Adopting the RE-AIM analytic framework for rural program evaluation: experiences from the Advance Care Planning via Group Visits (ACP-GV) national evaluation.

Introduction: To support rigorous evaluation across a national portfolio of grants, the United States Department of Veterans Affairs (VA) Office of Rural Health (ORH) adopted an analytic framework to guide their grantees' evaluation of initiatives that reach rural veterans and to standardize the reporting of outcomes and impacts. Advance Care Planning via Group Visits (ACP-GV), one of ORH's Enterprise-Wide Initiatives, also followed the Reach, Effectiveness, Adoption, Implementation, and Maintenance (RE-AIM) framework. ACP-GV is a national patient-centered intervention delivered in a large, veterans integrated healthcare system. This manuscript describes how RE-AIM was used to evaluate this national program and lessons learned from ORH's annual reporting feedback to ACP-GV on their use of the framework to describe evaluation impacts. Methods: We used patient, provider, and site-level administrative health care data from the VA Corporate Data Warehouse and national program management databases for federal fiscal years (FY) spanning October 1, 2018-September 30, 2023. Measures included cumulative and past FY metrics developed to assess program impacts. Results: RE-AIM constructs included the following cumulative and annual program evaluation results. ACP-GV reached 54,167 unique veterans, including 19,032 unique rural veterans between FY 2018 to FY 2023. During FY 2023, implementation adherence to the ACP-GV model was noted in 91.7% of program completers, with 55% of these completers reporting a knowledge increase and 14% reporting a substantial knowledge increase (effectiveness). As of FY 2023, 66 ACP-GV sites were active, and 1,556 VA staff were trained in the intervention (adoption). Of the 66 active sites in FY 2023, 27 were sites previously funded by ORH and continued to offer ACP-GV after the conclusion of three years of seed funding (maintenance). Discussion: Lessons learned developing RE-AIM metrics collaboratively with program developers, implementers, and evaluators allowed for a balance of clinical and scientific input in decision-making, while the ORH annual reporting feedback provided specificity and emphasis for including both cumulative, annual, and rural specific metrics. ACP-GV's use of RE-AIM metrics is a key step towards improving rural veteran health outcomes and describing real world program impacts.

Editorial: The Relationship Between Internalized Racism and Mental Health Symptoms in Black Adolescents.

Since the 1890s, scholars such as W.E.B. DuBois have understood that Black people living under conditions of pervasive White supremacist oppression are subjected to constant assaults on their self-image.1 In the intervening years, Fanon,2 Morrison,3 and many others have described the complex psychological consequences of Black Americans attempting to live and adapt to the dominant culture, which devalues Black lives and Black cultural traditions, and how these devaluing messages reaffirm their inferior status in society. The pioneering doll studies conducted by psychologists Kenneth and Mamie Clark in the 1940s4-in which Black (and White) child participants expressed a preference for White dolls over Black dolls-demonstrated to a broad audience that Black children, by the age of 5 years, understand that being Black is a marker of inferior status. The Clarks' groundbreaking work brought attention to racism's impact on childhood identity development, opening the door for further explorations. The term internalized racism (IR) is widely used today in mental health research to describe how members of racially subordinated groups (eg, Black Americans and people of color) can consciously and unconsciously accept the dominant culture's view of their inferior status and hold associated negative self-evaluations (eg, less beautiful, less intelligent, etc), beginning in the earliest years of life.5.

Switching on emission in Zn(II) coordination complexes by tempering Namido character.

A series of four-coordinate zinc(II) complexes is presented in which the amido vs. imino character of a ligated nitrogen donor correlates to the luminescence intensity. DFT analysis points to a distinct mechanism for this trend wherein emission can be switched on by restricting non-radiative decay pathways through the resonance-induced delocalization of amido ligand lone-pairs.

A National audit of the care of patients with acute kidney injury in England and Wales in 2019 and the association with patient outcomes.

