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This article explores the challenges of designing equitable selection criteria for a pre-university 'talent development' programme for high school learners from disadvantaged communities. It is argued that by giving due consideration to personal and environmental factors, it becomes possible to more reliably assess academic talent in inequitable contexts. The authors suggest that the experiences of the Go to University to Succeed (GUTS) programme in selecting learners could be transferred to other countries which, like South Africa, grapple with large inequities in socio-economic status and quality of education. [ABSTRACT FROM AUTHOR]

The terms often used in conceptualisations of academic talent are highly variable, with each term employed holding specific ideological implications. This article aims to provide a broad overview of the concept of 'academic talent' in the international and South African literature. In an attempt to connect international academic discourses to the local context, the review explores several discourses of academic talent within the South African context. It is argued that holistic, student-centred approaches towards nurturing academic talent will allow for contextual considerations in the identification of individuals selected to participate in talent development programmes. It is also argued that inclusive approaches to developing talent appear to be premised on the view that learners from educationally disadvantaged backgrounds can be nurtured towards academic success. Addressing educational disadvantage is not a 'quick ix' but requires intensive support and an understanding of issues facing disadvantaged learners (including values orientation conflicts, self-esteem and self-concept). What is pertinent in the article is that the assumptions and values upon which the constructs are based need to take into account individuals within a particular context. Contextual variability, therefore, requires reformulations of the construct. [ABSTRACT FROM AUTHOR]

Scleractinian corals have demonstrated the ability to shuffle their endosymbiotic dinoflagellate communities (genus Symbiodinium) during periods of acute environmental stress. This has been proposed as a mechanism of acclimation, which would be increased by a diverse and flexible association with Symbiodinium. Conventional molecular techniques used to evaluate Symbiodinium diversity are unable to identify genetic lineages present at background levels below 10%. Next generation sequencing ( NGS) offers a solution to this problem and can resolve microorganism diversity at much finer scales. Here we apply NGS to evaluate Symbiodinium diversity and host specificity in Acropora corals from contrasting regions of Western Australia. The application of 454 pyrosequencing allowed for detection of Symbiodinium operational taxonomic units ( OTUs) occurring at frequencies as low as 0.001%, offering a 10 000-fold increase in sensitivity compared to traditional methods. All coral species from both regions were overwhelmingly dominated by a single clade C OTU (accounting for 98% of all recovered sequences). Only 8.5% of colonies associated with multiple clades (clades C and D, or C and G), suggesting a high level of symbiont specificity in Acropora assemblages in Western Australia. While only 40% of the OTUs were shared between regions, the dominance of a single OTU resulted in no significant difference in Symbiodinium community structure, demonstrating that the coral-algal symbiosis can remain stable across more than 15° of latitude and a range of sea surface temperature profiles. This study validates the use of NGS platforms as tools for providing fine-scale estimates of Symbiodinium diversity and can offer critical insight into the flexibility of the coral-algal symbiosis. [ABSTRACT FROM AUTHOR]

