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Despite overwhelming international evidence of elevated rates of poor mental health in LGBTQ+ youth compared to their cis-heterosexual peers, we know relatively little about effective mental health services for this population group. This study aims to produce the first early intervention model of “what works” to support LGBTQ+ youth with emerging mental health problems. Utilizing a mixed method case study, we collected data across 12 UK mental health service case study sites that involved: (a) interviews with young people, parents, and mental health practitioners (n = 93); (b) documentary analysis; (c) nonparticipant observation. The data analysis strategy was theoretical using the “explanation-building” analytical technique. Our analysis suggests an intersectional youth rights approach with 13 principles that must be enacted to provide good mental health services as advocated by the United Nations Convention on the Rights of the Child and World Health Organization. This approach should address the multiple forms of marginalization and stigmatization that LGBTQ+ youth may experience, enable informed independent decision-making, and uphold the right to freedom of safe self-expression. A rights-based approach to mental health services for LGBTQ+ young people is not prominent. This needs to change if we are to tackle this mental health inequality and improve the mental well-being of LGBTQ+ youth worldwide.

Introduction:C3 is central for all complement activation pathways, thus making it an attractive therapeutic target. Many C3-targeted agents are under extensive development with one already approved for clinical use. However, most, if not all, C3 inhibitors are human or nonhuman primate C3-specific, making evaluating their efficacies in vivo before a clinical trial extremely difficult and costly. Methods:We first studied the compatibility of human C3 in the rat complement system, then developed a C3 humanized rat using the CRISPR/Cas9 technology. We thoroughly characterized the resultant human C3 humanized rats and tested the treatment efficacy of an established primate-specific C3 inhibitor in a model of complement-mediated hemolysis in the C3 humanized rats. Results:We found that supplementing human C3 protein into the C3-deficient rat blood restored its complement activity, which was inhibited by rat factor H or compstatin, suggesting that human C3 is compatible to the rat complement system. The newly developed C3 humanized rats appeared healthy and expressed human but not rat C3 without detectable spontaneous C3 activation. More importantly, complement-mediated hemolysis in the C3 humanized rats was also inhibited by compstatin both in vitro and in vivo. Conclusion:The successfully developed C3 humanized rats provided a much-desired rodent model to evaluate novel C3 inhibitors in vivo as potential drugs.

Mathematical knowledge and skills are critical in the development of students. In this article, we begin to unpack the concept of mathematics disabilities and how they are presented across classrooms. We explain commonly used terms such as, specific learning disability and dyscalculia, and emphasize how students qualify for math support. We provide overview regarding difficulties students encounter with math and how to support student learning.

Approximately 30–50% of people with serious mental illness have co-existing drug or alcohol problems (COSMHAD), associated with adverse health and social care outcomes. UK guidelines advocate both co-occurring needs being met within mental health services, but uncertainty remains about how to operationalise this to improve outcomes. Various unevaluated service configurations exist in the UK. A realist synthesis was done to identify, test, and refine programme theories of how context shapes the mechanisms through which UK service models for COSMHAD work, for whom, and in what circumstances. Structured and iterative realist searches of seven databases identified 5099 records. A two-stage screening process identified 132 papers. Three broad contextual factors shaped COSMHAD services across 11 programme theories: committed leadership, clear expectations regarding COSMHAD from mental health and substance use workforces, and clear care-coordination processes. These contextual factors led to increased staff empathy, confidence, legitimisation, and multidisciplinary ethos, which improved care coordination and increased the motivation of people with COSMHAD to work towards their goals. Our synthesis highlights that integrating COSMHAD care is complex, and both individual and cultural behavioural shifts in leadership, workforce, and service delivery are essential to ensure people with COSMHAD receive compassionate, trauma-informed care that meets their needs.

Many students with autism spectrum disorder (ASD) experience academic challenges and difficulties. These struggles are especially pronounced in mathematics with students with ASD performing significantly below than their peers without disabilities on measures of mathematical performance. The current study used a single case experimental design with concurrent multiple probe across students to investigate the effects of a point-of-view video modeling (POVM) intervention on accuracy of addition with regrouping word problems. The participants were three secondary grade level students with ASD. Findings showed that each student demonstrated considerable improvement during intervention over baseline levels, and subsequently sustaining their performance through the maintenance phase. Limitations, implications for practitioners and future research directions are presented.

