Correction: The SIRT1 Deacetylase Suppresses Intestinal Tumorigenesis and Colon Cancer Growth.

[This corrects the article DOI: 10.1371/journal.pone.0002020.].

Delivery of a national prenatal exome sequencing service in England: a mixed methods study exploring healthcare professionals' views and experiences.

Introduction: In October 2020, rapid prenatal exome sequencing (pES) was introduced into routine National Health Service (NHS) care in England, requiring the coordination of care from specialist genetics, fetal medicine (FM) and laboratory services. This mixed methods study explored the experiences of professionals involved in delivering the pES service during the first 2 years of its delivery in the NHS. Methods: A survey (n = 159) and semi-structured interviews (n = 63) with healthcare professionals, including clinical geneticists, FM specialists, and clinical scientists (interviews only) were used to address: 1) Views on the pES service; 2) Capacity and resources involved in offering pES; 3) Awareness, knowledge, and educational needs; and 4) Ambitions and goals for the future. Results: Overall, professionals were positive about the pES service with 77% rating it as Good or Excellent. A number of benefits were reported, including the increased opportunity for receiving actionable results for parental decision-making, improving equity of access to genomic tests and fostering close relationships between FM and genetics departments. Nonetheless, there was evidence that the shift to offering pES in a clinical setting had brought some challenges, such as additional clinic time, administrative processes, perceived lack of autonomy in decision-making regarding pES eligibility and difficulty engaging with peripheral maternity units. Concerns were also raised about the lack of confidence and gaps in genomics knowledge amongst non-genetics professionals - especially midwives. However, the findings also highlighted value in both FM, obstetric and genetics professionals benefiting from further training with a focus on recognising and managing prenatally diagnosed genetic conditions. Conclusion: Healthcare professionals are enthusiastic about the benefits of pES, and through multi-collaborative working, have developed relationships that have contributed to effective communication across specialisms. Although limitations on resources and variation in knowledge about pES have impacted service delivery, professionals were hopeful that improvements to infrastructure and the upskilling of all professionals involved in the pathway would optimise the benefits of pES for both parents and professionals.

Contextualizing risk, pathways, and solutions for the relationship between adverse childhood experiences (ACEs) and type 2 diabetes among inner-city African Americans: A qualitative analysis and development of a theoretical framework.

PURPOSE: Adverse childhood experiences (ACEs) confer significant risk for diabetes in adulthood. The purpose of this study was to explore perceptions about risk, potential pathways leading to diabetes, and solutions based on the lived experience. METHODS: Three focus groups were conducted. A semi-structured interview guide was used to explore prevalence and causes of ACEs, pathways to diabetes, and possible solutions. Grounded theory was used for analysis. Constant comparisons resulted in emergent themes that were indexed and compared with the rest of the data to establish analytical categories. Analytical categories were further refined as additional data was collected until groups of key themes or categories were identified and used to construct a theoretical framework. RESULTS: Participants totaled 23 across 3 groups. All participants were African American. Average age was 49, average number of years living with diabetes was 13 years. Participants included both men and women. Participants experienced one or more occasions of sexual abuse, physical and verbal abuse, and neglect. The major themes can be classified as A. Cause, B. Pathway, and C. Treatment/solution. LIMITATIONS: Findings may not generalize to the overall population with ACEs and diabetes. CONCLUSIONS: Three major themes were identified: family instability and financial hardship as risks for ACEs, maladaptive coping leading to diabetes, and social structure as a potential solution. Future research is needed to examine quantitatively, pathways to inform prevention at the primary, secondary, and tertiary levels of care for both the prevention of ACEs, mitigating risk for diabetes, and improving overall health.

First-trimester use of antiseizure medications and the risk of miscarriage: a population-based cohort study.

