Cost-outcome analysis of HIV testing and counseling, linkage, and defaulter tracing services in Bukoba, Tanzania.

Effective services along the HIV continuum of care from HIV testing and counseling to linkage, and from linkage to antiretroviral therapy (ART) initiation and retention, are key to improved health outcomes of persons living with HIV. A comprehensive analysis of the costs and outcomes of cascade services is needed to help allocate and prioritize resources to achieve UNAIDS targets. We evaluated the costs and population-level impact of a community-wide, integrated scale-up of testing, linkage, and defaulter-tracing programs implemented in Bukoba Municipal Council, Tanzania. Costs per identified HIV-positive client for provider-initiated, and home- and venue-based testing and counseling were $92.64 United States dollars (USD), $256.33 USD, and $281.57 USD, respectively. Costs per patient linked to HIV care and ART were $47.69 USD and $74.12 USD, respectively, during all ART-eligibility periods combined. Costs per defaulter traced and returned to HIV care were $47.56 USD and $206.77 USD, respectively. The provider-initiated testing and counseling was the most cost-effective modality. Testing approaches targeted to populations groups and geographic location with high testing positivity rates may improve the overall efficiency of testing services. The expansion of ART eligibility criteria and high linkage rate also result in efficiency gains and economies of scale of linkage services.

Endometriosis and menopausal hormone therapy impact the hysterectomy-ovarian cancer association.

OBJECTIVE: To evaluate the association between hysterectomy and ovarian cancer, and to understand how hormone therapy (HT) use and endometriosis affect this association. METHODS: We conducted a pooled analysis of self-reported data from 11 case-control studies in the Ovarian Cancer Association Consortium (OCAC). Women with (n = 5350) and without ovarian cancer (n = 7544) who never used HT or exclusively used either estrogen-only therapy (ET) or estrogen+progestin therapy (EPT) were included. Risk of invasive epithelial ovarian cancer adjusted for duration of ET and EPT use and stratified on history of endometriosis was determined using odds ratios (ORs) with 95% confidence intervals (CIs). RESULTS: Overall and among women without endometriosis, there was a positive association between ovarian cancer risk and hysterectomy (OR = 1.19, 95% CI 1.09-1.31 and OR = 1.20, 95% CI 1.09-1.32, respectively), but no association upon adjusting for duration of ET and EPT use (OR = 1.04, 95% CI 0.94-1.16 and OR = 1.06, 95% CI 0.95-1.18, respectively). Among women with a history of endometriosis, there was a slight inverse association between hysterectomy and ovarian cancer risk (OR = 0.93, 95% CI 0.69-1.26), but this association became stronger and statistically significant after adjusting for duration of ET and EPT use (OR = 0.69, 95% CI 0.48-0.99). CONCLUSIONS: The hysterectomy-ovarian cancer association is complex and cannot be understood without considering duration of ET and EPT use and history of endometriosis. Failure to take these exposures into account in prior studies casts doubt on their conclusions. Overall, hysterectomy is not risk-reducing for ovarian cancer, however the inverse association among women with endometriosis warrants further investigation.

Chemogenetic inhibition of corticostriatal circuits reduces cued reinstatement of methamphetamine seeking.

Methamphetamine (meth) causes enduring changes within the medial prefrontal cortex (mPFC) and the nucleus accumbens (NA). Projections from the mPFC to the NA have a distinct dorsal-ventral distribution, with the prelimbic (PL) mPFC projecting to the NAcore, and the infralimbic (IL) mPFC projecting to the NAshell. Inhibition of these circuits has opposing effects on cocaine relapse. Inhibition of PL-NAcore reduces cued reinstatement of cocaine seeking and IL-NAshell inhibition reinstates cocaine seeking. Meth, however, exhibits a different profile, as pharmacological inhibition of either the PL or IL decrease cued reinstatement of meth-seeking. The potentially opposing roles of the PL-NAcore and IL-NAshell projections remain to be explored in the context of cued meth seeking. Here we used an intersectional viral vector approach that employs a retrograde delivery of Cre from the NA and Cre-dependent expression of DREADD in the mPFC, in both male and female rats to inhibit or activate these parallel pathways. Inhibition of the PL-NAcore circuit reduced cued reinstatement of meth seeking under short and long-access meth self-administration and after withdrawal with and without extinction. Inhibition of the IL-NAshell also decreased meth cued reinstatement. Activation of the parallel circuits was without an effect. These studies show that inhibition of the PL-NAcore or the IL-NAshell circuits can inhibit reinstated meth seeking. Thus, the neural circuitry mediating cued reinstatement of meth seeking is similar to cocaine in the dorsal, but not ventral, mPFC-NA circuit.