Assessments for eating disorders rely primarily on self-report; yet, the denial of symptoms or symptom severity among adolescents with anorexia nervosa can complicate assessment and delay treatment in this population. The Parent Eating Disorder Examination (PEDE) is the first semi-structured interview formally developed to improve childhood eating disorder assessment by including caregiver perspectives. In this study, a large sample of adolescents with anorexia nervosa completed a self-report interview (the Eating Disorder Examination or EDE) and their parents completed the PEDE. The PEDE appeared to measure parents’ report of their child’s eating disorder symptoms consistently. Results from both interviews were related to one another but did not completely agree. This suggests that in an eating disorder assessment, the PEDE can provide additional information from caregivers that might reduce diagnostic confusion and lead to earlier intervention for youth with anorexia nervosa.

Ethically , behavior analysts are required to use the least aversive and restrictive procedures capable of managing behaviors of concern. This article introduces and discusses a multi-element paradigm for devising support plans that include ecological, positive programming, and focused-support proactive strategies for reducing the frequency of problem behavior occurrence. It also includes reactive strategies, i.e., separate independent variables. In this paradigm, reactive strategies are aimed solely at getting rapid, safe control over the incident, thereby reducing measured and quantified episodic severity. Behavior analysts who publish in mainstream behavioral journals do not always make it explicit how they, in fact, successfully employed non-aversive reactive procedures to achieve rapid/safe control over the severity of a behavioral incident. Three examples of published studies in the behavioral literature which successfully, though only implicitly, used non-aversive reactive strategies (NARS) to reduce the severity of the behaviors of concern are described. The multi-element paradigm discussed in the present article is illustrated by the support plans that address the challenging behavior of three children in a pre-school setting, using both proactive and reactive strategies. Reactive strategies were used for the purpose of reducing episodic severity (ES) and proactive strategies were aimed at reducing the frequency of occurrence. Following a comprehensive functional analysis and assessment (CFA) and the implementation of a multi-element behavior support (MEBS) plan, results show successful outcomes without the need for any aversive or restrictive procedures. When addressing severe behaviors of concern, in addition to reducing behavioral occurrence, safety should also be improved by reducing ES as a measured outcome and as a function of the reactive strategies employed, including in many cases, the use of strategic capitulation, i.e., providing the identified reinforcer for the target behavior.

The widespread use of PCR to quantify minimal residual disease has been hampered by the apparently wide variation in amplification efficiency (AE) of PCR primers. A new method to measure AE was developed on the basis of the Ct results of PCR amplification of single copies of a target molecule placed by limiting dilution into wells of a microplate. The mean one copy Ct of a population of primers or of a reference primer was calibrated against the AE determined by the standard method of regression analysis. The AE of a test primer could then be determined by relating its one copy Ct value to the calibrated mean one copy Ct value. This new method was much more precise than direct determination of AE by regression analysis. The AE of minimal residual disease primers, and of primers for eight other genes, was determined to be >95% and often close to 100%. A primer/plasmid standard was produced to enable transfer of the method to other laboratories. The one copy Ct method thus enables AE of a patient-specific primer to be simply and accurately determined.

Purpose: Autism spectrum disorder traits have been implicated in the psychopathology of eating disorders and may also be relevant for the development of orthorexia symptoms. Further, intolerance of uncertainty (IUS) may indirectly contribute to the development of disordered eating, as the displacement of anxiety onto food may help achieve a sense of control and maximise certainty. We examined a new cognitive model of eating pathology which assessed the role of IU and orthorexia symptoms as potential mediators of the relationship between autistic traits and disordered eating in a community sample. Methods: Three-hundred-and-ninety-six female participants (M= 20.07, SD = 4.52 years old) completed an online self-report questionnaire which assessed the variables of interest. Results: Despite finding significant bivariate correlations, our model results showed that autistic traits did not directly predict disordered eating or orthorexia symptoms. Significant indirect relationships were found between autistic traits and eating disorder symptoms through both IU and orthorexia symptoms. Conclusion: The findings provide partial support for our proposed model suggesting that autistic traits may increase the vulnerability for disordered eating, not directly, but through their associations with mechanisms such as IU and the development of problematic eating behaviours typical of orthorexia. Future research should focus on whether targeting IU may assist in preventing the development of disordered eating. Level of evidence: Level V, cross-sectional descriptive study.

