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It is projected that by 2045, racial/ethnic minorities in the U.S. will become the majority. Unfortunately, the numbers of racial/ethnic minority psychologists have not kept up with population trends. This discrepancy poses challenges for many psychology training sites, including the Department of Veterans Affairs (VA). There is a lack of data on what factors are important for psychology applicants, including racial/ethnic minority trainees when they are considering internship and postdoctoral training sites. This quality improvement project surveyed 237 VA psychology trainees (59% psychology interns, 32.5% psychology postdoctoral fellows, 69.6% White, 9.3% multiracial, 6.8% Asian American or Pacific Islander, 5.1% Black/African American, 4.2% Latinx American, 0.8% Native American, 0.8% Middle Eastern) to study what factors are important when considering training sites. Results indicated that overall, racial/ethnic minority and White trainees endorsed similar primary factors when considering training programs. Site related factors (e.g., perceived workload, training opportunities) and future work related factors (e.g., ease of licensure, obtaining a first job) were top considerations regardless of race/ethnicity. The groups diverged in secondary factors with racial/ethnic minorities desiring infusion of diversity in training more than White applicants and White applicants considering quality of life factors such as extracurricular opportunities and convenience of daily living more important than racial/ethnic minority applicants. Qualitative data indicated applicants perceived VA training sites to be more welcoming and offer more opportunities for learning about diversity than non-VA sites. Recommendations for recruiting psychology trainees in general, and then specifically for racial/ethnic minority applicants are discussed. (PsycInfo Database Record (c) 2021 APA, all rights reserved).

Limited data are available on the long-term clinical and immunologic consequences of SARS-CoV-2 infection in people with HIV (PWH).We measured SARS-CoV-2-specific humoral and cellular responses in people with and without HIV recovering from COVID-19 ( n = 39 and n = 43, respectively) using binding antibody, surrogate virus neutralization, intracellular cytokine staining, and inflammatory marker assays. We identified individuals experiencing postacute sequelae of SARS-CoV-2 infection (PASC) and evaluated immunologic parameters. We used linear regression and generalized linear models to examine differences by HIV status in the magnitude of inflammatory and virus-specific antibody and T-cell responses, as well as differences in the prevalence of PASC.Among PWH, we found broadly similar SARS-CoV-2-specific antibody and T-cell responses as compared with a well matched group of HIV-negative individuals. PWH had 70% lower relative levels of SARS-CoV-2-specific memory CD8 + T cells ( P = 0.007) and 53% higher relative levels of PD-1+ SARS-CoV-2-specific CD4 + T cells ( P = 0.007). Higher CD4 + /CD8 + ratio was associated with lower PD-1 expression on SARS-CoV-2-specific CD8 + T cells (0.34-fold effect, P = 0.02). HIV status was strongly associated with PASC (odds ratio 4.01, P = 0.008), and levels of certain inflammatory markers (IL-6, TNF-alpha, and IP-10) were associated with persistent symptoms.We identified potentially important differences in SARS-CoV-2-specific CD4 + and CD8 + T cells in PWH and HIV-negative participants that might have implications for long-term immunity conferred by natural infection. HIV status strongly predicted the presence of PASC. Larger and more detailed studies of PASC in PWH are urgently needed.

Background Mutations in the p110α catalytic subunit of phosphatidylinositol 3-kinase (PI3K), encoded by the PIK3CA gene, cause dysregulation of the PI3K pathway in 35–40% of patients with HR+/HER2– breast cancer. Preclinically, cancer cells harboring double or multiple PIK3CA mutations (mut) elicit hyperactivation of the PI3K pathway leading to enhanced sensitivity to p110α inhibitors. Methods To understand the role of multiple PIK3CAmut in predicting response to p110α inhibition, we estimated the clonality of multiple PIK3CAmut in circulating tumor DNA (ctDNA) from patients with HR+/HER2– metastatic breast cancer enrolled to a prospectively registered clinical trial of fulvestrant ± taselisib, and analyzed the subgroups against co-altered genes, pathways, and outcomes. Results ctDNA samples with clonal multiple PIK3CAmut had fewer co-alterations in receptor tyrosine kinase (RTK) or non-PIK3CA PI3K pathway genes compared to samples with subclonal multiple PIK3CAmut indicating a strong reliance on the PI3K pathway. This was validated in an independent cohort of breast cancer tumor specimens that underwent comprehensive genomic profiling. Furthermore, patients whose ctDNA harbored clonal multiple PIK3CAmut exhibited a significantly higher response rate and longer progression-free survival vs subclonal multiple PIK3CAmut. Conclusions Our study establishes clonal multiple PIK3CAmut as an important molecular determinant of response to p110α inhibition and provides rationale for further clinical investigation of p110α inhibitors alone or with rationally-selected therapies in breast cancer and potentially other solid tumor types.

Purpose of the Review Improved forest management is a promising avenue for climate change mitigation. However, we lack synthetic understanding of how different management actions impact aboveground carbon stocks, particularly at scales relevant for designing and implementing forest-based climate solutions. Here, we quantitatively assess and review the impacts of three common practices—application of inorganic NPK fertilizer, interplanting with N-fixing species, and thinning—on aboveground carbon stocks in plantation forests. Recent Findings Site-level empirical studies show both positive and negative effects of inorganic fertilization, interplanting, and thinning on aboveground carbon stocks in plantation forests. Recent findings and the results of our analysis suggest that these effects are heavily moderated by factors such as species selection, precipitation, time since practice, soil moisture regime, and previous land use. Interplanting of N-fixing crops initially has no effect on carbon storage in main tree crops, but the effect becomes positive in older stands. Conversely, the application of NPK fertilizers increases aboveground carbon stocks, though the effect lessens with time. Moreover, increases in aboveground carbon stocks may be partially or completely offset by emissions from the application of inorganic fertilizer. Thinning results in a strong reduction of aboveground carbon stocks, though the effect lessens with time. Summary Management practices tend to have strong directional effects on aboveground carbon stocks in plantation forests but are moderated by site-specific management, climatic, and edaphic factors. The effect sizes quantified in our meta-analysis can serve as benchmarks for the design and scoping of improved forest management projects as forest-based climate solutions. Overall, management actions can enhance the climate mitigation potential of plantation forests, if performed with sufficient attention to the nuances of local conditions.

Breakdown of the different tumor types among double-PIK3CA mutant samples based on their clonality and cis/trans status.

Mutual exclusivity of multi-PIK3CA mutations with other gene alterations in the PI3K pathway.

