Using reference equations to standardise incremental shuttle walk test performance in children and young people with chronic conditions and facilitate the evaluation of exercise capacity and disease severity.

AIMS: The aim was to evaluate whether standardised exercise performance during the incremental shuttle walk test (ISWT) can be used to assess disease severity in children and young people (CYP) with chronic conditions, through (1) identifying the most appropriate paediatric normative reference equation for the ISWT, (2) assessing how well CYP with haemophilia and cystic fibrosis (CF) perform against the values predicted by the best fit reference equation and (3) evaluating the association between standardised ISWT performance and disease severity. METHODS: A cross-sectional analysis was carried out using existing data from two independent studies (2018-2019) at paediatric hospitals in London,UK. CYP with haemophilia (n=35) and CF (n=134) aged 5-18 years were included. Published reference equations for standardising ISWT were evaluated through a comparison of populations, and Bland-Altman analysis was used to assess the level of agreement between distances predicted by each equation. Associations between ISWT and disease severity were assessed with linear regression. RESULTS: Three relevant reference equations were identified for the ISWT that standardised performance based on age, sex and body mass index (Vardhan, Lanza, Pinho). A systematic proportional bias of standardised ISWT was observed in all equations, most pronounced with Vardhan and Lanza; the male Pinho equation was identified as most appropriate. On average, CYP with CF and haemophilia performed worse than predicted by the Pihno equation, although the range was wide. Standardised ISWT, and not ISWT distance alone, was significantly associated with forced expiratory volume in 1 s in CYP with CF. Standardised ISWT in CYP with haemophilia was slightly associated with haemophilia joint health score, but this was not significant. CONCLUSIONS: ISWT performance may be useful in a clinic to identify those with worsening disease, but only when performance is standardised against a healthy reference population. The development of validated global reference equations is necessary for more robust assessment.

Perspectives of autistic adolescent girls and women on the determinants of their mental health and social and emotional well-being: A systematic review and thematic synthesis of lived experience.

LAY ABSTRACT: Difficulties with mental health and low levels of well-being are more common among autistic girls and women than non-autistic people, but we do not fully understand why. Research does not focus enough on what autistic girls and women could tell us about this. This review aims to summarise the studies where autistic girls and women explain things that affect their mental health and well-being to help us understand how to prevent these difficulties from developing. Three research databases were searched to find possibly relevant studies. There were 877 studies found, which two researchers screened according to particular criteria. They found 52 studies that could be included in this review. One researcher evaluated the quality of these studies and extracted the key information from them. This review summarises the views of 973 autistic girls and women aged between 13 and 70+. The findings from the 52 studies were analysed, and we found many factors that affect the mental health and well-being of autistic girls and women. These factors fall into two categories: (1) difficulties living in a world not designed for autistic people and (2) the impact of stigma due to being autistic.

Hair Collection for Cortisol Among Youth Experiencing Homelessness.

BACKGROUND: Investigations of chronic physiological stress measured by hair cortisol are rapidly expanding among community samples of adolescents and adults. However, research examining physiological stress among youth experiencing homelessness is nascent despite the youth's increased risk for adverse exposures and subsequent impaired mental health. OBJECTIVE: This article aimed to examine the feasibility of collecting hair for measuring cortisol among diverse youth experiencing homelessness and gain an understanding of variation in participation. METHODS: Analysis of survey and hair participation data from three pilot studies among youth experiencing homelessness was conducted. Survey measures included sociodemographic characteristics (age, race and ethnicity, sex assigned at birth, and sexual orientation) and reasons for nonparticipation. Descriptive analysis examined participation rates in hair collection for cortisol measurement, including sociodemographic differences in participation. RESULTS: Participation in the hair sampling for cortisol was high for the combined sample (88.4%), with some variation across the three pilot studies. Insufficient hair for cutting was the most common reason for not participating; Black and multiracial youth, as well as male youth, had a higher prevalence of nonparticipation. DISCUSSION: The collection of hair for cortisol research among youth experiencing homelessness is feasible, and integration of physiological measures of stress into research with this vulnerable population should be considered, given their high risk for adversity and death by suicide and drug overdose. Methodological considerations and avenues for potential research are discussed.

Real-world effectiveness of airway clearance techniques in children with cystic fibrosis.