BACKGROUND: Antiseizure medications (ASMs) during the first trimester of pregnancy have been associated with an increased risk of miscarriage. METHODS: We carried out a population-based cohort study using routinely collected healthcare data from the UK, 1995-2018. Pregnancies were identified in the Clinical Practice Research Datalink and we estimated the HR of miscarriage associated with prescriptions of ASMs during the first trimester of pregnancy, using Cox regression, adjusting for potential confounders, including ASM indications. RESULTS: ASMs were prescribed during the first trimester in 7832 (0.8%) of 1 023 787 included pregnancies. 14.5% of pregnancies with first-trimester exposure to ASMs ended in miscarriage, while 12.2% without ASM exposure in the first trimester ended in miscarriage; after adjustment, there was a 1.06-fold relative hazard of miscarriage (95% CI 1.00 to 1.13) in women with first-trimester ASM use. After restricting to women with specific ASM indications, this association was not evident in women with epilepsy (adjusted HR 0.98, 95% CI 0.89 to 1.08), but was observed in women with bipolar or other psychiatric conditions (1.08, 95% CI 1.00 to 1.16) although CIs overlapped. Compared with discontinuation of ASMs prior to pregnancy, there was no evidence of increased risk of miscarriage for first-trimester ASM use in women with bipolar or other psychiatric conditions (1.02, 95% CI 0.87 to 1.20). CONCLUSION: We found no clear evidence to suggest that first-trimester ASM use increased the risk of miscarriage. Taken together, our analyses suggest that apparent associations between first-trimester ASM use and miscarriage may be the result of confounding by the presence of a bipolar disorder or associated unmeasured variables.

Fast magnetization transfer saturation imaging of the brain using MP2RAGE T1 mapping.

PURPOSE: Magnetization transfer saturation (MTsat) mapping is commonly used to examine the macromolecular content of brain tissue. This study compared variable flip angle (VFA) T1 mapping against compressed-sensing MP2RAGE (csMP2RAGE) T1 mapping for accelerating MTsat imaging. METHODS: VFA, MP2RAGE, and csMP2RAGE were compared against inversion-recovery T1 in an aqueous phantom at 3 T. The same 1-mm VFA, MP2RAGE, and csMP2RAGE protocols were acquired in 4 healthy subjects to compare T1 and MTsat. Bloch-McConnell simulations were used to investigate differences between the phantom and in vivo T1 results. Ten healthy controls were imaged twice with the csMP2RAGE MTsat protocol to quantify repeatability. RESULTS: The MP2RAGE and csMP2RAGE protocols were 13.7% and 32.4% faster than the VFA protocol, respectively. At these scan times, all approaches provided strong repeatability and accurate T1 times (< 5% difference) in the phantom, but T1 accuracy was more impacted by T2 for VFA than for MP2RAGE. In vivo, VFA estimated longer T1 times than MP2RAGE and csMP2RAGE. Simulations suggest that the differences in the T1 measured using VFA, MP2RAGE, and inversion recovery could be explained by the magnetization-transfer effects. In the test-retest experiment, we found that the csMP2RAGE has a minimum detectable change of 2.3% for T1 mapping and 7.8% for MTsat imaging. CONCLUSIONS: We demonstrated that MP2RAGE can be used in place of VFA T1 mapping in an MTsat protocol. Furthermore, a shorter scan time and high repeatability can be achieved using the csMP2RAGE sequence.

Eosinophilic Myocarditis Resulting in Ventricular Tachycardia Storm.

Eosinophilic myocarditis (EM) is a rare but potentially fatal complication of sustained eosinophilia that is characterized by eosinophilic infiltration into myocardial tissue. There are various etiologies of EM that can be classified into general categories: reactive, clonal, and idiopathic. We present a case of EM caused by chronic eosinophilic leukemia, a rare myeloproliferative neoplasm that frequently presents with sustained peripheral eosinophilia. This case displays several serious complications of EM, including recurrent ventricular tachycardia storm, cardiogenic shock, and mural thrombus formation despite anticoagulation. Diagnosis of EM can be difficult as formal diagnosis requires an endomyocardial biopsy. Once EM is suspected, identifying the underlying etiology of eosinophilia is critical for timely implementation of disease-specific therapy.

Historic Redlining and Impact of Structural Racism on Diabetes Prevalence in a Nationally Representative Sample of U.S. Adults.

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.

Intimate partner violence in the lives of Indigenous and Black women in the upper Midwest of the United States during the COVID-19 pandemic: A mixed-methods protocol examining help-seeking behaviours and experiences.

Violent behaviour perpetrated against women has long-lasting negative physical and mental health consequences for women, their children, their families, and their communities. Intimate partner violence (IPV) is associated with many adverse physical, psychological, and emotional consequences. Structural racism and historical trauma affect women's trust and further hinder the ability of Indigenous and Black women to seek help after experiencing IPV. The availability of IPV support services, which can include shelter, food, group therapy, legal assistance, and advocacy, can be inaccessible to women due to the inability to access often limited resources in urban environments and reasons compounded by potential geographic distance if living in rural areas or living in community. Understanding the unique reasons why Indigenous and Black women do not seek help, and the barriers they experience when seeking help after IPV, is critical. Pandemics have the potential to create further complexities on how IPV is experienced. Black and Indigenous women experiencing IPV were therefore at even greater risk for IPV-related harm because of state and local "stay at home" measures put in place to minimise the spread COVID-19. The purpose of this manuscript is to explicate the methods for a large R01 study in the Upper Midwest.

