Multiple Contributory Factors Research Articles

Abstract C097: PVT1 exon 9-dependent overexpression of RSAD2 is a characteristic of prostate cancer in males of African ancestry

Abstract Aggressive prostate cancer (PCa), including castrate-resistant and neuroendocrine subtypes, is projected to increase in incidence 5% each year. Aggressive PCa disproportionally impacts African American men, has limited effective treatment options and high mortality rates. Although racial disparities are established in PCa development, attributed to multiple contributory factors including systemic racism, differences in socioeconomic status and distrust in the medical system, work is still needed to understand the contribution of biological factors. We found the exon 9 region of plasmacytoma variant translocation 1 (PVT1) overexpressed in aggressive PCa cell lines derived from African American (AA) men. We found PVT1 exon 9 overexpression induced phenotypic changes to normal prostate epithelial cells in vitro and led to tumor formation in vivo. RNA-sequencing analysis revealed 156 significantly differentially expressed genes influenced by PVT1 exon 9 overexpression and radical S-adenosyl methionine domain containing 2 (RSAD2) was the top significantly overexpressed gene (log2Fold change 1.71, p-value < 0.05). We utilized the GSE223405 publicly available dataset to identify whether our identified PVT1 exon 9 downstream genes were enriched in AA prostate cancer cells. RSAD2 was significantly overexpressed in AA prostate cancer cells compared to prostate cancer cells from men of European ancestry (moEA) (log2Fold change 6.18, p-value < 0.05). Comparing normal cells to prostate cancer cells between these groups, we found that normal AA prostate cells had significantly higher expression of RSAD2 (log2fold change 4.25, p-value < 0.001) whereas moEA samples did not (log2fold change 0.837, p-value=0.150). From analysis of data obtained from cBioPortal, we found RSAD2 alteration significantly correlates (p-value < 0.001) with self-identified race and copy number overexpression of RSAD2 was found to be enriched in AA patients (18.16% moEA versus 24% AA). Finally, we found 88.6% of the significantly differentially expressed genes within our PVT1 exon 9 RNA-sequencing dataset were significantly differentially expressed in GSE223405 AA samples and of those, 51.7% of genes exhibited a similar differential expression pattern suggesting that the PVT1 exon 9/RSAD2 dependent pathway may be more prominent in AA men. Mechanistically, we found two differing pathways of RSAD2 overexpression in aggressive prostate cancer cell models, one dependent and one independent of PVT1 exon 9 overexpression, with similar but differing biological functions related to epigenetic processes and metabolism. Ongoing work is investigating the RSAD2 and PVT1 exon 9 expression axis in a diverse set of human prostate cancer tissues and investigating their utilization as a therapeutic target in prostate cancer. Citation Format: Rachel E. Sexton-Bonacci1, Murtaza Barkarar1, Chindeum Udekwu1, Olorunseun O. Ogunwobi1. PVT1 exon 9-dependent overexpression of RSAD2 is a characteristic of prostate cancer in males of African ancestry [abstract]. In: Proceedings of the 17th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2024 Sep 21-24; Los Angeles, CA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2024;33(9 Suppl):Abstract nr C097.

Factors contributing to in-school bullying victimization among early adolescents – focus group discussions

Introduction: Bullying is a significant peer problem among school going adolescents which has many reported undesirable consequences. Identification of contributory factors of victimization is beneficial in addressing the bullying prevention programs.Objectives: To identify and explore the contributory factors of bullying victimization among school going adolescents in selected educational zone in Sri Lanka.Methods: Focus group discussions (FGD) were conducted among grade eight students from six randomly selected schools from each category of schools in the Kegalle educational zone. A convenient sampling technique was used to select the participants for each FGD. Thematic analysis was performed manually on the collected data.Results: Five main themes, namely, external appearance, problems with speech, suffering from illnesses, socioeconomic background and being a ‘newcomer’ were identified in the thematic analysis.Conclusions & Recommendations: Multiple contributory factors of in-school bullying victimization were identified in these focus group discussions. Therefore, the necessity of addressing the above factors, when addressing them in prevention programs is highlighted.

