Showing papers by "University of Cologne published in 2017"

Risks of Breast, Ovarian, and Contralateral Breast Cancer for BRCA1 and BRCA2 Mutation Carriers

Abstract: Importance: The clinical management of BRCA1 and BRCA2 mutation carriers requires accurate, prospective cancer risk estimates. Objectives: To estimate age-specific risks of breast, ovarian, and contralateral breast cancer for mutation carriers and to evaluate risk modification by family cancer history and mutation location. Design, Setting, and Participants: Prospective cohort study of 6036 BRCA1 and 3820 BRCA2 female carriers (5046 unaffected and 4810 with breast or ovarian cancer or both at baseline) recruited in 1997-2011 through the International BRCA1/2 Carrier Cohort Study, the Breast Cancer Family Registry and the Kathleen Cuningham Foundation Consortium for Research into Familial Breast Cancer, with ascertainment through family clinics (94%) and population-based studies (6%). The majority were from large national studies in the United Kingdom (EMBRACE), the Netherlands (HEBON), and France (GENEPSO). Follow-up ended December 2013; median follow-up was 5 years. Exposures: BRCA1/2 mutations, family cancer history, and mutation location. Main Outcomes and Measures: Annual incidences, standardized incidence ratios, and cumulative risks of breast, ovarian, and contralateral breast cancer. Results: Among 3886 women (median age, 38 years; interquartile range [IQR], 30-46 years) eligible for the breast cancer analysis, 5066 women (median age, 38 years; IQR, 31-47 years) eligible for the ovarian cancer analysis, and 2213 women (median age, 47 years; IQR, 40-55 years) eligible for the contralateral breast cancer analysis, 426 were diagnosed with breast cancer, 109 with ovarian cancer, and 245 with contralateral breast cancer during follow-up. The cumulative breast cancer risk to age 80 years was 72% (95% CI, 65%-79%) for BRCA1 and 69% (95% CI, 61%-77%) for BRCA2 carriers. Breast cancer incidences increased rapidly in early adulthood until ages 30 to 40 years for BRCA1 and until ages 40 to 50 years for BRCA2 carriers, then remained at a similar, constant incidence (20-30 per 1000 person-years) until age 80 years. The cumulative ovarian cancer risk to age 80 years was 44% (95% CI, 36%-53%) for BRCA1 and 17% (95% CI, 11%-25%) for BRCA2 carriers. For contralateral breast cancer, the cumulative risk 20 years after breast cancer diagnosis was 40% (95% CI, 35%-45%) for BRCA1 and 26% (95% CI, 20%-33%) for BRCA2 carriers (hazard ratio [HR] for comparing BRCA2 vs BRCA1, 0.62; 95% CI, 0.47-0.82; P=.001 for difference). Breast cancer risk increased with increasing number of first- and second-degree relatives diagnosed as having breast cancer for both BRCA1 (HR for ≥2 vs 0 affected relatives, 1.99; 95% CI, 1.41-2.82; P<.001 for trend) and BRCA2 carriers (HR, 1.91; 95% CI, 1.08-3.37; P=.02 for trend). Breast cancer risk was higher if mutations were located outside vs within the regions bounded by positions c.2282-c.4071 in BRCA1 (HR, 1.46; 95% CI, 1.11-1.93; P=.007) and c.2831-c.6401 in BRCA2 (HR, 1.93; 95% CI, 1.36-2.74; P<.001). Conclusions and Relevance: These findings provide estimates of cancer risk based on BRCA1 and BRCA2 mutation carrier status using prospective data collection and demonstrate the potential importance of family history and mutation location in risk assessment.

Topological superconductors: a review

Abstract: This review elaborates pedagogically on the fundamental concept, basic theory, expected properties, and materials realizations of topological superconductors. The relation between topological superconductivity and Majorana fermions are explained, and the difference between dispersive Majorana fermions and a localized Majorana zero mode is emphasized. A variety of routes to topological superconductivity are explained with an emphasis on the roles of spin-orbit coupling. Present experimental situations and possible signatures of topological superconductivity are summarized with an emphasis on intrinsic topological superconductors.

