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Anxiety disorders have been on the rise among adolescents over the past decade. The COVID-19 pandemic appears to have contributed to this increase, putting further pressure on often already overburdened health systems. Universal prevention programs may offer a potential solution, but few have been evaluated in the context of a pandemic. The objective of this article is to measure the impact of a universal prevention program--the HORS-PISTE program--on several anxiety-related variables in the context of a pandemic. The HORS-PISTE program consists of 10 workshops spread over the two first years of high school, secondary 1 and 2 (grade 7 and 8 equivalent). Workshops are held in a classroom setting and focus on the development of psychosocial skills. The study was conducted in Quebec with 1,202 secondary 1 and 2 students (48.7% girls, 51.3% boys) with an average age of 12.58 years ("SD" = 0.75). They completed an assessment protocol before and after participating in the HORS-PISTE program in the autumn of 2020. Their answers were subjected to descriptive analysis and multivariate analysis of variance. Results indicate a significant decrease in symptoms for several of the measured variables between the two measurement times, such as those associated with panic disorder, generalized anxiety disorder, and test anxiety. The results also show a decrease in some variables related to the interference of anxiety symptoms and the cognitive and behavioral vulnerabilities targeted by the program. The discussion highlights possible explanations for the results, as well as how universal prevention programs may contribute to the prevention of anxiety during adolescence, especially in a pandemic context.

This study was interested in the level of correspondence between high school students' self-perceptions of academic competence and achievement. The objectives were to (a) identify different profiles of students in terms of correspondence between perceptions of general academic competence and achievement in language arts and mathematics, (b) describe the personal and family characteristics of the students in these profiles, and (c) associate personality traits defined by the Big-Five with these profiles. A latent class analysis and a multinominal logistic regression were conducted on the data collected from 309 ninth and tenth graders. Among the most salient results, five profiles of students were identified, three of which with competence perceptions corresponding with achievement (i.e., high achievers with high self-perceived competence (SPC), average achievers with average SPC, and low achievers with lower SPC) and two with competence perceptions showing no or little correspondence with achievement (i.e., low achievers with higher SPC and average achievers with lower SPC). Also, students scoring high on openness to experience and conscientiousness were more likely to belong to the profile of high achievers with high SPC. These findings contribute to the literature on the possible reasons why students hold accurate or biased self-perceptions of competence.

Pundits, politicians, and academics have long worried about potentially low rates of civic participation among STEM-oriented students. Does studying STEM actually decrease the odds that young people will be actively involved in democracy? To answer this question, we created a dataset of over 23 million students in the United States, matched to national validated voting records. This novel dataset is the largest known individual-level dataset in the United States, connecting high school and college students to voting outcomes. It also contains a rich set of demographic and academic variables, to account for many of the common issues related to students' selection into STEM coursework. We consider two measures of STEM participation: Advanced Placement (AP) exam taking in high school and college major. Using both measures, we find that, across model specifications, the estimated relationships between STEM and voting are small in magnitude--about the same effect size as a single get-out-the-vote mailer. Our analyses demonstrate that, on average, marginally more STEM coursework in high school and college does not contribute noticeably to the low voting rates among young people in the United States.

Abstract Prevention programs, such as mindfulness-based interventions (MBIs), are often implemented in schools to prevent psychological disorders from emerging in children and to support their mental health. This study used a randomized cluster design to evaluate the impact of a MBI, called Mission Méditation, on the well-being and the mental health of elementary school children’s. 13 classrooms of an elementary school were randomly allocated to the experimental condition (7 classrooms, n = 127 students) or the waitlist control condition (6 classrooms, n = 104 students). Participants in the experimental condition received a 10-week MBI. Regression analyses revealed significant differences between conditions for inattention. Participants in the MBI condition reported no change in pre- to post-intervention, whereas participants in the control condition reported pre- to post-intervention increases. Results also showed significant differences in perceived competence. Participants in the MBI condition reported a non-significant decrease in perceive competence, whereas participants in the control condition reported significantly higher perceive competence scores from pre- to post-intervention. Results do not indicate that the MBI had a significant impact on participant’s well-being and mental health. This suggests that MBIs may not have an added value when compared to other preventive interventions geared towards well-being and mental health promotion in school settings.

We investigate whether and how Achieve Atlanta’s college scholarship and associated services impact college enrollment, persistence, and graduation among Atlanta Public School graduates experiencing low household income. Qualifying for the scholarship of up to $5,000 per year does not meaningfully change college enrollment among those near the high school GPA eligibility thresholds. However, scholarship receipt does have large and statistically significant effects on early college persistence (i.e., 14%) that continue through BA degree completion within 4 years (22%), although scholarship receipt does not impact graduation from 2-year colleges. We discuss how the selection criteria and processes of place-based programs intended for those from economically disadvantaged backgrounds may influence results for different types of students.

