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Objective: To describe the national rate of social risk factor screening adoption among federally qualified health centers (FQHCs), examine organizational factors associated with social risk screening adoption, and identify barriers to utilizing a standardized screening tool in 2020. Data Source: 2020 Uniform Data System, a 100% sample of all US FQHCs (N = 1375). Study Design: We used multivariable linear probability models to assess the association between social risk screening adoption and key FQHC characteristics. We used descriptive statistics to describe variations in screening tool types and barriers to utilizing standardized tools. We thematically categorized open-ended responses about tools and barriers. Data Collection: None. Principal Findings: In 2020, 68.9% of FQHCs screened patients for any social risk factors. Characteristics associated with a greater likelihood of screening adoption included having high proportions of patients best served in a language other than English (18.8 percentage point [PP] increase, 95% CI: 6.0, 31.6) and being larger in size (10.3 PP increase, 95% CI: 0.7, 20.0). Having higher proportions of uninsured patients (14.2 PP decrease, 95% CI: -25.5, -0.3) and participating in Medicaid-managed care contracts (7.3 PP decrease, 95% CI: -14.2, -0.3) were associated with lower screening likelihood. Among screening FQHCs, the Protocol for Responding to and Assessing Patients' Assets, Risks, and Experiences (PRAPARE) was the most common tool (47.1%). Among non-screening FQHCs, common barriers to using a standardized tool included lack of staff training to discuss social issues (25.2%), inability to include screening in patient intake (21.7%), and lack of funding for addressing social needs (19.2%). Conclusions: Though most FQHCs screened for social risk factors in 2020, various barriers have prevented nearly 1 in 3 FQHCs from adopting a screening tool. Policies that provide FQHCs with resources to support training and workflow changes may increase screening uptake and facilitate engagement with other sectors. KEYWORDS cross-sector collaboration, federally qualified health centers, safety net, social determinants of health, social risk factor screening What is known on this topic * The COVID-19 pandemic elucidated the importance of cross-sector collaborations between health care, public health, and social services to jointly advance health equity, which may be facilitated through social risk screening. * Federally qualified health centers (FQHCs) are safety-net providers that serve over 30 million low-income people in the United States, and many FQHCs collect social risk data. * FQHCs are pivotal health care partners because of their social risk screening efforts, but there is limited data about the characteristics and barriers associated with social risk screening at FQHCs. What this study adds * Using a 100% sample of US FQHCs, we identified the patient- and organization-level characteristics associated with social risk screening at FQHCs in 2020, the first year of the COVID-19 pandemic. * Despite high rates of social risk screening at FQHCs, one in three FQHCs did not screen; FQHCs with higher proportions of uninsured patients and FQHCs smaller in size were less likely to screen. * In the first-known national examination of barriers to standardized social risk screening at FQHCs, common barriers included lack of staff training, inability to include screening in workflow, and limited funding., 1 | INTRODUCTION The onset of the Coronavirus 2019 (COVID-19) pandemic disrupted communities globally. In the United States (US), the impact of the pandemic was especially devastating for marginalized communities [...]

We explored the association between the use of a hospital-based food pantry and subsequent emergency department (ED) utilization among Medicaid patients with diabetes in a large safety-net health system. Leveraging 2015-2019 electronic health record data, we used a staggered difference-in-differences approach to measure changes in ED use before vs after food pantry use. Food pantry use was associated with a 7.3 percentage point decrease per patient per quarter (95% confidence interval, −13.8 to −0.8) in the probability of subsequent ED utilization (P= .03). Addressing food insecurity through hospital-based food pantries may be one mechanism for reducing ED use among low-income patients with diabetes.

Osteochondral lesions of the talus are a common sequelae of trauma and are often associated with ankle sprains and ankle fractures. Because the surface of the talus is composed primarily of hyaline cartilage, the regenerative capacity of these injuries is limited. Therefore, several open and arthroscopic techniques have been described to treat osteochondral injuries of the talus and underlying bone marrow lesions. Throughout this review, these treatment options are discussed along with their indications and currently reported outcomes. A commentary on the authors’ preferences among these techniques is also provided.

Prescription opioids are the gold standard for treating moderate to severe pain despite their well-documented adverse effects. Of all prescription medications, opioids are abused most widely, and fatal overdoses have reached epidemic levels. One strategy for improving the margin of safety of opioids is combining them with non-opioid drugs to decrease the opioid dose needed for pain relief, thereby reducing adverse effects that occur with larger doses. The N-methyl-D-aspartate receptor antagonist ketamine has been used safely as an analgesic but only under a very limited range of conditions. The current studies characterized the antinociceptive, behavioral suppressant, and gastrointestinal effects of morphine and ketamine alone and in mixtures to determine their interaction in 24 adult male Sprague–Dawley rats (n = 8 per assay). Given alone, both morphine and ketamine produced antinociception, decreased responding for food, and reduced gastrointestinal transit (i.e. produced constipation). The effects of morphine:ketamine mixtures generally were additive, except for the antinociceptive effects of 1:1 mixtures for which the difference in slope (i.e. non-parallel shift) between the observed and predicted effects suggested synergy at smaller doses and additivity at larger doses. The potency of morphine to produce constipation was not enhanced by administration of morphine:ketamine mixtures with antinociceptive effects. The nature of the interaction between morphine and ketamine for adverse effects such as dependence, withdrawal, abuse, or respiratory depression remains unknown but also might be related to the ratio of each drug in mixtures. It will be important to identify conditions that produce the largest potential therapeutic window in humans.

