between partial sea-ice cover in winter and spring versus predominantly open water in summer and autumn. Observations over recent decades show that surface air and ocean temperatures have increased, sea-ice extent has decreased, ocean stratification has weakened, and water chemistry and ecosystem components have changed, the latter in a direction often described as “Atlantification” or “borealisation,” with a less “Arctic” appearance. Temporal and spatial changes in the Barents Sea have a wider relevance, both in the context of large-scale climatic (air, water mass and sea-ice) transport processes and in comparison to other Arctic regions. These observed changes also have socioeconomic consequences, including for fisheries and other human activities. While several of the ongoing changes are monitored and quantified, observation and knowledge gaps remain, especially for winter months when field observations and sample collections are still sparse. Knowledge of the interplay of physical and biogeochemical drivers and ecosystem responses, including complex feedback processes, needs further development.Still Arctic? — The changing Barents SeapublishedVersio

Genomic analyses identify hundreds of variants associated with age at menarche and support a role for puberty timing in cancer risk

The timing of puberty is a highly polygenic childhood trait that is epidemiologically associated with various adult diseases. Using 1000 Genomes Project-imputed genotype data in up to similar to 370,000 women, we identify 389 independent signals (P <5 x 10(-8)) for age at menarche, a milestone in female pubertal development. In Icelandic data, these signals explain similar to 7.4% of the population variance in age at menarche, corresponding to similar to 25% of the estimated heritability. We implicate similar to 250 genes via coding variation or associated expression, demonstrating significant enrichment in neural tissues. Rare variants near the imprinted genes MKRN3 and DLK1 were identified, exhibiting large effects when paternally inherited. Mendelian randomization analyses suggest causal inverse associations, independent of body mass index (BMI), between puberty timing and risks for breast and endometrial cancers in women and prostate cancer in men. In aggregate, our findings highlight the complexity of the genetic regulation of puberty timing and support causal links with cancer susceptibility

New genetic loci link adipose and insulin biology to body fat distribution.

Body fat distribution is a heritable trait and a well-established predictor of adverse metabolic outcomes, independent of overall adiposity. To increase our understanding of the genetic basis of body fat distribution and its molecular links to cardiometabolic traits, here we conduct genome-wide association meta-analyses of traits related to waist and hip circumferences in up to 224,459 individuals. We identify 49 loci (33 new) associated with waist-to-hip ratio adjusted for body mass index (BMI), and an additional 19 loci newly associated with related waist and hip circumference measures (P < 5 × 10(-8)). In total, 20 of the 49 waist-to-hip ratio adjusted for BMI loci show significant sexual dimorphism, 19 of which display a stronger effect in women. The identified loci were enriched for genes expressed in adipose tissue and for putative regulatory elements in adipocytes. Pathway analyses implicated adipogenesis, angiogenesis, transcriptional regulation and insulin resistance as processes affecting fat distribution, providing insight into potential pathophysiological mechanisms

Repositioning of the global epicentre of non-optimal cholesterol

High blood cholesterol is typically considered a feature of wealthy western countries(1,2). However, dietary and behavioural determinants of blood cholesterol are changing rapidly throughout the world(3) and countries are using lipid-lowering medications at varying rates. These changes can have distinct effects on the levels of high-density lipoprotein (HDL) cholesterol and non-HDL cholesterol, which have different effects on human health(4,5). However, the trends of HDL and non-HDL cholesterol levels over time have not been previously reported in a global analysis. Here we pooled 1,127 population-based studies that measured blood lipids in 102.6 million individuals aged 18 years and older to estimate trends from 1980 to 2018 in mean total, non-HDL and HDL cholesterol levels for 200 countries. Globally, there was little change in total or non-HDL cholesterol from 1980 to 2018. This was a net effect of increases in low- and middle-income countries, especially in east and southeast Asia, and decreases in high-income western countries, especially those in northwestern Europe, and in central and eastern Europe. As a result, countries with the highest level of non-HDL cholesterol-which is a marker of cardiovascular riskchanged from those in western Europe such as Belgium, Finland, Greenland, Iceland, Norway, Sweden, Switzerland and Malta in 1980 to those in Asia and the Pacific, such as Tokelau, Malaysia, The Philippines and Thailand. In 2017, high non-HDL cholesterol was responsible for an estimated 3.9 million (95% credible interval 3.7 million-4.2 million) worldwide deaths, half of which occurred in east, southeast and south Asia. The global repositioning of lipid-related risk, with non-optimal cholesterol shifting from a distinct feature of high-income countries in northwestern Europe, north America and Australasia to one that affects countries in east and southeast Asia and Oceania should motivate the use of population-based policies and personal interventions to improve nutrition and enhance access to treatment throughout the world.Peer reviewe