BACKGROUND: Acute kidney injury (AKI) is a common complication of hospitalisations. This national audit assessed the care received by patients with AKI in hospital Trusts in England and Wales. METHODS: Twenty four hospital Trusts across England and Wales took part. Patients with AKI stage2/3 were identified using the UK Renal Registry AKI master patient index. Data was returned through a secure portal with linkage to hospital episode statistic mortality and hospitalisation data. Completion rates of AKI care standards and regional variations in care were established. RESULTS: 989 AKI episodes were included in the analyses. In-hospital 30-day mortality was 31-33.1% (AKI 2/3). Standard AKI interventions were completed in >80% of episodes. Significant inter-hospital variation remained in attainment of AKI care standards after adjustment for age and sex. Recording of urinalysis (41.9%) and timely imaging (37.2%) were low. Information on discharge summaries relating to medication changes/re-commencement and follow-up blood tests associated with reduced mortality. No quality indicators relating to clinical management associated with mortality. Better communication on discharge summaries associated with reduced mortality. CONCLUSIONS: Outcomes for patients with AKI in hospital remain poor. Regional variation in care exists. Work is needed to assess whether improving and standardising care improves patient outcomes.

How Should We Approach Faculty Who Create Hostile Learning Environments for Underrepresented Students and Trainees?

Faculty members who demonstrate resistance to or lack of skill in addressing negative bias in practice and learning environments can erode safety, especially among underrepresented students. This commentary on a case suggests how educators and leaders should respond to problematic behaviors of unwilling or unskilled faculty, prevent mistreatment of students and colleagues, and facilitate continuous faculty development. This commentary also considers strategies for motivating equity and building health care cultures of accountability.

Suicide rates in the UK Armed Forces, compared with the general workforce and merchant shipping during peacetime years since 1900.

INTRODUCTION: The main objective was to compare suicide rates and their trends across the three UK Armed forces (Royal Navy, Army and Royal Air Force) from 1900 to 2020. Further objectives were to compare suicide rates with those in the corresponding general population and in UK merchant shipping and to discuss preventative measures. METHODS: Examination of annual mortality reports and returns, death inquiry files and official statistics. The main outcome measure was the suicide rate per 100 000 population employed. RESULTS: Since 1990, there have been significant reductions in suicide rates in each of the Armed Forces, although a non-significant increase in the Army since 2010. Compared with the corresponding general population, during the most recent decade from 2010 up to 2020, suicide rates were 73% lower in the Royal Air Force, 56% lower in the Royal Navy and 43% lower in the Army. Suicide rates have been significantly decreased in the Royal Air Force since the 1950s, in the Royal Navy since the 1970s and in the Army since the 1980s (comparisons for the Royal Navy and the Army were not available from the late 1940s to the 1960s).During the earliest decades from 1900 to the 1930s, suicide rates in the Armed Forces were mostly quite similar or moderately increased compared with the general population, but far lower than in merchant shipping. Following legislative changes in the last 30 years, suicide rates through poisoning by gases and through firearms or explosives have fallen sharply. CONCLUSIONS: The study shows that suicide rates in the Armed Forces have been lower than in the general population over many decades. The sharp reductions in suicide rates over the last 30 years suggest the effectiveness of recent preventative measures, including reductions in access to a method of suicide and well-being initiatives.

Prevalence and Predictors of Barrett's Esophagus After Negative Initial Endoscopy: Analysis From Two National Databases.

