Search for Standard Model Higgs Boson Production in Association with a W Boson using a Neural Network

We present a search for standard model Higgs boson production in association with a W boson in proton-antiproton collisions at a center of mass energy of 1.96 TeV. The search employs data collected with the CDF II detector that correspond to an integrated luminosity of approximately 1.9 inverse fb. We select events consistent with a signature of a single charged lepton, missing transverse energy, and two jets. Jets corresponding to bottom quarks are identified with a secondary vertex tagging method, a jet probability tagging method, and a neural network filter. We use kinematic information in an artificial neural network to improve discrimination between signal and background compared to previous analyses. The observed number of events and the neural network output distributions are consistent with the standard model background expectations, and we set 95% confidence level upper limits on the production cross section times branching fraction ranging from 1.2 to 1.1 pb or 7.5 to 102 times the standard model expectation for Higgs boson masses from 110 to $150 GeV/c^2, respectively.We present a search for standard model Higgs boson production in association with a W boson in proton-antiproton collisions (pp̅ →W±H→ℓνbb̅ ) at a center of mass energy of 1.96 TeV. The search employs data collected with the CDF II detector that correspond to an integrated luminosity of approximately 1.9  fb-1. We select events consistent with a signature of a single charged lepton (e±/μ±), missing transverse energy, and two jets. Jets corresponding to bottom quarks are identified with a secondary vertex tagging method, a jet probability tagging method, and a neural network filter. We use kinematic information in an artificial neural network to improve discrimination between signal and background compared to previous analyses. The observed number of events and the neural network output distributions are consistent with the standard model background expectations, and we set 95% confidence level upper limits on the production cross section times branching fraction ranging from 1.2 to 1.1 pb or 7.5 to 102 times the standard model expectation for Higgs boson masses from 110 to 150  GeV/c2, respectively.Peer reviewe

Antigen-specific Th17 cells are primed by distinct and complementary dendritic cell subsets in oropharyngeal candidiasis

Candida spp. can cause severe and chronic mucocutaneous and systemic infections in immunocompromised individuals. Protection from mucocutaneous candidiasis depends on T helper cells, in particular those secreting IL-17. The events regulating T cell activation and differentiation toward effector fates in response to fungal invasion in different tissues are poorly understood. Here we generated a Candida-specific TCR transgenic mouse reactive to a novel endogenous antigen that is conserved in multiple distant species of Candida, including the clinically highly relevant C. albicans and C. glabrata. Using TCR transgenic T cells in combination with an experimental model of oropharyngeal candidiasis (OPC) we investigated antigen presentation and Th17 priming by different subsets of dendritic cells (DCs) present in the infected oral mucosa. Candida- derived endogenous antigen accesses the draining lymph nodes and is directly presented by migratory DCs. Tissue-resident Flt3L-dependent DCs and CCR2-dependent monocyte-derived DCs collaborate in antigen presentation and T cell priming during OPC. In contrast, Langerhans cells, which are also present in the oral mucosa and have been shown to prime Th17 cells in the skin, are not required for induction of the Candida- specific T cell response upon oral challenge. This highlights the functional compartmentalization of specific DC subsets in different tissues. These data provide important new insights to our understanding of tissue-specific antifungal immunity

The natural history of pediatric Sturge-Weber Syndrome: A multinational cross-sectional study

Background Sturge-Weber Syndrome (SWS) is a capillary-venous malformation which includes the brain (leptomeningeal venous capillary malformation), the eye (choroidal angioma) and the skin (facial portwine birthmark, FPB). Structural epilepsy, glaucoma and FPBs pose therapeutic challenges. Considerable advances include improved neuroimaging, new antiseizure medication (ASM) and progress in epilepsy surgery. Yet, comprehensive data on epidemiology, clinical features, diagnostics, and treatment in contemporary pediatric SWS cohorts is scarce. Methods We conducted a multinational cross-sectional observational study in Germany, Switzerland and Austria to identify potential patients and build up a comprehensive database containing anonymized patient data. The patients’ guardians and child neurologists filled in detailed questionnaires on histories, clinical features, diagnostic and therapeutic measures. Results Forty-seven SWS patients from Germany, Switzerland or Austria participated in our survey (111 notifications, i.e. the participation rate was 43 %). Prevalence was 7.37/million in Germany, 4.60/million in Switzerland, 2.61/million in Austria. Severity of skin, eye and brain involvement varied highly. Forty-three patients (91 %) were diagnosed with epilepsy. Median age at first seizure was 6.5 months. Thirty-two percent of the cohort received ASM in monotherapy, fifty-three percent received combination therapy and thirteen percent received no ASM. Eight percent underwent epilepsy surgery. Conclusions In this European pediatric SWS cohort from a well-established tertiary child neurologist network, the condition was commonly diagnosed within the first year of life. 40 % of the cohort were seizure-free at inclusion; only 8.5 % of the cohort underwent epilepsy surgery. Our findings are concordant with published data from U.S. registries and case series. While our results indicate diagnostic improvement as compared to published studies, epilepsy management in SWS remains a challenge

Trajectories of Mental Distress and Resilience During the COVID-19 Pandemic Among Healthcare Workers

