Ebola Outbreak Containment: Real-Time Task and Resource Coordination With SORMAS

Background: Since the beginning of the Ebola outbreak in West Africa in 2014, more than 11,000 people died. For outbreaks of infectious diseases like this, the rapid implementation of control measures is a crucial factor for containment. In West African countries, outbreak surveillance is a paper-based process with significant delays in forwarding outbreak information, which affects the ability to react adequately to situational changes. Our objective therefore was to develop a tool that improves data collection, situation assessment, and coordination of response measures in outbreak surveillance processes for a better containment. Methods: We have developed the Surveillance and Outbreak Response Management System (SORMAS) based on findings from Nigeria's 2014 Ebola outbreak. We conducted a thorough requirements engineering and defined personas and processes. We also defined a data schema with specific variables to measure in outbreak situations. We designed our system to be a cloud application that consists of interfaces for both mobile devices and desktop computers to support all stakeholders in the process. In the field, health workers collect data on the outbreak situation via mobile applications and directly transmit it to control centers. At the control centers, health workers access SORMAS via desktop computers, receive instant updates on critical situations, react immediately on emergencies, and coordinate the implementation of control measures with SORMAS. Results: We have tested SORMAS in multiple workshops and a field study in July 2015. Results from workshops confirmed derived requirements and implemented features, but also led to further iterations on the systems regarding usability. Results from the field study are currently under assessment. General feedback showed high enthusiasm about the system and stressed its benefits for an effective outbreak containment of infectious diseases. Conclusions: SORMAS is a software tool to support health workers in efficiently handling outbreak situations of infectious diseases, such as Ebola. Our tool enables a bi-directional exchange of situational data between individual stakeholders in outbreak containment. This allows instant and seamless collection of data from the field and its instantaneous analysis in operational centers. By that, SORMAS accelerates the implementation of control measures, which is crucial for a successful outbreak containment.Peer Reviewe

Der Freiberger Dom: Architektur als Sprache

Das Lehr-Lern-Projekt beinhaltet die Ableitung und Erprobung von Handlungsempfehlungen und Werkzeugen für interdisziplinäre Praxis- und Forschungsprojekte anhand einer Projektarbeit, welche auf die Erstellung einer Besucher-App für den Freiberger Dom zielt

More than words: The influence of affective content and linguistic style matches in online reviews on conversion rates

Customers increasingly rely on other consumers' reviews to make purchase decisions online. New insights into the customer review phenomenon can be derived from studying the semantic content and style properties of verbatim customer reviews to examine their influence on online retail sites' conversion rates. The authors employ text mining to extract changes in affective content and linguistic style properties of customer book reviews on Amazon.com. A dynamic panel data model reveals that the influence of positive affective content on conversion rates is asymmetrical, such that greater increases in positive affective content in customer reviews have a smaller effect on subsequent increases in conversion rate. No such tapering-off effect occurs for changes in negative affective content in reviews. Furthermore, positive changes in affective cues and increasing congruence with the product interest group's typical linguistic style directly and conjointly increase conversion rates. These findings suggest that managers should identify and promote the most influential reviews in a given product category, provide instructions to stimulate reviewers to write powerful reviews, and adapt the style of their own editorial reviews to the relevant product category

A Standardized Method for the Construction of Tracer Specific PET and SPECT Rat Brain Templates:Validation and Implementation of a Toolbox

High-resolution anatomical image data in preclinical brain PET and SPECT studies is often not available, and inter-modality spatial normalization to an MRI brain template is frequently performed. However, this procedure can be challenging for tracers where substantial anatomical structures present limited tracer uptake. Therefore, we constructed and validated strain- and tracer-specific rat brain templates in Paxinos space to allow intra-modal registration. PET [18F]FDG, [11C]flumazenil, [11C]MeDAS, [11C]PK11195 and [11C]raclopride, and SPECT [99mTc]HMPAO brain scans were acquired from healthy male rats. Tracer-specific templates were constructed by averaging the scans, and by spatial normalization to a widely used MRI-based template. The added value of tracer-specific templates was evaluated by quantification of the residual error between original and realigned voxels after random misalignments of the data set. Additionally, the impact of strain differences, disease uptake patterns (focal and diffuse lesion), and the effect of image and template size on the registration errors were explored. Mean registration errors were 0.70 ± 0.32 mm for [18F]FDG (n = 25), 0.23 ± 0.10mm for [11C]flumazenil (n = 13), 0.88 ± 0.20 mm for [11C]MeDAS (n = 15), 0.64 ± 0.28 mm for [11C]PK11195 (n = 19), 0.34 ± 0.15 mm for [11C]raclopride (n = 6), and 0.40 ± 0.13 mm for [99mTc]HMPAO (n = 15). These values were smallest with tracer-specific templates, when compared to the use of [18F]FDG as reference template (p<0.001). Additionally, registration errors were smallest with strain-specific templates (p<0.05), and when images and templates had the same size (p ≤ 0.001). Moreover, highest registration errors were found for the focal lesion group (p<0.005) and the diffuse lesion group (p = n.s.). In the voxel-based analysis, the reported coordinates of the focal lesion model are consistent with the stereotaxic injection procedure. The use of PET/SPECT strain- and tracer-specific templates allows accurate registration of functional rat brain data, independent of disease specific uptake patterns and with registration error below spatial resolution of the cameras. The templates and the SAMIT package will be freely available for the research community [corrected]

