CLEAR - clozapine in early psychosis: study protocol for a multi-centre, randomised controlled trial of clozapine vs other antipsychotics for young people with treatment resistant schizophrenia in real world settings.

BACKGROUND: Clozapine is an antipsychotic drug with unique efficacy, and it is the only recommended treatment for treatment-resistant schizophrenia (TRS: failure to respond to at least two different antipsychotics). However, clozapine is also associated with a range of adverse effects which restrict its use, including blood dyscrasias, for which haematological monitoring is required. As treatment resistance is recognised earlier in the illness, the question of whether clozapine should be prescribed in children and young people is increasingly important. However, most research to date has been in older, chronic patients, and evidence regarding the efficacy and safety of clozapine in people under age 25 is lacking. The CLEAR (CLozapine in EARly psychosis) trial will assess whether clozapine is more effective than treatment as usual (TAU), at the level of clinical symptoms, patient rated outcomes, quality of life and cost-effectiveness in people below 25 years of age. Additionally, a nested biomarker study will investigate the mechanisms of action of clozapine compared to TAU. METHODS AND DESIGN: This is the protocol of a multi-centre, open label, blind-rated, randomised controlled effectiveness trial of clozapine vs TAU (any other oral antipsychotic monotherapy licenced in the British National Formulary) for 12 weeks in 260 children and young people with TRS (12-24 years old). AIM AND OBJECTIVES: The primary outcome is the change in blind-rated Positive and Negative Syndrome Scale scores at 12 weeks from baseline. Secondary outcomes include blind-rated Clinical Global Impression, patient-rated outcomes, quality of life, adverse effects, and treatment adherence. Patients will be followed up for 12 months and will be invited to give consent for longer term follow-up using clinical records and potential re-contact for further research. For mechanism of action, change in brain magnetic resonance imaging (MRI) biomarkers and peripheral inflammatory markers will be measured over 12 weeks. DISCUSSION: The CLEAR trial will contribute knowledge on clozapine effectiveness, safety and cost-effectiveness compared to standard antipsychotics in young people with TRS, and the results may guide future clinical treatment recommendation for early psychosis. TRIAL REGISTRATION: ISRCTN Number: 37176025, IRAS Number: 1004947. TRIAL STATUS: In set-up. Protocol version 4.0 01/08/23. Current up to date protocol available here: https://fundingawards.nihr.ac.uk/award/NIHR131175# /.

Long-Term Outcomes of the Restoration of Uterovaginal Continuity and Vaginoplasty-Utero-Colo-Neovaginoplasty-in Cervicovaginal Agenesis Using the Sigmoid Colon.

INTRODUCTION AND HYPOTHESIS: Congenital cervicovaginal agenesis in the presence of a functional endometrium is a rare Müllerian anomaly. The management ranges from hysterectomy historically to various reconstructive procedures more recently. We report our experience with utero-colo-vaginoplasty in the management of this anomaly and its long-term follow-up. METHODS: The case records of all the patients with vaginal or cervicovaginal agenesis in our hospital from January 2002 to December 2019 were reviewed retrospectively. The patients were then called for an outpatient visit and examined in detail. The anatomical variations, surgical procedures and outcomes were recorded and analysed. RESULTS: Sixteen patients aged 14 to 26 years were included during the study period. They presented with cyclical painful cryptomenorrhea. Magnetic resonance imaging (MRI) confirmed cervicovaginal or distal vaginal agenesis. All the patients underwent utero-colo-vaginoplasty. Intraoperative rectal injury led to post-operative faecal leak from the perineal wound in one patient in the post-operative period. Restoration of painless menstrual flow was possible in all 16 cases. Long-term complications were seen in 4 patients. These were stenosis of the perineal neovaginal orifice in 2 patients, obstruction at colo-uterine anastomosis in 1 patient and mucosal prolapse at the neovagina in 1 patient. Three of these patients needed secondary surgical procedures. Five were sexually active and reported consummation of penetrative intercourse. None of them had conceived. CONCLUSION: In our experience, utero-colo-vaginoplasty allows for regular painless menstruation and coitus with minimal long-term complications. The sole disadvantage is the failure to conceive.