Understanding the relationship between social risk factors and functional limitation among stroke survivors in the US.

BACKGROUND: Stroke is the fifth leading cause of death and disability in the United States. Social risk factors contribute to recovery from stroke, however the relationship between social risk factors and functional limitation among stroke survivors remains unknown. METHODS: Data on 2,888 adults with stroke from the National Health Interview Survey from 2016-2018 was analyzed. The primary independent variables included six social risk factors: economic instability, lack of community, educational deficit, food insecurity, social isolation, and inadequate access to care. The outcome measure was functional limitation count. Negative binomial regression models were run to test the relationship between the independent and dependent variables adjusting for covariates. RESULTS: Overall, 56% of the study participants were aged 65+, 70% were Non-Hispanic White, and 95% had at least one comorbidity. The mean functional limitation count was 1.8. In the unadjusted model, each social risk factor was significantly associated with functional limitation. In the fully adjusted model, significant association with functional limitation was found in individuals reporting economic instability (Incidence rate ratio [IRR] 1.65, 95% CI 1.33, 2.06), food insecurity (IRR 1.28, 95% CI 1.15, 1.42), and social isolation (IRR 1.64, 95% CI 1.48, 1.82). CONCLUSIONS: Social risk factors such as economic instability, food insecurity and social isolation are significantly associated with functional limitation in adults with stroke. Interventions designed to address both social and medical needs have the potential to improve physical functioning and other clinical outcomes in stroke survivors.

Relationship between delay discounting, delay aversion and psychosocial domains of diabetes care.

PURPOSE: Delay discounting and aversion are important areas for diabetes management; however, little has been done to understand the relationship with psychosocial outcomes among adults with type 2 diabetes. METHODS: This study used data from 365 adults with type 2 diabetes to evaluate relationships between delay discounting and aversion and psychosocial outcomes. Delay discounting and aversion were measured with the validated Quick Delay Questionnaire. Psychosocial outcomes included depression, measured by the PHQ, anxiety by the GAD scale, perceived stress by the PSS, and social support by the Duke Social Support and Stress Scale. Multiple linear regression was used to assess the relationship between delay discounting and aversion on psychological health and social support controlling for relevant covariates. RESULTS: Mean age of the sample was 61.8 years, 54.5 % were NHB, 41.8 % NHW, and 3.7 % Hispanic/Other. After adjusting for covariates, delay aversion was significantly associated with depression (beta = 0.35; p < 0.001), anxiety (beta = 0.52; p < 0.001), perceived stress (beta = 0.22; p < 0.001), and lower family support (beta = -0.62; p < 0.05). Delay discounting was significantly associated with depression (beta = 0.32; p < 0.001), anxiety (beta = 0.46; p < 0.001), and perceived stress (beta = 0.26; p < 0.001). LIMITATIONS: This data is cross-sectional, future work should examine the longitudinal relationship while also including additional psychosocial outcomes. CONCLUSIONS: Delay discounting and aversion are significantly associated with poor psychosocial outcomes, including lower social support. As the body of evidence grows, additional research is needed to better understand the construct, mechanisms, and the impact of choice settings to better inform intervention development.

The human brain connectome weighted by the myelin content and total intra-axonal cross-sectional area of white matter tracts.

A central goal in neuroscience is the development of a comprehensive mapping between structural and functional brain features, which facilitates mechanistic interpretation of brain function. However, the interpretability of structure-function brain models remains limited by a lack of biological detail. Here, we characterize human structural brain networks weighted by multiple white matter microstructural features including total intra-axonal cross-sectional area and myelin content. We report edge-weight-dependent spatial distributions, variance, small-worldness, rich club, hubs, as well as relationships with function, edge length, and myelin. Contrasting networks weighted by the total intra-axonal cross-sectional area and myelin content of white matter tracts, we find opposite relationships with functional connectivity, an edge-length-independent inverse relationship with each other, and the lack of a canonical rich club in myelin-weighted networks. When controlling for edge length, networks weighted by either fractional anisotropy, radial diffusivity, or neurite density show no relationship with whole-brain functional connectivity. We conclude that the co-utilization of structural networks weighted by total intra-axonal cross-sectional area and myelin content could improve our understanding of the mechanisms mediating the structure-function brain relationship.