BACKGROUND & AIMS: Guidelines suggest a single screening esophagogastroduodenoscopy (EGD) in patients with multiple risk factors for Barrett's esophagus (BE). We aimed to determine BE prevalence and predictors on repeat EGD after a negative initial EGD, using 2 large national databases (GI Quality Improvement Consortium [GIQuIC] and TriNetX). METHODS: Patients who underwent at least 2 EGDs were included and those with BE or esophageal adenocarcinoma detected at initial EGD were excluded. Patient demographics and prevalence of BE on repeat EGD were collected. Multivariate logistic regression was performed to assess for independent risk factors for BE detected on the repeat EGD. RESULTS: In 214,318 and 153,445 patients undergoing at least 2 EGDs over a median follow-up of 28-35 months, the prevalence of BE on repeat EGD was 1.7% in GIQuIC and 3.4% in TriNetX, respectively (26%-45% of baseline BE prevalence). Most (89%) patients had nondysplastic BE. The prevalence of BE remained stable over time (from 1 to >5 years from negative initial EGD) but increased with increasing number of risk factors. BE prevalence in a high-risk population (gastroesophageal reflux disease plus ≥1 risk factor for BE) was 3%-4%. CONCLUSIONS: In this study of >350,000 patients, rates of BE on repeat EGD ranged from 1.7%-3.4%, and were higher in those with multiple risk factors. Most were likely missed at initial evaluation, underscoring the importance of a high-quality initial endoscopic examination. Although routine repeat endoscopic BE screening after a negative initial examination is not recommended, repeat screening may be considered in carefully selected patients with gastroesophageal reflux disease and ≥2 risk factors for BE, potentially using nonendoscopic tools.

Student- and School-Level Factors Associated With Mental Health and Well-Being in Early Adolescence.

OBJECTIVE: Adolescence is a key developmental window that may determine long-term mental health. As schools may influence mental health of students, this study aimed to examine the association of school-level characteristics with students' mental health over time. METHOD: Longitudinal data from a cluster randomized controlled trial comprising 8,376 students (55% female; aged 11-14 years at baseline) across 84 schools in the United Kingdom were analyzed. Data collection started in the academic years 2016/2017 (cohort 1) and 2017/2018 (cohort 2), with follow-up at 1, 1.5, and 2 years. Students' mental health (risk for depression [Center for Epidemiologic Studies Depression Scale], social-emotional-behavioral difficulties [Strength and Difficulties Questionnaire]) and well-being (Warwick-Edinburgh Mental Well-Being Scale) and relationships with student- and school-level characteristics were explored using multilevel regression models. RESULTS: Mental health difficulties and poorer well-being increased over time, particularly in girls. Differences among schools represented a small but statistically significant proportion of variation (95% CI) in students' mental health at each time point: depression, 1.7% (0.9%-2.5%) to 2.5% (1.6%-3.4%); social-emotional-behavioral difficulties, 1.9% (1.1%-2.7%) to 2.8% (2.1%-3.5%); and well-being, 1.8% (0.9%-2.7%) to 2.2% (1.4%-3.0%). Better student-rated school climate analyzed as a time-varying factor at the student and school level was associated with lower risk of depression (regression coefficient [95%CI] student level: -4.25 [-4.48, -4.01]; school level: -4.28 [-5.81, -2.75]), fewer social-emotional-behavioral difficulties (student level: -2.46 [-2.57, -2.35]; school level: -2.36 [-3.08, -1.63]), and higher well-being (student level: 3.88 [3.70, 4.05]; school-level: 4.28 [3.17, 5.38]), which was a stable relationship. CONCLUSION: Student-rated school climate predicted mental health in early adolescence. Policy and system interventions that focus on school climate may promote students' mental health.

Editorial: Cash Transfers to Families Living in Poverty: Can Benefits for Children Extend to the Next Generation?

Childhood poverty is the most widespread and important modifiable risk factor for the development of a range of health outcomes, including childhood-onset mental health problems.1 In the United States, 30 million children are growing up impoverished, which ranks among the highest per capita rates of child poverty among high-income countries.2 As a nation, the United States does less to support its poor children and their families than any other wealthy country, despite scientific evidence that growing up in poverty significantly increases lifetime risk of physical and mental health problems, reduces likelihood of academic and vocational success, and leads to poorer social outcomes for children.1 Meanwhile, 2 decades of research in low- and middle-income countries has demonstrated that directly providing poor families with financial support (commonly referred to as cash transfer programs)-delivered as one-time lump sum or smaller payments over time-produces reliably positive effects on a range of outcomes, including improved parental mental health, food security, housing security, educational and vocational attainment, female empowerment within families, as well as family savings and ownership of durable goods.3-6 Critics of cash transfer programs, who argue that poor families will exhibit temptation spending patterns (ie, alcohol, entertainment, etc), are increasingly being proven wrong by this literature, as studies have shown that recipient families tend to invest in the supports their children need to thrive.7.

