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Introduction: Cytomegalovirus (CMV) retinitis in the setting of pediatric retinoblastoma is exceedingly unusual. Here, we present the first reported case of CMV retinitis in an enucleated eye with retinoblastoma after chemotherapy in the western hemisphere. Case Presentation: A 2-year-old Hispanic male without a family history of retinoblastoma presented with a 3-month history of right eye exotropia and squinting. Clinical examination revealed dense white vitreous opacities in the right eye. Ocular oncology evaluation unveiled an exudative retinal detachment with vitreous seeds, subretinal seeding, and a tumor emanating from the retina in the superonasal quadrant of the right eye. The patient was diagnosed with unilateral Group D retinoblastoma, and RB1 sequencing revealed a pathogenic variant with mosaicism. Treatment involved systemic chemotherapy, intravitreal chemotherapy, and cryotherapy. However, the patient developed a rhegmatogenous retinal detachment with diffuse vitreous hemorrhage and ultimately underwent right eye enucleation. Interestingly, histopathological analysis of the enucleated eye revealed concomitant CMV retinitis alongside retinoblastoma. After consultation with infectious disease, antiviral treatment was not initiated as the patient remained asymptomatic and maintained a recovered immune system. Repeat CMV PCR confirmed viral clearance. The patient received a prosthetic eye and continues to be monitored for retinoblastoma recurrence. Conclusion: Clinicians should be aware of the potential for CMV retinitis to develop in retinoblastoma patients receiving chemotherapy, which may complicate clinical decision-making and management. Timely identification of CMV retinitis in this setting may improve patient ocular outcomes and overall prognosis.

1,4-naphthoquinones (NQs) catalytically oxidize H2S to per- and polysufides and sulfoxides, reduce oxygen to superoxide and hydrogen peroxide, and can form NQ-SH adducts through Michael addition. Here, we measured oxygen consumption and used sulfur-specific fluorophores, liquid chromatography tandem mass spectrometry (LC-MS/MS), and UV-Vis spectrometry to examine H2S oxidation by NQs with various substituent groups. In general, the order of H2S oxidization was DCNQ ~ juglone > 1,4-NQ > plumbagin >DMNQ ~ 2-MNQ > menadione, although this order varied somewhat depending on the experimental conditions. DMNQ does not form adducts with GSH or cysteine (Cys), yet it readily oxidizes H2S to polysulfides and sulfoxides. This suggests that H2S oxidation occurs at the carbonyl moiety and not at the quinoid 2 or 3 carbons, although the latter cannot be ruled out. We found little evidence from oxygen consumption studies or LC-MS/MS that NQs directly oxidize H2S2–4, and we propose that apparent reactions of NQs with inorganic polysulfides are due to H2S impurities in the polysulfides or an equilibrium between H2S and H2Sn. Collectively, NQ oxidation of H2S forms a variety of products that include hydropersulfides, hydropolysulfides, sulfenylpolysulfides, sulfite, and thiosulfate, and some of these reactions may proceed until an insoluble S8 colloid is formed.

Abstract Background Human immunodeficiency virus and acquired immune deficiency syndrome (HIV/AIDS) is still among the leading causes of disease burden and mortality in sub-Saharan Africa (SSA), and the world is not on track to meet targets set for ending the epidemic by the Joint United Nations Programme on HIV/AIDS (UNAIDS) and the United Nations Sustainable Development Goals (SDGs). Precise HIV burden information is critical for effective geographic and epidemiological targeting of prevention and treatment interventions. Age- and sex-specific HIV prevalence estimates are widely available at the national level, and region-wide local estimates were recently published for adults overall. We add further dimensionality to previous analyses by estimating HIV prevalence at local scales, stratified into sex-specific 5-year age groups for adults ages 15–59 years across SSA. Methods We analyzed data from 91 seroprevalence surveys and sentinel surveillance among antenatal care clinic (ANC) attendees using model-based geostatistical methods to produce estimates of HIV prevalence across 43 countries in SSA, from years 2000 to 2018, at a 5 × 5-km resolution and presented among second administrative level (typically districts or counties) units. Results We found substantial variation in HIV prevalence across localities, ages, and sexes that have been masked in earlier analyses. Within-country variation in prevalence in 2018 was a median 3.5 times greater across ages and sexes, compared to for all adults combined. We note large within-district prevalence differences between age groups: for men, 50% of districts displayed at least a 14-fold difference between age groups with the highest and lowest prevalence, and at least a 9-fold difference for women. Prevalence trends also varied over time; between 2000 and 2018, 70% of all districts saw a reduction in prevalence greater than five percentage points in at least one sex and age group. Meanwhile, over 30% of all districts saw at least a five percentage point prevalence increase in one or more sex and age group. Conclusions As the HIV epidemic persists and evolves in SSA, geographic and demographic shifts in prevention and treatment efforts are necessary. These estimates offer epidemiologically informative detail to better guide more targeted interventions, vital for combating HIV in SSA.