Association analysis identifies 65 new breast cancer risk loci

Abstract: Breast cancer risk is influenced by rare coding variants in susceptibility genes, such as BRCA1, and many common, mostly non-coding variants. However, much of the genetic contribution to breast cancer risk remains unknown. Here we report the results of a genome-wide association study of breast cancer in 122,977 cases and 105,974 controls of European ancestry and 14,068 cases and 13,104 controls of East Asian ancestry. We identified 65 new loci that are associated with overall breast cancer risk at P < 5 × 10-8. The majority of credible risk single-nucleotide polymorphisms in these loci fall in distal regulatory elements, and by integrating in silico data to predict target genes in breast cells at each locus, we demonstrate a strong overlap between candidate target genes and somatic driver genes in breast tumours. We also find that heritability of breast cancer due to all single-nucleotide polymorphisms in regulatory features was 2-5-fold enriched relative to the genome-wide average, with strong enrichment for particular transcription factor binding sites. These results provide further insight into genetic susceptibility to breast cancer and will improve the use of genetic risk scores for individualized screening and prevention.

The Role of Soil Microorganisms in Plant Mineral Nutrition—Current Knowledge and Future Directions

Abstract: In their natural environment plants are part of a rich ecosystem including numerous and diverse microorganisms in the soil. It has been long recognized that some of these microbes, such as mycorrhizal fungi or nitrogen fixing symbiotic bacteria, play important roles in plant performance by improving mineral nutrition. However, the full range of microbes associated with plants and their potential to replace synthetic agricultural inputs has only recently started to be uncovered. In the last few years a great progress has been made in the knowledge on composition of rhizospheric microbiomes and their dynamics. There is clear evidence that plants shape microbiome structures, most probably by root exudates, and also that bacteria have developed various adaptations to thrive in the rhizospheric niche. The mechanisms of these interactions and the processes driving the alterations in microbiomes are however largely unknown. In this review we focus on the interaction of plants and root associated bacteria enhancing plant mineral nutrition, summarizing the current knowledge in several research fields that can converge to improve our understanding of the molecular mechanisms underpinning this phenomenon.

Rare coding variants in PLCG2, ABI3, and TREM2 implicate microglial-mediated innate immunity in Alzheimer's disease

Abstract: We identified rare coding variants associated with Alzheimer's disease in a three-stage case–control study of 85,133 subjects. In stage 1, we genotyped 34,174 samples using a whole-exome microarray. In stage 2, we tested associated variants (P < 1 × 10−4) in 35,962 independent samples using de novo genotyping and imputed genotypes. In stage 3, we used an additional 14,997 samples to test the most significant stage 2 associations (P < 5 × 10−8) using imputed genotypes. We observed three new genome-wide significant nonsynonymous variants associated with Alzheimer's disease: a protective variant in PLCG2 (rs72824905: p.Pro522Arg, P = 5.38 × 10−10, odds ratio (OR) = 0.68, minor allele frequency (MAF)cases = 0.0059, MAFcontrols = 0.0093), a risk variant in ABI3 (rs616338: p.Ser209Phe, P = 4.56 × 10−10, OR = 1.43, MAFcases = 0.011, MAFcontrols = 0.008), and a new genome-wide significant variant in TREM2 (rs143332484: p.Arg62His, P = 1.55 × 10−14, OR = 1.67, MAFcases = 0.0143, MAFcontrols = 0.0089), a known susceptibility gene for Alzheimer's disease. These protein-altering changes are in genes highly expressed in microglia and highlight an immune-related protein–protein interaction network enriched for previously identified risk genes in Alzheimer's disease. These genetic findings provide additional evidence that the microglia-mediated innate immune response contributes directly to the development of Alzheimer's disease.