Objective: To describe social needs among low-income adults and estimate the relationship between level of unmet social needs and key indicators of health care access and quality. Data Source: National survey data from 12 states from the 2017 Behavioral Risk Factor Surveillance System, which added a 'Social Determinants of Health' Module in 2017. Study Design: We examined differences in eight measures of health care access and quality (eg, check-up in last 12 months, inability to see doctor due to cost, receipt of eye examination for diabetics) for low-income adults with 0, 1, 2-3, and 4+ unmet social needs based on 7 social needs measures. We used adjusted logistic regression models to estimate the association between level of unmet need and each outcome. Principal Findings: Most common unmet social needs included not having enough money for balanced meals (33 percent) or food (32 percent). After adjusting for observable characteristics, higher levels of unmet social need were associated with poorer access and quality. Compared to those with no reported unmet needs, having 4+ unmet needs was significantly associated with reduced probability of having a yearly check-up (65 percent vs 78 percent, adjusted difference = -7.1 percentage points (PP)), receiving a flu vaccine (33 percent vs 42 percent, adjusted difference = -5.4 PP), having a personal doctor (74 percent vs 80 percent, adjusted difference = -3.1 PP), and having a foot (63 percent vs 80 percent, adjusted difference = -12.8 PP) or eye examination (61 percent vs 73 percent, adjusted difference = -12.6 PP) for diabetic patients, and increased probability of being unable to see a doctor due to cost (44 percent vs 9 percent, adjusted difference = 27.9 PP) and having diabetes affect the eyes (22 percent vs 19 percent, adjusted difference = 8.0 PP) at [alpha] = 0.05. Conclusions: Higher levels of unmet social needs were associated with poorer access to and quality of care among low-income adults. Addressing social needs both inside and outside of health care settings may help mitigate these negative effects. Additional research on if and how to effectively do so is critical. KEYWORDS access to care, quality of care, social needs, 1 | INTRODUCTION Over the last two decades, the critical link between unmet social needs, such as food insecurity, housing instability, and financial stress, and adverse health outcomes has become [...]

Recent research has supported the use of student-centered teaching practices, such as active learning, because of its effectiveness in improving student learning and retention when compared with traditional, lecture-based teaching practices. Despite evidence supporting the effectiveness of active learning in improving STEM undergraduate education, the adoption of active learning by instructors has been slow for reasons, including negative student response to active learning. In this systematic literature review, we examine students 'negative responses to active learning and reasons for the negative responses noted in 57 published STEM studies. Our findings identify three types of negative responses: affect, engagement, and evaluation. The reasons behind negative response represented six overarching categories based on student feedback: limited value, lack of time, difficulty and increased workload, lack of guidance, logistical difficulties, unfamiliarity with active learning, lack of preparation, and confidence. We leverage different theoretical perspectives to explain the reasons behind negative responses and offer insights for lowering the barrier for instructors to adopt active learning in STEM classrooms., An important goal for higher education, particularly for science, technology, engineering, and mathematics (STEM) fields, is ensuring that graduates develop the skills to succeed in the workplace (AAAS, 2010; Freeman [...]

Mendelian randomization (MR) has increasingly been utilized as a tool for establishing causal relations between modifiable exposures and osteoarthritis (OA). The goal of this review was to summarize available MR studies of OA that evaluate the causal role of modifiable risk factors on OA. This review was performed following the Preferred Reporting Items for Systematic Reviews and Meta‐Analysis (PRISMA) Extension for Scoping Reviews model. We performed a literature search for relevant studies published before December 2021 across multiple databases using the search terms “osteoarthritis” and (“Mendelian randomization” or “polygenic risk score”). We reported the MR estimates of causal associations between exposures and OA and then assessed methodologic quality of abstracted studies according to their efforts to validate the three key MR assumptions. Our search identified 45 studies reporting on 141 exposure‐association analyses. All studies performed a formal instrumental variable analysis to estimate the causal effect of exposure on OA. Causal associations (P< 0.05) were reported in 60 of these analyses representing 36 unique publications, and MR‐Egger sensitivity analyses were performed in 45 of these analyses. MR studies provided support for causal associations of OA with increased levels of adiposity, coffee consumption, bone mineral density, and sleep disturbance, and decreased levels of serum calcium and low‐density lipoprotein cholesterol. These results highlight the potential benefits of weight reduction and improvement of sleep quality to reduce the risk of OA and call for a better understanding of the relations of coffee consumption and serum calcium to OA risk.

Human immunodeficiency virus (HIV) persistence during antiretroviral therapy (ART) is associated with heightened plasma interleukin-10 (IL-10) levels and PD-1 expression. We hypothesized that IL-10 and PD-1 blockade would lead to control of viral rebound following analytical treatment interruption (ATI). Twenty-eight ART-treated, simian immunodeficiency virus (SIV)mac239-infected rhesus macaques (RMs) were treated with anti-IL-10, anti-IL-10 plus anti-PD-1 (combo) or vehicle. ART was interrupted 12 weeks after introduction of immunotherapy. Durable control of viral rebound was observed in nine out of ten combo-treated RMs for >24 weeks post-ATI. Induction of inflammatory cytokines, proliferation of effector CD8+T cells in lymph nodes and reduced expression of BCL-2 in CD4+T cells pre-ATI predicted control of viral rebound. Twenty-four weeks post-ATI, lower viral load was associated with higher frequencies of memory T cells expressing TCF-1 and of SIV-specific CD4+and CD8+T cells in blood and lymph nodes of combo-treated RMs. These results map a path to achieve long-lasting control of HIV and/or SIV following discontinuation of ART.

