Role of microstructure in the electron–hole interaction of hybrid lead halide perovskites

Organic–inorganic metal halide perovskites have demonstrated high power conversion efficiencies in solar cells and promising performance in a wide range of optoelectronic devices. The existence and stability of bound electron–hole pairs in these materials and their role in the operation of devices with different architectures remains a controversial issue. Here we demonstrate, through a combination of optical spectroscopy and multiscale modelling as a function of the degree of polycrystallinity and temperature, that the electron–hole interaction is sensitive to the microstructure of the material. The long-range order is disrupted by polycrystalline disorder and the variations in electrostatic potential found for smaller crystals suppress exciton formation, while larger crystals of the same composition demonstrate an unambiguous excitonic state. We conclude that fabrication procedures and morphology strongly influence perovskite behaviour, with both free carrier and excitonic regimes possible, with strong implications for optoelectronic devices

Early blood pressure, antihypotensive therapy and outcomes at 18–22 months’ corrected age in extremely preterm infants

Investigate relationships between early blood pressure (BP) changes, receipt of anti-hypotensive therapy, and 18 – 22 month corrected age (CA) outcomes for extremely preterm infants

Resource utilisation and costs in predementia and dementia: a systematic review protocol

Introduction Dementia is the fastest growing major cause of disability globally with a mounting social and financial impact for patients and their families but also to health and social care systems. This review aims to systematically synthesise evidence on the utilisation of resources and costs incurred by patients and their caregivers and by health and social care services across the full spectrum of dementia, from its preceding preclinical stage to end of life. The main drivers of resources used and costs will also be identified. Methods and analysis A systematic literature review was conducted in MEDLINE, EMBASE, CDSR, CENTRAL, DARE, EconLit, CEA Registry, TRIP, NHS EED, SCI, RePEc and OpenGrey between January 2000 and beginning of May 2017. Two reviewers will independently assess each study for inclusion and disagreements will be resolved by a third reviewer. Data will be extracted using a predefined data extraction form following best practice. Study quality will be assessed with the Effective Public Health Practice Project quality assessment tool. The reporting of costing methodology will be assessed using the British Medical Journal checklist. A narrative synthesis of all studies will be presented for resources used and costs incurred, by level of disease severity when available. If feasible, the data will be synthesised using appropriate statistical techniques. Ethics and dissemination Included articles will be reviewed for an ethics statement. The findings of the review will be disseminated in a related peer-reviewed journal and presented at conferences. They will also contribute to the work developed in the Real World Outcomes across the Alzheimer’s disease spectrum for better care: multi-modal data access platform (ROADMAP)

Assessment of Corticosteroid Therapy and Death or Disability According to Pretreatment Risk of Death or Bronchopulmonary Dysplasia in Extremely Preterm Infants