The application of natural language processing and machine learning (ML) in electronic health records (EHRs) may help reduce dementia underdiagnosis, but models that are not designed to reflect minority populations may instead perpetuate underdiagnosis. To improve the identification of undiagnosed dementia, particularly in Black Americans (BAs), we developed support vector machine (SVM) ML models to assign dementia risk scores based on features identified in unstructured EHR data (via latent Dirichlet allocation and stable topic extraction in n = 1 M notes) and structured EHR data. We hypothesized that separate models would show differentiation between racial groups, so the models were fit separately for BAs (n = 5 K with dementia ICD codes, n = 5 K without) and White Americans (WAs; n = 5 K with codes, n = 5 K without). To validate our method, scores were generated for separate samples of BAs (n = 10 K) and WAs (n = 10 K) without dementia codes, and the EHRs of 1.2 K of these patients were reviewed by dementia experts. All subjects were age 65+ and drawn from the VA, which meant that the samples were disproportionately male. A strong positive relationship was observed between SVM-generated risk scores and undiagnosed dementia. BAs were more likely than WAs to have undiagnosed dementia per chart review, both overall (15.3% vs. 9.5%) and among Veterans with >90th percentile cutoff scores (25.6% vs. 15.3%). With chart reviews as the reference standard and varied cutoff scores, the BA model performed slightly better than the WA model (AUC = 0.86 with negative predictive value [NPV] = 0.98, positive predictive value [PPV] = 0.26, sensitivity = 0.61, specificity = 0.92 and accuracy = 0.91 at >90th percentile cutoff vs. AUC = 0.77 with NPV = 0.98, PPV = 0.15, sensitivity = 0.43, specificity = 0.91 and accuracy = 0.89 at >90th). Our findings suggest that race-specific ML models can help identify BAs who may have undiagnosed dementia. Future studies should examine model generalizability in settings with more females and test whether incorporating these models into clinical settings increases the referral of undiagnosed BAs to specialists.

Burgundian Inventories of Philip the Bold and Margaret of Flanders Abstract: At the start of the fifteenth century, two dynastic inventories werecompiled, prompted by the death of two key European rulers. The first came into being on the death of Philip the Bold, Duke of Burgundy in 1404, the second on the death of his wife Margaret of Flanders, less than a year later in 1405. These two dynastic inventories preserve references to thousands of moveable objects, but still remain underexplored by historians. This article will reassess these inventories in light of the ‘material turn’ to reconstruct the political theatres and actors involved in their construction. In addition, it will examine the objects of the inventories to reveal the ways in which they operated as agents of dynastic power, maintaining and creating networks of social relations at a critical political moment for the Burgundian dynasty.

