Providing environmentally sustainable nephrology care: focus in low- and middle-income countries.

Health care on a global scale significantly contributes to carbon emissions, with high-income countries being the primary culprits. Within health care, dialysis plays a significant role as a major source of emissions. Low- and middle-income countries have a high burden of kidney disease and are facing an increasing demand for dialysis. This reality presents multiple opportunities to plan for environmentally sustainable and quality kidney care. By placing a stronger emphasis on primary and secondary prevention of kidney disease and its progression, within the framework of universal health coverage, as well as empowering patients to enhance self-care, we can significantly reduce the need for costly and environmentally detrimental kidney replacement therapy. Mandating the adoption of lean and innovative low-carbon dialysis practices while also promoting the growth of kidney transplantation would enable low- and middle-income countries to take the lead in implementing environmentally friendly nephrology practices and reducing costs, thus optimizing sustainability and the well-being of individuals living with kidney disease.

Ethnic differences in treatment outcome for children and young people accessing mental health support.

Children and Young People (CYP) from minoritized ethnic backgrounds experience structural inequalities in Children and Young People's Mental Health Settings (CYPMHS). This mixed methods study explores whether CYP's ethnicity is associated with their treatment outcomes (operationalised as 'measurable change') from CYPMHS. A multilevel multi-nominal regression analysis, controlling for age, gender, referral source, presenting difficulty, case closure reason, suggests that CYP from Asian backgrounds (OR = 0.82, CI [0.70, 0.96]) and Mixed-race (odds ratio (OR) = 0.80; 95% CI [0.69, 0.92]) are less likely to report measurable improvement in mental health difficulties compared to White British CYP. Three themes from a thematic analysis of semi-structured interviews with 15 CYP from minoritized ethnic backgrounds focused on views and experiences of ending mental health support are also presented. CYP view personalised support and the right therapist as conducive to good endings and valued a range of outcomes pertaining to empowerment. Experiences of stigma and inequalities may begin to explain the less positive outcomes experienced by Asian and Mixed-race CYP found in the regression analysis. The implications of these findings and future areas of research are suggested.

Reef environments shape microbial partners in a highly connected coral population.

Evidence is mounting that composition of microorganisms within a host can play an essential role in total holobiont health. In corals, for instance, studies have identified algal and bacterial taxa that can significantly influence coral host function and these communities depend on environmental context. However, few studies have linked host genetics to algal and microbial partners across environments within a single coral population. Here, using 2b-RAD sequencing of corals and metabarcoding of their associated algal (ITS2) and bacterial (16S) communities, we show evidence that reef zones (locales that differ in proximity to shore and other environmental characteristics) structure algal and bacterial communities at different scales in a highly connected coral population (Acropora hyacinthus) in French Polynesia. Fore reef (FR) algal communities in Mo'orea were more diverse than back reef (BR) communities, suggesting that these BR conditions constrain diversity. Interestingly, in FR corals, host genetic diversity correlated with bacterial diversity, which could imply genotype by genotype interactions between these holobiont members. Our results illuminate that local reef conditions play an important role in shaping unique host-microbial partner combinations, which may have fitness consequences for dispersive coral populations arriving in novel environments.

Impact of COVID-19 on radiology training: Royal College of Radiologists Junior Radiologists Forum national survey.

AIM: To obtain a national snapshot of radiology trainees' experience during the first wave of the pandemic. MATERIALS AND METHODS: A 25-item questionnaire was disseminated to representatives from all training regions across the UK in July 2020. Each representative collated the collective experiences of trainees in their training programme in key domains, including redeployment, shielding, training, and teaching. RESULTS: Ninety-five percent (38 of 40) of representatives completed the questionnaire. Trainees in up to 76% of training programmes were redeployed to wards and some trainees were shielding in 81% of programmes. Only 27% of programmes enabled remote reporting for isolating or shielding trainees. Sixty-two percent of respondents felt their well-being needs were supported. There was an overall increase in the attendance, volume, and quality of teaching and training nationally due to improved accessibility via remote-learning methods. Significant challenges were described with reporting, interventional procedures, and multidisciplinary team meeting attendance, although 62% of programmes noted an increase in service provision. Less in-person feedback was reported with in-person training still deemed necessary for practical skills. The Royal College of Radiologists Junior Radiologists Forum webinars were well received by all trainees with continuation of the series recommended. CONCLUSION: The COVID-19 pandemic has had a clear impact on many areas of radiology training in the UK. Early strategies have been adopted to mitigate the challenges faced by trainees and opportunities for future improvement are highlighted.