P05 Osteoporosis in thalassemia; a case with multifactorial aetiology

Abstract Introduction Thalassemia patients are prone to osteoporosis due to multifactorial reasons, including anaemia, bone marrow expansion, iron overload and hypogonadism. Case description A 41-year-old British Asian male with beta thalassemia major was referred to rheumatology in 2018 for osteoporosis. In 2008, aged 27 years, whilst playing football, he developed a distal radial fracture and ulnar styloid process fracture and a DEXA scan had revealed low bone mineral density (BMD) for age. Subsequently, he was started on Ibandronic acid by his haematologist for a total of 10 years. After he was referred to rheumatology in 2018, bisphosphonates were discontinued as he had 5% improvement in BMD, a decade of bisphosphonates and no further fractures. Further assessment revealed multiple contributory factors for his osteoporosis. • Consistency low vitamin D – 9.6 nmol/L in 2009, average value of 20 • He was diagnosed with hypogonadism, poor compliance with IM testosterone injections • He had diabetes which was not optimally controlled • Evidence of iron overload with average serum ferritin of 2000 ug/L with deferasirox While these factors were optimised, it was decided to adopt a watch and wait policy with regards to specific osteoporosis treatment. Review in 2023 revealed serum testosterone level of 20.1 nmol/L (6.9-23.2) with better compliance with testosterone injections. Fructosamine levels were 310 (normal range 200-285) but it has reduced from a peak of 370. Serum ferritin levels have reduced to 776 down from a high of 5600. Normal vitamin D levels were maintained. The DEXA scan in 2023 revealed a spine T score of −2.4 which showed 10.2% increase in bone mineral density. DEXA scan in 2020 revealed T score of −3.1 in spine and −1.9 in hips. The P1NP level was 56 (19-69) which has reduced from 100 in 2021. Improvements in BMD and bone turnover markers were achieved through optimising contributory factors without any specific osteoporosis treatment. He will be monitored with periodic BMD and bone turnover markers. Discussion Anaemia and subsequent bone marrow expansion is a recognised cause for osteoporosis in thalassemia patients. While regular blood transfusions inhibit bone marrow expansion, ineffective erythropoiesis is not fully supressed. This patient received 3 units of blood every 4 weeks. Bone marrow expansion occurs mostly in trabecular bone resulting in low BMD is areas which generally have increased amount of trabecular bone such as the spine. Our patient had a lower BMD in the spine compared to the femoral neck. Iron overload directly disrupts bone formation and can result in endocrinopathies which contributes to osteoporosis. Hypogonadism is another well-recognised cause and is primarily results from iron deposition in pituitary and at times in the gonads. Hormonal replacement therapy reduces bone loss. Studies have shown that hypogonadic patients have more severe osteoporosis and predominant involvement of the femoral neck. Iron overload can cause diabetes mellitus and impaired growth hormone/ insulin growth factor-1 (IGF-1) axis which can contribute to osteoporosis. Our patient did have diabetes but had normal IGF-1 levels when checked previously. Deferoxamine which is one of iron chelating agents have been shown to reduce collagen synthesis and increases osteoblast apoptosis which might contribute to the development of osteoporosis. Vitamin D levels are well known to be low in patients with thalassemia compared to the general population. While there are no RCT’s to show that bisphosphonates reduce fracture risk, surrogate markers such as increased BMD and reduction in bone turnover markers are known to occur. Therefore, current guidance (Standards for the Clinical Care of Children and Adults with Thalassaemia in the UK) recommends bisphosphonates to be considered in patients with a low BMD for age (Z-score < −2.0, T-score < −2.5 if post-menopausal or over 50), if there are fragility fractures or falling BMD despite adequate vitamin D levels, and hormone supplementation. Key learning points Learning point Important to assess for osteoporosis in thalassaemic patients. There are multiple factors contributing to the development of osteoporosis which needs to be addressed together with endocrinologist and haematologist. Bisphosphonates are recommended though further RCT evidence is required to support this

The Immune Response in the Uteri and Placentae of Chlamydia abortus-Infected Ewes and Its Association with Pregnancy Outcomes.