Significant Reduction in the Diagnosis of Barrett's Esophagus and Related Dysplasia During the COVID-19 Pandemic.

INTRODUCTION: The coronavirus disease 19 (COVID-19) pandemic disrupted endoscopy practices, creating unprecedented decreases in cancer screening and surveillance services. We aimed to assess the impact of the pandemic on the proportion of patients diagnosed with Barrett's esophagus (BE) and BE-related dysplasia and adherence to established quality indicators. METHODS: Data from all esophagogastroduodenoscopies in the GI Quality Improvement Consortium, a national repository of matched endoscopy and pathology data, were analyzed from January 2018 to December 2022. Four cohorts were created based on procedure date and COVID-19 data: pre-pandemic (January 2018 to February 2020), pandemic-phase I (March 2020 to July 2020), pandemic-phase II (August 2020 to May 2021), and pandemic-phase III (June 2021 to December 2022). Observed and expected number of BE and BE-related dysplasia cases per month and adherence to the Seattle biopsy protocol and recommended surveillance intervals for nondysplastic BE (NDBE) were evaluated. RESULTS: Among 2,446,857 esophagogastroduodenoscopies performed during the study period, 104,124 (4.3%) had pathology-confirmed BE. The histologic distribution was 87.4% NDBE, 1.8% low-grade dysplasia, 2.4% indefinite for dysplasia, and 1.4% high-grade dysplasia. The number of monthly BE (-47.9% pandemic-phase I, -21.5% pandemic-phase II, and -19.0% pandemic-phase III) and BE-related dysplasia (high-grade dysplasia: 41.2%, -27.7%, and -19.0%; low-grade dysplasia: 49.1%, -35.3%, and -26.5%; any dysplasia: 46.7%, -32.3%, and -27.9%) diagnoses were significantly reduced during the pandemic phases compared with pre-pandemic data. Adherence rates to the Seattle protocol and recommended surveillance intervals for NDBE did not decline during the pandemic. DISCUSSION: There was a significant decline in the number of BE and BE-related dysplasia diagnoses during the COVID-19 pandemic, with an approximately 50% reduction in the number of cases of dysplasia diagnosed in the early pandemic. The absence of a compensatory increase in diagnoses in the pandemic-phase II and III periods may result in deleterious downstream effects on esophageal adenocarcinoma morbidity and mortality.

An international simulated-use study to assess nurses' preferences between two lanreotide syringes for patients with neuroendocrine tumours or acromegaly (PRESTO 3).

PURPOSE: PRESTO 3 evaluated nurses' preference for the Somatuline® Autogel® syringe versus the Lanreotide Pharmathen syringe after injection-pad testing. METHODS: This international simulated-use study included oncology/endocrinology nurses with ≥ 1 years' experience in managing neuroendocrine tumours (NETs) and/or acromegaly. Each nurse tested both syringes twice in a randomised order before completing an electronic survey. The primary objective was to assess overall preference (%, 95% confidence interval [CI]) for the Somatuline Autogel syringe versus the Lanreotide Pharmathen syringe. Secondary objectives included rating syringe performance and ranking the importance of syringe attributes. RESULTS: Ninety-four nurses were enrolled: mean age, 41.0 (SD, 11.5) years. The percentage of nurses stating a preference ("strong" or "slight") for the Somatuline Autogel syringe (86.2% [95% CI 77.5-92.4%]) was significantly higher than 50% (p < 0.0001). Performance rating was significantly higher for the Somatuline Autogel syringe versus Lanreotide Pharmathen syringe for 10 of the 11 attributes tested (p < 0.05). The syringe attributes considered most important when injecting patients in routine clinical practice were "easy to use from preparation to injection" (30.9%) and "comfortable to handle during use from preparation to injection" (16.0%). The attribute most commonly rated as least important was "fast administration from preparation to injection" (26.6%). CONCLUSION: Nurses strongly preferred the user experience of the Somatuline Autogel syringe over the Lanreotide Pharmathen syringe. "Ease of use" and "comfortable to handle" were the most important syringe attributes, and performance rating was significantly higher with Somatuline Autogel versus Lanreotide Pharmathen syringe for all but one attribute.

