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Objective This case will illustrate the interdisciplinary management of an adolescent female patient with amelogenesis imperfecta (AI). It will contrast this approach and compare it to the previous "multidisciplinary" treatment rendered before the patient was referred for a second opinion. Clinical considerations The patient had a family history of AI affecting all of her permanent teeth. There were many impacted teeth. The majority of her family and relatives afflicted by this opted for dentures. The patient had undergone 2 years of treatment and was told that her "braces would be removed next week." Her new dentist was concerned because the case was not ready to restore. Conclusion He recommended referral to another orthodontist for a second opinion and formulation of an interdisciplinary treatment plan that would include a periodontist, endodontist, and restorative dentist. The patient's family accepted the second opinion referral and restarted treatment with an interdisciplinary team. The restorative dentist was the quarterback for this integrated and sequenced approach. The case was ultimately restored. A 35 year follow-up shows stability with a caries free, periodontally healthy, esthetic result.

Prey state and prey density mediate antipredator responses that can shift community structure and alter ecosystem processes. For example, well-nourished prey at low densities (i.e., prey with higher per capita predation risk) should respond strongly to predators. Although prey state and density often co-vary across habitats, it is unclear if prey responses to predator cues are habitat-specific. We used mesocosms to compare the habitat-specific responses of purple sea urchins (Strongylocentrotus purpuratus) to waterborne cues from predatory lobsters (Panulirus interruptus). We predicted that urchins from kelp forests (i.e., in well-nourished condition) tested at low densities typically observed in this habitat would respond more strongly to predation risk than barren urchins (i.e., in less nourished condition) tested at high densities typically observed in this habitat. Indeed, when tested at densities associated with respective habitats, urchins from forests, but not barrens, reduced kelp grazing by 69% when exposed to lobster risk cues. Barren urchins that were unresponsive to predator cues at natural, high densities suddenly responded strongly to lobster cues when conspecific densities were reduced. Strong responses of low densities of barren urchins persisted across feeding history (i.e. 0-64 days of starvation). This suggests that barren urchins can respond to predators but typically do not because of high conspecific densities. Because high densities of urchins in barrens should weaken the non-consumptive effects of lobsters, urchins in these habitats may continue to graze in the presence of predators thereby providing a feedback that maintains urchin barrens.

With 20 million living veterans and millions more immediate family members, and approximately 9 million veterans enrolled in the nationally networked VA healthcare system, representing the interests and needs of veterans in this complex community is a substantial endeavor. Based on the importance of engaging Veterans in research, the VA Health Services Research and Development (HSR&D) Service convened a Working Group of VA researchers and Veterans to conduct a review of patient engagement models and develop recommendations for an approach to engage Veterans in health research that would incorporate their unique lived experiences and interests, and their perspectives on research priorities. The Working Group considered the specific context for Veteran engagement in research that includes other VA stakeholders from the operational and clinical leadership of the VA Health Administration (VHA). The resulting model identifies the range of potential stakeholders and three domains of relevant constructs—processes expected to facilitate Veteran engagement in research with other stakeholders, individual stakeholder and external factors, and outcomes. The expectation is that Veteran engagement will benefit research to policy and practice translation, including increasing the transparency of research and producing knowledge that is readily accepted and implemented in healthcare.

On March 23rd, 2020, elite soccer academies in the UK closed in compliance with the government enforced lockdown intended to contain the COVID-19 pandemic. This forced parents, players, and coaches to reconsider how they interacted with, and supported, one another. The aims of the present study were (a) to explore the perceptions of players, parents, and coaches (i.e., the athletic triangle) regarding how they interacted and collaborated with one another during the COVID-19 pandemic to support wellbeing and performance, and; (b) to identify opportunities to enhance workings of those within the athletic triangle resulting from adaptions made following enforced lockdown. Using an interpretive description methodology, semi-structured interviews were conducted with five coaches, six players, and six parents from an English elite academy soccer club. Interviews were analyzed using thematic analysis. Findings highlighted (a) the importance of support and the different means of communication used between members of the athletic triangle to facilitate such support; (b) the increased understanding of each member of the athletic triangle, leading to enhanced relationships, and; (c) how members of the athletic triangle adapted practice to facilitate relationship development during the pandemic and beyond. The identification of these considerations has implications for coach and parent education initiatives to allow for optimal functioning of the athletic triangle as elite academy soccer clubs return from lockdown. These include (a) the importance of continued communication between coach, athlete and parent; (b) increasing understanding of each individual within the athletic triangle; and (c) utilizing key interpersonal and technological skills learnt during the lockdown to further facilitate engagement within the athletic triangle.

To assess the independent and joint contribution of the individual components of metabolic syndrome, and known risk factors for gestational diabetes (GDM), on risk of GDM.Two thousand nine hundred and fifteen women from Australia and New Zealand, who participated in The Screening for Pregnancy Endpoints Study (SCOPE), were included. Using the SCOPE clinical data set and biomarkers obtained at 14-16 weeks' gestation, a logistic regression model was fitted to the binary outcome GDM, with individual metabolic syndrome components (waist circumference, blood pressure, glucose, HDL-C, triglycerides), recruitment site, and other established factors associated with GDM. Hierarchical partitioning was used to assess the relative contribution of each variable.Of the 2915 women, 103 women (3.5%) developed GDM. The deviance explained by the logistic regression model containing all variables was 18.65% and the AUC was 0.809. Seventy percent of the independent effect was accounted for by metabolic syndrome components. The highest independent relative contribution to GDM was circulating triglycerides (17 ± 3%), followed by waist circumference (13 ± 3%). Glucose and maternal BMI contributed 12 ± 2% and 12 ± 3%, respectively. The remaining factors had an independent relative contribution of 10%.Triglyceride concentrations had the highest independent relative importance for risk of GDM. Increased focus for lowering triglycerides as an important risk factor for GDM is warranted.

