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Context.—: United States' clinical practice guidelines (CPGs) are often produced by professional societies and used worldwide in daily medical practice. However, studies in various medical specialties demonstrate underrepresentation of women and racial and ethnic minority groups in CPGs. The representation of authors by gender, race, and ethnicity of US pathology CPGs has not been previously evaluated., Objective.—: To assess if women and individuals from racial and ethnic minority groups are underrepresented as authors of pathology CPGs., Design.—: The gender, race, ethnicity, and terminal degrees of authors of 18 CPGs from the College of American Pathologists were coded by using photographs and other available information online and compared to their representation in academic pathology per Association of American Medical Colleges benchmark data., Results.—: Two hundred seventy-five author positions (202 physician author positions) were analyzed. Women overall (119 of 275; 43.3%) and women physicians (65 of 202; 32.2%) held fewer positions than all men and men physicians. Women physicians were significantly underrepresented in physician author positions, while White men physicians were significantly overrepresented in all, first, senior, and corresponding authorship roles when compared to the proportion of women and White men physicians among pathology faculty, respectively. Asian men and women physicians were underrepresented as compared to their representation among pathology faculty., Conclusions.—: Men, particularly White men physicians, are overrepresented among pathology CPG author positions, while women physicians and some physicians from racial and ethnic minority groups are underrepresented. Further research is needed to understand the impact of these findings on the careers of underrepresented physicians and the content of guidelines., (© 2024 College of American Pathologists.)

Introduction: Polycystic ovary syndrome (PCOS) is the most prevalent reproductive endocrinopathy in women, ranging from 5% to 26% depending on diagnostic criteria applied. Common manifestations of PCOS include overweight and obesity, abnormal menstrual cycles, pelvic pain, increased facial and body hair, acne, and infertility. These abnormalities and associated complications have significant military operational and readiness implications. There is a large gap in research regarding active duty servicewomen (ADW) with PCOS. Therefore, the purpose of this study is to describe ADW's experience of living with PCOS and to describe the service-branch-specific differences among these women., Materials and Methods: Moderator's guide, audiotapes, transcripts, and field notes. This was a qualitative descriptive study using focus groups and individual interviews. The David Grant Medical Center Institutional Review Board at Travis AFB, CA, USA, approved the study protocol. Women with PCOS were recruited from U.S. Air Force, Army, and Navy locations. Data were analyzed using constant comparative content analysis., Results: Twenty-three servicewomen from 19 occupations across the Army, Navy, Air Force, and Marine Corps participated. Three overarching categories emerged: (1) challenges managing PCOS symptoms, (2) navigating the military health care system, and (3) navigating PCOS as a service member., Conclusions: Servicewomen may have significant career consequences related to PCOS sequelae, such as overweight, obesity, uncontrolled menstrual cycle, and pain. Managing the myriad of symptoms can distract women while deployed, in austere conditions, or at their home stations. As one of the most common cardiometabolic, reproductive endocrinologic conditions in women, PCOS has not received the attention, awareness, education, or research necessary to sufficiently support ADW with this condition. It is imperative that evidence-based strategies are developed to inform relevant and high-quality care for these warfighters. Future qualitative studies are needed to further describe specific stressors and needs of ADW with PCOS. Future intervention studies are also needed to evaluate effective management options for ADW with PCOS., (© The Association of Military Surgeons of the United States 2023. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

The 2022 mpox outbreak predominantly impacted gay, bisexual, and other men who have sex with men (gbMSM). Two models were developed to support situational awareness and management decisions in Canada. A compartmental model characterized epidemic drivers at national/provincial levels, while an agent-based model (ABM) assessed municipal-level impacts of vaccination. The models were parameterized and calibrated using empirical case and vaccination data between 2022 and 2023. The compartmental model explored: (1) the epidemic trajectory through community transmission, (2) the potential for transmission among non-gbMSM, and (3) impacts of vaccination and the proportion of gbMSM contributing to disease transmission. The ABM incorporated sexual-contact data and modeled: (1) effects of vaccine uptake on disease dynamics, and (2) impacts of case importation on outbreak resurgence. The calibrated, compartmental model followed the trajectory of the epidemic, which peaked in July 2022, and died out in December 2022. Most cases occurred among gbMSM, and epidemic trajectories were not consistent with sustained transmission among non-gbMSM. The ABM suggested that unprioritized vaccination strategies could increase the outbreak size by 47%, and that consistent importation (≥5 cases per 10 000) is necessary for outbreak resurgence. These models can inform time-sensitive situational awareness and policy decisions for similar future outbreaks., (© 2023 His Majesty the King in Right of Canada and The Authors. Journal of Medical Virology published by Wiley Periodicals LLC. Reproduced with the permission of the Minister of Health.)

Importance: Rates of hospital-acquired venous thromboembolism (HA-VTE) are increasing among pediatric patients. Identifying at-risk patients for whom prophylactic interventions should be considered remains challenging., Objective: To determine whether use of a previously validated HA-VTE prognostic model, together with pediatric hematologist review, could reduce pediatric inpatient rates of HA-VTE., Design, Setting, and Participants: This pragmatic randomized clinical trial was performed from November 2, 2020, through January 31, 2022, at a single-center academic children's hospital (Monroe Carell Jr Children's Hospital at Vanderbilt). All pediatric hospital admissions (aged <22 years) under inpatient status were included and randomized., Intervention: All patients had an HA-VTE probability automatically calculated daily, which was visible to the hematology research team for patients in the intervention group. Patients with an elevated risk (predicted probability ≥2.5%) underwent additional medical record review by the research team to determine eligibility for thromboprophylaxis., Main Outcomes and Measures: The primary outcome was rate of HA-VTE. Secondary outcomes included rates of prophylactic anticoagulation and anticoagulation-associated bleeding events., Results: A total of 17 427 hospitalizations met eligibility criteria, were randomized, and were included in the primary analysis: patients had a median (IQR) age of 1.7 (0 to 11.1) years; there were 9143 (52.5%) female patients and 8284 (47.5%) male patients, and there were 445 (2.6%) Asian patients, 2739 (15.9%) Black patients, and 11 752 (67.4%) White patients. The 2 groups were evenly balanced in number (8717 in the intervention group and 8710 in the control group) and patient characteristics. A total of 58 patients (0.7%) in the control group and 77 (0.9%) in the intervention group developed HA-VTE (risk difference: 2.2 per 1000 patients; 95% CI, -0.4 to 4.8 per 1000 patients; P = .10). Recommendations to initiate thromboprophylaxis were accepted by primary clinical teams 25.8% of the time (74 of 287 hospitalizations). Minor bleeding events were rare among patients who received anticoagulation (3 of 74 [4.1%]), and no major bleeding events were observed during the study period. Among patients randomized to the control group, the model exhibited high discrimination accuracy (C statistic, 0.799, 95% CI, 0.725 to 0.856)., Conclusions and Relevance: In this randomized clinical trial of the use of a HA-VTE prognostic model to reduce pediatric inpatient rates of HA-VTE, despite the use of an accurate and validated prognostic model for HA-VTE, there was substantial reluctance by primary clinical teams to initiate thromboprophylaxis as recommended. In this context, rates of HA-VTE between the control and intervention groups were not different. Future research is needed to identify improved strategies for prevention of HA-VTE and to overcome clinician concerns regarding thromboprophylaxis., Trial Registration: ClinicalTrials.gov Identifier: NCT04574895.

Background: Strategies for supporting evidence-informed health policy are a recognized but understudied area of policy dissemination and implementation science. Codesign describes a set of strategies potentially well suited to address the complexity presented by policy formation and implementation. We examine the health policy literature describing the use of codesign in initiatives intended to combine diverse sources of knowledge and evidence in policymaking., Methods: The search included PubMed, MEDLINE, PsychInfo, CINAHL, Web of Science, and Google Scholar in November 2022 and included papers published between 1996 and 2022. Terms included codesign, health, policy, and system terminology. Title and abstracts were reviewed in duplicate and included if efforts informed policy or system-level decision-making. Extracted data followed scoping review guidelines for location, evaluation method, health focus, codesign definition, description, level of health system user input, sectors involved, and reported benefits and challenges., Results: From 550 titles, 23 citations describing 32 policy codesign studies were included from multiple continents (Australia/New Zealand, 32%; UK/Europe, 32%; South America, 14%; Africa, 9%; USA/Canada 23%). Document type was primarily case study (77%). The area of health focus was widely distributed. Policy type was more commonly little p policy (47%), followed by big p policy (25%), and service innovations that included policy-enabled funding (25%). Models and frameworks originated from formal design (e.g., human-centered or participatory design (44%), political science (38%), or health service research (16%). Reported outcomes included community mobilization (50%), policy feasibility (41%), improved multisector alignment (31%), and introduction of novel ideas and critical thinking (47%). Studies engaging policy users in full decision-making roles self-reported higher levels of community mobilization and community needs than other types of engagement., Discussion: Policy codesign is theoretically promising and is gaining interest among diverse health sectors for addressing the complexity of policy formation and implementation. The maturity of the science is just emerging. We observed trends in the association of codesign strategies and outcomes that suggests a research agenda in this area could provide practical insights for tailoring policy codesign to respond to local contextual factors including values, needs, and resources., (© 2023. BioMed Central Ltd., part of Springer Nature.)