The enzootic abortion of ewes, caused by the bacterium Chlamydia abortus (C. abortus), is one of the main causes of abortion in sheep. There are multiple contributory factors, including chlamydial growth, host immune response, and hormonal balance, that result in different pregnancy outcomes, such as abortion, the birth of weak lambs that may die, or healthy lambs. This study aimed to determine the relationship between phenotypical patterns of immune cell infiltration and different pregnancy outcomes in twin-bearing sheep (both lambs born dead; one alive and one dead; both alive) when experimentally infected with C. abortus. Both the sheep uteri and placentae were collected after parturition. All samples were analysed for specific immune cell features, including cell surface antigens and the T-regulatory (Treg) cell-associated transcription factor and cytokines, by immunohistochemistry and in situ hybridisation. Some of these immunological antigens were evaluated in ovine reproductive tissues for the first time. Differential patterns of T helper/Treg cells revealed significant group effects in the placentae. It suggests the potential role that the balance of lymphocyte subsets may play in affecting different pregnancy outcomes in C. abortus-infected sheep. The present study provides novel detailed information about the immune responses observed at the maternofoetal interface in sheep at the time of pre-term abortion or lambing.

The impact of modernization on allergy and asthma development

Background: In recent years, an increase of allergies and asthma has been observed throughout the world, more so in Western countries than in less developed ones. Although genetics may play a role in this increase, there are many other factors that may have contributed to the upsurge. Objective: The purpose of the present report was to review the many factors associated with modernization and lifestyle that may have contributed to the allergy and/or asthma epidemic, with a particular focus on those aspects that have particular relevance for the allergist/immunologist. Results: The marked rise in allergy and asthma has been significantly seen in more-developed countries, greater in urban than in rural areas, more pronounced in affluent than in poorer societies, and in individuals who have migrated from developing countries to industrialized countries. A widely accepted explanation for this rise is the "hygiene hypothesis," which postulates a critical dependence on microbial infection for maintenance of a healthy balanced immune system and that extremely clean external environments, often found in the developed world, can derail equilibrated immune development. With the control of infectious diseases, the immune system shifts from a balanced equilibrated immunologic structure to a more Th2 driven proinflammatory state often associated with IgE and eosinophil-related disorders. Conclusion: Modernization has been associated with increased development of allergies and asthma through a cleaner environment and more exposure to allergens and to multiple other contributory factors. The marked reduction in infectious diseases in recent decades permitted the immune system to switch from fighting infectious disease agents and parasites to reacting adversely (hypersensitivity) to benign environmental agents (allergens) and even to self-antigens (autoimmunity).