Comparative Analysis of ESBL-Positive Escherichia coli isolates from Animals and Humans from the UK, the Netherlands and Germany

The putative virulence and antimicrobial resistance gene contents of extended spectrum β-lactamase (ESBL)-positive E. coli (n=629) isolated between 2005 and 2009 from humans, animals and animal food products in Germany, The Netherlands and the UK were compared using a microarray approach to test the suitability of this approach with regard to determining their similarities. A selection of isolates (n=313) were also analysed by multilocus sequence typing (MLST). Isolates harbouring blaCTX-M-group-1 dominated (66%, n=418) and originated from both animals and cases of human infections in all three countries; 23% (n=144) of all isolates contained both blaCTX-M-group-1 and blaOXA-1-like genes, predominantly from humans (n=127) and UK cattle (n=15). The antimicrobial resistance and virulence gene profiles of this collection of isolates were highly diverse. A substantial number of human isolates (32%, n=87) did not share more than 40% similarity (based on the Jaccard coefficient) with animal isolates. A further 43% of human isolates from the three countries (n=117) were at least 40% similar to each other and to five isolates from UK cattle and one each from Dutch chicken meat and a German dog; the members of this group usually harboured genes such as mph(A), mrx, aac(6’)-Ib, catB3, blaOXA-1-like and blaCTX-M-group-1. forty-four per cent of the MLST-typed isolates in this group belonged to ST131 (n=18) and 22% to ST405 (n=9), all from humans. Among animal isolates subjected to MLST (n=258), only 1.2% (n=3) were more than 70% similar to human isolates in gene profiles and shared the same MLST clonal complex with the corresponding human isolates. The results suggest that minimising human-to-human transmission is essential to control the spread of ESBL-positive E. coli in humans

Simulated Microgravity Compromises Mouse Oocyte Maturation by Disrupting Meiotic Spindle Organization and Inducing Cytoplasmic Blebbing

In the present study, we discovered that mouse oocyte maturation was inhibited by simulated microgravity via disturbing spindle organization. We cultured mouse oocytes under microgravity condition simulated by NASA's rotary cell culture system, examined the maturation rate and observed the spindle morphology (organization of cytoskeleton) during the mouse oocytes meiotic maturation. While the rate of germinal vesicle breakdown did not differ between 1 g gravity and simulated microgravity, rate of oocyte maturation decreased significantly in simulated microgravity. The rate of maturation was 8.94% in simulated microgravity and was 73.0% in 1 g gravity. The results show that the maturation of mouse oocytes in vitro was inhibited by the simulated microgravity. The spindle morphology observation shows that the microtubules and chromosomes can not form a complete spindle during oocyte meiotic maturation under simulated microgravity. And the disorder of γ-tubulin may partially result in disorganization of microtubules under simulated microgravity. These observations suggest that the meiotic spindle organization is gravity dependent. Although the spindle organization was disrupted by simulated microgravity, the function and organization of microfilaments were not pronouncedly affected by simulated microgravity. And we found that simulated microgravity induced oocytes cytoplasmic blebbing via an unknown mechanism. Transmission electron microscope detection showed that the components of the blebs were identified with the cytoplasm. Collectively, these results indicated that the simulated microgravity inhibits mouse oocyte maturation via disturbing spindle organization and inducing cytoplasmic blebbing

Neurologic Involvement in Children and Adolescents Hospitalized in the United States for COVID-19 or Multisystem Inflammatory Syndrome