Objectives This study aims to examine the proportions of patients referred to mental health, social and voluntary, community and social enterprise (VCSE) services and general practice and to assess care gaps among people presenting to the hospital following self-harm.Design Population-based observational study. Data were extracted from hospital records.Setting Three emergency departments (EDs) in Manchester, UK.Participants 26 090 patients aged 15+ years who presented to participating EDs following self-harm and who received a psychosocial assessment by a mental health specialist.Primary and secondary outcome measures Primary outcome measures are as follows: care gaps, estimated from the proportion of patients with evidence of social and mental health needs with no new or active referral to mental health, social and VCSE services. Secondary outcome measures are as follows: proportions of referrals by groups of patients, estimated mental health and social needs of patients. Indicators of mental health and social need were developed with academic clinicians (psychiatrist, general practitioner and social worker) and expert lived experience contributors.Results 96.2% (25 893/26 909) of individuals were estimated as having mental health needs. Among this group, 29.9% (6503/21 719) had no new or active referral to mental health services (indicating a care gap). Mental healthcare gaps were greater in men and those who were aged under 35 years, from a black, South Asian or Chinese ethnic group, living in the most deprived areas and had no mental health diagnosis, or alcohol, substance misuse, anxiety or trauma-related disorder. 52.8% (14 219/26 909) had social needs, with care gaps greater for men, individuals aged 45–64 and those who were unemployed or had a diagnosed mental disorder.Conclusions Care gaps were higher among hospital-presenting groups known to have increased risks of suicide: men, those in middle age, unemployed individuals and those misusing substances. Improved access to mental health, social and VCSE services and general practice care is vital to reduce inequities in access to self-harm aftercare.

Interventions targeting children’s eco-anxiety have focused on fostering hope, however this is disconnected from children’s need to explore and express despair regarding the climate crisis. Adults can help by acknowledging and discussing these emotions with children.

The consequences of human activity on climate change are increasingly apparent. For example, they are causing ecological degradation and affecting human and animal health. Rightly so, it is considered as the most important challenge of this century. Researchers in psychology and mental health developed an interest in the direct and indirect effects of climate and ecological change on people's psychological wellbeing, which is referred to as a concept described as eco-anxiety or eco-distress. It is worth emphasizing that climate issues are taking a larger place in the school curriculum for youth in elementary, middle and high schools. Youth are thus increasingly aware of the major threat and understandably report legitimate concerns and worries. For some youth, eco-anxiety leads to greater involvement and activism, as can be seen by the international movement set out and led by youth activist Greta Thunberg. However, eco-anxiety can also lead to feelings of hopelessness and disengagement. Despite contributing the least to the climate and ecological crises, youth will be most affected by the impacts, and will carry the burden of the climate crisis throughout their lives. Researchers, educators and mental health professionals must therefore find ways to foster youth psychosocial wellbeing and resilience alongside ensuring that their voices are heard. To this end, it is vital that young people feel able to openly discuss climate change and associated issues alongside the distressing thoughts and feelings they engender. This can be supported by using various psychological approaches to develop effective interventions. Researchers and clinicians in child mental health could gain from drawing from research in positive psychology to develop such interventions. In this review and commentary, we will outline how eco-anxiety and child psychological wellbeing can be framed within a positive psychology framework, including the relevance of self-determined motivation. Insights from interventions based on positive psychology including exercises to foster hope, forgiveness and meaning making will also be discussed. We will highlight how such interventions can be adapted as powerful tools to foster child wellbeing and cope with their eco-anxiety.