The hippocampus and amygdala play an important role in the pathophysiology of posttraumatic stress disorder (PTSD). In fact, chronic PTSD has been consistently linked to reductions in hippocampal and amygdala volume. However, the acute impact posttraumatic stress has on the volume of these brain regions has received limited attention. Determining the acute impact posttraumatic stress has on brain volume may improve our understanding of the development of PTSD. Therefore, the present study recruited participants acutely (i.e., ∼1-month posttrauma) following trauma exposure and examined the relationship between brain volume (assessed at ∼1-month posttrauma) and posttraumatic stress symptoms (assessed at ∼1 and >3-months posttrauma) to determine whether brain volume was associated with acute posttraumatic stress symptom expression. Twenty-one trauma-exposed (TE) patients and 19 nontrauma-exposed (NTE) controls were recruited for the present study. Brain volume was assessed by structural magnetic resonance imaging completed during the ∼1-month assessment. Left hippocampal volumes were smaller in TE than NTE participants. Among TE participants, bilateral hippocampal volumes decreased as the number of days posttrauma increased. Further, bilateral hippocampal volumes varied negatively with the severity of posttraumatic stress symptoms at ∼1-month posttrauma. The present findings suggest that there is a progressive decrease in hippocampal volume acutely (e.g., within approximately 1 month) following trauma exposure, and demonstrates that acutely assessed hippocampal volumes vary with posttraumatic stress symptom expression. (PsycInfo Database Record (c) 2021 APA, all rights reserved).

Introduction Sickle cell disease (SCD) is the most common abnormal genetic blood disease that affects ∼100,000 Americans. Approximately 20% to 37% of children with sickle cell anemia have silent cerebral infarcts by the age of 14 years old. Neurocognitive deficits are identified in infants and preschool children with SCD. The purpose of this systematic literature review is to provide a comprehensive understanding of the prevalence, severity, and the associated risk factors for neurodevelopmental delays (NDDs) in children with SCD 5 years of age and younger. Methods Systematic search of 6 databases identified 2467 potentially relevant publications and 8 were identified through a manual search. Only 24 articles met the inclusion criteria. Results We identified an increased prevalence of NDDs (cognitive, motor, or both). Children experienced deficits with language, attention and behavior, executive functioning, school readiness and/or academic performance, and motor skills (fine and gross motor functioning). Risk factors include silent cerebral infarcts and strokes, SCD genotype (HbSS>HbSC), other biological, and social factors. Conclusion NDDs are common in children ages 0 to 5 years old with SCD. There is an opportunity to improve adherence to national guideline recommendations and early detection practices by pediatricians, hematologists, and other health care providers.

Mixed-halide perovskites offer bandgap tunability essential for multijunction solar cells; however, a detrimental halide segregation under light is often observed. Here we combine simultaneous in situ photoluminescence and X-ray diffraction measurements to demonstrate clear differences in compositional and optoelectronic changes associated with halide segregation in MAPb(Br0.5I0.5)3 and FA0.83Cs0.17Pb(Br0.4I0.6)3 films. We report evidence for low-barrier ionic pathways in MAPb(Br0.5I0.5)3, which allow for the rearrangement of halide ions in localized volumes of perovskite without significant compositional changes to the bulk material. In contrast, FA0.83Cs0.17Pb(Br0.4I0.6)3 lacks such low-barrier ionic pathways and is, consequently, more stable against halide segregation. However, under prolonged illumination, it exhibits a considerable ionic rearrangement throughout the bulk material, which may be triggered by an initial demixing of A-site cations, altering the composition of the bulk perovskite and reducing its stability against halide segregation. Our work elucidates links between composition, ionic pathways, and halide segregation, and it facilitates the future engineering of phase-stable mixed-halide perovskites.

Deceased organ donor intervention research aims to increase organ quality and quantity for transplantation. We assessed the proportion of kidney transplant candidates who would accept "intervention organs," participate in organ intervention research, and factors influencing acceptance. Kidney transplant candidates were presented 12 hypothetical scenarios, which varied three attributes, donor age, predicted waiting time to receive another organ offer, and research risk to the organ. Candidates were also randomly assigned to one of two conditions varying recipient risk. For each scenario, candidates agreed to accept the intervention organ or remain waitlisted. We fit a multivariable logit model to determine the association between scenario attributes and the acceptance decision. Of 249 participants, most (96%) accepted intervention organs under some or all conditions. Factors independently associated with candidates' greater likelihood of accepting an intervention organ included: low risk to the kidney from the intervention (OR 20.53 [95% Confidence Interval (CI), 13.91-30.29]); younger donor age (OR 3.72 [95% CI, 2.83-4.89]), longer time until the next organ offer (OR 3.48 [95% CI, 2.65-4.57]), and greater trust in their transplant physician (OR 1.03 [95% CI, 1.00-1.06]). Candidates with a lower likelihood of acceptance had been waitlisted longer (OR 0.97 per month [95% CI, 0.96-0.99]) and were Black (OR 0.21 [95% CI, 0.08-0.55]). Most candidates would accept an intervention organ, which should encourage transplant leaders to conduct deceased donor organ intervention trials.

Disclosed in this communication is a thorough study on the dearomative addition of organomagnesium nucleophiles to N-alkyl pyridinium electrophiles. The regiochemical outcomes have observable and predictable trends associated with the substituent patterns on the pyridinium electrophile. Often, the substituent effects can be either additive, giving high selectivities, or ablative, giving competing outcomes. Additionally, the nature of the organometallic nucleophilic component was also investigated for its role in the regioselective outcome. The effects of either reactive component are important to both the overall reactivity and site of nucleophilic addition. The utility of these observed trends is demonstrated in a concise, dearomative synthesis of a tricyclic compound shown to have insecticidal activity.