Low-threshold mechanosensory C-fibres, C-tactile afferents (CTs), respond optimally to sensations associated with a human caress. Additionally, CT-stimulation activates brain regions associated with processing affective states. This evidence has led to the social touch hypothesis, that CTs have a key role in encoding the affective properties of social touch. Thus, to date, the affective touch literature has focussed on gentle stroking touch. However, social touch interactions involve many touch types, including static, higher force touch such as hugging and holding. This study aimed to broaden our understanding of the social touch hypothesis by investigating relative preference for static vs dynamic touch and the influence of force on these preferences. Additionally, as recent literature has highlighted individual differences in CT-touch sensitivity, this study investigated the influence of affective touch experiences and attitudes, autistic traits, depressive symptomology and perceived stress on CT-touch sensitivity. Directly experienced, robotic touch responses were obtained through a lab-based study and vicarious touch responses through an online study where participants rated affective touch videos. Individual differences were determined by self-report questionnaire measures. In general, static touch was preferred over CT-non-optimal stroking touch, however, consistent with previous reports, CT-optimal stroking (velocity 1-10 cm/s) was rated most pleasant. However, static and CT-optimal vicarious touch were rated comparably for dorsal hand touch. For all velocities, 0.4N was preferred over 0.05N and 1.5N robotic touch. Participant dynamic touch quadratic terms were calculated for robotic and vicarious touch as a proxy CT-sensitivity measure. Attitudes to intimate touch significantly predict robotic and vicarious quadratic terms, as well as vicarious static dorsal hand touch ratings. Perceived stress negatively predicted robotic static touch ratings. This study has identified individual difference predictors of CT-touch sensitivity. Additionally, it has highlighted the context dependence of affective touch responses and the need to consider static, as well as dynamic affective touch., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Ali et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: A significant gap exists between the production of research evidence and its use in behavioral health policymaking. Organizations providing consulting and support activities for improving policy represent a promising source for strengthening the infrastructure to address this gap. Understanding the characteristics and activities of these evidence-to-policy intermediary (EPI) organizations can inform the development of capacity-building activities, leading to strengthened evidence-to-policy infrastructure and more widespread evidence-based policymaking., Methods: Online surveys were sent to 51 organizations from English-speaking countries involved in evidence-to-policy activities in behavioral health. The survey was grounded in a rapid evidence review of the academic literature regarding strategies used to influence research use in policymaking. The review identified 17 strategies, which were classified into four activity categories. We administered the surveys via Qualtrics and calculated the descriptive statistics, scales, and internal consistency statistics using R., Results: A total of 31 individuals completed the surveys from 27 organizations (53% response rate) in four English-speaking countries. EPIs were evenly split between university (49%) and non-university (51%) settings. Nearly all EPIs conducted direct program support (mean = 4.19/5 [sd = 1.25]) and knowledge-building (4.03 [1.17]) activities. However, engagement with traditionally marginalized and non-traditional partners (2.84 [1.39]) and development of evidence reviews using formal critical appraisal methods (2.81 [1.70]) were uncommon. EPIs tend to be specialized, focusing on a group of highly related strategies rather than incorporating multiple evidence-to-policy strategies in their portfolios. Inter-item consistency was moderate to high, with scale α's ranging from 0.67 to 0.85. Ratings of respondents' willingness to pay for training in one of three evidence dissemination strategies revealed high interest in program and policy design., Conclusions: Our results suggest that evidence-to-policy strategies are frequently used by existing EPIs; however, organizations tend to specialize rather than engage in a breadth of strategies. Furthermore, few organizations reported consistently engaging with non-traditional or community partners. Focusing on building capacity for a network of new and existing EPIs could be a promising strategy for growing the infrastructure needed for evidence-informed behavioral health policymaking., (© 2023. The Author(s).)

Background and Method: Pretrial detention makes up 75% of juvenile detention admissions and contributes to the disproportionate contact of minoritized youth in the juvenile carceral system. Given that prior evidence largely examines differences between Black and white youth, this study expands research on disproportionate contact in the pretrial detention setting to Hispanic/Latinx, Indigenous, and Asian youth. With a sample of over 44,000 juvenile cases in a northwest state, we used a generalized linear mixed model to estimate the effect of individual level characteristics while accounting for the random effect of differences at the county level. Additionally, we utilized Critical Race Theory (CRT) in formulating our theoretical model and predictions and apply CRT in our analysis and discussion of our results. In doing so we hope to build upon its application in public health discourse for naming and deconstructing processes that lead to unjust social and health stratification., Results: After factoring in gender, age, crime severity, previous offenses, and variation between counties, our analyses show that Black, Hispanic/Latinx, and American Indian/Alaskan Native youth are more likely to experience pretrial detention than white youth. The likelihood of pretrial detention for Asian youth and for youth identified as "Other" or "Unknown" was not significantly different from white youth., Conclusions: As the iatrogenic effects of detention are disproportionately imposed upon youth of color-particularly Black, Indigenous, and Hispanic/Latinx youth-the disparities present in our study reveal further evidence of institutional racism. In this way, we can see how this carceral process operates as a mechanism of racialized social stratification as put forth by CRT. Considering implications for policy or further research, persistent disparity highlights an enduring need for building or strengthening diversion programs and alternatives to the carceral system, with emphasis on those that are culturally responsive., (© 2023. The Author(s).)

Much has been documented on the association between stress and health. Both direct and indirect pathways have been identified and explored extensively, helping us understand trajectories from healthy individuals to reductions in well-being, and development of preclinical and disease states. Some of these pathways are well established within the field; physiology, affect regulation, and social relationships. The purpose of this review is to push beyond what is known separately about these pathways and provide a means to integrate them using one common mechanism. We propose that social touch, specifically affective touch, may be the missing active ingredient fundamental to our understanding of how close relationships contribute to stress and health. We provide empirical evidence detailing how affective touch is fundamental to the development of our stress systems, critical to the development of attachment bonds and subsequent social relationships across the life course. We will also explore how we can use this in applied contexts and incorporate it into existing interventions.

Background: Community social services are often fragmented and difficult to navigate. This presents a barrier to programs, such as health navigation, that focus on connecting individuals to available services. Existing service mapping efforts, such as those generated by 2-1-1, are helpful but limited in the specificity they provide, particularly with regard to whether services are based on evidence-informed principles. This may lead to a distrust of service quality or poor referral match., Methods: We developed a novel service mapping protocol to identify local, evidence-informed, family-based services, and compared results to 2-1-1's resource list., Results: Our mapping protocol identified more evidence-informed services than 2-1-1 and collected greater detail related to accessibility., Conclusions: Recommendations for integrating this approach into routine community mapping efforts (e.g., 2-1-1) or as a stand-alone approach are discussed.

Science advisory boards and policy organizations have called for adolescent brain science to be incorporated into juvenile probation operations. To achieve this, Opportunity-Based Probation (OBP), a probation model that integrates knowledge of adolescent development and behavior change principles, was developed in collaboration with a local juvenile probation department. The current study compares outcomes (recidivism and probation violations) for youth in the OBP condition versus probation as usual. Inverse probability weighting (IPW) and coarsened exact matching (CEM) were used to estimate causal effects of OBP's average treatment effect (ATE). Results indicated clear effects of OBP on reducing criminal legal referrals, but no significant effects were observed for probation violations. Overall, results provide promising recidivism-reduction effects in support of developmentally grounded redesigns of juvenile probation., Competing Interests: The authors declared no potential conflicts of interest.

