A study protocol to characterise pathophysiological and molecular markers of rheumatic heart disease and degenerative aortic stenosis using multiparametric cardiovascular imaging and multiomics techniques.

INTRODUCTION: Rheumatic heart disease (RHD), degenerative aortic stenosis (AS), and congenital valve diseases are prevalent in sub-Saharan Africa. Many knowledge gaps remain in understanding disease mechanisms, stratifying phenotypes, and prognostication. Therefore, we aimed to characterise patients through clinical profiling, imaging, histology, and molecular biomarkers to improve our understanding of the pathophysiology, diagnosis, and prognosis of RHD and AS. METHODS: In this cross-sectional, case-controlled study, we plan to recruit RHD and AS patients and compare them to matched controls. Living participants will undergo clinical assessment, echocardiography, CMR and blood sampling for circulatory biomarker analyses. Tissue samples will be obtained from patients undergoing valve replacement, while healthy tissues will be obtained from cadavers. Immunohistology, proteomics, metabolomics, and transcriptome analyses will be used to analyse circulatory- and tissue-specific biomarkers. Univariate and multivariate statistical analyses will be used for hypothesis testing and identification of important biomarkers. In summary, this study aims to delineate the pathophysiology of RHD and degenerative AS using multiparametric CMR imaging. In addition to discover novel biomarkers and explore the pathomechanisms associated with RHD and AS through high-throughput profiling of the tissue and blood proteome and metabolome and provide a proof of concept of the suitability of using cadaveric tissues as controls for cardiovascular disease studies.

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.

Pinch Grafting: A Systematic Review of Modern Perspectives and Applications in Dermatologic Surgery and Wound Healing.

BACKGROUND: Pinch grafting has experienced a resurgence in interest in recent years, stemming from its simplicity, safety, and potential in restoring tissue integrity. While historically employed for chronic nonhealing wounds, pinch grafts have shown promise following surgical procedures, particularly those involving the lower extremities. OBJECTIVE: To systematically review the literature and present an updated overview of the current applications of pinch grafting. METHODS: A systematic review was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. In collaboration with a medical reference librarian, the PubMed, Embase, Scopus, and Web of Science databases were searched for studies reporting on the use of pinch grafting from 2000 onward. The references of each included article were also screened. RESULTS: Ten articles met final inclusion criteria. In total, 300 patients underwent pinch grafting for treatment of skin ulceration, while an additional 35 cases were performed as an alternative to primary closure following skin cancer resection. Overall, pinch grafting was safe and well tolerated, with minimal adverse outcomes reported. CONCLUSION: Pinch grafting is a safe, straightforward, and effective technique to promote the healing of chronic wounds. While the procedure shows early promise in emerging applications within dermatologic surgery, only about 10% of the reported cases involved this indication, reflecting a need for further research in this area.

The development and diversity of religious cognition and behavior: Protocol for Wave 1 data collection with children and parents by the Developing Belief Network.

The Developing Belief Network is a consortium of researchers studying human development in diverse social-cultural settings, with a focus on the interplay between general cognitive development and culturally specific processes of socialization and cultural transmission in early and middle childhood. The current manuscript describes the study protocol for the network's first wave of data collection, which aims to explore the development and diversity of religious cognition and behavior. This work is guided by three key research questions: (1) How do children represent and reason about religious and supernatural agents? (2) How do children represent and reason about religion as an aspect of social identity? (3) How are religious and supernatural beliefs transmitted within and between generations? The protocol is designed to address these questions via a set of nine tasks for children between the ages of 4 and 10 years, a comprehensive survey completed by their parents/caregivers, and a task designed to elicit conversations between children and caregivers. This study is being conducted in 39 distinct cultural-religious groups (to date), spanning 17 countries and 13 languages. In this manuscript, we provide detailed descriptions of all elements of this study protocol, give a brief overview of the ways in which this protocol has been adapted for use in diverse religious communities, and present the final, English-language study materials for 6 of the 39 cultural-religious groups who are currently being recruited for this study: Protestant Americans, Catholic Americans, American members of the Church of Jesus Christ of Latter-day Saints, Jewish Americans, Muslim Americans, and religiously unaffiliated Americans.

Penile fibrosis-still scarring urologists today: a narrative review.