International audience; The purpose of this study was to examine the association between young players’ perception of mother’s and father’s responsiveness with their self-esteem, anxiety (i.e., worry), and thriving (i.e., positive affect, vitality, and life satisfaction). In total, 314 male British rugby players with a mean age of 16.23 years (SD = 0.26) completed the study in two phases: n = 124 (first dataset), and n = 192 (second dataset). Participants trained on average 3.14 times/week (SD = 0.94) and had been involved in rugby for an average of 8.21 years (SD = 2.89). Participants completed questionnaires measuring perceived parental responsiveness (PPR) for their mother and father, self-esteem, worry about sport performance, and thriving indicators (i.e., positive affect, vitality, and life satisfaction). The results consistently indicated that participants’ perceptions of their mother’s and father’s responsiveness positively related to thriving, and negatively related to their worry about sport performance, mediated by their self-esteem. Overall, the study highlights the need for parents to be provided with insights into the value of being responsive to their child and being encouraged to regularly talk with their child regarding their needs and desires, and seeking to understand how their child perceives the support they currently receive.

We investigated genome folding across the eukaryotic tree of life. We find two types of three-dimensional(3D) genome architectures at the chromosome scale. Each type appears and disappears repeatedlyduring eukaryotic evolution. The type of genome architecture that an organism exhibits correlates with theabsence of condensin II subunits. Moreover, condensin II depletion converts the architecture of thehuman genome to a state resembling that seen in organisms such as fungi or mosquitoes. In this state,centromeres cluster together at nucleoli, and heterochromatin domains merge. We propose a physicalmodel in which lengthwise compaction of chromosomes by condensin II during mitosis determineschromosome-scale genome architecture, with effects that are retained during the subsequent interphase.This mechanism likely has been conserved since the last common ancestor of all eukaryotes., C.H. is supported by the Boehringer Ingelheim Fonds; C.H., Á.S.C., and B.D.R. are supported by an ERC CoG (772471, “CohesinLooping”); A.M.O.E. and B.D.R. are supported by the Dutch Research Council (NWO-Echo); and J.A.R. and R.H.M. are supported by the Dutch Cancer Society (KWF). T.v.S. and B.v.S. are supported by NIH Common Fund “4D Nucleome” Program grant U54DK107965. H.T. and E.d.W. are supported by an ERC StG (637597, “HAP-PHEN”). J.A.R., T.v.S., H.T., R.H.M., B.v.S., and E.d.W. are part of the Oncode Institute, which is partly financed by the Dutch Cancer Society. Work at the Center for Theoretical Biological Physics is sponsored by the NSF (grants PHY-2019745 and CHE-1614101) and by the Welch Foundation (grant C-1792). V.G.C. is funded by FAPESP (São Paulo State Research Foundation and Higher Education Personnel) grants 2016/13998-8 and 2017/09662-7. J.N.O. is a CPRIT Scholar in Cancer Research. E.L.A. was supported by an NSF Physics Frontiers Center Award (PHY-2019745), the Welch Foundation (Q-1866), a USDA Agriculture and Food Research Initiative grant (2017-05741), the Behavioral Plasticity Research Institute (NSF DBI-2021795), and an NIH Encyclopedia of DNA Elements Mapping Center Award (UM1HG009375). Hi-C data for the 24 species were created by the DNA Zoo Consortium (www.dnazoo.org). DNA Zoo is supported by Illumina, Inc.; IBM; and the Pawsey Supercomputing Center. P.K. is supported by the University of Western Australia. L.L.M. was supported by NIH (1R01NS114491) and NSF awards (1557923, 1548121, and 1645219) and the Human Frontiers Science Program (RGP0060/2017). The draft A. californica project was supported by NHGRI. J.L.G.-S. received funding from the ERC (grant agreement no. 740041), the Spanish Ministerio de Economía y Competitividad (grant no. BFU2016-74961-P), and the institutional grant Unidad de Excelencia María de Maeztu (MDM-2016-0687). R.D.K. is supported by NIH grant RO1DK121366. V.H. is supported by NIH grant NIH1P41HD071837. K.M. is supported by a MEXT grant (20H05936). M.C.W. is supported by the NIH grants R01AG045183, R01AT009050, R01AG062257, and DP1DK113644 and by the Welch Foundation. E.F. was supported by NHGRI

International audience; Objective: The purpose of this study was to examine the influence of parental responsive support (observed) and perceived parental responsive support on athletes’ self-perceptions and thriving. Methods: Forty-one French-speaking Belgian individual sport athletes aged 12-15 years (M = 13.13, SD = 0.90) and one of their parent’s spent 10 minutes discussing three important athletes’ sport-related goals for the next season. The discussion was video-taped and coded to identify parents’ responsive support behaviors. After the discussion, athletes responded to a series of questionnaires measuring perceived parental responsiveness, self-efficacy, self-esteem, and thriving indicators (i.e., positive affect, vitality, life satisfaction, and health quality). Results: The results show that observed and perceived parental responsive support contributed to athletes’ proximal perceptions of self-efficacy. Both parental observed responsive support and athletes’ perceived parental responsiveness, mediated by athletes’ self-efficacy, were positively related to athlete’s self-esteem. Further, athletes’ perceived parental responsiveness was positively related with thriving while mediated in series by self-efficacy and self-esteem. Conclusion: Overall, it appears that parents’ responsive support (observed) and athletes’ perception of responsive support are associated with positive self-perceptions and optimal wellbeing in young athletes. This study demonstrates that parents can provide responsive support to their children in the sport context. These results add further weight to suggestions that sport organizations should actively include, rather than exclude, parents in their processes.

The purpose of this study was to explore the transitional experiences of British swimmers as they attempted to qualify for the Olympic Games and gain a place in the British Swimming World Class Performance Programme. An interpretive phenomenological analysis (IPA) approach was adopted (Smith JA. Psychol Health 1996;11:261-271). Six swimmers (aged 20-25 years), one of each of their parents, and four coaches completed interviews leading up to and following Olympic trials over an eight-month period. Audio recordings were transcribed verbatim and analyzed following the guidelines set out by Smith and Osborne (Smith JA, Osborn M. Qualitative psychology: A practical guide to research methods. London: Sage; 2003:51-80). Results indicated that athletes' transition experiences were characterized by a range of demands, which were categorized into five higher-order themes (a) Questioning "Am I good enough?"; (b) Managing and fulfilling expectations; (c) Operating within an environment that is working against them; (d) Lacking support and understanding of self and demands; and (e) Maintaining balance versus being an international swimmer. Overall, the results indicate that this attempted transition is complex, challenging, and unique and largely influenced by self-confidence. Addressing the individual factors impacting on athletes' self-confidence appears critical to enhancing swimmers' transitional experiences at the highest level.