Serine and threonine phosphoproteome of NIH-3T3 cells bearing PIK3CA E726K/H1047R vs H1047R.

Purpose:To comprehensively characterize tissue-specific and molecular subclasses of multiple PIK3CA (multi-PIK3CA) mutations and assess their impact on potential therapeutic outcomes.Experimental Design:We profiled a pan-cancer cohort comprised of 352,392 samples across 66 tumor types using a targeted hybrid capture-based next-generation sequencing panel covering at least 324 cancer-related genes. Molecularly defined subgroups, allelic configuration, clonality, and mutational signatures were identified and tested for association with PI3K inhibitor therapeutic response.Results:Multi-PIK3CA mutations are found in 11% of all PIK3CA-mutant tumors, including 9% of low tumor mutational burden (TMB) PIK3CA-mutant tumors, and are enriched in breast and gynecologic cancers. Multi-PIK3CA mutations are frequently clonal and in cis on the same allele and occur at characteristic positions across tumor types. These mutations tend to be mutually exclusive of mutations in other driver genes, and of genes in the PI3K pathway. Among PIK3CA-mutant tumors with a high TMB, 18% are multi-PIK3CA mutant and often harbor an apolipoprotein B mRNA-editing enzyme, catalytic polypeptide (APOBEC) mutational signature. Despite large differences in specific allele combinations comprising multi-PIK3CA mutant tumors, especially across cancer types, patients with different classes of multi-PIK3CA mutant estrogen receptor–positive, HER2-negative breast cancers respond similarly to PI3K inhibition.Conclusions:Our pan-tumor study provides biological insights into the genetic heterogeneity and tissue specificities of multi-PIK3CA mutations, with potential clinical utility to guide PI3K inhibition strategies.

Prevalence of different PIK3CA mutation subgroups based on tumor mutational burden (TMB) and APOBEC status.

Table S1: Clinico-demographic characteristics of single- and multi-PIK3CA mutant tumors; Table S2: Prevalence of single and multi-PIK3CA mutated tumors across all tumor types; Table S3: Prevalence of single and multi-PIK3CA mutated tumors across pan-tumor histological subtypes; Table S4: Prevalence of single and multi-PIK3CA mutated tumors in different receptor subgroups of breast cancer; Table S5: Clonality predictions for double PIK3CA mutated tumors in different tumor types; Table S6: Prediction of cis/trans orientation for double PIK3CA mutated tumors in different tumor types; Table S7: Patterns of co-occurrence and mutual exclusivity between multi-PIK3CA mutations and other gene alterations in the overall cohort and specific tumor types; Table S8: Comparison of co-occurring alterations in multi-PIK3CA and single-PIK3CA mutant tumors; Table S9: Prevalence of multi-PIK3CA mutations based on status of tumor mutational burden; Table S10: Breakdown of PIK3CA mutations in different classes of mutational signatures in patients with a high tumor mutational burden; Table S11: Prevalence of single- and multi-PIK3CA mutations based on tumor mutational burden and APOBEC signatures; Table S12: Prevalence of specific pairs of PIK3CA mutations across different tumor types; Table S13: Prevalence of specific pairs of PIK3CA mutations at the codon level, across different tumor types; Table S14: Codon enrichment between single and multi-PIK3CA mutant tumors across different tumor types.

Read support for double-PIK3CA mutation pairs in the determination of cis/trans status.

Comparison of co-alteration prevalence in single- and multi-PIK3CA mutated tumors.

Patterns of mutual exclusivity as well as co-occurrence between multi-PIK3CA mutations and alterations in other cancer associated genes.

Progression-free survival of patients with PIK3CA mutant tumors in the SANDPIPER study stratified by treatment arm and the quantity of PIK3CA mutations detected.

Objective : Catholic Religious and Ethical Directives restrict access to contraception, yet offering contraception during a delivery hospitalization facilitates birth spacing and is a convenient option for patients during the postpartum period. We assessed patient and provider experiences with hospital transparency around postpartum contraceptive care in Illinois Catholic hospitals. Study Design : We interviewed 44 participants with experience in Illinois Catholic hospitals: 21 patients, and 23 providers, including clinicians, nurses, doulas, and postpartum program staff. We used an open-ended interview approach, with a semi-structured guide focused on postpartum contraceptive care. We conducted interviews by phone between November 2019 and June 2020. We audio-recorded interviews, transcribed them verbatim, and coded transcripts in Dedoose. We developed narrative memos for each code, identifying themes and sub-themes. We organized these in a matrix for analysis and present here themes regarding hospital transparency that emerged across interviews. Results : Many patients knew they were delivering in a Catholic hospital; however, few were aware that Catholic policies limited their healthcare options. Patients expressed a desire for hospitals to be transparent, even “very vocal,” about religious restrictions and described consequences of restrictions on patient care. Patients lacked information to make contraceptive decisions, experienced limits on or delays in care, and some lost continuity with trusted providers. Consequences for providers included moral distress in trying to provide care using workarounds such as documenting false medical diagnoses. Conclusions : Religious restrictions on postpartum contraception restrict access, cause unnecessary delays in care, and lead to misdiagnosis and marginalization of contraceptive care. Restrictions also cause moral distress to providers who balance career repercussions and professional integrity with patient needs. Implications : To protect patient autonomy, especially during the vulnerable postpartum period, Catholic hospitals should increase transparency regarding limitations on reproductive health care. Insurers and policy-makers should guarantee that patients have the option to receive care at hospitals without these limitations and facilitate public education about what to expect at Catholic facilities.

In August 2016, the Wisconsin Department of Health Services notified the U.S. Centers for Disease Control and Prevention of multidrug-resistant (MDR) Salmonella enterica serovar Heidelberg infections in people who reported contact with dairy calves. Federal and state partners investigated this to identify the source and scope of the outbreak and to prevent further illnesses. Cases were defined as human Salmonella Heidelberg infection caused by a strain that had one of seven pulsed-field gel electrophoresis (PFGE) patterns or was related by whole genome sequencing (WGS), with illness onset from January 1, 2015, through July 2, 2018. Patient exposure and calf purchase information was collected and analyzed; calves were traced back from the point of purchase. Isolates obtained from animal and environmental samples collected on-farm were supplied by veterinary diagnostic laboratories and compared with patient isolates using PFGE and WGS. Antimicrobial susceptibility testing by standardized broth microdilution was performed. Sixty-eight patients from 17 states were identified. Forty (63%) of 64 patients noted cattle contact before illness. Thirteen (33%) of 40 patients with exposure to calves reported that calves were sick or had died. Seven individuals purchased calves from a single Wisconsin livestock market. One hundred forty cattle from 14 states were infected with the outbreak strain. WGS indicated that human, cattle, and environmental isolates from the livestock market were genetically closely related. Most isolates (88%) had resistance or reduced susceptibility to antibiotics of ≥5 antibiotic classes. This resistance profile included first-line antibiotic treatments for patients with severe salmonellosis, including ampicillin, ceftriaxone, and ciprofloxacin. In this outbreak, MDR Salmonella Heidelberg likely spread from sick calves to humans, emphasizing the importance of illness surveillance in animal populations to prevent future spillover of this zoonotic disease.