Background and Objective: Implantation of penile prosthesis (PP) into scarred and fibrotic corpora can be a difficult challenge. In this review article, we provide a review of penile fibrosis, discuss current medical and surgical management and summarize preventative strategies. Methods: In this study, we searched PubMed between the years 2000-2023 for publications with search strategy: "penile fibrosis" OR "scarred corpora" OR "fibrosed corpora". Key Content and Findings: This search returned a total of 137 articles. We examine the evidence for preoperative patient evaluation and penile ultrasound (US), oral phosphodiesterase-5 inhibitors, pentoxifylline, and L-arginine, vacuum device therapy and the use of surgical approaches and tools in the context of complex penile fibrosis cases. Severe penile fibrosis is most associated with priapism and infection. Estimating the degree of fibrosis via preoperative US may help set realistic patient expectations. Phosphodiesterase inhibitors and L-arginine reduce fibrosis in animal models however their impact in humans remains unclear despite theoretical advantage for their use. Vacuum device therapy may preserve penile length following priapism and infected PP cases. The use of Coloplast Narrow-Based or AMS-700 CXR implants are used primarily for severe fibrosis. Various surgical excisional/incisional techniques, the Carrion-Rossello, Mooreville Uramix cavernotomes and reverse cutting scissors are all options, and their use varies from case to case. Finally, prevention of penile fibrosis in patients with history of penile implant infection and the safety of early implantation of a penile implant in patients with refractory priapism is encouraged. Conclusions: The management of penile fibrosis remains a challenge but there are multiple options to assist clinicians. Complex cases should be managed and studied at high volume centers.

Bidding against the wind: A choice experiment in green energy, green jobs and offshore views in North Carolina, USA.

Offshore wind development is in its nascent stages in the United States. Recent research indicates that the visual impacts of offshore wind farms are viewed negatively by the general population. This North Carolina application is the first US-focused discrete choice experiment that explicitly asks respondents to consider the positive local and global benefits from offshore wind development, such as job creation and greenhouse gas emission reductions, simultaneously with their visual impacts. We find significant willingness to pay (WTP) for reducing the visual impacts of offshore wind farms, and that the extent of disamenity varies in the population and with placement along developed tourist towns (as much as $783/year for three years) or preserved coastlines (as much as $451/year for three years). We also find that some preference classes value projects that create permanent jobs and reduce carbon emissions. We use our estimates of preferences for the positive and negative attributes to explore specific wind farm configurations and locations that could achieve positive consensus in a heterogenous population.

A hypomorphic variant of choroideremia is associated with a novel intronic mutation that leads to exon skipping.

INTRODUCTION: Molecular confirmation of pathogenic sequence variants in the CHM gene is required prior to enrolment in retinal gene therapy clinical trials for choroideremia. Individuals with mild choroideremia have been reported. The molecular basis of genotype-phenotype associations is of clinical relevance since it may impact on selection for retinal gene therapy. METHODS AND MATERIALS: Genetic testing and RNA analysis were undertaken in a patient with mild choroideremia to confirm the pathogenicity of a novel intronic variant in CHM and to explore the mechanism underlying the mild clinical phenotype. RESULTS: A 42-year-old male presented with visual field loss. Fundoscopy and autofluorescence imaging demonstrated mild choroideremia for his age. Genetic analysis revealed a variant at a splice acceptor site in the CHM gene (c.1350-3C > G). RNA analysis demonstrated two out-of-frame transcripts, suggesting pathogenicity, without any detectable wildtype transcripts. One of the two out-of-frame transcripts is present in very low levels in healthy controls. DISCUSSION: Mild choroideremia may result from +3 or -3 splice site variants in CHM. It is presumed that the resulting mRNA transcripts may be partly functional, thereby preventing the development of the null phenotype. Choroideremia patients with such variants may present challenges for gene therapy since there may be residual transcript activity which could result in long-lasting visual function which is atypical for this disease.

Hypomorphic CDHR1 variants may result in retinitis pigmentosa with relative preservation of cone function.