Prevalence of Self-Reported Swallowing Difficulties and Swallowing-Related Quality of Life Among Community-Dwelling Older Adults in India.

Self-reported swallowing difficulties are highly prevalent but underreported among older adults. The aging population in India is increasing, yet there is a lack of empirical data on self-reported swallowing difficulties in older adults. In the present study, we aimed to estimate the prevalence of self-reported swallowing difficulties and assess the swallowing-related quality of life (QOL) among community-dwelling older adults in India. We recruited 361 older adults (60-91 years) from the community. Participants completed the Eating Assessment Tool-10 (EAT-10) to assess self-reported swallowing difficulties and the Dysphagia Handicap Index (DHI) to assess swallowing-related QOL. Participants rated the EAT-10 from 0 for 'no problem' to 4 for 'severe problem'. The DHI rating included 0 for 'never', 2 for 'sometimes', and 4 for 'always'. The total scores of EAT-10 and DHI were summarised using descriptive statistics. Statistically significant differences between pass-fail groups of EAT-10 and DHI were evaluated using an independent t-test and multivariate analysis of variance test, respectively. The overall mean score for EAT-10 was 3.34, and 7.56 for DHI, with higher scores observed among females. 36.6% of older adults self-reported experiencing swallowing difficulties, while 47.4% self-reported having poor swallowing-related QOL at p < 0.05. A strong positive correlation (r = 0.86) was found between EAT-10 and total DHI scores at p < 0.001. The present study sheds light on the widespread yet underreported issue of self-reported swallowing difficulties and the impact on swallowing-related QOL among older adults in India. These findings emphasize the urgent need for early swallowing screening programs among older adults.

Impact of Truncation on Optoelectronic Properties of Azaborole Helicenes.

Herein, we report configurationally stable singly-truncated (ST) and structurally flexible doubly-truncated (DT) helically chiral compounds derived from azabora[7]helicenes by a hypothetical removal of a single or two C=C double bonds. The singly-truncated constitutional isomers were synthesized from either benzoisoquinoline (BIQ) or phenantherene building blocks and the corresponding biaryls in excellent yields to give azabora[5]helicenes with a pendant phenyl ring at a sterically hindered position. These systems highlight the electronic impact of the nitrogen donor substitution position. The compounds with a disrupted BIQ moiety (STN) possess remarkable photoluminescence quantum yields of up to 0.53 in the solid state and a blue emission in solution with dissymmetry factors of up to ca. 3×10-3 . Upon cooling to 79 K all compounds exhibit phosphorescence with lifetimes of up to ca. 0.5 s. A methyl complex of azabora[7]helicene showing excellent configurational stability was used as a chiral inducer embedded in an emissive polymer (F8BT) to produce circularly polarized organic light emitting diodes with an electroluminescence dissymmetry factor gEL of up to 0.54.

Effect of managed transition on mental health outcomes for young people at the child-adult mental health service boundary: a randomised clinical trial.

BACKGROUND: Poor transition planning contributes to discontinuity of care at the child-adult mental health service boundary (SB), adversely affecting mental health outcomes in young people (YP). The aim of the study was to determine whether managed transition (MT) improves mental health outcomes of YP reaching the child/adolescent mental health service (CAMHS) boundary compared with usual care (UC). METHODS: A two-arm cluster-randomised trial (ISRCTN83240263 and NCT03013595) with clusters allocated 1:2 between MT and UC. Recruitment took place in 40 CAMHS (eight European countries) between October 2015 and December 2016. Eligible participants were CAMHS service users who were receiving treatment or had a diagnosed mental disorder, had an IQ ⩾ 70 and were within 1 year of reaching the SB. MT was a multi-component intervention that included CAMHS training, systematic identification of YP approaching SB, a structured assessment (Transition Readiness and Appropriateness Measure) and sharing of information between CAMHS and adult mental health services. The primary outcome was HoNOSCA (Health of the Nation Outcome Scale for Children and Adolescents) score 15-months post-entry to the trial. RESULTS: The mean difference in HoNOSCA scores between the MT and UC arms at 15 months was -1.11 points (95% confidence interval -2.07 to -0.14, p = 0.03). The cost of delivering the intervention was relatively modest (€17-€65 per service user). CONCLUSIONS: MT led to improved mental health of YP after the SB but the magnitude of the effect was small. The intervention can be implemented at low cost and form part of planned and purposeful transitional care.