BackgroundIntimate partner violence (IPV) is a major public health problem and is the most common form of violence against women. Women with HIV in serodifferent relationships may be at an increased risk of IPV compared to women without HIV, hindering their ability to adhere to antiretroviral therapy, clinic appointments, and condom use during sex. This study assessed the prevalence and correlates of IPV in the past year among women with HIV in serodifferent relationships in Nairobi, Kenya.MethodsThis cross-sectional study included women with HIV in serodifferent relationships who were at least 18 years old and provided written informed consent. Their experience of physical, sexual, or emotional violence in the past year by the current partner was assessed using 13 questions adapted from the World Health Organization survey on violence against women. Standardized instruments were used to assess sociodemographic and behavioral factors. Associations between intimate partner violence and other variables were evaluated using log binomial regression models.ResultsOf the 159 women enrolled, 47 (29.6%, 95% CI 22.9-37.2%) reported IPV in the past year. Of these, 32 (68.1%) reported emotional, 27 (57.4%) physical, and 27 (57.4%) sexual violence. In the multivariate model, pregnancy (adjusted prevalence ratio [aPR] 2.14, 95% CI 1.09-4.20), alcohol use (minimal drinking aPR 1.91, 95% CI 1.10-3.33; moderate/severe drinking aPR 1.17, 95% CI 0.53-2.59), male partner controlling behavior (aPR 2.09, 95% CI 1.24-3.51), and past physical violence (aPR 1.93, 95% CI 1.22-3.05) remained significantly associated with a higher prevalence of IPV in the past year.ConclusionThis study identified a high prevalence of IPV in the past year among women with HIV in serodifferent relationships. Pregnant women and women who had experienced prior violence had a higher prevalence of IPV. These data highlight the need to screen for IPV during clinic visits, and to offer evidence based interventions to support women in serodifferent relationships who have experienced IPV.

Major depressive disorder is a common and disabling disorder with high rates of treatment resistance. Evidence suggests it is characterized by distributed network dysfunction that may be variable across patients, challenging the identification of quantitative biological substrates. We carried out this study to determine whether application of a novel computational approach to a large sample of high spatiotemporal resolution direct neural recordings in humans could unlock the functional organization and coordinated activity patterns of depression networks. This group level analysis of depression networks from heterogenous intracranial recordings was possible due to application of a correlational model-based method for inferring whole-brain neural activity. We then applied a network framework to discover brain dynamics across this model that could classify depression. We found a highly distributed pattern of neural activity and connectivity across cortical and subcortical structures that was present in the majority of depressed subjects. Furthermore, we found that this depression signature consisted of two subnetworks across individuals. The first was characterized by left temporal lobe hypoconnectivity and pathological beta activity. The second was characterized by a hypoactive, but hyperconnected left frontal cortex. These findings have applications toward personalization of therapy.

The IPCC special report on the ocean and cryosphere in a changing climate (SROCC) highlights with high confidence that declining Arctic sea ice extents and increased ship-based transportation are impacting the livelihoods of Arctic Indigenous peoples. Current IPCC assessments cannot address the local scale impacts and adaptive needs of Arctic Indigenous communities based on the global, top-down model approaches used. Inuit maintain the longest unrecorded climate history of sea ice in Canada, and to support Inuit community needs, a decolonized, Inuit knowledge-based approach was co-developed in the community of Mittimatalik, Nunavut (Canada) to create the Mittimatalik siku asijjipallianinga (sea ice climate atlas) 1997–2019. This paper presents the novel approach used to develop the atlas based on Inuit knowledge, earth observations and Canadian Ice Service (CIS) sea ice charts, and demonstrates its application. The atlas provides an adaptation tool that Mittimatalik can use to share locations of known and changing sea ice conditions to plan for safe sea ice travel. These maps can also be used to support the safety and situational awareness of territorial and national search and rescue partners, often coming from outside the region and having limited knowledge of local sea ice conditions. The atlas demonstrates the scientific merit of Inuit knowledge in environmental assessments for negotiating a proposal to extend the shipping seasons for the nearby Mary River Mine. The timing and rates of sea ice freeze-up (October–December) in Mittimatalik are highly variable. There were no significant trends to indicate that sea ice is freezing up later to support increased shipping opportunities into the fall. The atlas shows that the first 2 weeks of November are critical for landfast ice formation, and icebreaking at this time would compromise the integrity of the sea ice for safe travel, wildlife migration and reproduction into the winter months. There was evidence that sea ice break-up (May–July) and the fracturing of the nearby floe edge have been occurring earlier in the last 10 years (2010–2019). Shipping earlier into the break-up season could accelerate the break-up of an already declining sea ice travel season, that Inuit are struggling to maintain.