Background: Understanding of the role social factors play in chronic pain is growing, with more adaptive and satisfying social relationships helping pain management. During the COVID-19 pandemic, social distancing measures facilitated a naturalistic study of how changes to social interaction affected chronic pain intensity., Methods: In a cross-sectional correlational design, questionnaire data was collected over a 38-day period during the March 2020 COVID-19 lockdown, individuals with chronic pain were asked about their current pain experience as well as notable social factors which might relate to pain., Results: Multiple regression analysis revealed social satisfaction significantly predicted pain experience, with a reduction in social participation during COVID-19 lockdowns increasing pain disability, and increased social satisfaction associated with decreasing pain intensity., Conclusions: While pain management often focuses on the functional aspects of pain alleviation, these findings suggest psychological aspects of socialising satisfaction also impact pain experience. Pain management strategies should consider ways to increase social satisfaction in individuals with chronic pain, perhaps by facilitating socialisation in the home using remote communication methods similar to those which became popular during the COVID-19 lockdown., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2022 Donaghy et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: Pediatric patients have increasing rates of hospital-associated venous thromboembolism (HA-VTE), and while several risk-prediction models have been developed, few are designed to assess all general pediatric patients, and none has been shown to improve patient outcomes when implemented in routine clinical care., Methods: The Children's Likelihood Of Thrombosis (CLOT) trial is an ongoing pragmatic randomized trial being conducted starting November 2, 2020, in the inpatient units at Monroe Carell Jr. Children's Hospital at Vanderbilt in Nashville, TN, USA. All admitted patients who are 21 years of age and younger are automatically enrolled in the trial and randomly assigned to receive either the current standard-of-care anticoagulation practice or the study intervention. Patients randomized to the intervention arm are assigned an HA-VTE risk probability that is calculated from a validated VTE risk-prediction model; the model is updated daily with the most recent clinical information. Patients in the intervention arm with elevated risk (predicted probability of HA-VTE ≥ 0.025) have an additional review of their clinical course by a team of dedicated hematologists, who make recommendations including pharmacologic prophylaxis with anticoagulation, if appropriate. The anticipated enrollment is approximately 15,000 patients. The primary outcome is the occurrence of HA-VTE. Secondary outcomes include initiation of anticoagulation, reasons for not initiating anticoagulation among patients for whom it was recommended, and adverse bleeding events. Subgroup analyses will be conducted among patients with elevated HA-VTE risk., Discussion: This ongoing pragmatic randomized trial will provide a prospective assessment of a pediatric risk-prediction tool used to identify hospitalized patients at elevated risk of developing HA-VTE.  TRIAL REGISTRATION: ClinicalTrials.gov NCT04574895. Registered on September 28, 2020. Date of first patient enrollment: November 2, 2020., (© 2022. The Author(s).)

Objectives: Patients presenting with dysphagia can encounter a pathway to therapy and relief that is expensive and frustrating. High resolution impedance planimetry (HRIP) is a new mechanism for enhancing and possibly hastening that process. A balloon with integrated pressure sensors is utilized to measure luminal geometry and pressure by volume-controlled distention. Esophagogastric junction (EGJ) distensibility and body contractility are assessed at the time of other endoscopic procedures. Here we describe a single-center experience utilizing HRIP in the endoscopic evaluation of patients presenting with dysphagia., Methods: A prospectively maintained registry of patients undergoing impedance planimetry assessments at an academic medical center was queried for demographics, procedural details, and patient-reported outcomes., Results: Data was reviewed for 122 procedures performed by two providers. HRIP was performed in 63 (52%) patients for initial dysphagia assessment, 36 (30%) for follow-up assessment, and 20 (16%) as a procedural adjunct at the time of other planned procedures. HRIP contractile response was characterized as normal in 36%, absent in 32%, and diminished/disorganized in 14%. These results motivated clinical planning for surgical referral in 7 (5%) patients, 31 (26%) additional testing, and 82 (68%) continued medical management and follow-up., Discussion: HRIP is an emerging endoscopic modality which can streamline diagnostic work-up and therapeutic planning for patients with symptomatic dysphagia. Using functional esophageal assessment at the time of other diagnostic and therapeutic procedures, HRIP may expedite care and lead to improved patient satisfaction and clinical outcomes.

Growing concern about the use of incarceration is driving significant reform in juvenile legal system decision-making and is likely to have a substantial impact on the role residential options play in the future continuum of care. It appears inevitable that surviving institutions or alternative residential models will be increasingly scrutinized for their impact on youth development. While rehabilitative models focused on youth development are a promising and growing part of residential institutions, few tools are available to measure quality. For institutions to sustain a focus on quality assessment, programs should use an organized and specified treatment model`` against which staff behavior can be assessed. This study examined the concurrent validity and item functioning of corresponding youth and expert ratings of social and therapeutic climate across multiple sites in a state-wide juvenile residential setting ( n = 225 paired observations). Results suggest that the reliability of expert ratings of therapeutic climate exceeds the reliability of youth ratings, whereas reliability for other indicators of social climate are roughly equal between rater types. In addition, youth and expert ratings had weak concurrent validity. Implications for the use of youth versus expertly trained raters for measuring social and therapeutic environment are discussed., (© 2022 American Academy of Psychiatry and the Law.)

Objective: To explore the feasibility of a rapid, community-engaged strategy to prioritize health equity policy options as informed by research evidence, community-voiced needs, and public health priorities., Data Sources: Data came from residents in a midsized, demographically, and geographically diverse county over a period of 8 months in 2020 and an evidence review of the health equity policy literature during the same time period., Study Design: A descriptive case study is used to explore the feasibility and potential value of a community codesigned approach to establish community priorities for health equity policy., Data Collection/extraction Methods: Evidence synthesis of health equity policy was conducted parallel to 15 community listening sessions across the county to elicit information on health needs. We used scoping review methods to obtain literature from academic databases and scholarly public health and policy organizations. This information was cross walked with themes from the listening sessions to identify 10 priority policy areas, which were taken back to the community for 15 participatory discussion and ranking sessions., Principal Findings: The process appeared to authentically engage the input of 200 community members representative of minoritized groups while identifying 99 evidence-informed policy levers to promote health equity. Discussion and ranking activities were successful in facilitating community discussion and policy decision making. Remote platforms may have limited the engagement of some residents while promoting the participation of others. Conducting information integration within the research team prior to community policy ranking sessions limited the community ownership over how policies were interpreted and communicated., Conclusions: A combination of information integration and community ranking activities can be used to achieve community-engaged policy prioritization of options in a fairly rapid period of time. While this process provides an example of authentic community ownership of policy prioritization, the compressed timeline limited the community's engagement in the information integration phase., (© 2022 The Authors. Health Services Research published by Wiley Periodicals LLC on behalf of Health Research and Educational Trust.)

Affiliative tactile interactions buffer social mammals against neurobiological and behavioral effects of stress. The aim of this study was to investigate the cutaneous mechanisms underlying such beneficial consequences of touch by determining whether daily stroking, specifically targeted to activate a velocity/force tuned class of low-threshold c-fiber mechanoreceptor (CLTM), confers resilience against established markers of chronic unpredictable mild stress (CMS). Adult male Sprague Dawley rats were exposed to 2 weeks of CMS. Throughout the CMS protocol, some rats were stroked daily, either at CLTM optimal velocity (5 cm/s) or outside the CLTM optimal range (30 cm/s). A third CMS exposed group did not receive any tactile stimulation. The effect of CMS on serum corticosterone levels, anxiety- and depressive-like behaviors in these three groups was assessed in comparison to a control group of non-CMS exposed rats. While stroking did not mitigate the effects of CMS on body weight gain, CLTM optimal velocity stroking did significantly reduce CMS-induced elevations in corticosterone following an acute forced-swim. Rats receiving CLTM optimal stroking also showed significantly fewer anxiety-like behaviors (elevated plus-maze) than the other CMS exposed rats. In terms of depressive-like behavior, whereas the same velocity-specific resilience was observed in a forced-swim test and social interaction test both groups of stroked rats spent significantly less time interacting than control rats, though they also spent significantly less time in the corner than non-stroked CMS rats. Together, these findings support the theory CLTMs play a functional role in regulating the physiological condition of the body., (© 2020 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.)

