Autochthonous Case of Pulmonary Histoplasmosis, Switzerland.

In Europe, pulmonary histoplasmosis is rarely diagnosed except in travelers. We report a probable autochthonous case of severe chronic pulmonary histoplasmosis in an immunocompetent man in Switzerland without travel history outside of Europe. Diagnosis was achieved by histopathology, fungal culture, and serology, but the source of the infection remains speculative

North-South cooperation through BIOTA: An interdisciplinary monitoring programme in arid and semi-arid southern Africa

Connecting disciplines in a north– South collaboration has many advantages: mutualisms evolve, synergies are created and spin-offs emerge. The BIOTA South (Biodiversity Monitoring Transect Analysis in southern Africa) programme, with its long-term vision to generate knowledge of biodiversity along a north–south transect in southern Africa, is providing opportunities for research, technology transfer and capacity building while focusing on potential solutions for critical challenges that face this environmentally vulnerable part of the subcontinen

Virological failure after 1 year of first-line ART is not associated with HIV minority drug resistance in rural Cameroon

Objectives The aim of this study was to describe clinical and virological outcomes in therapy-naive HIV-1-positive patients treated in a routine ART programme in rural Cameroon. Methods In a prospective cohort, 300 consecutive patients starting first-line ART were enrolled and followed for 12 months. Among 238 patients with available viral load data at Month 12, logistic regression was used to analyse risk factors for virological failure (≥1000 HIV RNA copies/mL) including clinical, immunological and virological parameters, as well as data on drug adherence. Population sequencing was performed to detect the presence of drug-resistance mutations in patients with virological failure at Month 12; minority drug-resistance mutations at baseline were analysed using next-generation sequencing in these patients and matched controls. Results At Month 12, 38/238 (16%) patients experienced virological failure (≥1000 HIV RNA copies/mL). Patients with virological failure were younger, had lower CD4 cell counts and were more often WHO stage 3 or 4 at baseline. Sixty-three percent of patients with virological failure developed at least one drug-resistance mutation. The M184V (n = 18) and K103N (n = 10) mutations were most common. At baseline, 6/30 patients (20%) experiencing virological failure and 6/35 (17%) matched controls had evidence of minority drug-resistance mutations using next-generation sequencing (P = 0.77). Lower CD4 count at baseline (OR per 100 cells/mm3 lower 1.41, 95% CI 1.02-1.96, P = 0.04) and poorer adherence (OR per 1% lower 1.05, 95% CI 1.02-1.08, P < 0.001) were associated with a higher risk of virological failure. Unavailability of ART at the treatment centre was the single most common cause for incomplete adherence. Conclusions Virological failure after 1 year of ART was not associated with minority drug resistance at baseline but with incomplete adherence. Strategies to assure adherence and uninterrupted drug supplies are pivotal factors for therapy succes

Monte-Carlo Simulations of Radiation-Induced Activation in a Fast-Neutron and Gamma- Based Cargo Inspection System

An air cargo inspection system combining two nuclear reaction based techniques, namely Fast-Neutron Resonance Radiography and Dual-Discrete-Energy Gamma Radiography is currently being developed. This system is expected to allow detection of standard and improvised explosives as well as special nuclear materials. An important aspect for the applicability of nuclear techniques in an airport inspection facility is the inventory and lifetimes of radioactive isotopes produced by the neutron and gamma radiation inside the cargo, as well as the dose delivered by these isotopes to people in contact with the cargo during and following the interrogation procedure. Using MCNPX and CINDER90 we have calculated the activation levels for several typical inspection scenarios. One example is the activation of various metal samples embedded in a cotton-filled container. To validate the simulation results, a benchmark experiment was performed, in which metal samples were activated by fast-neutrons in a water-filled glass jar. The induced activity was determined by analyzing the gamma spectra. Based on the calculated radioactive inventory in the container, the dose levels due to the induced gamma radiation were calculated at several distances from the container and in relevant time windows after the irradiation, in order to evaluate the radiation exposure of the cargo handling staff, air crew and passengers during flight. The possibility of remanent long-lived radioactive inventory after cargo is delivered to the client is also of concern and was evaluated.Comment: Proceedings of FNDA 201

Simple Viscous Flows: from Boundary Layers to the Renormalization Group

The seemingly simple problem of determining the drag on a body moving through a very viscous fluid has, for over 150 years, been a source of theoretical confusion, mathematical paradoxes, and experimental artifacts, primarily arising from the complex boundary layer structure of the flow near the body and at infinity. We review the extensive experimental and theoretical literature on this problem, with special emphasis on the logical relationship between different approaches. The survey begins with the developments of matched asymptotic expansions, and concludes with a discussion of perturbative renormalization group techniques, adapted from quantum field theory to differential equations. The renormalization group calculations lead to a new prediction for the drag coefficient, one which can both reproduce and surpass the results of matched asymptotics

Longitudinal development of antibody responses in COVID-19 patients of different severity with ELISA, peptide, and glycan arrays : an immunological case series