IntroductionThe postpartum period can be challenging for women living with HIV. Understanding how the postpartum period impacts ART adherence and condomless sex could inform the development of comprehensive sexual and reproductive health and HIV services tailored to the needs of women living with HIV during this critical interval.MethodsIn a longitudinal cohort study of HIV-seropositive Kenyan women, late ART refills and self-reported condomless sex were compared between the woman's pregnancy and the postpartum period. Analyses were conducted using generalized estimating equations and adjusted for alcohol use, depressive symptoms, intimate partner violence (IPV), and having a recent regular partner. Effect modification was explored for selected variables.Results and discussion151 women contributed visits. Late ART refills occurred at 7% (32/439) of pregnancy visits compared to 18% (178/1016) during the postpartum period (adjusted relative risk [aRR] 2.44, 95% confidence interval [CI] 1.62-3.67). This association differed by women's education level. Women with ≥8 years of education had late ART refills more during the postpartum period than pregnancy (aRR 3.00, 95%CI 1.95-4.62). In contrast, in women with ConclusionImproved support for ART adherence during the postpartum period and addressing IPV to limit condomless sex could improve HIV treatment and prevention outcomes for HIV-seropositive women as well as their infants and sexual partners.

Truly transdisciplinary approaches are needed to tackle the complex problems that the Arctic is facing at the moment. Collaboration between Indigenous rights holders and researchers through co-creative research approaches can result in high-quality research outcomes, but crucially also address colonial legacies and power imbalances, enhance mutual trust, and respect the rights of Indigenous Peoples. However, to be successful, collaborative research projects have specific requirements regarding research designs, timeframes, and dissemination of results, which often do not fit into the frameworks of academic calendars and funding guidelines. Funding agencies in particular play an important role in enabling (or disabling) meaningful collaboration between Indigenous rights holders and researchers. There is an urgent need to re-think existing funding-structures. This article will propose a new paradigm for the financing of Arctic research, which centres around the inclusion of Indigenous partners, researchers, and institutions from the initial planning stages of funding programmes to the final stages of research projects. These findings and recommendations have been contextualized based on critical reflections of the co-authors, a group of Indigenous and non-Indigenous partners, who have practiced their own collaborative work process, the challenges encountered, and lessons learned.

Abstract Background Physical activity plays a fundamental role in the health and well-being of children. Walking is the most common form of physical activity and the journey to and from school provides an opportunity for children to be active every day. This study examines how child and parent perceptions of barriers to active school travel influences children’s behaviour. Methods Participants were recruited from 48 elementary schools in Southwestern Ontario, Canada. The study sample includes 1296 children (ages 9–14 years) who live within walking distance of their school, defined as 1.6 km network distance. Chi-square analysis examined differences between child and parent perceptions of barriers to active school travel. Logistic regression models examined how parent and child perceptions of barriers influence active school travel behaviour, while controlling for key intrapersonal, interpersonal, and physical environment factors. Results The results indicate that there are significant differences in how parents and children perceive barriers to active school travel. Model results find older children, children without siblings, households with no vehicles, and children who live closer to school are most likely to use active school travel. Parent perceptions of barriers are found to have a greater influence on children’s active school travel behaviour than children’s perceptions. Different perceptions of barriers influence active school travel to school compared to returning home from school. Conclusions Child and parent perceptions of barriers to active school travel differ and have different impacts on children’s travel behaviour. Understanding how child and parent perceptions of barriers differ can help policymakers and practitioners develop specialized interventions aimed at increasing children’s use of active school travel and children’s overall physical activity. Interventions used to promote active school travel should focus on safety, as well as perceptions of distance to break parental habits of routinely driving their children to school. Overall, this study highlights the importance of considering both child and parent perceptions to create a safe and accessible environment to allow for an increase in active school travel behaviour among elementary school children who live within walking distance of their school.