Introduction: In a previously published randomized controlled trial, automated self-association training (ASAT), a novel digital intervention, was found to extend the rapid antidepressant effect of a single infusion of ketamine for at least 30 days. In this secondary analysis, we aimed to understand the potential role of implicit self-esteem in the combined antidepressant effect of ketamine and ASAT training, by investigating the novel synergistic treatment’s effects on implicit self-associations and their relation to symptom improvement. Methods: A total of 154 adults (ages 18–60) with treatment-resistant unipolar depression and lower-than-normative explicit self-esteem were randomized in a double-blind, parallel-arm design to receive one of three treatment allocations: an active/active treatment combination consisting of one infusion of ketamine (0.5 mg/kg) followed by four days of ASAT ( ~ 30–40 min/day), or one of two control arms that lacked either the active drug or the active behavioral component. The Implicit Association Test (IAT) was used to behaviorally assess the strength of association between self-related stimuli and negative concepts. Linear regression models were used to test the relationship between group assignment, IAT scores acquired immediately post-treatment, and both acute and extended clinical outcomes (% change in Montgomery-Asberg Depression Rating Scale scores, relative to pre-treatment baseline) in the trial. Results: The group assigned to ketamine + ASAT intervention, compared to the other groups, had a pattern of IAT scores indicating more positive self-associations immediately after treatment relative to the control arms (F(1, 131) = 3.979; p= 0.048). In regression models, IAT scores tracked with concurrent (acute post-treatment) % change in MADRS scores across all treatment arms (p= 0.001), and mediated more extended (Day 30) depression improvements specifically for the ketamine+ASAT arm (group * IAT interaction term: β = –0.201; p= 0.049). Discussion: Our findings suggest that changing implicit self-worth during a post-ketamine ‘plasticity window’ is one key mechanism whereby the novel ketamine+ASAT treatment combination exerts its antidepressant benefit, confirming the intended treatment target at the level of implicit cognition. Future studies should seek to further enhance the reliability of the biobehavioral intervention’s impact on implicit cognition, as this mechanism appears linked to the intervention’s enduring clinical benefits.

Background: Despite decades of advocacy for disaggregated data collection and reporting for Asian American, Native Hawaiian, and Pacific Islander (AA and NHPI) people, significant gaps remain in our ability to understand AA and NHPI individuals’ access to care. We assess inequities in access to care measures between non-Hispanic White and AA and NHPI adult Medicaid enrollees. Methods: We used the 2014–15 Nationwide Adult Medicaid Consumer Assessment of Healthcare Providers and Systems, the first-and-only nationally representative sample of Medicaid enrollees. Our main outcomes were access to needed care, access to a personal doctor, timely access to a checkup, and timely access to specialty care. Using multivariable linear probability models, we assessed the relationship between racial/ethnic group and our outcomes, both in the aggregate and disaggregated into ten racial/ethnic groups, and adjusted for enrollee-level sociodemographic characteristics, health status, and state-level Medicaid expansion status. Results: In aggregate, AA and NHPI enrollees reported worse access to care than White enrollees on all four metrics (p&lt; 0.001). The magnitude of disparities varied across the ten AA and NHPI ethnic groups. Disparities relative to White enrollees were particularly large in magnitude, roughly 1.5 to 2 times greater, for Chinese, Korean, and Vietnamese enrollees than for the aggregated AA and NHPI group. Conclusions: Despite comparable insurance coverage, there were inequities in multiple access to care metrics between non-Hispanic White and AA and NHPI Medicaid enrollees. Collection of disaggregated health data on AA and NHPI patients reveals important variation in access to care by ethnic group.

Human immunodeficiency virus (HIV) cure efforts are increasingly focused on harnessing CD8+T cell functions, which requires a deeper understanding of CD8+T cells promoting HIV control. Here we identifiy an antigen-responsive TOXhiTCF1+CD39+CD8+T cell population with high expression of inhibitory receptors and low expression of canonical cytolytic molecules. Transcriptional analysis of simian immunodeficiency virus (SIV)-specific CD8+T cells and proteomic analysis of purified CD8+T cell subsets identified TOXhiTCF1+CD39+CD8+T cells as intermediate effectors that retained stem-like features with a lineage relationship with terminal effector T cells. TOXhiTCF1+CD39+CD8+T cells were found at higher frequency than TCF1−CD39+CD8+T cells in follicular microenvironments and were preferentially located in proximity of SIV-RNA+cells. Their frequency was associated with reduced plasma viremia and lower SIV reservoir size. Highly similar TOXhiTCF1+CD39+CD8+T cells were detected in lymph nodes from antiretroviral therapy-naive and antiretroviral therapy-suppressed people living with HIV, suggesting this population of CD8+T cells contributes to limiting SIV and HIV persistence.