Current status and solutions for gender equity in anaesthesia research.

Despite increasing numbers of women entering anaesthesia, they remain persistently under-represented within academic anaesthesia and research. Gender discordance is seen across multiple aspects of research, including authorship, editorship, peer review, grant receipt, speaking and leading. Women are also under-represented at higher faculty ranks and in department chair positions. These inequities are further magnified for women with intersectional identities, such as those who identify as Black, indigenous and women of colour. Several barriers to participation in research have been identified to date, including a disproportionate amount of family responsibilities, a disproportionate burden of clinical service, gender bias, sexual harassment and the gender pay gap. Several strategies to improve gender equity have been proposed. Increasing access to formal mentorship of women in academic medicine is frequently cited and has been used by healthcare institutions and medical societies. Senior faculty and leaders must also be conscious of including women in sponsorship and networking opportunities. Institutions should provide support for parents of all genders, including supportive parental leave policies and flexible work models. Women should also be materially supported to attend formal educational conferences targeted for women, aimed at improving networking, peer support and professional development. Finally, leaders must display a clear intolerance for sexual harassment and discrimination to drive culture change. Peers and leaders alike, of all genders, can act as upstanders and speak up on behalf of targets of discrimination, both in the moment or after the fact. Gender inequities have persisted for far too long and can no longer be ignored. Diversifying the anaesthesia research community is essential to the future of the field.

Novel Mechanisms of Ozone-Induced Pulmonary Inflammation and Resolution, and the Potential Protective Role of Scavenger Receptor BI.

INTRODUCTION: Increases in ambient levels of ozone (O3), a criteria air pollutant, have been associated with increased susceptibility and exacerbations of chronic pulmonary diseases through lung injury and inflammation. O3 induces pulmonary inflammation, in part by generating damage-associated molecular patterns (DAMPs), which are recognized by pattern recognition receptors (PRRs), such as toll-like receptors (TLRs) and scavenger receptors (SRs). This inflammatory response is mediated in part by alveolar macrophages (AMs), which highly express PRRs, including scavenger receptor BI (SR-BI). Once pulmonary inflammation has been induced, an active process of resolution occurs in order to prevent secondary necrosis and to restore tissue homeostasis. The processes known to promote the resolution of inflammation include the clearance by macrophages of apoptotic cells, known as efferocytosis, and the production of specialized pro-resolving mediators (SPMs). Impaired efferocytosis and production of SPMs have been associated with the pathogenesis of chronic lung diseases; however, these impairments have yet to be linked with exposure to air pollutants. SPECIFIC AIMS: The primary goals of this study were: Aim 1 - to define the role of SR-BI in O3-derived pulmonary inflammation and resolution of injury; and Aim 2 - to determine if O3 exposure alters pulmonary production of SPMs and processes known to promote the resolution of pulmonary inflammation and injury. METHODS: To address Aim 1, female wild-type (WT) and SR-BI-deficient, or knock-out (SR-BI KO), mice were exposed to either O3 or filtered air. In one set of experiments mice were instilled with an oxidized phospholipid (oxPL). Bronchoalveolar lavage fluid (BALF) and lung tissue were collected for the analyses of inflammatory and injury markers and oxPL. To estimate efferocytosis, mice were administered apoptotic cells (derived from the Jurkat T cell line) after O3 or filtered air exposure.To address Aim 2, male WT mice were exposed to either O3 or filtered air, and levels of SPMs were assessed in the lung, as well as markers of inflammation and injury in BALF. In some experiments SPMs were administered before exposure to O3or filtered air, to determine whether SPMs could mitigate inflammatory or resolution responses. Efferocytosis was measured as in Aim 1. RESULTS: For Aim 1, SR-BI protein levels increased in the lung tissue of mice exposed to O3, compared with mice exposed to filtered air. Compared with WT controls, SR-BI KO mice had a significant increase in the number of neutrophils in their airspace 24 hours post O3 exposure. The oxPL levels increased in the airspace of both WT and SR-BI KO mice after O3 exposure, compared with filtered air controls. Four hours after instillation of an oxPL, SR-BI KO mice had an increase in BALF neutrophils and total protein, and a nonsignificant increase in macrophages compared with WT controls. O3 exposure decreased efferocytosis in both WT and SR-BI KO female mice.For Aim 2, mice given SPM supplementation before O3 exposure showed significantly increased AM efferocytosis when compared with the O3exposure control mice and also showed some mitigation of the effects of O3 on inflammation and injury. Several SPMs and their precursors were measured in lung tissue using reverse-phase high performance liquid chromatography (HPLC) with tandem mass spectrometry (MS/MS). At 24 hours after O3 exposure 14R-hydroxydocosahexaenoic acid (HDHA) and 10,17-dihydroxydocosahexaenoic acid (diHDoHE) were significantly decreased in lung tissue, but at 6 hours after exposure, levels of these SPMs increased. CONCLUSIONS: Our findings identify novel mechanisms by which O3 may induce pulmonary inflammation and also increase susceptibility to and exacerbations of chronic lung diseases.