Abstract Background The clinical specialty of obstetrics is under particular scrutiny with increasing litigation costs and unnecessary tests and procedures done in attempts to prevent litigation. We aimed to identify reports evaluating or comparing the effectiveness of medical liability reforms and quality improvement strategies in improving litigation-related outcomes in obstetrics. Methods We conducted a rapid scoping review with a 6-week timeline. MEDLINE, EMBASE, LexisNexis Academic, the Legal Scholarship Network, Justis, LegalTrac, QuickLaw, and HeinOnline were searched for publications in English from 2004 until June 2015. The selection criteria for screening were established a priori and pilot-tested. We included reports comparing or evaluating the impact of obstetrics-related medical liability reforms and quality improvement strategies on cost containment and litigation settlement across all countries. All levels of screening were done by two reviewers independently, and discrepancies were resolved by a third reviewer. In addition, two reviewers independently extracted relevant data using a pre-tested form, and discrepancies were resolved by a third reviewer. The results were summarized descriptively. Results The search resulted in 2729 citations, of which 14 reports met our eligibility criteria. Several initiatives for improving the medical malpractice litigation system were found, including no-fault approaches, patient safety policy initiatives, communication and resolution, caps on compensation and attorney fees, alternative payment system and liabilities, and limitations on litigation. Conclusions Only a few litigation policies in obstetrics were evaluated or compared. Included documents showed that initiatives to reduce medical malpractice litigation could be associated with a decrease in adverse and malpractice events. However, due to heterogeneous settings (e.g., economic structure, healthcare system) and variation in the outcomes reported, the advantages and disadvantages of initiatives may vary.

Abstract Background Scoping reviews are used to identify knowledge gaps, set research agendas, and identify implications for decision-making. The conduct and reporting of scoping reviews is inconsistent in the literature. We conducted a scoping review to identify: papers that utilized and/or described scoping review methods; guidelines for reporting scoping reviews; and studies that assessed the quality of reporting of scoping reviews. Methods We searched nine electronic databases for published and unpublished literature scoping review papers, scoping review methodology, and reporting guidance for scoping reviews. Two independent reviewers screened citations for inclusion. Data abstraction was performed by one reviewer and verified by a second reviewer. Quantitative (e.g. frequencies of methods) and qualitative (i.e. content analysis of the methods) syntheses were conducted. Results After searching 1525 citations and 874 full-text papers, 516 articles were included, of which 494 were scoping reviews. The 494 scoping reviews were disseminated between 1999 and 2014, with 45 % published after 2012. Most of the scoping reviews were conducted in North America (53 %) or Europe (38 %), and reported a public source of funding (64 %). The number of studies included in the scoping reviews ranged from 1 to 2600 (mean of 118). Using the Joanna Briggs Institute methodology guidance for scoping reviews, only 13 % of the scoping reviews reported the use of a protocol, 36 % used two reviewers for selecting citations for inclusion, 29 % used two reviewers for full-text screening, 30 % used two reviewers for data charting, and 43 % used a pre-defined charting form. In most cases, the results of the scoping review were used to identify evidence gaps (85 %), provide recommendations for future research (84 %), or identify strengths and limitations (69 %). We did not identify any guidelines for reporting scoping reviews or studies that assessed the quality of scoping review reporting. Conclusion The number of scoping reviews conducted per year has steadily increased since 2012. Scoping reviews are used to inform research agendas and identify implications for policy or practice. As such, improvements in reporting and conduct are imperative. Further research on scoping review methodology is warranted, and in particular, there is need for a guideline to standardize reporting.

