Time-heterogeneity of the Förster Radius from Dipole Orientational Dynamics Explains Observed Dynamic Shift.

Förster resonance energy transfer (FRET) is a quantum mechanical phenomenon involving the non-radiative transfer of energy between coupled electric dipoles. Due to the strong dependence of FRET on the distance between the dipoles, it is frequently used as a "molecular ruler" in biology, chemistry, and physics. This is done by placing dipolar molecules called dyes on molecules of interest. In time-resolved confocal single-molecule FRET (smFRET) experiments, the joint distribution of the FRET efficiency and the donor fluorescence lifetime can reveal underlying molecular conformational dynamics via deviation from their theoretical Förster relationship. This deviation is referred to as a dynamic shift. Quantifying the dynamic shift caused by the motion of the fluorescent dyes is essential to decoupling the dynamics of the studied molecules and the dyes. We develop novel Langevin models for the dye linker dynamics, including rotational dynamics, based on first physics principles and proper dye linker chemistry to match accessible volumes predicted by molecular dynamics simulations. By simulating the dyes' stochastic translational and rotational dynamics, we show that the observed dynamic shift can largely be attributed to the mutual orientational dynamics of the electric dipole moments associated with the dyes, not their accessible volume.

Minority stress theory: Application, critique, and continued relevance.

The minority stress model has been influential in guiding research on sexual and gender minority health and well-being in psychology and related social and health sciences. Minority stress has theoretical roots in psychology, sociology, public health, and social welfare. Meyer provided the first integrative articulation of minority stress in 2003 as an explanatory theory aimed at understanding the social, psychological, and structural factors accounting for mental health inequalities facing sexual minority populations. This article reviews developments in minority stress theory over the past two decades, focusing on critiques, applications, and reflections on its continued relevance in the context of rapidly changing social and policy contexts.

A retrospective analysis of the use of electronic consultation in general internal medicine.

BACKGROUND: General internists in Canada are subspecialty providers in the inpatient and outpatient settings. Electronic consultations (eConsult) allow primary care providers (PCPs) to virtually consult specialists to address clinical questions. There is a paucity of literature examining the utility and benefits of eConsults by general internists. AIMS: To determine how an eConsult service is used to access general internists. METHODS: A retrospective cross-sectional analysis of internal medicine cases was completed between 1 January 2016 and 31 December 2019 via the ChamplainBASE eConsult service. Two authors derived and validated a general internal medicine (GIM)-specific taxonomy using the validated: (i) Taxonomy of Generic Clinical Questions; and (ii) Internal Classification for Primary Care. Two hundred seventy-six cases were coded following taxonomy validation. ChamplainBASE utilisation summary and closeout survey data were also analysed. RESULTS: eConsults were responded to in a median of 3.1 days and took 15 min to complete. The eConsult's helpfulness and educational value were rated as 4 to 5/5 and often provided advice for a new or additional course of action. In-person referral was avoided in 40% of cases. The majority of eConsults consisted of a single question (88%) related to diagnostic clarification. The median remuneration per eConsult was $50. CONCLUSIONS: The majority of eConsults to general internists sought diagnostic clarification and confirmed the view of general internists as expert diagnosticians. eConsults cost less than an in-person consultation and were viewed favourably by PCPs. Further research can consider the eConsult provider experience and whether eConsults should become a required part of GIM ambulatory practice.

Ethnic and Sexual Identity-Related Inequalities in Adolescent Health and Well-Being in a National Population-Based Study.