Purpose: Boys represent a small proportion of samples in randomized clinical trials (RCT) investigating evidence-based treatment for adolescents with anorexia nervosa (AN). Consequently, knowledge of potential gender differences in clinical characteristics and treatment response in adolescents is considerably limited. Methods: Secondary analyses of aggregated data from two RCTs were used to characterize baseline and end-of-treatment clinical features in male and female adolescents with AN (n= 228, 10.53% male). Mixed analyses of variance were used to investigate potential gender differences in treatment response relative to weight outcomes (% median BMI) and eating disorder cognitions (Eating Disorder Examination Global scores; EDE). Results: There were no significant gender differences in prior inpatient care, illness duration, psychiatric comorbidity, or psychotropic medication use at baseline. Nor were there significant gender differences in binge eating, purging, or driven exercise at baseline or end-of-treatment. Girls reported elevated weight and shape concern compared to boys at baseline but overall reduction in EDE Global scores over the course of treatment did not differ according to gender. Boys gained more relative weight during treatment than girls, but this difference was statistically non-significant. Conclusion: Overall findings do not suggest significant differences in treatment outcome relative to weight or ED cognitions, by gender. Current evidence suggests that, with the exception of shape and weight concerns, boys present with cognitive and behavioral symptoms as severe as their female counterparts which underscores the need for increased accuracy in assessment of these disorders in boys and young men. Level of evidence: Level 1, secondary data analysis of randomized controlled trials

Atypical anorexia nervosa (AN) has received minimal empirical attention regarding effective diagnosis and treatment. Family-based treatment (FBT) might be a promising treatment for atypical AN, yet it is unclear as to what adaptations are needed to the current manualized FBT for AN model. The objective of the current study was to identify how FBT practitioners applied FBT for atypical AN for adolescents in their clinical practice, and if there were any implementation challenges and adaptations to the model for this population. The current study employed fundamental qualitative description, with the aim of capturing practitioners’ reflections on working with adolescents with atypical AN in clinical practice. A purposeful sample of practitioners with training in FBT were recruited and each participant completed an individual, semi-structured interview. Data was analyzed using conventional content analysis. A total of 23 practitioners participated in this study. The results indicate that practitioners maintained some fidelity to manualized FBT in treating atypical AN, but they differed in their discussions around target weights, what constitutes weight restoration, and the dosage for FBT phases. Salient practice challenges included operationalizing the Diagnostic and Statistical Manual of Mental Disorders – 5th Edition(DSM-5) definition of atypical AN, identifying a ‘goal weight’ for adolescents and activating parents to take charge of the re-nourishment process. The results of this qualitative study demonstrate practitioner reflections on the delivery and adaptations of FBT for adolescents with atypical AN. These reflections highlight the need to establish the delivery of coherent and consistent treatment and messaging with patients and families. Further, practitioners’ reflections highlight common strategies to increase the sense of urgency in parents to support their child with atypical AN.

In this article, we illustrate how mathematics and special education teachers can collaboratively plan together to differentiate mathematics instruction for students with exceptionalities. We describe a structured, collaborative planning protocol that is the first phase of a Mathematics-Specific Consultation for Students with Exceptionalities (MSC-SE). Using the exemplar triad of a third-grade mathematics teacher, a special education resource teacher, and a third-grade student diagnosed with Attention Deficit with Hyperactivity Disorder (ADHD) and Specific Learning Disabilities (SLD), we show what this planning looks like for the specific content area of fractions. We highlight how these teachers, in collaboration with the student, work together purposefully to understand what her strengths are, why she is having difficulty, and what mathematics-related supports she needs. Within this context, we discuss how the two teachers develop a mathematics instructional hypothesis that provides them a focused and informed foundation for developing an individualized instruction/intervention plan for their student.

