Resilience and HIV: a review of the definition and study of resilience

We use a socioecological model of health to define resilience, review the definition and study of resilience among persons living with human immunodeficiency virus (PLWH) in the existing peer-reviewed literature, and discuss the strengths and limitations of how resilience is defined and studied in HIV research. We conducted a review of resilience research for HIV-related behaviors/outcomes of antiretroviral therapy (ART) adherence, clinic attendance, CD4 cell count, viral load, viral suppression, and/or immune functioning among PLWH. We performed searches using PubMed, PsycINFO and Google Scholar databases. The initial search generated 14,296 articles across the three databases, but based on our screening of these articles and inclusion criteria, n = 54 articles were included for review. The majority of HIV resilience research defines resilience only at the individual (i.e., psychological) level or studies individual and limited interpersonal resilience (e.g., social support). Furthermore, the preponderance of HIV resilience research uses general measures of resilience; these measures have not been developed with or tailored to the needs of PLWH. Our review suggests that a socioecological model of health approach can more fully represent the construct of resilience. Furthermore, measures specific to PLWH that capture individual, interpersonal, and neighborhood resilience are needed

Development of Long and Short Forms of the Multilevel Resilience Resource Measure for African American/Black Adults Living with HIV

Understanding resilience in relation to HIV-related outcomes may help address racial/ethnic disparities, however, significant gaps in its measurement preclude in-depth study. Thus, this research aims to develop and evaluate the psychometric properties of long and short forms of the Multilevel Resilience Resource Measure for African American/Black Adults Living with HIV. To develop the items, we conducted a mixed methods study (N = 48) and reviewed published resilience measures. We completed content validity index analyses to ensure the items reflected the resilience construct. Next, we conducted 20 cognitive interviews and a field survey (N = 400). The long and short forms demonstrated acceptable to excellent psychometric properties based on factorial validity, internal consistency and convergent validity and on measurement invariance (conducted for the short form only). These measures provide a comprehensive framework to examine resilience and HIV-related outcomes and can inform resilience-building interventions to reduce racial and ethnic health disparities

Multilevel Resilience and HIV Virologic Suppression Among African American/Black Adults in the Southeastern United States

Objective: To assess overall and by neighborhood risk environments whether multilevel resilience resources were associated with HIV virologic suppression among African American/Black adults in the Southeastern United States. Setting and Methods: This clinical cohort sub-study included 436 African American/Black participants enrolled in two parent HIV clinical cohorts. Resilience was assessed using the Multilevel Resilience Resource Measure (MRM) for African American/Black adults living with HIV, where endorsement of a MRM statement indicated agreement that a resilience resource helped a participant continue HIV care despite challenges or was present in a participant’s neighborhood. Modified Poisson regression models estimated adjusted prevalence ratios (aPRs) for virologic suppression as a function of categorical MRM scores, controlling for demographic, clinical, and behavioral characteristics at or prior to sub-study enrollment. We assessed for effect measure modification (EMM) by neighborhood risk environments. Results: Compared to participants with lesser endorsement of multilevel resilience resources, aPRs for virologic suppression among those with greater or moderate endorsement were 1.03 (95% confidence interval: 0.96–1.11) and 1.03 (0.96–1.11), respectively. Regarding multilevel resilience resource endorsement, there was no strong evidence for EMM by levels of neighborhood risk environments. Conclusions: Modest positive associations between higher multilevel resilience resource endorsement and virologic suppression were at times most compatible with the data. However, null findings were also compatible. There was no strong evidence for EMM concerning multilevel resilience resource endorsement, which could have been due to random error. Prospective studies assessing EMM by levels of the neighborhood risk environment with larger sample sizes are needed

Association of genetic variation with systolic and diastolic blood pressure among African Americans: the Candidate Gene Association Resource study