Assessing inter-rater agreement of the intellectual disability-frailty index short form: A descriptive pilot study.

Frailty is a health concern for many adults with intellectual disability and should be measured to detect at-risk conditions, monitor disease, plan treatment, and gauge mortality. This descriptive pilot study evaluated measurement consistency (inter-rater agreement) of the Intellectual Disability-Frailty Index Short Form among multiple assessors with 20 adults (M age = 48.3 years) who had intellectual and multiple disabilities. Agreement percentages were computed for (a) non-frail, pre-frail, and frail categories derived from total index scores, and (b) each of 17 deficits listed on the form. Low average inter-rater agreement (<85%) was obtained on the index frail categories, several of the assessed deficits had acceptable inter-rater agreement (84.2-100%), while the majority of deficits were associated with moderate-to-low agreement percentages. Though research supports the Intellectual Disability-Frailty Index Short Form as a valid and practical frailty assessment instrument, our findings suggest that full-scale inter-rater agreement must be improved by adding more specificity to the form, clarifying instructions for assessors, and providing competency-based training in assessment implementation.

Prevalence and correlates of pre-diabetes in Sub-Saharan Africa using Demographic and Health Survey Data: a cross-sectional study.

OBJECTIVE: The objective is to investigate the prevalence of pre-diabetes in Namibia and South Africa and to determine sociodemographic correlates of disease using population data. DESIGN: Cross-sectional study. SETTING: Demographic and Health Survey for emerging (Namibia) and established (South Africa) economies in Sub-Saharan Africa collected laboratory data that allowed determination of pre-diabetes status. PARTICIPANTS: 3141 adults over age 18 from the 2013 Namibia survey, weighted to a population of 2176, and 4964 adults over age 18 from the 2016 South Africa survey, weighted to a population of 4627 had blood glucose/glycated haemoglobin (HbA1c) and diabetes information were included in the analysis. OUTCOME MEASURES: Pre-diabetes was defined as not being diagnosed with diabetes and having a blood sugar measurement of 100-125 mg/dL in Namibia or an HbA1c measurement of 5.7%-6.4%. Logistic models were run for each country separately, with pre-diabetes as the outcome and a series of sociodemographic variables (age, gender, urban/rural residence, number of children, employment status, wealth index, education level, and ethnicity (in South Africa) or religion (in Namibia)) entered as variables to investigate the independent relationship of each. RESULTS: The weighted prevalence of pre-diabetes was 18.7% in Namibia and 70.1% in South Africa. Rural residence was independently associated with higher odds of pre-diabetes in Namibia (1.47, 95% CI 1.05 to 2.06), while both younger age (0.98, 95% CI 0.97 to 0.99) and urban residence (0.80, 95% CI 0.66 to 0.99) were independently associated with odds of pre-diabetes in South Africa. CONCLUSIONS: The prevalence of pre-diabetes was 18.7% in Namibia and 70.1% in South Africa. Correlates of pre-diabetes differed between the two countries with rural residents having higher odds of pre-diabetes in Namibia and urban residents with higher odds in South Africa. Aggressive interventions, including population level education and awareness programmes, and individual level education and lifestyle interventions that account for country-specific contextual factors are urgently needed to prevent progression to diabetes.

Relationship between Satisfaction Scores and Racial/Ethnic and Sex Concordance in Primary Care.

