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Children and young people are increasingly being referred to specialist gender services, and available data on their characteristics are limited. The Longitudinal Outcomes of Gender Identity in Children (LOGIC) study is the first independently funded UK research programme to comprehensively assess quality of life, autism, service use and the psychological well-being of children and adolescents referred to gender services.
Aims
The aim of this baseline assessment is to obtain a multidimensional profile of children and young people on the waiting list for the gender service.
Method
Data were obtained from 617 parents and caregivers and 565 children and young people, representing a quarter of those on the waiting list eligible to participate. Participants were assessed across a range of domains including gender identity, gender dysphoria, mental health and well-being, autism, physical health, service use and quality of life.
Results
Gender dysphoria rates among our sample were high, particularly among adolescents. Almost all participants had socially transitioned. Compared with children, adolescents reported significantly poorer quality of life, particularly in relation to self-perception and psychological well-being. Relative to reference population samples, our cohort demonstrated elevated levels of mental ill health and reduced quality of life, although the magnitude of these differences varied. In addition, 59% of young people aged 11 years or over reported self-harm in the past year. Over half of the cohort had received a psychiatric diagnosis, and co-occurrence rates were high. A third of the cohort was either diagnosed with autism or undergoing assessment for autism.
Conclusions
Self-perception and psychological well-being represent particularly impaired quality of life dimensions for adolescents on the waiting list for the UK’s gender service. Complementing existing knowledge, differences emerged between young people and children, reflecting that the onset of puberty is a critical factor in the well-being of this cohort.
This paper examines Britain’s process of electrification following a disruptive stock market boom and bust in 1882. This is done by noting the companies that raise finance on British stock exchanges, the amounts raised, and the returns earned on that money. It also examines the impact of the Lighting Act of 1882, finding that the Act inhibited investment, but with important exceptions. We find the Act was not a barrier to entrepreneurs alert to the possibilities of electrification. However, the limited British electrical investment after the 1882 crash was more heavily and successfully concentrated on supplying electricity to end users than on developing electrical equipment. When electrification began in earnest after 1888, upon the amendment of the 1882 Lighting Act, there existed only a very weak engineering base to support it, leading to slow, expensive, and unimaginative electrification.
Alexandrov’s estimate states that if $\Omega $ is a bounded open convex domain in $\mathbb {R}^n$ and $u:\bar \Omega \to \mathbb {R}$ is a convex solution of the Monge-Ampère equation $\det D^2 u = f$ that vanishes on $\partial \Omega $, then
We establish a variety of improvements of this, depending on the geometry of $\partial \Omega $. For example, we show that if the curvature is bounded away from $0$, then the estimate remains valid if $\omega (\delta )$ is replaced by $C_\Omega \delta ^{\frac 12 + \frac 1{2n}}$. We determine the sharp constant $C_\Omega $ when $n=2$, and when $n\ge 3$ and $\partial \Omega $ is $C^2$, we determine the sharp asymptotics of the optimal modulus of continuity $\omega _\Omega (\delta )$ as $\delta \to 0$. For arbitrary convex domains, we characterize the scaling of the optimal modulus $\omega _\Omega $. Our results imply in particular that unless $\partial \Omega $ has a flat spot, $\omega _\Omega (\delta ) = o(\delta ^{1/n})$ as $\delta \to 0$, and under very mild nondegeneracy conditions, they yield the improved Hölder estimate, $\omega _\Omega (\delta ) \le C \delta ^\alpha $ for some $\alpha>1/n$.
The grief of relatives of patients who died of COVID-19 in an intensive care unit (ICU) has exacted an enormous toll worldwide.
Aims
To determine the prevalence of probable prolonged grief disorder (PGD) at 12 months post-loss and beyond. We also sought to examine circumstances of the death during the COVID-19 pandemic that might pose a heightened risk of PGD, and the associations between probable PGD diagnosis, quality of life and social disconnection.
Method
We conducted an observational, cross-sectional multicentre study of the next of kin of those who died of COVID-19 between March 2020 and December 2021. Participants were recruited from ICUs in South-East London. The Prolonged Grief Disorder Scale (PG-13-R), Quality-of-Life Scale (QOLS) and Oxford Grief-Social Disconnection Scale (OG-SD) were used.