Rate of tree carbon accumulation increases continuously with tree size.

Forests are major components of the global carbon cycle, providing substantial feedback to atmospheric greenhouse gas concentrations. Our ability to understand and predict changes in the forest carbon cycle--particularly net primary productivity and carbon storage--increasingly relies on models that represent biological processes across several scales of biological organization, from tree leaves to forest stands. Yet, despite advances in our understanding of productivity at the scales of leaves and stands, no consensus exists about the nature of productivity at the scale of the individual tree, in part because we lack a broad empirical assessment of whether rates of absolute tree mass growth (and thus carbon accumulation) decrease, remain constant, or increase as trees increase in size and age. Here we present a global analysis of 403 tropical and temperate tree species, showing that for most species mass growth rate increases continuously with tree size. Thus, large, old trees do not act simply as senescent carbon reservoirs but actively fix large amounts of carbon compared to smaller trees; at the extreme, a single big tree can add the same amount of carbon to the forest within a year as is contained in an entire mid-sized tree. The apparent paradoxes of individual tree growth increasing with tree size despite declining leaf-level and stand-level productivity can be explained, respectively, by increases in a tree's total leaf area that outpace declines in productivity per unit of leaf area and, among other factors, age-related reductions in population density. Our results resolve conflicting assumptions about the nature of tree growth, inform efforts to undertand and model forest carbon dynamics, and have additional implications for theories of resource allocation and plant senescence.

Impact of COVID-19 on UK radiology training: a questionnaire study.

AIM: To understand the impact of COVID-19 on radiology trainee experience and well-being. MATERIALS AND METHODS: A questionnaire designed to capture the impact of COVID-19 on radiology training, working patterns, and well-being was sent to all speciality trainees in a regional UK radiology school. The survey was distributed at the beginning of May 2020 and responses collected over 2 weeks. Trainees were questioned about changes that had occurred over a time period starting at the beginning of the COVID-19 pandemic. All survey responses (n=29) were anonymised and the results were subsequently analysed. RESULTS: Sixty-two percent (29 of 47) of trainees within the deanery, who were spread across seven different hospital sites, responded to the questionnaire. All trainees felt that overall radiology workload had decreased in response to COVID-19. Seventy-two percent (21/29) stated that their workload had significantly decreased. Seventy percent (19/27) reported decreased subspecialty experience, and 19% (5/27) reported a complete lack of subspecialty training. Twenty-four percent (7/29) of trainees were redeployed from radiology to clinical ward-based work. Forty-eight percent reported experiencing a worsening in their well-being compared to before the pandemic. CONCLUSION: The first wave of the COVID-19 pandemic had a significant impact on training and well-being. Lessons learnt from this report should help prepare for a second-wave of COVID-19 or future pandemics.