PURPOSE: Retinitis pigmentosa (RP) associated with biallelic variants in CDHR1 has rarely been reported, and detailed phenotyping data are not available. RP implies relative preservation of foveal cones, when compared to cone-rod dystrophy associated with biallelic null variants in CDHR1. We hypothesize that RP may occur in association with one or more hypomorphic CDHR1 alleles. MATERIALS AND METHODS: Retrospective report of a 48-year-old patient with CDHR1-associated RP with a hypomorphic missense variant c.562 G>A, p. (Gly188Ser) and a novel, unreported variant affecting a canonical splice acceptor site (c.784-1 G>C). Clinical examination, multimodal retinal imaging, electroretinography, visual field testing, and mesopic microperimetry were undertaken 8 years apart. Scotopic microperimetry was also performed. The DNA sequence context of the variants was examined to identify theoretical CRISPR-Cas9 base-editing strategies. RESULTS: The patient presented at 35 years with a 12-year history of nyctalopia. His best corrected visual acuity was 20/20. Clinical presentation, multimodal retinal imaging studies, electroretinography, and mesopic microperimetry were typical of a progressive rod-cone dystrophy (i.e. classic RP). There were no scotomas within the central field as would be expected at this age in CDHR1-associated cone-rod dystrophy. Scotopic microperimetry suggested some preservation of macular cone over rod function, although both were severely impaired. A suitable CRISPR adenine base editor was identified that could theoretically correct the missense variant c.562 G>A, p. (Gly188Ser). CONCLUSIONS: CDHR1-associated RP shows a relative preservation of cone function in the presence of a presumed hypomorphic allele and may be considered a hypomorphic disease phenotype. Further work is required to identify modifying factors that determine disease phenotype since macular dystrophy, with relative sparing of rods, may also occur with hypomorphic CDHR1 alleles.

Ethical and Practical Considerations of Perimortem Gamete Procurement for Palliative Care Providers.

Requests for perimortem gamete procurement (PGP) typically arise by a surrogate decision maker after the unexpected death or incapacitation of a reproductive-aged individual. Palliative care clinicians should have a working knowledge of the medical, ethical, and practical considerations pertaining to such requests. In this paper, we describe a case in which the PGP request originated from an incapacitated patient's parents. We review the technologies associated with PGP and posthumous assisted reproduction (PAR) and discuss the ethical and legal issues involved in such cases, including recent position statements from national and international reproductive health groups. Finally, we provider readers with a stepwise approach for considering requests for PGP.

Liposomal and Nonliposomal Bupivacaine for Mohs Surgery: A Systematic Review.

BACKGROUND: Lidocaine is the most commonly used local anesthetic for Mohs micrographic surgery (MMS), but given its limited half-life, postoperative pain remains a significant concern for patients. Bupivacaine is used in various surgical subspecialty procedures and has demonstrated improved pain control compared with lidocaine. However, its role in MMS is insufficiently explored. OBJECTIVE: To systematically review the current literature for reports on use of bupivacaine, traditional nonliposomal and newer liposomal formulations, for MMS. METHODS: A systematic review was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses 2020 guidelines. The MEDLINE, PubMed, and EMBASE databases were queried for articles presenting original data on the use of bupivacaine for MMS. RESULTS: Of 483 potentially relevant articles, 3 studies met final inclusion criteria, capturing a total of 253 patients involved in primary investigations comparing bupivacaine to traditional local anesthesia for MMS. Bupivacaine was well-tolerated and associated with comparable or modestly reduced intraoperative and postoperative pain and opioid use. CONCLUSION: Bupivacaine may have a role in prolonging intraoperative anesthesia, reducing acute postoperative pain, and reducing postoperative opioid use after MMS. However, large, prospective studies are needed to solidify the generalizability and clinical utility of these findings.

3D Acoustic Wave Sparsely Activated Localization Microscopy With Phase Change Contrast Agents.

OBJECTIVE: The aim of this study is to demonstrate 3-dimensional (3D) acoustic wave sparsely activated localization microscopy (AWSALM) of microvascular flow in vivo using phase change contrast agents (PCCAs). MATERIALS AND METHODS: Three-dimensional AWSALM using acoustically activable PCCAs was evaluated on a crossed tube microflow phantom, the kidney of New Zealand White rabbits, and the brain of C57BL/6J mice through intact skull. A mixture of C 3 F 8 and C 4 F 10 low-boiling-point fluorocarbon gas was used to generate PCCAs with an appropriate activation pressure. A multiplexed 8-MHz matrix array connected to a 256-channel ultrasound research platform was used for transmitting activation and imaging ultrasound pulses and recording echoes. The in vitro and in vivo echo data were subsequently beamformed and processed using a set of customized algorithms for generating 3D super-resolution ultrasound images through localizing and tracking activated contrast agents. RESULTS: With 3D AWSALM, the acoustic activation of PCCAs can be controlled both spatially and temporally, enabling contrast on demand and capable of revealing 3D microvascular connectivity. The spatial resolution of the 3D AWSALM images measured using Fourier shell correlation is 64 µm, presenting a 9-time improvement compared with the point spread function and 1.5 times compared with half the wavelength. Compared with the microbubble-based approach, more signals were localized in the microvasculature at similar concentrations while retaining sparsity and longer tracks in larger vessels. Transcranial imaging was demonstrated as a proof of principle of PCCA activation in the mouse brain with 3D AWSALM. CONCLUSIONS: Three-dimensional AWSALM generates volumetric ultrasound super-resolution microvascular images in vivo with spatiotemporal selectivity and enhanced microvascular penetration.