Inflammation and metabolism in tissue repair and regeneration

Abstract: Tissue repair after injury is a complex, metabolically demanding process. Depending on the tissue’s regenerative capacity and the quality of the inflammatory response, the outcome is generally imperfect, with some degree of fibrosis, which is defined by aberrant accumulation of collagenous connective tissue. Inflammatory cells multitask at the wound site by facilitating wound debridement and producing chemokines, metabolites, and growth factors. If this well-orchestrated response becomes dysregulated, the wound can become chronic or progressively fibrotic, with both outcomes impairing tissue function, which can ultimately lead to organ failure and death. Here we review the current understanding of the role of inflammation and cell metabolism in tissue-regenerative responses, highlight emerging concepts that may expand therapeutic perspectives, and briefly discuss where important knowledge gaps remain.

Cellular senescence drives age-dependent hepatic steatosis.

Abstract: The incidence of non-alcoholic fatty liver disease (NAFLD) increases with age. Cellular senescence refers to a state of irreversible cell-cycle arrest combined with the secretion of proinflammatory cytokines and mitochondrial dysfunction. Senescent cells contribute to age-related tissue degeneration. Here we show that the accumulation of senescent cells promotes hepatic fat accumulation and steatosis. We report a close correlation between hepatic fat accumulation and markers of hepatocyte senescence. The elimination of senescent cells by suicide gene-meditated ablation of p16Ink4a-expressing senescent cells in INK-ATTAC mice or by treatment with a combination of the senolytic drugs dasatinib and quercetin (D+Q) reduces overall hepatic steatosis. Conversely, inducing hepatocyte senescence promotes fat accumulation in vitro and in vivo. Mechanistically, we show that mitochondria in senescent cells lose the ability to metabolize fatty acids efficiently. Our study demonstrates that cellular senescence drives hepatic steatosis and elimination of senescent cells may be a novel therapeutic strategy to reduce steatosis.

German Multicenter Study Investigating 177Lu-PSMA-617 Radioligand Therapy in Advanced Prostate Cancer Patients.

Abstract: 177Lutetium labeled PSMA-617 is a promising new therapeutic agent for radioligand therapy (RLT) of patients with metastatic castration resistant prostate cancer (mCRPC). Initiated by the German Society of Nuclear Medicine a retrospective multicenter data analysis was started in 2015 to evaluate efficacy and safety of 177Lu-PSMA-617 in a large cohort of patients. Methods: 145 patients (median age 73 years, range 43-88) with mCRPC were treated with 177Lu-PSMA-617 in 12 therapy centres between February 2014 and July 2015 with one to four therapy cycles and an activity range of 2 to 8 GBq per cycle. Toxicity was categorized by the common toxicity criteria for adverse events (CTCAE 4.0) based on serial blood tests and the attending physician’s report. Primary endpoint for efficacy was biochemical response as defined by a PSA decline ≥ 50% from baseline to at least two weeks after start of RLT. Results: A total of 248 therapy cycles were performed in 145 patients. Data for biochemical response were available in 99 patients and data for physician-reported/lab-based toxicity in 145/121 patients. The median follow-up was 16 weeks (range 2-30 weeks). Nineteen patients died during the observation period. Grade 3 to 4 hematotoxicity occurred in 18 patients: 10%, 4% and 3% of the patients experienced anemia, thrombocytopenia and leukopenia, respectively. Xerostomia occurred in 8%. Overall biochemical response rate was 45% following all therapy cycles, while 40% of patients already responded after a single cycle. Elevated alkaline phosphatase and presence of visceral metastases were negative predictors and the total number of therapy cycles positive predictors of biochemical response. Conclusion: The present retrospective multicenter study of 177Lu-PSMA-617 RLT demonstrates favorable safety and high efficacy exceeding those of other third line systemic therapies in mCRPC patients. Future Phase II/III studies are warranted to elucidate the survival benefit of this new therapy in patients with mCRPC.