Background: Recent reports have highlighted patients with COVID-19 and vaccine recipients diagnosed with coagulation factor inhibitors. This is challenging. as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has been identified as a prothrombotic risk factor, with heparin treatment decreasing mortality. However, both infection and vaccination have been associated with immune-mediated hematologic abnormalities, including thrombocytopenia, further rendering these groups at risk for both hemorrhagic and thrombotic events., Objectives: We sought to characterize the incidence and clinical findings of coagulation factor inhibitors in patients with COVID-19 and vaccine recipients., Methods: We queried the US Centers for Disease Control and Prevention's Vaccine Adverse Event Reporting System (VAERS), a publicly accessible database, for reports of potential bleeding episodes or coagulation disturbances associated with SARS-CoV-2 vaccination. We performed an additional comprehensive literature review to identify reports of SARS-CoV-2 infection or vaccination-associated coagulation factor inhibitors., Results: VAERS data showed 58 cases of coagulation factor inhibitors, suggesting a rate of 1.2 cases per 10 million doses. A total of 775 articles were screened and 15 were suitable for inclusion, with six reports of inhibitors after vaccination and nine reports of inhibitors after infection. Inhibitor specificity for factor VIII was most common. Among reported cases, two patients expired due to hemorrhage, one following infection and one following vaccination., Conclusion: The incidence of coagulation factor inhibitors in patients with SARS-CoV-2 vaccination and infection appears similar to the general population. Nonetheless, given the importance of heparin therapy in treating hospital patients, recognition of inhibitors is important., (© 2022 The Authors. Research and Practice in Thrombosis and Haemostasis published by Wiley Periodicals LLC on behalf of International Society on Thrombosis and Haemostasis (ISTH).)

Background: Youth experiencing homelessness have disproportionate contact with the criminal legal system. This system contact represents a critical inflection point for enhancing risk or opportunities for stabilization; however, the policy and scholarly traditions examining the criminal legal system have not traditionally incorporated housing or other social determinants as a central focus of intervention., Methods: We conducted a scoping review using PRISMA-ScR guidelines to examine how the research literature is currently addressing housing within the context of youth involvement in the legal system. Databases searched included PubMed, Web of Science, and Academic Search Complete. Google Scholar was used to identify papers not indexed in the academic databases of interest. Database searches were conducted between September and December 2019 and articles were restricted to those published in English between the year 2000 and 2019. Key study components extracted included demographic information regarding each sample, type of article, study methodology, direction of effects of interest, outcome measures and primary findings, as well as theoretical frameworks engaged by the authors., Results: The search results returned 2154 titles for review. After screening all 2154 titles, 75 met eligibility for inclusion. Abstract reviews were conducted for all 75 papers. 36 abstracts met eligibility criteria and underwent full-text review. Ultimately, 29 articles satisfied eligibility criteria and were included in this scoping review., Conclusions: Publications are primarily focused on the social epidemiology of risk factors and behaviors determining youth justice contact, but relatively less so on studies of interventions targeting youth delinquency, crime reduction, or recidivism that included housing support. The lack of continuity in theorizing from epidemiology to applied science in this area represents a gap in the literature that is likely reducing the effectiveness of interventions to interrupt patterns of legal system contact for youth. Integrating a public health framework that emphasizes the upstream social determinants leading to contact with the youth justice system would represent a paradigm shift for the field that would have beneficial effects on long term health outcomes for youth., (© 2022. The Author(s).)

B-cell acute lymphoblastic leukemia (B-ALL) is the most common pediatric malignancy with a highly favorable overall prognosis. Central nervous system (CNS) relapse of B-ALL is relatively rare and is associated with inferior survival outcomes. We present two patients with B-ALL who developed isolated CNS relapse following confirmed infection with severe acute respiratory syndrome coronavirus 2. In addition to individual and disease factors, we posit that delays in therapy together with immune system modulation because of severe acute respiratory syndrome coronavirus 2 may account for these 2 cases of CNS relapsed B-ALL. We report on this clinical observation to raise awareness of this potential association., Competing Interests: The authors declare no conflict of interest., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Thrombosis with thrombocytopenia syndrome (TTS) is a potentially life-threatening condition associated with adenoviral-vectored COVID-19 vaccination. It presents similarly to spontaneous heparin-induced thrombocytopenia. Twelve cases of cerebral venous sinus thrombosis after vaccination with the Ad26.COV2.S COVID-19 vaccine (Janssen/Johnson & Johnson) have previously been described., Objective: To describe surveillance data and reporting rates of all reported TTS cases after COVID-19 vaccination in the United States., Design: Case series., Setting: United States., Patients: Case patients receiving a COVID-19 vaccine from 14 December 2020 through 31 August 2021 with thrombocytopenia and thrombosis (excluding isolated ischemic stroke or myocardial infarction) reported to the Vaccine Adverse Event Reporting System. If thrombosis was only in an extremity vein or pulmonary embolism, a positive enzyme-linked immunosorbent assay for antiplatelet factor 4 antibodies or functional heparin-induced thrombocytopenia platelet test result was required., Measurements: Reporting rates (cases per million vaccine doses) and descriptive epidemiology., Results: A total of 57 TTS cases were confirmed after vaccination with Ad26.COV2.S ( n  = 54) or a messenger RNA (mRNA)-based COVID-19 vaccine ( n  = 3). Reporting rates for TTS were 3.83 per million vaccine doses (Ad26.COV2.S) and 0.00855 per million vaccine doses (mRNA-based COVID-19 vaccines). The median age of patients with TTS after Ad26.COV2.S vaccination was 44.5 years (range, 18 to 70 years), and 69% of patients were women. Of the TTS cases after mRNA-based COVID-19 vaccination, 2 occurred in men older than 50 years and 1 in a woman aged 50 to 59 years. All cases after Ad26.COV2.S vaccination involved hospitalization, including 36 (67%) with intensive care unit admission. Outcomes of hospitalizations after Ad26.COV2.S vaccination included death (15%), discharge to postacute care (17%), and discharge home (68%)., Limitations: Underreporting and incomplete case follow-up., Conclusion: Thrombosis with thrombocytopenia syndrome is a rare but serious adverse event associated with Ad26.COV2.S vaccination. The different demographic characteristics of the 3 cases reported after mRNA-based COVID-19 vaccines and the much lower reporting rate suggest that these cases represent a background rate., Primary Funding Source: Centers for Disease Control and Prevention.

Introduction: Acute traumatic coagulopathy (ATC) is an endogenous impairment in hemostasis that often contributes to early mortality after trauma. Endothelial glycocalyx damage is associated with trauma-induced coagulation abnormalities; however, the specific relationship between hyaluronan (HA), a key glycocalyx constituent, and ATC has not been evaluated., Methods: We performed a secondary analysis of prospectively collected data from a recent study in which trauma patients (>18 years) admitted to our Level I trauma center with an ABC Score≥2 were enrolled. Partial thromboplastin time (PTT), international normalized ratio (INR), and thromboelastography (TEG) parameters were recorded at arrival. Injury characteristics and clinical outcomes were obtained. Plasma HA levels were measured in healthy controls (HC) and in trauma subjects at arrival (t = 0 h) and 12, 24, and 48 h. ATC was defined as admission INR>1.2 or PTT≥36.5 s. Comparisons of HA levels were assessed, and Spearman's correlations were performed between 0 h and 24 h HA levels, coagulation measures and clinical outcomes. P values < 0.05 were considered significant., Results: Forty-eight trauma patients and 22 controls were enrolled for study. Sixteen trauma subjects were coagulopathic at admission. HA levels in subjects with ATC were higher than non-coagulopathic subjects at all time points and elevated above HC levels at 24 and 48 h. At arrival, HA levels correlated with TEG R-time, PTT, and INR. HA levels at 24 h correlated with increased transfusion requirements and intensive care unit and hospital lengths of stay., Conclusion: Shed HA is associated with early coagulation abnormalities in trauma patients, which may contribute to worse outcomes. These findings highlight the need for additional studies to evaluate the mechanistic role of HA in ATC., Competing Interests: The authors report no conflicts of interest., (Copyright © 2021 by the Shock Society.)