Selective Valve Removal for Melody Valve Endocarditis: Practice Variations in a Multicenter Experience.

Guidelines for management of Melody transcatheter pulmonary valve (TPV) infective endocarditis (IE) are lacking. We aimed to identify factors associated with surgical valve removal versus antimicrobial therapy in Melody TPV IE. Multicenter retrospective analysis of all patients receiving Melody TPV from 10/2010 to 3/2019 was performed to identify cases of IE. Surgical explants versus non-surgical cases were compared. Of the 663 Melody TPV implants, there were 66 cases of IE in 59 patients (59/663, 8.8%). 39/66 (59%) were treated with IV antimicrobials and 27/66(41%) underwent valve explantation. 26/59 patients (44%) were treated medically without explantation or recurrence with average follow-up time of 3.5 years (range:1-9). 32% of Streptococcus cases, 53% of MSSA, and all MRSA cases were explanted. 2 of the 4 deaths had MSSA. CART analysis demonstrated two important parameters associated with explantation: a peak echo gradient ≥ 47 mmHg at IE diagnosis(OR 10.6, p < 0.001) and a peak echo gradient increase of > 24 mmHg compared to baseline (OR 6.7, p = 0.01). Rates of explantation varied by institution (27 to 64%). In our multicenter experience, 44% of patients with Melody IE were successfully medically treated without valve explantation or recurrence. The degree of valve stenosis at time of IE diagnosis was strongly associated with explantation. Rates of explantation varied significantly among the institutions.

Aberrant Cerebellar Resting-State Functional Connectivity Related to Reading Performance in Struggling Readers.

Reading is a critical neurodevelopmental skill for school-aged children, which requires a distributed network of brain regions including the cerebellum. However, we do not know how functional connectivity between the cerebellum and other brain regions contributes to reading. Here we used resting-state functional connectivity to understand the cerebellum's role in decoding, reading speed, and comprehension in a group of struggling readers (RD) and a group of adolescents and children with typical reading abilities (TD). We observed an increase in functional connectivity between the sensorimotor network and the left angular gyrus, left lateral occipital cortex, and right inferior frontal gyrus in the RD group relative to the TD group. Additionally, functional connectivity between the cerebellum network and the precentral gyrus was decreased and was related to reading fluency in the RD group. Seed-based analysis revealed increased functional connectivity between crus 1, lobule 6, and lobule 8 of the cerebellum and brain regions related to the default mode network and the motor system for the RD group. We also found associations between reading performance and the functional connectivity between lobule 8 of the cerebellum and the left angular gyrus for both groups, with stronger relationships in the TD group. Specifically, the RD group displayed a positive relationship between functional connectivity, whereas the TD group displayed the opposite relationship. These results suggest that the cerebellum is involved in multiple components of reading performance and that functional connectivity differences observed in the RD group may contribute to poor reading performance.

Research participant understanding and engagement in an institutional, self-consent biobank model.

The number of institutional and governmental biobanks and the target enrollment sizes of modern biobanks are increasing, affording more opportunities for the public to participate in biobanking efforts. In parallel with these expansions are pressures to increase the efficiency of obtaining informed consent using shorter consent forms that cover a broader scope of research and increasingly include provisions for return of research or clinical genetic test results to participants. Given these changes, how well these participants understand genetics, their level of understanding of what they are consenting to, and their wishes to engage longitudinally and receive biobank results are not well understood. We surveyed participants in a large, medical system-based biobank who had enrolled through a two-page, self-consent process about their baseline knowledge of genetics, understanding and recall of the consent process, wishes for future contact and engagement, and level of interest in receiving clinical genetic testing results. A total of 856 consented persons participated in the survey (67% women; 67% white). Participants' general reported genetics knowledge was relatively high (mean 11.60 of 15 questions answered correctly) as was recall of key elements from the two-page consent form. Overall participant enthusiasm for future contact by the biobank and for receiving clinical genetic testing results was high. The use of a two-page, self-consent process in a large, institutional biobank resulted in high levels of consent recall and enthusiasm for future ongoing engagement and receipt of genetic testing results by participants.