Application of motivational interviewing to group: Teaching advance care planning via group visits for clinical professionals.

OBJECTIVE: Advance Care Planning (ACP) via Group Visits (ACP-GV) is an innovative patient-centered intervention used in the United States Department of Veterans Affairs (VA) healthcare system. The goal of ACP-GV is to spread ACP to veterans and caregivers in medically underserved rural areas. Veterans, caregivers and those they trust participate in a group led by clinicians in Veterans Health Administration healthcare and/or community-based settings. To learn how to facilitate ACP-GV, clinicians attend ACP-GV training. The training teaches the ACP-GV group model and the theoretical components of Motivational Interviewing (MI) (Rollnick & Miller, 1995), which are used to empower participants to have conversations about their healthcare values and preferences. Therefore, the aim is to describe the specific MI techniques utilized by group facilitators in the innovative ACP-GV intervention. DISCUSSION: We provide exemplars for how group facilitators apply the MI techniques to the group discussion with participants. Lastly, we provide a scripted case example of a coded MI-concordant session of ACP-GV delivered with veterans in a healthcare setting that can be used in future training and education for clinicians interested in facilitating ACP using a group modality. CONCLUSION: MI is a key aspect of delivering ACP-GV, a high-quality, patient-centered intervention for veterans, caregivers and those they trust.

Empatía, agresividad y perdón en contextos de vulnerabilidad, hostilidad y seguridad en niños y adolescentes

Introducción: El objetivo de este artículo fue identificar las variables que mejor predicen las medidas de agresión, empatía y perdón, como también las principales diferencias en contextos vulnerables, hostiles y seguros, en una muestra de niños, niñas y adolescentes pertenecientes a una población vulnerable. Método: se realizó un estudio cuantitativo transversal con una muestra no probabilística incidental de 85 participantes, se emplearon medidas psicométricas para la empatía, agresión y perdón. Los participantes fueron convocados en una fundación de atención a víctimas para realizar una entrevista y aplicar el test. Resultados: Se encontraron efectos estadísticamente significativos entre las variables del modelo verificado, donde la empatía predice la agresión en el contexto hostil, pero no en el vulnerable y seguro. A su vez, la empatía predice el perdón en los contextos vulnerables y seguros, y la agresión predice el perdón en el modelo hostil, pero no es significativo su efecto en el contexto vulnerable y seguro. Además, la empatía tiene un papel clave en la comprensión del perdón, dado que se asocia a conductas agresivas en los contextos de hostilidad, mientras que un modelo de perdón debería ser diferencial en estos contextos. Conclusiones: Los hallazgos de este estudio brindan evidencia empírica que sustenta la importancia de la implementación de estrategias para mejorar las habilidades relacionadas con la empatía en niños y adolescentes, desde la perspectiva de la educación para la paz y el perdón. Además, se demostró que los aspectos como el clima familiar, las vulnerabilidades de los contextos de riesgo y la misma cultura, pueden determinar el desarrollo de habilidades socioemocionales que favorecen el perdón, empatía y otras capacidades interpersonales.

Introduction: The aim of this study was to identify the variables that best predict measures of aggression, empathy, and forgiveness, as well as the main differences in vulnerable, hostile and safe contexts, in a sample of children and adolescents belonging to a vulnerable population. Method: A cross-sectional quantitative study was conducted with a non-probabilistic incidental sample of 85 participants. Psychometric measures of empathy, aggression, and forgiveness were used. The participants were invited to a victim assistance foundation for an interview and test application. Results: Statistically significant effects were found among the variables in the verified model, where empathy predicts aggression in the hostile context, but not in the vulnerable and safe context. In turn, empathy predicts forgiveness in the vulnerable and safe contexts, and aggression predicts forgiveness in the hostile model, but its effect in the vulnerable and safe context is not significant. Furthermore, empathy plays a key role in understanding forgiveness, given that it is associated with aggressive behaviors in the hostile contexts, whereas a forgiveness model should be differential in these contexts. Conclusions: The findings of this study provide empirical evidence that supports the importance of implementing strategies to improve empathy-related skills in children and adolescents, from the perspective of peace education and forgiveness. In addition, it was shown that aspects such as family climate, vulnerabilities of risk contexts and culture itself, can determine the development of socioemotional skills that favor forgiveness, empathy, and other interpersonal skills.