IMPORTANCE: Meta-analyses suggest that corticosteroids may be associated with increased survival without cerebral palsy in infants at high risk of bronchopulmonary dysplasia (BPD) but are associated with adverse neurologic outcomes in low-risk infants. Whether this association exists in contemporary practice is uncertain because most randomized clinical trials administered corticosteroids earlier and at higher doses than currently recommended. OBJECTIVE: To evaluate whether the pretreatment risk of death or grade 2 or 3 BPD at 36 weeks\u27 postmenstrual age modified the association between postnatal corticosteroid therapy and death or disability at 2 years\u27 corrected age in extremely preterm infants. DESIGN, SETTING, AND PARTICIPANTS: This cohort study analyzed data on 482 matched pairs of infants from 45 participating US hospitals in the National Institute of Child Health and Human Development Neonatal Research Network Generic Database (GDB). Infants were included in the cohort if they were born at less than 27 weeks\u27 gestation between April 1, 2011, and March 31, 2017; survived the first 7 postnatal days; and had 2-year death or developmental follow-up data collected between January 2013 and December 2019. Corticosteroid-treated infants were propensity score matched with untreated controls. Data were analyzed from September 1, 2019, to November 30, 2022. EXPOSURE: Systemic corticosteroid therapy to prevent BPD that was initiated between day 8 and day 42 after birth. MAIN OUTCOMES AND MEASURES: The primary outcome was death or moderate to severe neurodevelopmental impairment at 2 years\u27 corrected age. The secondary outcome was death or moderate to severe cerebral palsy at 2 years\u27 corrected age. RESULTS: A total of 482 matched pairs of infants (mean [SD] gestational age, 24.1 [1.1] weeks]; 270 males [56.0%]) were included from 656 corticosteroid-treated infants and 2796 potential controls. Most treated infants (363 [75.3%]) received dexamethasone. The risk of death or disability associated with corticosteroid therapy was inversely associated with the estimated pretreatment probability of death or grade 2 or 3 BPD. The risk difference for death or neurodevelopmental impairment associated with corticosteroids decreased by 2.7% (95% CI, 1.9%-3.5%) for each 10% increase in the pretreatment risk of death or grade 2 or 3 BPD. This risk transitioned from estimated net harm to benefit when the pretreatment risk of death or grade 2 or 3 BPD exceeded 53% (95% CI, 44%-61%). For death or cerebral palsy, the risk difference decreased by 3.6% (95% CI, 2.9%-4.4%) for each 10% increase in the risk of death or grade 2 or 3 BPD and transitioned from estimated net harm to benefit at a pretreatment risk of 40% (95% CI, 33%-46%). CONCLUSIONS AND RELEVANCE: Results of this study suggested that corticosteroids were associated with a reduced risk of death or disability in infants at moderate to high pretreatment risk of death or grade 2 or 3 BPD but with possible harm in infants at lower risk

Cognitive behavioural therapy for adults with dissociative seizures (CODES): a pragmatic, multicentre, randomised controlled trial.