Results
A total of 73 relatives were recruited and assessed, all of them over a year after their loss. Twenty-five (34.2%; 95% CI 23.1–45.4%) relatives of patients who died in the ICU met the criteria for PGD. Those who met the criteria had significantly worse quality of life (QOLS score mean difference 26; 95% CI 17–34; P < 0.001) and endorsed greater social disconnection (OG-SD score means difference 41; 95% CI 27–54; P < 0.001).
Conclusions
The findings suggest that rates of PGD are elevated among relatives of patients who died of COVID-19 in the ICU. This, coupled with worse quality of life and greater social disconnection experienced by those meeting the criteria, suggests the need to attend to the social deprivations and social dysfunctions of this population group.
Empowering the Participant Voice (EPV) is an NCATS-funded six-CTSA collaboration to develop, demonstrate, and disseminate a low-cost infrastructure for collecting timely feedback from research participants, fostering trust, and providing data for improving clinical translational research. EPV leverages the validated Research Participant Perception Survey (RPPS) and the popular REDCap electronic data-capture platform. This report describes the development of infrastructure designed to overcome identified institutional barriers to routinely collecting participant feedback using RPPS and demonstration use cases. Sites engaged local stakeholders iteratively, incorporating feedback about anticipated value and potential concerns into project design. The team defined common standards and operations, developed software, and produced a detailed planning and implementation Guide. By May 2023, 2,575 participants diverse in age, race, ethnicity, and sex had responded to approximately 13,850 survey invitations (18.6%); 29% of responses included free-text comments. EPV infrastructure enabled sites to routinely access local and multi-site research participant experience data on an interactive analytics dashboard. The EPV learning collaborative continues to test initiatives to improve survey reach and optimize infrastructure and process. Broad uptake of EPV will expand the evidence base, enable hypothesis generation, and drive research-on-research locally and nationally to enhance the clinical research enterprise.
Return to driving after moderate-to-severe traumatic brain injury (TBI) is often a key step in recovery to regain independence. Survivors are often eager to resume driving and may do so despite having residual cognitive limitations from their injury. A better understanding is needed of how cognition and self-awareness impact survivors’ driving after injury. This study examined the influence of cognition and self-awareness on driving patterns following moderate-to-severe TBI.
Participants and Methods:
Participants were 350 adults aged 19-87 years (mean age = 46 years; 70% male) with history of moderate-to-severe TBI, who resumed driving and were enrolled in the TBI Model System. Cross-sectional data were obtained ranging 1-30 years post injury, including questions on driving practices, the Brief Test of Adult Cognition by Telephone (BTACT), and the Functional Independence Measure (FIM). Self-awareness of cognitive function was measured via the discrepancy between dichotomized ratings (intact versus impaired) of objective cognitive testing (BTACT) and self-reported cognitive function (FIM Cognition subscale). Driving patterns included frequency (driving 'more than once a week’ versus 'once a week or less') and restricted driving behavior (total number of driving situations the survivor described as restricted, ranging 0-15). Regression analyses were conducted to examine the relationships between cognition, self-awareness, and each driving outcome (frequency and restriction), followed by causal mediation analyses to examine the mediating effect of self-awareness. Demographics (age, sex, education), injury characteristics (time since injury, injury severity, history of seizures in past year), and medical/social factors (family income, motor function, urban-rural classification) were included in the models as covariates.
Results:
Thirty-nine percent of survivors had impaired self-awareness, 88% of survivors drove numerous times per week, and the average survivor reported limited driving in 6 situations (out of 15 total situations). Cognition was inversely related to impaired self-awareness (OR = 0.03, p < 0.001) and inversely related to restricted driving behavior (b = -0.79, p < 0.001). Motor function was positively related to impaired self-awareness (OR = 1.28, p < 0.01). Cognition was not related to driving frequency, and self-awareness did not mediate the relationships between cognition and driving patterns (all p > 0.05).
Conclusions:
Most survivors who drive after their injury are driving frequently, but the situations they drive in differ based on their cognitive ability. Impaired self-awareness of cognitive deficits is common after TBI, and self-awareness of cognitive function does not affect driving patterns. Future research needs to focus on how cognition affects nuanced aspects of driving behavior after injury (i.e., types of situations survivors drive in).
Risk of suicide-related behaviors is elevated among military personnel transitioning to civilian life. An earlier report showed that high-risk U.S. Army soldiers could be identified shortly before this transition with a machine learning model that included predictors from administrative systems, self-report surveys, and geospatial data. Based on this result, a Veterans Affairs and Army initiative was launched to evaluate a suicide-prevention intervention for high-risk transitioning soldiers. To make targeting practical, though, a streamlined model and risk calculator were needed that used only a short series of self-report survey questions.