Background: Subtropical coral reefs are comparatively understudied compared to tropical coral reef ecosystems, yet also host a diverse and abundant array of marine life and provide substantial socio-economic benefits to communities. Research into the impacts of ocean warming on subtropical coral reefs has increased over the past two decades due to increase frequency and intensity of bleaching and degradation of these ecosystems. Understanding the extent of research effort and type of evidence assessing the response of subtropical corals and reefs to ocean warming provides valuable insight into global patterns in research efforts allowing critical knowledge gaps to be identified. A comprehensive understanding the impact of ocean warming on these systems will underpin our ability to predict and respond to future changes on subtropical coral reefs. Here, a systematic-map approach is used to identify recent research effort, from 2010 to 2023, and highlight patterns in the type, scale, and location of research conducted and as well as identify the availability of data and evidence reported., Methods: Primary literature was identified by searching Scopus and Science Citation Index Expanded through Web of Science Core Collection databases. The methodologies provided in a previously published systematic map protocol were applied, and 90 primary research publications were subsequently identified. Data extraction from the identified literature included bibliometric data, discipline and type of research, type of data reported and how it was recorded, and data availability., Findings: The identified literature consisted primarily of experimental (49%) and observational (39%) studies. The majority of the primary literature investigated corals in the ecoregions of Southern China (13%), Western Mediterranean (10%) and across a total of seven ecoregions grouped within Oceania (29%). Stressors reported in the literature as drivers of ocean warming reflect the standardisation of methods applied in reporting of events within the literature. Standardised metrics related to degree heating weeks (DHW) and marine heatwaves (MHW) have been reported when assessing the occurrence and severity of drivers, and are increasing in recent years, particularly in Australia. Finally, the need for increased research effort across much of the subtropics is evident, particularly for understudied regions such as the Western Indian Ocean where there are far fewer studies than other similar subtropical coral reef ecosystems., Conclusions: Climatic change, increasing ocean temperatures, and the impacts to subtropical and temperate coral reefs are of increasing concern to policy makers and researchers alike. This systematic map provides a broad overview of research topics and effort around the globe since 2010 and identifies areas where more research effort is urgently needed. Our study has identified major research clusters in Asia, Australia, the Mediterranean, and North America and gaps of research in regions such as the East Indian Oceans. Of the research conducted to date approximately one third reports on evidence related to marine protected areas and the vast majority of evidence is from close/territorial sea locations, providing important knowledge base for management of these areas. Of the 17 studies reporting on specific extreme events (rather than experimental studies which is the majority of evidence identified here) 13 have been published since 2019, with the majority reporting on events occurring in 2019/20 indicating a trend of increasing evidence in recent years (a total of 7 studies from 2010 to 2013, compared to over 10 studies published annually since 2019 up to mid-2023)., Competing Interests: Declarations. Ethics approval and consent to participate: Not applicable. Consent for publication: Not applicable. Competing interests: The authors declare that they have no competing interests., (© 2024. The Author(s).)

Persistent SARS-CoV-2 infections may act as viral reservoirs that could seed future outbreaks 1-5 , give rise to highly divergent lineages 6-8 and contribute to cases with post-acute COVID-19 sequelae (long COVID) 9,10 . However, the population prevalence of persistent infections, their viral load kinetics and evolutionary dynamics over the course of infections remain largely unknown. Here, using viral sequence data collected as part of a national infection survey, we identified 381 individuals with SARS-CoV-2 RNA at high titre persisting for at least 30 days, of which 54 had viral RNA persisting at least 60 days. We refer to these as 'persistent infections' as available evidence suggests that they represent ongoing viral replication, although the persistence of non-replicating RNA cannot be ruled out in all. Individuals with persistent infection had more than 50% higher odds of self-reporting long COVID than individuals with non-persistent infection. We estimate that 0.1-0.5% of infections may become persistent with typically rebounding high viral loads and last for at least 60 days. In some individuals, we identified many viral amino acid substitutions, indicating periods of strong positive selection, whereas others had no consensus change in the sequences for prolonged periods, consistent with weak selection. Substitutions included mutations that are lineage defining for SARS-CoV-2 variants, at target sites for monoclonal antibodies and/or are commonly found in immunocompromised people 11-14 . This work has profound implications for understanding and characterizing SARS-CoV-2 infection, epidemiology and evolution., (© 2024. The Author(s).)

Groundwater is a vital ecosystem of the global water cycle, hosting unique biodiversity and providing essential services to societies. Despite being the largest unfrozen freshwater resource, in a period of depletion by extraction and pollution, groundwater environments have been repeatedly overlooked in global biodiversity conservation agendas. Disregarding the importance of groundwater as an ecosystem ignores its critical role in preserving surface biomes. To foster timely global conservation of groundwater, we propose elevating the concept of keystone species into the realm of ecosystems, claiming groundwater as a keystone ecosystem that influences the integrity of many dependent ecosystems. Our global analysis shows that over half of land surface areas (52.6%) has a medium-to-high interaction with groundwater, reaching up to 74.9% when deserts and high mountains are excluded. We postulate that the intrinsic transboundary features of groundwater are critical for shifting perspectives towards more holistic approaches in aquatic ecology and beyond. Furthermore, we propose eight key themes to develop a science-policy integrated groundwater conservation agenda. Given ecosystems above and below the ground intersect at many levels, considering groundwater as an essential component of planetary health is pivotal to reduce biodiversity loss and buffer against climate change., (© 2023 The Authors. Global Change Biology published by John Wiley & Sons Ltd.)