Measurable residual disease (MRD) assessed by multiparametric flow cytometry (MFC) has gained importance in clinical decision‐making for acute myeloid leukemia (AML) patients. However, complying with the recent In Vitro Diagnostic Regulations (IVDR) in Europe and Food and Drug Administration (FDA) guidance in the United States requires rigorous validation prior to their use in investigational clinical trials and diagnostics. Validating AML MRD‐MFC assays poses challenges due to the unique underlying disease biology and paucity of patient specimens. In this study, we describe an experimental framework for validation that meets regulatory expectations. Our validation efforts focused on evaluating assay accuracy, analytical specificity, analytical and functional sensitivity (limit of blank (LoB), detection (LLoD) and quantitation (LLoQ)), precision, linearity, sample/reagent stability and establishing the assay background frequencies. Correlation between different MFC methods was highly significant (r= 0.99 for %blasts and r= 0.93 for %LAIPs). The analysis of LAIP specificity accurately discriminated from negative control cells. The assay demonstrated a LoB of 0.03, LLoD of 0.04, and LLoQ of 0.1%. Precision experiments yielded highly reproducible results (Coefficient of Variation <20%). Stability experiments demonstrated reliable measurement of samples up to 96 h from collection. Furthermore, the reference range of LAIP frequencies in non‐AML patients was below 0.1%, ranging from 0.0% to 0.04%. In this manuscript, we present the validation of an AML MFC‐MRD assay using BM/PB patient specimens, adhering to best practices. Our approach is expected to assist other laboratories in expediting their validation activities to fulfill recent health authority guidelines.

In spite of considerable evidence of the effectiveness of active learning and other contemporary teaching methods, barriers to adoption of those methods, such as possible student resistance, continue to exist. This study addresses student resistance by analyzing data from 1,051 students who completed our Student Response to Instructional Practices (StRIP) instrument in 18 introductory engineering courses where active learning was implemented. Through descriptive statistics, correlation analyses, and hierarchical linear regression modeling, we demonstrate that students 'perceptions of their instructors ' use of explanation and facilitation strategies can have a significant impact on student resistance. This study provides a more complete picture of the relative efficacy of these strategies to reduce resistance and confirms that students 'perceptions of their instructors' use of these strategies can influence both how students engage with active learning and how students evaluate the course and instructor. We provide evidence-based advice for both new and experienced instructors to reduce student resistance to active learning and other contemporary teaching methods., Tremendous effort has been invested to improve STEM (science, technology, engineering, and mathematics) education by developing and documenting the effectiveness of contemporary teaching methods such as active learning (Freeman et [...]

Natural science datasets frequently violate assumptions of independence. Samples may be clustered (e.g., by study site, subject, or experimental batch), leading to spurious associations, poor model fitting, and confounded analyses. While largely unaddressed in deep learning, this problem has been handled in the statistics community through mixed effects models, which separate cluster-invariant fixed effects from cluster-specific random effects. We propose a general-purpose framework for Adversarially-Regularized Mixed Effects Deep learning (ARMED) models through non-intrusive additions to existing neural networks: 1) an adversarial classifier constraining the original model to learn only cluster-invariant features, 2) a random effects subnetwork capturing cluster-specific features, and 3) an approach to apply random effects to clusters unseen during training. We apply ARMED to dense, convolutional, and autoencoder neural networks on 4 datasets including simulated nonlinear data, dementia prognosis and diagnosis, and live-cell image analysis. Compared to prior techniques, ARMED models better distinguish confounded from true associations in simulations and learn more biologically plausible features in clinical applications. They can also quantify inter-cluster variance and visualize cluster effects in data. Finally, ARMED matches or improves performance on data from clusters seen during training (5-28% relative improvement) and generalization to unseen clusters (2-9% relative improvement) versus conventional models.

Byline: KEVIN NGUYEN PHOTOGRAPHS BY MATT MARTIN It Was a Year for the Books These were our favorites of 2018-and their authors were cool enough to recommend their favorites, too [...]

Objectives: Toward common methods for system monitoring and evaluation, we proposed a key performance indicator framework and discussed lessons learned while implementing a statewide exposure notification (EN) system in California during the COVID-19 epidemic.Materials and Methods: California deployed the Google Apple Exposure Notification framework, branded CA Notify, on December 10, 2020, to supplement traditional COVID-19 contact tracing programs. For system evaluation, we defined 6 key performance indicators: adoption, retention, sharing of unique codes, identification of potential contacts, behavior change, and impact. We aggregated and analyzed data from December 10, 2020, to July 1, 2021, in compliance with the CA Notify privacy policy.Results: We estimated CA Notify adoption at nearly 11 million smartphone activations during the study period. Among 1 654 201 CA Notify users who received a positive test result for SARS-CoV-2, 446 634 (27%) shared their unique code, leading to ENs for other CA Notify users who were in close proximity to the SARS-CoV-2–positive individual. We identified at least 122 970 CA Notify users as contacts through this process. Contact identification occurred a median of 4 days after symptom onset or specimen collection date of the user who received a positive test result for SARS-CoV-2.Practice Implications: Smartphone-based EN systems are promising new tools to supplement traditional contact tracing and public health interventions, particularly when efficient scaling is not feasible for other approaches. Methods to collect and interpret appropriate measures of system performance must be refined while maintaining trust and privacy.

