Search

Importance: Historic redlining, the practice by the Home Owners' Loan Corporation (HOLC) of systematically denying credit to borrowers in neighborhoods that were inhabited by primarily African American individuals, has been associated with poor community outcomes, but the association with individual risk of death is not clear., Objective: To examine if exposure to residential redlining practices by HOLC in 1940 is associated with increased risk of death later in life., Design, Setting, and Participants: The study linked individuals who resided within HOLC-graded neighborhoods (defined as Census Enumeration Districts) in 1940 with administrative death records data. The study estimated hazard ratios as well as age-specific life expectancy gaps (at age 55, 65, and 75 years) for HOLC grading exposure. This was done using methods that adapted standard parametric survival analysis to data with limited mortality coverage windows and incomplete observations of survivors. The analysis sample consisted of 961 719 individual-level observations across 13 912 enumeration districts within 30 of the largest US cities (based on 1940 population counts) across 23 states. Data were analyzed between December 1, 2023, and September 4, 2024., Main Outcome and Measures: The exposure was HOLC grade based on historic HOLC maps, with A representing "best" or creditworthy areas; B, "still desirable"; C, "definitely declining"; and D, "hazardous" areas not worthy of credit (ie, redlined), and the main outcome was age at death from the Social Security Numident file., Results: The 961 719-person individual sample had a mean (SD) age of 19.26 (9.26) years in 1940 and a mean (SD) age at death of 76.83 (9.22) years. In a model adjusted for sex (52.48% female; 47.52% male), race and ethnicity (7.36% African American; 92.64% White), and latent place effects, a 1-unit lower HOLC grade was associated with an 8% (hazard ratio, 1.08 [95% CI, 1.07-1.09]) increased risk of death. At age 65 years, these hazard differentials translated into an estimated life expectancy gap of -0.49 (95% CI, -0.56 to -0.43) years for each 1-unit decrease of the HOLC grade., Conclusion: This study found that individuals who resided within redlined neighborhoods in 1940 had lower life expectancy later in life than individuals who resided within other HOLC-graded areas.

Objective: To evaluate the evidence on the relationship between delay discounting and clinical diabetes outcomes, identify current measures, and recommend areas for future work., Methods: A reproducible search using OVID Medline, PsycINFO, PubMed, Science Direct, and Scopus was conducted. Articles published from database creation up to March 2024 were searched. Medical Subject Heading (MeSH) terms and keywords representing delay discounting and diabetes were used. Outcomes included hemoglobin A1c (HbA1c), LDL, body mass index (BMI), blood pressure, quality of life (QOL), psychosocial factors, self-care behaviors, and diabetes complications., Results: A total of 15 articles met the inclusion criteria and were included for final synthesis. Overall, 14 studies included in this review found a significant relationship between delay discounting and diabetes-related outcomes, such that higher delay discounting is significantly related to worse diabetes outcomes for HbA1c, self-care behaviors, BMI, stress, and quality of life across self-reported measures of delay discounting and delay discounting tasks., Conclusions: Evidence supports the relationship between delay discounting and diabetes-related outcomes and self-care behaviors across measures of delay discounting and type of diabetes. To understand delay discounting as a mechanism driving diabetes outcomes and to develop targeted interventions, additional work using a multidisciplinary approach is needed to validate the construct, identify pathways, and refine intervention approaches that can be tested to improve population health., Competing Interests: Declarations: Conflict of Interest: The authors declare that they do not have a conflict of interest., (© 2024. The Author(s), under exclusive licence to Society of General Internal Medicine.)

While COVID-19 immunizations can improve outcomes from SARS-CoV-2, vaccine rates in the United States have been lowest among children under age 11 and among rural agricultural communities. This study examined factors influencing pediatric COVID-19 vaccine uptake among rural agricultural and predominantly Hispanic communities in Washington State. We conducted in-depth interviews with school district employees and students and held English and Spanish focus group discussions with parents, all of which were audio-recorded and transcribed. We used inductive coding with constant comparison approach to capture emergent themes. We identified five factors that influenced pediatric COVID-19 vaccine uptake in a rural community, including: 1) concerns and misinformation surrounding the new vaccine; 2) witnessing others' vaccine and pandemic experiences; 3) participation in social activities; 4) politicization of and political climate surrounding the vaccine; and 5) health education surrounding the vaccines. To increase pediatric COVID-19 vaccine uptake in rural communities, school districts, students, and parents should receive accurate information and reassurance to dispel health concerns and misinformation, without politicization of the vaccine and fears surrounding vaccine regulations. Social networks can be leveraged to encourage vaccine uptake by sharing positive vaccination vignettes. Clinical Trial Registration: ClinicalTrials.gov Identifier: NCT04859699https://clinicaltrials.gov/ct2/show/NCT04859699., Competing Interests: Declaration of competing interest The authors declare no conflict of interest., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Introduction: Immune effector cell-associated neurotoxicity syndrome (ICANS) is a common side-effect of chimeric antigen receptor T-cell (CAR-T) therapy, with symptoms ranging from mild to occasionally life-threatening. The neurological, cognitive, psychiatric and psychosocial sequelae of ICANS are diverse and not well defined, posing a challenge for diagnosis and management. The recovery trajectory of the syndrome is uncertain. Patients are rarely examined in this population pretherapy, adding a layer of complexity to specifying symptoms pertinent solely to CAR-T treatment. We present a protocol of a prospective longitudinal research study of adult patients in a single Australian haematology service undergoing CAR-T therapy. The study will describe neurocognitive features specific to ICANS, characterise the underlying syndrome, capture recovery, identify predictors of differential postinfusion outcomes and determine a set of cognitive instruments necessary to monitor patients acutely., Methods and Analysis: This is a prospective longitudinal study that comprises neuropsychological and neurological examinations occurring prior to CAR-T, during the acute post-treatment period, 28 days, 6 months and 12 months post infusion. Data will be sourced from objective psychometric measures, clinical examinations, self-report questionnaires of psychopathology and accounts of subjective cognitive complaint., Ethics and Dissemination: This study aims to guide diagnosis, management and monitoring of neurocognitive features of CAR-T cell therapy. Results of this study will be disseminated through publication in peer-reviewed journals and presentations at scientific conferences. All procedures involving human subjects/patients were approved by the Peter MacCallum Cancer Centre Human Research Ethics Committee (21/145)., Competing Interests: MAA reports honoraria from AstraZeneca, Janssen, Abbvie, Beigene, Takeda, CSL, Novartis, Kite, Gilead and Roche. Employee of the Walter and Eliza Hall institute which receives Milestone payments in relation to venetoclax. CS reports no disclosures. SvdL reports honoraria from Kite. IR served on scientific advisory boards, received conference travel support and/or speaker honoraria from Roche, Novartis, Merck and Biogen. IR is supported by MS Australia and the Trish Multiple Sclerosis Research Foundation. SR reports no disclosures. FD reports no disclosures. SL reports honoraria from Otsuka and Lundbeck. She has received research support from the National Health and Medical Research Council and Royal Melbourne Hospital. MDowling reports honoraria and conference support from Kite and Gilead and honoraria from Novartis. MDowling also receives royalties from Abbvie in relation to venetoclax via the Walter and Eliza Hall institute. MDickinson reports advisory boards, research funding from Novartis, Kite, BMS and Gilead. TK served on scientific advisory boards for MS International Federation and World Health Organisation, BMS, Roche, Janssen, Sanofi Genzyme, Novartis, Merck and Biogen, steering committee for Brain Atrophy Initiative by Sanofi Genzyme, received conference travel support and/or speaker honoraria from WebMD Global, Eisai, Novartis, Biogen, Roche, Sanofi-Genzyme, Teva, BioCSL and Merck and received research or educational event support from Biogen, Novartis, Genzyme, Roche, Celgene and Merck. SJH reports the following disclosures: AbbVie: consultancy, advisory board; Amgen: consultancy, honoraria, advisory board, research funding; Celgene: consultancy, honoraria, advisory board, research funding; CSL Bering: honoraria; GSK: consultancy, research funding, advisory board; Janssen Cilag: consultancy, honoraria, advisory board, research funding; Novartis: consultancy, honoraria, advisory board, research funding; Roche/Genetec: consultancy, honoraria, advisory board; Takeda: consultancy, honoraria, advisory board; Haemalogix: scientific advisory board, research funding; Sanofi: consultancy/advisory role; Terumo: consultancy/advisory role/expert testimony. CM has received conference travel support from Merck, Novartis and Biogen. He has received research support from the National Health and Medical Research Council, Multiple Sclerosis Australia, The University of Melbourne, The Royal Melbourne Hospital Neuroscience Foundation and Dementia Australia., (Copyright © Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Importance: No clear process exists for categorizing social risks in a way that informs effective social risk screening and intervention development., Objective: To investigate social risk profiles and associations of those profiles with clinical outcomes in adults with diabetes using latent profile analysis., Design, Setting, and Participants: For this cross-sectional study, a latent profile analysis was conducted using data for adults with type 2 diabetes collected at 2 primary care clinics in the Southeastern US from 2013 to 2014. Data were analyzed from November to December 2023., Main Outcomes and Measures: Participants completed validated questionnaires for 26 social risk factors within 5 domains of social determinants of health: socioeconomic, neighborhood, education, food, and social and community context. In addition, participants completed questions that assessed psychological risk and behavioral risk. A 3-step latent profile analysis was used to identify different subgroups within the sample. Profiles were then regressed on outcomes of hemoglobin A1c (HbA1c), blood pressure, and quality of life., Results: A total of 615 participants (mean [SD] age, 61.3 [10.9] years; 379 men [61.6%]) were included. Five latent class profiles were identified. The lowest risk group had significantly higher mental health-related quality of life compared with a group with higher neighborhood risk (β, 1.11; 95% CI, 0.67 to 1.55). The second group had low economic risk but high neighborhood risk and served as the reference group. The third group had high economic and neighborhood risk and had significantly higher blood pressure (β, 8.08; 95% CI, 2.16 to 14.01) compared with the reference. The fourth group had high psychological and behavioral risks but low socioeconomic and neighborhood risks. This group had significantly higher HbA1c (β, 0.47; 95% CI, 0.01 to 0.92) and lower mental health-related quality of life (β, -1.83; 95% CI, -2.41 to -1.24) compared with the reference. The highest risk group indicated high risk in all domains, had significantly higher HbA1c (β, 1.07; 95% CI, 0.50 to 1.63), and had lower mental health-related quality of life (β, -2.15; 95% CI, -2.87 to -1.42) compared with the reference., Conclusions and Relevance: These findings suggest that social risk profiles can be identified according to social, psychological, and behavioral risk domains and the health outcome of concern among adults with diabetes. Future work should consider the use of social risk profiles in intervention development and testing.