Development, behaviour and sensory processing in Marshall-Smith syndrome and Malan syndrome: phenotype comparison in two related syndromes.

BACKGROUND: Ultrarare Marshall-Smith and Malan syndromes, caused by changes of the gene nuclear factor I X (NFIX), are characterised by intellectual disability (ID) and behavioural problems, although questions remain. Here, development and behaviour are studied and compared in a cross-sectional study, and results are presented with genetic findings. METHODS: Behavioural phenotypes are compared of eight individuals with Marshall-Smith syndrome (three male individuals) and seven with Malan syndrome (four male individuals). Long-term follow-up assessment of cognition and adaptive behaviour was possible in three individuals with Marshall-Smith syndrome. RESULTS: Marshall-Smith syndrome individuals have more severe ID, less adaptive behaviour, more impaired speech and less reciprocal interaction compared with individuals with Malan syndrome. Sensory processing difficulties occur in both syndromes. Follow-up measurement of cognition and adaptive behaviour in Marshall-Smith syndrome shows different individual learning curves over time. CONCLUSIONS: Results show significant between and within syndrome variability. Different NFIX variants underlie distinct clinical phenotypes leading to separate entities. Cognitive, adaptive and sensory impairments are common in both syndromes and increase the risk of challenging behaviour. This study highlights the value of considering behaviour within developmental and environmental context. To improve quality of life, adaptations to environment and treatment are suggested to create a better person-environment fit.

Correction to: Coral Symbiodinium Community Composition Across the Belize Mesoamerican Barrier Reef System is Influenced by Host Species and Thermal Variability.

The authors regret that acknowledgment for Dr. Adrian Marchetti was omitted from the manuscript. The correct acknowledgment is written below.

Coral Symbiodinium Community Composition Across the Belize Mesoamerican Barrier Reef System is Influenced by Host Species and Thermal Variability.

Reef-building corals maintain a symbiotic relationship with dinoflagellate algae of the genus Symbiodinium, and this symbiosis is vital for the survival of the coral holobiont. Symbiodinium community composition within the coral host has been shown to influence a coral's ability to resist and recover from stress. A multitude of stressors including ocean warming, ocean acidification, and eutrophication have been linked to global scale decline in coral health and cover in recent decades. Three distinct thermal regimes (highTP, modTP, and lowTP) following an inshore-offshore gradient of declining average temperatures and thermal variation were identified on the Belize Mesoamerican Barrier Reef System (MBRS). Quantitative metabarcoding of the ITS-2 locus was employed to investigate differences and similarities in Symbiodinium genetic diversity of the Caribbean corals Siderastrea siderea, S. radians, and Pseudodiploria strigosa between the three thermal regimes. A total of ten Symbiodinium lineages were identified across the three coral host species. S. siderea was associated with distinct Symbiodinium communities; however, Symbiodinium communities of its congener, S. radians and P. strigosa, were more similar to one another. Thermal regime played a role in defining Symbiodinium communities in S. siderea but not S. radians or P. strigosa. Against expectations, Symbiodinium trenchii, a symbiont known to confer thermal tolerance, was dominant only in S. siderea at one sampled offshore site and was rare inshore, suggesting that coral thermal tolerance in more thermally variable inshore habitats is achieved through alternative mechanisms. Overall, thermal parameters alone were likely not the only primary drivers of Symbiodinium community composition, suggesting that environmental variables unrelated to temperature (i.e., light availability or nutrients) may play key roles in structuring coral-algal communities in Belize and that the relative importance of these environmental variables may vary by coral host species.