BACKGROUND: Cystic fibrosis (CF) is commonly characterised by thick respiratory mucus. From diagnosis, people with CF are prescribed daily physiotherapy, including airway clearance techniques (ACTs). ACTs consume a large proportion of treatment time, yet the efficacy and effectiveness of ACTs are poorly understood. This study aimed to evaluate associations between the quality and quantity of ACTs and lung function in children and young people with CF. METHODS: Project Fizzyo, a longitudinal observational cohort study in the UK, used remote monitoring with electronic pressure sensors attached to four different commercial ACT devices to record real-time, breath-by-breath pressure data during usual ACTs undertaken at home over 16 months in 145 children. ACTs were categorised either as conformant or not with current ACT recommendations based on breath pressure and length measurements, or as missed treatments if not recorded. Daily, weekly and monthly associations between ACT category and lung function were investigated using linear mixed effects regression models adjusting for clinical confounders. RESULTS: After exclusions, 45 224 ACT treatments (135 individuals) and 21 069 days without treatments (141 individuals) were analysed. The mean±sd age of participants was 10.2±2.9 years. Conformant ACTs (21%) had significantly higher forced expiratory volume in 1 s (FEV1) (mean effect size 0.23 (95% CI 0.19-0.27) FEV1 % pred per treatment) than non-conformant (79%) or missed treatments. There was no benefit from non-conformant or missed treatments and no significant difference in FEV1 between them (mean effect size 0.02 (95% CI -0.01-0.05) FEV1 % pred per treatment). CONCLUSIONS: ACTs are beneficial when performed as recommended, but most people use techniques that do not improve lung function. Work is needed to monitor and improve ACT quality and to increase the proportion of people doing effective airway clearance at home.

Aging as Adaptation.

In traditional gerontological terms, adaptation is usually understood as the production of physical aids to mitigate the impairment effects caused by age-related disabilities, or as those alterations organizations need to make under the concept of reasonable adjustment to prevent age discrimination (in the UK, e.g., age has been a protected characteristic under the Equality Act since 2010). This article will be the first to examine aging in relation to theories of adaptation within cultural studies and the humanities. It is thus an interdisciplinary intervention within the field of cultural gerontology and cultural theories of adaptation. Adaptation studies in cultural studies and the humanities have moved away from fidelity criticism (the issue of how faithful an adaptation is to its original) toward thinking of adaptation as a creative, improvisational space. We ask if theories of adaptation as understood within cultural studies and the humanities can help us develop a more productive and creative way of conceptualizing the aging process, which reframes aging in terms of transformational and collaborative adaptation. Moreover, for women in particular, this process of adaptation involves engagement with ideas of women's experience that encompass an adaptive, intergenerational understanding of feminism. Our article draws on interviews with the producer and scriptwriter of the Representage theater group's play My Turn Now. The script for the play is adapted from a 1993 coauthored book written by a group of 6 women who were then in their 60s and 70s, who founded a networking group for older women.

The presence, action, and influence of bystanders who witness sexual harassment against medical students.

PURPOSE: Sexual harassment (SH) is a widespread problem in academia, with a disproportionate impact on female medical students and those who experience marginalization via multiple systems of oppression (e.g. racism, heterosexism). Bystander intervention education is a potential approach which frames violence as a community issue where all members have a role to play in response and prevention. This study assessed the presence and influence of bystanders in SH situations for students at two medical schools. MATERIALS AND METHODS: Data came from a larger U.S. campus climate study administered online in 2019 and 2020. The sample included 584 students who responded to validated survey questions about sexual harassment experiences, bystander behavior, disclosure, perceptions of the university response to SH, and demographics. RESULTS: More than one-third of respondents experienced some form of SH by a faculty/staff member. Bystanders were present for more than half of these incidents, yet they rarely intervened. When bystanders intervened, people were more likely to disclose an incident than not. CONCLUSIONS: The results indicate that there are many missed opportunities for intervention and given the profound impact that SH has on the well-being of medical students, continued work is needed to determine effective intervention and prevention methods.[Box: see text].

Why Do Students Participate in Campus Sexual Assault Climate Surveys?