Purpose: This study employed an intersectional framework to examine impact of inequalities related to sexual minority (SM) and ethnic minority (EM) identities in risk for health, well-being, and health-related behaviors in a nationally representative sample. Methods: Participants included 9789 (51% female) adolescents aged 17 years from the U.K.-wide Millennium Cohort Study, with data on self-identified sexual and ethnic identities. Adolescents were grouped into White heterosexual, White-SM, EM-heterosexual, and EM-SM categories. Questionnaires assessed mental health (e.g., self-reported psychological distress, doctor-diagnosed depression, attempted suicide), general health (self-rated health, chronic illness, body mass index), and health-related behaviors (e.g., smoking, substance use). Associations were analyzed using multivariable logistic regression. Results: SM individuals (White: 18% and EM: 3%) had increased odds for mental health difficulties and attempted suicide, with higher odds for White-SM individuals than for EM-SM individuals. Compared with White heterosexual individuals, White-SM and EM-SM individuals had higher risk for psychological distress (adjusted odds ratios [OR] 3.47/2.24 for White-SM/EM-SM, respectively) and emotional symptoms (OR 3.17/1.65). They had higher odds for attempted suicide (OR 2.78/2.02), self-harm (OR 3.06/1.52), and poor sleep quality (OR 1.88/1.67). In contrast, the White heterosexual and White-SM groups had similarly high proportions reporting risky behaviors except for drug use (OR 1.45) and risky sex (OR 1.40), which were more common in White-SM individuals. EM-heterosexual and EM-SM individuals had decreased odds for health-related behaviors. Conclusion: SM (White and EM) individuals had substantially worse mental health compared with heterosexual peers. Adverse health-related behaviors were more common in White-SM individuals. Investigation into the mechanisms leading to these differences is needed.

Assessing construct validity of the Beighton Score as a measure of generalized joint hypermobility in varsity athletes.

The Beighton Score (BS) is a tool that dichotomizes those who have generalized joint hypermobility (GJH) and those who do not. Unfortunately, the BS is often used in populations that it was not originally developed for, including athletes for screening purposes. The construct validity of the BS remains unknown in this population. This secondary analysis investigated the construct validity of the BS by comparing varsity athletes' passive shoulder and hip ranges of motion (ROMs) to their respective BS and individual forward bend tests (FBTs). There were statistically significant but weak correlations between shoulder ROMs and the BS (r=0.142, p=0.021). Mean hip ROMs were greater by 5-degrees in those with positive FBTs compared to those with negative FBTs. This difference falls within typical measurement errors that occur in practice. Therefore, our results do not support the construct validity of the BS as a measure of GJH in healthy athletes.

Le score de Beighton (BS) est un outil qui permet de distinguer les personnes souffrant d'hypermobilité articulaire généralisée de celles qui n'en souffrent pas. Malheureusement, le score de Beighton est souvent utilisé dans des populations pour lesquelles il n'a pas été conçu à l'origine, notamment les athlètes, à des fins de dépistage. La validité de construit du score de Beighton reste inconnue dans cette population. Cette analyse secondaire a étudié la validité conceptuelle du score de Beighton en comparant les amplitudes de mouvement passives de l'épaule et de la hanche des athlètes universitaires à leur score de Beighton et à leurs tests individuels de flexion avant. Des corrélations statistiquement significatives mais faibles ont été observées entre les amplitudes de mouvement des épaules et le score de Beighton (r=0,142, p=0,021). Les amplitudes moyennes de flexion de la hanche étaient supérieures de 5 degrés chez les personnes ayant subi un test de flexion avant positif par rapport à celles ayant subi un test de flexion avant négatif. Cette différence s'inscrit dans le cadre des erreurs de mesure typiques qui se produisent au cours de la pratique. Par conséquent, nos résultats ne confirment pas la validité conceptuelle du score de Beighton en tant que mesure de l'hypermobilité articulaire généralisée chez les athlètes en bonne santé.

Past Experiences and Anticipated Futures in the Lives of Transgender and Nonbinary People.