Screening for Vitamin D Deficiency in Adults: Updated Evidence Report and Systematic Review for the US Preventive Services Task Force.

Importance: Low serum vitamin D levels have been associated with adverse clinical outcomes; identifying and treating deficiency may improve outcomes. Objective: To review the evidence about screening for vitamin D deficiency in adults. Data Sources: PubMed, EMBASE, the Cochrane Library, and trial registries through March 12, 2020; bibliographies from retrieved articles, outside experts, and surveillance of the literature through November 30, 2020. Study Selection: Fair- or good-quality, English-language randomized clinical trials (RCTs) of screening with serum 25-hydroxyvitamin D (25[OH]D) compared with no screening, or treatment with vitamin D (with or without calcium) compared with placebo or no treatment conducted in nonpregnant adults; nonrandomized controlled intervention studies for harms only. Treatment was limited to studies enrolling or analyzing participants with low serum vitamin D levels. Data Extraction and Synthesis: Two reviewers assessed titles/abstracts and full-text articles, extracted data, and assessed study quality; when at least 3 similar studies were available, meta-analyses were conducted. Main Outcomes and Measures: Mortality, incident fractures, falls, diabetes, cardiovascular events, cancer, depression, physical functioning, and infection. Results: Forty-six studies (N = 16 205) (77 publications) were included. No studies directly evaluated the health benefits or harms of screening. Among community-dwelling populations, treatment was not significantly associated with mortality (pooled absolute risk difference [ARD], 0.3% [95% CI, -0.6% to 1.1%]; 8 RCTs, n = 2006), any fractures (pooled ARD, -0.3% [95% CI, -2.1% to 1.6%]; 6 RCTs, n = 2186), incidence of diabetes (pooled ARD, 0.1% [95% CI, -1.3% to 1.6%]; 5 RCTs, n = 3356), incidence of cardiovascular disease (2 RCTs; hazard ratio, 1.00 [95% CI, 0.74 to 1.35] and 1.09 [95% CI, 0.68 to 1.76]), incidence of cancer (2 RCTs; hazard ratio, 0.97 [95% CI, 0.68 to 1.39] and 1.01 [95% CI, 0.65 to 1.58], or depression (3 RCTs, various measures reported). The pooled ARD for incidence of participants with 1 or more falls was -4.3% (95% CI, -11.6% to 2.9%; 6 RCTs). The evidence was mixed for the effect of treatment on physical functioning (2 RCTs) and limited for the effect on infection (1 RCT). The incidence of adverse events and kidney stones was similar between treatment and control groups. Conclusions and Relevance: No studies evaluated the direct benefits or harms of screening for vitamin D deficiency. Among asymptomatic, community-dwelling populations with low vitamin D levels, the evidence suggests that treatment with vitamin D has no effect on mortality or the incidence of fractures, falls, depression, diabetes, cardiovascular disease, cancer, or adverse events. The evidence is inconclusive about the effect of treatment on physical functioning and infection.

Screening for Lung Cancer With Low-Dose Computed Tomography: Updated Evidence Report and Systematic Review for the US Preventive Services Task Force.