Addressing Burnout in the Primary Care Setting: The Impact of an Evidence-Based Mindfulness Toolkit.

BACKGROUND: Burnout is insidious and manifests over prolonged, repeated exposure to occupational stressors. There is a growing crisis among health care workers (HCWs) due to high levels of burnout and associated adverse outcomes. Identifying and addressing burnout can be problematic due to extensive variances of perceived occupational stressors across HCWs. PURPOSE: Mindfulness-based training can enhance individual HCWs' abilities to perceive and constructively respond to stresses endemic in the health care environment. It can reduce the prevalence of burnout in the primary care setting. An evidence-based multimodal Mindfulness-Based Stress Reduction toolkit (MBSR TK) was designed, implemented, and evaluated for its impact on HCWs' self-reported stress levels (SRSL). IMPLEMENTATION STRATEGIES: A pre-post-program evaluation explored the impact of a multimodal toolkit program on HCW SRSL with the Mini-Z burnout survey (MZBS). The MBSR TK program, consisting of a 45 minute introduction and 4 biweekly 15 minute mindfulness sessions offering acupressure, meditation, journaling for gratitude, and self-compassion was designed, delivered, and evaluated with HCWs across 2 military primary care clinics in South Texas. RESULTS: All HCWs across 2 Air Force family practice clinics were invited to participate in all toolkit components. Seventy percent of all HCWs (N = 90) attended the introduction session. Thirty-seven (41%) HCWs completed pre and post MZBSs, and these responses are included in the data analysis section. The most represented HCWs were registered nurses, physician assistants, and technicians, respectively, at 24%, 21%, and 18%. The Wilcoxon Signed-Rank test examined changes in HCWs' SRSL after participation in the MBSR TK program. HCWs who attended the introduction plus one biweekly session showed statistically significant decreases in self-reported stress (P = 0.018) and burnout (P = 0.045) and a significant increase in electronic health record proficiency (P = 0.033). CONCLUSIONS: Multimodal mindfulness toolkits to address SRSL burnout are practical, accessible, easily implemented, adaptive to any environment, and can decrease burnout with participation with just one 15 minute session. This MBSR TK implementation effectively lowered self-reported stress in HCWs who are repeatedly challenged to adapt to various settings around the world during peacetime, wars, natural disasters, humanitarian crises, and now, pandemics.

Ovarian Serous Cystadenoma of the Epididymis: A Case Report.

Paratesticular cystadenomas remain a very rare entity, typically presenting as a painless mass, often indistinguishable from the testicle. As such, the predominant management seems to be complete excision via various approaches, which often proves curative. Given its rarity, post-operative surveillance has not been standardized; most patients and providers elect a more conservative surveillance approach. Based on the available literature, this seems appropriate, given the lack of morbidity or recurrence associated with these types of tumors.

Patients' attitudes to bedside teaching after the COVID-19 pandemic.

BACKGROUND: Bedside teaching (BST) is a method of structured clinical teaching where the patient is central in education. We had previously explored the patients' perceptions of BST using both a qualitative research study and validation of a questionnaire, both showing strong support by patients for BST once basic rules of respect and confidentiality are followed. With the COVID-19 pandemic, clinical education transitioned to online/virtual learning. AIM: The aim of this study was to explore patients' attitudes towards reintroduction of BST as the pandemic restrictions have lifted. METHODS: Patients were invited to complete a validated questionnaire exploring their attitudes towards BST. A descriptive analysis was performed. Results were compared to a previous study performed before the COVID-19 pandemic. RESULTS: Four hundred patients consented to complete the questionnaires. Participants included women attending for antenatal (40%), postnatal (33%) and gynaecology issues (28%). Most patients (> 94%) reported that they were happy to be involved in BST. Patients believed that they should not be asked to participate in BST should they feel stressed or unwell (69%). These findings were the same as our previous study, performed prior to the pandemic. CONCLUSION: This study shows extensive and persisting patient support for BST. BST is unique in that it allows students to gain a deeper understanding of the disease which are hard to elicit through online/virtual methods.