BACKGROUNDThe presence and reactivation of chronic viral infections, such as EBV, CMV, and HIV, have been proposed as potential contributors to long COVID (LC), but studies in well-characterized postacute cohorts of individuals with COVID-19 over a longer time course consistent with current case definitions of LC are limited.METHODSIn a cohort of 280 adults with prior SARS-CoV-2 infection, we assessed the presence and types of LC symptoms and prior medical history (including COVID-19 history and HIV status) and performed serological testing for EBV and CMV using a commercial laboratory. We used covariate-adjusted binary logistic regression models to identify independent associations between variables and LC symptoms.RESULTSWe observed that LC symptoms, such as fatigue and neurocognitive dysfunction, at a median of 4 months following initial diagnosis were independently associated with serological evidence suggesting recent EBV reactivation (early antigen-diffuse IgG positivity) or high nuclear antigen (EBNA) IgG levels but not with ongoing EBV viremia. Serological evidence suggesting recent EBV reactivation (early antigen-diffuse IgG positivity) was most strongly associated with fatigue (OR = 2.12). Underlying HIV infection was also independently associated with neurocognitive LC (OR = 2.5). Interestingly, participants who had serologic evidence of prior CMV infection were less likely to develop neurocognitive LC (OR = 0.52).CONCLUSIONOverall, these findings suggest differential effects of chronic viral coinfections on the likelihood of developing LC and association with distinct syndromic patterns. Further assessment during the acute phase of COVID-19 is warranted.TRIAL REGISTRATIONLong-term Impact of Infection with Novel Coronavirus; ClinicalTrials.gov NCT04362150.FUNDINGThis work was supported by NIH/National Institute of Allergy and Infectious Diseases grants (3R01AI141003-03S1, R01AI158013, and K24AI145806); the Zuckerberg San Francisco General Hospital Department of Medicine and Division of HIV, Infectious Diseases, and Global Medicine; and the UCSF-Bay Area Center for AIDS Research (P30-AI027763).

Purpose:To comprehensively characterize tissue-specific and molecular subclasses of multiple PIK3CA (multi-PIK3CA) mutations and assess their impact on potential therapeutic outcomes.Experimental Design:We profiled a pan-cancer cohort comprised of 352,392 samples across 66 tumor types using a targeted hybrid capture-based next-generation sequencing panel covering at least 324 cancer-related genes. Molecularly defined subgroups, allelic configuration, clonality, and mutational signatures were identified and tested for association with PI3K inhibitor therapeutic response.Results:Multi-PIK3CA mutations are found in 11% of all PIK3CA-mutant tumors, including 9% of low tumor mutational burden (TMB) PIK3CA-mutant tumors, and are enriched in breast and gynecologic cancers. Multi-PIK3CA mutations are frequently clonal and in cis on the same allele and occur at characteristic positions across tumor types. These mutations tend to be mutually exclusive of mutations in other driver genes, and of genes in the PI3K pathway. Among PIK3CA-mutant tumors with a high TMB, 18% are multi-PIK3CA mutant and often harbor an apolipoprotein B mRNA-editing enzyme, catalytic polypeptide (APOBEC) mutational signature. Despite large differences in specific allele combinations comprising multi-PIK3CA mutant tumors, especially across cancer types, patients with different classes of multi-PIK3CA mutant estrogen receptor–positive, HER2-negative breast cancers respond similarly to PI3K inhibition.Conclusions:Our pan-tumor study provides biological insights into the genetic heterogeneity and tissue specificities of multi-PIK3CA mutations, with potential clinical utility to guide PI3K inhibition strategies.

Currently available mRNA vaccines are extremely safe and effective to prevent severe SARS-CoV-2 infections. However, the emergence of variants of concerns (VOCs) has highlighted the importance of high population-based vaccine rates to effectively suppress viral transmission and breakthrough infections. While initially left out from vaccine efforts, children have become one of the most affected age groups and are key targets to stop community and household spread. Antibodies are central for vaccine-induced protection and emerging data points to the importance of additional Fc effector functions like opsononophagocytosis or cytotoxicity, particularly in the context of VOCs that escape neutralizing antibodies. Here, we observed delayed induction and reduced magnitude of vaccine-induced antibody titers in children 5-11 years receiving two doses of the age-recommended 10 μg dose of the Pfizer SARS-CoV-2 BNT162b2 vaccine compared to adolescents (12–15 years) or adults receiving the 30 μg dose. Conversely, children mounted equivalent or more robust neutralization and opsonophagocytic functions at peak immunogenicity, pointing to a qualitatively more robust humoral functional response in children. Moreover, broad cross-VOC responses were observed across children, with enhanced IgM and parallel IgG cross-reactivity to VOCs in children compared to adults. Collectively, these data argue that despite the lower magnitude of the BNT162b2-induced antibody response in children, vaccine-induced immunity in children target VOCs broadly and exhibit enhanced functionality that may contribute to the attenuation of disease.