Fatty acid isotopic composition in Atlantic pollock is not influenced by environmentally relevant dietary fat concentrations.

The application of fatty acid (FA) isotopic analysis has great potential in elucidating food web structure, but it has not experienced the same wide-spread use as amino acid isotopic analyses. The failure to adopt FA isotopic methods is almost certainly linked to a lack of reliable information on trophic fractionation of FA, particularly in higher predators. In this work, we attempt to address this shortfall, through comparison of FA δ13C values in captive Atlantic pollock (Pollachius virens) liver and their known diets. Since catabolism is likely the main cause of fractionation and it may vary with dietary fat content, we investigated the impact of dietary fat concentration on isotopic discrimination in FA. We fed Atlantic pollock three formulated diets with similar FA isotopic compositions but different fat concentrations (5-9% of diet), representative of the range found in natural prey, for 20 weeks. At the conclusion of the study, δ13C values of liver FA were very similar to the FA within the corresponding diets, with most discrimination factors < 1. For all FA except 22:6n-3, dietary fat had no effect on discrimination factors. Only for 22:6n-3 did fish fed the highest fat diet have lower δ13C values than the diet consumed. Thus, these FA-specific discrimination factors can be applied to evaluate diets in marine fish consuming natural diets and will serve as additional and valuable biomarkers in fish feeding ecology.

Remote assessment of ADHD in children and adolescents: recommendations from the European ADHD Guidelines Group following the clinical experience during the COVID-19 pandemic.

The COVID-19 pandemic led ADHD services to modify the clinical practice to reduce in-person contact as much as possible to minimise viral spread. This had far-reaching effects on day-to-day clinical practice as remote assessments were widely adopted. Despite the attenuation of the acute threat from COVID, many clinical services are retaining some remote practices. The lack of clear evidence-based guidance about the most appropriate way to conduct remote assessments meant that these changes were typically implemented in a localised, ad hoc, and un-coordinated way. Here, the European ADHD Guidelines Group (EAGG) discusses the strengths and weaknesses of remote assessment methods of children and adolescents with ADHD in a narrative review based on available data and expert opinions to highlight key recommendations for future studies and clinical practice. We conclude that going forward, despite remote working in clinical services functioning adequately during the pandemic, all required components of ADHD assessment should still be completed following national/international guidelines; however, the process may need adaptation. Social restrictions, including changes in education provision, can either mask or exacerbate features associated with ADHD and therefore assessment should carefully chart symptom profile and impairment prior to, as well as during an ongoing pandemic. While remote assessments are valuable in allowing clinical services to continue despite restrictions and may have benefits for routine care in the post-pandemic world, particular attention must be paid to those who may be at high risk but not be able to use/access remote technologies and prioritize these groups for conventional face-to-face assessments.

Reversible redox switching between local and global aromaticity for core-modified expanded carbaisophlorinoids.

Two dithienothiophene based 28π antiaromatic macrocycles with benzene and azulene units and their effects on local and global (anti)aromaticity have been described. Experimental and computational studies confirmed the presence of weak paratropic and strong diatropic ring current effects in neutral and dicationic states, respectively.

Demographic, clinical, and service-use characteristics related to the clinician's recommendation to transition from child to adult mental health services.