A curious case of confusion

A curious case of confusion

Multiple overlapping risk factors for childhood wheeze among children in Benin

BackgroundThe African continent is currently facing an epidemiological transition characterized by a shift from communicable to non-communicable diseases. Prominent amongst the latter are allergies and asthma. In that context, wheeze has multiple potential contributory factors that could include some of the endemic helminth infections, as well as environmental exposures, such as household air pollution. We sought to determine the relative importance of these risk factors among children in Benin.MethodsWe included 964 children aged 6–14 years living in the commune of Comé, south–west Benin. All children were participants in the longitudinal monitoring cohort of the DeWorm3 trial designed to evaluate multiple rounds of community mass treatment with albendazole for interruption of the transmission of soil transmitted helminths (STH). We administered a standard ISAAC questionnaire to determine the presence of wheeze. In addition, we assessed exposure to household air pollution and to other potential allergy-inducing factors, dietary intake and anthropometry. Using STH infection status assessed at the pretreatment baseline timepoint, we used multivariate statistical modelling, controlling for covariates, to investigate associations between wheeze and the different factors measured.ResultsThe prevalence of wheezing history was 5.2%, of current wheezing was 4.6% and of severe wheezing was 3.1%, while STH infections were found in 5.6% of children. These profiles did not vary as a function of either age or gender. Infection with Ascaris lumbricoides, but not hookworm species, was significantly associated with both current wheeze (adjusted Odds Ratio (aOR) = 4.3; 95% CI [1.5–12.0]) and severe wheeze (aOR = 9.2; 95% CI [3.1–27.8]). Significant positive associations with current wheeze, independent of each other and of STH infection status, were also found for (i) use of open cookstoves (aOR = 3.9; 95% CI [1.3–11.5]), (ii) use of palm cakes for fire lighting (aOR = 3.4; 95% CI [1.1–9.9]), (iii) contact with domestic animals and/or rodents (aOR = 2.5; 95% CI [1.1–6.0]), (iv) being overweight (aOR = 9.7; 95% CI [1.7–55.9]). Use of open cookstoves and being overweight were also independent risk factors for severe wheeze (aOR = 3.9; 95% CI [1.1–13.7]) and aOR = 10.3; 95% CI [1.8–60.0], respectively).ConclusionsChildren infected with A. lumbricoides appear to be at elevated risk of wheeze. Deworming may be an important intervention to reduce these symptoms. Improving cooking methods to reduce household air pollution, modifying dietary habits to avoid overweight, and keeping animals out of the house are all additional measures that could also contribute to reducing childrens’ risk of wheeze. Policymakers in LMIC should consider tailoring public health measures to reflect the importance of these different risk factors.

Twenty-year experience and outcomes in a national paediatric pulmonary hypertension service

Abstract Background/Introduction Paediatric pulmonary hypertension (PH) is an important cause of childhood morbidity and mortality, but there are limited data on the range of associated diseases (including several paediatric-specific aetiologies), contributions of different PH subtypes, therapeutic strategies and clinical outcomes in paediatric patients. Purpose In this study, we report the 20-year experience of a UK National Paediatric Pulmonary Hypertension Service focusing on the aetiology, management and outcomes of children with PH. Methods Consecutive patients presenting to the service between January 2001 and January 2021 were included in this retrospective study. Other inclusion criteria were: age ≤18 years at diagnosis and diagnosis of PH following specialist assessment. Only incident patients (without pre-existing PH) were entered in the survival analysis. Results A total of 1104 (81.5%) PH patients were included during the study period: 51% female, median age 2.6 [0.8–8.2] years. The most common PH diagnosis was group 1 (pulmonary arterial hypertension, PAH) in 532 (48.2%) patients, followed by group 3 PH (due to lung disease) in 358 (32.4%), group 2 (101, 9.1%), group 5 (93, 8.4%), and group 4 disease (20, 1.8%). The most common PAH subgroup was PAH associated with congenital heart disease (CHD, 63.3%), followed by idiopathic PAH (22.4%). One quarter of patients (23.6%) had multiple contributory factors for PH, fitting more than one diagnostic group. Resolution of PH, defined as normalisation of pulmonary artery pressures following cessation of PAH therapy, occurred in 172 (15.6%) patients at a median age of 3.7 [2.1–5.7] years and was more common in group 3 than other PH groups (33.5% vs. 9.1% at 5 years post-diagnosis, p<0.0001). Overall, 909 (82.3%) patients received PAH therapy. Patients with group 3 PH were as likely to receive PAH therapy as an initial treatment strategy as group 1 patients (86.6% vs. 82.3%, p=0.11), but were more likely to receive sildenafil monotherapy (p=0.002) and less likely to be offered triple therapy (p<0.0001). During follow-up, maintenance or escalation to triple therapy was required in 103 (9.3%) patients and was far more common in idiopathic compared to other PAH subgroups (37.7% vs. 7.8%, p<0.0001). Transplant-free survival was 86.7% (95% CI: 84.5–88.9%) at 1 year, 74.2% (95% CI: 71.1–77.5%) at 5 years, and 68.9% (95% CI: 65.1–73%) at 10 years (Figure 1). PAH related to CHD had the highest transplant-free survival (HR 0.62, 95% CI: 0.46–0.84, p=0.002). Group 2 had the lowest transplant-free survival (HR 2.09, 95% CI: 1.42–3.09, p=0.0002) whereas groups 3,4 and 5 did not differ significantly from PAH (Figure 2). Conclusions In this large, national cohort of paediatric PH patients, the most common type of PH was PAH, followed by group 3 PH. Multiple contributory causes for PH are common and PH resolution was not uncommon, especially in group 3 patients. Despite widespread use of PAH therapy, the prognosis remains guarded. Funding Acknowledgement Type of funding sources: Private grant(s) and/or Sponsorship. Main funding source(s): Dr Constantine has received a PhD grant from Janssen-Cilag Ltd. as the CHAMPION PhD Fellow. Figure 1Figure 2