The presence and reactivation of chronic viral infections such as Epstein-Barr virus (EBV), cytomegalovirus (CMV) and human immunodeficiency virus (HIV) have been proposed as potential contributors to Long COVID (LC), but studies in well-characterized post-acute cohorts of individuals with COVID-19 over a longer time course consistent with current case definitions of LC are limited.In a cohort of 280 adults with prior SARS-CoV-2 infection, we assessed the presence and types of LC symptoms and prior medical history (including COVID-19 history and HIV status), and performed serological testing for EBV and CMV using a commercial laboratory. We used covariate-adjusted binary logistic regression models to identify independent associations between variables and LC symptoms.We observed that LC symptoms such as fatigue and neurocognitive dysfunction at a median of 4months following initial diagnosis were independently associated with serological evidence suggesting recent EBV reactivation (early antigen-D [EA-D] IgG positivity) or high nuclear antigen (EBNA) IgG levels, but not with ongoing EBV viremia. Serological evidence suggesting recent EBV reactivation (EA-D IgG) was most strongly associated with fatigue (OR 2.12). Underlying HIV infection was also independently associated with neurocognitive LC (OR 2.5). Interestingly, participants who had serologic evidence of prior CMV infection were less likely to develop neurocognitive LC (OR 0.52).Overall, these findings suggest differential effects of chronic viral co-infections on the likelihood of developing LC and predicted distinct syndromic patterns. Further assessment during the acute phase of COVID-19 is warranted.Long-term Impact of Infection with Novel Coronavirus (LIINC); NCT04362150FUNDING. This work was supported by the National Institute of Allergy and Infectious Diseases NIH/NIAID 3R01AI141003-03S1 to TJ Henrich, R01AI158013 to M Gandhi and M Spinelli, K24AI145806 to P Hunt, and by the Zuckerberg San Francisco Hospital Department of Medicine and Division of HIV, Infectious Diseases, and Global Medicine. MJP is supported on K23 A137522 and received support from the UCSFBay Area Center for AIDS Research (P30-AI027763).

Understanding the differences in biomarker prevalence that may exist among diverse populations is invaluable to accurately forecast biomarker-driven clinical trial enrollment metrics and to advance inclusive research and health equity. This study evaluated the frequency and types ofAnalyses were conducted using real-world genomic data from adult patients with BC treated in an academic or community setting in the United States and whose tumor tissue was submitted for comprehensive genomic profiling.Of 36,151 patients with BC (median age, 58 years; 99% female), the breakdown by predicted genetic ancestry was 75% European, 14% African, 6% Central/South American, 3% East Asian, and 1% South Asian. We demonstrated that patients of African ancestry are less likely to have tumors that harborThis analysis established that tumor

PURPOSE Understanding the differences in biomarker prevalence that may exist among diverse populations is invaluable to accurately forecast biomarker-driven clinical trial enrollment metrics and to advance inclusive research and health equity. This study evaluated the frequency and types of PIK3CA mutations ( PIK3CAmut) detected in predicted genetic ancestry subgroups across breast cancer (BC) subtypes. METHODS Analyses were conducted using real-world genomic data from adult patients with BC treated in an academic or community setting in the United States and whose tumor tissue was submitted for comprehensive genomic profiling. RESULTS Of 36,151 patients with BC (median age, 58 years; 99% female), the breakdown by predicted genetic ancestry was 75% European, 14% African, 6% Central/South American, 3% East Asian, and 1% South Asian. We demonstrated that patients of African ancestry are less likely to have tumors that harbor PIK3CAmut compared with patients of European ancestry with estrogen receptor–positive/human epidermal growth factor receptor 2–negative (ER+/HER2–) BC (37% [949/2,593] v 44% [7,706/17,637]; q = 4.39E-11) and triple-negative breast cancer (8% [179/2,199] v 14% [991/7,072]; q = 6.07E-13). Moreover, we found that PIK3CAmut were predominantly composed of hotspot mutations, of which mutations at H1047 were the most prevalent across BC subtypes (35%-41% ER+/HER2– BC; 43%-61% HER2+ BC; 40%-59% triple-negative breast cancer). CONCLUSION This analysis established that tumor PIK3CAmut prevalence can differ among predicted genetic ancestries across BC subtypes on the basis of the largest comprehensive genomic profiling data set of patients with cancer treated in the United States. This study highlights the need for equitable representation in research studies, which is imperative to ensuring better health outcomes for all.

Background SARS-CoV-2 nucleocapsid antigen can be detected in plasma, but little is known about its performance as a diagnostic test for acute SARS-CoV-2 infection or infectious viral shedding among nonhospitalized individuals. Methods We used data generated from anterior nasal and blood samples collected in a longitudinal household cohort of SARS-CoV-2 cases and contacts. Participants were classified as true positives if polymerase chain reaction (PCR) positive for SARS-CoV-2 and as true negatives if PCR negative and seronegative. Infectious viral shedding was determined by the cytopathic effect from viral culture. Stratified by 7 days after symptom onset, we constructed receiver operating characteristic (ROC) curves to describe optimized accuracy (Youden index), optimized sensitivity, and specificity. Results Of 80 participants, 58 (73%) were true positives while 22 (27%) were true negatives. Using the manufacturer's cutoff of 1.25 pg/mL for evaluating infection, sensitivity was higher from 0 to 7 days (77.6% [95% confidence interval {CI}, 64%–88.2%]) than from 8 to 14 days (43.2% [95% CI, 31.1%–54.5%]) after symptom onset; specificity was unchanged at 100% (95% CI, 88.1%–100%). This test had higher sensitivity (100% [95% CI, 88.4%–100%]) and lower specificity (65% [95% CI, 40.8%–84.6%]) for infectious viral shedding as compared with infection, particularly within the first week of symptom onset. Although the presence of N-antigen correlated with infectious viral shedding (r = 0.63; P < .01), sensitivity still declined over time. Additional cutoffs from ROC curves were identified to optimize sensitivity and specificity. Conclusions We found that this SARS-CoV-2 N-antigen test was highly sensitive for detecting early but not late infectious viral shedding, making it a viable screening test for community-dwelling individuals to inform isolation practices.

Opioid-related harms disproportionately affect rural communities. Recent research-based policy changes have called for reductions in opioid prescribing and substitution of safe and effective alternatives to opioids for treating chronic pain, but such alternatives are often difficult to access in rural areas. Telehealth services can help address this disparity by bringing evidence-based, biopsychosocial chronic-pain services to rural and underserved patients with chronic pain. This article describes a 2-year pilot project for delivering chronic-pain care by pain specialists from central hubs at Veterans Health Administration (VA) medical centers to spokes at VA community-based outpatient clinics (CBOCs). The VA Puget Sound Pain Telehealth pilot program offered pain education classes, cognitive-behavioral therapy groups, opioid-safety education, and acupuncture education. The program delivered 501 encounters to patients from 1 hub to 4 CBOC spoke sites from 2016 to 2018, and supported training, administration, equipment acquisition, and grant-writing. The quality-improvement project was rolled out using existing local resources. We present initial findings about the patients who utilized Pain Telehealth, share lessons learned, and discuss future directions for expansion. (PsycInfo Database Record (c) 2021 APA, all rights reserved).