Abstract Background Critically unwell babies in intensive care units may develop acute renal failure. Options for renal replacement therapy are limited by their small size and available technology. Objectives To determine the clinical efficacy, outcomes and safety profile of the NIDUS® (a novel infant haemodialysis device) for babies under 8 kg, compared with current renal replacement therapy. Design A clinical investigation using a non-blinded cluster stepped wedge design with paediatric intensive care units randomised to sequences. Setting Paediatric intensive care units in six UK hospitals. Participants Children under 8 kg who required renal replacement therapy for fluid overload or biochemical disturbance. Interventions Continuous renal replacement therapy was provided by the usual methods: peritoneal dialysis and continuous haemofiltration (during control periods) and by the NIDUS (during intervention periods), a novel device designed for babies with a smaller circuit and filter and volumetric control of ultrafiltration. Main outcome measures Primary outcome was precision of ultrafiltration compared with prescription; secondary outcomes included biochemical clearances, accuracy of reported ultrafiltration and mortality. Data sources Bedside study data collected by weighing bags of fluid entering and leaving the device were entered into the study database along with case descriptors. Some secondary outcome data was collected via the Paediatric Intensive Care Audit Network. Results Ninety-seven participants were recruited by study closure, 62 to control and 35 to intervention. The primary outcome was obtained from 62 control but only 21 intervention patients, largely because of technical difficulties using NIDUS. The analysis comparing the available primary outcomes showed that ultrafiltration with NIDUS was closer to that prescribed than with control: standard deviations controls 18.75, intervention 2.95 (ml/hour), adjusted ratio 0.13, 95% confidence interval (0.03 to 0.71); p = 0.018. The mean clearances for creatinine, urea and phosphate were lower on peritoneal dialysis than NIDUS, which were in turn lower than continuous veno-venous haemofiltration. The variability in the clearances was in the same order. Of the 62 control patients, 10 died (2/62 on peritoneal dialysis; 7/13 on continuous haemofiltration) before discharge from paediatric intensive care unit (16%), compared with 12 out of 35 (34%) in the NIDUS group: p = 0.04, 95% confidence interval for difference (0 to 36%). Harms No important adverse events occurred and the NIDUS has an acceptable safety profile compared with other renal replacement therapies in this critically ill population with multi-organ failure. Mortality was lowest for Peritoneal Dialysis, highest for continuous haemofiltration, with the NIDUS in-between. Only one serious adverse device event which was reported to the Medicines and Healthcare products Regulatory Agency. Conclusions NIDUS works effectively, delivering appropriate blood clearances and accurate, controllable fluid removal (ultrafiltration), indicating that it has an important place alongside other dialysis modalities for infant renal replacement therapy. Future work Findings from this study indicate some modifications are required to NIDUS to improve usability. Further studies on use of the NIDUS device in other populations of babies for example those with chronic renal failure, and long-term outcomes are required. Trial registration This trial is registered as ISRCTN 13787486. Funding This award was funded by the National Institute for Health and Care Research (NIHR) Efficacy and Mechanism Evaluation Programme (NIHR award ref: 14/23/26) and is published in full in Efficacy and Mechanism Evaluation; Vol. 11, No. 1. See the NIHR Funding and Awards website for further award information. Plain language summary Why do this study? Some children in intensive care are so poorly that their kidneys do not work well, and they need help, called dialysis, to get rid of fluid and chemicals from their blood. For babies, we currently use peritoneal dialysis, where fluid is cycled in and out of the tummy, or adapted machines designed for bigger children (continuous veno-venous haemofiltration). A new machine, the NIDUS® (Allmed, www.allmedgroup.com), was developed specifically for babies weighing under 8 kg with much smaller tubing. NIDUS worked well when studied in Newcastle but needed testing elsewhere. What was the question? How well does NIDUS work compared to other dialysis methods? What are the problems? What did we do? The study was done in six paediatric intensive care units who used their usual dialysis methods (=control) in the first part of the study and then later swapped to using the NIDUS (=intervention). What did we find? We recruited 97 participants, 62 to control (49 peritoneal dialysis, 13 continuous veno-venous haemofiltration) and 35 intervention (NIDUS). We found NIDUS provided much better control of fluid removal. The CVVH machines were more efficient at blood cleaning than NIDUS, which was better than peritoneal dialysis. What does this mean? We learnt a lot about babies needing kidney support in paediatric intensive care units and that all methods have advantages and disadvantages. We showed that NIDUS could be very useful for some participants because it cleans blood effectively and gives accurate, controllable fluid removal. We have gathered important information to help us improve NIDUS to make it easier to use and run. Many parents responded to our questionnaire and most told us they felt it was acceptable to be approached about taking part in research despite the circumstances. This is very important for future research studies. We are very grateful to families for their generosity in becoming involved in this study. Scientific summary Background Critically unwell babies in paediatric intensive care units (PICUs) may develop acute renal failure and require management with renal replacement therapy. Although mortality and morbidity vary and are related to the underlying diagnosis, survival of babies in paediatric intensive care is worse for those with fluid overload. Babies requiring renal replacement treatment present specific therapeutic challenges because of their small size and the current technology available. Difficulties with vascular access and blood flows, fluid balance, loss of circuits, filter clotting and hypotensive episodes at initiation are all described in the literature. The need for new solutions and improved technology is well recognised. Continuous veno-venous haemofiltration (CVVH) machines in use in the UK at the time of this study are not approved for use in babies weighing 80%) were similar. The median (IQR) age in controls 10.5 (7, 38) days was similar to that in the intervention group 11 (7, 61) days; the range of age of participants was between 1 and 477 days (approximately 15 months). The median (IQR) weights 3.2 (2.9, 3.9) and 3.7 (3.1, 5.6) kg were similar between control and intervention. Availability of primary outcome The primary outcome was available on all 62 control patients but only 21 of the 35 intervention patients. This was due to a range of reasons including difficulties in obtaining the information needed to compute the UF rate (accurate timing and weighing data) and technical difficulties using the NIDUS: full details are in the report. Precision of UF Analysis comparing the 62 control patients with the 21 intervention patients with a primary outcome showed that UF with the NIDUS was closer to that prescribed than with control: standard deviations (SDs) controls 18.75, intervention 2.95 (ml/hour), adjusted ratio 0.13, 95% confidence interval (0.03 to 0.71); p = 0.018. For the NIDUS and CVVH devices, an important measure was to compare the difference between the actual fluid removal measured and that reported by the device. This had a mean closer to zero for the NIDUS than CVVH (means −0.44 vs. 11.6 ml/hour, respectively), with less variation in NIDUS than CVVH (SDs 3.2 vs. 28.4 ml/hour). Biochemical clearances The initial intention was to compare clearance rate on NIDUS with the control group. However, for these variables combining PD and CVVH in this way proved to be misleading because NIDUS clearances rates were intermediate between those of PD and CVVH. The clearance for creatinine on PD was smaller and less variable (mean 0.08, SD 0.03 ml/min/kg) than on the NIDUS (mean 0.46, SD 0.30 ml/min/kg), which was in turn smaller and less variable than for CVVH (mean 1.20, SD 0.72 ml/min/kg). The pattern was repeated for urea: PD (0.12, 0.06), NIDUS (0.48, 0.30) and CVVH (1.15, 0.67), all in ml/min/kg, and also for phosphate: PD (0.07, 0.04), NIDUS (0.44, 0.27) and CVVH (1.16, 0.71), all in ml/min/kg. All pairwise treatment comparisons of means and of SDs gave p

