Publications by authors named "W Clay Smith"

6,613 Publications

Antibody semorinemab reduces tau pathology in a transgenic mouse model and engages tau in patients with Alzheimer's disease.

Sci Transl Med 2021 May;13(593)

Department of Pathology, Genentech Inc., San Francisco, CA 94080, USA.

Tau has become an attractive alternative target for passive immunotherapy efforts for Alzheimer's disease (AD). The anatomical distribution and extent of tau pathology correlate with disease course and severity better than other disease markers to date. We describe here the generation, preclinical characterization, and phase 1 clinical characterization of semorinemab, a humanized anti-tau monoclonal antibody with an immunoglobulin G4 (igG4) isotype backbone. Semorinemab binds all six human tau isoforms and protects neurons against tau oligomer neurotoxicity in cocultures of neurons and microglia. In addition, when administered intraperitoneally once weekly for 13 weeks, murine versions of semorinemab reduced the accumulation of tau pathology in a transgenic mouse model of tauopathy, independent of antibody effector function status. Semorinemab also showed clear evidence of target engagement in vivo, with increases in systemic tau concentrations observed in tau transgenic mice, nonhuman primates, and humans. Higher concentrations of systemic tau were observed after dosing in AD participants compared to healthy control participants. No concerning safety signals were observed in the phase 1 clinical trial at single doses up to 16,800 mg and multiple doses totaling 33,600 mg in a month.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1126/scitranslmed.abb2639DOI Listing
May 2021

Prevalence of SARS-CoV-2 Antibodies in a Multistate Academic Medical Center.

Mayo Clin Proc 2021 05 26;96(5):1165-1174. Epub 2021 Mar 26.

Mayo Clinic, Phoenix, AZ.

Objective: To estimate the seroprevalence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibodies in health care personnel.

Methods: The Mayo Clinic Serology Screening Program was created to provide a voluntary, two-stage testing program for SARS-CoV-2 antibodies to health care personnel. The first stage used a dried blood spot screening test initiated on June 15, 2020. Those participants identified as reactive were advised to have confirmatory testing via a venipuncture. Venipuncture results through August 8, 2020, were considered. Consent and authorization for testing was required to participate in the screening program. This report, which was conducted under an institutional review board-approved protocol, only includes employees who have further authorized their records for use in research.

Results: A total of 81,113 health care personnel were eligible for the program, and of these 29,606 participated in the screening program. A total of 4284 (14.5%) of the dried blood spot test results were "reactive" and warranted confirmatory testing. Confirmatory testing was completed on 4094 (95.6%) of the screen reactive with an overall seroprevalence rate of 0.60% (95% CI, 0.52% to 0.69%). Significant variation in seroprevalence was observed by region of the country and age group.

Conclusion: The seroprevalence for SARS-CoV-2 antibodies through August 8, 2020, was found to be lower than previously reported in other health care organizations. There was an observation that seroprevalence may be associated with community disease burden.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.mayocp.2021.03.015DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7997730PMC
May 2021

Uncalibrated, Two Source Photo-Polarimetric Stereo.

IEEE Trans Pattern Anal Mach Intell 2021 May 6;PP. Epub 2021 May 6.

In this paper we present methods for estimating shape from polarisation and shading information, i.e. photo-polarimetric shape estimation, under varying, but unknown, illumination, i.e. in an uncalibrated scenario. We propose several alternative photo-polarimetric constraints that depend upon the partial derivatives of the surface and show how to express them in a unified system of partial differential equations of which previous work is a special case. By careful combination and manipulation of the constraints, we show how to eliminate non-linearities such that a discrete version of the problem can be solved using linear least squares. We derive a minimal, combinatorial approach for two source illumination estimation which we use with RANSAC for robust light direction and intensity estimation. We also introduce a new method for estimating a polarisation image from multichannel data and provide methods for estimating albedo and refractive index. We evaluate lighting, shape, albedo and refractive index estimation methods on both synthetic and real-world data showing improvements over existing state-of-the-art.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1109/TPAMI.2021.3078101DOI Listing
May 2021

Consequences of school closure on access to education: Lessons from the 2013-2016 Ebola pandemic.