Restoring forest cover is a key action for mitigating climate change. Although monoculture plantations dominate existing commitments to restore forest cover, we lack a synthetic view of how carbon accumulates in these systems. Here, we assemble a global database of 4756 field-plot measurements from monoculture plantations across all forested continents. With these data, we model carbon accumulation in aboveground live tree biomass and examine the biological, environmental, and human drivers that influence this growth. Our results identify four-fold variation in carbon accumulation rates across tree genera, plant functional types, and biomes, as well as the key mediators (e.g., genus of tree, endemism of species, prior land use) of variation in these rates. Our nonlinear growth models advance our understanding of carbon accumulation in forests relative to mean annual rates, particularly during the next few decades that are critical for mitigating climate change.

Introduction: Collaborative care improves depression and anxiety outcomes. In this naturalistic, observational case study, we adapted an evidence-based depression collaborative care protocol for the assessment and treatment of posttraumatic stress disorder (PTSD) and sought to demonstrate that the protocol could be implemented in Veterans Affairs (VA) primary care. Method: Based on feedback from a content expert panel, clinical stakeholders, and a pilot study conducted in a postdeployment clinic, the original depression collaborative care protocol was modified to include PTSD assessment and support for PTSD medication adherence, self-management, and engagement in evidence-based PTSD care. Results: The modified program was implemented from November 2012 to March 2017, and 239 patients with PTSD were referred. Nearly two thirds (n = 185) enrolled, and they participated in the program for an average of 4 to 5 months and completed calls approximately once per month. Among patients with more than one assessment of clinical outcomes, 53.4% (n = 94) reported clinically significant improvement in depression on the Patient Health Questionnaire-9 (≥ 5-point decrease), and 42.2% (n = 35) reported clinically significant improvement on the PTSD Checklist (≥ 10-point decrease). Veterans and clinical staff described the modified collaborative care program positively in qualitative interviews. Discussion: Our findings suggest that a depression collaborative care program can be modified to support treatment of PTSD in primary care. The modified program was acceptable to both veterans and clinical staff and showed potential for positive clinical change in an uncontrolled quality improvement study. (PsycInfo Database Record (c) 2021 APA, all rights reserved).

Background In 2018, the Centers for Disease Control and Prevention and the Vermont Department of Health investigated an outbreak of multidrug-resistant Shigella sonnei infections in a retirement community that offered a continuum of care from independent living through skilled nursing care. The investigation identified 24 culture-confirmed cases. Isolates were resistant to trimethoprim-sulfamethoxazole, ampicillin, and ceftriaxone, and had decreased susceptibility to azithromycin and ciprofloxacin. Methods To evaluate clinical and microbiologic response, we reviewed inpatient and outpatient medical records for treatment outcomes among the 24 patients with culture-confirmed S. sonnei infection. We defined clinical failure as diarrhea (≥3 loose stools per day) for ≥1 day after treatment finished, and microbiologic failure as a stool culture that yielded S. sonnei after treatment finished. We used broth microdilution to perform antimicrobial susceptibility testing, and whole genome sequencing to identify resistance mechanisms. Results Isolates contained macrolide resistance genes mph(A) and erm(B) and had azithromycin minimum inhibitory concentrations above the Clinical and Laboratory Standards Institute epidemiological cutoff value of ≤16 µg/mL. Among 24 patients with culture-confirmed Shigella infection, 4 were treated with azithromycin; all had clinical treatment failure and 2 also had microbiologic treatment failure. Isolates were susceptible to ciprofloxacin but contained a gyrA mutation; 2 patients failed treatment with ciprofloxacin. Conclusions These azithromycin treatment failures demonstrate the importance of clinical breakpoints to aid clinicians in identifying alternative treatment options for resistant strains. Additionally, these treatment failures highlight a need for comprehensive susceptibility testing and systematic outcome studies, particularly given the emergence of multidrug-resistant Shigella among an expanding range of patient populations.

This study explored rates of non-attendance (i.e., non-initiation, inconsistent attendance, early discontinuation) in cognitive processing therapy (CPT) and other posttraumatic stress disorder (PTSD) focused individual and group psychotherapies (i.e., interventions with at least some PTSD and/or trauma-related content) and characterized veterans' self-reported reasons for non-attendance in these treatments. Baseline and 6-month follow-up data from the Telemedicine Outreach for PTSD study, a pragmatic randomized effectiveness trial conducted in 11 Veterans Health Administration community-based outpatient clinics, was examined (N = 265 veterans). Over 90% of veterans with a scheduled psychotherapy appointment attended at least one appointment by 6-month follow-up. Self-reported treatment completion was higher for veterans attending individual CPT (25%) than for those attending PTSD-focused individual (4.4%) and group psychotherapy (15.5%). However, rates of inconsistent attendance (13.3%) and early discontinuation (18.3%) were also higher in veterans attending CPT when compared to other forms of PTSD-focused psychotherapy (inconsistent attendance-individual: 2.2%, group: 6.9%; early discontinuation-individual: 14.6%; group: 10.3%). Issues with scheduling appointments was one of the most frequently reported reasons for non-attendance across treatments (> 20%). Logistical barriers, including transportation (CPT), therapy taking too much time (PTSD-focused individual psychotherapy) and not being able to afford counseling (PTSD-focused group psychotherapy), were also commonly cited (i.e., > 15%). Those scheduled to attend CPT (26%) or PTSD-focused individual psychotherapy (11%) also cited treatment efficacy concerns as a reason for non-attendance. Findings suggest logistical barriers, particularly scheduling convenient appointments, and beliefs about treatment may be important to address when engaging veterans in psychotherapy for PTSD. (PsycINFO Database Record (c) 2019 APA, all rights reserved).