Background: The delivery of evidence-supported treatments (EST) in children's mental health could be a valuable measure for monitoring mental healthcare quality; however, efforts to monitor the use of EST in real world systems are hindered by the lack of pragmatic methods. This mixed methods study examined the implementation and agency response rate of a pragmatic, claims-based measure of EST designed to be applied as a universal quality measure for child psychotherapy encounters in a state Medicaid system., Methods: Implementation potential of the EST measure was assessed with healthcare leader rankings of the reporting method's acceptability, appropriateness and feasibility (n = 53), and post-implementation ratings of EST rate accuracy. Ability of the healthcare system to monitor EST through claims was measured by examining the agency responsivity in using the claims-based measure across 98 Medicaid-contracted community mental health (CMH) agencies in Washington State., Results: The analysis found the reporting method had high implementation potential. The method was able to measure the use of an EST for 83% of children covered by Medicaid with 58% CMH agencies reporting > 0 ESTs in one quarter. Qualitative analyses revealed that the most significant barrier to reporting ESTs was the operability of electronic health record systems and agencies' mixed views regarding the accuracy and benefits of reporting., Conclusions: Measurement of child mental health ESTs through Medicaid claims reporting has acceptable implementation potential and promising real world responsiveness from CMH agencies in one state. Variation in reporting by agency site and low to moderate perceived value by agency leaders suggests the need for additional implementation supports for wider uptake., (© 2021. The Author(s).)

The aggregation of the amyloid beta (Aβ) protein into plaques is a pathological feature of Alzheimer's disease (AD). While amyloid aggregates have been extensively studied in vitro, their structural aspects and associated chemistry in the brain are not fully understood. In this report, we demonstrate, using infrared spectroscopic imaging, that Aβ plaques exhibit significant heterogeneities in terms of their secondary structure and phospholipid content. We show that the capabilities of discrete frequency infrared imaging (DFIR) are ideally suited for characterization of amyloid deposits in brain tissues and employ DFIR to identify nonplaque β-sheet aggregates distributed throughout brain tissues. We further demonstrate that phospholipid-rich β-sheet deposits exist outside of plaques in all diseased tissues, indicating their potential clinical significance. This is the very first application of DFIR toward a characterization of protein aggregates in an AD brain and provides a rapid, label-free approach that allows us to uncover β-sheet heterogeneities in the AD, which may be significant for targeted therapeutic strategies in the future.

Tactile sensitivities are common in Autism Spectrum Conditions (autism). Psychophysically, slow, gentle stroking touch is typically rated as more pleasant than faster or slower touch. Vicarious ratings of social touch results in a similar pattern of velocity dependent hedonic ratings as directly felt touch. Here we investigated whether adults and children's vicarious ratings vary according to autism diagnosis and self-reported autistic traits. Adults' scoring high on the AQ rated stroking touch on the palm as less pleasant than a Low AQ group. However, in contrast to our hypothesis, we did not find any effect of autism diagnosis on children's touch ratings despite parental reports highlighting significant somatosensory sensitivities. These results are discussed in terms of underpinning sensory and cognitive factors., (© 2021. The Author(s).)

Affective sharing is a bottom-up process involving automatic processing of sensory inputs that facilitate vicarious experience of another's emotional state. It is grounded directly in the prior experiences of the perceiver. In adults, vicarious ratings of affective touch match the known velocity tuning and hypothesised anatomical distribution of C-tactile afferents (CT), a subclass of C-fibre which respond preferentially to low force/velocity stroking touch, typically perceived as pleasant. Given the centrality of touch to early nurturing interactions, here we examined whether primary school aged children's vicarious ratings of affective touch show the same anatomical and velocity specific patterns reported in adults. Forty-four children aged between 8 and 11 (mean age 9, 24 male) rated a sequence of video clips depicting one individual being touched by another on 5 different upper-body sites (palm, dorsal forearm, ventral forearm, upper-arm and back) at 3 different velocities (static, CT optimal, slow stroking and non-CT optimal, fast stroking). Immediately after viewing each clip, participants were asked to rate how pleasant they perceived the touch to be. While children rated the CT optimal velocity significantly higher than static or non-CT optimal touch, unlike adults their ratings did not vary across skin sites. This difference may reflect the fact children's ratings are grounded in bottom-up affective resonance while adults also draw on top-down cognitive evaluation of the broader social context when rating the stimuli., Competing Interests: The authors have declared that no competing interests exist.

Importance: Cerebral venous sinus thrombosis (CVST) with thrombocytopenia, a rare and serious condition, has been described in Europe following receipt of the ChAdOx1 nCoV-19 vaccine (Oxford/AstraZeneca), which uses a chimpanzee adenoviral vector. A mechanism similar to autoimmune heparin-induced thrombocytopenia (HIT) has been proposed. In the US, the Ad26.COV2.S COVID-19 vaccine (Janssen/Johnson & Johnson), which uses a human adenoviral vector, received Emergency Use Authorization (EUA) on February 27, 2021. By April 12, 2021, approximately 7 million Ad26.COV2.S vaccine doses had been given in the US, and 6 cases of CVST with thrombocytopenia had been identified among the recipients, resulting in a temporary national pause in vaccination with this product on April 13, 2021., Objective: To describe reports of CVST with thrombocytopenia following Ad26.COV2.S vaccine receipt., Design, Setting, and Participants: Case series of 12 US patients with CVST and thrombocytopenia following use of Ad26.COV2.S vaccine under EUA reported to the Vaccine Adverse Event Reporting System (VAERS) from March 2 to April 21, 2021 (with follow-up reported through April 21, 2021)., Exposures: Receipt of Ad26.COV2.S vaccine., Main Outcomes and Measures: Clinical course, imaging, laboratory tests, and outcomes after CVST diagnosis obtained from VAERS reports, medical record review, and discussion with clinicians., Results: Patients' ages ranged from 18 to younger than 60 years; all were White women, reported from 11 states. Seven patients had at least 1 CVST risk factor, including obesity (n = 6), hypothyroidism (n = 1), and oral contraceptive use (n = 1); none had documented prior heparin exposure. Time from Ad26.COV2.S vaccination to symptom onset ranged from 6 to 15 days. Eleven patients initially presented with headache; 1 patient initially presented with back pain and later developed headache. Of the 12 patients with CVST, 7 also had intracerebral hemorrhage; 8 had non-CVST thromboses. After diagnosis of CVST, 6 patients initially received heparin treatment. Platelet nadir ranged from 9 ×103/µL to 127 ×103/µL. All 11 patients tested for the heparin-platelet factor 4 HIT antibody by enzyme-linked immunosorbent assay (ELISA) screening had positive results. All patients were hospitalized (10 in an intensive care unit [ICU]). As of April 21, 2021, outcomes were death (n = 3), continued ICU care (n = 3), continued non-ICU hospitalization (n = 2), and discharged home (n = 4)., Conclusions and Relevance: The initial 12 US cases of CVST with thrombocytopenia after Ad26.COV2.S vaccination represent serious events. This case series may inform clinical guidance as Ad26.COV2.S vaccination resumes in the US as well as investigations into the potential relationship between Ad26.COV2.S vaccine and CVST with thrombocytopenia.

Background: Hospital-associated venous thromboembolism (HA-VTE) is an increasing cause of morbidity in pediatric populations, yet identification of high-risk patients remains challenging. General pediatric models have been derived from case-control studies, but few have been validated. We developed and validated a predictive model for pediatric HA-VTE using a large, retrospective cohort., Methods: The derivation cohort included 111 352 admissions to Monroe Carell Jr. Children's Hospital at Vanderbilt. Potential variables were identified a priori, and corresponding data were extracted. Logistic regression was used to estimate the association of potential risk factors with development of HA-VTE. Variable inclusion in the model was based on univariate analysis, availability in routine medical records, and clinician expertise. The model was validated by using a separate cohort with 44 138 admissions., Results: A total of 815 encounters were identified with HA-VTE in the derivation cohort. Variables strongly associated with HA-VTE include history of thrombosis (odds ratio [OR] 8.7; 95% confidence interval [CI] 6.6-11.3; P < .01), presence of a central line (OR 4.9; 95% CI 4.0-5.8; P < .01), and patients with cardiology conditions (OR 4.0; 95% CI 3.3-4.8; P < .01). Eleven variables were included, which yielded excellent discriminatory ability in both the derivation cohort (concordance statistic = 0.908) and the validation cohort (concordance statistic = 0.904)., Conclusions: We created and validated a risk-prediction model that identifies pediatric patients at risk for HA-VTE development. We anticipate early identification of high-risk patients will increase prophylactic interventions and decrease the incidence of pediatric HA-VTE., Competing Interests: POTENTIAL CONFLICT OF INTEREST: The authors have indicated they have no potential conflicts of interest to disclose., (Copyright © 2021 by the American Academy of Pediatrics.)