Position Paper on Olfactory Dysfunction

Abstract: Background: Olfactory dysfunction is an increasingly recognised condition, associated with reduced quality of life and major health outcomes such as neurodegeneration and death. However, translational research in this field is limited by heterogeneity in methodological approach, including definitions of impairment, improvement and appropriate assessment techniques. Accordingly, effective treatments are limited. In an effort to encourage high quality and comparable work in this field, among others, we propose the following ideas and recommendations. Whilst full recommendations are outlined in the main document, key points include: -Patients with suspected olfactory loss should undergo a full examination of the head and neck, including rigid nasal endoscopy. -Subjective olfactory assessment should not be undertaken in isolation, given its poor reliability. -Psychophysical assessment tools used in clinical and research settings should include reliable and validated tests of odour threshold, and/or one of odour identification or discrimination. -Comprehensive chemosensory assessment should include gustatory screening. -Smell training can be helpful in patients with olfactory loss of several aetiologies. Conclusions: We hope the current manuscript will encourage clinicians and researchers to adopt a common language, and in so doing, increase the methodological quality, consistency and generalisability of work in this field.

Soil networks become more connected and take up more carbon as nature restoration progresses

Abstract: Soil organisms have an important role in aboveground community dynamics and ecosystem functioning in terrestrial ecosystems. However, most studies have considered soil biota as a black box or focussed on specific groups, whereas little is known about entire soil networks. Here we show that during the course of nature restoration on abandoned arable land a compositional shift in soil biota, preceded by tightening of the belowground networks, corresponds with enhanced efficiency of carbon uptake. In mid- and long-term abandoned field soil, carbon uptake by fungi increases without an increase in fungal biomass or shift in bacterial-to-fungal ratio. The implication of our findings is that during nature restoration the efficiency of nutrient cycling and carbon uptake can increase by a shift in fungal composition and/or fungal activity. Therefore, we propose that relationships between soil food web structure and carbon cycling in soils need to be reconsidered.

Occurrence of carbapenemase-producing Klebsiella pneumoniae and Escherichia coli in the European survey of carbapenemase-producing Enterobacteriaceae (EuSCAPE): a prospective, multinational study.

Abstract: Summary Background Gaps in the diagnostic capacity and heterogeneity of national surveillance and reporting standards in Europe make it difficult to contain carbapenemase-producing Enterobacteriaceae. We report the development of a consistent sampling framework and the results of the first structured survey on the occurrence of carbapenemase-producing Klebsiella pneumoniae and Escherichia coli in European hospitals. Methods National expert laboratories recruited hospitals with diagnostic capacities, who collected the first ten carbapenem non-susceptible clinical isolates of K pneumoniae or E coli and ten susceptible same-species comparator isolates and pertinent patient and hospital information. Isolates and data were relayed back to national expert laboratories, which made laboratory-substantiated information available for central analysis. Findings Between Nov 1, 2013, and April 30, 2014, 455 sentinel hospitals in 36 countries submitted 2703 clinical isolates (2301 [85%] K pneumoniae and 402 (15%) E coli ). 850 (37%) of 2301 K pneumoniae samples and 77 (19%) of 402 E coli samples were carbapenemase (KPC, NDM, OXA-48-like, or VIM) producers. The ratio of K pneumoniae to E coli was 11:1. 1·3 patients per 10 000 hospital admissions had positive clinical specimens. Prevalence differed greatly, with the highest rates in Mediterranean and Balkan countries. Carbapenemase-producing K pneumoniae isolates showed high resistance to last-line antibiotics. Interpretation This initiative shows an encouraging commitment by all participants, and suggests that challenges in the establishment of a continent-wide enhanced sentinel surveillance for carbapenemase-producing Enterobacteriaeceae can be overcome. Strengthening infection control efforts in hospitals is crucial for controlling spread through local and national health care networks. Funding European Centre for Disease Prevention and Control.