This article is made available for unrestricted research re-use and secondary analysis in any form or by any means with acknowledgement of the original source. These permissions are granted for the duration of the World Health Organization (WHO) declaration of COVID-19 as a global pandemic.Importance Coronavirus disease 2019 (COVID-19) affects the nervous system in adult patients. The spectrum of neurologic involvement in children and adolescents is unclear. Objective To understand the range and severity of neurologic involvement among children and adolescents associated with COVID-19. Setting, Design, and Participants Case series of patients (age <21 years) hospitalized between March 15, 2020, and December 15, 2020, with positive severe acute respiratory syndrome coronavirus 2 test result (reverse transcriptase-polymerase chain reaction and/or antibody) at 61 US hospitals in the Overcoming COVID-19 public health registry, including 616 (36%) meeting criteria for multisystem inflammatory syndrome in children. Patients with neurologic involvement had acute neurologic signs, symptoms, or diseases on presentation or during hospitalization. Life-threatening involvement was adjudicated by experts based on clinical and/or neuroradiologic features. Exposures Severe acute respiratory syndrome coronavirus 2. Main Outcomes and Measures Type and severity of neurologic involvement, laboratory and imaging data, and outcomes (death or survival with new neurologic deficits) at hospital discharge. Results Of 1695 patients (909 [54%] male; median [interquartile range] age, 9.1 [2.4-15.3] years), 365 (22%) from 52 sites had documented neurologic involvement. Patients with neurologic involvement were more likely to have underlying neurologic disorders (81 of 365 [22%]) compared with those without (113 of 1330 [8%]), but a similar number were previously healthy (195 [53%] vs 723 [54%]) and met criteria for multisystem inflammatory syndrome in children (126 [35%] vs 490 [37%]). Among those with neurologic involvement, 322 (88%) had transient symptoms and survived, and 43 (12%) developed life-threatening conditions clinically adjudicated to be associated with COVID-19, including severe encephalopathy (n = 15; 5 with splenial lesions), stroke (n = 12), central nervous system infection/demyelination (n = 8), Guillain-Barré syndrome/variants (n = 4), and acute fulminant cerebral edema (n = 4). Compared with those without life-threatening conditions (n = 322), those with life-threatening neurologic conditions had higher neutrophil-to-lymphocyte ratios (median, 12.2 vs 4.4) and higher reported frequency of D-dimer greater than 3 μg/mL fibrinogen equivalent units (21 [49%] vs 72 [22%]). Of 43 patients who developed COVID-19–related life-threatening neurologic involvement, 17 survivors (40%) had new neurologic deficits at hospital discharge, and 11 patients (26%) died. Conclusions and Relevance In this study, many children and adolescents hospitalized for COVID-19 or multisystem inflammatory syndrome in children had neurologic involvement, mostly transient symptoms. A range of life-threatening and fatal neurologic conditions associated with COVID-19 infrequently occurred. Effects on long-term neurodevelopmental outcomes are unknown

A Solve-RD ClinVar-based reanalysis of 1522 index cases from ERN-ITHACA reveals common pitfalls and misinterpretations in exome sequencing

Purpose Within the Solve-RD project (https://solve-rd.eu/), the European Reference Network for Intellectual disability, TeleHealth, Autism and Congenital Anomalies aimed to investigate whether a reanalysis of exomes from unsolved cases based on ClinVar annotations could establish additional diagnoses. We present the results of the “ClinVar low-hanging fruit” reanalysis, reasons for the failure of previous analyses, and lessons learned. Methods Data from the first 3576 exomes (1522 probands and 2054 relatives) collected from European Reference Network for Intellectual disability, TeleHealth, Autism and Congenital Anomalies was reanalyzed by the Solve-RD consortium by evaluating for the presence of single-nucleotide variant, and small insertions and deletions already reported as (likely) pathogenic in ClinVar. Variants were filtered according to frequency, genotype, and mode of inheritance and reinterpreted. Results We identified causal variants in 59 cases (3.9%), 50 of them also raised by other approaches and 9 leading to new diagnoses, highlighting interpretation challenges: variants in genes not known to be involved in human disease at the time of the first analysis, misleading genotypes, or variants undetected by local pipelines (variants in off-target regions, low quality filters, low allelic balance, or high frequency). Conclusion The “ClinVar low-hanging fruit” analysis represents an effective, fast, and easy approach to recover causal variants from exome sequencing data, herewith contributing to the reduction of the diagnostic deadlock

Retrospective evaluation of whole exome and genome mutation calls in 746 cancer samples

Funder: NCI U24CA211006Abstract: The Cancer Genome Atlas (TCGA) and International Cancer Genome Consortium (ICGC) curated consensus somatic mutation calls using whole exome sequencing (WES) and whole genome sequencing (WGS), respectively. Here, as part of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium, which aggregated whole genome sequencing data from 2,658 cancers across 38 tumour types, we compare WES and WGS side-by-side from 746 TCGA samples, finding that ~80% of mutations overlap in covered exonic regions. We estimate that low variant allele fraction (VAF < 15%) and clonal heterogeneity contribute up to 68% of private WGS mutations and 71% of private WES mutations. We observe that ~30% of private WGS mutations trace to mutations identified by a single variant caller in WES consensus efforts. WGS captures both ~50% more variation in exonic regions and un-observed mutations in loci with variable GC-content. Together, our analysis highlights technological divergences between two reproducible somatic variant detection efforts