Two-drug regimens for the treatment of HIV in Africa.

Two-drug regimens for the treatment of HIV are increasingly available. The oral regimen of dolutegravir plus lamivudine is recommended as a preferred option in multiple national guidelines but is not currently included in WHO HIV treatment guidelines nor widely used in Africa. Long-acting injectable cabotegravir and rilpivirine is being rolled out in the USA, Europe, and Australia but its use in sub-Saharan Africa is currently restricted to clinical trials. Given the increasing life expectancy, rising prevalence of non-communicable diseases, and resulting polypharmacy among people living with HIV, there are potential advantages to the use of two-drug regimens, particularly in African women, adolescents, and older adults. This Viewpoint reviews existing evidence and highlights the risks, benefits, and key knowledge gaps for the use of two-drug regimens in settings using the public health approach in Africa. We suggest that a two-drug regimen of dolutegravir and lamivudine can be safely used as a switch option for virologically suppressed individuals in settings using the public health approach once chronic hepatitis B has been excluded. Individuals with HIV who are switched to two-drug regimens should receive a full course of hepatitis B vaccinations. More efficacy data is needed to support dolutegravir plus lamivudine combination in the test and treat approach, and long-acting cabotegravir and rilpivirine in the public health system in sub-Saharan Africa.

A Multimodal Exertional Test for concussion: a pilot study in healthy athletes.

Introduction: Exertional tests have become a promising tool to assist clinicians in the management of concussions, however require expensive equipment, extensive spaces, and specialized clinician expertise. As such, we developed a test with minimal resource requirements encompassing key elements of sport and physical activity. The purpose of this study was to pilot test the Multimodal Exertional Test (MET) protocol in a sample of healthy interuniversity athletes. Methods: The MET comprises four stages, each featuring three distinct tasks. The test begins with engaging in squats, alternating reverse lunges, and hip hinges (Stage 1). The next stage progressively evolves into executing these tasks within specified time limits (Stage 2). Following this, the test advances to a stage that incorporates cognitive tasks (Stage 3), and the final stage demands greater levels of physical exertion, cognition, and multi-directional movements (Stage 4). Heart rate (HR) was obtained during each stage of the MET and participants' symptom severity scores were recorded following each task. Results: Fourteen healthy interuniversity athletes (n = 8 female, n = 6 male) participated in the study. HR was obtained for 10 of the 14 athletes (females: n = 6, males: n = 4). Increases in average and maximum HR were identified between pre-MET and Stage 1, and between Stages 3 and 4. Consistent with the tasks in each stage, there were no increases in average and maximum HR observed between MET Stages 1 to 3. Female athletes exhibited higher average and maximum HRs compared to male athletes during all four stages. All 14 athletes reported minimal changes in symptom severity following each task. Conclusion: Among healthy athletes, the MET elicits an increase in average and maximum HR throughout the protocol without symptom provocation. Female athletes exhibit higher HRs during all four stages in comparison to male athletes.

Cellular and Molecular Immunity to Influenza Viruses and Vaccines.

Immune responses to influenza (flu) antigens reflect memory of prior infections or vaccinations, which might influence immunity to new flu antigens. Memory of past antigens has been termed "original antigenic sin" or, more recently, "immune imprinting" and "seniority". We have researched a comparison between the immune response to live flu infections and inactivated flu vaccinations. A brief history of antibody generation theories is presented, culminating in new findings about the immune-network theory and suggesting that a network of clones exists between anti-idiotypic antibodies and T cell receptors. Findings regarding the 2009 pandemic flu strain and immune responses to it are presented, including memory B cells and conserved regions within the hemagglutinin protein. The importance of CD4+ memory T cells and cytotoxic CD8+ T cells responding to both infections and vaccinations are discussed and compared. Innate immune cells, like natural killer (NK) cells and macrophages, are discussed regarding their roles in adaptive immune responses. Antigen presentation via macroautophagy processes is described. New vaccines in development are mentioned along with the results of some clinical trials. The manuscript concludes with how repeated vaccinations are impacting the immune system and a sketch of what might be behind the imprinting phenomenon, including future research directions.

Prevalence of adolescent mental disorders in Kenya, Indonesia, and Viet Nam measured by the National Adolescent Mental Health Surveys (NAMHS): a multi-national cross-sectional study.