Neurophobia: The fear of neurology among medical students and interns in Sudan 2020

Neurophobia is the fear of neuroscience and clinical neurology, inability to utilize the basic neurological knowledge at the bedside. Most of the general practitioners display less confidence when dealing with neurological cases. The exact reasons for neurophobia are not well known and it likely as a result of multiple contributory factors. Our study aimed to assess the attitude toward Neurology and to explore the reasons for this attitude.

A Review of Differential Attainment in Recruitment in the UK Medical Profession

Differential attainment is the phenomenon where groups of people, in this case, members of the medical profession, experience differences in their achievement based on factors which are beyond their control. There are multiple contributory factors including gender, age, race, ethnicity, socio-economic and disability. The evidence suggests that medical professionals from Black and minority ethnic backgrounds, women, those with a disability, international medical graduates, those from low socioeconomic status and from geographical low participation (in higher education) areas tend to find barriers in every stage of recruitment to medical schools and later during their careers. There is emerging data over the last 5 years (post-2014) of organisations such as General Medical Council, Medical Schools Council and members of the Academy of Royal Colleges that are striving to offer transparency and annual reports which offer the opportunity for reflection and self-assessment.
 
 The British Association of Physicians of Indian Origin has been leading a collaborative initiative with the ‘Alliance for Equality in Healthcare Professions’ to tackle the full range of differential attainment. This collaboration brings multiple stakeholder organisations and grassroots bodies around the table with international experts in reviewing the evidence, the data from focus groups and working to develop tangible, SMART interventions to address these disparities. This review on DA in recruitment is one of six such themes which will constitute the ‘Bridging the Gap’ report due in line with the Silver Jubilee celebrations of BAPIO in September 2021. The report will present evidence-based, consensus on recommendations for action at national, regional and local level and areas for further collaborative research.

A Contemporary Review on Drought Modeling Using Machine Learning Approaches

Drought is the least understood natural disaster due to the complex relationship of multiple contributory factors. Its beginning and end are hard to gauge, and they can last for months or even for years. India has faced many droughts in the last few decades. Predicting future droughts is vital for framing drought management plans to sustain natural resources. The data-driven modelling for forecasting the metrological time series prediction is becoming more powerful and flexible with computational intelligence techniques. Machine learning (ML) techniques have demonstrated success in the drought prediction process and are becoming popular to predict the weather, especially the minimum temperature using backpropagation algorithms. The favourite ML techniques for weather forecasting include support vector machines (SVM), support vector regression, random forest, decision tree, logistic regression, Naive Bayes, linear regression, gradient boosting tree, k-nearest neighbours (KNN), the adaptive neuro-fuzzy inference system, the feed-forward neural networks, Markovian chain, Bayesian network, hidden Markov models, and autoregressive moving averages, evolutionary algorithms, deep learning and many more. This paper presents a recent review of the literature using ML in drought prediction, the drought indices, dataset, and performance metrics.

Pain in the neurodegenerating brain: insights into pharmacotherapy for Alzheimer disease and Parkinson disease.

Pain in the neurodegenerating brain: insights into pharmacotherapy for Alzheimer disease and Parkinson disease.

Increased transcriptome variation and localised DNA methylation changes in oocytes from aged mice revealed by parallel single-cell analysis.