The Office for National Statistics Coronavirus (COVID-19) Infection Survey (ONS-CIS) is the largest surveillance study of SARS-CoV-2 positivity in the community, and collected data on the United Kingdom (UK) epidemic from April 2020 until March 2023 before being paused. Here, we report on the epidemiological and evolutionary dynamics of SARS-CoV-2 determined by analysing the sequenced samples collected by the ONS-CIS during this period. We observed a series of sweeps or partial sweeps, with each sweeping lineage having a distinct growth advantage compared to their predecessors, although this was also accompanied by a gradual fall in average viral burdens from June 2021 to March 2023. The sweeps also generated an alternating pattern in which most samples had either S-gene target failure (SGTF) or non-SGTF over time. Evolution was characterized by steadily increasing divergence and diversity within lineages, but with step increases in divergence associated with each sweeping major lineage. This led to a faster overall rate of evolution when measured at the between-lineage level compared to within lineages, and fluctuating levels of diversity. These observations highlight the value of viral sequencing integrated into community surveillance studies to monitor the viral epidemiology and evolution of SARS-CoV-2, and potentially other pathogens.

Purpose: To evaluate and compare surgical outcomes for syndromes with optically empty vitreous (SOEV)-associated rhegmatogenous retinal detachments., Design: A retrospective, cross-sectional, 2-arm study of a single pediatric vitreoretinal surgeon's patients from a quaternary referral center with SOEV was performed to examine visual and anatomical outcomes of rhegmatogenous retinal detachment and laser prophylaxis., Subjects: Patients identified either through slit-lamp examination (presence of an optically empty or void space in the vitreous gel structure) or genetic testing. Fifty-six eyes of 49 patients were identified in the retinal detachment arm. Sixty eyes of 48 patients were identified in the laser prophylaxis arm., Methods: Comparison of initial retinal detachment (RD) surgical repair via pars plana vitrectomy (PPV), scleral buckle (SB), or PPV-SB with final anatomical success, best-corrected visual acuity (BCVA), and number of surgical procedures. Secondary analysis was performed looking at eyes failing their initial SB, eyes with a giant retinal tear at presentation, eyes failing RD repair within specific time intervals, and eyes where hyaloid was elevated during initial vitrectomy. An additional study arm examined the outcomes of final BCVA and the presence and timing of developing a retinal tear or RD in eyes who received laser prophylaxis., Main Outcome Measures: Visual acuity, surgical repair techniques (PPV, SB, PPV-SB), number of surgeries, anatomical retinal reattachment success., Results: Initial SB had statistically significant better final BCVA (P < 0.01) and better final anatomical success (P < 0.01). No statistical difference in the number of surgeries needed to achieve anatomical success between the initial SB versus initial PPV-SB/PPV. Hyaloidal elevation during the initial vitrectomy was associated with improved final BCVA and higher final anatomical success without the use of silicone oil (P < 0.01 and 0.04 respectively). Lastly, eyes that developed RDs after laser prophylaxis had better final BCVA than untreated eyes (P < 0.05)., Conclusion: Initial SB yields better overall outcomes in SOEV presenting with rhegmatogenous retinal detachment. Stickler Type-1 patients had similar outcomes compared with other SOEV, suggesting both populations should be treated with similar approaches., Financial Disclosure(s): The author(s) have no proprietary or commercial interest in any materials discussed in this article., (Copyright © 2023 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