Authors:
William C Smith

Int Rev Educ 2021 Apr 26:1-26. Epub 2021 Apr 26.

Moray House School of Education and Sport, University of Edinburgh, Edinburgh, UK.

The COVID-19 pandemic has seen an unprecedented shutdown of society. Among the various safety measures taken, much attention has been given to school closure as a non-pharmaceutical mitigation tool to curb the spread of the disease through ensuring "social" (physical) distancing. Nearly 1.725 billion children in over 95% of countries worldwide have been affected by school closures implemented in April 2020 as the virus continued to spread. In the field of education, policymakers' attention has been directed at keeping students on board through remote learning and addressing the immediate needs of schools upon reopening. The study presented in this article focuses on who remains absent after schools resume. Using publicly available survey data from the USAID Demographic Health Surveys Program and the UNICEF Multiple Indicator Cluster Survey from before and after the 2013-2016 Ebola pandemic in Guinea and Sierra Leone in West Africa, the author examined changes in school enrolment and dropout patterns, with targeted consideration given to traditionally marginalised groups. At the time, schools closed for between seven to nine months in the two countries; this length and intensity makes this Ebola pandemic the only health crisis in the recent past to come close to the pandemic-related school closures experienced in 2020. The author's findings suggest that post-Ebola, youth in the poorest households saw the largest increase in school dropout. Exceeding expected pre-Ebola dropout rates, an additional 17,400 of the poorest secondary-age youth were out of school. This evidence is important for minimising the likely post-COVID-19 expansion in inequality. The author's findings point to the need for sustainable planning that looks beyond the reopening of educational institutions to include comprehensive financial support packages for groups most likely to be affected.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s11159-021-09900-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8074702PMC
April 2021

Prevalence of bovine viral diarrhea virus antibodies and risk factors in dairy cattle in Gondar city, Northwest Ethiopia.

Prev Vet Med 2021 Apr 21;191:105363. Epub 2021 Apr 21.

One Health Institute, School of Veterinary Medicine, University of California, Davis, USA.

Bovine viral diarrhea (BVD) is a disease that affects cattle and other ruminants worldwide and causes considerable economic losses. A cross-sectional study was carried out between December 2017 and July 2018 with the aim to estimate the prevalence of Bovine Viral Diarrhea virus (BVDV) antibodies and to identify potential risk factors associated with the occurrence of the disease in dairy cattle in peri-urban areas of Gondar city, Northwest Ethiopia. A total of 339 serum samples obtained from randomly selected dairy cattle aged 6 months and older were assayed using a BVDV antibody competitive-Enzyme Linked Immunosorbent Assay (c-ELISA) kit. Descriptive statistics were used to estimate antibody prevalence of BVDV at animal and herd-level and logistic regression was used to identify potential risk factors. The study findings showed that the animal-level antibody prevalence of BVDV in the study area was 26.84 % (95 % CI: 22.1 %-31.6 %) and the herd-level seroprevalence was 68.3 % (95 % CI: 56.2 %-80.4 %). Logistic regression model demonstrated that age >2 years (OR = 4.75, 95 % CI: 2.20-10.26), herd size >11 (OR = 7.28, 95 % CI: 2.50-21.22), and poor farm hygiene (OR = 3.69, 95 % CI: 1.94-7.02), are potential risk factors associated with BVDV infection (P < 0.05). However, sex, faecal consistency and housing system were not associated with BVDV serostatus. The animal- and herd-level seroprevalence reports in Northwest Ethiopia can serve as a baseline finding for future BVD epidemiological investigations and to inform future control programs in the study region.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.prevetmed.2021.105363DOI Listing
April 2021