The study aimed to develop an understanding of female coaches’ and sport science practitioners’ experience and support provision in relation to the menstrual cycle when working with female athletes. Following receipt of institutional ethical approval, 14 female coaches and practitioners (32.9 ± 6.9 years) participated in individual semi-structured interviews. Following analysis, two themes were developed: (1) Knowledge and awareness and (2) Support and management. Overall, it appeared that participants varied in their understanding and awareness of the impact of the menstrual cycle on sport performance, somewhat influenced by their own personal experiences. Participants’ knowledge and awareness subsequently impacted the support they provided to female athletes. Additionally, individual experiences and perceived secrecy relating to the menstrual cycle impacted on the informational and emotional support participants provided. Together, the findings highlight the importance of all coaches and practitioners enhancing their knowledge and understanding regarding the menstrual cycle and proactively providing support to athletes. Education to enhance coaches’ and practitioners’ knowledge and understanding will help to create a more open and supportive environment in sport, hopefully allowing for personal discomfort regarding the menstrual cycle to be addressed.

10549 Background: In Kansas, breast cancer (BC) incidence is similar in Black and white women, yet Black women are 42% more likely to die from the disease. In models where screening is equal, there is no difference in survival from early-stage BC. Barriers to BC early detection in Black women include provider lack of knowledge in cancer risk, performing risk assessments and providing culturally sensitive education to patients. Our team developed a didactic and case-based learning intervention using Project ECHO (Extension for Community Health Outcomes) to improve provider knowledge on performing BC risk assessment and enhance risk stratified screening in Community Health Clinics (CHCs). A Community Advisory Board (CAB) was established to address barriers to early detection. Methods: CHCs participated in five 1-hour ECHO sessions June thru August 2021. Session topics focused on calculating BC risk, community resources, and cultural sensitivity and were led by experts in breast oncology, risk, genetics, screening, and health care equity. Pre/post surveys administered to participants assessed knowledge and satisfaction and continuing education credits were offered. A CAB member survey gained insight into organizational characteristics and community reach. Asset mapping identified barriers, resources, and opportunities to promote BC screening. Descriptive statistical analyses and the RE-AIM framework were used to assess reach and scalability of the ECHO. Results: Seventy-seven individuals from 16 CHCs registered to participate with a mean of 26 attendees at each session and 34% attending two or more. Participants were physicians (19%), advanced practice providers (18%), nurses (29%), and allied health professionals (34%). Sixty-three (82%) completed the baseline survey and 10 (13%) completed the post-ECHO survey. At baseline, 32% of participants reported lack of training and time as barriers to performing risk assessment. While post-ECHO survey responses were low, 60% reported their knowledge greatly or moderately improved across all topics. Participants reported clinical practice change in assessing personal history of cancer and collecting family history beyond first degree relatives. CAB members reported a broad range of expertise in community engagement and development (44%), direct patient care (15%), healthcare access (15%) and patient advocacy (26%). CAB education and collaboration led to support for tomosynthesis for women screened in our state funded BC screening program, Early Detection Works (EDW). Ongoing asset mapping identified gaps in access for Black women to the EDW program. Conclusions: Project BRA demonstrated successful participation in a limited series Project ECHO and achieved perceived changes in knowledge on performing BC risk assessment. Next steps include incorporating CAB informed opportunities to expand risk-based screening across Kansas and advocate for improved access to risk stratified screening.

BackgroundData on fluctuation of antibodies directed against domain 1 (anti-D1) of β2-glycoprotein I (β2GPI) are scarce. Patients with antiphospholipid syndrome (APS) and all three criteria tests for antiphospholipid antibodies (aPL) display higher titers of anti-D1, which correlate with anti-β2GPI levels.ObjectivesThis project aims at evaluating predictors of the variation of anti-D1 titers over time in a large international cohort of persistently aPL positive patients.MethodsAntiPhospholipid Syndrome Alliance For Clinical Trials and InternatiOnal Networking (APS ACTION) Registry was created to study the course of persistently aPL-positive patients with or without autoimmune disorders over at least 10 years. Inclusion criteria are positive aPL by Updated Sapporo Criteria tested within one year prior to enrolment. Patients are followed every 12±3 months with clinical data and blood collection. Patients with available blood samples from at least three time points were included in this analysis. Anti-β2GPI and anti-D1 IgG were tested by chemiluminescence (BioFlash, Werfen) at APS ACTION core laboratories. Positive results were defined as >20 CU, according to the manufacturer. Clinical data were retrieved from APS ACTION online database. Anti-D1 titers within the same subject were compared by Friedman’s test. A mixed linear model was built to identify predictors of the fluctuation of anti-D1 antibody titers over time.ResultsIn this longitudinal study, 230 patients with anti-D1 tested at 4 time points were included (Table 1). Patients with thrombotic APS had anti-D1 titers significantly higher than those without thrombosis (p=0.022). Among 135 patients with at least one anti-D1 positive result, anti-D1 titers varied significantly over time (Friedman statistics: 508.5, pTable 1.Demographic and Clinical Characteristics of 230 APS ACTION Registry Patients with anti-D1 tested ≥3 time points during the follow-upAnti-D1 pos samplesAnti-D1 neg samplesp-valueOverall sample(n=135)(n=95)(n=230)Age [years] mean (SD)42.3 (11.8)48.8 (13.0)0.000145.0 (12.7)%Female (n)71.9 (97)65.3 (62)0.35869.1 (159)Associated systemic autoimmune disease39.3 (53)44.2 (42)0.53941.3 (95)aPL without APS19.3 (26)34.7 (33)0.01025.7 (59)Thrombotic APS54.1 (73)53.7 (51)53.9 (124)Obstetric APS11.9 (16)5.3 (5)9.1 (21)Thrombotic/+obstetric APS14.8 (20)6.3 (6)11.3 (26)aCL IgG89.5 (119/133)25.5 (24/94)63.0 (143/227)aCL, IgM36.1 (48/133)27.7 (26/94)0.23432.6 (74/227)Anti-2GPI, IgG93.2 (124/133)39.4 (37/94)70.9 (161/227)Anti-2GPI, IgM34.6 (46/133)21.3 (20/94)0.04329.1 (66/227)LA82.8 (82/99)59.5 (44/74)0.00172.8 (126/173)ConclusionTreatment with HCQ and vascular events during follow-up were identified as significant predictors of the fluctuation of anti-D1 antibody titers over time.Disclosure of InterestsNone declared.