BACKGROUND: Mental disorders are the leading global cause of health burden among adolescents. However, prevalence data for mental disorders among adolescents in low-income and middle-income countries are scarce with often limited generalisability. This study aimed to generate nationally representative prevalence estimates for mental disorders in adolescents in Kenya, Indonesia, and Viet Nam. METHODS: As part of the National Adolescent Mental Health Surveys (NAMHS), a multinational cross-sectional study, nationally representative household surveys were conducted in Kenya, Indonesia, and Viet Nam between March and December, 2021. Adolescents aged 10-17 years and their primary caregiver were interviewed from households selected randomly according to sampling frames specifically designed to elicit nationally representative results. Six mental disorders (social phobia, generalised anxiety disorder, major depressive disorder, post-traumatic stress disorder, conduct disorder, and attention-deficit hyperactivity disorder) were assessed with the Diagnostic Interview Schedule for Children, Version 5. Suicidal behaviours and self-harm in the past 12 months were also assessed. Prevalence in the past 12 months and past 4 weeks was calculated for each mental disorder and collectively for any mental disorder (ie, of the six mental disorders assessed). Prevalence of suicidal behaviours (ie, ideation, planning, and attempt) and self-harm in the past 12 months was calculated, along with adjusted odds ratios (aORs) to show the association with prevalence of any mental disorder in the past 12 months. Inverse probability weighting was applied to generate national estimates with corresponding 95% CIs. FINDINGS: Final samples consisted of 5155 households (ie, adolescent and primary caregiver pairs) from Kenya, 5664 households from Indonesia, and 5996 households from Viet Nam. In Kenya, 2416 (46·9%) adolescents were male and 2739 (53·1%) were female; in Indonesia, 2803 (49·5%) adolescents were male and 2861 (50·5%) were female; and in Viet Nam, 3151 (52·5%) were male and 2845 (47·4%) were female. Prevalence of any mental disorder in the past 12 months was 12·1% (95% CI 10·9-13·5) in Kenya, 5·5% (4·3-6·9) in Indonesia, and 3·3% (2·7-4·1) in Viet Nam. Prevalence in the past 4 weeks was 9·4% (8·3-10·6) in Kenya, 4·4% (3·4-5·6) in Indonesia, and 2·7% (2·2-3·3) in Viet Nam. The prevalence of suicidal behaviours in the past 12 months was low in all three countries, with suicide ideation ranging from 1·4% in Indonesia (1·0-2·0) and Viet Nam (1·0-1·9) to 4·6% (3·9-5·3) in Kenya, suicide planning ranging from 0·4% in Indonesia (0·3-0·8) and Viet Nam (0·2-0·6) to 2·4% (1·9-2·9) in Kenya, and suicide attempts ranging from 0·2% in Indonesia (0·1-0·4) and Viet Nam (0·1-0·3) to 1·0% (0·7-1·4) in Kenya. The prevalence of self-harm in the past 12 months was also low in all three countries, ranging from 0·9% (0·6-1·3) in Indonesia to 1·2% (0·9-1·7) in Kenya. However, the prevalence of suicidal behaviours and self-harm in the past 12 months was significantly higher among those with any mental disorder in the past 12 months than those without (eg, aORs for suicidal ideation ranged from 7·1 [3·1-15·9] in Indonesia to 14·7 [7·5-28·6] in Viet Nam). INTERPRETATION: NAMHS provides the first national adolescent mental disorders prevalence estimates for Kenya, Indonesia, and Viet Nam. These data can inform mental health and broader health policies in low-income and middle-income countries. FUNDING: The University of Queensland in America (TUQIA) through support from Pivotal Ventures, a Melinda French Gates company.

The Prevalence and Patterns of Maltreatment, Childhood Adversity, and Mental Health Disorders in an Australian Out-Of-Home Care Sample.

This study aimed to explore key characteristics of the out-of-home care subgroup of a nationally representative Australian sample. To ensure that mental health services are appropriately targeted, it is critical that we understand the differential impacts of childhood experiences for this cohort. Using the Australian Child Maltreatment Study (N = 8503), we explored patterns of childhood maltreatment and adversity of participants who reported ever being placed in out-of-home care, such as foster care or kinship care. In addition, the prevalence of current and lifetime diagnosis of four mental health disorders were explored. Results showed that the care experienced subgroup reported more types of maltreatment and adverse experiences than the control group. They were also more likely to meet diagnostic threshold for post-traumatic stress disorder, generalised anxiety disorder and major depressive disorder than the control group. These findings can be used to guide mental health practitioners to target interventions more effectively within the out-of-home care cohort.