Methods
We revised the original model in a sample of n = 8335 observations from the Study to Assess Risk and Resilience in Servicemembers-Longitudinal Study (STARRS-LS) who participated in one of three Army STARRS 2011–2014 baseline surveys while in service and in one or more subsequent panel surveys (LS1: 2016–2018, LS2: 2018–2019) after leaving service. We trained ensemble machine learning models with constrained numbers of item-level survey predictors in a 70% training sample. The outcome was self-reported post-transition suicide attempts (SA). The models were validated in the 30% test sample.
Results
Twelve-month post-transition SA prevalence was 1.0% (s.e. = 0.1). The best constrained model, with only 17 predictors, had a test sample ROC-AUC of 0.85 (s.e. = 0.03). The 10–30% of respondents with the highest predicted risk included 44.9–92.5% of 12-month SAs.
Conclusions
An accurate SA risk calculator based on a short self-report survey can target transitioning soldiers shortly before leaving service for intervention to prevent post-transition SA.
Only a limited number of patients with major depressive disorder (MDD) respond to a first course of antidepressant medication (ADM). We investigated the feasibility of creating a baseline model to determine which of these would be among patients beginning ADM treatment in the US Veterans Health Administration (VHA).
Methods
A 2018–2020 national sample of n = 660 VHA patients receiving ADM treatment for MDD completed an extensive baseline self-report assessment near the beginning of treatment and a 3-month self-report follow-up assessment. Using baseline self-report data along with administrative and geospatial data, an ensemble machine learning method was used to develop a model for 3-month treatment response defined by the Quick Inventory of Depression Symptomatology Self-Report and a modified Sheehan Disability Scale. The model was developed in a 70% training sample and tested in the remaining 30% test sample.
Results
In total, 35.7% of patients responded to treatment. The prediction model had an area under the ROC curve (s.e.) of 0.66 (0.04) in the test sample. A strong gradient in probability (s.e.) of treatment response was found across three subsamples of the test sample using training sample thresholds for high [45.6% (5.5)], intermediate [34.5% (7.6)], and low [11.1% (4.9)] probabilities of response. Baseline symptom severity, comorbidity, treatment characteristics (expectations, history, and aspects of current treatment), and protective/resilience factors were the most important predictors.
Conclusions
Although these results are promising, parallel models to predict response to alternative treatments based on data collected before initiating treatment would be needed for such models to help guide treatment selection.
Negative emotionality (NE) was evaluated as a candidate mechanism linking prenatal maternal affective symptoms and offspring internalizing problems during the preschool/early school age period. The participants were 335 mother–infant dyads from the Maternal Adversity, Vulnerability and Neurodevelopment project. A Confirmatory Bifactor Analysis (CFA) based on self-report measures of prenatal depression and pregnancy-specific anxiety generated a general factor representing overlapping symptoms of prenatal maternal psychopathology and four distinct symptom factors representing pregnancy-specific anxiety, negative affect, anhedonia and somatization. NE was rated by the mother at 18 and 36 months. CFA based on measures of father, mother, child-rated measures and a semistructured interview generated a general internalizing factor representing overlapping symptoms of child internalizing psychopathology accounting for the unique contribution of each informant. Path analyses revealed significant relationships among the general maternal affective psychopathology, the pregnancy- specific anxiety, and the child internalizing factors. Child NE mediated only the relationship between pregnancy-specific anxiety and the child internalizing factors. We highlighted the conditions in which prenatal maternal affective symptoms predicts child internalizing problems emerging early in development, including consideration of different mechanistic pathways for different maternal prenatal symptom presentations and child temperament.
Fewer than half of patients with major depressive disorder (MDD) respond to psychotherapy. Pre-emptively informing patients of their likelihood of responding could be useful as part of a patient-centered treatment decision-support plan.
Methods
This prospective observational study examined a national sample of 807 patients beginning psychotherapy for MDD at the Veterans Health Administration. Patients completed a self-report survey at baseline and 3-months follow-up (data collected 2018–2020). We developed a machine learning (ML) model to predict psychotherapy response at 3 months using baseline survey, administrative, and geospatial variables in a 70% training sample. Model performance was then evaluated in the 30% test sample.