Background: Schools and outdoor public spaces play a substantial role in children's physical activity. Yet, the COVID-19 shelter-in-place mandates bound many children to their available home spaces for learning, movement, and development. The exact effect this mandate had on children's physical activity may vary among families.Objective: To understand, from the perspective of parents, how the COVID-19 shelter-in-place mandates affected children's physical activity, while also considering families' socioeconomic status.Design: Open-ended survey.Setting: Online.Method: Data were collected from 321 parents living in the United States of America. Parents answered an open-ended prompt to describe their children's physical activity during COVID-19 shelter-in-place mandates. Following data collection, inductive and deductive content analysis examined patterns in the data.Results: Analyses indicated that shelter-in-place mandates restricted children's opportunities for physical activity. However, if families had access to outdoor spaces or equipment, they could encourage and support more physical activity opportunities than those without. Families in the lower-income bracket had less access to outdoor space and subsequently those children had fewer opportunities to be physically active. Parents supported their children's physical activity through their involvement and encouragement.Conclusion: These findings underscore the importance of access to outdoor spaces and equipment for increasing children's physical activity. Findings can be used by educators and policymakers to equitably support families of lower socioeconomic status who reported less access to outdoor spaces.

Myosin-2 is essential for processes as diverse as cell division and muscle contraction. Dephosphorylation of its regulatory light chain promotes an inactive, ‘shutdown’ state with the filament-forming tail folded onto the two heads1, which prevents filament formation and inactivates the motors2. The mechanism by which this happens is unclear. Here we report a cryo-electron microscopy structure of shutdown smooth muscle myosin with a resolution of 6 A in the head region. A pseudo-atomic model, obtained by flexible fitting of crystal structures into the density and molecular dynamics simulations, describes interaction interfaces at the atomic level. The N-terminal extension of one regulatory light chain interacts with the tail, and the other with the partner head, revealing how the regulatory light chains stabilize the shutdown state in different ways and how their phosphorylation would allow myosin activation. Additional interactions between the three segments of the coiled coil, the motor domains and the light chains stabilize the shutdown molecule. The structure of the lever in each head is competent to generate force upon activation. This shutdown structure is relevant to all isoforms of myosin-2 and provides a framework for understanding their disease-causing mutations. The structure of myosin-2 in the shutdown state reveals how the shutdown state is stabilized and how phosphorylation of light chains allows myosin to be activated.

Background Renal allograft survival is negatively affected by the development of de novo posttransplant donor-specific antibodies (dnDSA). We sought to determine whether treatment with intravenous immunoglobulin (IVIG) could remove or reduce the intensity of dnDSA. Methods A single-center study of 12 recipients with dnDSA and stable function who received IVIG 1 g/kg monthly for 6 months were compared with a contemporaneous cohort of 24 recipients with dnDSA who did not receive IVIG. Results The median time to first dnDSA was 6 months (interquartile range [IQR], 1-12), and follow-up was 83 months (IQR, 58-94) posttransplant. Resolution of dnDSA occurred in 27% of IVIG vs 46% of control recipients (P = .48). Fifty-eight percent of recipients in both cohorts demonstrated a reduction in the intensity of the dominant DSA at last follow-up (P =1.0). A reduction in the number of dnDSAs occurred in 58% vs 62% of the IVIG and control cohorts, respectively (P = .81). Post-dnDSA, acute rejection occurred in 8% of the IVIG vs 42% in the control group (P = .06). Forty-two percent of IVIG-treated vs 49% of control recipients had a deterioration in function from first dnDSA until most recent follow-up (P = .81). Actuarial graft survivals were equivalent between groups. Conclusions IVIG treatment of dnDSA in recipients with stable graft function had no impact on DSA clearance or MFI reduction, but this outcome may also be owing to sample size. Larger studies or alternate dosing regimens may be required to determine if there is any role for the use of IVIG as a treatment for dnDSA.

Objective The aim of this study was to obtain feedback from key stakeholders and end users to identify program strengths and weaknesses to plan for wider dissemination and implementation of the Virtual Acute Care for Elders (Virtual ACE) program, a novel intervention that improves outcomes for older surgical patients. Background Virtual ACE was developed to deliver evidence-based geriatric care without requiring daily presence of a geriatrician. Previous work demonstrated that Virtual ACE increased mobility and decreased delirium rates for surgical patients. Methods We conducted semi-structured interviews with 30 key stakeholders (physicians, nurses, hospital leadership, nurse managers, information technology staff, and physical/occupational therapists) involved in the implementation and use of the program. Results Our stakeholders indicated that Virtual ACE was extremely empowering for bedside nurses. The program helped nurses identify older patients who were at risk for a difficult postoperative recovery. Virtual ACE also gave them skills to manage complex older patients and more effectively communicate their needs to surgeons and other providers. Nurse managers felt that Virtual ACE helped them allocate limited resources and plan their unit staffing assignments to better manage the needs of older patients. The main criticism was that the Virtual ACE Tracker that displayed patient status was difficult to interpret and could be improved by a better design interface. Stakeholders also felt that program training needed to be improved to accommodate staff turnover. Conclusions Although respondents identified areas for improvement, our stakeholders felt that Virtual ACE empowered them and provided effective tools to improve outcomes for older surgical patients.

