We study the effect of physician workforce diversity on the demand for preventive care among African American men. In an experiment in Oakland, California, we randomize black men to black or ...non-black male medical doctors. We use a two-stage design, measuring decisions before (pre-consultation) and after (post-consultation) meeting their assigned doctor. Subjects select a similar number of preventives in the pre-consultation stage, but are much more likely to select every preventive service, particularly invasive services, once meeting with a racially concordant doctor. Our findings suggest black doctors could reduce the black-white male gap in cardiovascular mortality by 19 percent.
In order for precision health to address health disparities, engagement of diverse racial/ethnic minority communities and the physicians that serve them is critical.
A community-based participatory ...research approach with mixed methods was employed to gain a deeper understanding of precision health research and practice among American Indian, African American, Latino, Chinese, and Vietnamese groups and physicians that serve these communities. A survey assessed demographics and opinions of precision health, genetic testing, and precision health research. Focus groups (n=12) with each racial/ethnic minority group and physicians further explored attitudes about these topics.
One hundred community members (American Indian n=17, African American n=13, Chinese n=17, Latino n=27, and Vietnamese n=26) and 14 physicians completed the survey and participated in the focus groups. Familiarity with precision health was low among community members and high among physicians. Most groups were enthusiastic about the approach, especially if it considered influences on health in addition to genes (eg, environmental, behavioral, social factors). Significant concerns were expressed by African American and American Indian participants about precision health practice and research based on past abuses in biomedical research. In addition, physician and community members shared concerns such as security and confidentiality of genetic information, cost and affordability of genetic tests and precision medicine, discrimination and disparities, distrust of medical and research and pharmaceutical institutions, language barriers, and physician's specialty.
Engagement of racial/ethnic minority communities and the providers who serve them is important for advancing a precision health approach to addressing health disparities.
Well-characterized disparities in clinical research have disproportionately affected patients of color, particularly in underserved communities. To tackle these barriers, Genentech formed the ...External Council for Advancing Inclusive Research, a 14-person committee dedicated to developing strategies to increase clinical research participation. To help improve the recruitment and retention of patients of color, this article chronicles our efforts to tangibly address the clinical research barriers at the system, study, and patient levels over the last four years. These efforts are one of the initial steps to fully realize the promise of personalized health care and provide increased patient benefit at less cost to society. Instead of simply acknowledging the problem, here we illuminate the collaborative and multilevel strategies that have been effective in delivering meaningful progress for patients.
Cytotoxic T-lymphocytes (CTL) play an important role in the immune system's defense against human immunodeficiency virus (HIV) infection. The functional status of CTL closely relates to the ...progression of HIV disease. We have validated the characteristics of the assay for HIV-1 gag- and pol-specific-CD8/HLA-A2 T-cells from peripheral blood by flow cytometry. Sixty-nine healthy individuals and 38 HIV-patients with HLA-A2 antigen-positive subjects were included in the study. Neither HIV-1 gag- nor pol-specific-CD8/HLA-A2 T-cells were determined in these healthy subjects. HIV-1 gag- and pol-specific-CD8/HLA-A2 T-cells could be detected in HIV-patients. The frequency of specific CTL was 58% (22/38) in the patient group. There was a significantly inverse correlation (
p
<
0.05) between HIV-1 gag- and pol-specific-CD8/HLA-A2 T-cells and HIV plasma viremia in the patients.
The HIV-1 gag- or pol-specific-CD8/HLA-A2 T-cells assay is sensitive and specific, being able to detect at the single T-cell level. This assay may provide a versatile tool for structured HIV treatment and for monitoring vaccination efficacy.