Objective: The aim of this analysis was to create a parsimonious tool to screen for high social risk using item response theory to discriminate across social risk factors in adults with type 2 diabetes., Methods: Cross-sectional data of 615 adults with diabetes recruited from two primary care clinics were used. Participants completed assessments including validated scales on economic instability (financial hardship), neighborhood and built environment (crime, violence, neighborhood rating), education (highest education, health literacy), food environment (food insecurity), social and community context (social isolation), and psychological risk factors (perceived stress, depression, serious psychological distress, diabetes distress). Item response theory (IRT) models were used to understand the association between a participant's underlying level of a particular social risk factor and the probability of that response. A two-parameter logistic IRT model was used with each of the 12 social determinant factors being added as a separate parameter in the model. Higher values in item discrimination indicate better ability of a specific social risk factor in differentiating participants from each other., Results: Rate of crime reported in a neighborhood (discrimination 3.13, SE 0.50; item difficulty - 0.68, SE 0.07) and neighborhood rating (discrimination 4.02, SE 0.87; item difficulty - 1.04, SE 0.08) had the highest discrimination., Conclusions: Based on these findings, crime and neighborhood rating discriminate best between individuals with type 2 diabetes who have high social risk and those with low social risk. These two questions can be used as a parsimonious social risk screening tool to identify high social risk., (© 2024. The Author(s), under exclusive licence to Society of General Internal Medicine.)

Objective: We investigated direct and indirect relationships between historic redlining and prevalence of diabetes in a U.S. national sample., Research Design and Methods: Using a previously validated conceptual model, we hypothesized pathways between structural racism and prevalence of diabetes via discrimination, incarceration, poverty, substance use, housing, education, unemployment, and food access. We combined census tract-level data, including diabetes prevalence from the Centers for Disease Control and Prevention PLACES 2019 database, redlining using historic Home Owners' Loan Corporation (HOLC) maps from the Mapping Inequality project, and census data from the Opportunity Insights database. HOLC grade (a score between 1 [best] and 4 [redlined]) for each census tract was based on overlap with historically HOLC-graded areas. The final analytic sample consisted of 11,375 U.S. census tracts. Structural equation modeling was used to investigate direct and indirect relationships adjusting for the 2010 population., Results: Redlining was directly associated with higher crude prevalence of diabetes within a census tract (r = 0.01; P = 0.008) after adjusting for the 2010 population (χ2(54) = 69,900.95; P < 0.001; root mean square error of approximation = 0; comparative fit index = 1). Redlining was indirectly associated with diabetes prevalence via incarceration (r = 0.06; P < 0.001), poverty (r = -0.10; P < 0.001), discrimination (r = 0.14; P < 0.001); substance use (measured by binge drinking: r = -0.65, P < 0.001; and smoking: r = 0.35, P < 0.001), housing (r = 0.06; P < 0.001), education (r = -0.17; P < 0.001), unemployment (r = -0.17; P < 0.001), and food access (r = 0.14; P < 0.001) after adjusting for the 2010 population., Conclusions: Redlining has significant direct and indirect relationships with diabetes prevalence. Incarceration, poverty, discrimination, substance use, housing, education, unemployment, and food access may be possible targets for interventions aiming to mitigate the impact of structural racism on diabetes., (© 2024 by the American Diabetes Association.)

In standard SMLM methods, the photoswitching of single fluorescent molecules and the data acquisition processes are independent, which leads to the detection of single molecule blinking events on several consecutive frames. This mismatch results in several data points with reduced localization precision, and it also increases the possibilities of overlapping. Here we discuss how the synchronization of the fluorophores' ON state to the camera exposure time increases the average intensity of the captured point spread functions and hence improves the localization precision. Simulations and theoretical results show that such synchronization leads to fewer localizations with 15% higher sum signal on average, while reducing the probability of overlaps by 10%., Competing Interests: The authors declare no conflicts of interest., (© 2024 Optica Publishing Group.)

Three-dimensional (3D) ultrasound imaging has contributed to our understanding of fetal developmental processes by providing rich contextual information of the inherently 3D anatomies. However, its use is limited in clinical settings, due to the high purchasing costs and limited diagnostic practicality. Freehand 2D ultrasound imaging, in contrast, is routinely used in standard obstetric exams, but inherently lacks a 3D representation of the anatomies, which limits its potential for more advanced assessment. Such full representations are challenging to recover even with external tracking devices due to internal fetal movement which is independent from the operator-led trajectory of the probe. Capitalizing on the flexibility offered by freehand 2D ultrasound acquisition, we propose ImplicitVol to reconstruct 3D volumes from non-sensor-tracked 2D ultrasound sweeps. Conventionally, reconstructions are performed on a discrete voxel grid. We, however, employ a deep neural network to represent, for the first time, the reconstructed volume as an implicit function. Specifically, ImplicitVol takes a set of 2D images as input, predicts their locations in 3D space, jointly refines the inferred locations, and learns a full volumetric reconstruction. When testing natively-acquired and volume-sampled 2D ultrasound video sequences collected from different manufacturers, the 3D volumes reconstructed by ImplicitVol show significantly better visual and semantic quality than the existing interpolation-based reconstruction approaches. The inherent continuity of implicit representation also enables ImplicitVol to reconstruct the volume to arbitrarily high resolutions. As formulated, ImplicitVol has the potential to integrate seamlessly into the clinical workflow, while providing richer information for diagnosis and evaluation of the developing brain., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)

Introduction: ROSSEY is a community-academic partnership aiming to develop and test a COVID-19 risk communication intervention for elementary school students and families in Yakima County, Washington. We describe the ROSSEY study protocol that will be implemented in the Yakima School District., Methods: Aim 1 is to identify the community's social, ethical, and behavioral needs and resources for students to return to school and maintain onsite learning. We will conduct semi-structured interviews with students and school employees and focus groups with parents. Aim 2 is to evaluate the effectiveness of risk communication on students' school attendance. We will conduct a cluster randomized control trial. We will enroll 14 Yakima School District elementary schools with 900 student participants and randomize the schools into the COVID-19 risk communication intervention or control group. Aim 3 will assess implementation of the risk communication intervention and schools' COVID-19 mitigation strategies. We will use the RE-AIM framework to guide this work, which will entail conducting semi-structured interviews with students and school employees and focus groups with parents., Discussion: Implementation of science-based risk communication can educate the community on the benefits and safety of COVID-19 testing and vaccination. Risk communication may also inform families about the role of COVID-19 testing and vaccines as part of mitigation strategies to allow for safe in-person learning. Schools have extraordinary influence to promote children's health through policy and practice change. Study findings will provide evidence to facilitate policy decisions and best practices at schools that facilitate adoption of COVID-19 risk communication., Trial Registration: ClinicalTrials.govNCT04859699. Registered on April 26, 2021., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023. Published by Elsevier Inc.)

Background: Prolonged periods of immunosuppression during hematopoietic stem cell transplant (HSCT) can result in serious infectious complications and contribute to transplant-related morbidity and mortality. Adherence to standardized pre and postinfection screening guidelines, prescribed medications, and early identification of infectious symptoms through comprehensive patient and family education are crucial to minimizing infectious complications. Advanced practice nurses (APNs) are key members of the multidisciplinary care team in the HSCT specialty, maintaining a specialized skillset and scope of practice which includes a holistic based, preventative medicine and risk mitigation approach., Methods: This review sought to describe the role of the APN in HSCT care and to further examine existing APN led models of care which focus on infection prevention and education throughout the HSCT treatment journey., Results: No studies specifically examined the APN role in infectious diseases risk assessment, screening, and management throughout the HSCT journey were identified throughout our review, however, there was considerable evidence to demonstrate the benefits of APN led care in the oncology and solid organ transplantation specialty which led to improvements in continuity of care, overall patient outcomes, and multidisciplinary team collaboration. The key themes identified in our review, were the role of the APN in the delivery of comprehensive patient and family education, the role of the APN in supporting, mentoring, and educating junior medical and nursing teams, the collaboration between the APN and the multidisciplinary care team, and the role of the APN in prompt recognition, triage, and management of treatment related complications, such as infection., (© 2024 Wiley Periodicals LLC.)