Racial/ethnic and sex concordance between patients and providers has been suggested as an important consideration in improving satisfaction and increasing health equity. We aimed to guide local efforts by understanding the relationship between satisfaction with care and patient-provider racial/ethnic and sex concordance within our academic medical center's primary care clinic. METHODS: Satisfaction data for encounters from August 2016 to August 2019 were matched to data from the medical record for patient demographics and comorbidities. Data on 33 providers were also obtained, and racial/ethnic and sex concordance between patients and providers was determined for each of the 3672 unique encounters. The primary outcome was top-box scoring on the CGCAHPS overall satisfaction scale (0-8 vs. 9-10). Generalized mixed-effects logistic regression, including provider- and patient-level factors as fixed effects and a random intercept effect for providers, were used to determine whether concordance had an independent relationship with satisfaction. RESULTS: 89.0% of the NHW-concordant pairs and 90.4% of the Minority Race/Ethnicity-concordant pairs indicated satisfaction, while 90.1% of the male-concordant and 85.1% of the female-concordant pairs indicated satisfaction. When fully adjusted, the female-concordant (OR = 0.58, 95% CI 0.35-0.94) and male-discordant (OR = 0.68, 95% CI 0.51-0.91) pairs reported significantly lower top-box satisfaction compared to the male-concordant pairs. Significant differences did not exist in racial/ethnic concordance. CONCLUSIONS: In this sample, differences in sex concordance were noted; however, patient- and provider-level factors may be more influential in driving patient satisfaction than race/ethnicity in this health system.

Fifteen-minute consultation: How to approach the initial discussions of dysmorphism with parents.

Approaching discussions and introducing the idea of dysmorphology to parents and families can be perceived as difficult and even daunting by health professionals resulting in uneasiness in how best to initiate important dialogues sensitively and accessibly.Here, we offer a structured approach to the assessment of, and subsequent initial discussion around, dysmorphism and potential syndromic features in babies and children.

Ungulate responses and habituation to unmanned aerial vehicles in Africa's savanna.

This article tests the hypothesis that "the likelihood that the species will react and level at which they do to the unmanned aerial vehicle (UAV) is related to the altitude, number of passes, sound intensity, type of UAV, takeoff distance, and species." This paper examined the behavioral responses of a group of free ranging ungulate species (Oryx, Kudu, Springbok, Giraffe, Eland, Hartebeest, and Impala) found in an animal reserve in Namibia to the presence of different in-flight UAV models. The study included 397 passes (trials) over 99 flights at altitudes ranging from 15 to 55 meters in three categories of response level: No response, Alert, and Movement. The ungulates were unhabituated to the UAVs and the study was conducted in the presence of stress-inducing events that occur naturally in the environment. Certain species were found to be more reactive than others, in addition to several displaying different response levels in single or mixed herd environments. Zebras were found to be less responsive in mixed herd environments while Oryx were present, as compared to when the Oryx were not; suggesting that some species may respond based on other species perception of threat or their relative fitness levels. The UAVs also produced inconsistent response rates between movement and alert behavior. The reference vehicle, Phantom 3 was much more likely than the Mavic to induce an alert response, while both having similar probabilities of inducing a movement response. Furthermore, the Custom X8 showed significantly more alert and movement responses than the other UAVs. This shows there may be several aspects to the UAVs that affect the responses of the ungulates. For instance, the sound intensity may alert the species more often, but close proximity may induce a movement response. More generally, the data shows that when the UAV is flying above 50 meters and has a measured sound intensity below 50 dB, the likelihood of inducing a movement response on an ungulate species is below 6% regardless of the vehicle on the first pass over the animals. Additionally, with each subsequent pass the likelihood of response dropped by approximately 20 percent. The results suggest a stronger correlation between flight altitude and response across the different ungulates, and the evidence suggests rapid habituation to the UAVs.

Evolution of a Cocurricular Program to Support Student Professional Identity Formation.

OBJECTIVE: Describe the development, implementation, and assessment of a cocurricular program intentionally designed to foster professional identity formation at a private institution. METHODS: A cocurricular committee was established which developed a cocurriculum program in 3 phases. The committee utilized a gap analysis to inform the development of a continuing-education-based elective program (phase I), broadened program components and enhanced assessment (phase II), and continued to strengthen select areas of the affective domains through a second gap analysis and implement a summative assessment (phase III). RESULTS: Over 2 academic years, the completion rates for reflections, continuing education programming, and community outreach in the most recent academic year were consistently above 80% by the final due date. Rates of the mentor-mentee meetings fell below 50%; however, this component is tracked by the faculty member and not the students. Community outreach monitoring was managed by the committee for the first time in the 2021-2022 academic year and completion rates increased from 64% to 82%. Student reflections indicated consistent progression toward practice readiness from first- to third-year pharmacy students. For the Pharmacy Affective Domain Situational Judgment test, 22% and 16% of first-year pharmacy students were flagged during the first and second year implemented, respectively, and only 8% of the third-year pharmacy students were flagged in both years. CONCLUSION: Utilization of a cocurricular committee has been vital for the development, progression, and assessment of the cocurriculum at a single private institution.