The purpose of the current study is to explore students' reasons for participating in a campus sexual assault climate survey to determine if patterns exist based on various identities and experiences. More specifically, we were interested in the most frequently reported reasons for participating, and whether they differed by key demographic variables. As part of a campus climate survey administration at two campuses, 4,020 students responded to survey questions asking why they participated in the survey (Sample 1, n = 2,937 and Sample 2, n = 1,083). To examine which demographic variables predicted reasons for taking the survey while controlling for other potential correlates, we conducted logistic regression analyses. The reasons provided by students as to why they completed the campus climate survey differed by identity characteristics, suggesting that researchers must consider the demographic makeup of their institutions when designing sampling and recruitment plans and tailoring them to their student populations. For example, while gender emerged as salient for differing reasons for participation (e.g., women more likely to participate because of the issue's importance and wanting their opinions heard more), intersectional analysis by race and gender indicates that White men (and Asian men, in Sample 1) most consistently indicated different reasons for participation, with significantly greater odds than their White and Asian women counterparts to participate for the cash incentives. This information could help improve the recruitment of representative samples for campus sexual assault surveys and therefore provide more accurate data that can be used to deliver effective intervention and prevention efforts.

Quantity and quality of airway clearance in children and young people with cystic fibrosis.

Children and young people with CF (CYPwCF) get advice about using positive expiratory pressure (PEP) or oscillating PEP (OPEP) devices to clear sticky mucus from their lungs. However, little is known about the quantity (number of treatments, breaths, or sets) or quality (breath pressures and lengths) of these daily airway clearance techniques (ACTs) undertaken at home. This study used electronic pressure sensors to record real time breath-by-breath data from 145 CYPwCF (6-16y) during routine ACTs over 2 months. ACT quantity and quality were benchmarked against individual prescriptions and accepted recommendations for device use. In total 742,084 breaths from 9,081 treatments were recorded. Individual CYPwCF maintained consistent patterns of ACT quantity and quality over time. Overall, 60% of CYPwCF did at least half their prescribed treatments, while 27% did fewer than a quarter. About 77% of pre-teens did the right number of daily treatments compared with only 56% of teenagers. CYPwCF usually did the right number of breaths. ACT quality (recommended breath length and pressure) varied between participants and depended on device. Breath pressures, lengths and pressure-length relationships were significantly different between ACT devices. PEP devices encouraged longer breaths with lower pressures, while OPEP devices encouraged shorter breaths with higher pressures. More breaths per treatment were within advised ranges for both pressure and length using PEP (30-31%) than OPEP devices (1-3%). Objective measures of quantity and quality may help to optimise ACT device selection and support CYPwCF to do regular effective ACTs.

College Students' Engagement in Violence Prevention Discussions with Peers.

The bystander intervention (BI) model recognizes a range of prosocial helping behaviors individuals can perform to support sexual and dating violence (S/DV) prevention efforts. Individuals can demonstrate a commitment to ending violence through proactive BI, such as participating in prevention initiatives or talking with peers about ways to keep safe, which are different than reactive BI behaviors when violence is underway. Given the anchoring of the BI model in Diffusion of Innovation Theory, which articulates the uptake of new behaviors throughout a population or community and the role of change agent aids in that process, investigating demographic, and other individual-level correlates, of proactive behaviors may help identify those students who are particularly positioned to help diffuse and normalize anti-violence behaviors. The purpose of this study was to examine (1) the occurrence of students' engagement in peer discussions about violence prevention in the past year and (2) the correlates of reporting to have those discussions among university students in a cross-sectional study implemented on two campuses in the Mid-Atlantic U.S. Results showed that the most common discussion was talking to friends about being safe in dating relationships and the least common was talking with friends about participating in violence-prevention-related activities, with 66.2% and 22.5% having done so, respectively. Women, younger students, and those reporting to know a survivor of either DV or SV were more likely to report having discussions, compared to men, older students, and those not knowing a survivor. Additional relationships were detected between other individual characteristics, knowledge about violence/victimization, and climate-related variables but differed depending on whether participants participated in the DV or SV-related survey module. Findings suggest the need for BI training initiatives to emphasize proactive engagement and peer discussions, and that gender continues to be a robust indicator of violence-prevention actions.

Post-concussive syndrome to primary central nervous system lymphoma: An insidious presentation.