At parties, people would ask Dexter Palmer, 'What do you do?' 'I'm a writer,' he'd reply. They'd ask the inevitable follow-up, 'What are you working on?' 'Well, this book about [...]

THE WANGS VS. THE WORLDBy Jade Chang354 pp. Houghton Mifflin Harcourt. $26. The best moment of ''The Wangs vs. the World'' comes when young Andrew Wang attempts his first stand-up [...]

AimsWhile interdisciplinary protocols and expedited surgical treatment improve the management of hip fractures in the elderly, the impact of such interventions on patients specifically undergoing arthroplasty for a femoral neck fracture is not clear. We sought to evaluate the efficacy of an interdisciplinary protocol for the management of patients with a femoral neck fracture who are treated with an arthroplasty.MethodsIn 2017, our institution introduced a standardized interdisciplinary hip fracture protocol. We retrospectively reviewed adult patients who underwent hemiarthroplasty (HA) or total hip arthroplasty (THA) for femoral neck fracture between July 2012 and March 2020, and compared patient characteristics and outcomes between those treated before and after the introduction of the protocol.ResultsA total of 157 patients were treated before the introduction of the protocol (35 (22.3%) with a THA), and 114 patients were treated after its introduction (37 (32.5%) with a THA). The demographic details and medical comorbidities were similar in the two groups. Patients treated after the introduction of the protocol had a significantly reduced median time between admission and surgery (22.8 hours (interquartile range (IQR) 18.8 to 27.7) compared with 24.8 hours (IQR 18.4 to 43.3) (p = 0.042), and a trend towards a reduced mean time to surgery (24.1 hours (SD 10.7) compared with 46.5 hours (SD 165.0); p = 0.150), indicating reduction in outliers. Patients treated after the introduction of the protocol had a significantly decreased rate of major complications (4.4% vs 17.2%; p = 0.005), decreased median hospital length of stay in hospital (4.0 days vs 4.8 days; p = 0.008), increased rate of discharge home (26.3% vs 14.7%; p = 0.030), and decreased one-year mortality (14.7% vs 26.3%; p = 0.049). The 90-day readmission rate (18.2% vs 21.7%; p = 0.528) and 30-day mortality (3.7% vs 5.1%; p = 0.767) did not significantly differ. Patients who underwent HA were significantly older than those who underwent THA (82.1 years (SD 10.4) vs 71.1 years (SD 9.5); p < 0.001), more medically complex (mean Charlson Comorbidity Index 6.4 (SD 2.6) vs 4.1 (SD 2.2); p < 0.001), and more likely to develop delirium (8.5% vs 0%; p = 0.024).ConclusionThe introduction of an interdisciplinary protocol for the management of elderly patients with a femoral neck fracture was associated with reduced time to surgery, length of stay, complications, and one-year mortality. Such interventions are critical in improving outcomes and reducing costs for an ageing population.Cite this article: Bone Joint J2021;103-B(7 Supple B):3–8.

As much as we love Honda's coveted roadster, there's one area that has always bothered many owners and admirers: the power plant. The F20/F22 is an amazing motor right from [...]

Exceptional clinical responses produced by the first chimeric antigen receptor T [CAR‐T] cell therapies, and their entry into commercial markets prompted a logarithmic increase in the number of next generation CAR‐T clinical trials. As a result, there is a growing interest in understanding the analytical approaches utilized for reliable monitoring of these “living” drugs, and the challenges encountered during their clinical development. Multiparametric flow cytometry (MFC) assays have played a crucial role in understanding the phenotype and function of first approved CAR‐T therapies. Herein, three main areas for monitoring CAR‐T therapies in clinical trials are discussed: (1) analytical considerations critical for development of MFC assays for the reliable enumeration of CAR‐T levels, (2) operational challenges associated with clinical trial sampling and transportation, and (3) differential cellular kinetics observed by MFC and qPCR analyses and their relationship with efficacy (measurable residual disease levels). Initial experiences described here may enable design of fit‐for‐purpose tools and help to more rapidly advance the development of next generation CAR‐T therapies.

Background: There is controversy regarding the effectiveness of postoperative antibiotics to prevent wound infection. Some surgeons still use a routine postoperative oral antibiotic regimen. The purpose of this study was to review a series of cases and document statistically any difference in infection rates and whether routine postoperative antibiotics in foot and ankle surgery are justified.Methods: A retrospective chart review of 649 patients was performed who underwent elective foot and ankle surgery. Six hundred thirty-one patient charts were included in the final analysis. Evaluated were patients who did and did not receive postoperative oral antibiotics in order to identify whether a difference in infection rate or wound healing occurred. The study also evaluated risk factors for developing infection following foot and ankle surgery.Results: The number of infections in patients receiving postoperative oral antibiotics was 6 (3%), while the number of infections in those who did not receive postoperative oral antibiotics was 10 (2%) (P= .597). The difference of deep versus superficial infections and delays in wound healing between the 2 groups was not statistically significant. Patients who developed infections were older and had a higher prevalence of hypertension, a history of neoplasm, and a greater American Society of Anesthesiologists Classification of Physical Health.Conclusion: This study suggests that routine use of postoperative antibiotics in foot and ankle surgery does not affect wound complications or infection rates. Additionally, patients who are older and those with multiple medical problems may be at higher risk for developing postoperative infection following foot and ankle surgeries.Level of Evidence: Level III, retrospective comparative series.