The current study investigated the effectiveness of an intensive writing intervention focusing on mathematical reasoning through written expression. A group pretest–intervention–posttest comparison experimental design was used to implement a 12-lesson intervention, delivered through a combination of Google Classroom and in-person classroom teacher support, to fifth-grade students with specific learning disabilities (n= 19). Although underpowered, our results indicated the intensive writing intervention led to all students in the intervention group (n= 11) significantly outperforming the students in the control group (n= 8) on subtraction and division word problems requiring an explanation of their solution in written form. Additionally, student treatment interviews revealed the strategy was both enjoyable and helpful in solving and explaining their word problem solutions and the teacher provided insight into potential additional scaffolds to support the most intensive students. Lessons learned and implications for research and practice are presented.

Background Traumatic hemorrhage is a prevalent cause of death nationally, with >50% of civilian deaths estimated to be preventable with more timely intervention. This study investigated the efficacy of training large and diverse audiences in bleeding control methods including tourniquets in community health fair settings.Methods A booth was utilized for bleeding control training at community health fairs via direct demonstrations of pressure, wound packing, and commercial and improvised tourniquet application followed by hands-on practice. Participants self-rated their perceived abilities while instructors rated the participant competency.Results 117 community members participated during two fairs, though not every person completed every portion of the training. Average age was 33 (range 6-82) and the majority were female (65.0%). There was no difference in self-perceived skill compared to trainer grading of participant’s ability to identify life-threatening bleeding (112 (97.4%) vs 106 (97.2%); P= 1), apply pressure (113 (98.3%) vs 106 (97.2%); P= .68), and pack a wound (102 (88.7%) vs 92 (84.4%); P= .43). No difference in difficulty was noted in placing commercial vs improvised tourniquets (16 (43%) vs 14 (45%); P= .87). However, participants were overconfident in their ability to place tourniquets compared to trainer grading, respectively (112 (98.2%) vs 100 (91.7%; P= .03)).Discussion Community fair classes provide opportunities to train large and diverse audiences in bleeding control techniques. However, participants overestimated their ability to appropriately apply tourniquets. Further investigation is needed into best educational approaches to optimize the impact of bleeding control kits that have been distributed in multiple states.

Population ageing poses many challenges in the landscape of general medicine. One of these is the requirement for more geriatricians to minimise future strain on healthcare systems. Previous studies have identified that, while demand for geriatricians is on the rise, interest among medical students for a career in geriatrics falls behind. We utilised a new augmented reality technology (the Microsoft HoloLens 2) to deliver students a remote bedside teaching experience. Features of this teaching included bi-directional communication, exposure to physical signs, and use of holograms around the patient bedside as a teaching aid. Given its convenience, scope and engagement potential, this educational tool has potential to be used effectively throughout medical training.

Chronic inflammation and gut microbiota dysbiosis, in particular the bloom of genotoxin-producing E. coli strains, are risk factors for the development of colorectal cancer. Here, we sought to determine whether precision editing of gut microbiota metabolism and composition could decrease the risk for tumor development in mouse models of colitis-associated colorectal cancer (CAC). Expansion of experimentally introduced E. coli strains in the azoxymethane/dextran sulfate sodium colitis model was driven by molybdoenzyme-dependent metabolic pathways. Oral administration of sodium tungstate inhibited E. coli molybdoenzymes and selectively decreased gut colonization with genotoxin-producing E. coli and other Enterobacteriaceae. Restricting the bloom of Enterobacteriaceae decreased intestinal inflammation and reduced the incidence of colonic tumors in two models of CAC, the azoxymethane/dextran sulfate sodium colitis model and azoxymethane-treated, Il10-deficient mice. We conclude that metabolic targeting of protumoral Enterobacteriaceae during chronic inflammation is a suitable strategy to prevent the development of malignancies arising from gut microbiota dysbiosis.

This systematic review of literature synthesizes research on video-based instruction (VBI) to teach mathematics to students with autism spectrum disorder (ASD). Eleven studies, including gray literature, were included in the synthesis resulting in data analysis of performance from 29 participants. To better align with transparent reporting guidelines of PRISMA (Moher et al., PLoS Medicine 6(7), 2009), we synthesize information regarding participants, intervention outcomes, and study design. Effects of student and study-level outcomes are presented in non-overlapping data (PND) and improvement rate difference (IRD). Findings show VBI has considerable support for positive effects across types of VBI, student characteristics, and mathematical concepts. Effective interventions incorporated academic and behavioral components with evidence base. With six studies demonstrating strong evidence, 16 individual cases of effect, and research spanning at least three research teams and research locations, results indicate that VBI meets minimum evidence set forth by Reichow et al., (Journal of Autism and Developmental Disorders 38:1311–1319, 2008) to be an established evidence-based practice to teach mathematics to students with ASD.