Importance: Lung cancer is the leading cause of cancer-related death in the US. Objective: To review the evidence on screening for lung cancer with low-dose computed tomography (LDCT) to inform the US Preventive Services Task Force (USPSTF). Data Sources: MEDLINE, Cochrane Library, and trial registries through May 2019; references; experts; and literature surveillance through November 20, 2020. Study Selection: English-language studies of screening with LDCT, accuracy of LDCT, risk prediction models, or treatment for early-stage lung cancer. Data Extraction and Synthesis: Dual review of abstracts, full-text articles, and study quality; qualitative synthesis of findings. Data were not pooled because of heterogeneity of populations and screening protocols. Main Outcomes and Measures: Lung cancer incidence, lung cancer mortality, all-cause mortality, test accuracy, and harms. Results: This review included 223 publications. Seven randomized clinical trials (RCTs) (N = 86 486) evaluated lung cancer screening with LDCT; the National Lung Screening Trial (NLST, N = 53 454) and Nederlands-Leuvens Longkanker Screenings Onderzoek (NELSON, N = 15 792) were the largest RCTs. Participants were more likely to benefit than the US screening-eligible population (eg, based on life expectancy). The NLST found a reduction in lung cancer mortality (incidence rate ratio [IRR], 0.85 [95% CI, 0.75-0.96]; number needed to screen [NNS] to prevent 1 lung cancer death, 323 over 6.5 years of follow-up) with 3 rounds of annual LDCT screening compared with chest radiograph for high-risk current and former smokers aged 55 to 74 years. NELSON found a reduction in lung cancer mortality (IRR, 0.75 [95% CI, 0.61-0.90]; NNS to prevent 1 lung cancer death of 130 over 10 years of follow-up) with 4 rounds of LDCT screening with increasing intervals compared with no screening for high-risk current and former smokers aged 50 to 74 years. Harms of screening included radiation-induced cancer, false-positive results leading to unnecessary tests and invasive procedures, overdiagnosis, incidental findings, and increases in distress. For every 1000 persons screened in the NLST, false-positive results led to 17 invasive procedures (number needed to harm, 59) and fewer than 1 person having a major complication. Overdiagnosis estimates varied greatly (0%-67% chance that a lung cancer was overdiagnosed). Incidental findings were common, and estimates varied widely (4.4%-40.7% of persons screened). Conclusions and Relevance: Screening high-risk persons with LDCT can reduce lung cancer mortality but also causes false-positive results leading to unnecessary tests and invasive procedures, overdiagnosis, incidental findings, increases in distress, and, rarely, radiation-induced cancers. Most studies reviewed did not use current nodule evaluation protocols, which might reduce false-positive results and invasive procedures for false-positive results.

Prácticas de retiro del equipo de protección personal para personal sanitario.

RESUMENCuando se retira el equipo de protección personal (EPP), los patógenos pueden transferirse desde el EPP al cuerpo de los trabajadores de la salud, poniendo en riesgo de exposición e infección tanto a ellos mismos como a sus pacientes. Entre marzo de 2017 y abril de 2018 se observaron las prácticas de retirada del EPP del personal sanitario que atendía pacientes con infecciones respiratorias virales en un hospital de atención de enfermedades agudas. Un observador capacitado registró el desempeño del personal sanitario cuando retiraba el EPP dentro de las habitaciones de los pacientes, utilizando una lista de verificación predefinida basada en las directrices de los Centros para el Control y Prevención de Enfermedades (Centers for Disease Control and Prevention, CDC). Se observaron 162 prácticas de retirada durante el cuidado de 52 pacientes infectados con patógenos virales respiratorios. De estos 52 pacientes, 30 estaban en aislamiento por gota y contacto, 21 en aislamiento por gota y uno en aislamiento de contacto. En general, en 90% de los casos la retirada del EPP observada se realizó de manera incorrecta, ya sea en cuanto a la secuencia de retirada, la técnica de retirada o el uso del EPP apropiado. Los errores más comunes consistieron en quitarse la bata por adelante, retirar la pantalla facial de la mascarilla y tocar superficies y EPP potencialmente contaminados durante el proceso. Las desviaciones del protocolo recomendado para retirar el EPP son comunes y pueden aumentar el potencial de contaminación de la ropa o la piel del personal sanitario después de proporcionar atención. Existe una clara necesidad de cambiar el enfoque utilizado para capacitar al personal en las prácticas de retirada del EPP.

Surgical Management of Lumbar Radiculopathy: a Systematic Review.

BACKGROUND: Lumbar radiculopathy is characterized by radiating pain with or without motor weakness or sensory disturbances; the point prevalence ranges from 1.6 to 13.4%. The objective of this review was to determine the efficacy, safety, and cost of surgical versus nonsurgical management of symptomatic lumbar radiculopathy in adults. METHODS: We searched PubMed from January 1, 2007, to April 10, 2019 with hand searches of systematic reviews for studies prior to 2007. One reviewer extracted data and a second checked for accuracy. Two reviewers completed independent risk of bias and strength of evidence ratings. RESULTS: We included seven RCTs (N = 1158) and three cost-effectiveness analysis. Surgery reduced leg pain by 6 to 26 points more than nonsurgical interventions as measured on a 0- to 100-point visual analog scale of pain at up to 26 weeks follow-up; differences between groups did not persist at 1 year or later. The evidence was somewhat mixed for function and disability in follow-up through 26 weeks (standardized mean difference [SMD] - 0.16 (95% CI, - 0.30 to - 0.03); minimal differences were observed at 2 years (SMD - 0.06 (95% CI, - 0.20 to 0.07). There were similar improvements in quality of life, neurologic symptoms, and return to work. No surgical deaths occurred and surgical morbidity was infrequent. The incidence of reoperations ranged from 0 to 10%. The average cost per quality-adjusted life year gained from a healthcare payor perspective ranged from $51,156 to $83,322 for surgery compared to nonsurgical interventions. DISCUSSION: Most findings are based on a body of RCT evidence graded as low to very low certainty. Compared with nonsurgical interventions, surgery probably reduces pain and improves function in the short- and medium-term, but this difference does not persist in the long-term. Although surgery appears to be safe, it may or may not be cost-effective depending on a decision maker's willingness to pay threshold.