There have been recent advances in safer blood component preparation and use of adjuvant blood derivatives, which have limited safety and efficacy data on use in children. This article reviews the literature on use of whole blood, solvent/detergent-treated plasma, pathogen-reduced platelets, and fibrinogen concentrate in pediatric patients. Many countries have adopted pathogen-reduced blood product technology, and hospitals in the United States are slowly adopting these products. The pediatric transfusion medicine community needs to appraise the evidence for their use and continue to advocate the inclusion of children in the most robust randomized clinical trials for novel blood components., Competing Interests: Disclosure The authors have nothing to disclose., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Taste perception has been reported to vary with changes in affective state. Distortions of taste perception, including blunted recognition thresholds, intensity, and hedonic ratings have been identified in those suffering from depressive disorders. Serotonin is a key neurotransmitter implicated in the etiology of anxiety and depression; systemic and peripheral manipulations of serotonin signaling have previously been shown to modulate taste detection. However, the specific effects of central serotonin function on taste processing have not been widely investigated. Here, in a double-blind placebo-controlled study, acute tryptophan depletion was used to investigate the effect of reduced central serotonin function on taste perception. Twenty-five female participants aged 18-28 attended the laboratory on two occasions at least 1 week apart. On one visit, they received a tryptophan depleting drink and on the other, a control drink was administered. Approximately, 6 h after drink consumption, they completed a taste perception task which measured detection thresholds and supra-threshold perceptions of the intensity and pleasantness of four basic tastes (sweet, sour, bitter, and salt). While acutely reducing central levels of serotonin had no effect on the detection thresholds of sweet, bitter, or sour tastes, it significantly enhanced detection of salt. For supra-threshold stimuli, acutely reduced serotonin levels significantly enhanced the perceived intensity of both bitter and sour tastes and blunted pleasantness ratings of bitter quinine. These findings show manipulation of central serotonin levels can modulate taste perception and are consistent with previous reports that depletion of central serotonin levels enhances neural and behavioral responsiveness to aversive signals., (© The Author(s) 2020. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Traumatic injury and hemorrhagic shock result in endothelial cell activation and vascular dysfunction that, if not corrected, can propagate multiorgan failure. Angiopoietin-1 and angiopoietin-2 are important regulators of endothelial cell function, and the ratio of plasma angiopoietin-2-to-1 is a useful indicator of overall vascular health. We therefore characterized plasma angiopoietin-2/-1 ratios over time after trauma in adults in an effort to gain insight into the pathophysiology that may drive post-traumatic vasculopathy and organ injury. We performed a single-center prospective observational study to measure plasma angiopoietin-1 and -2 levels and determine angiopoietin-2/-1 ratios in adult trauma patients upon hospital arrival and after 12, 24, and 48 h. Compared with levels in healthy adults, angiopoietin-1 levels were significantly elevated at hospital arrival, and angiopoietin-2 levels were significantly elevated at 12, 24, and 48 h. These kinetics translated in angiopoietin-2/-1 ratios that were significantly greater than controls at 24 and 48 h. After regression analysis, elevated angiopoietin-2 levels were independently associated with blunt injuries at admission, with coagulopathy at admission and 12 h, and with hemorrhagic shock at 24 and 48 h. Significant correlations were observed between both angiopoietins and 24-h transfusion requirements. Angiopoietin-2/-1 ratios correlated with mechanical ventilation duration and intensive care unit and hospital lengths of stay. In this study, we demonstrate novel temporal associations between angiopoietin dysregulation and blunt injuries, acute coagulopathy, and hemorrhagic shock. Moreover, our findings highlight the presence of endothelial activation following traumatic insults in adults that may contribute to worse clinical outcomes.

In the United Kingdom, the most common reasons for a child to come under the care of social services are neglect and abuse. Such early childhood adversity is a risk factor for social-isolation and poor mental health in adulthood. Touch is a key channel for nurturing interactions, and previous studies have shown links between early somatosensory input, experience dependent neural plasticity, and later life emotional functioning. The aim of the present study was to test the relationship between childhood neglect/abuse and later life experiences, attitudes, and hedonic ratings of affective touch. Here, affective touch is defined as low force, dynamic touch which C-Tactile afferents (CTs) respond optimally to. We hypothesized that a childhood lacking in early nurturing tactile stimulation would be associated with reduced sensitivity to socially relevant affective touch in adulthood. To test this, 19 care leavers (average 9.32 ± 3.70 years in foster care) and 32 non-care leavers were recruited through opportunity sampling (mean age = 21.25 ± 1.74 years). Participants completed a range of psychophysical somatosensory tests. First, they rated the pleasantness of CT-optimal (3 cm/s) and non-CT-optimal (0.3 and 30 cm/s) stroking touch applied to their forearm, both robotically and by an experimenter. They also made vicarious ratings of the anticipated pleasantness of social tactile interactions depicted in a series of videos. Finally, they filled in the Childhood Trauma Questionnaire (CTQ) and the Touch Experiences and Attitudes Questionnaire (TEAQ). As expected, care leavers reported significantly higher levels of childhood trauma than the control group. They also reported significantly lower levels of positive childhood touch compared to non-care leavers, but their attitudes and experiences of current intimate and affiliative touch did not differ. Across all psychophysical tests, care leavers showed specific reduction in sensitivity to the affective value of CT targeted 3 cm/s touch. The results of this study support the hypothesis that a lack of nurturing touch in early developmental periods leads to blunted sensitivity to the specific social value of affective touch. Future research should investigate the neural and physiological mechanisms underlying the observed effect., (Copyright © 2020 Devine, Walker, Makdani, Stockton, McFarquhar, McGlone and Trotter.)

Objectives: Results from preclinical and adult sepsis studies suggest that the balance of circulating angiopoietin-1 and -2 levels, represented as angiopoietin-2/-1 ratios, plays a pivotal role in mediating vascular dysfunction and organ injury during sepsis. However, the relationship of plasma angiopoietins with organ injury and clinical outcomes in children with sepsis remains unknown. We sought to determine whether plasma angiopoietin-1 and -2 levels and angiopoietin-2/-1 ratios in the acute phase of sepsis correlated with measures of organ injury and clinical outcomes in children with sepsis., Design: Prospective observational cohort study., Setting: PICU within a tertiary freestanding children's hospital., Patients: Children 18 years old or less and greater than 3 kg admitted to the PICU for sepsis., Interventions: None., Measurements and Main Results: Plasma angiopoietin-1 and -2 levels were measured in 38 children with sepsis 0-6, 24, 48, and 72 hours following PICU admission. Children with elevated pediatric Sequential Organ Failure Assessment scores on the third day after PICU admission demonstrated significantly higher 24-72-hour angiopoietin-2/-1 ratios predominantly as a function of higher angiopoietin-2 levels. In children with sepsis-induced organ dysfunction, angiopoietin-2/-1 ratios correlated with oxygenation indices and serum levels of creatinine and bilirubin. Forty-eight- and 72-hour angiopoietin-2/-1 ratios correlated with PICU length of stay (Spearman rho = 0.485, p = 0.004 and rho = 0.440, p = 0.015, respectively)., Conclusions: In the acute phase of sepsis in children, plasma angiopoietin-2/-1 ratios rise significantly above control levels and correlate with measures of organ injury and worse clinical outcomes after 24 hours. Our findings suggest that angiopoietin dysregulation begins early in sepsis and, if sustained, may promote greater organ injury that can lead to worse clinical outcomes.