BACKGROUND: Dissociative seizures are paroxysmal events resembling epilepsy or syncope with characteristic features that allow them to be distinguished from other medical conditions. We aimed to compare the effectiveness of cognitive behavioural therapy (CBT) plus standardised medical care with standardised medical care alone for the reduction of dissociative seizure frequency. METHODS: In this pragmatic, parallel-arm, multicentre randomised controlled trial, we initially recruited participants at 27 neurology or epilepsy services in England, Scotland, and Wales. Adults (≥18 years) who had dissociative seizures in the previous 8 weeks and no epileptic seizures in the previous 12 months were subsequently randomly assigned (1:1) from 17 liaison or neuropsychiatry services following psychiatric assessment, to receive standardised medical care or CBT plus standardised medical care, using a web-based system. Randomisation was stratified by neuropsychiatry or liaison psychiatry recruitment site. The trial manager, chief investigator, all treating clinicians, and patients were aware of treatment allocation, but outcome data collectors and trial statisticians were unaware of treatment allocation. Patients were followed up 6 months and 12 months after randomisation. The primary outcome was monthly dissociative seizure frequency (ie, frequency in the previous 4 weeks) assessed at 12 months. Secondary outcomes assessed at 12 months were: seizure severity (intensity) and bothersomeness; longest period of seizure freedom in the previous 6 months; complete seizure freedom in the previous 3 months; a greater than 50% reduction in seizure frequency relative to baseline; changes in dissociative seizures (rated by others); health-related quality of life; psychosocial functioning; psychiatric symptoms, psychological distress, and somatic symptom burden; and clinical impression of improvement and satisfaction. p values and statistical significance for outcomes were reported without correction for multiple comparisons as per our protocol. Primary and secondary outcomes were assessed in the intention-to-treat population with multiple imputation for missing observations. This trial is registered with the International Standard Randomised Controlled Trial registry, ISRCTN05681227, and ClinicalTrials.gov, NCT02325544. FINDINGS: Between Jan 16, 2015, and May 31, 2017, we randomly assigned 368 patients to receive CBT plus standardised medical care (n=186) or standardised medical care alone (n=182); of whom 313 had primary outcome data at 12 months (156 [84%] of 186 patients in the CBT plus standardised medical care group and 157 [86%] of 182 patients in the standardised medical care group). At 12 months, no significant difference in monthly dissociative seizure frequency was identified between the groups (median 4 seizures [IQR 0-20] in the CBT plus standardised medical care group vs 7 seizures [1-35] in the standardised medical care group; estimated incidence rate ratio [IRR] 0·78 [95% CI 0·56-1·09]; p=0·144). Dissociative seizures were rated as less bothersome in the CBT plus standardised medical care group than the standardised medical care group (estimated mean difference -0·53 [95% CI -0·97 to -0·08]; p=0·020). The CBT plus standardised medical care group had a longer period of dissociative seizure freedom in the previous 6 months (estimated IRR 1·64 [95% CI 1·22 to 2·20]; p=0·001), reported better health-related quality of life on the EuroQoL-5 Dimensions-5 Level Health Today visual analogue scale (estimated mean difference 6·16 [95% CI 1·48 to 10·84]; p=0·010), less impairment in psychosocial functioning on the Work and Social Adjustment Scale (estimated mean difference -4·12 [95% CI -6·35 to -1·89]; p<0·001), less overall psychological distress than the standardised medical care group on the Clinical Outcomes in Routine Evaluation-10 scale (estimated mean difference -1·65 [95% CI -2·96 to -0·35]; p=0·013), and fewer somatic symptoms on the modified Patient Health Questionnaire-15 scale (estimated mean difference -1·67 [95% CI -2·90 to -0·44]; p=0·008). Clinical improvement at 12 months was greater in the CBT plus standardised medical care group than the standardised medical care alone group as reported by patients (estimated mean difference 0·66 [95% CI 0·26 to 1·04]; p=0·001) and by clinicians (estimated mean difference 0·47 [95% CI 0·21 to 0·73]; p<0·001), and the CBT plus standardised medical care group had greater satisfaction with treatment than did the standardised medical care group (estimated mean difference 0·90 [95% CI 0·48 to 1·31]; p<0·001). No significant differences in patient-reported seizure severity (estimated mean difference -0·11 [95% CI -0·50 to 0·29]; p=0·593) or seizure freedom in the last 3 months of the study (estimated odds ratio [OR] 1·77 [95% CI 0·93 to 3·37]; p=0·083) were identified between the groups. Furthermore, no significant differences were identified in the proportion of patients who had a more than 50% reduction in dissociative seizure frequency compared with baseline (OR 1·27 [95% CI 0·80 to 2·02]; p=0·313). Additionally, the 12-item Short Form survey-version 2 scores (estimated mean difference for the Physical Component Summary score 1·78 [95% CI -0·37 to 3·92]; p=0·105; estimated mean difference for the Mental Component Summary score 2·22 [95% CI -0·30 to 4·75]; p=0·084), the Generalised Anxiety Disorder-7 scale score (estimated mean difference -1·09 [95% CI -2·27 to 0·09]; p=0·069), and the Patient Health Questionnaire-9 scale depression score (estimated mean difference -1·10 [95% CI -2·41 to 0·21]; p=0·099) did not differ significantly between groups. Changes in dissociative seizures (rated by others) could not be assessed due to insufficient data. During the 12-month period, the number of adverse events was similar between the groups: 57 (31%) of 186 participants in the CBT plus standardised medical care group reported 97 adverse events and 53 (29%) of 182 participants in the standardised medical care group reported 79 adverse events. INTERPRETATION: CBT plus standardised medical care had no statistically significant advantage compared with standardised medical care alone for the reduction of monthly seizures. However, improvements were observed in a number of clinically relevant secondary outcomes following CBT plus standardised medical care when compared with standardised medical care alone. Thus, adults with dissociative seizures might benefit from the addition of dissociative seizure-specific CBT to specialist care from neurologists and psychiatrists. Future work is needed to identify patients who would benefit most from a dissociative seizure-specific CBT approach. FUNDING: National Institute for Health Research, Health Technology Assessment programme