Extending the new era of genomic testing into pregnancy management: A proposed model for Australian prenatal services.

BACKGROUND: Trio exome sequencing can be used to investigate congenital abnormalities identified on pregnancy ultrasound, but its use in an Australian context has not been assessed. AIMS: Assess clinical outcomes and changes in management after expedited genomic testing in the prenatal period to guide the development of a model for widespread implementation. MATERIALS AND METHODS: Forty-three prospective referrals for whole exome sequencing, including 40 trios (parents and pregnancy), two singletons and one duo were assessed in a tertiary hospital setting with access to a state-wide pathology laboratory. Diagnostic yield, turn-around time (TAT), gestational age at reporting, pregnancy outcome, change in management and future pregnancy status were assessed for each family. RESULTS: A clinically significant genomic diagnosis was made in 15/43 pregnancies (35%), with an average TAT of 12 days. Gestational age at time of report ranged from 16 + 5 to 31 + 6 weeks (median 21 + 3 weeks). Molecular diagnoses included neuromuscular and skeletal disorders, RASopathies and a range of other rare Mendelian disorders. The majority of families actively used the results in pregnancy decision making as well as in management of future pregnancies. CONCLUSIONS: Rapid second trimester prenatal genomic testing can be successfully delivered to investigate structural abnormalities in pregnancy, providing crucial guidance for current and future pregnancy management. The time-sensitive nature of this testing requires close laboratory and clinical collaboration to ensure appropriate referral and result communication. We found the establishment of a prenatal coordinator role and dedicated reporting team to be important facilitators. We propose this as a model for genomic testing in other prenatal services.

The Prevalence of Peer Sexual Harassment During Childhood in Australia.

Sexual harassment inflicted by adolescents on their peers is a major public health issue, but its prevalence across childhood is not known. We provide the first nationally representative data on the prevalence of peer sexual harassment across childhood, using cross-sectional data from the Australian Child Maltreatment Study (ACMS). The ACMS surveyed 8,503 people aged 16 and over about their experiences of child maltreatment and associated health outcomes. The prevalence of peer sexual harassment was assessed using the Juvenile Victimization Questionnaire (JVQ)-R2 Adapted Version (ACMS), with survey data weighted to reflect characteristics of the Australian population. Overall, 1 in 10 (10.4% (95% Confidence Intervals (CI) [9.7, 11.3])) Australians experienced peer sexual harassment during childhood. Peer sexual harassment is an issue disproportionately affecting gender-diverse individuals (24.0%, 95% CI [15.5, 35.2]) and women (15.3%, 95% CI [14.0, 16.7%]), compared to men (5.0%, 95% CI [4.3, 5.9]). Rates of peer sexual harassment were also very high among sexuality diverse participants (prevalence estimates ranging between 14.2% and 29.8%). Peer sexual harassment was predominately inflicted by male peers (9.6%, 95% CI [8.9, 10.4]), compared to 1.8% (95% CI [1.5, 2.2]) reporting harassment from female peers. These findings have implications for understanding and reducing attitudes supporting peer sexual harassment in childhood, particularly against girls and gender and sexuality diverse youth, and associations with other gendered violence both in childhood and later life.

Top journals publishing articles related to drowning prevention: a bibliometric analysis 2000-2022.

BACKGROUND: Drowning is a worldwide problem. Scholarly publications about drowning prevention play a crucial role in bringing data to policy makers and prevention specialists. This study presents a bibliometric analysis of published articles related to unintentional drowning prevention included in the comprehensive, curated injury literature database, SafetyLit®. METHODS: Thorough searches of drowning-related search terms in English and non- English translations identified articles published in journals between 2000 and 2022. RESULTS: There was a 3-fold increase in publications between 2000 and 2022, with 2,937 articles published in 941 journals. Articles were published in 20 different languages. Five journals published 16% of the articles and sixty-one top journals published 50% of the articles. Eighty-nine percent of the top journals were included in PubMed; 82% were indexed in MEDLINE®; and professional areas of expertise of article authors spanned 18 categories. CONCLUSIONS: This study can facilitate journal selection for drowning researchers to ultimately increase the publication of scientific literature globally.