Drugs called somatostatin analogues (SSAs) can be used to treat patients with neuroendocrine tumours or acromegaly over a prolonged period of time. SSAs are given as injections and act by slowing the production of hormones by the body and in some cases reducing the growth of the tumour. To help to provide the best care possible, it is important that the syringe used for the injection is easy to use and delivers the SSA effectively. Somatuline Autogel is a syringe that can be used to inject an SSA called lanreotide. Previous studies showed that patients and nurses preferred the injection experience when using the Somatuline Autogel syringe compared with a syringe used to inject another SSA called octreotide long-acting release. A new syringe used for lanreotide injections has been developed recently by a company called Pharmathen. In the PRESTO 3 study, we compared the user experience of the Somatuline Autogel syringe and the Lanreotide Pharmathen syringe. We asked 94 nurses from Europe and the US to test both syringes, in a randomised order, using injection pads, and then to answer questions about their overall preference between the two syringes and how well the syringe performed for a set of syringe features. Overall, 86% of nurses preferred the Somatuline Autogel syringe over the Lanreotide Pharmathen syringe. Of the 11 features of the syringe that we assessed, 10 were rated higher for the Somatuline Autogel syringe than the Lanreotide Pharmathen syringe. The syringe features "ease of use" and "comfortable to handle" were considered the most important. The results of the PRESTO 3 study indicated that there is a difference in the user experience between the syringes, particularly for confidence and ease of use, and that it is important to offer syringe choices to nurses who are using SSA injections to treat patients.

A biomechanical assessment of tissue-engineered polymer neo-uteri after orthotopic implantation.

OBJECTIVE: To assess the in vivo biomechanical maturation of tissue-engineered neo-uteri that have previously supported live births in a rabbit model. DESIGN: Nonclinical animal study. SETTING: University-based research laboratory. ANIMALS: Eighteen adult female rabbits. INTERVENTION: Biodegradable poly-DL-lactide-co-glycolide-coated polyglycolic acid scaffolds seeded with autologous uterine-derived endometrial and myometrial cells. Nonseeded scaffolds and seeded, tissue-engineered neo-uteri were implanted into one uterine horn of rabbits for 1, 3, or 6 months, excised, and biomechanically assessed in comparison to native uterine tissue. MAIN OUTCOME MEASURES: Tensile stress-relaxation testing, strain-to-failure testing, and viscoelastic modeling. RESULTS: By evaluating the biomechanical data with several viscoelastic models, it was revealed that tissue-engineered uteri were more mechanically robust than nonseeded scaffolds. For example, the 10% instantaneous stress of the tissue-engineered neo-uteri was 2.1 times higher than the nonseeded scaffolds at the 1-month time point, 1.6 times higher at the 3-month time point, and 1.5 times higher at the 6-month time point. Additionally, as the duration of implantation increased, the engineered constructs became more mechanically robust (e.g., 10% instantaneous stress of the tissue-engineered neo-uteri increased from 22 kPa at 1 month to 42 kPa at 6 months). Compared with native tissue values, tissue-engineered neo-uteri achieved or surpassed native tissue values by the 6-month time point. CONCLUSION: The present study evaluated the mechanical characteristics of novel tissue-engineered neo-uteri that have previously been reported to support live births in the rabbit model. We demonstrate that the biomechanics of these implants closely resemble those of native tissue, giving further credence to their development as a clinical solution to uterine factor infertility.

Thermally activated delayed fluorescence in a deep red dinuclear iridium(iii) complex: a hidden mechanism for short luminescence lifetimes.