The Black Hole in the Most Massive Ultracompact Dwarf Galaxy M59-UCD3

We examine the internal properties of the most massive ultracompact dwarf galaxy (UCD), M59-UCD3, by combining adaptive optics assisted near-IR integral field spectroscopy from Gemini/NIFS, and Hubble Space Telescope (HST) imaging. We use the multi-band HST imaging to create a mass model that suggests and accounts for the presence of multiple stellar populations and structural components. We combine these mass models with kinematics measurements from Gemini/NIFS to find a best-fit stellar mass-to-light ratio ($M/L$) and black hole (BH) mass using Jeans Anisotropic Models (JAM), axisymmetric Schwarzschild models, and triaxial Schwarzschild models. The best fit parameters in the JAM and axisymmetric Schwarzschild models have black holes between 2.5 and 5.9 million solar masses. The triaxial Schwarzschild models point toward a similar BH mass, but show a minimum $\chi^2$ at a BH mass of $\sim 0$. Models with a BH in all three techniques provide better fits to the central $V_{rms}$ profiles, and thus we estimate the BH mass to be $4.2^{+2.1}_{-1.7} \times 10^{6}$ M$_\odot$ (estimated 1$\sigma$ uncertainties). We also present deep radio imaging of M59-UCD3 and two other UCDs in Virgo with dynamical BH mass measurements, and compare these to X-ray measurements to check for consistency with the fundamental plane of BH accretion. We detect faint radio emission in M59cO, but find only upper limits for M60-UCD1 and M59-UCD3 despite X-ray detections in both these sources. The BH mass and nuclear light profile of M59-UCD3 suggests it is the tidally stripped remnant of a $\sim$10$^{9-10}$ M$_\odot$ galaxy.Comment: 17 pages, 14 figures, 5 table

Role of microstructure in the electron–hole interaction of hybrid lead halide perovskites

Solar cells based on hybrid inorganic-organic halide perovskites have demonstrated high power conversion efficiencies in a range of architectures. The existence and stability of bound electron-hole pairs in these materials, and their role in the exceptional performance of optoelectronic devices, remains a controversial issue. Here we demonstrate, through a combination of optical spectroscopy and multiscale modeling as a function of the degree of polycrystallinity and temperature, that the electron-hole interaction is sensitive to the microstructure of the material. The long-range order is disrupted by polycrystalline disorder and the variations in electrostatic potential found for smaller crystals suppress exciton formation, while larger crystals of the same composition demonstrate an unambiguous excitonic state. We conclude that fabrication procedures and morphology strongly influence perovskite behaviour, with both free carrier and excitonic regimes possible, with strong implications for optoelectronic devices

Safety and pharmacokinetics of multiple dose myo-inositol in preterm infants

BACKGROUND: Preterm infants with respiratory distress syndrome (RDS) given inositol had reduced bronchopulmonary dysplasia (BPD), death and severe retinopathy of prematurity (ROP). We assessed the safety and pharmacokinetics of daily inositol to select a dose providing serum levels previously associated with benefit, and to learn if accumulation occurred when administered throughout the normal period of retinal vascularization. METHODS: Infants ≤ 29 wk GA (n = 122, 14 centers) were randomized and treated with placebo or inositol at 10, 40, or 80 mg/kg/d. Intravenous administration converted to enteral when feedings were established, and continued to the first of 10 wk, 34 wk postmenstrual age (PMA) or discharge. Serum collection employed a sparse sampling population pharmacokinetics design. Inositol urine losses and feeding intakes were measured. Safety was prospectively monitored. RESULTS: At 80 mg/kg/d mean serum levels reached 140 mg/l, similar to Hallman's findings. Levels declined after 2 wk, converging in all groups by 6 wk. Analyses showed a mean volume of distribution 0.657 l/kg, clearance 0.058 l/kg/h, and half-life 7.90 h. Adverse events and comorbidities were fewer in the inositol groups, but not significantly so. CONCLUSION: Multiple dose inositol at 80 mg/kg/d was not associated with increased adverse events, achieves previously effective serum levels, and is appropriate for investigation in a phase III trial