Ramy Youssef is a Muslim American stand-up comic with his own raunchy HBO special, a Golden Globe - winning TV show, and a new production deal with A24. Though he plays himself, the Ramy of Ramy is amplified. That day, the real Youssef had just been cast in a Taco Bell ad; on Ramy, his character finds a MetroCard on the ground with $120 on it. [Extracted from the article]

The primary human immunodeficiency virus (HIV) reservoir is composed of resting memory CD4+T cells, which often express the immune checkpoint receptors programmed cell death protein 1 (PD-1) and cytotoxic T lymphocyte-associated protein 4 (CTLA-4), which limit T cell activation via synergistic mechanisms. Using simian immunodeficiency virus (SIV)-infected, long-term antiretroviral therapy (ART)-treated rhesus macaques, we demonstrate that PD-1, CTLA-4 and dual CTLA-4/PD-1 immune checkpoint blockade using monoclonal antibodies is well tolerated, with evidence of bioactivity in blood and lymph nodes. Dual blockade was remarkably more effective than PD-1 blockade alone in enhancing T cell cycling and differentiation, expanding effector-memory T cells and inducing robust viral reactivation in plasma and peripheral blood mononuclear cells. In lymph nodes, dual CTLA-4/PD-1 blockade, but not PD-1 alone, decreased the total and intact SIV-DNA in CD4+T cells, and SIV-DNA and SIV-RNA in B cell follicles, a major site of viral persistence during ART. None of the tested interventions enhanced SIV-specific CD8+T cell responses during ART or viral control after ART interruption. Thus, despite CTLA-4/PD-1 blockade inducing robust latency reversal and reducing total levels of integrated virus, the degree of reservoir clearance was still insufficient to achieve viral control. These results suggest that immune checkpoint blockade regimens targeting PD-1 and/or CTLA-4, if performed in people living with HIV with sustained aviremia, are unlikely to induce HIV remission in the absence of additional interventions.

Targeted therapeutics are needed for triple-negative breast cancer (TNBC). In this study, we investigated the activation of Src family of cytoplasmic tyrosine kinases (SFKs) and two SFK substrates—CUB-domain containing protein 1 (CDCP1) and protein kinase C δ (PKCδ)—in 56 formalin-fixed, paraffin-embedded (FFPE) TNBCs. Expression of SFK phosphorylated at Y416 (SFK_pY416+) in tumor cells was strongly associated with phosphorylation of CDCP1 and PKCδ (CDCP1_ pY743+and PKCδ_pY311+), as assessed by immunohistochemistry, indicating increased SFK activity in situ. To enable biochemical analysis, protein extraction from FFPE tissue was optimized. Cleaved CDCP1 isoform (70 kDa) was expressed to a varying degree in all samples but only phosphorylated in TNBC tumor cells that expressed SFK_pY416. Interestingly, active SFK was found to be biphosphorylated (SFK_pY416+/pY527+). Biphosphorylated active SFK was observed more frequently in forkhead box protein A1 (FOXA1)−TNBCs. In addition, in SFK_pY416−samples, FOXA1+TNBC tended to be SFK_pY527+(classic inactive SFK), and FOXA1−TNBC tended to be SFK_pY527−(SFK poised for activation). Strong SFK_pY416 staining was also observed in tumor-infiltrating lymphocytes in a subset of TNBCs with high tumor-infiltrating lymphocyte content. This report will facilitate protein biochemical analysis of FFPE tumor samples and justifies the development of therapies targeting the SFK/CDCP1/PKCδ pathway for TNBC treatment.

ABSTRACTIntroduction: Alzheimer’s disease (AD) is the most common cause of major neurocognitive disorders with a prevalence in the US of about 5.7 million in 2018. With the disease burden projected to increase dramatically in the coming years, it is imperative to review the current available treatment regimens for their safety and utility. The cholinesterase inhibitors (ChEIs) have continued to play a pivotal role in managing the symptoms and possibly slowing the rate of progression of AD since 1993. Owing to their being a mainstay in the treatment of AD, the safety and efficacy of prescribing these drugs needs to be reviewed often, especially with the approval of new formulations and doses.Areas covered: The three ChEIs currently approved by the FDA are donepezil, rivastigmine and galantamine. This article will review the safety and tolerability of these ChEIs and analyze the potential disease modifying properties of these drugs. The authors have reviewed all recent literature including review articles, meta-analyzes, clinical trials and more.Expert opinion: These ChEIs differ subtly in their mechanisms of action, in their tolerability and safety and FDA-approved indications. All are considered first-line, symptomatic treatments of the various phases of AD and may even have potentially disease-modifying effects.

The aim of this study was to investigate the biomechanical properties of the InternalBrace for lisfranc injuries.