PURPOSE: The service configuration with distinct child and adolescent mental health services (CAMHS) and adult mental health services (AMHS) may be a barrier to continuity of care. Because of a lack of transition policy, CAMHS clinicians have to decide whether and when a young person should transition to AMHS. This study describes which characteristics are associated with the clinicians' advice to continue treatment at AMHS. METHODS: Demographic, family, clinical, treatment, and service-use characteristics of the MILESTONE cohort of 763 young people from 39 CAMHS in Europe were assessed using multi-informant and standardized assessment tools. Logistic mixed models were fitted to assess the relationship between these characteristics and clinicians' transition recommendations. RESULTS: Young people with higher clinician-rated severity of psychopathology scores, with self- and parent-reported need for ongoing treatment, with lower everyday functional skills and without self-reported psychotic experiences were more likely to be recommended to continue treatment. Among those who had been recommended to continue treatment, young people who used psychotropic medication, who had been in CAMHS for more than a year, and for whom appropriate AMHS were available were more likely to be recommended to continue treatment at AMHS. Young people whose parents indicated a need for ongoing treatment were more likely to be recommended to stay in CAMHS. CONCLUSION: Although the decision regarding continuity of treatment was mostly determined by a small set of clinical characteristics, the recommendation to continue treatment at AMHS was mostly affected by service-use related characteristics, such as the availability of appropriate services.

Transition from child and adolescent mental health care to adult services for young people with Attention-Deficit/Hyperactivity Disorder (ADHD) or Autism Spectrum Disorder (ASD) in Europe: Barriers and recommendations.

Transition in mental health care is the process ensuring continuity of care of a young patient arriving at the CAMHS (Child and Adolescent Mental Health Service) age boundary within mental health services. Transition refers to a transfer to an adult mental health service (AMHS), to private care or other mental health community services. A transition plan can also lead to a managed end of specialized care with involvement of a general practitioner or social services. For young people with a diagnosis of ADHD (Attention Deficit Hyperactivity Disorder) or ASD (Autism Spectrum Disorder), two disorders that persist into adulthood, an optimal transition would ensure continuity of care or facilitate access to specialized care in the case of a discharge. Transition typically occurs during adolescence, a known sensitive period when young people may experience major changes at several levels: physiological, psychological and social. Any barrier in the transition process resulting in discontinuity of care may worsen the symptoms of ADHD or ASD and can ultimately adversely affect the global mental health of young people with such neurodevelopmental disorders. The objectives of this narrative review are: 1/to identify the barriers in the transition process in mental health services often faced by young people with these two disorders; 2/to highlight specific recommendations for strengthening the CAMHS-AMHS interface that have been proposed by various countries in Europe.

Intracerebral Haemorrhage: A Rare Presentation of Phaeochromocytoma.

Phaeochromocytoma is a rare childhood adrenal medullary catecholamine secreting tumour, arising from the chromaffin cells of the sympathetic origin derived from the neural crest cells. Only a few cases have been reported in the literature so far. We report an uncommon presentation in a 5-year-old boy with intracerebral haemorrhage, hemiplegia, and paroxysmal hypertension. Magnetic resonance imaging of the brain showed chronic and acute hemorrhagic infarcts in the left cerebral hemisphere and no vascular anomaly seen on cerebral venogram. Computed tomography scan abdomen showed a mass in the lesser sac and urinary catecholamines were elevated. The patient underwent exploratory laparotomy and the mass was excised in toto. Histopathological examination (HPE) confirmed the diagnosis. This case illustrates the need for keeping in mind atypical presentations of phaeochromocytoma especially in children; as it is a treatable cause of hypertension and early diagnosis with adequate management can prevent morbidity and fatal outcomes.

Modular Synthesis of Organoboron Helically Chiral Compounds: Cutouts from Extended Helices.

Two types of helically chiral compounds bearing one and two boron atoms were synthesized by a modular approach. Formation of the helical scaffolds was executed by the introduction of boron to flexible biaryl and triaryl derived from small achiral building blocks. All-ortho-fused azabora[7]helicenes feature exceptional configurational stability, blue or green fluorescence with quantum yields (Φfl ) of 18-24 % in solution, green or yellow solid-state emission (Φfl up to 23 %), and strong chiroptical response with large dissymmetry factors of up to 1.12×10-2 . Azabora[9]helicenes consisting of angularly and linearly fused rings are blue emitters exhibiting Φfl of up to 47 % in CH2 Cl2 and 25 % in the solid state. As revealed by the DFT calculations, their P-M interconversion pathway is more complex than that of H1. Single-crystal X-ray analysis shows clear differences in the packing arrangement of methyl and phenyl derivatives. These molecules are proposed as primary structures of extended helices.