In this study, we evaluated the impact of viral variant, in addition to other variables, on within-host viral burden, by analysing cycle threshold (Ct) values derived from nose and throat swabs, collected as part of the UK COVID-19 Infection Survey. Because viral burden distributions determined from community survey data can be biased due to the impact of variant epidemiology on the time-since-infection of samples, we developed a method to explicitly adjust observed Ct value distributions to account for the expected bias. By analysing the adjusted Ct values using partial least squares regression, we found that among unvaccinated individuals with no known prior exposure, viral burden was 44% lower among Alpha variant infections, compared to those with the predecessor strain, B.1.177. Vaccination reduced viral burden by 67%, and among vaccinated individuals, viral burden was 286% higher among Delta variant, compared to Alpha variant, infections. In addition, viral burden increased by 17% for every 10-year age increment of the infected individual. In summary, within-host viral burden increases with age, is reduced by vaccination, and is influenced by the interplay of vaccination status and viral variant., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Fryer et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Case: A 45-year-old female patient presented with left knee pain after a ski accident. Magnetic Resonance Imaging (MRI) showed complete rupture of the anterior cruciate ligament, posterior cruciate ligament, proximal Medial Collateral Ligament (MCL), and medial patellofemoral ligament. The lateral meniscal root was torn with the posterior horn incarcerated superiorly into the popliteal hiatus, rendering high risk of plastic deformation. An unconventional 2-staged surgical approach was performed., Conclusion: Where risk of meniscal plastic deformation is high in the setting of multiligamentous knee injury (MLKI), diagnosis and careful surgical planning are central to a successful outcome. Treatment of intra-articular structures in operative stage 1 in MLKI is possible and was necessary in this case., Competing Interests: Disclosure: The Disclosure of Potential Conflicts of Interest forms are provided with the online version of the article (http://links.lww.com/JBJSCC/C141)., (Copyright © 2023 by The Journal of Bone and Joint Surgery, Incorporated.)

Background: Student burnout during medical education is a prevalent and critical problem. Burnout has reaching consequences, including negative health outcomes for students, financial loss for schools, and worsened patient care as students transition to practice. Global Health Outreach Experiences (GHOEs), known to enhance cultural awareness and clinical knowledge among medical students, are offered in most programs. Prior studies document that GHOEs benefit physicians suffering from burnout, with effects demonstrating improvement over 6 months. No study, to our knowledge, has assessed the influence GHOEs may have on medical student burnout with a comparable control group. This study examines whether participation in a GHOE, compared to a standard break from school, has a positive effect on burnout., Methods: A case control study utilizing the Copenhagen Burnout Inventory was conducted on medical students. 41 students participated in a one-week, spring break GHOE and 252 were randomly selected as non-participating students in a control group. Assessments were gathered 1 week prior, 1 week after, and 10 weeks after spring break. Response across the surveys in chronological order included 22, 20, 19 GHOE and 70, 66, 50 control participants., Results: A significant reduction in personal burnout (PB) (P = 0.0161), studies related burnout (SRB) (P = 0.0056), and colleagues related burnout (CRB) (P = 0.0357) was found among GHOE attendees compared to control participants at 10-weeks after spring break. When modeled with potential confounders, CRB and SRB reductions remained significant., Conclusion: GHOEs may be a potential tool for institutions to combat burnout rates in their students. The benefits of GHOEs appear to enhance over time., (© 2023. The Author(s).)