Introduction Human papillomavirus (HPV) is the causative agent of nearly all cervical cancers. Despite the proven safety and efficacy of HPV vaccines in preventing HPV-related cancers, the global vaccine coverage rate is estimated to only be 15%. HPV vaccine coverage rates are more actively tracked and reported for adolescents 17 years and younger but there is still a critical window of opportunity to intervene and promote HPV vaccination among young adults aged 18–26 years who are still eligible to be vaccinated. This protocol for a qualitative evidence synthesis aims to review perspectives of HPV vaccination among young adults (18–26 years) and identify facilitators and barriers that influence HPV vaccination uptake and decision-making.Methods and analysis Seven databases will be searched from 1 January 2006 to the date of final search. For inclusion, studies must report HPV vaccination perspectives of young adults aged 18–26 years and use qualitative study methods or analysis techniques. Studies will be screened in a two-stage process guided by the eligibility criteria. Final included studies will be evaluated for methodological strengths and limitations using the Critical Appraisal Skills Programme quality assessment tool for qualitative studies. After data extraction, framework analysis will be used to analyse the data applying the socioecological model. Finally, the Grading of Recommendations Assessment, Development and Evaluation - Confidence in the Evidence from Reviews of Qualitative research will be applied to evaluate the confidence in synthesised qualitative findings. The methodology of this review follows the Cochrane Handbook guidelines on qualitative evidence syntheses.Ethics and dissemination Formal ethical approval is not required for this study. Findings will be disseminated through peer-reviewed publications, conference presentations and professional networks.PROSPERO registration number CRD42023417052.

Past research suggests that internet use can increase the risks of internalizing symptoms in adolescents. However, bidirectional relationships between adolescent internet use and anxiety symptoms have received very little attention. Furthermore, few studies have examined these links according to sex. The present study attempts to fill this gap by investigating longitudinal associations between Canadian boys’ and girls’ internet use and symptoms of generalized anxiety and social anxiety using data from the Quebec longitudinal Study of Child Development. A sample of 1324 adolescents (698 girls, 626 boys) self-reported the number of hours per week they spent on the internet and their symptoms of generalized and social anxiety at ages 15 and 17. We estimated two cross-lagged panel models with social or generalized anxiety symptoms and internet use at age 15 predicting those same variables at age 17. Sex was used as a grouping variable and socioeconomic status was included as a control variable. Internet use at 15 predicted generalized and social anxiety symptoms at age 17 in girls, but not boys. Social and generalized anxiety symptoms at age 15 did not predict internet use at age 17 for both boys and girls. These results suggest that internet use can be a significant risk factor for the development of anxiety symptoms in adolescent girls. Girls may be more vulnerable to the negative effects of internet use due to increased sensitivity to social comparisons. Thus, helping girls develop healthier internet use habits should be a target for promoting their mental health.

The policy orientations of advanced neoliberal democracies situate young people as rational actors who are responsible for their own career outcomes. While career scholars have been critical of how this routinely ignores the unequal effects of structural constraints on personal agency, they have long suggested that young people should have access to the best available ‘roadmaps’ and advice to navigate the uncertainties baked into the contemporary economic landscape. Complementing the significant attention that is given to the (potentially emancipatory) experience of formal careers guidance, we present findings from a multi-method study. We explore young Australians’ (aged 15–24) navigation of careers information through a nationally representative survey (n = 1103), focus groups with 90 participants and an analysis of 15,227 social media comments. We suggest that the variety of formal and informal sources pursued and accessed by young people forms a relational ‘ecology’. This relationality is twofold. First, information is often sequential, and engagements with one source can inform the experience or pursuit of another. Second, navigation of the ecology is marked by a high level of intersubjectivity through interpersonal support networks including peers, family and formal service provision. These insights trouble a widespread, but perhaps simplistic, reading of young people having largely internalised a neoliberal sensibility of ‘entrepreneurial selfhood’ in their active pursuit of a range of career advice. Throughout our analysis, we attend to the ways that engagement in the career information ecology is shaped by social inequalities, further underscoring challenges facing careers guidance and social justice goals.

Background Family involvement has been identified as a key aspect of clinical practice that may help to prevent suicide. Aims To investigate how families can be effectively involved in supporting a patient accessing crisis mental health services. Method A multi-site ethnographic investigation was undertaken with two crisis resolution home treatment teams in England. Data included 27 observations of clinical practice and interviews with 6 patients, 4 family members, and 13 healthcare professionals. Data were analysed using framework analysis. Results Three overarching themes described how families and carers are involved in mental healthcare. Families played a key role in keeping patients safe by reducing access to means of self-harm. They also provided useful contextual information to healthcare professionals delivering the service. However, delivering a home-based service can be challenging in the absence of a supportive family environment or because of practical problems such as the lack of suitable private spaces within the home. At an organisational level, service design and delivery can be adjusted to promote family involvement. Conclusions Findings from this study indicate that better communication and dissemination of safety and care plans, shared learning, signposting to carer groups and support for carers may facilitate better family involvement. Organisationally, offering flexible appointment times and alternative spaces for appointments may help improve services for patients.

Objective: To identify the key contributors to postoperative mortality in patients undergoing orthotopic heart transplantation (OHT) for late Fontan failure. Methods: This retrospective review of failing Fontan patients who underwent OHT in our tertiary care center between 2007 and 2019 included adult patients with congenital heart disease and single ventricle physiology who were palliated with a Fontan circulation for >1 year. We excluded patients undergoing combined heart-liver transplantation. Results: The study cohort comprised 31 patients, including 18 males (58.1%), with a mean weight of 58.4 kg, median age at Fontan of 6.9 years (interquartile range [IQR], 2-38 years), and a median age at OHT of 27.1 years (IQR, 16.7-53.3). Almost all (93.5%) of the patients were in New York Heart Association class III-IV, and the majority (74.2%) were in Interagency Registry for Mechanically Assisted Circulatory Support class 3. Overall survival at 30 days, 1 year, and 5 years after OHT was 81%, 71%, and 67%, respectively. Major intraoperative bleeding was associated with increased mortality after OHT (odds ratio, 30; 95% confidence interval, 2.8-322; P = .002). Neither preoperative systemic ventricular function nor the development of primary graft dysfunction (PGD) was significantly associated with postoperative death. Nevertheless, PGD determined significant morbidity of this population. Conclusions: In our cohort, major intraoperative bleeding was the key factor associated with mortality after OHT for late Fontan failure. Novel strategies for the prevention and management of postoperative bleeding will improve outcomes in this group of patients.