A better understanding of early brain changes that precede loss of independence in diseases like Alzheimer’s disease (AD) is critical for development of disease-modifying therapies. Quantitative MRI, such as T2 relaxometry, can identify microstructural changes relevant to early stages of pathology. Recent evidence suggests heterogeneity of T2 may be a more informative measure of early pathology than absolute T2. Here we test whether T2 markers of brain integrity precede the volume changes we know are present in established AD and whether such changes are most marked in medial temporal lobe (MTL) subfields known to be most affected early in AD. We show that T2 heterogeneity was greater in people with mild cognitive impairment (MCI; n=49) compared to healthy older controls (n=99) in all MTL subfields, but this increase was greatest in MTL cortices, and smallest in dentate gyrus. This reflects the spatio-temporal progression of neurodegeneration in AD. T2 heterogeneity in the entorhinal cortex also predicted cognitive decline over a year in people with MCI, where measures of volume or T2 in any other subfield or whole hippocampus could not. Increases in T2 heterogeneity in MTL cortices may reflect localised pathological change and may present as one of the earliest detectible brain changes prior to atrophy. Finally, we describe a mechanism by which memory, as measured by accuracy and reaction time on a paired associate learning task, deteriorates with age. Age-related memory deficits were explained in part by lower subfield volumes, which in turn were directly associated with greater T2 heterogeneity. We propose that tissue with high T2 heterogeneity represents extant tissue at risk of permanent damage but with the potential for therapeutic rescue. This has implications for early detection of neurodegenerative disease.

Background Although secure messaging (SM) between patients and clinical team members is a recommended component of continuous care, uptake by patients remains relatively low. We designed a multicomponent Supported Adoption Program (SAP) to increase SM adoption among patients using the Veterans Health Administration (VHA) for primary care. Objective Our goals were to (1) conduct a multisite, randomized, encouragement design trial to test the effectiveness of an SAP designed to increase patient engagement with SM through VHA’s online patient portal (My HealtheVet [MHV]) and (2) evaluate the impact of the SAP and patient-level SM adoption on perceived provider autonomy support and communication. Patient-reported barriers to SM adoption were also assessed. Methods We randomized 1195 patients at 3 VHA facilities who had MHV portal accounts but had never used SM. Half were randomized to receive the SAP, and half served as controls receiving usual care. The SAP consisted of encouragement to adopt SM via mailed educational materials, proactive SM sent to patients, and telephone-based motivational interviews. We examined differences in SM adoption rates between SAP recipients and controls at 9 months and 21 months. Follow-up telephone surveys were conducted to assess perceived provider autonomy support and self-report of telephone communication with clinical teams. Results Patients randomized to the SAP had significantly higher rates of SM adoption than the control group (101/595, 17.0% vs 40/600, 6.7%; P Conclusions The multicomponent SAP was successful in increasing use of SM 10 percentage points above standard care; new SM adopters reported improved perceptions of provider autonomy support and less use of the telephone to communicate with their providers. Still, despite the encouragement and technical assistance provided through the SAP, adoption rates were lower than anticipated, reaching only 24% at 21 months (10% above controls). Common barriers to adoption such as limited perceived need for SM may be more challenging to address and require different interventions than barriers related to patient self-efficacy or technical difficulties. Trial Registration ClinicalTrials.gov NCT02665468; https://clinicaltrials.gov/ct2/show/NCT02665468

The role and importance of parents within sport cannot be underestimated. It is only as a result of parents’ support and encouragement that many children are able to participate in sport. More than this, parents are vital in helping to ensure that the experience children have in sport is not only enjoyable but also safe. Unfortunately, parents are not always able to prevent their children encountering harm in sport and, in fact, some parents can find themselves negatively contributing to children’s well-being and safety in sport. This chapter seeks to unpack the complexity of the parent role within youth sport, particularly with regard to children’s welfare. It starts by reviewing the roles of parents in sport and associated consequences of parental involvement. Next, a review of parents’ involvement in safeguarding children in sport is presented. Finally, the chapter concludes by outlining key strategies that clubs, coaches, and parents can take to ensure that parents are able to be involved in the most positive ways in sport.

This 2020 International Consensus on Cardiopulmonary Resuscitation and Emergency Cardiovascular Care Science With Treatment Recommendations (CoSTR) for pediatric life support is based on the most extensive evidence evaluation ever performed by the Pediatric Life Support Task Force. Three types of evidence evaluation were used in this review: systematic reviews, scoping reviews, and evidence updates. Per agreement with the evidence evaluation recommendations of the International Liaison Committee on Resuscitation, only systematic reviews could result in a new or revised treatment recommendation. Systematic reviews performed for this 2020 CoSTR for pediatric life support included the topics of sequencing of airway-breaths-compressions versus compressions-airway-breaths in the delivery of pediatric basic life support, the initial timing and dose intervals for epinephrine administration during resuscitation, and the targets for oxygen and carbon dioxide levels in pediatric patients after return of spontaneous circulation. The most controversial topics included the initial timing and dose intervals of epinephrine administration (new treatment recommendations were made) and the administration of fluid for infants and children with septic shock (this latter topic was evaluated by evidence update). All evidence reviews identified the paucity of pediatric data and the need for more research involving resuscitation of infants and children.

Prcis Patients with chronic kidney disease are at increased risk for choroidal effusion development following glaucoma surgery. Purpose Choroidal effusion is a postoperative complication of glaucoma surgery that results from a transudative fluid collection in the suprachoroidal space. Kidney disease alters bodily fluid dynamics through a variety of mechanisms. The relationship between chronic kidney disease and choroidal effusion following glaucoma surgery has not previously been studied. The purpose of this study was to determine the relationship between chronic kidney disease and choroidal effusion development after glaucoma surgery. Patients and methods This retrospective cohort study consisted of 86 eyes from 86 patients who received glaucoma filtering surgery or transscleral cyclophotocoagulation within the study timeframe. Forty-three patients had chronic kidney disease and 43 patients did not have kidney disease. The main outcome of this study was the development of choroidal effusion measured by Pearson's chi-squared test and multivariate analyses using a binomial regression with a log link. Results Ten patients (23.3%) in the chronic kidney disease group developed choroidal effusion while two patients (4.7%) in the no-kidney disease group developed choroidal effusion (relative risk, 5.0; 95% confidence interval 1.16 to 21.5; P=0.013). The association between chronic kidney disease and choroidal effusion showed mixed results in the multivariate analyses, with some analyses showing a significant association and others showing no significant association. Conclusions In both the univariate analysis and multivariate analysis, chronic kidney disease was found to be significantly associated with choroidal effusion after glaucoma surgery.