The high luminescence efficiency of cyclometallated iridium(iii) complexes, including those widely used in OLEDs, is typically attributed solely to the formally spin-forbidden phosphorescence process being facilitated by spin-orbit coupling with the Ir(iii) centre. In this work, we provide unequivocal evidence that an additional mechanism can also participate, namely a thermally activated delayed fluorescence (TADF) pathway. TADF is well-established in other materials, including in purely organic compounds, but has never been observed in iridium complexes. Our findings may transform the design of iridium(iii) complexes by including an additional, faster fluorescent radiative decay pathway. We discover it here in a new dinuclear complex, 1, of the form [Ir(N^C)2]2(µ-L), where N^C represents a conventional N^C-cyclometallating ligand, and L is a bis-N^O-chelating bridging ligand derived from 4,6-bis(2-hydroxyphenyl)-pyrimidine. Complex 1 forms selectively as the rac diastereoisomer upon reaction of [Ir(N^C)2(µ-Cl)]2 with H2L under mild conditions, with none of the alternative meso isomer being separated. Its structure is confirmed by X-ray diffraction. Complex 1 displays deep-red luminescence in solution or in polystyrene film at room temperature (λem = 643 nm). Variable-temperature emission spectroscopy uncovers the TADF pathway, involving the thermally activated re-population of S1 from T1. At room temperature, TADF reduces the photoluminescence lifetime in film by a factor of around 2, to 1 µs. The TADF pathway is associated with a small S1-T1 energy gap ΔEST of approximately 50 meV. Calculations that take into account the splitting of the T1 sublevels through spin-orbit coupling perfectly reproduce the experimentally observed temperature-dependence of the lifetime over the range 20-300K. A solution-processed OLED comprising 1 doped into the emitting layer at 5 wt% displays red electroluminescence, λEL = 625 nm, with an EQE of 5.5% and maximum luminance of 6300 cd m-2.

Choice of gDNA isolation method has a significant impact on average murine Telomere Length estimates.

Telomere Length (TL) and integrity is significantly associated with age-related disease, multiple genetic and environmental factors. We observe mouse genomic DNA (gDNA) isolation methods to have a significant impact on average TL estimates. The canonical qPCR method does not measure TL directly but via the ratio of telomere repeats to a single copy gene (SCG) generating a T/S ratio. We use a monochromatic-multiplex-qPCR (mmqPCR) method which multiplexes the PCR and enables quantification of the target and the single copy gene within the same qPCR reaction. We demonstrate that TL measurements, from murine gDNA, isolated via Spin Columns (SC) and Magnetic Beads (MB), generate significantly smaller T/S ratios compared to gDNA isolated via traditional phenol/chloroform methods. The former methods may impede correct TL estimation by producing non representative fragment sets and reducing qPCR efficacy. This work highlights discrepancies in TL measurements due to different extraction techniques. We recommend the use of gDNA isolation methods that are shown to preserve DNA length and integrity, such as phenol/chloroform isolation. We propose that widely used high throughput DNA isolation methodologies can create spurious associations within a sample set, thus creating misleading data. We suggest that published TL associations should be revisited in the light of these data.

Head injury in older adults presenting to the ambulance service: who do we convey to the emergency department, and what clinical variables are associated with an intracranial bleed? A retrospective case-control study.