Background Mutations in p110α, encoded by PIK3CA, are present in ~40% of HR+/HER2- BCs. GDC-0077, a PI3Kα-selective inhibitor and mutant PI3Kα degrader, elicits antitumor activity in PIK3CAmut preclinical models as a single agent and when combined with endocrine therapy (ET). New evidence suggests BCs harboring multiple PIK3CAmut exhibit increased signaling through the PI3K/AKT pathway and are more sensitive to PI3Kα inhibitors compared with BCs with a single PIK3CAmut. We report a preliminary analysis of PIK3CAmut status with clinical outcomes from an ongoing study of GDC-0077 alone or with ET (letrozole/fulvestrant) ± palbociclib (palbo) in pts with PIK3CAmut HR+/HER2- mBC (NCT03006172). Methods Detectable PIK3CAmut from local tumor tissue/blood-based assay or tumor tissue by cobas PIK3CA assay were required to enroll. Plasma-derived circulating tumor (ct) DNA was collected at baseline (BL), cycle 1 day 15 (C1D15), and C2D1 (in the cohort where GDC-0077 starts at C1D15) to detect PIK3CAmut. Paired tumor samples were analyzed for Ki67 and pAKT/pS6 expression by immunohistochemistry. Single vs multiple PIK3CAmut was correlated with the percentage of pharmacodynamic (PD) inhibition of Ki67/pAKT/pS6 expression; with the PIK3CAmut allele frequency ratio between BL and C1D15 or C2D1 (MAFr15); with best overall response (BOR, RECIST v1.1); and with time on treatment (TOT) in days. Statistical analyses: Kruskal-Wallis and Mann-Whitney-Wilcoxon for group and pairwise comparisons, respectively, and two-sample proportion testing for categorical comparisons. Results Data cutoff was 03/20/2020. PIK3CAmut were detected in 87/103 (84.5%) pts with BL ctDNA available for sequencing. Multiple PIK3CAmut were detected in 21/87 (24.1%) BL ctDNA samples: 9 from pts treated with single-agent GDC-0077; 8 from pts treated with GDC-0077 + letrozole/fulvestrant; and 4 from pts treated with GDC-0077 + letrozole/fulvestrant + palbo. The median number of lines of prior therapy for metastatic disease was not different between pts with multiple (3.0 lines) vs single (2.5 lines) PIK3CAmut detected at BL (p = 0.205). Median percentage inhibition of Ki67/pAKT/pS6 expression was greater in pts with multiple (-65.8, -70.3, -66.8%, respectively) vs single (-42.1, -34.1, -29.5%) PIK3CAmut detected at BL (p = 0.095, 0.002, 0.056). Median MAFr15 was lower in pts with multiple (MAFr15 0.01) vs single PIK3CAmut (MAFr15 0.15) detected at BL (p = 0.004). Of 73 pts with both BL ctDNA-detected PIK3CAmut and BOR data, 16/16 (100%) with multiple PIK3CAmut experienced BOR of partial response (PR) or stable disease (SD) while 42/57 (73.7%) with single PIK3CAmut experienced BOR of PR or SD (p = 0.051). No pts with multiple PIK3CAmut detected experienced a BOR of progressive disease. Median TOT was greater in pts with multiple PIK3CAmut (196 days) vs single PIK3CAmut (140.5 days) detected at BL, but this was not significant (p = 0.1804). Conclusions The fraction of pts in which multiple PIK3CAmut were identified from BL ctDNA in this HR+/HER2- mBC dataset (24.1%) was slightly higher than reported elsewhere. This may be due to the method of detection (blood vs tissue) and/or the definition of multiple PIK3CAmut used. Pts in which multiple PIK3CAmut were detected by ctDNA exhibited greater depth of PD biomarker inhibition in tumors and experienced PR/SD more often compared with pts in which only one PIK3CAmut was detected. However, no significant associations were observed with the number of prior lines of therapy for metastatic disease or TOT. The dataset is currently too small to assess the impact of different treatment regimens in this study but will be re-evaluated as the data mature. Citation Format: Komal Jhaveri, Dejan Juric, Andrea Varga, Nicolas Turner, Peter Schmid, Cristina Saura, Mafalda Oliveira, Ian E Krop, Kevin Kalinsky, Antoine Italiano, Erika Hamilton, Valentina Gambardella, Andrés Cervantes, Philippe L Bedard, Bonnie P Liu, Jessica W Chen, Junko Aimi, Stephanie Royer-Joo, Jennifer L Schutzman, Katherine E Hutchinson. Preliminary correlative analysis of clinical outcomes with PIK3CA mutation (mut) status from a phase I/Ib study of GDC-0077 in patients (pts) with hormone receptor-positive/HER2-negative metastatic breast cancer (HR+/HER2- mBC) [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS5-12.

Currently available mRNA vaccines are extremely safe and effective to prevent severe SARS-CoV-2 infections. However, the emergence of novel variants of concerns has highlighted the importance of high population-based vaccine rates to effectively suppress viral transmission and breakthrough infections. While initially left out from vaccine efforts, children have become one of the most affected age groups and are key targets to stop community and household spread. Antibodies are central for vaccine induced protection and emerging data points to the importance of additional Fc effector functions like opsononophagocytosis or cytotoxicity, particularly in the context of variants of concern that escape neutralizing antibodies. Here, we observed delayed induction and reduced magnitude of vaccine induced antibody titers in children 5-11 years receiving two doses of the age recommended 10 μg dose of the Pfizer SARS-CoV-2 BNT162b2 vaccine compared to adolescents (12-15 years) or adults receiving the 30 μg dose. Conversely, children mounted equivalent or more robust neutralization and opsonophagocytic functions at peak immunogenicity, pointing to a qualitatively more robust humoral functional response in children. Moreover, broad cross-variants of concern responses were observed across children, with enhanced IgM and parallel IgG cross-reactivity to variants of concern (VOCs) in children compared to adults. Collectively, these data argue that despite the lower magnitude of the BNT162b2 induced antibody response in children, vaccine induced immunity in children target VOCs broadly and exhibit enhanced functionality that may contribute to attenuation of disease.

Both mindfulness-based stress reduction (MBSR) and cognitive-behavioral therapy (CBT) are effective for chronic low back pain (CLBP), but little is known regarding who might benefit more from one than the other. Using data from a randomized trial comparing MBSR, CBT, and usual care (UC) for adults aged 20 to 70 years with CLBP (N = 297), we examined baseline characteristics that moderated treatment effects or were associated with improvement regardless of treatment. Outcomes included 8-week function (modified Roland Disability Questionnaire), pain bothersomeness (0-10 numerical rating scale), and depression (Patient Health Questionnaire-8). There were differences in the effects of CBT versus MBSR on pain based on participant gender (P = .03) and baseline depressive symptoms (P = .01), but the only statistically significant moderator after Bonferroni correction was the nonjudging dimension of mindfulness. Scores on this measure moderated the effects of CBT versus MBSR on both function (P = .001) and pain (P = .04). Pain control beliefs (P.001) and lower anxiety (P.001) predicted improvement regardless of treatment. Replication of these findings is needed to guide treatment decision-making for CLBP. TRIAL REGISTRATION: The trial and analysis plan were preregistered in ClinicalTrials.gov (Identifier: NCT01467843). PERSPECTIVE: Although few potential moderators and nonspecific predictors of benefits from CBT or MBSR for CLBP were statistically significant after adjustment for multiple comparisons, these findings suggest potentially fruitful directions for confirmatory research while providing reassurance that patients could reasonably expect to benefit from either treatment.