Development and validation of quantitative PCR assays for HIV-associated cryptococcal meningitis in sub-Saharan Africa: a diagnostic accuracy study.

BACKGROUND: HIV-associated cryptococcal meningitis is the second leading cause of AIDS-related deaths, with a 10-week mortality rate of 25-30%. Fungal load assessed by colony-forming unit (CFU) counts is used as a prognostic marker and to monitor response to treatment in research studies. PCR-based assessment of fungal load could be quicker and less labour-intensive. We sought to design, optimise, and validate quantitative PCR (qPCR) assays for the detection, identification, and quantification of Cryptococcus infections in patients with cryptococcal meningitis in sub-Saharan Africa. METHODS: We developed and validated species-specific qPCR assays based on DNA amplification of QSP1 (QSP1A specific to Cryptococcus neoformans, QSP1B/C specific to Cryptococcus deneoformans, and QSP1D specific to Cryptococcus gattii species) and a pan-Cryptococcus assay based on a multicopy 28S rRNA gene. This was a longitudinal study that validated the designed assays on cerebrospinal fluid (CSF) of 209 patients with cryptococcal meningitis at baseline (day 0) and during anti-fungal therapy (day 7 and day 14), from the AMBITION-cm trial in Botswana and Malawi (2018-21). Eligible patients were aged 18 years or older and presenting with a first case of cryptococcal meningitis. FINDINGS: When compared with quantitative cryptococcal culture as the reference, the sensitivity of the 28S rRNA was 98·2% (95% CI 95·1-99·5) and of the QSP1 assay was 90·4% (85·2-94·0) in CSF at day 0. Quantification of the fungal load with QSP1 and 28S rRNA qPCR correlated with quantitative cryptococcal culture (R2=0·73 and R2=0·78, respectively). Both Botswana and Malawi had a predominant C neoformans prevalence of 67% (95% CI 55-75) and 68% (57-73), respectively, and lower C gattii rates of 21% (14-31) and 8% (4-14), respectively. We identified ten patients that, after 14 days of treatment, harboured viable but non-culturable yeasts based on QSP1 RNA detection (without any positive CFU in CSF culture). INTERPRETATION: QSP1 and 28S rRNA assays are useful in identifying Cryptococcus species. qPCR results correlate well with baseline quantitative cryptococcal culture and show a similar decline in fungal load during induction therapy. These assays could be a faster alternative to quantitative cryptococcal culture to determine fungal load clearance. The clinical implications of the possible detection of viable but non-culturable cells in CSF during induction therapy remain unclear. FUNDING: European and Developing Countries Clinical Trials Partnership; Swedish International Development Cooperation Agency; Wellcome Trust/UK Medical Research Council/UKAID Joint Global Health Trials; and UK National Institute for Health Research.

Global guideline for the diagnosis and management of cryptococcosis: an initiative of the ECMM and ISHAM in cooperation with the ASM.

Cryptococcosis is a major worldwide disseminated invasive fungal infection. Cryptococcosis, particularly in its most lethal manifestation of cryptococcal meningitis, accounts for substantial mortality and morbidity. The breadth of the clinical cryptococcosis syndromes, the different patient types at-risk and affected, and the vastly disparate resource settings where clinicians practice pose a complex array of challenges. Expert contributors from diverse regions of the world have collated data, reviewed the evidence, and provided insightful guideline recommendations for health practitioners across the globe. This guideline offers updated practical guidance and implementable recommendations on the clinical approaches, screening, diagnosis, management, and follow-up care of a patient with cryptococcosis and serves as a comprehensive synthesis of current evidence on cryptococcosis. This Review seeks to facilitate optimal clinical decision making on cryptococcosis and addresses the myriad of clinical complications by incorporating data from historical and contemporary clinical trials. This guideline is grounded on a set of core management principles, while acknowledging the practical challenges of antifungal access and resource limitations faced by many clinicians and patients. More than 70 societies internationally have endorsed the content, structure, evidence, recommendation, and pragmatic wisdom of this global cryptococcosis guideline to inform clinicians about the past, present, and future of care for a patient with cryptococcosis.