Background/Objectives : The recent COVID-19 pandemic posed a significant psychological challenge for healthcare workers. Resilience and the extent of psychological stress varied across professional groups and individual circumstances. This study aims to longitudinally capture the trajectories of psychological stress and resilience among medical personnel during the pandemic and identify various contributing factors. Methods : Over a period of three years, healthcare workers from five locations (Bonn, Cologne, Ulm, Erlangen, and Dresden) were surveyed regarding their psychological stress (PHQ-4) and other aspects of mental health. Data were collected at five different points during the pandemic. Using Growth Mixture Modeling (GMM), various stress trajectories during the crisis were modeled without initial adjustment for covariates to allow for an unbiased identification of latent classes. Differences in demographic and occupational factors (e.g., age, gender, profession) were analyzed across the identified trajectory groups in subsequent steps. Results : The application of GMM revealed three distinct profiles of psychological stress and resilience among the respondents, largely consistent with the literature. The largest group was the ‘resilience’ group (81%), followed by the ‘recovery’ (10%) and ‘delayed’ groups (9%). Group membership was consistent with self-reported trajectories over the course of the pandemic. It was not possible to predict individual trajectories based on the results of a short resilience questionnaire (RS-5). Conclusions : The COVID-19 pandemic had multiple psychological impacts on healthcare workers, manifesting in clearly differentiated group trajectories of distress over time. While a majority of respondents in this sample exhibited a stable trajectory with low distress, other groups showed varying stress responses over time. These findings highlight the necessity of longitudinal approaches to understand the complex interplay of stressors and coping mechanisms during prolonged crises.This work was supported by the German Research Foundation (DFG), grant number 458628023, and the Open Access Publication Fund of the University of Bonn.German Research Foundation (DFG)Open Access Publication Fund of the University of Bon

Microarray-based identification and RT-PCR test screening for epithelial-specific mRNAs in peripheral blood of patients with colon cancer

BACKGROUND: The efficacy of screening for colorectal cancer using a simple blood-based assay for the detection of tumor cells disseminated in the circulation at an early stage of the disease is gaining positive feedback from several lines of research. This method seems able to reduce colorectal cancer mortality and may replace colonoscopy as the most effective means of detecting colonic lesions. METHODS: In this work, we present a new microarray-based high-throughput screening method to identifying candidate marker mRNAs for the early detection of epithelial cells diluted in peripheral blood cells. This method includes 1. direct comparison of different samples of colonic mucosa and of blood cells to identify consistent epithelial-specific mRNAs from among 20,000 cDNA assayed by microarray slides; 2. identification of candidate marker mRNAs by data analysis, which allowed selection of only 10 putative differentially expressed genes; 3. Selection of some of the most suitable mRNAs (TMEM69, RANBP3 and PRSS22) that were assayed in blood samples from normal subjects and patients with colon cancer as possible markers for the presence of epithelial cells in the blood, using reverse transcription – polymerase chain reaction (RT-PCR). RESULTS: Our present results seem to provide an indication, for the first time obtained by genome-scale screening, that a suitable and consistent colon epithelium mRNA marker may be difficult to identify. CONCLUSION: The design of new approaches to identify such markers is warranted

Epithelial atypia in biopsies performed for microcalcifications. Practical considerations about 2,833 serially sectioned surgical biopsies with a long follow-up

This study analyzes the occurrence of epithelial atypia in 2,833 serially sectioned surgical breast biopsies (SB) performed for microcalcifications (median number of blocks per SB:26) and the occurrence of subsequent cancer after an initial diagnosis of epithelial atypia (median follow-up 160 months). Epithelial atypia (flat epithelial atypia, atypical ductal hyperplasia, and lobular neoplasia) were found in 971 SB, with and without a concomitant cancer in 301 (31%) and 670 (69%) SB, respectively. Thus, isolated epithelial atypia were found in 670 out of the 2,833 SB (23%). Concomitant cancers corresponded to ductal carcinomas in situ and micro-invasive (77%), invasive ductal carcinomas not otherwise specified (15%), invasive lobular carcinomas (4%), and tubular carcinomas (4%). Fifteen out of the 443 patients with isolated epithelial atypia developed a subsequent ipsilateral (n = 14) and contralateral (n = 1) invasive cancer. The high slide rating might explain the high percentages of epithelial atypia and concomitant cancers and the low percentage of subsequent cancer after a diagnosis of epithelial atypia as a single lesion. Epithelial atypia could be more a risk marker of concomitant than subsequent cancer

Linking microbial community assembly and function: diversity, multitrophic interactions and post-disturbance microbiome reassembly

Microbes are the motors of terrestrial ecosystems. They mobilize nutrients, promote plant growth and suppress plant diseases. Diverse microbial communities are however under increased pressure due to intensive agricultural practices, as well as more frequent and severe climatic extremes, such as drought or flooding. In order to protect soil fertility, it is therefore important to understand how microbial diversity impacts soil functioning and how this is affected by disturbances. In this thesis, I examined how bacterial diversity, multitrophic interactions and post-disturbance community reassembly impact microbial community functioning. Bacterial diversity was shown to positively influence plant growth promotion via increased nutrient mobilization. Further, interactions of bacteria with other soil organisms, such as protists that feed on bacteria, can modulate the effect of beneficial bacteria by upregulating bacterial secondary metabolite production. It is also suggested that minor disturbance to the bacterial community or the creation of niches can further increase the establishment success of beneficial bacteria in soil and in the root zone (the rhizosphere). Strong disturbances to soil microbial communities not only decreased soil bacterial diversity, but also selected for slow-growing organisms with high efficiency. Decreases in soil diversity further constrained the bacterial communities that can colonize plant root surfaces, illustrating long-lasting effects of disturbances on ecosystems even after apparent recovery. Overall, the results of this thesis emphasize the potential of using multispecies consortia for improving the establishment and functioning of plant-beneficial bacteria in the rhizosphere and illustrate the long-term effects disturbances can have on soil and rhizosphere microbial communities