Angiotensin receptor blocker vs ACE inhibitor effects on HDL functionality in patients on maintenance hemodialysis.

BACKGROUND AND AIMS: Angiotensin receptor blockers (ARB) and angiotensin converting enzyme inhibitors (ACEI) reduce cardiovascular events in the general population. Maintenance hemodialysis (MHD) patients are at high cardiovascular risk but few studies have directly addressed the comparative efficacy of these drugs. MHD disrupts the normally atheroprotective actions of high density lipoprotein (HDL), therefore, we compared ACEI or ARB treatment on HDL functions in MHD. METHODS AND RESULTS: HDL was isolated at the starting point (pre) and 3-6 months later (post) in 30 MHD randomly assigned to placebo, ramipril or valsartan. Outcomes included cholesterol efflux, inflammatory cytokine response, effects on Toll-like receptors (TLR), superoxide production, methylarginine and serum amyloid A (SAA) levels. HDL from ARB- or ACEI-treated subjects was more effective in maintaining efflux than HDL of placebo. HDL from ARB- or ACEI-treated subjects but not placebo lessened cellular superoxide production. In contrast, neither ARB nor ACEI improved HDL anti-inflammatory effect. Indeed, HDL of ACEI-treated subjects potentiated the cytokine responses in association with activation of TLR but did not alter the HDL content of methylarginines or SAA. CONCLUSION: Both ACEI and ARB stabilized HDL cholesterol acceptor function and sustained cellular anti-oxidative effects but not anti-inflammatory effects, and ACEI-treatment instead amplified the HDL inflammatory response. The findings reveal possible utility of antagonizing angiotensin actions in MDH and suggest a possible mechanism for superiority of ARB vs ACEI in the setting of advanced kidney disease.

Prognostic Markers of Outcome in Patients Undergoing Infra-inguinal Revascularisation: A Prospective Observational Pilot Study.

OBJECTIVES: The aim was to investigate whether cardiopulmonary exercise testing (CPET) variables derived from cycle and arm ergonometry correlate, and whether CPET variables and pre-operative N-terminal pro-brain natriuretic peptide (NT-proBNP) have prognostic significance and if the combination of the two has incremental value. METHODS: A prospective observational pilot study was conducted; 70 patients who underwent infra-inguinal bypass surgery were recruited. Pre-operatively subjects underwent CPET with both arm and leg ergonometry, to measure peak oxygen consumption, anaerobic threshold (AT), and ventilatory equivalents. In addition pre-operative serum samples of NT-proBNP were obtained. The primary endpoint was 1 year all-cause mortality; in addition, data were collected on complications, morbidity, length of stay, and major adverse cardiac events (MACE). RESULTS: The 1 year mortality rate was 6%, the overall complications rate was 23%, and the combined incidence of MACE and 1 year mortality was 10%. Cycle ergonometry peak VO2 14 mL/kg/min (RR 5.5, 95% CI 1.4-22.4, p = .007) and AT < 10mL/kg/min (RR 3.0, 95% CI 1.1-7.0, p = .03) were predictors of post-operative complications. Pre-operative NT-proBNP > 320 ng/L (RR 18, 95% CI 2.5-140 p = .0003) was the sole predictor of 1 year mortality or MACE. CONCLUSION: The measurement of pre-operative NT-proBNP in peripheral vascular disease patients undergoing infra-inguinal bypass can predict 1 year mortality and MACE. CPET variables from cycle ergonometry are predictors of post-operative complications in this patient group.

Associations between participation in family activities and adolescent school problems.