A bioenergy-focused versus a reforestation-focused mitigation pathway yields disparate carbon storage and climate responses.

Limiting global warming to 2 °C requires urgent action on land-based mitigation. This study evaluates the biogeochemical and biogeophysical implications of two alternative land-based mitigation scenarios that aim to achieve the same radiative forcing. One scenario is primarily driven by bioenergy expansion (SSP226Lu-BIOCROP), while the other involves re/afforestation (SSP126Lu-REFOREST). We find that overall, SSP126Lu-REFOREST is a more efficient strategy for removing CO2 from the atmosphere by 2100, resulting in a net carbon sink of 242 ~ 483 PgC with smaller uncertainties compared to SSP226Lu-BIOCROP, which exhibits a wider range of -78 ~ 621 PgC. However, SSP126Lu-REFOREST leads to a relatively warmer planetary climate than SSP226Lu-BIOCROP, and this relative warming can be intensified in certain re/afforested regions where local climates are not favorable for tree growth. Despite the cooling effect on a global scale, SSP226Lu-BIOCROP reshuffles regional warming hotspots, amplifying summer temperatures in vulnerable tropical regions such as Central Africa and Southeast Asia. Our findings highlight the need for strategic land use planning to identify suitable regions for re/afforestation and bioenergy expansion, thereby improving the likelihood of achieving the intended climate mitigation outcomes.

Tracking cryptococcal meningitis to monitor HIV program success during the Treat-All era: an analysis of national data in Botswana.

BACKGROUND: Cryptococcal meningitis causes substantial mortality in high-HIV prevalence African countries despite advances in disease management and increasing antiretroviral therapy coverage. Reliable diagnosis of cryptococcal meningitis is cheap and more accessible than other indicators of AHD burden such as CD4 testing or investigation for disseminated tuberculosis; therefore, monitoring cryptococcal meningitis incidence has the potential to serve as a valuable metric of HIV programmatic success. METHODS: Botswana national meningitis surveillance data from 2015 to 2022 were obtained from electronic health records. All electronic laboratory records from cerebrospinal fluid samples analysed within government healthcare facilities in Botswana were extracted from a central online repository. Adjustments for missing data were made through triangulation with prospective cohort study datasets. Cryptococcal meningitis case frequency was enumerated using a case definition and incidence calculated using national census data. RESULTS: A total of 1,744 episodes of cryptococcal meningitis were identified; incidence declined from 15.0 (95% CI 13.4-16.7) cases/100,000 person-years in 2015 to 7.4 (95% CI 6.4-8.6) cases/100,000 person-years in 2022. However, the rate of decline slowed following the introduction of universal treatment in 2016. The highest incidence was observed in men and individuals aged 40-44. The proportion of cases diagnosed through cryptococcal antigen testing increased from 35.5% to 86.3%. CONCLUSION: Cryptococcal meningitis incidence has decreased in Botswana following expansion of ART coverage but persists at a stubbornly high incidence. Most cases are now diagnosed through the cheap and easy-to-use cryptococcal antigen test highlighting the potential of using cryptococcal meningitis as key metric of programme success in the Treat All era.

Prevalence of Diverse Genders and Sexualities in Australia and Associations With Five Forms of Child Maltreatment and Multi-type Maltreatment.

This study presents the most comprehensive national prevalence estimates of diverse gender and sexuality identities in Australians, and the associations with five separate types of child maltreatment and their overlap (multi-type maltreatment). Using Australian Child Maltreatment Study (ACMS) data (N = 8503), 9.5% of participants identified with a diverse sexuality and .9% with a diverse gender. Diverse identities were more prevalent in the youth cohort, with 17.7% of 16-24 years olds identifying with a diverse sexuality and 2.3% with a diverse gender. Gender and sexuality diversity also intersect - for example, with women (aged 16-24 and 25-44) more likely than men to identify as bisexual. The prevalence of physical abuse, sexual abuse, emotional abuse, neglect and exposure to domestic violence was very high for those with diverse sexuality and/or gender identities. Maltreatment was most prevalent for participants in the youth cohort with diverse gender identities (90.5% experiencing some form of child maltreatment; 77% multi-type maltreatment) or diverse sexualities (85.3% reporting any child maltreatment; 64.3% multi-type maltreatment). The strong association found between child maltreatment and diverse sexuality and gender identities is critical for understanding the social and mental health vulnerabilities of these groups, and informing services needed to support them.