Transgender and nonbinary people's life experiences are highly heterogenous and shaped by broader structural and cultural forces. We analyze experiences identified on lifeline interviews from 87 transgender and nonbinary adults in Atlanta, New York City, and San Francisco. We find that the type, timing, and relative importance of these experiences varied across categories. For example, experiences related to "Rejection and violence" were more often identified in childhood and in the past, whereas experiences related to "Gender-affirming medical interventions" were more often in adulthood and anticipated futures. Experiences related to "Community involvement," "Extracurriculars," "Gender exploration and revelation," and "Gender-affirming medical interventions" were labeled by respondents as relatively more important compared to other experiences, whereas experiences related to "Family of origin relationships," "Place of residence," "Rejection and violence," and "Sexuality" less important. These experiences were patterned according to the respondents' gender, birth cohort, race/ethnicity, and geographic location. In analyzing these lifeline data, we advance theoretical understandings of the salience of a variety of key experiences for transgender and nonbinary people at different points in the life course. Our life course approach provides empirical analyses of intra-individual processes over time for transgender and nonbinary people and provides insight into the usefulness of a lifeline method for life course studies more generally as it draws attention to within-person assessments of the distribution and importance of events over the course of a lifetime.

Limitations to Participation in Family of Origin Among Same Sex Couples: A Couple-Level Minority Stressor.

Emerging studies focus on minority stressors emanating from society's stigmatization of particular relationship forms (i.e., couple-level minority stressors). The present study examines how same-sex couples experience one such couple-level minority stressor: limitations to participation in families of origin. Qualitative data are drawn from a sub-sample of same-sex couples (N = 18) who participated in a large-scale study of minority stress among 120 same-sex couples distributed equally across two study sites (Atlanta and San Francisco) in 2012 and 2013. Instances of limitations to participation in families of origin ranged in severity, falling into three distinct areas: 1) partial acceptance, where some family members were accepting and others were not, 2) mixed messages where some family members said they were accepting but behaved as though they were not and, 3) rejection, where some family members were blatantly unwelcoming or hostile. These types of exclusion were also evidenced in dyadic minority stress processes of stress proliferation (e.g., stress discrepancies and stress contagion) causing additional stress for both partners. These narratives portray struggles associated with experiences of couple-level minority stress faced by people in same-sex relationships.

Relationship Identities Among Lesbian, Gay, and Bisexual Adults: An Exploratory Study.

Relationship identities are established through romantic interactions and informed by sociohistorical context. The associations between lesbian, gay, and bisexual (LGB) identities and identities in other domains, including relationship identities, have yet to receive sufficient attention from researchers. In this exploratory study, through a qualitative analysis of life-history interviews from the Generations Study, we identified participants who described their identity in terms of a romantic relationship (e.g., partner, husband/wife). In describing their relationship identities, two themes emerged: (a) negotiation of a relationship identity with other identities, such as gender or race/ethnicity and (b) navigating being visible or invisible within the LGB community and/or at the societal level. Together these themes suggest that relationships may be salient components of personal identity when sexual minority individuals in a couple either individually or jointly feel that they stand out (or that they become invisible).

Sexual Identity and Birth Cohort Differences in Social Support and Its Link with Well-Being among Sexual Minority Individuals.

This study examined sexual identity and birth cohort differences in social support and its association with well-being, using a longitudinal national probability sample of 706 cisgender and non-binary sexual minority individuals from the USA. The data allowed for extensive descriptions of perceived social support and support networks across subgroups. Findings demonstrated that sexual identity and birth cohort differences in overall sizes of support networks and levels of perceived social support were small. Furthermore, fixed effects analyses indicated that changes in the size of respondents' social support networks were not related to well-being, with a one-person change being associated with a .04 SD change in well-being or less, depending on the indicator of well-being being tested. Moreover, changes in perceived social support were only limitedly related to changes in respondents' well-being, a 1-point change in the scale of perceived social support being associated with a .11 SD change in life-satisfaction. Associations were smaller for overall well-being or psychological distress, the other two indicators of well-being used. Together, these findings could imply that cross-sectional research has overestimated the relevance of social support for the well-being of sexual minority individuals, but also that general social support is insufficiently tailored to the support needs of the sexual minority population.

Social change and relationship quality among sexual minority individuals: Does minority stress still matter?