ABSTRACT Methicillin-resistant Staphylococcus aureus (MRSA) is a global human health problem causing infections in both hospitals and the community. Companion animals, such as cats, dogs, and horses, are also frequently colonized by MRSA and can become infected. We sequenced the genomes of 46 multilocus sequence type (ST) 22 MRSA isolates from cats and dogs in the United Kingdom and compared these to an extensive population framework of human isolates from the same lineage. Phylogenomic analyses showed that all companion animal isolates were interspersed throughout the epidemic MRSA-15 (EMRSA-15) pandemic clade and clustered with human isolates from the United Kingdom, with human isolates basal to those from companion animals, suggesting a human source for isolates infecting companion animals. A number of isolates from the same veterinary hospital clustered together, suggesting that as in human hospitals, EMRSA-15 isolates are readily transmitted in the veterinary hospital setting. Genome-wide association analysis did not identify any host-specific single nucleotide polymorphisms (SNPs) or virulence factors. However, isolates from companion animals were significantly less likely to harbor a plasmid encoding erythromycin resistance. When this plasmid was present in animal-associated isolates, it was more likely to contain mutations mediating resistance to clindamycin. This finding is consistent with the low levels of erythromycin and high levels of clindamycin used in veterinary medicine in the United Kingdom. This study furthers the “one health” view of infectious diseases that the pathogen pool of human and animal populations are intrinsically linked and provides evidence that antibiotic usage in animal medicine is shaping the population of a major human pathogen.IMPORTANCE Methicillin-resistant Staphylococcus aureus (MRSA) is major problem in human medicine. Companion animals, such as cats, dogs, and horses, can also become colonized and infected by MRSA. Here, we demonstrate that a shared population of an important and globally disseminated lineage of MRSA can infect both humans and companion animals without undergoing host adaptation. This suggests that companion animals might act as a reservoir for human infections. We also show that the isolates from companion animals have differences in the presence of certain antibiotic resistance genes. This study furthers the “one health” view of infectious diseases by demonstrating that the pool of MRSA isolates in the human and animal populations are shared and highlights how different antibiotic usage patterns between human and veterinary medicine can shape the population of bacterial pathogens.

We investigated recreational vehicle (RV) water reservoirs in response to a case of pneumonia in which Legionella pneumophila was cultured both from the patient and a RV reservoir in which he travelled. Water samples processed and cultured at the CDC according to standard protocol were positive for Legionella spp. in 4/17 (24%) faucets, 1/11 (9%) water tanks from 4/20 (20%) RVs from three different campsites. Legionella spp. that were isolated included L. pneumophila (serogroups 1 and 6), L. anisa, L. feeleii, and L. quateriensis. Environmental controls from the potable water of the three campsites were culture-negative. A survey of maintenance practices by the RV users at the campsites revealed that chlorine disinfection of the water tanks was rarely performed. To prevent the possibility of Legionella infections, RV owners should implement regular chlorine disinfection of their water tanks and follow the recommended maintenance guidelines according to their owner's manuals.

The Cancer Prevention and Control Research Network is a national network recently established to focus on developing new interventions and disseminating and translating proven interventions into practice to reduce cancer burden and disparities, especially among minority and medically underserved populations. Jointly funded by the Centers for Disease Control and Prevention and the National Cancer Institute, the Cancer Prevention and Control Research Network consists of sites administered through Prevention Research Centers funded by the Centers for Disease Control and Prevention. The five sites are located in Kentucky, Massachusetts, South Carolina, Texas, Washington State, and West Virginia. The Cancer Prevention and Control Research Networks intervention areas include primary prevention of cancer through healthy eating, physical activity, sun avoidance, tobacco control, and early detection of cancer through screening. The Cancer Prevention and Control Research Network uses the methods of community-based participatory research and seeks to build on the cancer-relevant systematic reviews of the Guide to Community Preventive Services. Initial foci for the Cancer Prevention and Control Research Networks research work groups include projects to increase screening for breast, cervical, and colorectal cancers; to promote informed decision making for prostate cancer screening; and to validate educational materials developed for low-literacy populations.

Major depressive disorder is a common and disabling disorder with high rates of treatment resistance. Evidence suggests it is characterized by distributed network dysfunction that may be variable across patients, challenging the identification of quantitative biological substrates. We carried out this study to determine whether application of a novel computational approach to a large sample of high spatiotemporal resolution direct neural recordings in humans could unlock the functional organization and coordinated activity patterns of depression networks. This group level analysis of depression networks from heterogenous intracranial recordings was possible due to application of a correlational model-based method for inferring whole-brain neural activity. We then applied a network framework to discover brain dynamics across this model that could classify depression. We found a highly distributed pattern of neural activity and connectivity across cortical and subcortical structures that was present in the majority of depressed subjects. Furthermore, we found that this depression signature consisted of two subnetworks across individuals. The first was characterized by left temporal lobe hypoconnectivity and pathological beta activity. The second was characterized by a hypoactive, but hyperconnected left frontal cortex. These findings have applications toward personalization of therapy.