Primary central nervous system lymphoma (PCNSL) and central neurogenic hyperventilation (CNH) are both rare occurrences, especially when associated with Epstein-Barr Virus (EBV). We report a case of an immunocompetent individual who presented to the emergency department (ED) with vague neurological symptoms found to have an EBV-associated PCNSL complicated by CNH. This rare occurrence had an insidious presentation initially mistaken for "post-concussive syndrome" at an outside ED. Insidious neurological malignancies, posterior strokes, intracranial hematomas, and other life-threatening pathologies should always be on the differential in patients presenting to the ED with falls with associated neurological symptoms, especially with unexplained blood gas abnormalities.

Friendship quality among autistic and non-autistic (pre-) adolescents: Protective or risk factor for mental health?

LAY ABSTRACT: Autistic young people are often misunderstood by non-autistic young people, and this can lead to difficulties in their friendships. We know that friendship is very important for our mental health. For non-autistic young people, having good friendships is linked to better mental health and having problems in friendship can cause mental health problems. This study aimed to compare the positive and negative features of friendship that autistic non-autistic young people experience. The study also aimed to understand if having positive or negative friendship features is related to signs of mental health problems (anxiety and depression). 306 young people aged 9-16 took part in this study. These were 86 autistic boys, 18 autistic girls, 91 non-autistic boys and 111 non-autistic girls. The findings of this study showed that autistic young people have less positive friendship features than non-autistic young people. For all young people in the study, having more positive friendship features was related to fewer signs of depression, while having more negative friendship features was related to more signs of depression. Just for autistic girls, having more positive friendship features was related to more signs of anxiety. These findings show that support is needed to help autistic young people have more positive friendships. For example, by teaching non-autistic young people how to be supportive friends to their autistic peers.

Reduced to curtain twitchers? Age, ageism and the careers of four women actors.

Cultural gerontology has developed critical work around cultural representations of age and aging and their role in the reproduction of ageism. However, the cultural industries as producers and disseminators of representations remain under researched. This paper draws on a focus group with four older women actors to argue that workforce allocation and assumptions about audience demographics intersect with cultural attitudes around women's aging to impact on older women actors' career opportunities. We argue that ageism within the cultural industries is limiting our ability to develop diverse and non-ageist cultural representation of women's aging.

Quantity and quality of empathic responding by autistic and non-autistic adolescent girls and boys.

LAY ABSTRACT: Empathy is an important feature to feel for another person, evoking social support for the person in distress, and thus strengthening social cohesion. The question is to what extent empathic reactions can also be observed in autistic adolescents and autistic girls in particular, since their often mentioned good social skills might prevent their direct social environment from recognizing their autism. We examined 194 adolescents (autistic and non-autistic boys and girls) during an in vivo task in which the experimenter pretended to hurt herself while closing a binder. All responses by the participants were videotaped and coded by two independent coders. In line with our predictions, no group or gender differences appeared related to their attention for the event; yet autistic girls and boys showed less visible emotional arousal, which could indicate less affective empathy (feeling for someone), or which could indicate that autistic adolescents know less well how to show empathy. Autistic girls and boys reacted by comforting the experimenter equally often as their non-autistic peers, but autistic boys addressed the problem more often than any other group, while girls (autistic and non-autistic) more often addressed the emotion of the person in need. Our findings highlight that empathic behaviour is remarkably similar between autistic and non-autistic boys and girls. Indeed, only subtle differences exist, in terms of expressed emotional arousal and gender-specific comforting styles. Autistic girls' higher levels of emotion-focused comforting could be explained by well-developed social skills, camouflaging, or emotional investment in relationships with others.

Protocol for Project Fizzyo, an analytic longitudinal observational cohort study of physiotherapy for children and young people with cystic fibrosis, with interrupted time-series design.