Correction to: Comparative Effectiveness of Combining MTX with Biologic Drug Therapy Versus Either MTX or Biologics Alone for Early Rheumatoid Arthritis in Adults: a Systematic Review and Network Meta-analysis.

This article has been amended to include open access.

Sex Differences in HIV Testing - 20 PEPFAR-Supported Sub-Saharan African Countries, 2019.

Despite progress toward controlling the human immunodeficiency virus (HIV) epidemic, testing gaps remain, particularly among men and young persons in sub-Saharan Africa (1). This observational study used routinely collected programmatic data from 20 African countries reported to the U.S. President's Emergency Plan for AIDS Relief (PEPFAR) from October 2018 to September 2019 to assess HIV testing coverage and case finding among adults (defined as persons aged ≥15 years). Indicators included number of HIV tests conducted, number of HIV-positive test results, and percentage positivity rate. Overall, the majority of countries reported higher HIV case finding among women than among men. However, a slightly higher percentage positivity was recorded among men (4.7%) than among women (4.1%). Provider-initiated counseling and testing (PITC) in health facilities identified approximately two thirds of all new cases, but index testing had the highest percentage positivity in all countries among both sexes. Yields from voluntary counseling and testing (VCT) and mobile testing varied by sex and by country. These findings highlight the need to identify and implement the most efficient strategies for HIV case finding in these countries to close coverage gaps. Strategies might need to be tailored for men who remain underrepresented in the majority of HIV testing programs.

Defining treatment-resistant depression.

BACKGROUND: Varying conceptualizations of treatment-resistant depression (TRD) have made translating research findings or systematic reviews into clinical practice guidelines challenging and inconsistent. METHODS: We conducted a review for the Centers for Medicare & Medicaid Services and the Agency for Healthcare Research and Quality to clarify how experts and investigators have defined TRD and to review systematically how well this definition comports with TRD definitions in clinical trials through July 5, 2019. RESULTS: We found that no consensus definition existed for TRD. The most common TRD definition for major depressive disorder required a minimum of two prior treatment failures and confirmation of prior adequate dose and duration. The most common TRD definition for bipolar disorder required one prior treatment failure. No clear consensus emerged on defining adequacy of either dose or duration. Our systematic review found that only 17% of intervention studies enrolled samples meeting the most frequently specified criteria for TRD. Depressive outcomes and clinical global impressions were commonly measured; functional impairment and quality-of-life tools were rarely used. CONCLUSIONS: Two key steps are critical to advancing TRD research: (a) Developing a consensus definition of TRD that addresses how best to specify the number of prior treatment failures and the adequacy of dose and duration; and (b) identifying a core package of outcome measures that can be applied in a standardized manner. Our recommendations about stronger approaches to designing and conducting TRD research will foster better evidence to translate into clearer guidelines for treating patients with this serious condition.

Comparative Effectiveness of Combining MTX with Biologic Drug Therapy Versus Either MTX or Biologics Alone for Early Rheumatoid Arthritis in Adults: a Systematic Review and Network Meta-analysis.