Impact of Hospitalist Team Structure on Patient-Reported Satisfaction with Physician Performance.

BACKGROUND: Patient experience is valuable because it reflects how patients perceive the care they receive within the healthcare system and is associated with clinical outcomes. Also, as part of the Hospital Value-Based Purchasing (HVBP) program, the Center for Medicare and Medicaid Services (CMS) rewards hospitals with financial incentives for patient experience as measured by the Hospital Consumer Assessment of Healthcare Providers and Systems (HCAHPS) survey. It is unclear how the addition of residents and advanced practice clinicians (APCs) to hospitalist-led inpatient teams affects patient satisfaction as measured by the HCAHPS and Press Ganey survey. OBJECTIVE: To compare patient satisfaction with hospitalists on resident, APC, and solo hospitalist teams measured by HCAHPS and Press Ganey physician performance domain survey results. DESIGN: Retrospective observational cohort study. PARTICIPANTS: All patients discharged from the Internal Medicine inpatient service between July 1, 2015, and July 1, 2018, who met HCAHPS survey eligibility criteria and completed a patient experience survey. MAIN MEASURES: HCAHPS and Press Ganey physician performance domain survey results. KEY RESULTS: No differences were observed in the selection of "top box" scores on the HCAHPS physician performance domain between resident, APC, and solo hospitalist teams. Adjusted Press Ganey physician performance domain survey results demonstrated significant differences between solo hospitalist and resident teams, with solo hospitalists having higher scores in three areas: time physician spent with you (4.58 vs. 4.38, p = 0.050); physician kept you informed (4.63 vs. 4.43, p = 0.047); and physician skill (4.80 vs. 4.63, p = 0.027). Solo hospitalists were perceived to have higher physician skill in comparison with hospitalist-APC teams (4.80 vs. 4.69, p = 0.042). CONCLUSION: While Press Ganey survey results suggest that patients have greater satisfaction with physicians on solo hospitalist teams, these differences were not observed on the HCAHPS physician performance survey domain, suggesting physician team structure does not impact HVBP incentive payments by CMS.

Protocol for the development and validation procedure of the managing the link and strengthening transition from child to adult mental health care (MILESTONE) suite of measures.

BACKGROUND: Mental health disorders in the child and adolescent population are a pressing public health concern. Despite the high prevalence of psychopathology in this vulnerable population, the transition from Child and Adolescent Mental Health Services (CAMHS) to Adult Mental Health Services (AMHS) has many obstacles such as deficiencies in planning, organisational readiness and policy gaps. All these factors contribute to an inadequate and suboptimal transition process. A suite of measures is required that would allow young people to be assessed in a structured and standardised way to determine the on-going need for care and to improve communication across clinicians at CAMHS and AMHS. This will have the potential to reduce the overall health economic burden and could also improve the quality of life for patients travelling across the transition boundary. The MILESTONE (Managing the Link and Strengthening Transition from Child to Adult Mental Health Care) project aims to address the significant socioeconomic and societal challenge related to the transition process. This protocol paper describes the development of two MILESTONE transition-related measures: The Transition Readiness and Appropriateness Measure (TRAM), designed to be a decision-making aide for clinicians, and the Transition Related Outcome Measure (TROM), for examining the outcome of transition. METHODS: The TRAM and TROM have been developed and were validated following the US FDA Guidance for Patient-reported Outcome Measures which follows an incremental stepwise framework. The study gathers information from service users, parents, families and mental health care professionals who have experience working with young people undergoing the transition process from eight European countries. DISCUSSION: There is an urgent need for comprehensive measures that can assess transition across the CAMHS/AMHS boundary. This study protocol describes the process of development of two new transition measures: the TRAM and TROM. The TRAM has the potential to nurture better transitions as the findings can be summarised and provided to clinicians as a clinician-decision making support tool for identifying cases who need to transition and the TROM can be used to examine the outcomes of the transition process. TRIAL REGISTRATION: MILESTONE study registration: ISRCTN83240263 Registered 23-July-2015 - ClinicalTrials.gov NCT03013595 Registered 6 January 2017.