Working Paper No. 24787 We study the effect of diversity in the physician workforce on the demand for preventive care among African-American men. Black men have the lowest life expectancy of any ...major demographic group in the U.S., and much of the disadvantage is due to chronic diseases which are amenable to primary and secondary prevention. In a field experiment in Oakland, California, we randomize black men to black or non-black male medical doctors and to incentives for one of the five offered preventives - the flu vaccine. We use a two-stage design, measuring decisions about cardiovascular screening and the flu vaccine before (ex ante) and after (ex post) meeting their assigned doctor. Black men select a similar number of preventives in the ex-ante stage, but are much more likely to select every preventive service, particularly invasive services, once meeting with a doctor who is the same race. The effects are most pronounced for men who mistrust the medical system and for those who experienced greater hassle costs associated with their visit. Subjects are more likely to talk with a black doctor about their health problems and black doctors are more likely to write additional notes about the subjects. The results are most consistent with better patient-doctor communication during the encounter rather than differential quality of doctors or discrimination. Our findings suggest black doctors could help reduce cardiovascular mortality by 16 deaths per 100,000 per year - leading to a 19% reduction in the black-white male gap in cardiovascular mortality.
We study the effect of diversity in the physician workforce on the demand for preventive care among African-American men. Black men have the lowest life expectancy of any major demographic group in ...the U.S., and much of the disadvantage is due to chronic diseases which are amenable to primary and secondary prevention. In a field experiment in Oakland, California, we randomize black men to black or non-black male medical doctors and to incentives for one of the five offered preventives - the flu vaccine. We use a two-stage design, measuring decisions about cardiovascular screening and the flu vaccine before (ex ante) and after (ex post) meeting their assigned doctor. Black men select a similar number of preventives in the ex-ante stage, but are much more likely to select every preventive service, particularly invasive services, once meeting with a doctor who is the same race. The effects are most pronounced for men who mistrust the medical system and for those who experienced greater hassle costs associated with their visit. Subjects are more likely to talk with a black doctor about their health problems and black doctors are more likely to write additional notes about the subjects. The results are most consistent with better patient-doctor communication during the encounter rather than differential quality of doctors or discrimination. Our findings suggest black doctors could help reduce cardiovascular mortality by 16 deaths per 100,000 per year - leading to a 19% reduction in the black-white male gap in cardiovascular mortality.
The World Health Organization has declared the ongoing outbreak of COVID-19, which is caused by a novel coronavirus SARS-CoV-2, a pandemic. There is currently a lack of knowledge about the antibody ...response elicited from SARS-CoV-2 infection. One major immunological question concerns antigenic differences between SARS-CoV-2 and SARS-CoV. We address this question by analyzing plasma from patients infected by SARS-CoV-2 or SARS-CoV and from infected or immunized mice. Our results show that, although cross-reactivity in antibody binding to the spike protein is common, cross-neutralization of the live viruses may be rare, indicating the presence of a non-neutralizing antibody response to conserved epitopes in the spike. Whether such low or non-neutralizing antibody response leads to antibody-dependent disease enhancement needs to be addressed in the future. Overall, this study not only addresses a fundamental question regarding antigenicity differences between SARS-CoV-2 and SARS-CoV but also has implications for immunogen design and vaccine development.
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•Cross-reactive antigen binding is common between SARS-CoV and SARS-CoV-2•Cross-reactive antibody responses target both RBD and non-RBD regions•Cross-neutralization of live viruses may be rare between SARS-CoV and SARS-CoV-2
Lv et al. examine the antibody responses from patients infected by SARS-CoV-2 or SARS-CoV and from infected or immunized mice. The results show that cross-reactive binding to the spike protein is common, whereas cross-neutralization of the live viruses may be rare.