Background: Chargemaster prices are the list prices that providers and health systems assign to each of their medical services in the US. These charges are often several factors of magnitude higher than those extended to individuals with either private or public insurance, however, these list prices are billed in full to uninsured patients, putting them at increased risk of catastrophic health expenditures (CHE). The objective of this study was to examine the risk of CHE across insurance status, diabetes diagnosis and to examine disparity gaps across race/ethnicity., Methods: We perform a retrospective observational study on a nationally representative cohort of adult patients from the Medical Expenditure Panel Survey for the years 2002-2017. Using logistic regression models we estimate the risk of CHE across insurance status, diabetes diagnosis and explore disparity gaps across race/ethnicity., Results: Our fully adjusted results show that the relative odds of having CHE if uninsured is 5.9 (p < 0.01) compared to if insured, and 1.1 (p < 0.01) for patients with a diabetes diagnosis (compared to those without one). We note significant interactions between insurance status and diabetes diagnosis, with uninsured patients with a diabetes diagnosis being 9.5 times (p < 0.01) more likely to experience CHE than insured patients without a diabetes diagnosis. In terms of racial/ethnic disparities, we find that among the uninsured, non-Hispanic blacks are 13% (p < 0.05), and Hispanics 14.2% (p < 0.05), more likely to experience CHE than non-Hispanic whites. Among uninsured patients with diabetes, we further find that Hispanic patients are 39.3% (p < 0.05) more likely to have CHE than non-Hispanic white patients., Conclusions: Our findings indicate that uninsured patients with diabetes are at significantly elevated risks for CHE. These risks are further found to be disproportionately higher among uninsured racial/ethnic minorities, suggesting that CHE may present a channel through which structural economic and health disparities are perpetuated., (© 2024. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.)

Objective: Examine the association between historic residential redlining and present-day racial/ethnic composition of neighborhoods, racial/ethnic differences in social determinant of health domains, and risk of home evictions and food insecurity., Research Design and Methods: We examined data on 12,334 (for eviction sample), and 8996 (for food insecurity sample), census tracts in 213 counties across 37 states in the USA with data on exposure to historic redlining. First, we examined relationships between Home Owners' Loan Corporation (HOLC) redlining grades (A="Best", B="Still Desirable", C="Definitely Declining", D="Hazardous") and present-day racial/ethnic composition and racial/ethnic differences in social determinant of health domains of neighborhoods. Second, we examined whether historic redlining is associated with present-day home eviction rates (measured across eviction filings rates, and eviction judgment rates for 12,334 census tracts in 2018) and food insecurity (measured across low supermarket access, low supermarket access and income, low supermarket access and low car ownership for 8996 census tracts in 2019). Multivariable regression models were adjusted for census tract population, urban/rural designation, and county level fixed effects., Results: Relative to areas with a historic HOLC grading of "A (Best)", areas with a "D (Hazardous)" grading had a 2.59 (95%CI=1.99-3.19; p-value<0.01) higher rate of eviction filings, and a 1.03 (95%CI=0.80-1.27; p-value<0.01) higher rate of eviction judgments. Compared to areas with a historic HOLC grading of "A (Best)", areas rated with a "D (Hazardous)" had a 16.20 (95%CI=15.02-17.79; p-value<0.01) higher rate of food insecurity based on supermarket access and income, and a 6.15 (95%CI =5.53-6.76; p-value<0.01) higher rate of food insecurity based on supermarket access and car ownership., Conclusions: Historic residential redlining is significantly associated with present-day home evictions and food insecurity, highlighting persistent associations between structural racism and present-day social determinants of health., (© 2023. The Author(s), under exclusive licence to Society of General Internal Medicine.)

Maturation of the human fetal brain should follow precisely scheduled structural growth and folding of the cerebral cortex for optimal postnatal function 1 . We present a normative digital atlas of fetal brain maturation based on a prospective international cohort of healthy pregnant women 2 , selected using World Health Organization recommendations for growth standards 3 . Their fetuses were accurately dated in the first trimester, with satisfactory growth and neurodevelopment from early pregnancy to 2 years of age 4,5 . The atlas was produced using 1,059 optimal quality, three-dimensional ultrasound brain volumes from 899 of the fetuses and an automated analysis pipeline 6-8 . The atlas corresponds structurally to published magnetic resonance images 9 , but with finer anatomical details in deep grey matter. The between-study site variability represented less than 8.0% of the total variance of all brain measures, supporting pooling data from the eight study sites to produce patterns of normative maturation. We have thereby generated an average representation of each cerebral hemisphere between 14 and 31 weeks' gestation with quantification of intracranial volume variability and growth patterns. Emergent asymmetries were detectable from as early as 14 weeks, with peak asymmetries in regions associated with language development and functional lateralization between 20 and 26 weeks' gestation. These patterns were validated in 1,487 three-dimensional brain volumes from 1,295 different fetuses in the same cohort. We provide a unique spatiotemporal benchmark of fetal brain maturation from a large cohort with normative postnatal growth and neurodevelopment., (© 2023. The Author(s).)

The use of stochastic frontier models for inference on hospital efficiency is complicated by the inability to fully control for quality differences across hospitals. Additionally, the potential existence of cross-sectional dependence due to the presence of unobserved common factors leads to endogeneity problems that can bias both cost function and efficiency estimates. Using a panel consisting of 1518 hospitals for the years 1996-2013 (T = 18), I adopt techniques for dealing with long, cross-sectionally dependent panel data in order to estimate cost parameters and hospital specific efficiency. In particular, I employ the estimation technique proposed by Bai (Econometrica 77(4):1229-1279, 2009), which assumes that the unobservable heterogenous effects have a factor structure. I find evidence of considerable scale economies and that hospital cost inefficiencies have been increasing during the period of 1996-2013, and that the growth in expenditures is, in part, driven by spending that increases patient satisfaction, but that does not significantly contribute to improved patient health outcomes., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Streptococcus pneumoniae -induced hemolytic uremic syndrome (Sp-HUS) is a kidney disease characterized by microangiopathic hemolytic anemia, thrombocytopenia, and acute kidney injury. This disease is frequently underdiagnosed and its pathophysiology is poorly understood. In this work, we compared clinical strains, isolated from infant Sp-HUS patients, with a reference pathogenic strain D39, for host cytotoxicity and further explored the role of Sp-derived extracellular vesicles (EVs) in the pathogenesis of an HUS infection. In comparison with the wild-type strain, pneumococcal HUS strains caused significant lysis of human erythrocytes and increased the release of hydrogen peroxide. Isolated Sp-HUS EVs were characterized by performing dynamic light-scattering microscopy and proteomic analysis. Sp-HUS strain released EVs at a constant concentration during growth, yet the size of the EVs varied and several subpopulations emerged at later time points. The cargo of the Sp-HUS EVs included several virulence factors at high abundance, i.e., the ribosomal subunit assembly factor BipA, the pneumococcal surface protein A, the lytic enzyme LytC, several sugar utilization, and fatty acid synthesis proteins. Sp-HUS EVs strongly downregulated the expression of the endothelial surface marker platelet endothelial cell adhesion molecule-1 and were internalized by human endothelial cells. Sp-HUS EVs elicited the release of pro-inflammatory cytokines (interleukin [IL]-1β, IL-6) and chemokines (CCL2, CCL3, CXCL1) by human monocytes. These findings shed new light on the overall function of Sp-EVs, in the scope of infection-mediated HUS, and suggest new avenues of research for exploring the usefulness of Sp-EVs as therapeutic and diagnostic targets. IMPORTANCE Streptococcus pneumoniae -associated hemolytic uremic syndrome (Sp-HUS) is a serious and underdiagnosed deadly complication of invasive pneumococcal disease. Despite the introduction of the pneumococcal vaccine, cases of Sp-HUS continue to emerge, especially in children under the age of 2. While a lot has been studied regarding pneumococcal proteins and their role on Sp-HUS pathophysiology, little is known about the role of extracellular vesicles (EVs). In our work, we isolate and initially characterize EVs from a reference pathogenic strain (D39) and a strain isolated from a 2-year-old patient suffering from Sp-HUS. We demonstrate that despite lacking cytotoxicity toward human cells, Sp-HUS EVs are highly internalized by endothelial cells and can trigger cytokine and chemokine production in monocytes. In addition, this work specifically highlights the distinct morphological characteristics of Sp-HUS EVs and their unique cargo. Overall, this work sheds new light into potentially relevant players contained in EVs that might elucidate about pneumococcal EVs biogenesis or pose as interesting candidates for vaccine design., Competing Interests: The authors declare no conflict of interest.

Introduction: School-based COVID-19 testing may be an effective strategy for reducing transmission in schools and keeping schools open. The study objective was to examine community perspectives on school-based COVID-19 testing as a mitigation strategy to support safe school reopening., Methods: We conducted a qualitative study in Yakima County, an agricultural region of Washington state, where over half of residents are Hispanic/Latino. From June to July 2021, we interviewed 18 students (13 years old, on average) and 19 school employees, and conducted four focus groups (2 in Spanish, 2 in English) with 26 parents. We audio-recorded the semi-structured interviews and focus group discussions which were then transcribed. We used an inductive, constant comparison approach to code the transcripts and conducted a thematic analysis to generate themes., Results: We identified four main themes. Students, parents, and school employees desired a return to in-person learning (Theme 1). Schools implemented numerous COVID-19 mitigation strategies (e.g., masking) to facilitate a safe return to school but felt that adding testing would not be feasible due to a lack of resources and overworked staff (Theme 2). Parents and school employees' familiarity with COVID-19 testing procedures influenced their support for testing (Theme 3). Parents and school employees felt there were inadequate resources for individuals who test positive for COVID-19 (Theme 4)., Discussion: Schools require adequate resources and medical personnel to implement COVID-19 testing. Individuals also need resources after testing positive, including physical space to isolate, financial resources for those without paid time off, and delivery of food and other necessities to households in rural communities., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Ramirez, Bishop, Ibarra, Shah, Duran, Chae, Hassell, Garza, Linde, Garrison, Drain and Ko.)