Leading global physical activity guidelines advocate that young children need to engage in activities that strengthen musculoskeletal tissues and improve movement skill competency. The purpose of this study was to examine the effects of delivering strength and conditioning as part of the physical education curriculum on athletic motor skill competencies (AMSC), physical performance, and psychosocial factors. Forty-six school children aged 11&ndash, 14 were included in the study, and sub-divided firstly by sex and then into intervention and control groups. Intervention groups received nine lessons of strength and conditioning based activities over a six-week period, while the control groups continued with traditional physical education curricula. The resistance training skills battery (RTSB) and tuck jump assessment (TJA) assessed AMSC. Standing long jump distance assessed lower limb strength, and online surveys examined motivation, physical self-efficacy and self-esteem. Male and female intervention groups significantly improved RTSB (p &gt, 0.05) whereas no changes were observed in the control groups. No changes were observed in the intervention groups TJA and only trivial and small non-significant changes in standing long jump performance. Significant increases in motivation of the male intervention group occurred. Strength and conditioning integrated in physical education can improve AMSC in short-term interventions.

Background While many studies have tested the impact of a decision aid (DA) compared to not receiving any DA, far fewer have tested how different types of DAs affect key outcomes such as treatment choice, patient–provider communication, or decision process/satisfaction. This study tested the impact of a complex medical oriented DA compared to a more simplistic decision aid designed to encourage shared decision making in men with clinically localized prostate cancer. Methods 1028 men at 4 VA hospitals were recruited after a scheduled prostate biopsy. Participants completed baseline measures and were randomized to receive either a simple or complex DA. Participants were men with clinically localized cancer (N = 285) by biopsy and who completed a baseline survey. Survey measures: baseline (biopsy); immediately prior to seeing the physician for biopsy results (pre- encounter); one week following the physician visit (post-encounter). Outcome measures included treatment preference and treatment received, knowledge, preference for shared decision making, decision making process, and patients’ use and satisfaction with the DA. Results Participants who received the simple DA had greater interest in shared decision making after reading the DA (p = 0.03), found the DA more helpful (p’s Conclusions The simple DA led to increased desire for shared decision making and for less aggressive treatment. However, these differences disappeared following the physician visit, which appeared to change patients’ treatment preferences. Trial registration This trial was pre-registered prior to recruitment of participants.

PRéCIS:: This study addresses the paucity of literature examining glaucoma patients' distance from clinic on postoperative follow-up outcomes. Greater distance from clinic was associated with higher likelihood of loss to follow-up and missed appointments.To investigate the relationship of patient travel distance and interstate access to glaucoma surgery postoperative follow-up visit attendance.Retrospective longitudinal chart review of all noninstitutionalized adult glaucoma patients with initial trabeculectomies or drainage device implantations between April 4, 2014 and December 31, 2018. Patients were stratified into groups on the basis of straight-line distance from residence to University of North Carolina at Chapel Hill's Kittner Eye Center and distance from residence to interstate access. Corrective procedures, visual acuity, appointment cancellations, no-shows, and insurance data were recorded. Means were compared using 2-tailed Student t-test, Pearson χ, analysis of variance, and multivariate logistical regression determined odds ratios for loss to follow-up.In total, 199 patients met all inclusion criteria. Six-month postoperatively, patients50 miles from clinic had greater odds of loss to follow-up compared with patients25 miles (odds ratios, 3.47; 95% confidence interval, 1.24-4.12; P0.05). Patients50 miles from clinic had significantly more missed appointments than patients 25 to 50 miles away, and patients25 miles away (P=0.008). Patients20 miles from interstate access had greater loss to follow-up than those10 miles (t(150)=2.05; P0.05). Mean distance from clinic was 12.59 miles farther for patients lost to follow-up (t(197)=3.29; P0.01). Patients with Medicaid coverage had more missed appointments than those with Medicare plans (t(144)=-2.193; P0.05).Increased distance from clinic and interstate access are associated with increased missed appointments and loss to follow-up. Glaucoma specialists should consider these factors when choosing surgical interventions requiring frequent postoperative evaluations.

BACKGROUND Although secure messaging (SM) between patients and clinical team members is a recommended component of continuous care, uptake by patients remains relatively low. We designed a multicomponent Supported Adoption Program (SAP) to increase SM adoption among patients using the Veterans Health Administration (VHA) for primary care. OBJECTIVE Our goals were to (1) conduct a multisite, randomized, encouragement design trial to test the effectiveness of an SAP designed to increase patient engagement with SM through VHA’s online patient portal (My HealtheVet [MHV]) and (2) evaluate the impact of the SAP and patient-level SM adoption on perceived provider autonomy support and communication. Patient-reported barriers to SM adoption were also assessed. METHODS We randomized 1195 patients at 3 VHA facilities who had MHV portal accounts but had never used SM. Half were randomized to receive the SAP, and half served as controls receiving usual care. The SAP consisted of encouragement to adopt SM via mailed educational materials, proactive SM sent to patients, and telephone-based motivational interviews. We examined differences in SM adoption rates between SAP recipients and controls at 9 months and 21 months. Follow-up telephone surveys were conducted to assess perceived provider autonomy support and self-report of telephone communication with clinical teams. RESULTS Patients randomized to the SAP had significantly higher rates of SM adoption than the control group (101/595, 17.0% vs 40/600, 6.7%; PPP=.007) and less telephone use to communicate with their provider (68.8% vs 76.0%, P=.05), compared to patients in the control group. Patient-reported barriers to SM adoption included self-efficacy (eg, not comfortable using a computer, 24%), no perceived need for SM (22%), and difficulties with portal password or login (17%). CONCLUSIONS The multicomponent SAP was successful in increasing use of SM 10 percentage points above standard care; new SM adopters reported improved perceptions of provider autonomy support and less use of the telephone to communicate with their providers. Still, despite the encouragement and technical assistance provided through the SAP, adoption rates were lower than anticipated, reaching only 24% at 21 months (10% above controls). Common barriers to adoption such as limited perceived need for SM may be more challenging to address and require different interventions than barriers related to patient self-efficacy or technical difficulties. CLINICALTRIAL ClinicalTrials.gov NCT02665468; https://clinicaltrials.gov/ct2/show/NCT02665468