Managing the link and strengthening transition from child to adult mental health Care in Europe (MILESTONE): background, rationale and methodology.

BACKGROUND: Transition from distinct Child and Adolescent Mental Health (CAMHS) to Adult Mental Health Services (AMHS) is beset with multitude of problems affecting continuity of care for young people with mental health needs. Transition-related discontinuity of care is a major health, socioeconomic and societal challenge globally. The overall aim of the Managing the Link and Strengthening Transition from Child to Adult Mental Health Care in Europe (MILESTONE) project (2014-19) is to improve transition from CAMHS to AMHS in diverse healthcare settings across Europe. MILESTONE focuses on current service provision in Europe, new transition-related measures, long term outcomes of young people leaving CAMHS, improving transitional care through 'managed transition', ethics of transitioning and the training of health care professionals. METHODS: Data will be collected via systematic literature reviews, pan-European surveys, and focus groups with service providers, users and carers, and members of youth advocacy and mental health advocacy groups. A prospective cohort study will be conducted with a nested cluster randomised controlled trial in eight European Union (EU) countries (Belgium, Croatia, France, Germany, Ireland, Italy, Netherlands, UK) involving over 1000 CAMHS users, their carers, and clinicians. DISCUSSION: Improving transitional care can facilitate not only recovery but also mental health promotion and mental illness prevention for young people. MILESTONE will provide evidence of the organisational structures and processes influencing transition at the service interface across differing healthcare models in Europe and longitudinal outcomes for young people leaving CAMHS, solutions for improving transitional care in a cost-effective manner, training modules for clinicians, and commissioning and policy guidelines for service providers and policy makers. TRIAL REGISTRATION: "MILESTONE study" registration: ISRCTN ISRCTN83240263 Registered 23 July 2015; ClinicalTrials.gov NCT03013595 Registered 6 January 2017.

Correction to: Managing the link and strengthening transition from child to adult mental health Care in Europe (MILESTONE): background, rationale and methodology.

Following publication of the original article [1], the authors reported they wanted to reinstate a co-author, who previously declined his authorship due to a misinterpretation of authorship limitations per research center.

Life-threatening Medical Complications Due to Ovarian Hyperstimulation Syndrome: A Hidden Etiology.

Ovarian hyperstimulation syndrome is usually an iatrogenic complication in women taking ovulation induction medications during assisted reproduction. We hereby report the case of a 25 years old female who presented with hypertension, polyserositis with tense ascites and large cystic ovaries. She developed sigmoid and transverse sinus thrombosis. She had undergone a clandestine ovulation induction therapy as a commercial ovum donor. She fitted in severe category of ovarian hyperstimulation syndrome.

Paradoxical physiological responses to propranolol in a Rett syndrome patient: a case report.

BACKGROUND: Rett Syndrome (RTT), caused by a loss-of-function in the epigenetic modulator: X-linked methyl-CpG binding protein 2 (MeCP2), is a pervasive neurological disorder characterized by compromised brain functions, anxiety, severe mental retardation, language and learning disabilities, repetitive stereotyped hand movements and developmental regression. An imbalance in the sympathetic and the parasympathetic nervous system (dysautonomia) and the resulting autonomic storms is a frequent occurrence in patients with RTT. The prototypical beta blocker propranolol has been used to manage sympathetic hyperactivity in patients with RTT. CASE PRESENTATION: A 13 year old girl with RTT was referred to the Centre for Interventional Paediatric Psychopharmacology and Rare Diseases (CIPPRD), South London and Maudsley NHS Foundation Trust. Her clinical picture included disordered breathing with concomitant hyperventilation and apnoea, epilepsy, scoliosis, no QT prolongation (QT/QTc [372/467 ms on automated electrocardiogram [ECG], but manually calculated to be 440 ms]), no cardiac abnormalities (PR interval: 104 ms, QRS duration: 78 ms), and generalised anxiety disorder (ICD-10-CM Diagnosis Code F41.1). She was also constipated and was fed via percutaneous endoscopic gastrostomy (PEG). To manage the dysautonomia, propranolol was given (5 mg and 10 mg) and in parallel her physiological parameters, including heart rate, skin temperature and skin transpiration, were monitored continuously for 24 h as she went about her activities of daily living. Whilst her skin temperature increased and skin transpiration decreased, unexpectedly there was a significant paradoxical increase in the patient's average heart rate following propranolol treatment. CONCLUSION: Here, we present a unique case of a paradoxical increase in heart rate response following propranolol treatment for managing dysautonomia in a child with RTT. Further studies are warranted to better understand the underlying dysautonomia in patients with RTT and the impact this might have on treatment strategies in rare disorders such as RTT.