Importance: While the association between economic connectedness and social mobility has now been documented, the potential linkage between community-level economic connectedness and population health outcomes remains unknown., Objective: To examine the association between community social capital measures (defined as economic connectedness, social cohesion, and civic engagement) and population health outcomes (defined across prevalence of diabetes, hypertension, high cholesterol, kidney disease, and obesity)., Design, Setting, and Participants: This cross-sectional study included communities defined at the zip code tabulation area (ZCTA) level in all 50 US states. Data were collected from January 2021 to December 2022., Main Outcomes and Measures: Multivariable regression analyses were used to examine the association between population health outcomes and social capital. Adjusted analyses controlled for area demographic variables and county fixed effects. Heterogeneities within the associations based on the racial and ethnic makeup of communities were also examined., Results: In this cross-sectional study of 17 800 ZCTAs, across 50 US states, mean (SD) economic connectedness was 0.88 (0.32), indicating friendship sorting on income; the mean (SD) support ratio was 0.90 (0.10), indicating that 90% of ties were supported by a common friendship tie; and the mean (SD) volunteering rate was 0.08 (0.03), indicating that 8% of individuals within a given community were members of volunteering associations. Mean (SD) ZCTA diabetes prevalence was 10.8% (2.9); mean (SD) high blood pressure prevalence was 33.2% (6.2); mean (SD) high cholesterol prevalence was 32.7% (4.2), mean (SD) kidney disease prevalence was 3.0% (0.7), and mean (SD) obesity prevalence was 33.4% (5.6). Regression analyses found that a 1% increase in community economic connectedness was associated with significant decreases in prevalence of diabetes (-0.63%; 95% CI, -0.67% to -0.60%); hypertension (-0.31%; 95% CI, -0.33% to -0.29%); high cholesterol (-0.14%; 95% CI, -0.15% to -0.12%); kidney disease (-0.48%; 95% CI, -0.50% to -0.46%); and obesity (-0.28%; 95% CI, -0.29% to -0.27%). Second, a 1% increase in the community support ratio was associated with significant increases in prevalence of diabetes (0.21%; 95% CI, 0.16% to 0.26%); high blood pressure (0.16%; 95% CI, 0.13% to 0.19%); high cholesterol (0.16%; 95% CI, 0.13% to 0.19%); kidney disease (0.17%; 95% CI, 0.13% to 0.20%); and obesity (0.08%; 95% CI, 0.06% to 0.10%). Third, a 1% increase in the community volunteering rate was associated with significant increases in prevalence of high blood pressure (0.02%; 95% CI, 0.01% to 0.02%); high cholesterol (0.03%; 95% CI, 0.02% to 0.03%); and kidney disease (0.02%; 95% CI, 0.01% to 0.02%). Additional analyses found that the strength of these associations varied based on the majority racial and ethnic population composition of communities., Conclusions and Relevance: In this study, higher economic connectedness was significantly associated with better population health outcomes; however, higher community support ratios and volunteering rates were both significantly associated with worse population health. Associations also differed by majority racial and ethnic composition of communities.

There is emerging evidence that structural racism is a major contributor to poor health outcomes for ethnic minorities. Structural racism captures upstream historic racist events (such as slavery, black code, and Jim Crow laws) and more recent state-sanctioned racist laws in the form of redlining. Redlining refers to the practice of systematically denying various services (e.g., credit access) to residents of specific neighborhoods, often based on race/ethnicity and primarily within urban communities. Historical redlining is linked to increased risk of diabetes, hypertension, and early mortality due to heart disease with evidence suggesting it impacts health through suppressing economic opportunity and human capital, or the knowledge, skills, and value one contributes to society. Addressing structural racism has been a rallying call for change in recent years-drawing attention to the racialized impact of historical policies in the USA. Unfortunately, the enormous scope of work has also left people feeling incapable of effecting the very change they seek. This paper highlights a path forward by briefly discussing the origins of historical redlining, highlighting the modern-day consequences both on health and at the societal level, and suggest promising initiatives to address the impact., (© 2023. The Author(s), under exclusive licence to Society of General Internal Medicine.)

Objective: To evaluate the evidence on the role of structural racism as an upstream factor impacting diabetes outcomes, identify current gaps, and recommend areas for future work., Research Design and Methods: A reproducible search of Medline and Ovid was used. Structural factors based on the World Health Organization social determinants of health framework (governance, macroeconomic policy, social policy, public policy, and cultural and societal values) had to be included as measured variables or contextual factors discussed as upstream influences. Outcomes included 1) hemoglobin A1c (HbA1c), 2) LDL, 3) BMI, 4) quality of life, 5) self-efficacy, 6) mortality, 7) years of life lost, and 8) self-care behaviors., Results: Thirteen articles were included for final synthesis. Ten studies focused on governance, two on social policies, one on public policies, and one on cultural and societal values. Results highlight significant associations between structural racism and poorer clinical outcomes (HbA1c and blood pressure), worse self-care behaviors (diet and physical activity), lower standards of care, higher mortality, and more years of life lost for adults with diabetes., Conclusions: There is a paucity of work investigating the relationship between structural racism and diabetes outcomes. Five areas for future work include 1) more rigorous research on the relationship between structural racism, downstream social determinants, and health outcomes in diabetes, 2) policy assessments specific to diabetes outcomes, 3) research designed to examine pathways and mechanisms of influence, 4) intervention development to mitigate the impact of structural racism, and 5) tracking and monitoring of change over time., (© 2023 by the American Diabetes Association.)

Carbocyanines are among the best performing dyes in single-molecule localization microscopy (SMLM), but their performance critically relies on optimized photoswitching buffers. Here, we study the versatile role of thiols in cyanine photoswitching at varying intensities generated in a single acquisition by a microelectromechanical systems (MEMS) mirror placed in the excitation path. The key metrics we have analyzed as a function of the thiolate concentration are photon budget, on-state and off-state lifetimes and the corresponding impact on image resolution. We show that thiolate acts as a concentration bandpass filter for the maximum achievable resolution and determine a minimum of ∼1 mM is necessary to facilitate SMLM measurements. We also identify a concentration bandwidth of 1-16 mM in which the photoswitching performance can be balanced between high molecular brightness and high off-time to on-time ratios. Furthermore, we monitor the performance of the popular oxygen scavenger system based on glucose and glucose oxidase over time and show simple measures to avoid acidification during prolonged measurements. Finally, the impact of buffer settings is quantitatively tested on the distribution of the glucose transporter protein 4 within the plasma membrane of adipocytes. Our work provides a general strategy for achieving optimal resolution in SMLM with relevance for the development of novel buffers and dyes.

Importance: Prior research has identified associations between housing insecurity and poor health outcomes., Objective: To evaluate the association between US state Medicaid expansions and reductions in eviction; to examine the persistence of these associations and how they vary across US states and counties., Design, Setting, and Participants: This cohort study of 25 398 county-year observations (across 40 states) used US eviction and census data for the years 2002 through 2018 (ie, 17 years). County-level associations were estimated using interactive fixed effects counterfactual estimators, and models were selected using cross validation. Across-county treatment association heterogeneities were assessed using multivariable regression methods. Analyses were performed in July of 2022., Exposure: State-level Medicaid expansion under the Patient Protection and Affordable Care Act., Main Outcomes and Measures: Eviction judgments; eviction judgments per 100 renter-occupied households., Results: Among a total of 774 treated counties (with Medicaid expansion) and 720 control counties (untreated, without Medicaid expansion), mean (SD) eviction judgments for treated counties were 534.78 (1945.84) eviction judgments in the pre-2014 period (mean [SD] eviction rate, 2.25 [2.18] per 100 households), which decreased to 463.67 (1499.39) eviction judgments in the post-2014 period (mean [SD] eviction judgment rate, 2.02 [1.81] per 100 households). Control group mean (SD) county eviction judgments were 477.22 (1592.18) eviction judgments (mean [SD] eviction judgment rate, 1.91 per 100 households) pre-2014, and 490.22 (1575.19) eviction judgments (mean [SD] eviction judgment rate, 1.89 per 100 households) post-2014. Model estimates indicate that Medicaid expansion was associated with reductions in county eviction judgments by -66.49 (95% CI, -132.50 to -0.48; P = .047) and reductions of the eviction judgment rate by -0.25 (95% CI, -0.35 to -0.14; P < .001). Associations remained broadly consistent between 2014 and 2018, although some diminishment of associations occurred in 2018. Approximately 29% of the across-county treatment association variation was explained by across-state differences, while 9% was explained by county-level demographic and uninsurance differences., Conclusions and Relevance: In this cohort study, Medicaid expansion was associated with reductions in eviction judgments and eviction judgment rates; however, these associations were found to vary considerably both across as well as within states (across counties). These findings suggest that the channel between Medicaid expansion and evictions is sensitive to state environments as well as county specific population demographics and uninsurance levels.

Learning the art of any professional practice like engineering design or computer programming is a challenge for students and adds to the complexity of teaching such a technical discipline. Institutional regulations, along with industry expectations, increase the burden on the educator to develop a successful instructional environment. Critical systems thinking provides practitioners, in general, with a framework for understanding interrelation and complexities in a variety of problem situations. The art of systems thinking requires discourse on both the interdependencies, and multiple perspectives present in a problem situation. However, little guidance exists for educators in applying the concepts of critical systems thinking in their everyday practice of teaching a professional practice module at university level. This paper suggests a methodology based on action research and critical systems thinking concepts, to incorporate the art of systems thinking in the teaching of a professional practice module. The phases of action research are described from the critical systems perspective of Ulrich, in order to provide guidelines for an educator to embrace the complexity of professional practice education. Programming is used as a demonstration of the proposed methodology. The methodology incorporates systems thinking aspects such as the totality of conditioned realities, boundary critique, and acting as a witness sensitive to polemical argumentation on behalf of the affected. It demonstrates how Ulrich's approach involves - and respects - all stakeholders in a system and guides the individual educator to excel in teaching a professional practice module. By making a conscious effort to listen to the affected and to incorporate as many conditioned realities as possible, the educator should be able to improve student engagement, resulting in better skills. We provide a demonstration of the art of teaching a professional practice module methodology which enables the educator to develop the programming skills of students in a complex environment., Competing Interests: Conflict of interestThe authors have no conflicts of interest to declare that are relevant to the content of this article., (© The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature 2022, Springer Nature or its licensor holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.)