BACKGROUND: Comparative effectiveness of early rheumatoid arthritis (RA) treatments remains uncertain. PURPOSE: Compare benefits and harms of biologic drug therapies for adults with early RA within 1 year of diagnosis. DATA SOURCES: English language articles from the 2012 review to October 2017 identified through MEDLINE, Cochrane Library and International Pharmaceutical Abstracts, gray literature, expert recommendations, reference lists of published literature, and supplemental evidence data requests. STUDY SELECTION: Two persons independently selected studies based on predefined inclusion criteria. DATA EXTRACTION: One reviewer extracted data; a second reviewer checked accuracy. Two independent reviewers assigned risk of bias ratings. DATA SYNTHESIS: We identified 22 eligible studies with 9934 participants. Combination therapy with tumor necrosis factor (TNF) or non-TNF biologics plus methotrexate (MTX) improved disease control, remission, and functional capacity compared with monotherapy of either MTX or a biologic. Network meta-analyses found higher ACR50 response (50% improvement) for combination therapy of biologic plus MTX than for MTX monotherapy (relative risk range 1.20 [95% confidence interval (CI), 1.04 to 1.38] to 1.57 [95% CI, 1.30 to 1.88]). No significant differences emerged between treatment discontinuation rates because of adverse events or serious adverse events. Subgroup data (disease activity, prior therapy, demographics, serious conditions) were limited. LIMITATIONS: Trials enrolled almost exclusively selected populations with high disease activity. Network meta-analyses were derived from indirect comparisons relative to MTX due to the dearth of head-to-head studies comparing interventions. No eligible data on biosimilars were found. CONCLUSIONS: Qualitative and network meta-analyses suggest that the combination of MTX with TNF or non-TNF biologics reduces disease activity and improves remission when compared with MTX monotherapy. Overall adverse event and discontinuation rates were similar between treatment groups. REGISTRATION: PROSPERO (available at http://www.crd.york.ac.uk/PROSPERO/display_record.php?ID=CRD42017079260 ).

Threefold Increases in Population HIV Viral Load Suppression Among Men and Young Adults - Bukoba Municipal Council, Tanzania, 2014-2017.

Reducing HIV-related morbidity and mortality, and effectively eliminating HIV transmission risk, depends on use of antiretroviral therapy (ART) to achieve and maintain viral load suppression (VLS)* (1,2). By 2020, sub-Saharan African countries are working to achieve VLS among 90% of persons using ART and 73% of all persons living with HIV infection (1). In Tanzania, a country with 1.4 million persons with HIV infection, 49.6% of HIV-positive persons aged 15-49 years had achieved VLS in 2017, including only 21.5% of men and 44.6% of women aged 25-29 years (3). To identify interventions that might increase VLS in Tanzania, and reduce VLS-associated sex and age-group disparities, the Bukoba Combination Prevention Evaluation (BCPE) scaled up new HIV testing, linkage to care, and retention on ART interventions throughout Bukoba Municipal Council (Bukoba), Tanzania, during October 2014-March 2017 (4,5). Located on the western shore of Lake Victoria, Bukoba is a mixed urban and rural municipality of 150,000 persons and capital of Kagera Region. Of the 31 regions of Tanzania, Kagera has the fourth highest prevalence of HIV infection (6.8%) among residents aged 15-49 years (3). CDC analyzed data from BCPE preintervention and postintervention surveys and found that VLS prevalence among HIV-positive Bukoba residents aged 18-49 years increased approximately twofold overall (from 28.6% to 64.8%) and among women (33.3% to 67.8%) and approximately threefold among men (20.5% to 59.1%) and young adults aged 18-29 years (15.6% to 56.7%). During 2017, BCPE facility-based testing and linkage interventions were approved as new service delivery models by the Tanzania Ministry of Health, Community Development, Gender, Elderly and Children (4,5). After a successful rollout to 208 facilities in 11 regions in 2018, BCPE interventions are being scaled up in all regions of Tanzania in 2019 with support from the United States President's Emergency Plan for AIDS Relief (PEPFAR).†.

Personal protective equipment doffing practices of healthcare workers.

During the doffing of personal protective equipment (PPE), pathogens can be transferred from the PPE to the bodies of healthcare workers (HCWs), putting HCWs and patients at risk of exposure and infection. PPE doffing practices of HCWs who cared for patients with viral respiratory infections were observed at an acute care hospital from March 2017 to April 2018. A trained observer recorded doffing performance of HCWs inside the patient rooms using a pre-defined checklist based on the Centers for Disease Control and Prevention (CDC) guideline. Doffing practices were observed 162 times during care of 52 patients infected with respiratory viral pathogens. Out of the 52 patients, 30 were in droplet and contact isolation, 21 were in droplet isolation, and 1 was in contact isolation. Overall, 90% of observed doffing was incorrect, with respect to the doffing sequence, doffing technique, or use of appropriate PPE. Common errors were doffing gown from the front, removing face shield of the mask, and touching potentially contaminated surfaces and PPE during doffing. Deviations from the recommended PPE doffing protocol are common and can increase potential for contamination of the HCW's clothing or skin after providing care. There is a clear need to change the approach used to training HCWs in PPE doffing practices.

Gene network variation and alternative paths to convergent evolution in turtles.