Most familiar odors are complex mixtures of volatile molecules, which the olfactory system automatically synthesizes into a perceptual whole. However, odors are rarely encountered in isolation; thus, the brain must also separate distinct odor objects from complex and variable backgrounds. In vision, autistic traits are associated with superior performance in tasks that require focus on the local features of a perceptual scene. The aim of the present study was to determine whether the same advantage was observed in the analysis of olfactory scenes. To do this, we compared the ability of 1) 40 young adults (aged 16-35) with high (n = 20) and low levels of autistic traits and 2) 20 children (aged 7-11), with (n = 10) and without an autism spectrum disorder diagnosis, to identify individual odor objects presented within odor mixtures. First, we used a 4-alternative forced choice task to confirm that both adults and children were able to reliably identify 8 blended fragrances, representing food-related odors, when presented individually. We then used the same forced choice format to test participants' ability to identify the odors when they were combined in either binary or ternary mixtures. Adults with high levels of autistic traits showed superior performance on binary but not ternary mixture trials, whereas children with an autism spectrum disorder diagnosis outperformed age-matched neurotypical peers, irrespective of mixture complexity. These findings indicate that the local processing advantages associated with high levels of autistic traits in visual tasks are also apparent in a task requiring analytical processing of odor mixtures., (© The Author(s) 2020. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Research suggests that neighborhoods play an important role in shaping health outcomes across the life course, but the neighborhood-health link during the transition to adulthood period (18-29 years) is not well studied. A scoping review of 24 studies used thematic analysis to examine the theoretical and methodological approaches of the neighborhood-health literature during this period. Themes illustrate the varied approaches used in this research, including diversity in how neighborhood is defined, theoretical variation regarding the importance of the transition period and the neighborhood-health link, and the importance of gender and race/ethnicity to this area of study. While the literature on this topic is fragmented, with varied definitions and minimal theoretical coherence, all studies found some degree of support for the relationship between neighborhoods and health during the transition to adulthood. Our analysis suggests that future research should focus on developing a theoretical foundation for these relationships in order to clarify key concepts and advance a science to better understand how and why neighborhoods affect health during this period., Competing Interests: Declaration of competing interest None., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

The sense of touch is primarily considered a discriminative and exteroceptive sense, facilitating the detection, manipulation and exploration of objects, via an array of low-threshold mechanoreceptors and fast conducting A-beta (Aβ) afferents. However, a class of unmyelinated, low-threshold mechanoreceptors identified in the hairy skin of mammals have been proposed to constitute a second, anatomically distinct system coding the affective qualities of touch. Unlike Aβs, which increase their firing rate linearly with the velocity of a stimulus moving across their receptive field, the response of these C-tactile afferents (CTs) is described by an inverted 'U' curve fit, responding optimally to a skin temperature stimulus moving at between 1 and 10 cm/s. Given the distinct velocity tuning of these fast and slow touch fibres, here we used event-related potentials to compare the time course of neural responses to 1st (fast) and 2nd (slow) touch systems. We identified a higher amplitude P300 in response to fast, Aβ-targeted, versus slow CT-targeted, stroking touch. In contrast, we identified a previously described, C-fibre specific, ultra-late potential (ULP) associated with CT-targeted input. Of special note as regards the function of CTs is that the amplitude of the ULP was negatively correlated with self-reported levels of autistic traits, which is consistent with the hypothesized affective and social significance of this response. Taken together, these findings provide further support for distinct discriminative and affective touch systems and suggests the temporal resolution of EEG provides an as yet underutilized tool for exploring individual differences in response sensitivity to CT-targeted touch., (© 2019 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.)

We describe the modification of a commercially available tandem differential mobility mass spectrometer (DMS) that has been retrofitted to facilitate photodissociation (PD) of differential mobility-separated, mass-selected molecular ions. We first show that a mixture of protonated quinoline/isoquinoline (QH + /iQH + ) can be separated using differential mobility spectrometry. Efficient separation is facilitated by addition of methanol to the DMS environment and increased residence time within the DMS. In action spectroscopy experiments, we gate each isomer using appropriate DMS settings, trap the ions in the third quadrupole of a triple quadrupole mass spectrometer, and irradiate them with tunable light from an optical parametric oscillator (OPO). The resulting mass spectra are recorded as the OPO wavelength is scanned, giving PD action spectra. We compare our PD spectra with previously recorded spectra for the same species and show that our instrument reproduces previous works faithfully.

This pilot quasi-experimental trial tested a gender-responsive cognitive behavioral group intervention with 87 court-involved female adolescents (5 juvenile courts) who were at indicated risk for substance use disorder. Participants in the intervention (n = 57) received twice weekly group sessions for 10 weeks (20 sessions) focused on building emotional, thought and behavior regulation skills and generalizing these skills to relationally-based scenarios (GOAL: Girls Only Active Learning). Youth in the control condition (n = 30) received services as usual, which included non-gender-specific aggression management training, individual counseling and no services. The GOAL program was found to be acceptable to youth and parents and feasible to implement within a juvenile court setting using skilled facilitators. Compared to services as usual, the program significantly and meaningfully reduced self-reported delinquent behavior (β = 0.84, p < 0.05) over 6 months, and exhibited trend level effects for reduced substance use (β = 0.40, p = 0.07). The program had mixed or no effects on family conflict and emotion regulation skills. These findings are discussed in light of treatment mechanisms and gender-responsive services., Competing Interests: S.C.W., L.B. and C.H. are listed as inventors of the GOAL program under a University of Washington license and the invention was reported to the Department of Health and Human Services on 03/30/2018. No patent is pending. This does not alter our adherence to PLOS ONE policies on sharing data and materials.

Preterm birth is a significant risk factor for a range of long-term health problems and developmental disabilities. Though touch plays a central role in many perinatal care strategies, the neurobiological basis of these approaches is seldom considered. C-Tactile afferents (CTs) are a class of unmyelinated nerve fibre activated by low force, dynamic touch. Consistent with an interoceptive function, touch specifically targeted to activate CTs activates posterior insular cortex and has been reported to reduce autonomic arousal. The present study compared the effect of 5 min of CT optimal velocity stroking touch to 5 min of static touch on the heart-rate and oxygen saturation levels of preterm infants between 28- & 37-weeks gestational age. CT touch produced a significant decrease in infants' heart-rates and increase in their blood oxygenation levels, which sustained throughout a 5-min post-touch period. In contrast, there was no significant change in heart-rate or blood oxygenation levels of infants receiving static touch. These findings provide support for the hypothesis that CTs signal the affective quality of nurturing touch, providing a neurobiological substrate for the apparent beneficial effects of neonatal tactile interventions and offering insight for their optimisation., (Copyright © 2019 The Authors. Published by Elsevier Ltd.. All rights reserved.)

The psychostimulant drug ±3,4-methylenedioxymethamphetamine (MDMA) reportedly produces distinctive feelings of empathy and closeness with others. MDMA increases social behavior in animal models and has shown promise in psychiatric disorders, such as autism spectrum disorder (ASD) and post-traumatic stress disorder (PTSD). How it produces these prosocial effects is not known. This behavioral and psychophysiological study examined the effects of MDMA, compared with the prototypical stimulant methamphetamine (MA), on two measures of social behavior in healthy young adults: (i) responses to socially relevant, "affective" touch, and (ii) visual attention to emotional faces. Men and women (N = 36) attended four sessions in which they received MDMA (0.75 or 1.5 mg/kg), MA (20 mg), or a placebo in randomized order under double-blind conditions. Responses to experienced and observed affective touch (i.e., being touched or watching others being touched) were assessed using facial electromyography (EMG), a proxy of affective state. Responses to emotional faces were assessed using electrooculography (EOG) in a measure of attentional bias. Subjective ratings were also included. We hypothesized that MDMA, but not MA, would enhance the ratings of pleasantness and psychophysiological responses to affective touch and increase attentional bias toward positive facial expressions. Consistent with this, we found that MDMA, but not MA, selectively enhanced ratings of pleasantness of experienced affective touch. Neither drug altered the ratings of pleasantness of observed touch. On the EOG measure of attentional bias, MDMA, but not MA, increased attention toward happy faces. These results provide new evidence that MDMA can enhance the experience of positive social interactions; in this case, pleasantness of physical touch and attentional bias toward positive facial expressions. The findings are consistent with evidence that the prosocial effects are unique to MDMA relative to another stimulant. Understanding the behavioral and neurobiological processes underlying the distinctive social effects of MDMA is a key step to developing the drug for psychiatric disorders.

Background: Despite a sustained focus by policymakers and researchers on improving the standard of clinical care in public mental health services, the use of evidence-based practice remains low. Among other challenges, this reflects the difficulty of translating clinical research into useable policy that can be feasibly funded and monitored by state or large healthcare systems., Case Presentation: In this paper we present a case study of Washington State's strategy for monitoring the use of clinical elements at the session level for all Medicaid-funded children's mental health services. The implementation of this strategy reflects policy actions to promote effective practice while also actively influencing multiple other levels of the implementation ecology. The approach is informed by the Policy Ecology Framework, the Consolidated Framework for Implementation Research, the evidence-based policymaking literature, and common ontology and clinical elements models., Conclusions: We found the strategy developed in Washington State to be a feasible method of collecting session level information about the use of effective clinical mental health practices. In addition, the approach appears to be having influence on multiple layers of the implementation ecology that could be explored through further study., Competing Interests: The authors declare that they have no competing interests.