The regulated translocation of the glucose transporter, GLUT4, to the surface of adipocytes and muscle is a key action of insulin. This is underpinned by the delivery and fusion of GLUT4-containing vesicles with the plasma membrane. Recent studies have revealed that a further action of insulin is to mediate the dispersal of GLUT4 molecules away from the site of GLUT4 vesicle fusion with the plasma membrane. Although shown in adipocytes, whether insulin-stimulated dispersal occurs in other cells and/or is exhibited by other proteins remains a matter of debate. Here we show that insulin stimulates GLUT4 dispersal in the plasma membrane of adipocytes, induced pluripotent stem cell-derived cardiomyocytes and HeLa cells, suggesting that this phenomenon is specific to GLUT4 expressed in all cell types. By contrast, insulin-stimulated dispersal of TfR was not observed in HeLa cells, suggesting that the mechanism may be unique to GLUT4. Consistent with dispersal being an important physiological mechanism, we observed that insulin-stimulated GLUT4 dispersal is reduced under conditions of insulin resistance. Adipocytes of different sizes have been shown to exhibit distinct metabolic properties: larger adipocytes exhibit reduced insulin-stimulated glucose transport compared to smaller cells. Here we show that both GLUT4 delivery to the plasma membrane and GLUT4 dispersal are reduced in larger adipocytes, supporting the hypothesis that larger adipocytes are refractory to insulin challenge compared to their smaller counterparts, even within a supposedly homogeneous population of cells., (© 2022. The Author(s).)

Background: Effective January 1, 2021, US hospitals were required to upload information on their chargemaster prices (database of list prices), discounted cash prices (commonly charged to self-pay patients), and payer-specific negotiated prices., Objective: Examine how prices vary and are associated with hospital characteristics, market competition, and hospital quality., Design Setting and Participants: This observational study used data on 14 common medical services across 1599 hospitals in 2021. Descriptive and regression analyses were used to study price variation. Analyses adjust for hospital characteristics, market competition and state fixed effects., Results: Ninetieth -to-10th-percentile price markups factors (ratios) range between 3.2 and 11.5 for chargemaster; 6.1 and 19.7 for cash; and 6.6 and 30.0 for negotiated prices. Adjusted regression results indicate that hospitals' cash prices are on average 60% ( P <0.01) higher, and list prices are on average 164% ( P <0.01) higher, than negotiated prices. Systematic pricing differences across hospitals were noted, with urban hospitals having 14% ( P <0.01) lower prices than rural hospitals, teaching hospitals having 3% ( P <0.01) higher prices than nonteaching hospitals, and nonprofit hospitals pricing 9% ( P <0.01), and for-profit hospitals 39% ( P <0.01), higher than government owned hospitals. In addition, hospitals that contract with more insurance plans have higher prices, hospitals in more competitive markets have lower prices, and higher quality hospitals have on average 5% ( P <0.01) lower prices than lower quality hospitals., Conclusions: Prices all vary considerably across US hospitals. High quality hospitals are associated with lower pricing across all three sets of prices examined. Hospital price transparency may help consumers better identify hospitals that provide both high quality, and low cost, care., Competing Interests: The authors declare no conflict of interests., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Provider network structure has been linked to hospital cost, utilization, and to a lesser degree quality, outcomes; however, it remains unknown whether these relationships are heterogeneous across different acute care hospital characteristics and US states. The objective of this study is to evaluate whether there are heterogeneous relationships between hospital provider network structure and hospital outcomes (cost efficiency and quality); and to assess the sources of measured heterogeneous effects. We use recent causal random forest techniques to estimate (hospital specific) heterogeneous treatment effects between hospitals' provider network structures and their performance (across cost efficiency and quality). Using Medicare cost report, hospital quality and provider patient sharing data, we study a population of 3061 acute care hospitals in 2016. Our results show that provider networks are significantly associated with costs efficiency (P < .001 for 7/8 network measures), patient rating of their care (P < .1 in 5/8 network measures), heart failure readmissions (P < .01 for 3/8 network measures), and mortality rates (P < .02 in 5/8 cases). We find that fragmented provider structures are associated with higher costs efficiency and patient satisfaction, but also with higher heart failure readmission and mortality rates. These effects are further found to vary systematically with hospital characteristics such as capacity, case mix, ownership, and teaching status. This study used an observational design. In summary, we find that hospital treatment responses to different network structures vary systematically with hospital characteristics.., Competing Interests: The authors have no funding and conflicts of interest to disclose., (Copyright © 2022 the Author(s). Published by Wolters Kluwer Health, Inc.)

Climate change, biodiversity loss and large-scale environmental degradation are widely recognized as the biggest health threats of the 21st century, with the African continent already amongst the most severely affected and vulnerable to their further progression. The healthcare system's contribution to climate change and environmental degradation requires healthcare professionals to address environmental issues urgently. However, the foundation for context-relevant interventions across research, practice, and education is not readily available. Therefore, we conducted a convergent mixed-methods study to investigate South African healthcare professionals' knowledge, attitudes, practices, and barriers to environmental sustainability. Healthcare professionals participated in a cross-sectional questionnaire ( n = 100) and in-depth semi-structured focus group discussions ( n = 18). Data were analyzed using descriptive statistics and thematic analysis, respectively, and integrated to provide holistic findings. Our results confirm overwhelmingly positive attitudes and a high degree of interest in education, implementation, and taking on more corresponding responsibility, but a lack of substantial knowledge of the subject matter, and only tentative implementation of practices. Identified barriers include a lack of knowledge, resources, and policies. Further research, education, and policy development on overcoming these barriers is required. This will facilitate harnessing the extant enthusiasm and advance environmental sustainability in South Africa's healthcare practice.

Background: It remains widely debated whether chargemaster price markups are tied to hospital profitability., Objective: To evaluate the effect of chargemaster markups on hospital profitability in the presence of unobserved hospital-specific (time-invariant) confounders, and cross-sectional dependence due to latent (common) policy shocks., Design: We use interactive fixed effects methods to address concerns of unobserved hospital-specific (time-invariant) confounders, and cross-sectional dependence., Setting: US acute care hospitals, 1996 through 2017 (ie, 22 y)., Participants: Using primarily Medicare cost report data, we construct an unbalanced panel of 3499 acute care hospitals per year, or a total of 76,972 hospital-year observations., Measurements: Chargemaster markups (above cost), profits per hospital inpatient discharge., Results: Between 1996 and 2017, chargemaster markups increased (on average) by 155%, and the SD of the chargemaster markup distribution increased by 324%-indicating growing variability in the average markup strategies pursued by hospitals. Our preferred model specification implies that a unit increase of the hospital chargemaster markup is associated with a $261 ( P <0.01; 95% confidence interval: $232-$291) increase in profits per hospital inpatient discharge. These results are robust to a wide set of model specifications, the use of alternative profitability measurements, and the use of an alternative instrumental variable identification strategy. Additional subsample analysis that controls for a rich set of hospital quality measures and system affiliation information also yields similar results., Conclusion: We show that higher chargemaster markups are associated with higher hospital profitability. Additional research is needed to understand how chargemaster pricing impact health outcomes and health care disparities., Competing Interests: The authors declare no conflict of interest., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Objective: The association between structural racism, as captured by historic residential redlining practices under the Home Owners' Loan Corporation (HOLC), and present-day diabetes mortality, and years of life lost (YLL), remains unknown., Research Design and Methods: Age-standardized mortality and YLL data were combined with historic HOLC redlining data for the city of Seattle, WA (a sample of 109 census tract-level observations) for each of the years 1990 through 2014 (25 years). Spatial autoregressive regression analyses were used for assessment of the association between an area's historic HOLC redlining score and diabetes (and all-cause) mortality and YLL., Results: Spatial autoregressive model estimates indicate that an area's HOLC redlining score explains 45%-56% of the variation in the census tract-level diabetes mortality rate and 51%-60% of the variation in the census tract diabetes YLL rate between the years of 1990 and 2014. For 2014, estimates indicate that areas with a unit-higher HOLC grade are associated with 53.7% (95% CI 43.3-64.9; P < 0.01) higher diabetes mortality rates and 66.5% (53.7-80.4; P < 0.01) higher diabetes YLL rate. Magnitudes of marginal effects were consistently larger for diabetes than for all-cause outcomes., Conclusions: Results indicate sizable, and statistically significant, associations between historic redlining practices and present-day diabetes mortality and YLL rates. In addition, the persistence of these associations across the 1990-2014 period highlight a need for targeted action to undo the impact of historical redlining on current health., (© 2022 by the American Diabetes Association.)

Ceratocystis platani (CP), an ascomycetous fungus, is the agent of canker stain, a lethal vascular disease of Platanus species. Ceratocystis platani has been listed as a quarantine pest (EPPO A2 list) due to extensive damage caused in Southern Europe and the Mediterranean region. As traditional diagnostic assays are ineffective, a Real-Time PCR detection method based on EvaGreen, SYBR Green, and Taqman assays was previously developed, validated in-house, and included in the official EPPO standard PM7/14 (2). Here, we describe the results of a test performance study performed by nine European laboratories for the purpose of an interlaboratory validation. Verification of the DNA extracted from biological samples guaranteed the high quality of preparations, and the stability and the homogeneity of the aliquots intended for the laboratories. All of the laboratories reproduced nearly identical standard curves with efficiencies close to 100%. Testing of blind-coded DNA extracted from wood samples revealed that all performance parameters-diagnostic sensitivity, diagnostic specificity, accuracy and reproducibility-were best fit in most cases both at the laboratory and at the assay level. The previously established limit of detection, 3 fg per PCR reaction, was also validated with similar excellent results. The high interlaboratory performance of this Real-Time PCR method confirms its value as a primary tool to safeguard C. platani -free countries by way of an accurate monitoring, and to investigate the resistance level of potentially canker stain-resistant Platanus genotypes.