Background: Current evidence suggests that autistic individuals are at high risk for becoming and remaining in a cycle of homelessness. Key risk factors for homelessness disproportionately affect autistic people; however, we have limited understanding of how to best support autistic individuals accessing services. This gap in the evidence base is particularly acute for autistic women. Objective: As a first step to address this gap, we aimed to (1) map gaps in knowledge and practice; (2) identify priority areas for research and (3) develop recommendations for how to implement novel research and practice in this area. Methods: We conducted a collaborative workshop with an interdisciplinary group of 26 stakeholders to address our aims. Stakeholders included autistic women with experience of homelessness, researchers, health professionals, NGO representatives, and service providers. Results and recommendations: Two research priority areas were identified to map the prevalence and demographics of autistic women experiencing homelessness, and to delineate risk and protective factors for homelessness. Priority areas for improving provision of support included staff training to improve communication, awareness of autism and building trust with service providers, and recommendations for practical provision of support by services. Conclusions: Future research is critical to increase our knowledge of the pathways leading to homelessness for autistic women, and barriers to engaging with homelessness and social services. We need to use this knowledge to develop new ways of delivering targeted and inclusive support for autistic women, which could prevent or shorten periods of homelessness.

BackgroundIn most cases, the abstracts of articles in the medical domain are publicly available. Although these are accessible by everyone, they are hard to comprehend for a wider audience due to the complex medical vocabulary. Thus, simplifying these complex abstracts is essential to make medical research accessible to the general public. ObjectiveThis study aims to develop a deep learning–based text simplification (TS) approach that converts complex medical text into a simpler version while maintaining the quality of the generated text. MethodsA TS approach using reinforcement learning and transformer–based language models was developed. Relevance reward, Flesch-Kincaid reward, and lexical simplicity reward were optimized to help simplify jargon-dense complex medical paragraphs to their simpler versions while retaining the quality of the text. The model was trained using 3568 complex-simple medical paragraphs and evaluated on 480 paragraphs via the help of automated metrics and human annotation. ResultsThe proposed method outperformed previous baselines on Flesch-Kincaid scores (11.84) and achieved comparable performance with other baselines when measured using ROUGE-1 (0.39), ROUGE-2 (0.11), and SARI scores (0.40). Manual evaluation showed that percentage agreement between human annotators was more than 70% when factors such as fluency, coherence, and adequacy were considered. ConclusionsA unique medical TS approach is successfully developed that leverages reinforcement learning and accurately simplifies complex medical paragraphs, thereby increasing their readability. The proposed TS approach can be applied to automatically generate simplified text for complex medical text data, which would enhance the accessibility of biomedical research to a wider audience.

Abstract We previously shared results suggesting that the academic motivation of a sample of French‐Canadian adolescents remained stable from few weeks before the first wave to the second wave of the COVID‐19 pandemic. We here examine if this pattern persisted using data collected at a third time point.

A 53-year-old lady is known to have Von Hippel-Lindau syndrome with a long history of previous renal cell carcinomas (RCCs) in both kidneys. She was treated by partial nephrectomy for a right peripheral RCC and subsequently image guided radiofrequency ablation (RFA) of a left central RCC. She developed another de novo RCC adjacent to the right pelvic-ureteric junction (PUJ) 4 years after the initial RFA. Due to the close proximity to the PUJ and visibility of an ice ball with cryoablation (CRYO), the consensus from the MDT was that CRYO would be safer than RFA and she subsequently underwent percutaneous image guided CRYO to treat the small de novo RCC. Unfortunately, during the 1-month imaging follow up, she developed moderate hydronephrosis and a ureteric stricture needing long-term ureteric stent management. This case highlights the risk of ureteric injury caused by the thermal effect of the ice ball during image guided renal CRYO. Therefore, it is vital that all interventional radiologists adopt various manoeuvres to protect the ureter from the ice ball during CRYO in order to avoid the development of latent ureteric stricture.

Zika virus (ZIKV) is a mosquito-borne flavivirus with maternal infection associated with preterm birth, congenital malformations, and fetal death, and adult infection associated with Guillain-Barré syndrome. Recent widespread endemic transmission of ZIKV and the potential for future outbreaks necessitate the development of an effective vaccine. We developed a ZIKV vaccine candidate based on virus-like-particles (VLPs) generated following transfection of mammalian HEK293T cells using a plasmid encoding the pre-membrane/membrane (prM/M) and envelope (E) structural protein genes. VLPs were collected from cell culture supernatant and purified by column chromatography with yields of approximately 1-2mg/L. To promote increased particle yields, a single amino acid change of phenylalanine to alanine was made in the E fusion loop at position 108 (F108A) of the lead VLP vaccine candidate. This mutation resulted in a modest 2-fold increase in F108A VLP production with no detectable prM processing by furin to a mature particle, in contrast to the lead candidate (parent). To evaluate immunogenicity and efficacy, AG129 mice were immunized with a dose titration of either the immature F108A or lead VLP (each alum adjuvanted). The resulting VLP-specific binding antibody (Ab) levels were comparable. However, geometric mean neutralizing Ab (nAb) titers using a recombinant ZIKV reporter were significantly lower with F108A immunization compared to lead. After virus challenge, all lead VLP-immunized groups showed a significant 3- to 4-Log10 reduction in mean ZIKV RNAemia levels compared with control mice immunized only with alum, but the RNAemia reduction of 0.5 Log10 for F108A groups was statistically similar to the control. Successful viral control by the lead VLP candidate following challenge supports further vaccine development for this candidate. Notably, nAb titer levels in the lead, but not F108A, VLP-immunized mice inversely correlated with RNAemia. Further evaluation of sera by an in vitro Ab-dependent enhancement assay demonstrated that the F108A VLP-induced immune sera had a significantly higher capacity to promote ZIKV infection in FcγR-expressing cells. These data indicate that a single amino acid change in the fusion loop resulted in increased VLP yields but that the immature F108A particles were significantly diminished in their capacity to induce nAbs and provide protection against ZIKV challenge.