Outcomes and Adverse Effects of Voretigene Neparvovec Treatment for Biallelic RPE65-Mediated Inherited Retinal Dystrophies in a Cohort of Patients from a Single Center.

Our study evaluated the morphological and functional outcomes, and the side effects, of voretigene neparvovec (VN) gene therapy for RPE65-mediated inherited retinal dystrophies (IRDs) in 12 eyes (six patients) at the Oxford Eye Hospital with a mean follow-up duration of 8.2 (range 1-12) months. All patients reported a subjective vision improvement 1 month after gene therapy. Best-corrected visual acuity (BCVA) remained stable (baseline: 1.28 (±0.71) vs. last follow-up: 1.46 (±0.60); p = 0.25). Average white Full-Field Stimulus Testing (FST) showed a trend towards improvement (baseline: -4.41 (±10.62) dB vs. last follow-up: -11.98 (±13.83) dB; p = 0.18). No changes in central retinal thickness or macular volume were observed. The side effects included mild intraocular inflammation (two eyes) and cataracts (four eyes). Retinal atrophy occurred in 10 eyes (eight mild, two severe) but did not impact FST measurements during the follow-up period. Increased intraocular pressure (IOP) was noted in three patients (six eyes); four eyes (two patients) required glaucoma surgery. The overall safety and effectiveness of VN treatment in our cohort align with previous VN clinical trials, except for the higher occurrence of retinal atrophy and increased IOP in our cohort. This suggests that raised IOP and retinal atrophy may be more common than previously reported.

Timing is everything: Developmental changes in the associations between intergroup contact and bias.

Identifying developmental patterns in intergroup contact and its relation with bias is crucial for improving prevention strategies around intergroup relations. This study applied time-varying effects modeling (TVEM) to examine age-based changes in relations between contact and bias in a divided community that included 667 youth (M age = 15.74, SD = 1.97) from Belfast, Northern Ireland, a conflict-affected setting. The results suggest no change in the relation between contact frequency and bias; however, the relation between contact quality and bias increases from ages 10-14 and then levels off. Differences between Catholics, the historic minority group, and Protestants, the historic majority group, also emerged. The article concludes with implications for future research and interventions for youth growing up amid conflict.

Clinical Research on the Leading Causes of Severe Sight Impairment in the UK General and Working Populations.

Purpose: Clinical research brings the potential of improved diagnostics, sight-saving treatments, and more accessible services to those suffering with severe sight impairment (SSI). This report investigates whether registered ophthalmology clinical studies address the leading causes of SSI in the general and working populations of the United Kingdom (UK). Methods: The latest statistics on the leading causes of SSI in the UK general and working populations were identified by searching PubMed, Cochrane Library, and TRIP databases. Clinical study registries were searched to identify registered clinical studies (on or prior to 1st December 2022) on the leading causes of SSI. The relationship between the number of clinical studies on leading causes of SSI and the percentage of SSI certifications they account for was analyzed. Results: In the UK general population, the number of registered clinical studies on the leading causes of SSI is statistically significantly correlated (Spearman's rho = 0.86, p < 0.01) with the percentage of SSI certifications they account for. However, there is no correlation between the two in the UK working population (aged 16-64) (Spearman's rho = 0.15, p = 0.70). Eye conditions accounting for the most SSI certifications in individuals of working age have significantly less clinical research activity than those that cause the most SSI certifications in the general population. Out of the leading causes of SSI certifications studied, disorders of the visual cortex and congenital anomalies of the eye have the least clinical research activity. Conclusion: Clinical research into the leading causes of SSI in the general population is essential. However, it is important to consider eye conditions that cause the most severe visual impairment in individuals of working age due to the significant health and socioeconomic implications of sight loss in this population.

Choroideremia: The Endpoint Endgame.

Choroideremia is an X-linked retinal degeneration resulting from the progressive, centripetal loss of photoreceptors and choriocapillaris, secondary to the degeneration of the retinal pigment epithelium. Affected individuals present in late childhood or early teenage years with nyctalopia and progressive peripheral visual loss. Typically, by the fourth decade, the macula and fovea also degenerate, resulting in advanced sight loss. Currently, there are no approved treatments for this condition. Gene therapy offers the most promising therapeutic modality for halting or regressing functional loss. The aims of the current review are to highlight the lessons learnt from clinical trials in choroideremia, review endpoints, and propose a future strategy for clinical trials.