Results
32.0% of patients responded to treatment after 3 months. The best ML model had an AUC (SE) of 0.652 (0.038) in the test sample. Among the one-third of patients ranked by the model as most likely to respond, 50.0% in the test sample responded to psychotherapy. In comparison, among the remaining two-thirds of patients, <25% responded to psychotherapy. The model selected 43 predictors, of which nearly all were self-report variables.
Conclusions
Patients with MDD could pre-emptively be informed of their likelihood of responding to psychotherapy using a prediction tool based on self-report data. This tool could meaningfully help patients and providers in shared decision-making, although parallel information about the likelihood of responding to alternative treatments would be needed to inform decision-making across multiple treatments.
The phonetics/phonology interface refers to the relationship between the physical dimensions of phonetics and the abstract arrangement of phonemes and their manifestations within the phonological systems of languages. This chapter provides an overview of a range of approaches to the investigation of the phonetics/phonology interface, with particular attention to the relationships between phonetic factors such as positional prominence, acoustic salience and articulatory gestures, and phonological phenomena such as segment features and inventories, assimilation, and tone. I survey several clusters of theoretical orientation, each with distinct theoretical underpinnings and claims about the extent to which phonological concepts encode, reflect or direct phonetic details. I conclude with a discussion synthesising these seemingly disparate approaches, unifying them around a theme of linking the continuous physical dimensions of phonetic science with the abstract cognitive categories and rules of combination that typify phonological models. I discuss pedagogical implications and new directions in which facets of the interface can be explored.
The game of tennis has provided mathematicians with many interesting problems. In [1], the problem of finding the probability that a certain player wins a tennis tournament was studied. Gale [2] determined the best serving strategy in tennis. First, we assume Alice and Bob play a game of tennis using the standard (or Deuce/Ad) scoring system, without a tiebreaker, and that Alice serves the game. We also assume that the probability that Alice wins any point she serves is . Stewart [3] proved that the probability that Alice wins is
Studying phenotypic and genetic characteristics of age at onset (AAO) and polarity at onset (PAO) in bipolar disorder can provide new insights into disease pathology and facilitate the development of screening tools.
Aims
To examine the genetic architecture of AAO and PAO and their association with bipolar disorder disease characteristics.
Method
Genome-wide association studies (GWASs) and polygenic score (PGS) analyses of AAO (n = 12 977) and PAO (n = 6773) were conducted in patients with bipolar disorder from 34 cohorts and a replication sample (n = 2237). The association of onset with disease characteristics was investigated in two of these cohorts.
Results
Earlier AAO was associated with a higher probability of psychotic symptoms, suicidality, lower educational attainment, not living together and fewer episodes. Depressive onset correlated with suicidality and manic onset correlated with delusions and manic episodes. Systematic differences in AAO between cohorts and continents of origin were observed. This was also reflected in single-nucleotide variant-based heritability estimates, with higher heritabilities for stricter onset definitions. Increased PGS for autism spectrum disorder (β = −0.34 years, s.e. = 0.08), major depression (β = −0.34 years, s.e. = 0.08), schizophrenia (β = −0.39 years, s.e. = 0.08), and educational attainment (β = −0.31 years, s.e. = 0.08) were associated with an earlier AAO. The AAO GWAS identified one significant locus, but this finding did not replicate. Neither GWAS nor PGS analyses yielded significant associations with PAO.
Conclusions
AAO and PAO are associated with indicators of bipolar disorder severity. Individuals with an earlier onset show an increased polygenic liability for a broad spectrum of psychiatric traits. Systematic differences in AAO across cohorts, continents and phenotype definitions introduce significant heterogeneity, affecting analyses.
The use of online platforms for pediatric healthcare research is timely, given the current pandemic. These platforms facilitate trial efficiency integration including electronic consent, randomization, collection of patient/family survey data, delivery of an intervention, and basic data analysis.
Methods:
We created an online digital platform for a multicenter study that delivered an intervention for sleep disorders to parents of children with autism spectrum disorder (ASD). An advisory parent group provided input. Participants were randomized to receive either a sleep education pamphlet only or the sleep education pamphlet plus three quick-tips sheets and two videos that reinforced the material in the pamphlet (multimedia materials). Three measures – Family Inventory of Sleep Habits (FISH), Children’s Sleep Habits Questionnaire modified for ASD (CSHQ-ASD), and Parenting Sense of Competence (PSOC) – were completed before and after 12 weeks of sleep education.