The prevalence of hypertension in African Americans (AAs) is higher than in other US groups; yet, few have performed genome-wide association studies (GWASs) in AA. Among people of European descent, GWASs have identified genetic variants at 13 loci that are associated with blood pressure. It is unknown if these variants confer susceptibility in people of African ancestry. Here, we examined genome-wide and candidate gene associations with systolic blood pressure (SBP) and diastolic blood pressure (DBP) using the Candidate Gene Association Resource (CARe) consortium consisting of 8591 AAs. Genotypes included genome-wide single-nucleotide polymorphism (SNP) data utilizing the Affymetrix 6.0 array with imputation to 2.5 million HapMap SNPs and candidate gene SNP data utilizing a 50K cardiovascular gene-centric array (ITMAT-Broad-CARe [IBC] array). For Affymetrix data, the strongest signal for DBP was rs10474346 (P= 3.6 × 10−8) located near GPR98 and ARRDC3. For SBP, the strongest signal was rs2258119 in C21orf91 (P= 4.7 × 10−8). The top IBC association for SBP was rs2012318 (P= 6.4 × 10−6) near SLC25A42 and for DBP was rs2523586 (P= 1.3 × 10−6) near HLA-B. None of the top variants replicated in additional AA (n = 11 882) or European-American (n = 69 899) cohorts. We replicated previously reported European-American blood pressure SNPs in our AA samples (SH2B3, P= 0.009; TBX3-TBX5, P= 0.03; and CSK-ULK3, P= 0.0004). These genetic loci represent the best evidence of genetic influences on SBP and DBP in AAs to date. More broadly, this work supports that notion that blood pressure among AAs is a trait with genetic underpinnings but also with significant complexit

Association of genetic variation with systolic and diastolic blood pressure among African Americans: the Candidate Gene Association Resource study.

The prevalence of hypertension in African Americans (AAs) is higher than in other US groups; yet, few have performed genome-wide association studies (GWASs) in AA. Among people of European descent, GWASs have identified genetic variants at 13 loci that are associated with blood pressure. It is unknown if these variants confer susceptibility in people of African ancestry. Here, we examined genome-wide and candidate gene associations with systolic blood pressure (SBP) and diastolic blood pressure (DBP) using the Candidate Gene Association Resource (CARe) consortium consisting of 8591 AAs. Genotypes included genome-wide single-nucleotide polymorphism (SNP) data utilizing the Affymetrix 6.0 array with imputation to 2.5 million HapMap SNPs and candidate gene SNP data utilizing a 50K cardiovascular gene-centric array (ITMAT-Broad-CARe [IBC] array). For Affymetrix data, the strongest signal for DBP was rs10474346 (P= 3.6 × 10(-8)) located near GPR98 and ARRDC3. For SBP, the strongest signal was rs2258119 in C21orf91 (P= 4.7 × 10(-8)). The top IBC association for SBP was rs2012318 (P= 6.4 × 10(-6)) near SLC25A42 and for DBP was rs2523586 (P= 1.3 × 10(-6)) near HLA-B. None of the top variants replicated in additional AA (n = 11 882) or European-American (n = 69 899) cohorts. We replicated previously reported European-American blood pressure SNPs in our AA samples (SH2B3, P= 0.009; TBX3-TBX5, P= 0.03; and CSK-ULK3, P= 0.0004). These genetic loci represent the best evidence of genetic influences on SBP and DBP in AAs to date. More broadly, this work supports that notion that blood pressure among AAs is a trait with genetic underpinnings but also with significant complexity

Long-Baseline Neutrino Facility (LBNF) and Deep Underground Neutrino Experiment (DUNE) Conceptual Design Report Volume 2: The Physics Program for DUNE at LBNF

The Physics Program for the Deep Underground Neutrino Experiment (DUNE) at the Fermilab Long-Baseline Neutrino Facility (LBNF) is described

Whole-genome sequencing reveals host factors underlying critical COVID-19

Critical COVID-19 is caused by immune-mediated inflammatory lung injury. Host genetic variation influences the development of illness requiring critical care1 or hospitalization2,3,4 after infection with SARS-CoV-2. The GenOMICC (Genetics of Mortality in Critical Care) study enables the comparison of genomes from individuals who are critically ill with those of population controls to find underlying disease mechanisms. Here we use whole-genome sequencing in 7,491 critically ill individuals compared with 48,400 controls to discover and replicate 23 independent variants that significantly predispose to critical COVID-19. We identify 16 new independent associations, including variants within genes that are involved in interferon signalling (IL10RB and PLSCR1), leucocyte differentiation (BCL11A) and blood-type antigen secretor status (FUT2). Using transcriptome-wide association and colocalization to infer the effect of gene expression on disease severity, we find evidence that implicates multiple genes—including reduced expression of a membrane flippase (ATP11A), and increased expression of a mucin (MUC1)—in critical disease. Mendelian randomization provides evidence in support of causal roles for myeloid cell adhesion molecules (SELE, ICAM5 and CD209) and the coagulation factor F8, all of which are potentially druggable targets. Our results are broadly consistent with a multi-component model of COVID-19 pathophysiology, in which at least two distinct mechanisms can predispose to life-threatening disease: failure to control viral replication; or an enhanced tendency towards pulmonary inflammation and intravascular coagulation. We show that comparison between cases of critical illness and population controls is highly efficient for the detection of therapeutically relevant mechanisms of disease