Objective: This study examined whether positive changes in social attitudes and policies surrounding sexual minority relationships have translated to diminished deleterious effects of minority stress on relationship quality. Background: Sexual minority emerging adults now come of age at a time of greater equality and acceptance than previous generations. Research has demonstrated consistent negative effects of stigma-theorized as minority stress-on relationship quality for sexual minority individuals. However, given the improving social climate, questions remain regarding whether minority stress has the same deleterious effects on the romantic relationships of sexual minority emerging adults. Method: Five-hundred forty-nine individuals in relationships drawn from a US national probability sample completed a survey containing validated measures of minority stressors and relationship satisfaction. Responses from emerging adults (aged 18-25) were compared to two cohorts who came of age during the HIV/AIDS crisis (aged 34-41) and post Stonewall (aged 52-59). Results: Emerging adults were more satisfied with their relationships than older cohorts. Experiences of everyday discrimination were associated with decreased relationship satisfaction for all cohorts; however, felt stigma, stigma concealment, and internalized stigma were associated with lower relationship satisfaction for older but not younger cohorts. Conclusion: Findings illustrate the continued but shifting role of minority stress and provide the first evidence that social and policy changes may have translated into more positive relationship experiences for sexual minority emerging adults.

Distribution and Prevalence of Health in a National Probability Sample of Three Cohorts of Sexual Minority Adults in the United States.

Purpose: This study examined the health profile of a national probability sample of three cohorts of sexual minority people, and the ways that indicators of health vary among sexual minority people across age cohorts and other defining sociodemographic characteristics, including sexual identity, gender identity, and race/ethnicity. Methods: The Generations Study, the first national probability sample of three age cohorts of sexual minority people (n = 1507) in the United States collected in 2016-2017, was used to examine general health profiles across several broad domains: alcohol and drug abuse; general health, physical health, and health disability; mental health and psychological distress; and positive well-being, including general happiness, social well-being, and life satisfaction. Results: There were no cohort differences in substance abuse or positive well-being. The younger cohort was physically healthier, but had worse psychological health than both the middle and older cohorts. Conclusions: Cohort differences in physical health were consistent with patterns of aging, whereas for mental health, there were distinct cohort differences among sexual minority people. Given that compromised mental health in the early life course creates trajectories of vulnerability, these results point to the need for mental health prevention and intervention for younger cohorts of sexual minority people.

Co-clinical Modeling of the Activity of the BET Inhibitor Mivebresib (ABBV-075) in AML.

BACKGROUND/AIM: The therapeutic potential of bromodomain and extra-terminal motif (BET) inhibitors in hematological cancers has been well established in preclinical and early-stage clinical trials, although as of yet, no BETtargeting agent has achieved approval. To add insight into potential response to mivebresib (ABBV-075), a broadspectrum BET inhibitor, co-clinical modeling of individual patient biopsies was conducted in the context of a Phase I trial in acute myeloid leukemia (AML). MATERIALS AND METHODS: Co-clinical modeling involves taking the patient's biopsy and implanting it in mice with limited passage so that it closely retains the original characteristics of the malignancy and allows comparisons of response between animal model and clinical data. Procedures were developed, initially with neonate NOD/Shi-scid-IL2rγnull (NOG) mice and then optimized with juvenile NOG-EXL as host mice, eventually resulting in a robust rate of engraftment (16 out of 26, 62%). RESULTS: Results from the co-clinical AML patient-derived xenograft (PDX) modeling (6 with >60% inhibition of bone marrow blasts) were consistent with the equivalent clinical data from patients receiving mivebresib in monotherapy, and in combination with venetoclax. The modeling system also demonstrated the activity of a novel BD2-selective BET inhibitor (ABBV-744) in the preclinical AML setting. Both agents were also highly effective in inhibiting blast counts in the spleen (10/10 and 5/6 models, respectively). CONCLUSION: These findings confirm the validity of the model system in the co-clinical setting, establish highly relevant in vivo models for the discovery of cancer therapy, and indicate the therapeutic value of BET inhibitors for AML and, potentially, myelofibrosis treatment.

Hydrogen production rates of aluminum reacting with varying densities of supercritical water.