INTRODUCTION: Daily physiotherapy is believed to mitigate the progression of cystic fibrosis (CF) lung disease. However, physiotherapy airway clearance techniques (ACTs) are burdensome and the evidence guiding practice remains weak. This paper describes the protocol for Project Fizzyo, which uses innovative technology and analysis methods to remotely capture longitudinal daily data from physiotherapy treatments to measure adherence and prospectively evaluate associations with clinical outcomes. METHODS AND ANALYSIS: A cohort of 145 children and young people with CF aged 6-16 years were recruited. Each participant will record their usual physiotherapy sessions daily for 16 months, using remote monitoring sensors: (1) a bespoke ACT sensor, inserted into their usual ACT device and (2) a Fitbit Alta HR activity tracker. Real-time breath pressure during ACTs, and heart rate and daily step counts (Fitbit) are synced using specific software applications. An interrupted time-series design will facilitate evaluation of ACT interventions (feedback and ACT-driven gaming). Baseline, mid and endpoint assessments of spirometry, exercise capacity and quality of life and longitudinal clinical record data will also be collected.This large dataset will be analysed in R using big data analytics approaches. Distinct ACT and physical activity adherence profiles will be identified, using cluster analysis to define groups of individuals based on measured characteristics and any relationships to clinical profiles assessed. Changes in adherence to physiotherapy over time or in relation to ACT interventions will be quantified and evaluated in relation to clinical outcomes. ETHICS AND DISSEMINATION: Ethical approval for this study (IRAS: 228625) was granted by the London-Brighton and Sussex NREC (18/LO/1038). Findings will be disseminated via peer-reviewed publications, at conferences and via CF clinical networks. The statistical code will be published in the Fizzyo GitHub repository and the dataset stored in the Great Ormond Street Hospital Digital Research Environment. TRIAL REGISTRATION NUMBER: ISRCTN51624752; Pre-results.

Investigation of the effects of veterinarians' attire on ratings of trust, confidence, and comfort in a sample of pet owners in Canada.

OBJECTIVE: To examine companion animal owners' perceptions of appropriate veterinarian attire and investigate potential associations between a veterinarian's attire and clients' ratings of trust in, confidence in, and comfort with a veterinarian. SAMPLE: 449 pet owners. PROCEDURES: Participants were randomly assigned to complete a questionnaire containing photos of a male or female model veterinarian photographed in 8 attire types (formal attire, white dress shirt with black pants, white casual shirt with khaki pants, surgical scrubs, white casual shirt with jeans, surgical scrub top with jeans, surgical scrub top with khaki pants, and white laboratory coat with khaki pants). Participants were asked to rate their trust in, confidence in, and comfort with the pictured individual on a response scale of 1 (low) to 7 (high), rank photos according to their preferences for attire, and provide input on the importance of attire and other appearance-related subjects. Attire and gender of photographed individual and participant demographics were investigated for associations with trust, confidence, and comfort scores. RESULTS: Most (317/445 [71%]) respondents indicated veterinarians' attire was important. Attire type was significantly associated with respondents' trust, confidence, and comfort scores. Model veterinarian gender and participant education level were also associated with trust and comfort scores. CONCLUSIONS AND CLINICAL RELEVANCE: Veterinarians' attire is a form of nonverbal communication that is likely to inform clients' first impressions and may influence clients' trust in, confidence in, and comfort with a veterinarian. Veterinary personnel and veterinary management should consider how attire and general appearance represent staff members or their practice.

The Fully human anti-CD47 antibody SRF231 exerts dual-mechanism antitumor activity via engagement of the activating receptor CD32a.