Mortality in pulmonary arterial hypertension: prediction by the 2015 European pulmonary hypertension guidelines risk stratification model

Abstract: The 2015 European pulmonary hypertension (PH) guidelines propose a risk stratification strategy for patients with pulmonary arterial hypertension (PAH). Low-, intermediate- and high-risk strata are defined by estimated 1-year mortality risks of 10%, respectively. This risk assessment strategy awaits validation. We analysed data from patients with newly diagnosed PAH enrolled into COMPERA (Comparative, Prospective Registry of Newly Initiated Therapies for Pulmonary Hypertension), a European-based PH registry. An abbreviated version of the risk assessment strategy proposed by the European PH guidelines was applied, using the following variables: World Health Organization functional class, 6-min walking distance, brain natriuretic peptide or its N-terminal fragment, right atrial pressure, cardiac index and mixed venous oxygen saturation. Data from 1588 patients were analysed. Mortality rates were significantly different between the three risk strata (p An abbreviated version of the risk assessment strategy proposed by the current European PH guidelines provides accurate mortality estimates in patients with PAH.

Guidelines for the use of flow cytometry and cell sorting in immunological studies

Abstract: The marriage between immunology and cytometry is one of the most stable and productive in the recent history of science. A rapid search in PubMed shows that, as of July 2017, using “flow cytometry immunology” as a search term yields more than 68 000 articles, the first of which, interestingly, is not about lymphocytes. It might be stated that, after a short engagement, the exchange of the wedding rings between immunology and cytometry officially occurred when the idea to link fluorochromes to monoclonal antibodies came about. After this, recognizing different types of cells became relatively easy and feasible not only by using a simple fluorescence microscope, but also by a complex and sometimes esoteric instrument, the flow cytometer that is able to count hundreds of cells in a single second, and can provide repetitive results in a tireless manner. Given this, the possibility to analyse immune phenotypes in a variety of clinical conditions has changed the use of the flow cytometer, which was incidentally invented in the late 1960s to measure cellular DNA by using intercalating dyes, such as ethidium bromide. The epidemics of HIV/AIDS in the 1980s then gave a dramatic impulse to the technology of counting specific cells, since it became clear that the quantification of the number of peripheral blood CD4+ T cells was crucial to follow the course of the infection, and eventually for monitoring the therapy. As a consequence, the development of flow cytometers that had to be easy-to-use in all clinical laboratories helped to widely disseminate this technology. Nowadays, it is rare to find an immunological paper or read a conference abstract in which the authors did not use flow cytometry as the main tool to dissect the immune system and identify its fine and complex functions. Of note, recent developments have created the sophisticated technology of mass cytometry, which is able to simultaneously identify dozens of molecules at the single cell level and allows us to better understand the complexity and beauty of the immune system.

Benchmarking Complications Associated with Esophagectomy.

Abstract: Objective:Utilizing a standardized dataset with specific definitions to prospectively collect international data to provide a benchmark for complications and outcomes associated with esophagectomy.Summary of Background Data:Outcome reporting in oncologic surgery has suffered from the lack of a stand

Antibody 10-1074 suppresses viremia in HIV-1-infected individuals

Abstract: Florian Klein and colleagues report that treating viremic HIV-1-infected individuals with the broadly neutralizing antibody 10-1074 reduced virus levels in blood, but antibody-resistant virus did emerge. Monoclonal antibody 10-1074 targets the V3 glycan supersite on the HIV-1 envelope (Env) protein. It is among the most potent anti-HIV-1 neutralizing antibodies isolated so far. Here we report on its safety and activity in 33 individuals who received a single intravenous infusion of the antibody. 10-1074 was well tolerated and had a half-life of 24.0 d in participants without HIV-1 infection and 12.8 d in individuals with HIV-1 infection. Thirteen individuals with viremia received the highest dose of 30 mg/kg 10-1074. Eleven of these participants were 10-1074-sensitive and showed a rapid decline in viremia by a mean of 1.52 log10 copies/ml. Virologic analysis revealed the emergence of multiple independent 10-1074-resistant viruses in the first weeks after infusion. Emerging escape variants were generally resistant to the related V3-specific antibody PGT121, but remained sensitive to antibodies targeting nonoverlapping epitopes, such as the anti-CD4-binding-site antibodies 3BNC117 and VRC01. The results demonstrate the safety and activity of 10-1074 in humans and support the idea that antibodies targeting the V3 glycan supersite might be useful for the treatment and prevention of HIV-1 infection.