The aim of our study is to document our cases of choroidal melanoma treated with low dose rate (LDR) brachytherapy and to correlate the dosimetry and radiobiology with clinical effects and oncologic outcomes. Data from 157 patients treated from 2014 to 2018 with LDR brachytherapy were used for this investigation. Treatments used a collaborative ocular melanoma study eye plaque and Iodine-125 radioactive seeds. The seeds activities were chosen to deliver 85 Gy to the tumor apex or to a prescription point (if the apex < 5 mm). The plaque sizes used were 10, 12, 14, 16, 18, 20, and 22 mm including notched or deep notched. The plaques were modeled in Varian BrachyVision version 11.6 (Varian Medical Systems) with seed coordinates from the AAPM Task Group 129. The Task Group 43 from AAPM was used for brachytherapy dose planning. Dose data were extracted for the apex, prescription point, sclera, retina opposite to the implant, lens, macula, and optic disc. The radiobiological dosimetry were calculated using appropriate α/β ratios found in the literature and then correlated to clinical side effects. Average biologically effective dose for associated organs at risk were calculated in cases where toxicity occurred. These included: radiation cataract (70.66 Gy), disc atrophy (475.49 Gy), foveal atrophy (263.07 Gy), radiation papillopathy (373.45 Gy), radiation maculopathy (213.62 Gy), vitreous hemorrhage (1437.68 Gy), vascular occlusion (1080.93 Gy), nonproliferative retinopathy (1066.89 Gy), proliferative retinopathy (1590.71 Gy), exudative retinal detachment (1364.32 Gy), and rhegmatogenous retinal detachment (2265.54 Gy). Average biologically effective dose was higher in patients who developed radiation induced long term side effects than in the whole patient population except for radiation maculopathy. In spite of the small patient population and short-term follow-up, it is of interest to correlate the radiation induced effects and create a guideline for the improvement of the treatment of patients treated with LDR brachytherapy., (Copyright © 2022 American Association of Medical Dosimetrists. Published by Elsevier Inc. All rights reserved.)

(1) Background: Glaucoma is a leading cause of irreversible blindness worldwide. Unfortunately, no noticeable symptoms exist until mid- to late-stage glaucoma, leading to substantial costs to the patient and the healthcare system. (2) Methods: The Student Sight Savers Program, an initiative started at Johns Hopkins University, was designed to meet the needs of community screening for glaucoma. Several medical students at the Rocky Vista University in Saint George, Utah, were trained, and screened patients at local fairs and gathering places using a modified version of this program. Patients found to have elevated pressure (>21 mmHg) or other ocular abnormalities were referred for an ophthalmological examination. (3) Results: Individuals from medically underserved areas/populations (MUA/Ps) were nearly three times as likely to have elevated intraocular pressure as individuals not in underserved areas (p = 0.0141). A further analysis demonstrates that medical students can help reduce medical costs for patients and the healthcare system by providing referrals to ophthalmologists and reaching populations that are not usually screened for glaucoma. (4) Conclusions: Allowing medical students to perform community-based glaucoma screening events in MUA/Ps using handheld tonometers may decrease the cost burden associated with late diagnosis, and raise awareness about glaucoma, especially in underserved populations.

Adrenal incidentalomas are incidentally discovered adrenal masses greater than one centimeter in diameter. An association between insulin resistance and adrenal incidentalomas has been established. However, the pathophysiological link between these two conditions remains incompletely characterized. This review examines the literature on the interrelationship between insulin resistance and adrenal masses, their subtypes, and related pathophysiology. Some studies show that functional and non-functional adrenal masses elicit systemic insulin resistance, whereas others conclude the inverse. Insulin resistance, hyperinsulinemia, and the anabolic effects on adrenal gland tissue, which have insulin and insulin-like growth factor-1 receptors, offer possible pathophysiological links. Conversely, autonomous adrenal cortisol secretion generates visceral fat accumulation and insulin resistance. Further investigation into the mechanisms and timing of these two pathologies as they relate to one another is needed and could be valuable in the prevention, detection, and treatment of both conditions.