Over the last two decades, several studies have overlooked at-school belonging and engagement, two dimensions that are associated with several positive outcomes. However, the relative influence that contexts and interventions may have on these components has received much less attention. In this study, school belonging and engagement were examined as a function of the implementation and application of classroom rules. The study took place in two Moroccan schools, and participants were 238 students from 9th grade (101 boys, 137 girls; Mage = 15.1) living in the cities of Casablanca and Témara. They all completed a questionnaire that allowed to measure their belonging and engagement in conjunction with the manner in which rules are implemented and applied. Correlational and structural equation modeling methods were used to analyze the aforementioned relationships. Results showed that implementation of classroom rules had a positive effect on school belonging, which, in turn, had a positive effect on school engagement. These results indicated the need to conduct further empirical research to measure the contribution of classroom management practices on school belonging.

This study investigated the effects of online schooling and screen-based activities on Canadian children’s COVID-19-related trauma and generalized anxiety symptoms and how parents’ coping strategies influenced these associations. The participants were 121 Canadian children aged from 7 to 12. Parents were asked to report on their children’s school attendance, screen-based activities, and trauma and generalized anxiety symptoms, as well as their own coping strategies during the COVID-19 pandemic. Online schooling was associated with less trauma and generalized anxiety symptoms in children than school non-attendance. Screen-based activities were not directly associated with children’s trauma and anxiety symptoms, but the way parents coped with pandemic stressors moderated these associations. Parents’ active and adaptive coping strategies mitigated the effects of school non-attendance and increased screen-based activity use on children’s COVID-19-related symptoms. The findings not only highlight the detrimental effects of complete school closures, but they also underscore the importance of better equipping parents to cope with pandemic stressors. The findings also suggest that virtual school attendance might have similar benefits to in-person attendance, as it appears to protect against adverse mental health outcomes.

Recent conjectural morphological (‘word family’) approaches to early Chinese assign the aspirated causative verbs of the Mǐn group to Jerry Norman’s comparatively reconstructed Proto-Mǐn voiced aspirated *Dʰ-, proposing on this basis that *Dʰ- reflects prefixation of Old Chinese provenance. In this article, I argue that comparative phonological work on Mǐn has never suggested *Dʰ- for these items. In this case as elsewhere, morphological models can be of use but require grounding in comparative results.

Due to the COVID-19 pandemic, adolescents have experienced limitations in their everyday activities. Consequently, their mental health has become an area of concern. However, there has been much less of a focus on the factors and mechanisms contributing to how they have approached their various academic activities during the pandemic. The current study fills this gap by investigating associations between adolescents’ competence beliefs and perception of teachers’ emotional support and their achievement goals (mastery, performance, and work avoidance) at the onset of the second wave of this pandemic in Canada. Participants were 90 Canadian high school adolescents in grades 9 and 10 and they were surveyed in November of 2020. Data were analyzed using multiple regression and mediation analyses. Among the most salient results, competence beliefs were found to predict achievement goals, above and beyond teachers’ emotional support, and these beliefs were significantly and positively associated with mastery and performance orientation, and marginally and negatively associated with work avoidance orientation. Results also showed that competence beliefs mediated the association between teachers’ emotional support and the mastery goal orientation. These findings are discussed in light of relevant pre-pandemic evidence about the role of competence beliefs and teachers’ emotional support on achievement goal orientations.

A 69-year-old lady with 2 renal cell carcinomas, one sited at the upper pole of her solitary right kidney, underwent percutaneous image-guided cryoablation and developed urinothorax as a complication. This was diagnosed from pleural fluid analysis and radiology imaging with computed tomography (CT). Management included image-guided chest drain and retrograde ureteric stent insertion to divert the urine from entering the pleural cavity. CT images demonstrated a fistula between the site of renal puncture and the pleural cavity, indicating that the cryoprobes traversed the diaphragm during the procedure. This case highlights urinothorax as an unusual complication of cryoablation of renal cell carcinoma. Prompt diagnosis by interventional radiologists is crucial to avert from this potentially life-threatening complication.