Advancing maternal age causes a progressive reduction in fertility. The decline in developmental competence of the oocyte with age is likely to be a consequence of multiple contributory factors. Loss of epigenetic quality of the oocyte could impair early developmental events or programme adverse outcomes in offspring that manifest only later in life. Here, we undertake joint profiling of the transcriptome and DNA methylome of individual oocytes from reproductively young and old mice undergoing natural ovulation. We find reduced complexity as well as increased variance in the transcriptome of oocytes from aged females. This transcriptome heterogeneity is reflected in the identification of discrete sub‐populations. Oocytes with a transcriptome characteristic of immature chromatin configuration (NSN) clustered into two groups: one with reduced developmental competence, as indicated by lower expression of maternal effect genes, and one with a young‐like transcriptome. Oocytes from older females had on average reduced CpG methylation, but the characteristic bimodal methylation landscape of the oocyte was preserved. Germline differentially methylated regions of imprinted genes were appropriately methylated irrespective of age. For the majority of differentially expressed transcripts, the absence of correlated methylation changes suggests a post‐transcriptional basis for most age‐related effects on the transcriptome. However, we did find differences in gene body methylation at which there were corresponding changes in gene expression, indicating age‐related effects on transcription that translate into methylation differences. Interestingly, oocytes varied in expression and methylation of these genes, which could contribute to variable competence of oocytes or penetrance of maternal age‐related phenotypes in offspring.

Lessons from the triennial analysis of serious case reviews

Abstract Serious Case Reviews (SCRs) provide an important opportunity for professional learning when children have died or suffered serious harm from abuse or neglect. The triennial SCR analysis seeks to identify themes across SCRs to inform practice and guide the development of new strategies in order to prevent future harm to children. Neglect is a key feature of most serious case reviews; it is a complex issue with multiple contributory factors accumulating over time. Neglect is linked with unfavourable outcomes at individual and societal levels. Many of the families concerned are living in poverty and difficulties are exacerbated by the limitation of resources with which to support them. This article considers key messages for paediatric practice from the 2014–17 triennial review, particularly with respect to neglect and adolescent safeguarding concerns.

Multi-scale foraging decisions made by woodland caribou (Rangifer tarandus caribou) in summer

Multi-scale selection patterns can be understood from two perspectives: coarse-scale patterns as the summation of fine-scale patterns (scaling-up), or as a hierarchy produced from multiple contributory factors with differential effects on organismal fitness (hierarchical). We examined woodland caribou (Rangifer tarandus caribou (Gmelin, 1788)) selection of foraging locations across two spatiotemporal scales to test whether selection patterns between them were consistent (scaling-up) or different (hierarchical) to determine which framework most accurately describes their foraging behaviour. Seven adult female woodland caribou were equipped with GPS telemetry radio collars outfitted with high-definition video cameras that recorded woodland caribou foraging choices throughout the summer. Fine-scale data from videos combined with direct measurements in the field along movement trajectories obtained from GPS fixes were used to estimate (i) feeding station selection and (ii) food patch selection. We estimated resource selection functions for each scale following a use–availability structure. Woodland caribou exhibited resource selection at both scales. Apart from selection for species of the lichen Cladina (Nyl.) Nyl. and patches associated with high abundance of Cladina, few patterns were consistent across both scales. Our study suggests that even at very fine scales, woodland caribou selection for foraging locations is hierarchical in nature.

Provider–patient communication about prescription drug abuse: A qualitative analysis of the perspective of prescribers