People with severe mental illnesses such as schizophrenia are three times more likely to smoke than the wider population, contributing to widening health inequalities. Smoking remains the largest modifiable risk factor for this health inequality, but people with severe mental illness have not historically engaged with smoking cessation services. We aimed to test the effectiveness of a combined behavioural and pharmacological smoking cessation intervention targeted specifically at people with severe mental illness.

The narrow representation of body image in the media has been linked to body dissatisfaction, particularly among readers of women's fashion magazines. Some countries have made efforts to improve body image diversity in the media and the fashion industry. This has included attempts to regulate minimum body size of models (eg, Israel, France), and the development of codes of practices such as the Australian Industry Code of Conduct on Body Image. However, there is little evidence of whether these efforts have impacted media content. This study aimed to gauge the state of body image diversity in the print media 5 years after the introduction of the Australian Code of Conduct via a content analysis of 13 Australian women's fashion magazines published in 2015. Results revealed low levels of diversity in body size, ethnicity and age among models depicted in fashion magazine images. Models were predominantly young, white and underweight. The results suggest that efforts to improve body image diversity have had little impact on print media. Further research is needed to understand the barriers to increased diversity in the representation of body image in the media so that the industry and regulatory bodies can further address this important issue. This is increasingly pressing given the proliferation of content now enabled through online media platforms.

ABSTRACTMass shootings have become an important topic of scholarly research; however, few studies examine the relationship between masculinity and violence. This study investigates how masculinities are constructed using a thematic content analysis of the Isla Vista mass shooter's manifesto, My Twisted World: The Story of Elliot Rodger.Our analyses reveal how the shooter constructs and ‘does’ masculinity in adherence to masculine cultural ideals. Rodger reproduces hegemonic gender ideologies through his construction of masculinity in relation to physical embodiment and sexual prowess. Those who displayed these traits are constructed as superior men, characterizing men who lacked them as inferior. Interestingly, Rodger presents himself as lacking in these areas. As such, he draws on alternative masculine presentations to illustrate his manhood. When he does not receive societal confirmation of his masculinity, he experiences a crisis of masculinity and feelings of aggrieved entitlement wherein he directs his anger at racial minorities and women. He eventually adopts a violent masculinity and executes a violent retribution when his experiences do not live up to culturally defined gender expectations. The implications of these findings are discussed.

ABSTRACTThis quasi-experimental study explores changes in preservice teachers’ reported self-efficacy and knowledge of instructional strategies in supporting English language learners (ELLs) after participating in an electronic pen-pal project. Seventy-four preservice teachers (experimental = 35; control = 39) participated in this study. The intervention involved a semester-long online letter exchange between the experimental group and ELL pen-pal partners in public schools. The study addresses two questions: What are the effects of an E-Pal project on preservice content-area teachers’ (1) reported self-efficacy in supporting ELLs, and (2) knowledge about the nature of instructional supports for ELLs in mainstream classrooms? Questionnaire data were analyzed using several ANOVA tests. Overall, results suggested that the E-Pal project had a positive effect on the reported self-efficacy and knowledge of instructional support of preservice teachers who participated in the experiment compared to those who did not. These results suggest that incorporating technology in field experiences in teacher education programs is worth the investment.

Inflammatory diseases of the gastrointestinal tract are frequently associated with dysbiosis, characterized by changes in gut microbial communities that include an expansion of facultative anaerobic bacteria of the Enterobacteriaceae family (phylum Proteobacteria). Here we show that a dysbiotic expansion of Enterobacteriaceae during gut inflammation could be prevented by tungstate treatment, which selectively inhibited molybdenum-cofactor-dependent microbial respiratory pathways that are operational only during episodes of inflammation. By contrast, we found that tungstate treatment caused minimal changes in the microbiota composition under homeostatic conditions. Notably, tungstate-mediated microbiota editing reduced the severity of intestinal inflammation in mouse models of colitis. We conclude that precision editing of the microbiota composition by tungstate treatment ameliorates the adverse effects of dysbiosis in the inflamed gut.