Introduction: Isolated local recurrence of prostate cancer following primary radiotherapy or brachytherapy may be treated with focal salvage high dose rate brachytherapy, although there remains an absence of high quality evidence to support this approach. Methods: Men with prostate cancer treated consecutively between 2015 and 2018 using 19 Gy in a single fraction high dose rate brachytherapy (HDR) for locally recurrent prostate cancer were identified from an institutional database. Univariable analysis was performed to evaluate the relationship between patient, disease and treatment factors with biochemical progression free survival (bPFS). Results: 43 patients were eligible for evaluation. Median follow up duration was 26 months (range 1–60). Median bPFS was 35 months (95% confidence interval 25.6–44.4). Kaplan-Meier estimates for bPFS at 1, 2 and 3 years post salvage were 95.2%, 70.6% and 41.8% respectively. On univariable Cox regression analysis, only nadir PSA was significantly associated with bPFS although the majority of patients were also treated with androgen deprivation therapy. Only one late grade 3 genitourinary toxicity was observed. Conclusion: Focal salvage HDR brachytherapy may provide good biochemical control with a low risk of severe toxicity. Further evaluation within clinical trials are needed to establish its role in the management of locally recurrent prostate cancer.

Tisagenlecleucel is a CD19-specific chimeric antigen receptor (CAR)-T cell therapy approved for patients aged ≤25 years with relapsed or refractory B cell precursor acute lymphoblastic leukemia (B-ALL) and adults with relapsed or refractory diffuse large B cell lymphoma (DLBCL). The initial tisagenlecleucel manufacturing process technology was developed at an academic center and was subsequently transferred, optimized, validated, and scaled out to supply large global trials before commercialization. Tisagenlecleucel manufactured in two centralized facilities has been successfully used in global multicenter trials for B-ALL and DLBCL (>50 clinical centers in 12 countries). In this paper, we describe some of the continuous process improvements made to tisagenlecleucel manufacturing over time to meet global demand while maintaining and improving product quality. During early tisagenlecleucel clinical trials, process enhancements were made to address logistical challenges related to manufacturing for multicenter trials and to accommodate the variability observed in patient starting cellular material. These enhancements resulted in improvements in manufacturing capacity, process robustness, manufacturing success rates, and product quality, and reductions in throughput time. In summary, through continuous evaluation and improvements based on experience during global trials, a consistent and robust commercial manufacturing process for tisagenlecleucel has been developed, leading to improvements in manufacturing success when compared to the initial processes. Keywords: chimeric antigen receptor-T cell therapy, commercial manufacturing, immunotherapy, manufacturing process optimization, global manufacturing

Introduction: There is evidence to support use of external beam radiotherapy (EBRT) in combination with both low dose rate brachytherapy (LDR–EBRT) and high dose rate brachytherapy (HDR–EBRT) to treat intermediate and high risk prostate cancer. Methods: Men with intermediate and high risk prostate cancer treated using LDR–EBRT (treated between 1996 and 2007) and HDR–EBRT (treated between 2007 and 2012) were identified from an institutional database. Multivariable analysis was performed to evaluate the relationship between patient, disease and treatment factors with biochemical progression free survival (bPFS). Results: 116 men were treated with LDR-EBRT and 171 were treated with HDR–EBRT. At 5 years, bPFS was estimated to be 90.5% for the LDR–EBRT cohort and 77.6% for the HDR–EBRT cohort. On multivariable analysis, patients treated with HDR–EBRT were more than twice as likely to experience biochemical progression compared with LDR–EBRT (HR 2.33, 95% CI 1.12–4.07). Patients with Gleason ≥8 disease were more than five times more likely to experience biochemical progression compared with Gleason 6 disease (HR 5.47, 95% CI 1.26–23.64). Cumulative incidence of ≥grade 3 genitourinary and gastrointestinal toxicities for the LDR–EBRT and HDR–EBRT cohorts were 8% versus 4% and 5% versus 1% respectively, although these differences did not reach statistical significance. Conclusion: LDR–EBRT may provide more effective PSA control at 5 years compared with HDR–EBRT. Direct comparison of these treatments through randomised trials are recommended to investigate this hypothesis further. Keywords: Prostate cancer, Low dose rate brachytherapy, High dose rate brachytherapy, External beam radiotherapy

Macrophages are key cells in the innate immune system and play a role in a variety of diseases. However, macrophages are terminally differentiated and difficult to manipulate genetically via transfection or through CRISPR-Cas9 gene editing. To overcome this limitation, we provide a simplified protocol for the generation of mouse embryonic stem cells-derived macrophages (ESDM). Thus, genetic manipulation can be performed using embryonic stem cells, selecting for the desired changes, and finally producing macrophages to study the effects of the previous genetic manipulation. These studies can contribute to many areas of research, including atherosclerosis and inflammation. Production of ESDM has been previously achieved using embryoid body (EB) intermediates. Here, we optimized the EB method using a simplified medium, reducing the number of recombinant proteins and medium recipes required. Our EB-based differentiation protocol consists of three stages: 1) floating EB formation; 2) adherence of EBs and release of floating macrophage progenitors; and, 3) terminal differentiation of harvested macrophage progenitors. The advantages of this protocol include achieving independent floating EBs in stage 1 by using a rocker within the tissue culture incubator, as well as the exclusion of small EBs and cell clusters when harvesting macrophage progenitors via cell filtration.

Icequakes at or near the bed of a glacier have the potential to allow us to investigate the interaction of ice with the underlying till or bedrock. Understanding this interaction is important for studying basal sliding of glaciers and ice streams, a critical process in ice dynamics models used to constrain future sea-level rise projections. However, seismic observations on glaciers can be dominated by seismic energy from surface crevassing. We present a method of automatically detecting basal icequakes and discriminating them from surface crevassing, comparing this method to a commonly used spectrum-based method of detecting icequakes. We use data from Skeidararjökull, an outlet glacier of the Vatnajökull Ice Cap, South-East Iceland, to demonstrate that our method outperforms the commonly used spectrum-based method. Our method detects a higher number of basal icequakes, has a lower rate of incorrectly identifying crevassing as basal icequakes and detects an additional, spatially independent basal icequake cluster. We also show independently that the icequakes do not originate from near the glacier surface. We conclude that the method described here is more effective than currently implemented methods for detecting and discriminating basal icequakes from surface crevassing.