INTRODUCTION: Adolescent risk outcomes related to school issues are widespread, with about 20% parents reporting poor school engagement amongst their youth. Previous literature suggests that adolescents who report strong bonds with their parents are often identified as being less likely to engage in risky behaviours, such as substance use. The current study sought to examine the association between the frequencies of selected family activities and school problems amongst adolescents after adjustments for family connectedness and other characteristics. METHODS: Data were drawn from the National Longitudinal Survey of Youth, 1997. Of the 8984 youth interviewed, 3855 also had a sibling interviewed who met the selection criteria. School problem outcomes measured were suspension occurrence, poor grades and highest grade completed low for age. Independent variables of interest were self-reported frequency of family dinner, fun and religious activities in a typical week. Multivariable logistic models were estimated for each outcome, and multivariable linear probability models were estimated adjusting for family fixed effects. RESULTS: Adjusting for family connectedness, there were significant associations between certain family activities and adolescent school problem measures. However, these results did not remain significant in models with family fixed effects, suggesting that associations could be driven by family-level confounders. DISCUSSION: This study did not find strong evidence of a protective relationship between family activities and school problems. Therefore, it suggested that programme and policymakers be cautious in overstating the importance of family activities in preventing adolescent risk outcomes until true causal relationships can be determined.

Preimplant Normothermic Liver Perfusion of a Suboptimal Liver Donated After Circulatory Death.

Livers retrieved after circulatory death are associated with an increased incidence of primary nonfunction, early allograft dysfunction, and biliary strictures. The authors report a case of preimplant normothermic perfusion of a suboptimal liver from a 57-year-old donor after circulatory death who had been hospitalized for 9 days; predonation alanine transaminase level was 63 IU/L, and the period from withdrawal of life-supporting treatment to circulatory arrest was 150 minutes. After 5 hours of static cold storage, the liver was subject to normothermic machine perfusion with a plasma-free red cell-based perfusate. Perfusate lactate level fell from 7.2 to 0.3 mmol/L within 74 minutes of ex situ perfusion, at which point perfusate alanine transaminase level was 1152 IU/L and urea concentration was 9.4 mmol/L. After 132 minutes, normothermic perfusion was stopped and implantation begun. After transplantation, the patient made an uneventful recovery and was discharged on day 8; liver biochemistry was normal by day 19 and has remained normal thereafter. Donor common bile duct excised at implantation showed preservation of peribiliary glands, and cholangiography 6 months posttransplantation showed no evidence of cholangiopathy. Preimplant ex situ normothermic perfusion of the liver appears to be a promising way to evaluate a marginal liver before transplantation and may modify the response to ischemia.

Symptoms of generalized anxiety disorder but not panic disorder at age 15 years increase the risk of depression at 18 years in the Avon Longitudinal Study of Parents and Children (ALSPAC) cohort study.

BACKGROUND: Generalized anxiety disorder (GAD) and panic disorder (PD) differ in their biology and co-morbidities. We hypothesized that GAD but not PD symptoms at the age of 15 years are associated with depression diagnosis at 18 years. METHOD: Using longitudinal data from the Avon Longitudinal Study of Parents and Children (ALSPAC) birth cohort we examined relationships of GAD and PD symptoms (measured by the Development and Well-Being Assessment) at 15 years with depression at 18 years (by the Clinical Interview Schedule - Revised) using logistic regression. We excluded adolescents already depressed at 15 years and adjusted for social class, maternal education, birth order, gender, alcohol intake and smoking. We repeated these analyses following multiple imputation for missing data. RESULTS: In the sample with complete data (n = 2835), high and moderate GAD symptoms in adolescents not depressed at 15 years were associated with increased risk of depression at 18 years both in unadjusted analyses and adjusting for PD symptoms at 15 years and the above potential confounders. The adjusted odds ratio (OR) for depression at 18 years in adolescents with high relative to low GAD scores was 5.2 [95% confidence interval (CI) 3.0-9.1, overall p < 0.0001]. There were no associations between PD symptoms and depression at 18 years in any model (high relative to low PD scores, adjusted OR = 1.3, 95% CI 0.3-4.8, overall p = 0.737). Missing data imputation strengthened the relationship of GAD symptoms with depression (high relative to low GAD scores, OR = 6.2, 95% CI 3.9-9.9) but those for PD became weaker. CONCLUSIONS: Symptoms of GAD but not PD at 15 years are associated with depression at 18 years. Clinicians should be aware that adolescents with GAD symptoms may develop depression.