Purpose: To assess outcomes of small and medium choroidal melanoma (less than 5.0 mm in height) following Iodine-125 episcleral brachytherapy., Methods and Materials: Patients with small and medium choroidal melanoma that underwent Iodine-125 brachytherapy with apical height of 1.0 mm to 5.0 mm and largest basal diameter of ≤16.0 mm were included. Data were extracted from the original dosimetry plans to determine doses to vision critical structures with the prescription point to the apical height (actual dose, ABS guidelines) and, after simulation, with the prescription point to the height of 5.0 mm (simulated dose, COMS protocol). Visual acuity (VA) outcomes with actual dose and that predicted with the simulated dose were estimated along with local recurrence, ocular survival, and survival at 5 years., Results: A total of 339 patients with a mean age of 61.5 years with a mean follow up duration of 43.4 months were included. The mean dose reduction for lens, optic disc, and fovea was 34%, 39.4%, and 41.4%, respectively with actual dose when compared with simulated dose. The Kaplan-Meier estimations for 3 year event free rate of VA of 20/50 or better were 56% and 31% for actual dose and simulated dose, respectively. Only 3 events of local recurrence were observed (enucleated) yielding 5 year local control and ocular survival rate of 98%. Overall survival (OS) and metastasis free survival (MFS) were 95% and 87.5% at 5 years, respectively., Conclusions: Small and medium choroidal melanoma treated according to ABS has excellent outcomes. Brachytherapy planning using ABS guidelines as compared to COMS protocol may be associated with lower rates of radiation toxicity and vision loss., (Copyright © 2021 American Brachytherapy Society. Published by Elsevier Inc. All rights reserved.)

Stony corals (Scleractinia) form the basis for some of the most diverse ecosytems on Earth, but we have much to learn about their evolutionary history and systematic relationships. In order to improve our understanding of species in corals we here investigated phylogenetic relationships between morphologically defined species and genetic lineages in the genus Galaxea (Euphyllidae) using a combined phylogenomic and phylogeographic approach. Previous studies revealed the nominal species G. fascicularis included three genetically well-differentiated lineages (L, S & L+) in the western Pacific, but their distribution and relationship to other species in the genus was unknown. Based on genomic (RAD-seq) and mitochondrial sequence data (non-coding region between cytb and ND2) we investigated whether the morphological taxa represent genetically coherent entities and what is the phylogenetic relationship and spatial distribution of the three lineages of G. fascicularis throughout the observed species range. Using the RAD-seq data, we find that the genus Galaxea is monophyletic and contains three distinct clades: an Indo-Pacific, a Pacific, and a small clade restricted to the Chagos Archipelago. The three lineages of G. fascicularis were associated with different RAD-seq clades, with the 'L' lineage showing some morphological distinction from the other two lineages (larger more asymmetrical polyps). In addition to these, three more genetic lineages in G. fascicularis may be distinguished - a Chagossian, an Ogasawaran, and one from the Indian-Red Sea. Among nominal taxa for which we have multiple samples, G. horrescens was the only monophyletic species. The mitochondrial non-coding region is highly conserved apart of the length polymorphism used to define L, S & L+ lineages and lacks the power to distinguish morphological and genetic groups resolved with genomic RAD-sequencing. The polyphyletic nature of most species warrants a careful examination of the accepted taxonomy of this group with voucher collections and their comparison to type specimens to resolve species boundaries. Further insight to the speciation process in corals will require international cooperation for the sharing of specimens to facilitate scientific discovery., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Management strategies designed to conserve coral reefs threatened by climate change need to incorporate knowledge of the spatial distribution of inter- and intra-specific genetic diversity. We characterized patterns of genetic diversity and connectivity using single nucleotide polymorphisms (SNPs) in two reef-building corals to explore the eco-evolutionary processes that sustain populations in north-west Australia. Our sampling focused on the unique reefs of the Kimberley; we collected the broadcast spawning coral Acropora aspera ( n  = 534) and the brooding coral Isopora brueggemanni ( n  = 612) across inter-archipelago (tens to hundreds of kilometres), inter-reef (kilometres to tens of kilometres) and within-reef (tens of metres to a few kilometres) scales. Initial analysis of A. aspera identified four highly divergent lineages that were co-occurring but morphologically similar. Subsequent population analyses focused on the most abundant and widespread lineage, Acropora asp-c. Although the overall level of geographic subdivision was greater in the brooder than in the spawner, fundamental similarities in patterns of genetic structure were evident. Most notably, limits to gene flow were observed at scales <35 kilometres. Further, we observed four discrete clusters and a semi-permeable barrier to dispersal that were geographically consistent between species. Finally, sites experiencing bigger tides were more connected to the metapopulation and had greater gene diversity than those experiencing smaller tides. Our data indicate that the inshore reefs of the Kimberley are genetically isolated from neighbouring oceanic bioregions, but occasional dispersal between inshore archipelagos is important for the redistribution of evolutionarily important genetic diversity. Additionally, these results suggest that networks of marine reserves that effectively protect reefs from local pressures should be spaced within a few tens of kilometres to conserve the existing patterns of demographic and genetic connectivity., Competing Interests: None declared., (© 2020 The Authors. Evolutionary Applications published by John Wiley & Sons Ltd.)