BACKGROUND: CD47 is a broadly expressed cell surface glycoprotein associated with immune evasion. Interaction with the inhibitory receptor signal regulatory protein alpha (SIRPα), primarily expressed on myeloid cells, normally serves to restrict effector function (eg, phagocytosis and immune cell homeostasis). CD47/SIRPα antagonists, commonly referred to as 'macrophage checkpoint' inhibitors, are being developed as cancer interventions. SRF231 is an investigational fully human IgG4 anti-CD47 antibody that is currently under evaluation in a phase 1 clinical trial. The development and preclinical characterization of SRF231 are reported here. METHODS: SRF231 was characterized in assays designed to probe CD47/SIRPα blocking potential and effects on red blood cell (RBC) phagocytosis and agglutination. Additionally, SRF231-mediated phagocytosis and cell death were assessed in macrophage:tumor cell in vitro coculture systems. Further mechanistic studies were conducted within these coculture systems to ascertain the dependency of SRF231-mediated antitumor activity on Fc receptor engagement vs CD47/SIRPα blockade. In vivo, SRF231 was evaluated in a variety of hematologic xenograft models, and the mechanism of antitumor activity was assessed using cytokine and macrophage infiltration analyses following SRF231 treatment. RESULTS: SRF231 binds CD47 and disrupts the CD47/SIRPα interaction without causing hemagglutination or RBC phagocytosis. SRF231 exerts antitumor activity in vitro through both phagocytosis and cell death in a manner dependent on the activating Fc-gamma receptor (FcγR), CD32a. Through its Fc domain, SRF231 engagement with macrophage-derived CD32a serves dual purposes by eliciting FcγR-mediated phagocytosis of cancer cells and acting as a scaffold to drive CD47-mediated death signaling into tumor cells. Robust antitumor activity occurs across multiple hematologic xenograft models either as a single agent or in combination with rituximab. In tumor-bearing mice, SRF231 increases tumor macrophage infiltration and induction of the macrophage cytokines, mouse chemoattractant protein 1 and macrophage inflammatory protein 1 alpha. Macrophage depletion results in diminished SRF231 antitumor activity, underscoring a mechanistic role for macrophage engagement by SRF231. CONCLUSION: SRF231 elicits antitumor activity via apoptosis and phagocytosis involving macrophage engagement in a manner dependent on the FcγR, CD32a.

Effects of three diet history questions on the amount of information gained from a sample of pet owners in Ontario, Canada.

OBJECTIVE: To examine the effect of 3 diet history questions on the amount and type of diet-related information gathered from pet owners and to assess whether diet-related information obtained with each question in person differed from information obtained with a diet history survey. SAMPLE: 99 pet owners. PROCEDURES: Participants' responses to 1 of 3 randomly selected diet history questions ("Tell me everything he [or she] eats throughout a day, starting first thing in the morning right through to the end of the day"; "What kind of food does she [or he] eat?"; or "What kind of foods does he [or she] eat?") were recorded and coded for analysis. Participants completed a postinteraction diet history survey. Amount and type of diet-related information obtained were compared among responses to the 3 diet history questions and between the response to each question and the diet history survey. RESULTS: The "Tell me…" question elicited a significantly higher total number of diet-related items (combined number of main diet, treat, human food, medication, and dietary supplement items) than did the "What kind of food…" or "What kind of foods…" questions. The diet history survey captured significantly more information than did the "What kind of food…" or "What kind of foods…" questions; there was little difference between results of the diet history survey and the "Tell me…" question, except that treats were more frequently disclosed on the survey. CONCLUSIONS AND CLINICAL RELEVANCE: Findings reinforced the value of using broad, open questions or requests that invite expansion from clients for gathering diet-related information.

Discovery of Inhibitors for Proliferating Cell Nuclear Antigen Using a Computational-Based Linked-Multiple-Fragment Screen.

Proliferating cell nuclear antigen (PCNA) is a central factor in DNA replication and repair pathways that plays an essential role in genome stability. The functional roles of PCNA are mediated through an extensive list of protein-protein interactions, each of which transmits specific information in protein assemblies. The flexibility at the PCNA-protein interaction interfaces offers opportunities for the discovery of functionally selective inhibitors of DNA repair pathways. Current fragment-based drug design methodologies can be limited by the flexibility of protein interfaces. These factors motivated an approach to defining compounds that could leverage previously identified subpockets on PCNA that are suitable for fragment-binding sites. Methodologies for screening multiple connected fragment-binding events in distinct subpockets are deployed to improve the selection of fragment combinations. A flexible backbone based on N-alkyl-glycine amides offers a scaffold to combinatorically link multiple fragments for in silico screening libraries that explore the diversity of subpockets at protein interfaces. This approach was applied to discover new potential inhibitors of DNA replication and repair that target PCNA in a multiprotein recognition site. The screens of the libraries were designed to computationally filter ligands based upon the fragments and positions to <1%, which were synthesized and tested for direct binding to PCNA. Molecular dynamics simulations also revealed distinct features of these novel molecules that block key PCNA-protein interactions. Furthermore, a Bayesian classifier predicted 15 of the 16 new inhibitors to be modulators of protein-protein interactions, demonstrating the method's utility as an effective screening filter. The cellular activities of example ligands with similar affinity for PCNA demonstrate unique properties for novel selective synergy with therapeutic DNA-damaging agents in drug-resistant contexts.