Objectives Transgender people-those whose gender identity differs from their sex assigned at birth-are at risk for health disparities resulting from stressors such as discrimination and violence. Transgender people report more drug use than cisgender people; however, it is unclear whether they have higher likelihood of drug use disorders. We examined whether transgender patients have increased likelihood of documented drug use disorders relative to cisgender patients in the national Veterans Health Administration (VA). Methods Electronic health record data were extracted for VA outpatients from 10/1/09 to 7/31/17. Transgender status and past-year documentation of drug use disorders (any, opioid, amphetamine, cocaine, cannabis, sedative, hallucinogen) were measured using diagnostic codes. Logistic regression models estimated odds ratios for drug use disorders among transgender compared to cisgender patients, adjusted for age, race/ethnicity and year. Effect modification by presence of ≥1 mental health condition was tested using multiplicative interaction. Results Among 8,872,793 patients, 8619 (0.1%) were transgender. Transgender patients were more likely than cisgender patients to have any drug use disorder (Adjusted Odds Ratio [aOR] 1.67, 95% confidence interval [CI] 1.53-1.83), amphetamine (aOR 2.22, 95% CI 1.82-2.70), cocaine (aOR 1.59, 95% CI 1.29-1.95), and cannabis (aOR 1.82, 95% CI 1.62-2.05) use disorders. There was no significant interaction by presence of ≥1 mental health condition. Conclusions Transgender VA patients may have higher likelihood of certain drug use disorders than cisgender VA patients, particularly amphetamine use disorder. Future research should explore mechanisms underlying disparities and potential barriers to accessing treatment and harm reduction services faced by transgender people.

Trauma-focused psychotherapies for posttraumatic stress disorder (PTSD) are not widely utilized. Clinicians report concerns that direct discussion of traumatic experiences could undermine the therapeutic alliance, which may negatively impact retention and outcome. Studies among adolescents with PTSD found no difference in alliance between trauma-focused and non-trauma-focused psychotherapies, but this has not been tested among adults. The present study is a secondary analysis of a randomized trial of collaborative care, also known as care management, for PTSD. We examined patient-reported therapeutic alliance among 117 veterans with PTSD who participated in cognitive processing therapy (CPT, now called CPT + A; n = 54) or non-trauma-focused supportive psychotherapy for PTSD (n = 73) at VA community outpatient clinics. We tested the hypothesis that alliance in CPT would be noninferior to (i.e., not significantly worse than) non-trauma-focused psychotherapy using patient ratings on the Revised Helping Alliance Questionnaire. Patients' therapeutic alliance scores were high across both groups (CPT: M = 5.13, SD = 0.71, 95% CI [4.96, 5.30]; non-trauma-focused psychotherapy: M = 4.89, SD = 0.64, 95% CI [4.73, 5.05]). The difference between groups (0.23, 95% CI [0.01, 0.48]) was less than the "noninferiority margin" based on suggested clinical cutoffs (0.58 points on a 1-6 scale). These results held even after adjusting for veterans' demographic and clinical characteristics and change in PTSD symptoms from baseline to follow-up. Although there are concerns that direct discussion of traumatic experiences could worsen therapeutic alliance, patients report similar levels of alliance in CPT and non-trauma-focused supportive psychotherapy. (PsycInfo Database Record (c) 2020 APA, all rights reserved).

Environmental pressures mean that non-profit organizations are having to transition to an internal culture that blends values supporting both social and economic objectives. The authors examined th...

Enteric pathogens, such as non-typhoidal Salmonella, Campylobacter and Escherichia coli, can reside in the intestinal tract of many animals, including livestock, companion animals, small mammals and reptiles. Often, these animals can appear healthy; nonetheless, humans can become infected after direct or indirect contact, resulting in a substantial illness burden. An estimated 14% of the 3.2 million illnesses that occur in the United States of America (USA) each year from such enteric pathogens are attributable to animal contact. Surveillance for enteric pathogens in the USA includes the compilation and interpretation of both laboratory and epidemiologic data. However, the authors feel that a collaborative, multisectoral and transdisciplinary - or One Health - approach is needed for data collection and analysis, at every level. In addition, they suggest that the future of enteric illness surveillance lies in the development of improved technologies for pathogen detection and characterisation, such as genomic sequencing and metagenomics. In particular, using whole-genome sequencing to compare genetic sequences of enteric pathogens from humans, food, animals and the environment, can help to predict antimicrobial resistance among these pathogens, determine their genetic relatedness and identify outbreaks linked to a common source. In this paper, the authors describe three recent, multi-state human enteric illness outbreaks linked to animal contact in the USA and discuss how integrated disease surveillance was essential to outbreak detection and response. Additional datasharing between public health and animal health laboratories and epidemiologists at the local, national, regional and international level may help to improve surveillance for emerging animal and human health threats and lead to new opportunities for prevention.

Ceftriaxone-resistant Salmonella enterica serotype Typhi (Typhi), the bacterium that causes typhoid fever, is a growing public health threat. Extensively drug-resistant (XDR) Typhi is resistant to ceftriaxone and other antibiotics used for treatment, including ampicillin, chloramphenicol, ciprofloxacin, and trimethoprim-sulfamethoxazole (1). In March 2018, CDC began enhanced surveillance for ceftriaxone-resistant Typhi in response to an ongoing outbreak of XDR typhoid fever in Pakistan. CDC had previously reported the first five cases of XDR Typhi in the United States among patients who had spent time in Pakistan (2). These illnesses represented the first cases of ceftriaxone-resistant Typhi documented in the United States (3). This report provides an update on U.S. cases of XDR typhoid fever linked to Pakistan and describes a new, unrelated cluster of ceftriaxone-resistant Typhi infections linked to Iraq. Travelers to areas with endemic Typhi should receive typhoid vaccination before traveling and adhere to safe food and water precautions (4). Treatment of patients with typhoid fever should be guided by antimicrobial susceptibility testing whenever possible (5), and clinicians should consider travel history when selecting empiric therapy.