Without drastic efforts to reduce carbon emissions and mitigate globalized stressors, tropical coral reefs are in jeopardy. Strategic conservation and management requires identification of the environmental and socioeconomic factors driving the persistence of scleractinian coral assemblages-the foundation species of coral reef ecosystems. Here, we compiled coral abundance data from 2,584 Indo-Pacific reefs to evaluate the influence of 21 climate, social and environmental drivers on the ecology of reef coral assemblages. Higher abundances of framework-building corals were typically associated with: weaker thermal disturbances and longer intervals for potential recovery; slower human population growth; reduced access by human settlements and markets; and less nearby agriculture. We therefore propose a framework of three management strategies (protect, recover or transform) by considering: (1) if reefs were above or below a proposed threshold of >10% cover of the coral taxa important for structural complexity and carbonate production; and (2) reef exposure to severe thermal stress during the 2014-2017 global coral bleaching event. Our findings can guide urgent management efforts for coral reefs, by identifying key threats across multiple scales and strategic policy priorities that might sustain a network of functioning reefs in the Indo-Pacific to avoid ecosystem collapse.

A subset of men with prostate cancer develops aggressive disease. We sought to determine whether miR-182, an miRNA with reported oncogenic functions in the prostate, is associated with biochemical recurrence and aggressive disease. Prostate epithelial miR-182 expression was quantified via in situ hybridization of two prostate tissue microarrays and by laser-capture microdissection of prostate epithelium. miR-182 was significantly higher in cancer epithelium than adjacent benign epithelium (P < 0.0001). The ratio of cancer to benign miR-182 expression per patient was inversely associated with recurrence in a multivariate logistic regression model (odds ratio = 0.18; 95% CI, 0.03-0.89; P = 0.044). Correlation of miR-182 with mRNA expression in laser-capture microdissected benign prostate epithelium was used to predict prostatic miR-182 targets. Genes that were negatively correlated with miR-182 were enriched for its predicted targets and for genes previously identified as up-regulated in prostate cancer metastases. miR-182 expression was also negatively correlated with genes previously identified as up-regulated in primary prostate tumors from African American patients, who are at an increased risk of developing aggressive prostate cancer. Taken together, these results suggest that although miR-182 is expressed at higher levels in localized prostate cancer, its levels are lower in aggressive cancers, suggesting a biphasic role for this miRNA that may be exploited for prognostic and/or therapeutic purposes to reduce prostate cancer progression., (Copyright © 2019 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.)

The fibromuscular stroma of the prostate regulates normal epithelial differentiation and contributes to carcinogenesis in vivo. We developed and characterized a human 3D prostate organoid co-culture model that incorporates prostate stroma. Primary prostate stromal cells increased organoid formation and directed organoid morphology into a branched acini structure similar to what is observed in vivo. Organoid branching occurred distal to physical contact with stromal cells, demonstrating non-random branching. Stroma-induced phenotypes were similar in all patients examined, yet they maintained inter-patient heterogeneity in the degree of response. Stromal cells expressed growth factors involved in epithelial differentiation, which was not observed in non-prostatic fibroblasts. Organoids derived from areas of prostate cancer maintained differential expression of alpha-methylacyl-CoA racemase and showed increased viability and passaging when co-cultured with stroma. The addition of stroma to epithelial cells in vitro improves the ability of organoids to recapitulate features of the tissue and enhances the viability of organoids., (Copyright © 2019 The Author(s). Published by Elsevier Inc. All rights reserved.)