First pass success (FPS) can be defined as in vitro retrieval of clot in a single pass during mechanical thrombectomy (MT) for acute large vessel occlusion (LVO). Despite advancements in MT technology, retrieval of fibrin-rich clots remains a challenge. Therefore, the effect of stent retriever length on FPS for fibrin-rich clots was investigated by using SolitaireTM 6 × 40 versus 6 × 30 mm devices with a balloon guide catheter (BGC) or distal access catheter (DAC) and sheath, in an in vitro model of anterior circulation neurovascular anatomy. Additionally, vascular safety of the SolitaireTM 6 × 40 versus 6 × 30 mm devices was evaluated in a porcine model for differences in: luminal thrombus, inflammation, endothelial coverage, fibrin deposits, smooth muscle cell loss, elastic lamina and adventitia disruption, intimal hyperplasia, and lumen reduction, at 0, 30, and 90 days post-treatment. In vitro overall FPS was measured as: SolitaireTM 6 × 40 (95%) and SolitaireTM 6 × 30 (67%). FPS for clot location in middle cerebral artery was: (a) BGC (6 × 40 mm: 100%; 6 × 30 mm: 100%; n= 8); (b) DAC with 088 sheath (6 × 40 mm: 83%; 6 × 30 mm: 33%; n= 12). FPS for clot location in internal carotid artery was: (a) BGC (6 × 40 mm: 100%; 6 × 30 mm: 80%; n= 11); (b) DAC with 088 sheath (6 × 40 mm: 100%; 6 × 30 mm: 67%; n= 10). Stent length had a significant effect (Fisher’s exact test; p< 0.05) on FPS. In vivo evaluation in the porcine model showed no difference in vascular safety parameters between the SolitaireTM 6 × 40 and 6 × 30 mm devices (p> 0.05) at all time points in the study. Longer stent retrievers may be safe and effective in improving FPS for fibrin-rich clots in in vitro and in vivo models of LVO.

Brain metastases (BM) are frequently observed in advanced renal-cell carcinoma (RCC). Historically these individuals have been excluded from clinical trials, but recently, with better local control, many can receive aggressive therapy after treatment. We evaluate our single-institution experience over various treatment eras.

Chronic liver disease due to alcohol-use disorder contributes markedly to the global burden of disease and mortality1–3. Alcoholic hepatitis is a severe and life-threatening form of alcohol-associated liver disease. The gut microbiota promotes ethanol-induced liver disease in mice4, but little is known about the microbial factors that are responsible for this process. Here we identify cytolysin—a two-subunit exotoxin that is secreted by Enterococcus faecalis5,6—as a cause of hepatocyte death and liver injury. Compared with non-alcoholic individuals or patients with alcohol-use disorder, patients with alcoholic hepatitis have increased faecal numbers of E. faecalis. The presence of cytolysin-positive (cytolytic) E. faecaliscorrelated with the severity of liver disease and with mortality in patients with alcoholic hepatitis. Using humanized mice that were colonized with bacteria from the faeces of patients with alcoholic hepatitis, we investigated the therapeutic effects of bacteriophages that target cytolytic E. faecalis. We found that these bacteriophages decrease cytolysin in the liver and abolish ethanol-induced liver disease in humanized mice. Our findings link cytolytic E. faecaliswith more severe clinical outcomes and increased mortality in patients with alcoholic hepatitis. We show that bacteriophages can specifically target cytolytic E. faecalis, which provides a method for precisely editing the intestinal microbiota. A clinical trial with a larger cohort is required to validate the relevance of our findings in humans, and to test whether this therapeutic approach is effective for patients with alcoholic hepatitis.

IMPORTANCE: Empirical study findings to date are mixed on the association between team-based primary care initiatives and health care use and costs for Medicaid and commercially insured patients, especially those with multiple chronic conditions. OBJECTIVE: To evaluate the association of establishing team-based primary care with patient health care use and costs. DESIGN, SETTING, AND PARTICIPANTS: We used difference-in-differences to compare preutilization and postutilization rates between intervention and comparison practices with inverse probability weighting to balance observable differences. We fit a linear model using generalized estimating equations to adjust for clustering at 18 academically affiliated primary care practices in the Boston, Massachusetts, area between 2011 and 2015. The study included 83 953 patients accounting for 138 113 patient-years across 18 intervention practices and 238 455 patients accounting for 401 573 patient-years across 76 comparison practices. Data were analyzed between April and August 2018. EXPOSURES: Practices participated in a 4-year learning collaborative that created and supported team-based primary care. MAIN OUTCOMES AND MEASURES: Outpatient visits, hospitalizations, emergency department visits, ambulatory care–sensitive hospitalizations, ambulatory care–sensitive emergency department visits, and total costs of care. RESULTS: Of 322 408 participants, 176 259 (54.7%) were female; 64 030 (19.9%) were younger than 18 years and 258 378 (80.1%) were age 19 to 64 years. Intervention practices had fewer participants, with 2 or more chronic conditions (n = 51 155 [37.0%] vs n = 186 954 [46.6%]), more participants younger than 18 years (n = 337 931 [27.5%] vs n = 74 691 [18.6%]), higher Medicaid enrollment (n = 39 541 [28.6%] vs n = 81 417 [20.3%]), and similar sex distributions (75 023 women [54.4%] vs 220 097 women [54.8%]); however, after inverse probability weighting, observable patient characteristics were well balanced. Intervention practices had higher utilization in the preperiod. Patients in intervention practices experienced a 7.4% increase in annual outpatient visits relative to baseline (95% CI, 3.5%-11.3%; P &lt; .001) after adjusting for patient age, sex, comorbidity, zip code level sociodemographic characteristics, clinician characteristics, and plan fixed effects. In a subsample of patients with 2 or more chronic conditions, there was a statistically significant 18.6% reduction in hospitalizations (95% CI, 1.5%-33.0%; P = .03), 25.2% reduction in emergency department visits (95% CI, 6.6%-44.0%; P = .007), and a 36.7% reduction in ambulatory care–sensitive emergency department visits (95% CI, 9.2%-64.0%; P = .009). Among patients with less than 2 comorbidities, there was an increase in outpatient visits (9.2%; 95% CI, 5.10%-13.10%; P &lt; .001), hospitalizations (36.2%; 95% CI, 12.2-566.6; P = .003), and ambulatory care–sensitive hospitalizations (50.6%; 95% CI, 7.1%-329.2%; P = .02). CONCLUSIONS AND RELEVANCE: While establishing team-based care was not associated with differences in the full patient sample, there were substantial reductions in utilization among a subset of chronically ill patients. Team-based care practice transformation in primary care settings may be a valuable tool in improving the care of sicker patients, thereby reducing avoidable use; however, it may lead to greater use among healthier patients.