Background: Provider–patient communication underpins many initiatives aimed at reducing the public health burden associated with prescription drug abuse in the United States. The purpose of this qualitative analysis was to examine the characteristics of provider–patient communication about prescription drug abuse from the perspective of prescribers. Methods: From 2014 to 2015, 10 semi-structured interviews were conducted with a purposive sample of prescribers from multiple professions and medical fields in Central and South Central Appalachia. The interviews were conducted using a guide informed by Social Cognitive Theory and community theory research, audio-recorded, and transcribed verbatim. Thematic analysis, facilitated by NVivo 10 software, was used to generate themes. Results: Prescribers described 3 primary communication patterns with patients related to prescription drug abuse—informative, counteractive, and supportive. Prescribers also reported multiple factors—personal (e.g., education, experiences, and feelings of tension) and environmental (e.g., relationship with a patient, clinical resources, and policies on controlled prescription drugs)—that affect provider–patient communication and, by association, delivery of patient care related to prescription drug abuse. Conclusions: The findings suggest that provider–patient communication about prescription drug abuse is multidimensional and dynamic, characterized by multiple communication patterns and contributory factors. They have implications for (1) research aimed at advancing theoretical understanding of prescriber prescription drug abuse communication behaviors with patients and (2) interventions aimed at strengthening prescriber prescription drug abuse communication behaviors with patients.

Nighttime driving: visual, lighting and visibility challenges.

Nighttime driving is dangerous and is one of the most challenging driving situations for most drivers. Fatality rates are higher at night than in the day when adjusted for distances travelled, particularly for crashes involving pedestrians and cyclists. Although there are multiple contributory factors, the low light levels at night are believed to be the major cause of collisions with pedestrians and cyclists at night, most likely due to their reduced visibility. Understanding the visibility problems involved in nighttime driving is thus critical, given the increased risk to road safety. This review discusses research that highlights key differences in the nighttime road environment compared to the day and how this affects visual function and driving performance, together with an overview of studies investigating how driver age and visual status affect nighttime driving performance. Research that has focused on the visibility of vulnerable road users at nighttime (pedestrians and cyclists) is also included. Collectively, the research evidence suggests that visual function is reduced under the mesopic lighting conditions of night driving and that these effects are exacerbated by increasing age and visual impairment. Light and glare from road lighting and headlights have significant impacts on vision and night driving and these effects are likely to change with evolving technologies, such as LED streetlighting and headlights. Research also highlights the importance of the visibility of vulnerable road users at night and the role of retroreflective clothing in the 'biomotion' configuration for improving their conspicuity and hence safety.

Anterior Segment Optical Coherence Tomography: Is There a Clinical Role in the Management of Primary Angle Closure Disease?

Primary angle closure disease (PACD) covers a spectrum that includes primary angle closure suspect, primary angle closure, primary angle closure glaucoma, and acute primary angle closure. Accumulating evidence suggests that the pathogenesis of PACD is complex, with multiple contributory factors including variations in the anatomic or biometric characteristics of the angle segment structures. Advances in anterior segment optical coherence tomography technology have further enhanced our understanding of the risk factors and mechanisms involved in the disease process. This review discusses the potential clinical role of the anterior segment optical coherence tomography in the diagnosis, mechanistic evaluation, and as a predictor for future clinical outcomes of patients with PACD.

Sport and Exercise in Improving Outcomes After Solid Organ Transplantation: Overview From a UK Meeting.

Outcomes after solid organ transplantation continue to improve, but premature loss of life remains a major concern, with death from cerebrovascular disease and cardiovascular disease accounting for around 20% late deaths. There are multiple contributory factors including preexisting, and the posttransplant development of, cardiometabolic conditions (such as hypertension, diabetes mellitus, hyperlipidemia, and obesity). There is accumulating evidence that the regular engagement in exercise is an important factor affecting outcomes before, during, and after transplantation; yet most waitlist candidates and recipients have reduced levels of physical activity. The mechanisms whereby physical activity is associated with better outcomes and a reduction in risk factors for cardiovascular disease are incompletely understood. Attempts to increase physical activity in the transplant population, as in the general population, have had limited success. Use of concepts from Nudge theory provides an evidence-based approach that may help increase physical activity and so reduce premature mortality. Both National and International Transplant Games provide a vehicle for increasing physical activity in this population and may also help to reduce premature death by providing a forum for mutual support for recipients and their families as well as an excellent forum for highlighting the success and impact of organ donation.

55. A case of profound jaundice with multiple contributory factors

55. A case of profound jaundice with multiple contributory factors