This systematic review identified studies of nonmedical interventions designed to reduce risk for and improve clinical outcomes for type 2 diabetes. Specifically, this review sought to identify interventions that target structural racism and social determinants of health. To be included, studies were published in English; published between database initiation and January 2022; conducted in the United States; measured an intervention effect using a clinical trial, quasi-experimental, or pre-post design; included a population of adults at risk for or with type 2 diabetes; and targeted hemoglobin A1c levels, blood pressure, lipids, self-care, or quality of life as outcomes. The findings of our review indicate that interventions with targeted, multicomponent designs that combine both medical and nonmedical approaches can reduce risk for and improve clinical outcomes for type 2 diabetes. HbA1c levels improved significantly with the use of food supplementation with referral and diabetes support; the use of financial incentives with education and skills training; the use of housing relocation with counseling support; and the integration of nonmedical interventions into medical care using the electronic medical record. Our findings demonstrate that the literature on nonmedical interventions designed to address relevant social factors and target structural racism is limited. The article offers actionable strategies and identifies policy opportunities for targeting structural inequalities and decreasing social risk among adults with type 2 diabetes.

The quantification of subcortical volume development from 3D fetal ultrasound can provide important diagnostic information during pregnancy monitoring. However, manual segmentation of subcortical structures in ultrasound volumes is time-consuming and challenging due to low soft tissue contrast, speckle and shadowing artifacts. For this reason, we developed a convolutional neural network (CNN) for the automated segmentation of the choroid plexus (CP), lateral posterior ventricle horns (LPVH), cavum septum pellucidum et vergae (CSPV), and cerebellum (CB) from 3D ultrasound. As ground-truth labels are scarce and expensive to obtain, we applied few-shot learning, in which only a small number of manual annotations (n = 9) are used to train a CNN. We compared training a CNN with only a few individually annotated volumes versus many weakly labelled volumes obtained from atlas-based segmentations. This showed that segmentation performance close to intra-observer variability can be obtained with only a handful of manual annotations. Finally, the trained models were applied to a large number (n = 278) of ultrasound image volumes of a diverse, healthy population, obtaining novel US-specific growth curves of the respective structures during the second trimester of gestation., (Copyright © 2022. Published by Elsevier Inc.)

Objective: To evaluate whether certain healthcare provider network structures are more robust to systemic shocks such as those presented by the current COVID-19 pandemic., Design: Using multivariable regression analysis, we measure the effect that provider network structure, derived from Medicare patient sharing data, has on county level COVID-19 outcomes (across mortality and case rates). Our adjusted analysis includes county level socioeconomic and demographic controls, state fixed effects, and uses lagged network measures in order to address concerns of reverse causality., Setting: US county level COVID-19 population outcomes by 3 September 2020., Participants: Healthcare provider patient sharing network statistics were measured at the county level (with n=2541-2573 counties, depending on the network measure used)., Primary and Secondary Outcome Measures: COVID-19 mortality rate at the population level, COVID-19 mortality rate at the case level and the COVID-19 positive case rate., Results: We find that provider network structures where primary care physicians (PCPs) are relatively central, or that have greater betweenness or eigenvector centralisation, are associated with lower county level COVID-19 death rates. For the adjusted analysis, our results show that increasing either the relative centrality of PCPs (p value<0.05), or the network centralisation (p value<0.05 or p value<0.01), by 1 SD is associated with a COVID-19 death reduction of 1.0-1.8 per 100 000 individuals (or a death rate reduction of 2.7%-5.0%). We also find some suggestive evidence of an association between provider network structure and COVID-19 case rates., Conclusions: Provider network structures with greater relative centrality for PCPs when compared with other providers appear more robust to the systemic shock of COVID-19, as do network structures with greater betweenness and eigenvector centralisation. These findings suggest that how we organise our health systems may affect our ability to respond to systemic shocks such as the COVID-19 pandemic., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Objective: To evaluate whether medical event charges are associated with uninsured patients' probability of medical payment default and whether there exist racial/ethnic disparity gaps in medical payment defaults., Design: We use logistic regression models to analyse medical payment defaults. Our adjusted estimates further control for a rich set of patient and medical visit characteristics, region and time fixed effects., Setting: Uninsured US adult (non-elderly) population from 2002 to 2017., Participants: We use four nationally representative samples of uninsured patients from the Medical Expenditure Panel Survey across office-based (n=39 967), emergency (n=3269), outpatient (n=1739) and inpatient (n=340) events., Primary and Secondary Outcome Measures: Payment default, medical event charges and medical event payments., Results: Relative to uninsured non-Hispanic white (NHW) patients, uninsured non-Hispanic black (NHB) patients are 142% (p<0.01) more likely to default on medical payments for office-based visits, 27% (p<0.05) more likely to default on emergency department visit payments and 82% (p<0.1) more likely to default on an outpatient visit bill. Hispanic patients are 46% (p<0.01) more likely to default on an office-based visit, but 25% less likely to default on emergency department visit payments than NHW patients. Within our fully adjusted model, we find that racial/ethnic disparities persist for office-based visits. Our results further suggest that the probabilities of payment defaults for office-based, emergency and outpatient visits are all significantly (p<0.01) and positively associated with the medical event charges billed., Conclusions: Medical event charges are found to be broadly associated with payment defaults, and we further note disproportionate payment default disparities among NHB patients., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

The human gut acts as the main reservoir of microbes and a relevant source of life-threatening infections, especially in immunocompromised patients. There, the opportunistic fungal pathogen Candida albicans adapts to the host environment and additionally interacts with residing bacteria. We investigated fungal-bacterial interactions by coinfecting enterocytes with the yeast Candida albicans and the Gram-negative bacterium Proteus mirabilis resulting in enhanced host cell damage. This synergistic effect was conserved across different P. mirabilis isolates and occurred also with non- albicans Candida species and C. albicans mutants defective in filamentation or candidalysin production. Using bacterial deletion mutants, we identified the P. mirabilis hemolysin HpmA to be the key effector for host cell destruction. Spatially separated coinfections demonstrated that synergism between Candida and Proteus is induced by contact, but also by soluble factors. Specifically, we identified Candida -mediated glucose consumption and farnesol production as potential triggers for Proteus virulence. In summary, our study demonstrates that coinfection of enterocytes with C. albicans and P. mirabilis can result in increased host cell damage which is mediated by bacterial virulence factors as a result of fungal niche modification via nutrient consumption and production of soluble factors. This supports the notion that certain fungal-bacterial combinations have the potential to result in enhanced virulence in niches such as the gut and might therefore promote translocation and dissemination., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Niemiec, Kapitan, Himmel, Döll, Krüger, Köllner, Auge, Kage, Alteri, Mobley, Monsen, Linde, Nietzsche, Kniemeyer, Brakhage and Jacobsen.)

Most trees form symbioses with ectomycorrhizal fungi (EMF) which influence access to growth-limiting soil resources. Mesocosm experiments repeatedly show that EMF species differentially affect plant development, yet whether these effects ripple up to influence the growth of entire forests remains unknown. Here we tested the effects of EMF composition and functional genes relative to variation in well-known drivers of tree growth by combining paired molecular EMF surveys with high-resolution forest inventory data across 15 European countries. We show that EMF composition was linked to a three-fold difference in tree growth rate even when controlling for the primary abiotic drivers of tree growth. Fast tree growth was associated with EMF communities harboring high inorganic but low organic nitrogen acquisition gene proportions and EMF which form contact versus medium-distance fringe exploration types. These findings suggest that EMF composition is a strong bio-indicator of underlying drivers of tree growth and/or that variation of forest EMF communities causes differences in tree growth. While it may be too early to assign causality or directionality, our study is one of the first to link fine-scale variation within a key component of the forest microbiome to ecosystem functioning at a continental scale., (© 2021. The Author(s).)

Importance: While the Affordable Care Act (ACA) set out to eliminate insurer discrimination based on preexisting conditions, the ACA health exchanges allow insurers to select what markets to enter and afford them great freedom on how they design their physician networks. Strategic market participation and physician network design based on population race, ethnicity, and health characteristics may give rise to a present-day form of redlining within health insurance markets-ie, a systematic underprovision of insurance plans and in-network practitioners within areas that are populated with higher proportions of non-Hispanic Black residents., Objective: To examine if markets with relatively higher non-Hispanic Black populations have systematically fewer insurers and lower network inclusion of physicians residing within these areas., Design, Setting, and Participants: This cohort study conducted a regression analysis of the US ACA health insurance exchange marketplace across 34 states with federal exchanges and physicians located within the 500 most populous US cities in 2014. County-level data were sourced from individual market and issuer enrollment databases and county health rankings; census tract data came from a national database of physician networks in 2014 marketplace plans, US Census Bureau data, and the Centers for Disease Control and Prevention's PLACES database. Adjustment was made for a rich set of county (or census tract) controls and state fixed effects to capture broad market and/or policy differences across states. Analyses were performed in June 2021., Main Outcomes and Measures: The raw count of insurers within a county and the mean percentage of insurance networks that physicians participate in within each census tract., Results: A total of 2270 counties were examined within our first analyses. In the counties analyzed, a mean (SD) of 23.0% (3.2%) of the population was aged 18 years or younger, and a mean (SD) of 11.0% (15.8%) of the population had non-Hispanic Black race and ethnicity. For the second analysis, 16 006 to 25 096 census tracts were examined (depending on physician specialty). With adjustment for population size, age, and race and ethnicity, a 1-SD increase in the county non-Hispanic Black population was associated with a 14.1% reduction in the number of insurers (mean [SE] marginal effect size, -2.18 [0.13]; P < .001). Accounting for additional county-level risk selection controls and state fixed effects, a 1-SD increase in the non-Hispanic Black population was associated with a 2.3% reduction in available insurers (marginal effect size, -0.36 [0.17]; P = .04). For practitioners network breadth inclusion, a 1-SD increase in the non-Hispanic Black population was associated with a 15.8% (marginal effect size, -0.32 [0.01]; P < .001) to 24.7% (marginal effect size, -0.14 [0.02]; P < .001) reduction in the physicians' network participation depending on their specialty. Adjusting for additional state fixed effects yielded estimates of 6% (marginal effect size, -0.08 [0.01]; P < .001) to 13.5% (marginal effect size, -0.12 [0.02]; P < .001) reductions in practitioner network participation., Conclusions and Relevance: These findings suggest that strategic decisions by insurers may contribute toward markets with higher racial or ethnic minority populations having systematically fewer participating insurers, as well as a higher prevalence of local physicians not included in coverage networks. These findings call for further examination of potential insurance redlining within the ACA marketplaces.