The Kessler Psychological Distress Scale in Australian adolescents: Analysis of the second Australian Child and Adolescent Survey of Mental Health and Wellbeing.

INTRODUCTION: The 10-item Kessler Psychological Distress Scale (K10) is used to screen adolescents for mental disorders in Australian clinical practice; however, there are no Australian adolescent normative data. METHODS: Data were drawn from a nationally representative sample (N = 2964) of Australian adolescents (11-17 years). This study had three aims: (1) to examine concurrent validity between the K10 and Strengths and Difficulties Questionnaire (SDQ) emotional symptoms subscale, (2) to establish normative Australian adolescent K10 data and (3) to determine optimal K10 cut-off scores for screening for major depressive disorder (MDD) via receiver operator characteristic curve analysis and stratum-specific likelihood ratios. RESULTS: The K10 and SDQ emotional symptoms scales were moderately correlated (rs = 0.63, p < 0.001). Older female adolescents reported higher total K10 scores compared with younger female adolescents (15-17 years: M = 20.2, standard error [SE] = 0.3; 11-14 years: M = 16.8, SE = 0.3) and male adolescents (11-14 years: M = 16.6, SE = 0.2; 15-17 years: M = 16.0, SE=0.2). K10 scores to optimally discriminate those with and without MDD varied by age and sex and had low specificities. Stratum-specific likelihood ratios indicated adolescents with a K10 score of ≥30 will have a 12.9 (95% confidence interval = [10.2, 16.2]) increased likelihood of MDD. CONCLUSION: The K10 has utility for assessing psychological distress in health care and epidemiological research in Australian adolescents. Adolescents with K10 scores in the 'very high' range are at increased risk of MDD. Further assessment of these young people is indicated to identify those with or at risk of developing MDD.

Child sexual abuse by different classes and types of perpetrator: Prevalence and trends from an Australian national survey.

BACKGROUND: Little evidence exists about the prevalence of child sexual abuse (CSA) inflicted by different relational classes of perpetrators (e.g., parents; institutional adults; adolescents), and by individual types of perpetrators (e.g., fathers and male relatives; male teachers and male clergy; known and unknown adolescents). OBJECTIVE: To generate evidence of the prevalence of CSA by different perpetrators, and trends by victim gender and age group. PARTICIPANTS AND SETTING: The Australian Child Maltreatment Study collected information about CSA victimisation from a nationally-representative sample of 8503 individuals aged 16 and over. METHODS: We analysed data about 42 perpetrator types, collapsed into eight classes. We generated national prevalence estimates of CSA inflicted by each perpetrator class and individual perpetrator type, and compared results by victim gender and age group. RESULTS: Australian CSA prevalence was 28.5%, with the following prevalence by perpetrator classes: other known adolescents (non-romantic): 10.0%; parents/caregivers in the home: 7.8%; other known adults: 7.5%; unknown adults: 4.9%; adolescents (current/former romantic partners): 2.5%; institutional caregivers: 2.0%; siblings: 1.6%; unknown adolescents: 1.4%. Women experienced more CSA by all perpetrator classes except institutional caregivers. Age group comparison showed significant declines in CSA by parents/caregivers, and other known adults; and increases in CSA by adolescents (current/former romantic partners). Individual perpetrator type comparison showed declines in CSA by fathers, male relatives living in the home, non-resident male relatives, and other known male adults; and increases in CSA by known male adolescents, current boyfriends, and former boyfriends. CONCLUSIONS: CSA by adults has declined, indicating positive impacts of prevention efforts. However, CSA by adolescents has increased. Further declines in CSA by adults are required and possible. Targeted prevention of CSA by adolescents must be prioritised.

Trajectories of Loneliness During Adolescence Predict Subsequent Symptoms of Depression and Positive Wellbeing.