OBJECTIVE: Most older adults with traumatic brain injuries (TBI) reach the emergency department via the ambulance service. Older adults, often with mild TBI symptoms, risk being under-triaged and facing poor outcomes. This study aimed to identify whether sufficient information is available on the scene to an ambulance clinician to identify an older adult at risk of an intracranial haemorrhage following a head injury. METHODS: This was a retrospective case-control observational study involving one regional ambulance service in the UK and eight emergency departments. 3545 patients aged 60 years and over presented to one regional ambulance service with a head injury between the 1st of January 2020 and the 31st of December 2020. The primary outcome was an acute intracranial haemorrhage on head computed tomography (CT) scan in patients conveyed to the emergency department (ED). A secondary outcome was factors associated with conveyance to the ED by the ambulance clinician. RESULTS: In 2020, 2111 patients were conveyed to the ED and 162 patients were found to have an intracranial haemorrhage on their head CT scan. Falls from more than 2 m (adjusted odds ratio (aOR) 3.45, 95% CI 1.78-6.40), chronic kidney disease (CKD) (aOR 2.80, 95% CI 1.25-5.75) and Clopidogrel (aOR 1.98, 95% CI 1.04-3.59) were associated with an intracranial haemorrhage. Conveyance to the ED was associated with patients taking anticoagulant and antiplatelet medication or a visible head injury or head injury symptoms. CONCLUSION: This study highlights that while most older adults with a head injury are conveyed to the ED, only a minority will have an intracranial haemorrhage following their head injury. While mechanisms of injury such as falls from more than 2 m remain a predictor, this work highlights that Clopidogrel and CKD are also associated with an increased odds of tICH in older adults following a head injury. These findings may warrant a review of current ambulance head injury guidelines.

Mn-porphyrins in a four-helix bundle participate in photo-induced electron transfer with a bacterial reaction center.

Hybrid complexes incorporating synthetic Mn-porphyrins into an artificial four-helix bundle domain of bacterial reaction centers created a system to investigate new electron transfer pathways. The reactions were initiated by illumination of the bacterial reaction centers, whose primary photochemistry involves electron transfer from the bacteriochlorophyll dimer through a series of electron acceptors to the quinone electron acceptors. Porphyrins with diphenyl, dimesityl, or fluorinated substituents were synthesized containing either Mn or Zn. Electrochemical measurements revealed potentials for Mn(III)/Mn(II) transitions that are ~ 0.4 V higher for the fluorinated Mn-porphyrins than the diphenyl and dimesityl Mn-porphyrins. The synthetic porphyrins were introduced into the proteins by binding to a four-helix bundle domain that was genetically fused to the reaction center. Light excitation of the bacteriochlorophyll dimer of the reaction center resulted in new derivative signals, in the 400 to 450 nm region of light-minus-dark spectra, that are consistent with oxidation of the fluorinated Mn(II) porphyrins and reduction of the diphenyl and dimesityl Mn(III) porphyrins. These features recovered in the dark and were not observed in the Zn(II) porphyrins. The amplitudes of the signals were dependent upon the oxidation/reduction midpoint potentials of the bacteriochlorophyll dimer. These results are interpreted as photo-induced charge-separation processes resulting in redox changes of the Mn-porphyrins, demonstrating the utility of the hybrid artificial reaction center system to establish design guidelines for novel electron transfer reactions.

2†Pathways to detection of non-infectious childhood uveitis in the UK: findings from the UNICORN cohort study.

INTRODUCTION: Prompt detection of childhood uveitis is key to minimising negative impact. From an internationally unique inception cohort, we report pathways to disease detection.UNICORNS is a national childhood non-infectious uveitis study with longitudinal collection of a standardised clinical dataset and patient reported outcomes. Descriptive analysis of baseline characteristics are reported.Amongst 150 recruited children (51% female, 31% non-white ethnicity) age at detection ranged from 2-18yrs (median 10). In 69%, uveitis was diagnosed following onset of symptoms: time from first symptoms to uveitis detection ranged from 0-739days (median 7days), with longer time to detection for those presenting initially to their general practitioner. Non symptomatic children were detected through JIA/other disease surveillance (16%), routine optometry review (5%) or child visual health screening (1%). Commonest underlying diagnoses at uveitis detection were JIA (17%), TINU (9%, higher than pre-pandemic reported UK disease frequency) and sarcoid (1%). 60% had no known systemic disease at uveitis detection. At disease detection, in at least one eye: 34% had structural complications (associated with greater time to detection - 17 days versus 4 days for uncomplicated presentation).The larger relative proportions of children with non-JIA uveitis reported here increase the importance of improving awareness of childhood uveitis amongst the wider clinical communities. There is scope for improvement of pathways to detection. Forthcoming analysis on the full cohort (251 recruited to date across 33 hospitals and 4 nations) will provide nationally representative data on management and the determinants of visual and broader developmental/well-being outcomes.