Interview with several celebrities are presented including English actress Claire Foy, American actor John David Washington and Japanese-American filmmaker Hiro Murai. They discuss about their personal lives, career success as director, actor and actress and affiliations. Also emphasized are their other dream careers such as singers and dancers.

The purpose of this chapter is to review the available literature and describe the technique when utilizing arthroscopy in the treatment of ankle fractures. The high incidence of acute cartilage injuries and the difficulty diagnosing syndesmotic instability in ankle fractures have led to the adjunctive use of arthroscopy in their treatment since the 1990s. Although this remains a controversial topic, multiple studies have demonstrated the potential of ankle arthroscopy to help confirm anatomic reduction, limit the surgical exposure and soft tissue trauma, and to diagnose and treat associated intra-articular pathology in displaced ankle fractures.Level of Evidence:Diagnostic Level 4. See Instructions for Authors for a complete description of levels of evidence.

SEMI Standards charter is to develop standards that benefit the semiconductor industry. The SEMI organization has evolved over the last 40 years into an international organization with covering all aspects of semiconductor and flat panel materials and devices. SEMI Standards provides the framework for the development of consensus based standards documents. At present there are two published standards specific to silicon carbide, the first dealing with dimensions, properties and ordering information for SiC wafers, and the second defining a nomenclature for defects found on SiC: SEMI M55-0817 Specification for Polished Monocrystalline Silicon Carbide Wafers SEMI M81-0611 Guide to Defects Found on Monocrystalline Silicon Carbide Substrates Additional standards applicable to various semiconductor wafers also are available and new SiC related standards are being developed based on industry needs and volunteer participation.

The article discusses about long term friendships and presents interview with Martin Short and Steve Martin who were friends since last thirty two years and co-starred in ¡Three Amigos!. They discussed on topics including did they ever get a chance to explore the cities they are in, view on the idea that all comedy comes from a dark place, and that comedians are insecure and self-loathing

The article focuses on perspective of several eminent people over football player Colin Kaepernick's protest for the U.S. national anthem regarding police brutality towards African Americans. Topics discussed include consideration of Kaepernick's protest as creativity by filmmaker Ava DuVernay; Tamika Mallory, co-chairperson of the Women's March, believes an avoidance of football match; and approach of writer Christopher Petrella over analysis of social injustices by Kaepernick's protest.

The article offers information on different actors and actresses with analysis of their breakout roles in 2017. Topics discussed include association of Sofia Boutella with the "Atomic Blonde" film along with possession of toughness by being brought up in Algeria; attainment of breakout role in the "Mindhunter" television show by Jonathan Groff; ad involvement of Lakeith Stanfield in several acting projects such as the "Atlanta" television show.

DNA double-strand break repair by homologous recombination entails the resection of DNA ends to reveal ssDNA tails, which are used to invade a homologous DNA template. CtIP and its yeast ortholog Sae2 regulate the nuclease activity of MRE11 in the initial stage of resection. Deletion of CtIP in the mouse or SAE2in yeast engenders a more severe phenotype than MRE11 nuclease inactivation, indicative of a broader role of CtIP/Sae2. Here, we provide biochemical evidence that CtIP promotes long-range resection via the BLM-DNA2 pathway. Specifically, CtIP interacts with BLM and enhances its helicase activity, and it enhances DNA cleavage by DNA2. Thus, CtIP influences multiple aspects of end resection beyond MRE11 regulation.

The proteasome is a vital cellular machine that maintains protein homeostasis, which is of particular importance in multiple myeloma and possibly other cancers. Targeting of proteasome 20S peptidase activity with bortezomib and carfilzomib has been widely used to treat myeloma. However, not all patients respond to these compounds, and those who do eventually suffer relapse. Therefore, there is an urgent and unmet need to develop new drugs that target proteostasis through different mechanisms. We identified quinoline-8-thiol (8TQ) as a first-in-class inhibitor of the proteasome 19S subunit Rpn11. A derivative of 8TQ, capzimin, shows >5-fold selectivity for Rpn11 over the related JAMM proteases and >2 logs selectivity over several other metalloenzymes. Capzimin stabilized proteasome substrates, induced an unfolded protein response, and blocked proliferation of cancer cells, including those resistant to bortezomib. Proteomic analysis revealed that capzimin stabilized a subset of polyubiquitinated substrates. Identification of capzimin offers an alternative path to develop proteasome inhibitors for cancer therapy.