There is a need to identify the outcomes of changes in loneliness during adolescence, and to consider this within a multidimensional framework of loneliness. This study considered the effects of different trajectories of change in Isolation Loneliness and in Friendship Loneliness upon both positive wellbeing and symptoms of depression. To achieve this, 1782 (43% female; 12.92 years old at the start of the study, SD = 1.60) young people took part in a longitudinal study with four data points across 2 years. Four Isolation Loneliness trajectories and five Friendship Loneliness trajectories were identified. Youth who experienced low levels of Isolation Loneliness that subsequently increased appear to be at particular risk for poor outcomes. Similarly, initially high levels of Friendship Loneliness that decreased rapidly, or which began at a low level and only increased marginally, seem to also be a risk. Loneliness is a multi-dimensional construct and its development during adolescence impacts upon young people's depressive symptomatology and positive mental wellbeing.

Mindfulness-based interventions for preadolescent children: A comprehensive meta-analysis.

Among the many social and emotional learning (SEL) interventions available, mindfulness-based interventions (MBIs) have become increasingly popular, particularly for preadolescent children who were once thought to not possess the metacognitive abilities or cognitive resources to benefit from such training. Although previous research syntheses indicate that MBIs show promise in promoting positive outcomes across a range of domains, the effectiveness of MBIs for preadolescent children may be masked by the effects of older children who have comprised the majority of samples in past meta-analyses. Hence, to better understand the impact of mindfulness-based training on preadolescent children (ages 6-12 years), the present study reviewed treatment effect estimates across a range of outcomes, including mindfulness, attention, metacognition and cognitive flexibility, emotional and behavioral regulation, academic achievement and school functioning, positive emotion and self-appraisal, negative emotion and subjective distress, externalizing problems, internalizing problems, social competence and prosocial behavior, and physical health. Thirty-two studies (nparticipants = 3640) were identified and included in a random-effects meta-analyses. The results from multiple meta-analytical analyses conducted in the present study suggest that preadolescents have experienced significant benefits across attention, emotional and behavioral regulation, positive emotion and self-appraisal, and social competence and prosocial behavior (g = 0.19 to 0.39). However, the overall effect was deemed small (g = 0.34). Due to the lack of comparison studies with SEL interventions, it remains unclear whether MBIs are as effective as traditional approaches in promoting healthy development and academic achievement for preadolescent children. Additionally, results from the present meta-analysis suggest various recommendations for future studies to ensure a continued growth in understanding how MBIs can be used with children.

Observed humidity trends in dry regions contradict climate models.

Arid and semi-arid regions of the world are particularly vulnerable to greenhouse gas-driven hydroclimate change. Climate models are our primary tool for projecting the future hydroclimate that society in these regions must adapt to, but here, we present a concerning discrepancy between observed and model-based historical hydroclimate trends. Over the arid/semi-arid regions of the world, the predominant signal in all model simulations is an increase in atmospheric water vapor, on average, over the last four decades, in association with the increased water vapor-holding capacity of a warmer atmosphere. In observations, this increase in atmospheric water vapor has not happened, suggesting that the availability of moisture to satisfy the increased atmospheric demand is lower in reality than in models in arid/semi-arid regions. This discrepancy is most clear in locations that are arid/semi-arid year round, but it is also apparent in more humid regions during the most arid months of the year. It indicates a major gap in our understanding and modeling capabilities which could have severe implications for hydroclimate projections, including fire hazard, moving forward.

Pathways to care with HIV-associated cryptococcal meningitis in Botswana and Uganda: Findings from a qualitative methods study.

HIV-associated cryptococcal meningitis remains a key driver of AIDS-related mortality. Mortality is twice as high in those who present later to care and with severe symptoms such as confusion. We embedded a qualitative methods study within a randomised controlled trial in Gaborone, Botswana and Kampala, Uganda with the aim of understanding pathways to care. We conducted in-depth interviews with trial participants and surrogate decision makers and analysed data thematically. Between January 2020 and June 2021 we interviewed 58 individuals. Pathways to care were prolonged because headaches were disregarded by participants and healthcare workers as a common occurrence with a broad differential diagnosis of predominantly benign aetiologies. There was also a lack of awareness of cryptococcal meningitis, and it was often after HIV was diagnosed or disclosed that the pathway accelerated, resulting in hospital admission. We outline key recommendations to reduce mortality and argue for the integration of social and behavioural interventions within differentiated service delivery models for advanced HIV disease.