Aluminum particles, spanning in size from 10 µm to 3 mm, were reacted with varying densities of water at 655 K. The density of the water is varied from 50 g L-1 to 450 g L-1 in order to understand the effect of density on both reaction rates and yields. Low-density supercritical water is associated with properties that make it an efficient oxidizer: low viscosity, high diffusion, and low relative permittivity. Despite this, it was found that the high-density (450 g L-1) supercritical water was the most efficient oxidizer both in terms of reaction rate and hydrogen yield. The 10 µm powder had a peak reaction rate of approximately 675 cmH2 3 min-1 gAl -1 in the high-density water, and a peak reaction rate below 250 cmH2 3 min-1 gAl -1 in the low- and vapour-density water. A decline in peak reaction rate with decreasing water density was also observed for the 120 µm powder and the 3 mm slugs. These findings imply that the increased collision frequency, a property of the high-density water, outpaces reduction in the reaction enhancing properties associated with low-density supercritical water. Hydrogen yield was minimally affected by decreasing the oxidizer density from 450 g L-1 to 200 g L-1, but did drop off significantly in the vapour-density (50 g L-1) water.

Social Change and the Health of Sexual Minority Individuals: Do the Effects of Minority Stress and Community Connectedness Vary by Age Cohort?

This study examined the extent to which social stress stemming from a stigmatized social status (i.e., minority stress) was associated with three domains of health in younger as compared with older age cohorts of sexual minority individuals. Data were analyzed from the Generations Study, a longitudinal study using a probability sample (N = 1518) of age cohorts of sexual minority individuals in the USA. Exposure to a variety of minority stressors was associated with poorer health for all age cohorts. We hypothesized that because of improved social and legal environments in recent years, the associations between minority stress and health would be diminished in the younger cohort. As expected, we found that the associations between some minority stressors and health outcomes were diminished in the younger cohort compared to older cohorts. Positive associations between community connectedness and mental health and social well-being were observed for all participants but were attenuated in the younger cohort. Findings demonstrate the continuing negative association between minority stress and health among sexual minorities, which, despite some attenuation, persists even for young cohorts of sexual minority individuals in a more equal and accepting social climate.

'It's being a part of a grand tradition, a grand counter-culture which involves communities': A qualitative investigation of autistic community connectedness.

LAY ABSTRACT: A sense of being connected to other autistic people has been reported anecdotally. Friendships and connectedness may be important to autistic people and beneficial for their wellbeing. Our research aimed to understand the autistic community by interviewing 20 autistic people about their experiences of being connected to other autistic people. Participants were interviewed in person, over video, using a text-based software to type or over email. Participants detailed three parts of autistic community connectedness: a sense of belonging, social connection with autistic friends and political connectedness. The friendships autistic people had with one another were deemed to be very important to participants because it gave them confidence, provided companionship and made them happy. Some participants did not experience connectedness to the autistic community. These participants also found autism to be less important to their identity and had fewer positive feelings about being autistic. This research is important as it raises awareness that community connectedness is viewed as important to this group. It is possible that community connectedness may help protect the mental health of autistic people when they face stigma or negative life experiences in society.

Adjacent Joint Restriction Differentially Influences Intra- and Inter-rater Reliability and Agreement of Goniometric Measurements.

BACKGROUND: Reliability and agreement of goniometric measurements can be altered by variations in measurement technique such as restricting adjacent joints to influence bi-articular muscles. It is unknown if the influence of adjacent joint restriction is consistent across different range of motion (ROM) tests, as this has yet to be assessed within a single study. Additionally, between-study comparisons are challenged by differences between methodology, participants and raters, obscuring the development of a conceptual understanding of the extent to which adjacent joint restriction can influence goniometric ROM measurements. PURPOSE: To quantify intra- and inter-rater reliability and levels of agreement of goniometric measurements across five ROM tests, with and without adjacent joint restriction. STUDY DESIGN: Descriptive reliability study. METHODS: Three trained and experienced raters made two measurements of bilateral ankle dorsiflexion, first metatarsophalangeal dorsiflexion, hip extension, hip flexion, and shoulder flexion, with and without adjacent joint restriction. Intraclass correlation coefficient (ICC), standard error of measurement (SEM), along with participant, measurement/rater and random error variance were estimated. RESULTS: Eleven females (age 21.4 ±2.3 years) and 19 males (age 22.1 ±2.8 years) participated. Adjacent joint restriction did not influence the reliability and agreement in a consistent way across the five ROM tests. Changes in the inter-rater reliability and agreement were more pronounced compared to the intra-rater reliability and agreement. Assessing variance components (participant, measurement/rater and random error variance) that are used to calculate the ICC and SEM, improved interpretation of ICC and SEM scores. CONCLUSION: The effects of adjacent joint restriction on reliability and agreement of goniometric measurements depend on the ROM test and should be considered when comparing measurements between multiple raters. Reporting variance components that are used to calculate the ICC and SEM can improve interpretation and may improve between-study comparisons, towards developing a conceptual framework to guide goniometric measurement technique. LEVEL OF EVIDENCE: 3b.