BackgroundZika virus (ZIKV), a mosquito-borne flavivirus, is a re-emerging virus that constitutes a public health threat due to its recent global spread, recurrent outbreaks, and infections that are associated with neurological abnormalities in developing fetuses and Guillain-Barré syndrome in adults. To date, there are no approved vaccines against ZIKV infection. Various preclinical and clinical development programs are currently ongoing in an effort to bring forward a vaccine for ZIKV.Methodology/principle findingsWe have developed a ZIKV vaccine candidate based on Virus-Like-Particles (VLPs) produced in HEK293 mammalian cells using the prM (a precursor to M protein) and envelope (E) structural protein genes from ZIKV. Transient transfection of cells via plasmid and electroporation produced VLPs which were subsequently purified by column chromatography yielding approximately 2mg/L. Initially, immunogenicity and efficacy were evaluated in AG129 mice using a dose titration of VLP with and without Alhydrogel 2% (alum) adjuvant. We found that VLP with and without alum elicited ZIKV-specific serum neutralizing antibodies (nAbs) and that titers correlated with protection. A follow-up immunogenicity and efficacy study in rhesus macaques was performed using VLP formulated with alum. Multiple neutralization assay methods were performed on immune sera including a plaque reduction neutralization test, a microneutralization assay, and a Zika virus Renilla luciferase neutralization assay. All of these assays indicate that following immunization, VLP induces high titer nAbs which correlate with protection against ZIKV challenge.Conclusions/significanceThese studies confirm that ZIKV VLPs could be efficiently generated and purified. Upon VLP immunization, in both mice and NHPs, nAb was induced that correlate with protection against ZIKV challenge. These studies support translational efforts in developing a ZIKV VLP vaccine for evaluation in human clinical trials.

Adverse health outcomes and obesity are especially high among children with sleep deficiencies. Such health consequences may differentially affect children 2–5 years of age, during which time children undergo drastic shifts in sleep patterns and neurological development. To date, little epidemiologic research has examined the link between sleep and obesity-related health behaviors among this age group. We investigated the relationship between sleep and eating/physical activity behaviors among children aged 2–5 years old. In fall 2018, parents and teachers of 1,169 children attending 34 Early Childcare Education (ECE) centers in Georgia completed surveys on sleep patterns and obesity-related health and eating behaviors. In this analysis, sleep was not associated with various child eating behaviors either at home or in the classroom, however, shorter sleep duration was found to be associated with lower physical activity during the school day (p

Background There remains a significant need to eliminate the risk of recurrence of resected cancers. Cancer vaccines are well tolerated and activate tumor-specific immune effectors and lead to long-term survival in some patients. We hypothesized that vaccination with alphaviral replicon particles encoding tumor associated antigens would generate clinically significant antitumor immunity to enable prolonged overall survival (OS) in patients with both metastatic and resected cancer.Methods OS was monitored for patients with stage IV cancer treated in a phase I study of virus-like replicon particle (VRP)-carcinoembryonic antigen (CEA), an alphaviral replicon particle encoding a modified CEA. An expansion cohort of patients (n=12) with resected stage III colorectal cancer who had completed their standard postoperative adjuvant chemotherapy was administered VRP-CEA every 3 weeks for a total of 4 immunizations. OS and relapse-free survival (RFS) were determined, as well as preimmunization and postimmunization cellular and humoral immunity.Results Among the patients with stage IV cancer, median follow-up was 10.9 years and 5-year survival was 17%, (95% CI 6% to 33%). Among the patients with stage III cancer, the 5-year RFS was 75%, (95%CI 40% to 91%); no deaths were observed. At a median follow-up of 5.8 years (range: 3.9–7.0 years) all patients were still alive. All patients demonstrated CEA-specific humoral immunity. Patients with stage III cancer had an increase in CD8 +TEM (in 10/12) and decrease in FOXP3 +Tregs (in 10/12) following vaccination. Further, CEA-specific, IFNγ-producing CD8+granzyme B+TCM cells were increased.Conclusions VRP-CEA induces antigen-specific effector T cells while decreasing Tregs, suggesting favorable immune modulation. Long-term survivors were identified in both cohorts, suggesting the OS may be prolonged.

El artículo presenta los diseños y resultados de dos controladores tipo SISO de posición para un levitador magnético convencional, con la motivación de comparar las dinámicas de los sistemas posterior a la implementación de ambos métodos de control. Para el diseño de los controladores se obtuvo el modelo matemático aproximado de un levitador magnético a partir de características estáticas, de fuerza electromagnética e inductancia. Una vez establecido el modelo matemático se planteó una ley de control lineal a partir de una realimentación de estados con integrador, estimando la velocidad y corriente. Para el diseño del control no lineal se propuso una ley de control de tipo linealización entrada salida. Por último, se comparó la dinámica del sistema con los controladores implementados y se realizaron modificaciones de masa para verificar la robustez de los controladores, además de perturbaciones tales como fuerzas externas y ruido de tipo eléctrico. Finalmente, fue posible concluir que el controlador lineal tiene una respuesta satisfactoria en términos de error de estado estacionario, añadiendo un menor costo de procesamiento en comparación al controlador no lineal.