This paper describes a detailed protocol for three-dimensional (3D) culturing, handling, and evaluation of human primary prostate organoids. The process involves seeding of epithelial cells sparsely in a 3D matrix gel on a 96-well microplate with media changes to cultivate expansion into organoids. Morphology is then assessed by whole-well capturing of z-stack images. Compression of z-stacks creates a single in-focus image from which organoids are measured to quantify a variety of outputs, including circularity, roundness, and area.DNA, RNA, and protein can be collected from organoids recovered from the matrix gel. Cell populations of interest can be assessed by organoid dissociation and flow cytometry. Formalin-fixation-paraffin-embedding (FFPE) followed by sectioning is used for the histological assessment and antibody staining. Whole-mount immunofluorescent staining preserves organoid morphology and facilitates observation of protein localization in organoids in situ. Commercial assays that are traditionally used for 2D monolayer cells can be modified for 3D organoids. Used together, the techniques in this protocol provide a robust toolbox to quantify prostate organoid growth, morphologic characteristics, and expression of differentiation markers.

Objective: Recent studies have identified parents and children as two target groups whom Big Food hopes to positively influence through its corporate social responsibility (CSR) strategies. The current preliminary study aimed to gain an in-depth understanding of parents and children's awareness and interpretation of Big Food's CSR strategies to understand how CSR shapes their beliefs about companies., Design: Community-based qualitative semi-structured interviews., Setting: New South Wales, Australia., Subjects: Parents (n 15) and children aged 8-12 years (n 15)., Results: Parents and children showed unprompted recognition of CSR activities when shown McDonald's and Coca-Cola brand logos, indicating a strong level of association between the brands and activities that target the settings of children. When discussing CSR strategies some parents and most children saw value in the activities, viewing them as acts of merit or worth. For some parents and children, the companies' CSR activities were seen as a reflection of the company's moral attributes, which resonated with their own values of charity and health. For others, CSR strategies were in conflict with companies' core business. Finally, some also viewed the activities as harmful, representing a deceit of the public and a smokescreen for the companies' ultimately unethical behaviour., Conclusions: A large proportion of participants valued the CSR activities, signalling that denormalising CSR to sever the strong ties between the community and Big Food will be a difficult process for the public health community. Efforts to gain public acceptance for action on CSR may need greater levels of persuasion to gain public support of a comprehensive and restrictive approach.

The miR-183 cluster, which is comprised of paralogous miRs-183, -96 and -182, is overexpressed in many cancers, including prostate adenocarcinoma (PCa). Prior studies showed that overexpression of individual pre-miRs-182, -96 and -183 in prostate cells decreased zinc import, which is a characteristic feature of PCa tumours. Zinc is concentrated in healthy prostate 10-fold higher than any other tissue, and an >80% decrease in zinc is observed in PCa specimens. Here, we studied the effect of overexpression of the entire 4.8 kb miR-183 family cluster, including the intergenic region which contains highly conserved genomic regions, in prostate cells. This resulted in overexpression of mature miR-183 family miRs at levels that mimic cancer-related changes. Overexpression of the miR-183 cluster reduced zinc transporter and intracellular zinc levels in benign prostate cells, PCa xenografts and fresh prostate epithelial organoids. Microarray analysis of miR-183 family cluster overexpression in prostate cells showed an enrichment for cancer-related pathways including adhesion, migration and wound healing. An active secondary transcription start site was identified within the intergenic region of the miR-183 cluster, which may regulate expression of miR-182. Taken together, this study shows that physiologically relevant expression of the miR-183 family regulates zinc levels and carcinogenic pathways in prostate cells.