Development and psychometric properties of the Suicidality: Treatment Occurring in Paediatrics (STOP) Suicidality Assessment Scale (STOP-SAS) in children and adolescents.

BACKGROUND: To create a self-reported, internet-based questionnaire for the assessment of suicide risk in children and adolescents. METHODS: As part of the EU project 'Suicidality: Treatment Occurring in Paediatrics' (STOP project), we developed web-based Patient Reported Outcome Measures (PROMs) for children and adolescents and for proxy reports by parents and clinicians in order to assess suicidality. Based on a literature review, expert panels and focus groups of patients, we developed the items of the STOP Suicidality Assessment Scale (STOP-SAS) in Spanish and English, translated it into four more languages, and optimized it for web-based presentation using the HealthTrackerTM platform. Of the total 19 questions developed for the STOP-SAS, four questions that assess low-level suicidality were identified as screening questions (three of them for use with children, and all four for use with adolescents, parents and clinicians). A total of 395 adolescents, 110 children, 637 parents and 716 clinicians completed the questionnaire using the HealthTrackerTM, allowing us to evaluate the internal consistency and convergent validity of the STOP-SAS with the clinician-rated Columbia Suicide Severity Rating Scale (C-SSRS). Validity was also assessed with the receiver operating characteristic (ROC) area of the STOP-SAS with the C-SSRS. RESULTS: The STOP-SAS comprises 19 items in its adolescent, parent, and clinician versions, and 14 items in its children's version. Good internal consistency was found for adolescents (Cronbach's alpha: 0.965), children (Cronbach's alpha: 0.922), parents (Cronbach's alpha: 0.951) and clinicians (Cronbach's alpha: 0.955) versions. A strong correlation was found between the STOP-SAS and the C-SSRS for adolescents (r:0.670), parents (r:0.548), clinicians (r:0.863) and children (r:0.654). The ROC area was good for clinicians' (0.917), adolescents' (0.834) and parents' (0.756) versions but only fair (0.683) for children's version. CONCLUSIONS: The STOP-SAS is a comprehensive, web-based PROM developed on the HealthTrackerTM platform, and co-designed for use by adolescents, children, parents and clinicians. It allows the evaluation of aspects of suicidality and shows good reliability and validity.

Population genomic and genome-wide association studies of agroclimatic traits in sorghum.

Accelerating crop improvement in sorghum, a staple food for people in semiarid regions across the developing world, is key to ensuring global food security in the context of climate change. To facilitate gene discovery and molecular breeding in sorghum, we have characterized ~265,000 single nucleotide polymorphisms (SNPs) in 971 worldwide accessions that have adapted to diverse agroclimatic conditions. Using this genome-wide SNP map, we have characterized population structure with respect to geographic origin and morphological type and identified patterns of ancient crop diffusion to diverse agroclimatic regions across Africa and Asia. To better understand the genomic patterns of diversification in sorghum, we quantified variation in nucleotide diversity, linkage disequilibrium, and recombination rates across the genome. Analyzing nucleotide diversity in landraces, we find evidence of selective sweeps around starch metabolism genes, whereas in landrace-derived introgression lines, we find introgressions around known height and maturity loci. To identify additional loci underlying variation in major agroclimatic traits, we performed genome-wide association studies (GWAS) on plant height components and inflorescence architecture. GWAS maps several classical loci for plant height, candidate genes for inflorescence architecture. Finally, we trace the independent spread of multiple haplotypes carrying alleles for short stature or long inflorescence branches. This genome-wide map of SNP variation in sorghum provides a basis for crop improvement through marker-assisted breeding and genomic selection.