The house spider genome reveals an ancient whole-genome duplication during arachnid evolution

Abstract: Background: The duplication of genes can occur through various mechanisms and is thought to make a major contribution to the evolutionary diversification of organisms. There is increasing evidence ...

First light for GRAVITY: Phase referencing optical interferometry for the Very Large Telescope Interferometer

Abstract: GRAVITY is a new instrument to coherently combine the light of the European Southern Observatory Very Large Telescope Interferometer to form a telescope with an equivalent 130 m diameter angular resolution and a collecting area of 200 m2. The instrument comprises fiber fed integrated optics beam combination, high resolution spectroscopy, built-in beam analysis and control, near-infrared wavefront sensing, phase-tracking, dual-beam operation, and laser metrology. GRAVITY opens up to optical/infrared interferometry the techniques of phase referenced imaging and narrow angle astrometry, in many aspects following the concepts of radio interferometry. This article gives an overview of GRAVITY and reports on the performance and the first astronomical observations during commissioning in 2015/16. We demonstrate phase-tracking on stars as faint as mK ≈ 10 mag, phase-referenced interferometry of objects fainter than mK ≈ 15 mag with a limiting magnitude of mK ≈ 17 mag, minute long coherent integrations, a visibility accuracy of better than 0.25%, and spectro-differential phase and closure phase accuracy better than 0.5°, corresponding to a differential astrometric precision of better than ten microarcseconds (μas). The dual-beam astrometry, measuring the phase difference of two objects with laser metrology, is still under commissioning. First observations show residuals as low as 50 μas when following objects over several months. We illustrate the instrument performance with the observations of archetypical objects for the different instrument modes. Examples include the Galactic center supermassive black hole and its fast orbiting star S2 for phase referenced dual-beam observations and infrared wavefront sensing, the high mass X-ray binary BP Cru and the active galactic nucleus of PDS 456 for a few μas spectro-differential astrometry, the T Tauri star S CrA for a spectro-differential visibility analysis, ξ Tel and 24 Cap for high accuracy visibility observations, and η Car for interferometric imaging with GRAVITY.

Pan-cancer analysis of somatic copy-number alterations implicates IRS4 and IGF2 in enhancer hijacking.

Abstract: Extensive prior research focused on somatic copy-number alterations (SCNAs) affecting cancer genes, yet the extent to which recurrent SCNAs exert their influence through rearrangement of cis-regulatory elements (CREs) remains unclear. Here we present a framework for inferring cancer-related gene overexpression resulting from CRE reorganization (e.g., enhancer hijacking) by integrating SCNAs, gene expression data and information on topologically associating domains (TADs). Analysis of 7,416 cancer genomes uncovered several pan-cancer candidate genes, including IRS4, SMARCA1 and TERT. We demonstrate that IRS4 overexpression in lung cancer is associated with recurrent deletions in cis, and we present evidence supporting a tumor-promoting role. We additionally pursued cancer-type-specific analyses and uncovered IGF2 as a target for enhancer hijacking in colorectal cancer. Recurrent tandem duplications intersecting with a TAD boundary mediate de novo formation of a 3D contact domain comprising IGF2 and a lineage-specific super-enhancer, resulting in high-level gene activation. Our framework enables systematic inference of CRE rearrangements mediating dysregulation in cancer.

