The extent of SARS-CoV-2 infection throughout the United States population is currently unknown. High quality serology is key to avoiding medically costly diagnostic errors, as well as to assuring ...properly informed public health decisions. Here, we present an optimized ELISA-based serology protocol, from antigen production to data analyses, that helps define thresholds for IgG and IgM seropositivity with high specificities. Validation of this protocol is performed using traditionally collected serum as well as dried blood on mail-in blood sampling kits. Archival (pre-2019) samples are used as negative controls, and convalescent, PCR-diagnosed COVID-19 patient samples serve as positive controls. Using this protocol, minimal cross-reactivity is observed for the spike proteins of MERS, SARS1, OC43 and HKU1 viruses, and no cross reactivity is observed with anti-influenza A H1N1 HAI. Our protocol may thus help provide standardized, population-based data on the extent of SARS-CoV-2 seropositivity, immunity and infection.
Abstract Background Chronic granulomatous disease (CGD) is characterized by recurrent life-threatening bacterial and fungal infections and aberrant inflammation. Mutations in CYBB cause X-linked CGD ...and account for 65%-70% of cases in western countries. Objective To understand the clinical manifestations associated with the X-linked CGD carrier state. Methods We undertook a comprehensive retrospective study of 162 affected females. We examined dihydrorhodamine oxidation (DHR) data for percent (%) X chromosome inactivation. We correlated lyonization (%DHR+) with clinical features. Where possible, we followed %DHR+ levels over time. Results Clinical data were available for 93 females: The %DHR+ was 46% (mean) and 47% (median)(SD=24). Using %DHR+ as the criterion for X inactivation, 78% of patients had levels of inactivation 20-80%, suggesting random inactivation that was independent of age. In contrast, carriers with CGD-type infections had median %DHR+ of 8% (n=14, range 0.06-48 %); those with only autoimmune or inflammatory manifestations (AIM) had median %DHR+ of 39% (n=31, range 7.4-74%). Those with both infections and autoimmunity had low %DHR+ (n=6, range=3-14%). A %DHR+ <10 % was strongly associated with infections (OR:99). Strong association persisted when the %DHR+ was <20% (OR=12) Autoimmunity was not associated with %DHR+. In two sets of identical twins the %DHR+ populations tracked closely over time. While the %DHR+ populations were very similar between sisters, those between mothers and daughters were unrelated. Conclusions A low %DHR+ strongly predicts infection risk in X-linked CGD carriers, while the carrier state itself is associated with autoimmunity.
Standardized definitions of breast cancer clinical trial end points must be adopted to permit the consistent interpretation and analysis of breast cancer clinical trials and to facilitate cross-trial ...comparisons and meta-analyses. Standardizing terms will allow for uniformity in data collection across studies, which will optimize clinical trial utility and efficiency. A given end point term (eg, overall survival) used in a breast cancer trial should always encompass the same set of events (eg, death attributable to breast cancer, death attributable to cause other than breast cancer, death from unknown cause), and, in turn, each event within that end point should be commonly defined across end points and studies.
A panel of experts in breast cancer clinical trials representing medical oncology, biostatistics, and correlative science convened to formulate standard definitions and address the confusion that nonstandard definitions of widely used end point terms for a breast cancer clinical trial can generate. We propose standard definitions for efficacy end points and events in early-stage adjuvant breast cancer clinical trials. In some cases, it is expected that the standard end points may not address a specific trial question, so that modified or customized end points would need to be prospectively defined and consistently used.
The use of the proposed common end point definitions will facilitate interpretation of trial outcomes. This approach may be adopted to develop standard outcome definitions for use in trials involving other cancer sites.
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