Transboundary pathogens pose a threat to livelihood security in countries such as Zambia and Tanzania. This study aimed to investigate the seroprevalence of peste des petits ruminants virus (PPRV), foot and mouth disease virus (FMDV), sheep and goat pox virus (SGPV), Rift Valley fever virus (RVFV) and Brucella spp. in sheep and goats along the Tanzania-Zambia border. Another aim was to assess the association between certain predictor variables and seroprevalence, focusing on trade and proximity to an international border, to a town and to the Tanzania-Zambia highway. During September-October 2018, 486 serum samples from small ruminants in Zambia and 491 in Tanzania were collected and analyzed using enzyme-linked immunosorbent assays (ELISA). A questionnaire focused on management strategies was administered to each household. The animal-level seroprevalence in Zambia was 0.21% [95% confidence interval (CI) (0.01-1.14) for PPRV, 1.03% (95% CI 0.33-2.39) for FMDV, 0% (95% CI 0-0.76) for SGPV, 2.26% (95% CI 1.14-4.01) for RVFV and 1.65% (95% CI 0.71-3.22) for Brucella spp.]. In Tanzania, animal-level seroprevalence was 2.85% (95% CI 1.57-4.74) for PPRV, 16.9% (95% CI 13.7-20.5) for FMDV, 0.20% (95% CI 0.01-1.13) for SGPV, 3.26% (95% CI 1.87-5.24) for RVFV and 20.0% (95% CI 14.5-26.5) for Brucella spp. For PPRV (OR 6.83, 95% CI 1.37-34.0, p = 0.019) and FMDV (OR 5.68, 95% CI 1.58-20.3, p = 0.008), herds situated more than 30 km from an international border were more likely to be seropositive, while being located 10-30 km (OR 4.43, 95% CI 1.22-16.1 p = 0.024) from a border was identified as a risk factor for Brucella spp. For FMDV (OR 79.2, 95% CI 4.52-1388.9, p = 0.003), being situated within 30 km from a town was associated with seropositivity. Furthermore, contact with wild ruminants (OR 18.2, 95% CI 1.36-244), and the presence of sheep in the household (OR 5.20, 95% CI 1.00-26.9, p = 0.049), was associated with seropositivity for PPRV, and FMDV. No significant associations between trade or distance to the Tan-Zam highway and seroprevalence were found. We recommend that the impact of trade and proximity to borders, towns and roads should be further evaluated in larger studies, ideally incorporating aspects such as temporal trade fluctuations., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Lysholm, Lindahl, Munyeme, Misinzo, Mathew, Alvåsen, Dautu, Linde, Mitternacht, Olovsson, Wilén, Berg and Wensman.)

Cells communicate with their environment via surface receptors, but nanoscopic receptor organization with respect to complex cell surface morphology remains unclear. This is mainly due to a lack of accessible, robust and high-resolution methods. Here, we present an approach for mapping the topography of receptors at the cell surface with nanometer precision. The method involves coating glass coverslips with glycine, which preserves the fine membrane morphology while allowing immobilized cells to be positioned close to the optical surface. We developed an advanced and simplified algorithm for the analysis of single-molecule localization data acquired in a biplane detection scheme. These advancements enable direct and quantitative mapping of protein distribution on ruffled plasma membranes with near isotropic 3D nanometer resolution. As demonstrated successfully for CD4 and CD45 receptors, the described workflow is a straightforward quantitative technique to study molecules and their interactions at the complex surface nanomorphology of differentiated metazoan cells., (© 2022. The Author(s).)

Background: Prior work has shown that provider network structures correlate with outcomes such as patient costs, utilization, and care. However, it remains unknown whether certain provider networks are associated with reduced disparity gaps., Methods: We study the population of Medicare beneficiaries with diabetes who were continuously enrolled in Medicare FFS in 2016. Using multivariable regression analysis of county-level risk adjusted cost, hospitalization, emergency department visits, A1c testing, and preventable diabetes-related hospitalizations, we measure the effect that the relative network connectivity of primary care providers (PCPs) in relation to medical and surgical specialists (PCP/Specialist degree centrality ratio), derived from Medicare patient sharing data, has on non-Hispanic black-to-white disparity gaps controlling for county-level socioeconomic and demographic variables and state fixed effects., Results: Relative to non-Hispanic white, our adjusted results show that non-Hispanic black beneficiaries have $1673 (p<0.001) higher risk adjusted total costs, 2.6 (p<0.001) more hospitalizations (per 1000 beneficiaries), 11.6 (p<0.001) more ED visits (per 1000 beneficiaries), receive 2.2% (p<0.001) less A1c testing, and have 69.4 (p<0.01) more (per 100,000) avoidable diabetes-related hospital admissions. Our main results show that increasing the PCP/Specialist degree centrality ratio by one standard deviation is associated with a disparity gap decrease of 25.3% (p<0.01) in hospitalizations, 8.3% (p<0.05) in ED visits, 2.8% (p<0.01) in A1c testing, and 26.9% (p<0.1) in the volume of preventable diabetes-related hospital admissions., Conclusions: Network structures where PCPs are more central relative to medical and surgical specialists are associated with reduced non-Hispanic black-to-white disparity gaps, suggesting that how we organize and structure our health systems has implications for disparity gaps between non-Hispanic black and white Medicare beneficiaries with diabetes., (© 2021. Society of General Internal Medicine.)

Background: Physician accountable care organization (ACO) affiliation has been found to reduce cost and improve quality across metrics that are directly measured by the Medicare ACO programs. However, little is known about potential spillover effects from this program onto non-measured physician behavior such as antibiotic prescribing., Methods: Using a two-part structural selection model that accounts for selection into treatment (ACO group), and non-treatment (control group), we compare physician antibiotic prescribing across these groups with adjustment for volume, patient, physician and institutional characteristics. We also estimate heterogeneous treatment responses across specialties, focusing on physicians with a primary specialty of internal medicine, family or general practice, nurse practitioners, as well as general and orthopedic surgeons., Results: We find that ACO affiliation helps reduce antibiotic prescribing by 20.4 (95%CI = -26.65 to -14.16, p-value<0.001) prescriptions (about 19.5%) per year. We show that each additional hospital and practice affiliation increases prescriptions by 1.6 (95%CI = 1.27 to 1.95, p-value<0.001) and 1.7 (95%CI = 1.00 to 2.47, p-value<0.001), respectively. However, the use of electronic health records and high-quality medical training is associated with a decrease in antibiotic use of 7.9 (95%CI = -8.79 to -7.07, p-value<0.001) and 3.6 (95%CI = -4.47 to -2.73, p-value<0.001) claims, respectively. The treatment effects are found to vary with specialty, where internal medicine physicians experience an average decrease of 23.6 (95%CI = -29.98 to -17.20, p-value<0.001), family and general practice physicians a decrease of 22.1 (95%CI = -28.37 to -15.77, p-value<0.001), nurse practitioners a decrease of 7.1 (95%CI = -13.99 to -0.77, p-value = 0.028), general surgeons a decrease of 9.6 (95%CI = -16.02 to -3.25, p-value = 0.003), and orthopedic surgeons a reduction of 8.1 (95%CI = -14.84 to -1.42, p-value = 0.018) in their antibiotic prescribing per year., Conclusions: In assessing the impact of Medicare ACO programs it is important to account for spillover effects. Our study finds that ACO affiliation has had a measurable impact on physician antibiotic prescribing., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Safely returning underserved youth to school during the coronavirus disease 2019 (COVID-19) pandemic through diagnostic testing and health education is imperative to mitigate the ongoing negative impact of COVID-19 and reduce health inequalities in underserved communities. The Rapid Acceleration of Diagnostics-Underserved Populations program is a consortium of research projects across the United States funded by the National Institutes of Health to understand the factors associated with the disproportionate burden of the pandemic among underserved populations and to leverage mitigation strategies, including diagnostic testing, with a focus on reducing health disparities. In this article, we provide an overview and introduce the articles from 8 Rapid Acceleration of Diagnostics-Underserved Populations projects featured in the supplement "Navigating a Pandemic in the K-12 Setting: Keeping Our School Communities Safe" published in Pediatrics. These projects funded in the program's first phase focus on COVID-19 diagnostic testing approaches for youth and employees at schools in underserved communities to support safe in-person learning. In the articles comprising the supplement, researchers present barriers and facilitators of the community engagement process necessary to establish school-academic partnerships. These efforts showcase school-based implementation testing strategies during the COVID-19 pandemic but are translatable to tackling other challenges related to reducing health disparities., (Copyright © 2022 by the American Academy of Pediatrics.)

Physicians' relationships with the pharmaceutical industry have recently come under public scrutiny, particularly in the context of opioid drug prescribing. This study examines the effect of doctor-industry marketing interactions on subsequent prescribing patterns of opioids using linked Medicare Part D and Open Payments data for the years 2014-2017. Results indicate that both the number and the dollar-value of marketing visits increase physicians' patented opioid claims. Furthermore, direct-to-physician marketing of safer abuse-deterrent formulations of opioids is the primary driver of positive and persistent spillovers on the prescribing of less safe generic opioids - a result that we show appears to be driven by insurance coverage policies. These findings suggest that pharmaceutical marketing efforts may have unintended public health implications., (© 2021 John Wiley & Sons Ltd.)