Diversification of the turtle's shell comprises remarkable phenotypic transformations. For instance, two divergent species convergently evolved shell-closing systems with shoulder blade (scapula) segments that enable coordinated movements with the shell. We expected these unusual structures to originate via similar changes in underlying gene networks, as skeletal segment formation is an evolutionarily conserved developmental process. We tested this hypothesis by comparing transcriptomes of scapula tissue across three stages of embryonic development in three emydid turtles from natural populations. We found that alternative strategies for skeletal segmentation were associated with interspecific differences in gene co-expression networks. Notably, mesenchyme homeobox 2 (MEOX2) and HOXA3-5 were central hubs driving the activity of 2,806 genes in a candidate network for scapula segmentation, albeit in only one species. Even so, scapula muscle overgrowth corresponded to the activity of similar myogenic networks in both species. This and other derived developmental processes were not observed in the third species, which displayed the ancestral (unsegmented) scapula condition. Differential gene expression tests against this reference lineage supported histological and network analyses. Our findings illustrate that molecular underpinnings of convergent evolution, including during the diversification of the atypical turtle "body plan," are influenced by variation in underlying developmental processes.

Regionally Specific Effects of Oxytocin on Reinstatement of Cocaine Seeking in Male and Female Rats.

Background: Oxytocin reduces cued reinstatement of cocaine seeking in male and female rats, but the underlying neurobiology has not been uncovered. The majority of effort on this task has focused on oxytocin and dopamine interactions in the nucleus accumbens core. The nucleus accumbens core is a key neural substrate in relapse, and oxytocin administration in the nucleus accumbens core reduces reinstatement to methamphetamine cues. Further, the nucleus accumbens core has strong glutamatergic innervation from numerous regions including the prefrontal cortex. Thus, we hypothesize that oxytocin regulates presynaptic glutamate terminals in the nucleus accumbens core, thereby affecting reinstatement. Methods: To begin to evaluate this hypothesis, we examined the effects of intra-nucleus accumbens core oxytocin on extracellular glutamate levels in this region. We next determined if direct infusion of oxytocin into the nucleus accumbens core could attenuate cued reinstatement of cocaine seeking in a manner dependent on metabotropic glutamate 2/3 receptors. Finally, we tested if site-specific application of oxytocin in the prefrontal cortex reduced cued reinstatement of cocaine seeking. Results: We found an increase in nucleus accumbens core extracellular glutamate for several minutes following reverse dialysis of oxytocin. In male and female rats with a history of cocaine self-administration, site-specific application of oxytocin in the nucleus accumbens core and prefrontal cortex had opposing effects, decreasing and increasing cued reinstatement, respectively. The mGlu2/3 antagonist LY-341495 reversed oxytocin's ability to attenuate cued reinstatement. Conclusions: While the precise mechanism by which oxytocin increases nucleus accumbens core glutamate is yet to be determined, the present results clearly support oxytocin mediation of glutamate neurotransmission in the nucleus accumbens core that impacts cued cocaine seeking.

Sex-specific growth, shape, and their impacts on the life history of a long-lived vertebrate.

BACKGROUND: Individual growth rates both comprise and determine life-history phenotypes. Despite decades of interest in understanding the relationship between individual growth and life history, chelonian longevity has limited our ability to robustly estimate individual growth curves that span the life of both sexes. QUESTIONS: (1) Do patterns of growth in size and shape differ between the sexes of the painted turtle, Chrysemys picta? (2) Does individual variation in size and shape affect female reproductive effort? METHODS: Using 30 years of field data on shell morphology of a single population of painted turtles, we used principal components analysis to summarize multivariate size and shape. We assessed the ability of three non-linear growth models - the logistic, Gompertz, and von Bertalanffy - to predict size-at-age and used model comparison to justify sex-specific model fits. We correlated age-specific size and shape of females with their reproductive efforts. RESULTS: Model comparison supported separate fits of the von Bertalanffy growth function for each sex; non-overlapping confidence intervals imply differences in sex-specific asymptotic size, but not growth rate. Higher-order axes of variation in shell morphology described significant sexual dimorphism in shell shape related to the sphericity and curviness of the shell. Shell sphericity of females covaried with clutch size, mean egg mass, and total clutch mass. Irrespective of shell morphology, we found evidence of an egg number versus egg mass trade-off. Yet, females who matured at a larger size produced greater reproductive efforts.