Astronauts training for extravehicular activity (EVA) operations can spend many hours submerged underwater in a pressurized suit, called an extravehicular mobility unit (EMU), exposed to pressures exceeding 2 atmospheres absolute (ATA). To minimize the risk of decompression sickness (DCS) a 46% nitrox mixture is used. This limits the nitrogen partial pressure, decreasing the risk of DCS. The trade-off with using a 46% nitrox mixture is the increased potential for oxygen toxicity, which can lead to severe neurologic symptoms including seizures. Suited runs, which typically expose astronauts of 0.9-1.1 ATA for longer than six hours, routinely exceed the recommendation for central nervous system oxygen toxicity limits (CNSOTL) published by the National Oceanic and Atmospheric Administration (NOAA). Fortunately, in over 50,000 hours of suited training dives spanning 20 years of EVA training operations at NASA's Neutral Buoyancy Laboratory (NBL) there has never been an occurrence of oxygen toxicity. This lends support to anecdotal sentiment among certain members of the hyperbaric community that the NOAA CNSOTL recommendations might be overly conservative, at least for the oxygen pressure and time regime in which NBL operates. The NOAA CNSOTL recommendations are the result of expert consensus with a focus on safety and do not necessarily reflect rigorous experimental evidence. The data from the NBL suited dive operations provide a foundation of evidence that can help inform the expert discussion on dive-related neurologic oxygen toxicity performance and overnight recovery in young, healthy males., Competing Interests: The authors of this paper declare no conflicts of interest exist with this submission., (Copyright© Undersea and Hyperbaric Medical Society.)

Background: Arterial stiffness, measured by the augmentation index (AIX) from radial artery tonometry, and endothelial dysfunction, measured by brachial-artery flow-mediated vasodilation (FMD), have each been associated with increased risk of cardiovascular events. However, their interrelationship in peripheral artery disease (PAD) patients is poorly understood., Materials and Methods: In a cross-sectional analysis of 123 vascular surgery outpatients, the association between FMD and AIX was examined in controls with atherosclerotic risk factors (n = 32) and patients with PAD (n = 91). PAD was defined as claudication symptoms with an ankle-brachial index of <0.9 or a history of revascularization for symptomatic PAD. Controls had an ankle-brachial index ≥0.9 and no history of atherosclerotic vascular disease., Results: Compared to controls, patients with PAD had lower FMD (6.3 ± 3.8 versus 8.4 ± 3.7, P = 0.008), while central AIX normalized to 75 beats per minute (25.5 ± 9.0 versus 19.3 ± 8.6, P = 0.001) and peripheral AIX (91.3 ± 14.5 versus 81.3 ± 11.4, P = 0.001) were higher. FMD was not significantly correlated with either central or peripheral AIX (central AIX: P = 0.58; peripheral AIX: P = 0.89) across the entire cohort, or in either the patients with PAD (central AIX: P = 0.48; peripheral AIX: P = 0.23) or controls (central AIX: P = 0.43; peripheral AIX: P = 0.92). In a multivariate model including FMD, higher AIX remained independently associated with PAD., Conclusions: In an analysis of vascular surgery outpatients, no correlation between FMD and AIX was detected. Larger prospective studies are needed to determine whether the inclusion of both parameters improves predictive models for the early identification and potential risk stratification of PAD patients., (Published by Elsevier Inc.)

The rewarding sensation of touch in affiliative interactions is hypothesised to be underpinned by an unmyelinated system of nerve fibres called C-tactile afferents (CTs). CTs are velocity tuned, responding optimally to slow, gentle touch, typical of a caress. Here we used evaluative conditioning to examine whether CT activation carries a positive affective value. A set of neutral faces were paired with robotically delivered touch to the forearm. With half the faces touch was delivered at a CT optimal velocity of 3cm/s (CT touch) and with the other half at a faster, non-CT optimal velocity of 30cm/s (Control touch). Heart-rate and skin conductance responses (SCRs) were recorded throughout. Whilst rated equally approachable pre-conditioning, post-conditioning faces paired with CT touch were judged significantly more approachable than those paired with Control touch. CT touch also elicited significantly greater heart-rate deceleration and lower amplitude SCRs than Control touch. The results indicate CT touch carries a positive affective value, which can be acquired by socially relevant stimuli it is associated with., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Low intensity, non-noxious, stimulation of cutaneous somatosensory nerves has been shown to trigger oxytocin release and is associated with increased social motivation, plus reduced physiological and behavioural reactivity to stressors. However, to date, little attention has been paid to the specific nature of the mechanosensory nerves which mediate these effects. In recent years, the neuroscientific study of human skin nerves (microneurography studies on single peripheral nerve fibres) has led to the identification and characterisation of a class of touch sensitive nerve fibres named C-tactile afferents. Neither itch nor pain receptive, these unmyelinated, low threshold mechanoreceptors, found only in hairy skin, respond optimally to low force/velocity stroking touch. Notably, the speed of stroking which C-tactile afferents fire most strongly to is also that which people perceive to be most pleasant. The social touch hypothesis posits that this system of nerves has evolved in mammals to signal the rewarding value of physical contact in nurturing and social interactions. In support of this hypothesis, we review the evidence that cutaneous stimulation directly targeted to optimally activate C-tactile afferents reduces physiological arousal, carries a positive affective value and, under healthy conditions, inhibits responses to painful stimuli. These effects mirror those, we also review, which have been reported following endogenous release and exogenous administration of oxytocin. Taken together this suggests C-tactile afferent stimulation may mediate oxytocin release during affiliative tactile interactions., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

The rewarding sensation of touch in affiliative interactions is hypothesized to be underpinned by a specialized system of nerve fibers called C-Tactile afferents (CTs), which respond optimally to slowly moving, gentle touch, typical of a caress. However, empirical evidence to support the theory that CTs encode socially relevant, rewarding tactile information in humans is currently limited. While in healthy participants, touch applied at CT optimal velocities (1-10cm/sec) is reliably rated as subjectively pleasant, neuronopathy patients lacking large myelinated afferents, but with intact C-fibres, report that the conscious sensation elicited by stimulation of CTs is rather vague. Given this weak perceptual impact the value of self-report measures for assessing the specific affective value of CT activating touch appears limited. Therefore, we combined subjective ratings of touch pleasantness with implicit measures of affective state (facial electromyography) and autonomic arousal (heart rate) to determine whether CT activation carries a positive affective value. We recorded the activity of two key emotion-relevant facial muscle sites (zygomaticus major-smile muscle, positive affect & corrugator supercilii-frown muscle, negative affect) while participants evaluated the pleasantness of experimenter administered stroking touch, delivered using a soft brush, at two velocities (CT optimal 3cm/sec & CT non-optimal 30cm/sec), on two skin sites (CT innervated forearm & non-CT innervated palm). On both sites, 3cm/sec stroking touch was rated as more pleasant and produced greater heart rate deceleration than 30cm/sec stimulation. However, neither self-report ratings nor heart rate responses discriminated stimulation on the CT innervated arm from stroking of the non-CT innervated palm. In contrast, significantly greater activation of the zygomaticus major (smiling muscle) was seen specifically to CT optimal, 3cm/sec, stroking on the forearm in comparison to all other stimuli. These results offer the first empirical evidence in humans that tactile stimulation that optimally activates CTs carries a positive affective valence that can be measured implicitly.

A subclass of C-fibres, C-tactile afferents (CTs), have been discovered which respond preferentially to low force/velocity stroking touch, that is typically perceived as pleasant. Molecular genetic visualization of these low-threshold mechanosensitive C-fibres (CLTMs) in mice revealed a denser distribution in dorsal than ventral thoracic sites, scattered distal limb innervation and a complete absence from glabrous paw skin (Liu et al., 2007). Here we used third-party ratings to examine whether affective responses to social touch reflect the anatomical distribution and velocity tuning of CTs. Participants viewed and rated a sequence of video clips depicting one individual being touched by another at different skin sites and at 3 different velocities (static, 3cm/s, 30cm/s). Immediately after viewing each clip participants were asked to rate how pleasant they perceived the touch to be. Vicarious preferences matched the previously reported anatomical innervation density of rodent CLTMs, with touch on the back being rated significantly more pleasant than any other location. Furthermore, in contrast to all other skin sites, CT optimal (3cm/s) touch on the palm of the hand was not preferred to static touch, consistent with the anatomical absence of CTs in glabrous skin. Our findings demonstrate that humans recognise the specific rewarding value of CT optimal caressing touch and their preferences reflect the hypothesised anatomical distribution of CTs., (Copyright © 2016 Elsevier B.V. All rights reserved.)