The current COVID-19 pandemic is caused by the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). A better understanding of its immunogenicity can be important for the development of improved diagnostics, therapeutics, and vaccines. Here, we report the longitudinal analysis of three COVID-19 patients with moderate (1) and mild disease (2 and 3). Antibody serum responses were analyzed using spike glycoprotein enzyme linked immunosorbent assay (ELISA), full-proteome peptide, and glycan microarrays. ELISA immunoglobulin A, G, and M (IgA, IgG, and IgM) signals increased over time for individuals 1 and 2, whereas 3 only showed no clear positive IgG and IgM result. In contrast, peptide microarrays showed increasing IgA/G signal intensity and epitope spread only in the moderate patient 1 over time, whereas early but transient IgA and stable IgG responses were observed in the two mild cases 2 and 3. Glycan arrays showed an interaction of antibodies to fragments of high-mannose and core N-glycans, present on the viral shield. In contrast to protein ELISA, microarrays allow for a deeper understanding of IgA, IgG, and IgM antibody responses to specific epitopes of the whole proteome and glycans of SARS-CoV-2 in parallel. In the future, this may help to better understand and to monitor vaccination programs and monoclonal antibodies as therapeutics

3D-Image analysis platform monitoring relocation of pluripotency genes during reprogramming

Nuclear organization of chromatin is an important level of genome regulation with positional changes of genes occurring during reprogramming. Inherent variability of biological specimens, wide variety of sample preparation and imaging conditions, though pose significant challenges to data analysis and comparison. Here, we describe the development of a computational image analysis toolbox overcoming biological variability hurdles by a novel single cell randomizing normalization. We performed a comparative analysis of the relationship between spatial positioning of pluripotency genes with their genomic activity and determined the degree of similarity between fibroblasts, induced pluripotent stem cells and embryonic stem cells. Our analysis revealed a preferred positioning of actively transcribed Sox2, Oct4 and Nanog away from the nuclear periphery, but not from pericentric heterochromatin. Moreover, in the silent state, we found no common nuclear localization for any of the genes. Our results suggest that the surrounding gene density hinders relocation from an internal nuclear position. Altogether, our data do not support the hypothesis that the nuclear periphery acts as a general transcriptional silencer, rather suggesting that internal nuclear localization is compatible with expression in pluripotent cells but not sufficient for expression in mouse embryonic fibroblasts. Thus, our computational approach enables comparative analysis of topological relationships in spite of stark morphological variability typical of biological data sets

Towards a taxonomy of process quality characteristics for assessment

Previous assessment of process quality have focused on process capability (i.e. the ability of a process to meet its stated goals). This paper proposes a taxonomy of alternative process quality characteristics based on intrinsic and extrinsic quality attributes. The ultimate goal of this taxonomy is to provide a framework to conduct process assessments using different process quality aspects. Such a framework would considerably broaden process quality perspectives beyond the primary measure of process capability. It would also allow practitioners to identify and evaluate relevant quality characteristics for processes based on specific contexts and implications. For the process assessment model developers, it offers a list of process quality characteristics that could be used to develop relevant process measurement frameworks

Knowledge and attitude of final - year medical students in Germany towards palliative care - an interinstitutional questionnaire-based study

<p>Abstract</p> <p>Background</p> <p>To care for terminally ill and dying patients requires a thorough medical education, encompassing skills, knowledge, and attitudes in the field of palliative care. Undergraduate medical students in Germany will receive mandatory teaching in palliative care in the near future driven by recent changes in the Medical Licensure Act. Before new curricula can be implemented, the knowledge of medical students with respect to palliative care, their confidence to handle palliative care situations correctly, their therapeutic attitude, and their subjective assessment about previous teaching practices have to be better understood.</p> <p>Method</p> <p>We designed a composite, three-step questionnaire (self estimation of confidence, knowledge questions, and opinion on the actual and future medical curriculum) conducted online of final - year medical students at two universities in Germany.</p> <p>Results</p> <p>From a total of 318 enrolled students, 101 responded and described limited confidence in dealing with specific palliative care issues, except for pain therapy. With regard to questions examining their knowledge base in palliative care, only one third of the students (33%) answered more than half of the questions correctly. Only a small percentage of students stated they had gained sufficient knowledge and experience in palliative care during their studies, and the vast majority supported the introduction of palliative care as a mandatory part of the undergraduate curriculum.</p> <p>Conclusion</p> <p>This study identifies medical students' limited confidence and knowledge base in palliative care in 2 German universities, and underlines the importance of providing a mandatory palliative care curriculum.</p

Persistence within dendritic cells marks an antifungal evasion and dissemination strategy of Aspergillus terreus

Aspergillus terreus is an airborne human fungal pathogen causing life-threatening invasive aspergillosis in immunocompromised patients. In contrast to Aspergillus fumigatus, A. terreus infections are associated with high dissemination rates and poor response to antifungal treatment. Here, we compared the interaction of conidia from both fungal species with MUTZ-3-derived dendritic cells (DCs). After phagocytosis, A. fumigatus conidia rapidly escaped from DCs, whereas A. terreus conidia remained persisting with long-term survival. Escape from DCs was independent from DHN-melanin, as A. terreus conidia expressing wA showed no increased intracellular germination. Within DCs A. terreus conidia were protected from antifungals, whereas A. fumigatus conidia were efficiently cleared. Furthermore, while A. fumigatus conidia triggered expression of DC activation markers such as CD80, CD83, CD54, MHCII and CCR7, persistent A. terreus conidia were significantly less immunogenic. Moreover, DCs confronted with A. terreus conidia neither produced pro-inflammatory nor T-cell stimulating cytokines. However, TNF-α addition resulted in activation of DCs and provoked the expression of migration markers without inactivating intracellular A. terreus conidia. Therefore, persistence within DCs and possibly within other immune cells might contribute to the low response of A. terreus infections to antifungal treatment and could be responsible for its high dissemination rates