Importance: Little is known about whether a clinician having multiple hospital affiliations (ie, 1 clinician working across multiple teams and organizations) is associated with clinician practice style and cost. The measurement of this association requires adjusting for selection into multihospital affiliations based on both observable and unobservable clinician characteristics., Objective: To evaluate the association of multiple hospital affiliations with clinician service use, breadth of procedures used, and costs., Design, Setting, and Participants: This cohort study used Medicare Part B data from 2016 through 2017 in a fixed-effects panel data design to compare service use, procedure breadth, and costs between clinicians with multiple affiliations (treatment group) and clinicians with a single affiliation (control group), with adjustment for volume, patients, and clinician characteristics. The study also controlled for unobserved (time-invariant) clinician characteristics using individual clinician fixed effects. Clinicians with Medicare claims, a reported National Provider Identifier, and affiliation data within Medicare Physician Compare were included for a total sample of 1 073 252 observations (633 552 unique clinicians) for medical services and 358 669 observations (210 260 unique clinicians) for drug prescribing. Statistical analyses were performed from February 1 to October 15, 2021., Main Outcomes and Measures: Service use is the total number of medical (or drug) services that clinicians render to their Medicare beneficiaries within a given year, procedure breadth is the total number of unique Healthcare Common Procedure Coding System codes that are associated with clinicians' medical (or drug) services within a given year, and costs represent the total standardized amount paid by Medicare for the medical (or drug) services. Additional measures were multiple-hospital affiliations, Accountable Care Organization affiliation, and controls across clinician and patient characteristics., Results: The medical service sample consisted of 633 552 clinicians (248 359 women [39.2%]; mean [SD] of 19.6 [12.5] years of experience), and the drug service sample consisted of 210 260 clinicians (74 875 women [35.6%]; mean [SD] of 21.6 [12.3] years of experience). For medical services, clinicians with multiple practice affiliations used a mean 8.2% (95% CI, 7.5%-8.9%; P < .001) more medical services per patient, drew on a mean 5.4% (95% CI, 5.1%-5.7%; P < .001) wider set of procedures within their medical care, and incurred a mean 8.6% (95% CI, 7.9%-9.2%; P < .001) more in medical costs. Pertaining to drug services, clinicians with multiple practice affiliations used a mean 2.9% (95% CI, 1.9%-3.9%; P < .001) more drug services per patient, drew on a mean 1.0% (95% CI, 0.5%-1.4%; P < .001) wider set of procedures within their medical care, and incurred a mean 2.7% (95% CI, 1.6%-3.7%; P < .001) more in drug costs. Significant results were also found across extensive and intensive margins of hospital affiliation, and supplemental analysis further indicated heterogenous treatment associations across clinician specialties., Conclusions and Relevance: This cohort study found that a clinician having multihospital affiliations was associated with greater service use, procedure breadth, and costs across both medical and drug services. These findings suggest that clinician affiliations ought to be considered as part of health care delivery design and potential cost-containment strategies.

Homogeneous illumination in single-molecule localization microscopy (SMLM) is key for the quantitative analysis of super-resolution images. Therefore, different approaches for flat-field illumination have been introduced as alternative to the conventional Gaussian illumination. Here, we introduce a single microelectromechanical systems (MEMS) mirror as a tunable and cost-effective device for adapting wide-field illumination in SMLM. In flat-field mode the MEMS allowed for consistent SMLM metrics across the entire field of view. Employing single-molecule photoswitching, we developed a simple yet powerful routine to benchmark different illumination schemes on the basis of local emitter brightness and ON-state lifetime. Moreover, we propose that tuning the MEMS beyond optimal flat-field conditions enables to study the kinetics of photoswitchable fluorophores within a single acquisition., Competing Interests: The authors declare no competing financial interest., (© 2021 The Authors. Published by American Chemical Society.)

The resilience of forests is compromised by human-induced environmental influences pushing them towards tipping points and resulting in major shifts in ecosystem state that might be difficult to reverse, are difficult to predict and manage, and can have vast ecological, economic and social consequences. The literature on tipping points has grown rapidly, but almost exclusively based on aquatic and aboveground systems. So far little effort has been made to make links to soil systems, where change is not as drastically apparent, timescales may differ and recovery may be slower. Predicting belowground ecosystem state transitions and recovery, and their impacts on aboveground systems, remains a major scientific, practical and policy challenge. Recently observed major changes in aboveground tree condition across European forests are probably causally linked to ectomycorrhizal (EM) fungal changes belowground. Based on recent breakthroughs in data collection and analysis, we apply tipping point theory to forests, including their belowground component, focusing on EM fungi; link environmental thresholds for EM fungi with nutrient imbalances in forest trees; explore the role of phenotypic plasticity in EM fungal adaptation to, and recovery from, environmental change; and propose major positive feedback mechanisms to understand, address and predict forest ecosystem tipping points., (© 2021 The Authors New Phytologist © 2021 New Phytologist Foundation.)

Understanding biological function requires the identification and characterization of complex patterns of molecules. Single-molecule localization microscopy (SMLM) can quantitatively measure molecular components and interactions at resolutions far beyond the diffraction limit, but this information is only useful if these patterns can be quantified and interpreted. We provide a new approach for the analysis of SMLM data that develops the concept of structures and super-structures formed by interconnected elements, such as smaller protein clusters. Using a formal framework and a parameter-free algorithm, (super-)structures formed from smaller components are found to be abundant in classes of nuclear proteins, such as heterogeneous nuclear ribonucleoprotein particles (hnRNPs), but are absent from ceramides located in the plasma membrane. We suggest that mesoscopic structures formed by interconnected protein clusters are common within the nucleus and have an important role in the organization and function of the genome. Our algorithm, SuperStructure, can be used to analyze and explore complex SMLM data and extract functionally relevant information., (© 2021 Marenda et al.)

Objective: The segmentation of the breast from the chest wall is an important first step in the analysis of breast magnetic resonance images. 3D U-Nets have been shown to obtain high segmentation accuracy and appear to generalize well when trained on one scanner type and tested on another scanner, provided that a very similar MR protocol is used. There has, however, been little work addressing the problem of domain adaptation when image intensities or patient orientation differ markedly between the training set and an unseen test set. In this work we aim to address this domain shift problem., Method: We propose to apply extensive intensity augmentation in addition to geometric augmentation during training. We explored both style transfer and a novel intensity remapping approach as intensity augmentation strategies. For our experiments, we trained a 3D U-Net on T1-weighted scans. We tested our network on T2-weighted scans from the same dataset as well as on an additional independent test set acquired with a T1-weighted TWIST sequence and a different coil configuration., Results: By applying intensity augmentation we increased segmentation performance for the T2-weighted scans from a Dice of 0.71 to 0.88. This performance is very close to the baseline performance of training with T2-weighted scans (0.92). On the T1-weighted dataset we obtained a performance increase from 0.77 to 0.85., Conclusion: Our results show that the proposed intensity augmentation increases segmentation performance across different datasets., Significance: The proposed method can improve whole breast segmentation of clinical MR scans acquired with different protocols.

New knowledge on soil structure highlights its importance for hydrology and soil organic matter (SOM) stabilization, which however remains neglected in many wide used models. We present here a new model, KEYLINK, in which soil structure is integrated with the existing concepts on SOM pools, and elements from food web models, that is, those from direct trophic interactions among soil organisms. KEYLINK is, therefore, an attempt to integrate soil functional diversity and food webs in predictions of soil carbon (C) and soil water balances. We present a selection of equations that can be used for most models as well as basic parameter intervals, for example, key pools, functional groups' biomasses and growth rates. Parameter distributions can be determined with Bayesian calibration, and here an example is presented for food web growth rate parameters for a pine forest in Belgium. We show how these added equations can improve the functioning of the model in describing known phenomena. For this, five test cases are given as simulation examples: changing the input litter quality (recalcitrance and carbon to nitrogen ratio), excluding predators, increasing pH and changing initial soil porosity. These results overall show how KEYLINK is able to simulate the known effects of these parameters and can simulate the linked effects of biopore formation, hydrology and aggregation on soil functioning. Furthermore, the results show an important trophic cascade effect of predation on the complete C cycle with repercussions on the soil structure as ecosystem engineers are predated, and on SOM turnover when predation on fungivore and bacterivore populations are reduced. In summary, KEYLINK shows how soil functional diversity and trophic organization and their role in C and water cycling in soils should be considered in order to improve our predictions on C sequestration and C emissions from soils., Competing Interests: Jorge Curiel Yuste is an Academic Editor for PeerJ. Mathieu Javaux, Harry Vereecken and Andrea Schnepf are employed by Forschungszentrum Jülich GmbH., (© 2021 Flores et al.)

Previous research shows that public perceptions of climate change risk are strongly related to the individual willingness to support climate mitigation and adaptation policy. In this article, I investigate how public perceptions of climate change risk are affected by communications from political parties and the degree of polarization among them. Specifically, using survey data from Sweden, Norway, Australia, and New Zealand, I study the relationship between party source cues, perceived polarization, and public perceptions of climate change risk. The results reveal a positive relationship between party cues and perceptions of climate change risk, indicating that individuals adjust their risk perceptions to align with their party preference. Furthermore, a negative relationship between perceived polarization and individual risk perceptions is also discovered, showing that individuals tend to be less concerned with climate change the more polarization they perceive. However, the effect of perceived polarization is found to be limited to more abstract perceptions of risk, while being unrelated to perceptions of concrete risks. Even with some contextual variance, the results generally hold up well across the four countries., (© 2020 The Authors. Risk Analysis published by Wiley Periodicals LLC on behalf of Society for Risk Analysis.)