Blending Face-to-Face and Internet-Based Interventions for the Treatment of Mental Disorders in Adults: Systematic Review

Abstract: Background: Many studies have provided evidence for the effectiveness of Internet-based stand-alone interventions for mental disorders. A newer form of intervention combines the strengths of face-to-face (f2f) and Internet approaches (blended interventions). Objective: The aim of this review was to provide an overview of (1) the different formats of blended treatments for adults, (2) the stage of treatment in which these are applied, (3) their objective in combining face-to-face and Internet-based approaches, and (4) their effectiveness. Methods: Studies on blended concepts were identified through systematic searches in the MEDLINE, PsycINFO, Cochrane, and PubMed databases. Keywords included terms indicating face-to-face interventions (“inpatient,” “outpatient,” “face-to-face,” or “residential treatment”), which were combined with terms indicating Internet treatment (“internet,” “online,” or “web”) and terms indicating mental disorders (“mental health,” “depression,” “anxiety,” or “substance abuse”). We focused on three of the most common mental disorders (depression, anxiety, and substance abuse). Results: We identified 64 publications describing 44 studies, 27 of which were randomized controlled trials (RCTs). Results suggest that, compared with stand-alone face-to-face therapy, blended therapy may save clinician time, lead to lower dropout rates and greater abstinence rates of patients with substance abuse, or help maintain initially achieved changes within psychotherapy in the long-term effects of inpatient therapy. However, there is a lack of comparative outcome studies investigating the superiority of the outcomes of blended treatments in comparison with classic face-to-face or Internet-based treatments, as well as of studies identifying the optimal ratio of face-to-face and Internet sessions. Conclusions: Several studies have shown that, for common mental health disorders, blended interventions are feasible and can be more effective compared with no treatment controls. However, more RCTs on effectiveness and cost-effectiveness of blended treatments, especially compared with nonblended treatments are necessary.

Evolutionary genomics of the cold-adapted diatom Fragilariopsis cylindrus

Abstract: The Southern Ocean houses a diverse and productive community of organisms. Unicellular eukaryotic diatoms are the main primary producers in this environment, where photosynthesis is limited by low concentrations of dissolved iron and large seasonal fluctuations in light, temperature and the extent of sea ice. How diatoms have adapted to this extreme environment is largely unknown. Here we present insights into the genome evolution of a cold-adapted diatom from the Southern Ocean, Fragilariopsis cylindrus, based on a comparison with temperate diatoms. We find that approximately 24.7 per cent of the diploid F. cylindrus genome consists of genetic loci with alleles that are highly divergent (15.1 megabases of the total genome size of 61.1 megabases). These divergent alleles were differentially expressed across environmental conditions, including darkness, low iron, freezing, elevated temperature and increased CO2. Alleles with the largest ratio of non-synonymous to synonymous nucleotide substitutions also show the most pronounced condition-dependent expression, suggesting a correlation between diversifying selection and allelic differentiation. Divergent alleles may be involved in adaptation to environmental fluctuations in the Southern Ocean.

Transcatheter Treatment of Severe Tricuspid Regurgitation With the Edge-to-Edge MitraClip Technique

Abstract: Background:Current surgical and medical treatment options for severe tricuspid regurgitation (TR) are limited, and additional interventional approaches are required. In the present observational st...

Visual analogue scales (VAS): Measuring instruments for the documentation of symptoms and therapy monitoring in cases of allergic rhinitis in everyday health care: Position Paper of the German Society of Allergology (AeDA) and the German Society of Allergy and Clinical Immunology (DGAKI), ENT Section, in collaboration with the working group on Clinical Immunology, Allergology and Environmental Medicine of the German Society of Otorhinolaryngology, Head and Neck Surgery (DGHNOKHC).

Abstract: Backround Visual analogue scales (VAS) are psychometric measuring instruments designed to document the characteristics of disease-related symptom severity in individual patients and use this to achieve a rapid (statistically measurable and reproducible) classification of symptom severity and disease control. VAS can also be used in routine patient history taking and to monitor the course of a chronic disease such as allergic rhinitis (AR). More specifically, the VAS has been used to assess effectiveness of AR therapy in real life, both in intermittent and persistent disease.