Positron re-emission, reflection, and diffraction from W(100) surface at very low energies.

The energy distributions of scattered and re-emitted low-energy positrons from a W(100) surface were measured as a function of incident positron energy from 0 to 25 eV. Given that tungsten has a negative work function of about -3 eV for positrons, one can envisage three scenarios of very low-energy positron scattering from such a surface. First, a positron approaching the sample surface with energy say 1 eV above the vacuum level will see a potential barrier of about 2 eV height and will be reflected back to the vacuum. Second, when the energy of incident positrons increases up to the top of the surface potential barrier (positron work function), they start entering the solid and, therefore, the reflectivity of positrons from the surface reduces. Positrons entering the solid are thermalised within few picoseconds and have a chance to escape back to the vacuum with kinetic energy about 3 eV above the vacuum level undergoing so-calledre-emission. Third, coherent scattering of low-energy positrons may occur on the crystal surface, i.e. positron diffraction. All the three scenarios of low-energy positrons scattering are studied here experimentally. Measured spectra are very sensitive to the surface conditions of the sample: they change dramatically after surface oxidation or thin film deposition.

Neurodevelopmental outcomes in children and adults with Fetal Valproate Spectrum Disorder: A contribution from the ConcePTION project.

AIM: To describe the neurodevelopmental phenotype of older children and adults with a diagnosis of Fetal Valproate Spectrum Disorder (FVSD). METHODS: In this cross-sectional study, 90 caregivers were recruited and completed a series of questionnaires regarding the neurodevelopmental outcomes of 146 individuals aged 7-37 years (M = 18.1), including individuals with a formal diagnosis of FVSD (n = 99), individuals exposed to Valproate but without an FVSD diagnosis (n = 24), and individuals not exposed to Valproate (N = 23). The mean dose of valproate exposure for individuals with an FVSD diagnosis was 1470 mg/day. RESULTS: Individuals with a diagnosis of FVSD showed significantly higher levels of moderate (43.4%) and severe (14.4%) cognitive impairment than other groups (p = 0.003), high levels of required formal educational support (77.6%), and poorer academic competence than individuals not exposed to Valproate (p = 0.001). Overall psychosocial problems (p = 0.02), internalising problems (p = 0.05) and attention problems (p = 0.001), but not externalising problems, were elevated in individuals with a diagnosis of FVSD. Rates of neurodevelopmental disorders, particularly autistic spectrum disorders (62.9%) and sensory problems (80.6%) are particularly central to the FVSD phenotype. There was no evidence of a statistical dose-dependent effect, possibly due to the high mean dose of exposure having a uniformly negative impact across the sample. Individuals with FVSD had required a significant number of health and child development services. INTERPRETATION: Children and young adults with a diagnosis of FVSD are at an increased risk of a range of altered neurodevelopmental outcomes, highlighting the need for a multidisciplinary approach to clinical management across the lifespan.

Efficiency of charge transfer in changing the dissociation dynamics of OD+ transients formed after the photo-fragmentation of D2O.

We present an investigation of the relaxation dynamics of deuterated water molecules after direct photo-double ionization at 61 eV. We focus on the very rare D+ + O+ + D reaction channel in which the sequential fragmentation mechanisms were found to dominate the dynamics. Aided by theory, the state-selective formation and breakup of the transient OD+(a1Δ, b1Σ+) is traced, and the most likely dissociation path-OD+: a1Δ or b1Σ+ → A 3Π â†’ X 3Σ- → B 3Σ--involving a combination of spin-orbit and non-adiabatic charge transfer transitions is determined. The multi-step transition probability of this complex transition sequence in the intermediate fragment ion is directly evaluated as a function of the energy of the transient OD+ above its lowest dissociation limit from the measured ratio of the D+ + O+ + D and competing D+ + D+ + O sequential fragmentation channels, which are measured simultaneously. Our coupled-channel time-dependent dynamics calculations reproduce the general trends of these multi-state relative transition rates toward the three-body fragmentation channels.