Results:
Enrollment exceeded recruitment goals. Trial efficiency was improved, especially in data entry and automatic notification of participants related to survey completion. Most families commented favorably on the study. While study measures did not improve with treatment in either group (pamphlet or multimedia materials), parents reporting an improvement of ≥3 points in the FISH score showed a significantly improved change in the total CSHQ (P = 0.038).
Conclusion:
Our study demonstrates the feasibility of using online research delivery platforms to support studies in ASD, and more broadly, pediatric clinical and translational research. Online platforms may increase participant inclusion in enrollment and increase convenience and safety for participants and study personnel.
Stop the Bleed (STB) is a national initiative that provides lifesaving hemorrhagic control education. In 2019, pharmacists were added as health-care personnel eligible to become STB instructors. This study was conducted to evaluate the efficacy of pharmacist-led STB trainings for school employees in South Texas.
Methods:
Pharmacist-led STB trainings were provided to teachers and staff in Laredo, Texas. The 60-min trainings included a presentation followed by hands-on practice of tourniquet application, wound-packing, and direct pressure application. Training efficacy was assessed through anonymous pre- and postevent surveys, which evaluated changes in knowledge, comfort level, and willingness to assist in hemorrhage control interventions. Student volunteers (predominantly pharmacy and medical students) assisted in leading the hands-on portion, providing a unique interprofessional learning opportunity.
Results:
Participants with previous training (N = 98) were excluded, resulting in a final cohort of 437 (response rate 87.4%). Compared with baseline, comfort level using tourniquets (mean, 3.17/5 vs 4.20/5; P < 0.0001), opinion regarding tourniquet safety (2.59/3 vs 2.94/3; P < 0.0001), and knowledge regarding tourniquets (70.86/100 vs 75.84/100; P < 0.0001) and proper tourniquet placement (2.40/4 vs 3.15/4; P < 0.0001) significantly improved.
Conclusions:
Pharmacist-led STB trainings are efficacious in increasing school worker knowledge and willingness to respond in an emergency hemorrhagic situation.
We present the current status of a scalable computing framework to address the need of the multidisciplinary effort to study chemical dynamics. Specifically, we are enabling scientists to process and store experimental data, run large-scale computationally expensive high-fidelity physical simulations, and analyze these results using state-of-the-art data analytics, machine learning, and uncertainty quantification methods using heterogeneous computing resources. We present the results of this framework on a single metadata-driven workflow to accelerate an additive manufacturing use-case.
Modern Catholic social teaching, especially as articulated by the popes, the curia, and the bishops, has said little directly and formally about systems of finance. Where these voices have spoken, they have encouraged sound practices in broad outline and criticized obviously unsound and immoral behaviors. Unfortunately, their own financial management practices have not offered good models for what might be done. Nevertheless, key concepts like the logic of gift, the idea of solidarity and the common good, and the vision of integral human development, coupled with the competence and integrity of Catholics working in systems of finance, can imagine possibilities and generate inspiring models of professional conduct. The key to making this work well is to understand and embrace the possibility of pursuing work in the system of finance as a genuine Christian vocation that in its own way genuinely addresses human needs and helps to build the Kingdom of God. In service of this, the pastors of the Church at every level can and should affirm this profession as a vocation, encourage Catholics to bring their faith to their work, avoid unnecessary criticism of business practices, and assist business professionals to see more clearly the challenges and possibilities they face.
Institutionally deprived young children often display distinctive patterns of attachment, classified as insecure/other (INS/OTH), with their adoptive parents. The associations between INS/OTH and developmental trajectories of mental health and neurodevelopmental symptoms were examined. Age 4 attachment status was determined for 97 Romanian adoptees exposed to up to 24 months of deprivation in Romanian orphanages and 49 nondeprived UK adoptees. Autism, inattention/overactivity and disinhibited-social-engagement symptoms, emotional problems, and IQ were measured at 4, 6, 11, and 15 years and in young adulthood. Romanian adoptees with over 6 months deprivation (Rom>6) were more often classified as INS/OTH than UK and Romanian adoptees with less than 6 months deprivation combined. INS/OTH was associated with cognitive impairment at age 4 years. The interaction between deprivation, attachment status, and age for autism spectrum disorder assessment was significant, with greater symptom persistence in Rom>6 INS/OTH(+) than other groups. This effect was reduced when IQ at age 4 was controlled for. Age 4 INS/OTH in Rom>6 was associated with worse autism spectrum disorder outcomes up to two decades later. Its association with cognitive impairment at age 4 is consistent with INS/OTH being an early marker of this negative developmental trajectory, rather than its cause.