Although people with serious mental illnesses have a high risk of contracting blood-borne viral infections, sexual health has largely been neglected by researchers and policy makers involved in mental health. Failure to address this shortcoming could increase morbidity and mortality as a result of undetected and untreated infection. We did a systematic review and meta-analysis to estimate the prevalence of blood-borne viral infection in people with serious mental illness.

The BCR-ABL1sequence has advantages over the BCR-ABL1transcript as a molecular marker in chronic myeloid leukemia and has been used in research studies. We developed a DNA real-time quantitative PCR (qPCR) method for quantification of BCR-ABL1sequences, which is also potentially suitable for routine use. The BCR-ABL1breakpoint was sequenced after isolation by nested short-range PCR of DNA from blood, marrow, and cells on slides, obtained either at diagnosis or during treatment, or from artificial mixtures. PCR primers were chosen from a library of presynthesized and pretested BCR(n= 19) and ABL1(n= 568) primers. BCR-ABL1sequences were quantified relative to BCRsequences in 521 assays on 266 samples from 92 patients. For minimal residual disease detectable by DNA qPCR and RT-qPCR, DNA qPCR gave similar minimal residual disease results as RT-qPCR but had better precision at low minimal residual disease levels. The limit of detection of DNA qPCR depended on the amount of DNA assayed, being 10−5.8when 5 μg was assayed and 10−7.0when 80 μg was assayed. DNA qPCR may be useful and practical for monitoring the increasing number of patients with minimal residual disease around or below the limit of detection of RT-qPCR as the assay itself is simple and the up-front costs will be amortized if sequential assays are performed.

Capillary malformation–arteriovenous malformation (CM-AVM) is an autosomal dominant blood vascular (BV) disorder characterized by CM and fast flow BV lesions. Inactivating mutations of the RASA1gene are the cause of CM-AVM in most cases. RASA1 is a GTPase-activating protein that acts as a negative regulator of the Ras small GTP-binding protein. In addition, RASA1 performs Ras-independent functions in intracellular signal transduction. Whether CM-AVM results from loss of an ability of RASA1 to regulate Ras or loss of a Ras-independent function of RASA1 is unknown. To address this, we generated Rasa1knockin mice with an R780Q point mutation that abrogates RASA1 catalytic activity specifically. Homozygous Rasa1R780Q/R780Qmice showed the same severe BV abnormalities as Rasa1-null mice and died midgestation. This finding indicates that BV abnormalities in CM-AVM develop as a result of loss of an ability of RASA1 to control Ras activation and not loss of a Ras-independent function of this molecule. More important, findings indicate that inhibition of Ras signaling is likely to represent an effective means of therapy for this disease.

Objectives:To examine patients’ perspectives regarding long-term vitamin K antagonist (VKA) therapy and the potential transition to new oral anticoagulants (NOACs) such as dabigatran and rivaroxaban, and to determine if factors such as residential location affect these opinions.Design, setting and participants:Patients on VKA therapy for at least 12 weeks completed a questionnaire specifically designed for the study. They were recruited while attending point-of-care international normalized ratio (INR) testing at six South Australian general practice clinics during the period July–September 2013.Main outcome measures:Opinions of current VKA therapy, level of awareness of NOACs, and ratings of potential benefits and deterrents of transition to NOACs were sought.Results:Data from 290 participants were available for analysis (response rate 95.4%). The majority of the sample (79.5%, 229/288) were either satisfied or very satisfied with current VKA therapy. The mean score for the potential benefits of transition to NOACs was 7.6 (±4.2) out of a possible 20, which was significantly lower than the mean score 10.9 (±4.5) for the perceived deterrents to transition (p < 0.001). Rural patients (82.0%, 82/100) were significantly more likely (p = 0.001) to have not heard of NOACs than metropolitan patients (50.3%, 95/189) and also perceived significant less benefits in a transition to NOACs (p = 0.001).Conclusion:When considering potential transition from VKAs to NOACs it is important for prescribers to consider that some patients, in particular those from a rural location, may not perceive a significant benefit in transitioning or may have particular concerns in this area.