The SARS-CoV-2 virus is more transmissible than previous coronaviruses and causes a more serious illness than seasonal flu. The SARS-CoV-2 receptor binding domain (RBD) of the Spike protein binds to the human angiotensin-converting enzyme 2 (ACE2) receptor as a prelude to viral entry into the cell. Using a naïve llama single chain nanobody library and PCR maturation we have produced a nanobody, H11-D4, with a KD 9 nM for RBD that blocks the binding of RBD to the ACE2. Single particle cryo-electron microscopy revealed that H11-D4 binds to each of the three RBDs in the Spike trimer. The 1.8 Å crystal structure of the H11-D4 – RBD complex has illuminated the molecular interactions that drive the high affinity. H11-D4 binds to an epitope on RBD that overlaps with the ACE2 binding, explaining the blocking of ACE2 binding. The nanobody showed potent neutralising activity against live SARS-CoV-2 virus.

The novel coronavirus SARS-CoV-2 [coronavirus disease 2019 (COVID-19)] is a highly contagious and devastating virus that has currently infected over 2.5 million people worldwide and resulted in 177 641 deaths as of April 2020.1 Although most people diagnosed with COVID-19 exhibit mild-to-moderate symptoms, early reports from China described vulnerable patient populations, such as the elderly and those with chronic underlying medical conditions including the immunosuppressed, having more severe COVID-19-related illness compared to the general population.2,3 Solid organ transplant (SOT) recipients are one of the largest cohorts of immunosuppressed patients, yet little is known about their risk of contracting the virus, postinfection outcomes, and effect of immunosuppression on the clinical course of the disease. Unique challenges, such as immunosuppression management and interpretation of laboratory data, also exist. Current treatment strategies borrow upon prior experience from other pandemics, such as severe acute respiratory syndrome (SARS) and influenza A virus subtype.4 SARS-CoV-2 primarily affects the respiratory tract, progressing from pneumonia to acute respiratory distress syndrome in severe cases.5 In these cases, there is a recognized cytokine release syndrome (CRS) that when occurs results in multiorgan dysfunction and failure.6 The role of immunosuppression in mounting such inflammatory response is unclear. Inflammatory markers, such as C-reactive protein (CRP), lactate dehydrogenase (LDH), and D-dimer, may reflect disease progression and/or severity.7 Lymphopenia is reported as a common presentation among COVID-19 positive patients.8,9 Treatment options are limited. Antivirals such as hydroxychloroquine (HCQ) with or without azithromycin are widely used empiric options. Remdesivir, an RNA polymerase inhibitor, has shown in vitro activity against SARS-CoV-2 and is currently under phase 3 trial.10 Investigational agents to combat the cytokine response, such as tocilizumab, an interleukin 6 (IL-6) receptor inhibitor, are being studied. Although the exact role of immunosuppression on the progression of COVID-19 is unknown, early case reports of kidney transplant recipients suggest minimizing immunosuppression while continuing steroidal therapy.11 Evaluation of clinical symptoms, utility of biomarkers, and progression of disease are important to understand for optimizing the management in COVID-19 positive SOT recipients. The effect of COVID-19 on the heart, lung, liver, pancreas, and kidney transplant organ systems is not well described. Herein, we present our experience with 21 consecutive SOT recipients diagnosed with COVID-19 at the Houston Methodist J.C. Walter Transplant Center followed to April 22, 2020.

Background Early Alzheimer’s disease (AD) diagnosis is vital for development of disease-modifying therapies. Prior to significant brain tissue atrophy, several microstructural changes take place as a result of Alzheimer’s pathology. These include deposition of amyloid, tau and iron, as well as altered water homeostasis in tissue and some cell death. T2 relaxation time, a quantitative MRI measure, is sensitive to these changes and may be a useful non-invasive, early marker of tissue integrity which could predict conversion to dementia. We propose that different microstructural changes affect T2 in opposing ways, such that average ‘midpoint’ measures of T2 are less sensitive than measuring distribution width (heterogeneity). T2 heterogeneity in the brain may present a sensitive early marker of AD pathology. Methods In this cohort study, we tested 97 healthy older controls, 49 people with mild cognitive impairment (MCI) and 10 with a clinical diagnosis of AD. All participants underwent structural MRI including a multi-echo sequence for quantitative T2 assessment. Cognitive change over 1 year was assessed in 20 participants with MCI. T2 distributions were modelled in the hippocampus and thalamus using log-logistic distribution giving measures of log-median value (midpoint; T2μ) and distribution width (heterogeneity; T2σ). Results We show an increase in T2 heterogeneity (T2σ; p p = .149) in the hippocampus and thalamus. Hippocampal T2 heterogeneity predicted cognitive decline over 1 year in MCI participants (p = .018), but midpoint (p = .132) and volume (p = .315) did not. Age affects T2, but the effects described here are significant even after correcting for age. Conclusions We show that T2 heterogeneity can identify subtle changes in microstructural integrity of brain tissue in MCI and predict cognitive decline over a year. We describe a new model that considers the competing effects of factors that both increase and decrease T2. These two opposing forces suggest that previous conclusions based on T2 midpoint may have obscured the true potential of T2 as a marker of subtle neuropathology. We propose that T2 heterogeneity reflects microstructural integrity with potential to be a widely used early biomarker of conditions such as AD.