Individuals with the 2019 coronavirus disease (COVID-19) show varying severity of the disease, ranging from asymptomatic to requiring intensive care. Although monoclonal antibodies specific to the ...severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have been identified, we still lack an understanding of the overall landscape of B cell receptor (BCR) repertoires in individuals with COVID-19. We use high-throughput sequencing of bulk and plasma B cells collected at multiple time points during infection to characterize signatures of the B cell response to SARS-CoV-2 in 19 individuals. Using principled statistical approaches, we associate differential features of BCRs with different disease severity. We identify 38 significantly expanded clonal lineages shared among individuals as candidates for responses specific to SARS-CoV-2. Using single-cell sequencing, we verify the reactivity of BCRs shared among individuals to SARS-CoV-2 epitopes. Moreover, we identify the natural emergence of a BCR with cross-reactivity to SARS-CoV-1 and SARS-CoV-2 in some individuals. Our results provide insights important for development of rational therapies and vaccines against COVID-19.
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•Analysis of B cell repertoires with SARS-CoV-2 epitope-sorted B cell receptors•Differential sequence features of B cell receptors are associated with disease severity•Expansion of B cell clonal lineages in response to SARS-CoV-2•Shared B cell receptors emerge with cross-reactivity to SARS-CoV-1 and SARS-CoV-2
It is unclear how the dynamics of the humoral immune response to SARS-CoV-2 vary across individuals with different disease severity. Montague et al. develop a principled statistical approach based on time-course, high-throughput B cell repertoire sequences to identify shared, expanding, rare clonal B cell lineages as candidates for responses specific to SARS-CoV-2.
The increasing numbers of infected cases of coronavirus disease 2019 (COVID‐19) caused by severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) poses serious threats to public health and the ...global economy. Most SARS‐CoV‐2 neutralizing antibodies target the receptor binding domain (RBD) and some the N‐terminal domain (NTD) of the spike protein, which is the major antigen of SARS‐CoV‐2. While the antibody response to RBD has been extensively characterized, the antigenicity and immunogenicity of the NTD protein are less well studied. Using 227 plasma samples from COVID‐19 patients, we showed that SARS‐CoV‐2 NTD‐specific antibodies could be induced during infection. As compared to the results of SARS‐CoV‐2 RBD, the serological response of SARS‐CoV‐2 NTD is less cross‐reactive with SARS‐CoV, a pandemic strain that was identified in 2003. Furthermore, neutralizing antibodies are rarely elicited in a mice model when NTD is used as an immunogen. We subsequently demonstrate that NTD has an altered antigenicity when expressed alone. Overall, our results suggest that while NTD offers a supplementary strategy for serology testing, it may not be suitable as an immunogen for vaccine development.
Receptor binding domain (RBD) of the SARS‐CoV‐2 spike protein has been extensively studied in functional antibody screening and COVID‐19 vaccine design. To explore the function of N‐terminal domain (NTD) of spike protein, we reveal that NTD is a supplementary antigen for serology testing, but not a suitable immunogen for vaccine design.
Preterm birth is defined as delivery at <37 weeks of gestational age (GA) and exposes 15 million infants worldwide to serious early life diseases. Lowering the age of viability to 22 weeks GA ...entailed provision of intensive care to a greater number of extremely premature infants. Moreover, improved survival, especially at extremes of prematurity, comes with a rising incidence of early life diseases with short- and long-term sequelae. The transition from fetal to neonatal circulation is a substantial and complex physiologic adaptation, which normally happens rapidly and in an orderly sequence. Maternal chorioamnionitis or fetal growth restriction (FGR) are two common causes of preterm birth that are associated with impaired circulatory transition. Among many cytokines contributing to the pathogenesis of chorioamnionitis-related perinatal inflammatory diseases, the potent pro-inflammatory interleukin (IL)-1 has been shown to play a central role. The effects of utero-placental insufficiency-related FGR and in-utero hypoxia may also be mediated, in part, via the inflammatory cascade. In preclinical studies, blocking such inflammation, early and effectively, holds great promise for improving the transition of circulation. In this mini-review, we outline the mechanistic pathways leading to abnormalities in transitional circulation in chorioamnionitis and FGR. In addition, we explore the therapeutic potential of targeting IL-1 and its influence on perinatal transition in the context of chorioamnionitis and FGR.
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