Antimicrobial seed treatments recommended by Canadian guidance for sprouted vegetable production (2,000 ppm of hypochlorite for 15 to 20 min or 6 to 10% hydrogen peroxide for 10 min at room temperature) are not fully compliant with organic production principles. We investigated the effect of a sequential treatment consisting of a 10-min soak at 50°C in water followed by exposure to a 2.0% H2O2 plus 0.1% AcOH sanitizing solution against Escherichia coli O157:H7, Listeria monocytogenes, and Salmonella enterica inoculated onto alfalfa and radish seed. The sequential treatment was as effective as the recommended treatments and could reduce populations of all three species by a minimum of 3 log CFU/g using a reduced (1:2) ratio of seed to sanitizing solution and low concentrations of sanitizers approved for use in organic food production. However, the efficacy of all the treatments examined in this work was considerably reduced by storage of the seed for 4 weeks at either 11 or 75% relative humidity prior to treatment and assessment. None of the treatments could eradicate the target pathogens from seed, irrespective of time elapsed since inoculation. The results of this work suggest that the effect of storage should be considered in the assessment of antimicrobial treatments for sprouting vegetable seed. HIGHLIGHTS

Inter-organizational partnerships are known to encounter various tensions, including efficiency versus inclusiveness, internal versus external legitimacy, flexibility versus stability, and accounta...

PURPOSE: We studied effects of age and horizontal duction on deformation of the optic nerve (ON) head and peripapillary retina as reflected by displacement of vascular landmarks to explore the influence of adduction tethering. DESIGN: Cross-sectional study. METHODS: Setting: University. Study Population: Single eyes of 20 healthy young adults (average age 23.9±3.9 SD) years were compared to 20 older subjects (average age 61.4±9.3) years. Observational Procedure: The disc and peripapillary retina were imaged by scanning laser ophthalmoscopy in central gaze, and 35° abd- and adduction. Main Outcome Measure: Deformations of the disc and adjacent PPR were measured by comparing positions of epipapillary and epiretinal blood vessels. RESULTS: Vessels within the ONH of younger subjects shifted temporally during adduction and nasally during abduction. Displacement of the nasal hemi-disc in adduction was greater at 38.5±1.7μm (SEM) than the temporal half at 4.1±2.1μm (P

As SARS-CoV-2 is known to invade neural cell mitochondria, a plasma system for quantifying central nervous system proteins in living humans was used to investigate neuropathogenic mechanisms of long-COVID-19.SARS-CoV-2 proteins and mitochondrial proteins (MPs) in enriched plasma neuron-derived extracellular vesicles (NDEVs) and astrocyte-derived EVs (ADEVs) were quantified in resolved acute COVID-19 without post-acute sequelae of SARS-CoV-2 (PASC), PASC without neuropsychiatric manifestations (NP), PASC with NP and healthy controls.NDEV and ADEV mean levels of SARS-CoV-2 S1 and nucleocapsid (N) proteins were higher in all PASC sub-groups than controls, but only N levels were higher in PASC with than without NP. Exosome marker CD81-normalized NDEV mean levels of subunit 6 of MP respiratory chain complex I and subunit 10 of complex III, and neuroprotective MPs Humanin and mitochondrial open-reading frame of the 12S rRNA-c (MOTS-c) all were decreased significantly in PASC with NP but not in PASC without NP relative to controls. NDEV levels of MPs voltage-dependent anion-selective channel protein 1 (VDAC1) and N-methyl-D-aspartate receptor 1 (NMDAR1) were decreased in PASC without and with NP, whereas those of calcium channel MPs mitochondrial calcium uniporter (MCU), sodium/calcium exchanger (NCLX) and leucine zipper EF-hand containing transmembrane 1 protein (LETM1) were decreased only in PASC with NP. ADEV levels of MCU and NCLX only were increased in PASC without and with NP.Abnormal NDEV and ADEV levels of SARS-CoV-2 N and S1 protein and MPs correlate with NP and may be biomarkers for long-COVID prognostics and therapeutic trials. ANN NEUROL 2022;91:772-781.

BackgroundLimited data are available on the long-term clinical and immunologic consequences of SARS-CoV-2 infection in people with HIV (PWH).MethodsWe measured SARS-CoV-2 specific humoral and cellular responses in people with and without HIV recovering from COVID-19 (n=39 and n=43, respectively) using binding antibody, surrogate virus neutralization, intracellular cytokine staining, and inflammatory marker assays. We identified individuals experiencing post-acute sequelae of SARS-CoV-2 infection (PASC) and evaluated immunologic parameters. We used linear regression and generalized linear models to examine differences by HIV status in the magnitude of inflammatory and virus-specific antibody and T cell responses, as well as differences in the prevalence of PASC.ResultsAmong PWH, we found broadly similar SARS-CoV-2-specific antibody and T cell responses as compared with a well-matched group of HIV-negative individuals. PWH had 70% lower relative levels of SARS-CoV-2 specific memory CD8+ T cells (p=0.007) and 53% higher relative levels of PD-1+ SARS-CoV-2 specific CD4+ T cells (p=0.007). Higher CD4/CD8 ratio was associated with lower PD-1 expression on SARS-CoV-2 specific CD8+ T cells (0.34-fold effect, p=0.02). HIV status was strongly associated with PASC (odds ratio 4.01, p=0.008), and levels of certain inflammatory markers (IL-6, TNF-alpha, and IP-10) were associated with persistent symptoms.ConclusionsWe identified potentially important differences in SARS-CoV-2 specific CD4+ and CD8+ T cells in PWH and HIV-negative participants that might have implications for long-term immunity conferred by natural infection. HIV status strongly predicted the presence of PASC. Larger and more detailed studies of PASC in PWH are urgently needed.

Genomic surveillance is a critical tool for tracking emerging variants of SARS-CoV-2 (the virus that causes COVID-19), which can exhibit characteristics that potentially affect public health and clinical interventions, including increased transmissibility, illness severity, and capacity for immune escape. During June 2021-January 2022, CDC expanded genomic surveillance data sources to incorporate sequence data from public repositories to produce weighted estimates of variant proportions at the jurisdiction level and refined analytic methods to enhance the timeliness and accuracy of national and regional variant proportion estimates. These changes also allowed for more comprehensive variant proportion estimation at the jurisdictional level (i.e., U.S. state, district, territory, and freely associated state). The data in this report are a summary of findings of recent proportions of circulating variants that are updated weekly on CDC's COVID Data Tracker website to enable timely public health action.