Comparison of 5 Normalization Methods for Knee Joint Moments in the Single-Leg Squat.

Ratio scaling is the most common magnitude normalization approach for net joint moment (NJM) data. Generally, researchers compute a ratio between NJM and (some combination of) physical body characteristics (eg, mass, height, limb length, etc). However, 3 assumptions must be verified when normalizing NJM data this way. First, the regression line between NJM and the characteristic(s) used passes through the origin. Second, normalizing NJM eliminates its correlation with the characteristic(s). Third, the statistical interpretations following normalization are consistent with adjusted linear models. The study purpose was to assess these assumptions using data collected from 16 males and 16 females who performed a single-leg squat. Standard inverse dynamics analyses were conducted, and ratios were computed between the mediolateral and anteroposterior components of the knee NJM and participant mass, height, leg length, mass × height, and mass × leg length. Normalizing NJM-mediolateral by mass × height and mass × leg length satisfied all 3 assumptions. Normalizing NJM-anteroposterior by height and leg length satisfied all 3 assumptions. Therefore, if normalization of the knee NJM is deemed necessary to address a given research question, it can neither be assumed that using (any combination of) participant mass, height, or leg length as the denominator is appropriate nor consistent across joint axes.

Mechanical Energy Expenditure at Lumbar Spine and Lower Extremity Joints During the Single-Leg Squat Is Affected by the Nonstance Foot Position.

ABSTRACT: Hirsch, SM, Chapman, CJ, Frost, DM, and Beach, TAC. Mechanical energy expenditure at lumbar spine and lower extremity joints during the single-leg squat is affected by the nonstance foot position. J Strength Cond Res 36(9): 2417-2426, 2022-Previous research has shown that discrete kinematic and kinetic quantities during bodyweight single-leg squat (SLS) movements are affected by elevated foot positioning and sex of the performer, but generalizations are limited by the high-dimensional data structure reported. Using a 3D inverse dynamical linked-segment model, we quantified mechanical energy expenditure (MEE) at each joint in the kinetic chain, the total MEE (sum of MEE across aforesaid joints), and the relative contribution of each joint to total MEE during SLSs performed with elevated foot positioned beside stance leg (SLS-Side), and in-front of (SLS-Front) and behind (SLS-Back) the body. Total MEE differed between SLS variations ( p = 0.002), with the least amount observed in the SLS-Back (effect size [ES] = 0.066-0.069). Approximately 50% of total MEE was contributed by the knee joint in each SLS variation, whereas MEE at the ankle, hip, and lumbar spine (in absolute and relative terms) varied complexly as a function of the elevated foot position. Total MEE ( p = 0.0192, ES = 0.852) and the absolute MEE at the knee and spine was greater in men across the SLS variations performed ( p = 0.025-0.036, ES = 0.715-0.766), but only the lumbar spine contribution to total MEE was larger in men across all SLS variations ( p = 0.045, ES = 0.607). Otherwise, there were no other sex-specific responses observed. Biomechanically, SLS movements are generally "knee-dominant," but changing elevated foot position effectively redistributes MEE among other joints in the linkage. Consistent with the previous conclusions reached based on discrete kinematic and kinetic data, not all SLSs are equal.