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INTRODUCTION: Particulate air pollutants may induce neurotoxicity by increasing homocysteine levels, which can be lowered by high B vitamin intakes. Therefore, we examined whether intakes of three B vitamins (folate, B(12), and B(6)) modified the association between PM(2.5) exposure and incidence of all-cause dementia. METHODS: This study included 7183 women aged 65 to 80 years at baseline. B vitamin intakes from diet and supplements were estimated by food frequency questionnaires at baseline. The 3-year average PM(2.5) exposure was estimated using a spatiotemporal model. RESULTS: During a mean follow-up of 9 years, 342 participants developed all-cause dementia. We found that residing in locations with PM(2.5) exposure above the regulatory standard (12 μg/m(3)) was associated with a higher risk of dementia only among participants with lower intakes of these B vitamins. DISCUSSION: This is the first study suggesting that the putative neurotoxicity of PM(2.5) exposure may be attenuated by high B vitamin intakes.

Arterial stiffness may play a role in the development of dementia through poorly understood effects on brain microstructural integrity and perfusion.We examined markers of arterial stiffness (carotid-femoral pulse wave velocity [cfPWV]) and elevated systolic blood pressure (SBP) in relation to cognitive function and brain magnetic resonance imaging macrostructure (gray matter [GM] and white matter [WM] volumes), microstructure (diffusion based free water [FW] and fractional anisotropy [FA]), and cerebral blood flow (CBF) in WM and GM in models adjusted for age, race, sex, education, and apolipoprotein E ε4 status.Among 460 participants (70 ± 8 years; 44 dementia, 158 mild cognitive impairment, 258 normal cognition), higher cfPWV and SBP were independently associated with higher FW, higher WM hyperintensity volume, and worse cognition (global and executive function). Higher SBP alone was significantly associated with lower WM and GM CBF.Arterial stiffness is associated with impaired WM microstructure and global and executive cognitive function.

We investigate the electrical characteristics of Ni Schottky contacts on n-type GaN films that have undergone ultra-high-pressure annealing (UHPA), a key processing step for activating implanted Mg. Contacts deposited on these films exhibit low rectification and high leakage current compared to contacts on as-grown films. By employing an optimized surface treatment to restore the GaN surface following UHPA, we obtain Schottky contacts with a high rectification ratio of ∼109, a near-unity ideality factor of 1.03, and a barrier height of ∼0.9 eV. These characteristics enable the development of GaN junction barrier Schottky diodes employing Mg implantation and UHPA.

Previous disparities research has demonstrated that underrepresented racial minority patients have worse colorectal cancer outcomes and that they experience unnecessary delays in time to treatment. These delays may explain worse colorectal cancer outcomes for minority patients and serve as a marker of inequalities in our healthcare system.This study aims to quantify the mechanisms that contribute to this disparity in treatment delay.This is a retrospective analysis of colorectal cancer patients who underwent elective resection from 2004-2017. A causal inference mediation analysis using the counterfactual framework was utilized to estimate the extent to which racial disparities amongst patient factors explain the racial disparities in time to treatment. Mediators included income, education, comorbidities, insurance, and hospital type.This study was conducted at hospitals participating in the National Cancer Database.Stage I-III colorectal cancer patients, ≥18 years old, who underwent elective resection from 2004-2017 were included.The primary measures were indirect effect of mediators between race and delayed time to treatment.Of the 504,405 patients (370,051 colon, 134,354 rectal), 10%, 5%, 4% were Black, Hispanic and Other, respectively. In multivariable models, compared to White patients, these patients had 25%, 27% and 17% greater odds of delayed treatment. Mediation analyses suggested that 43%, 20%, 31% of the treatment delay among, respectively, could be removed if an intervention equalized income, education, comorbidities, insurance, and hospital type to that of White patients. Treatment at an academic hospital explained 15%-32% of the racial disparity and was the most potent mediator.This study was limited by its retrospective design; failure to capture all meaningful mediators.Black, Hispanic, and Other colorectal cancer patients experience treatment delays when compared to White patients. Equalization of the mediators used in this study could reduce treatment delays by 20-43% depending on racial/ethnic group. Future research should identify other causes of racial disparities in treatment delay and intervene upon them. See Video Abstract at http://links.lww.com/DCR/B871.

Background: Previous studies suggest that certain dietary patterns and constituents may be beneficial to brain health. Airborne exposures to fine particulate matter [particulate matter with aerodynamic diameter ≤2.5μm (PM2.5)] are neurotoxic, but the combined effects of dietary patterns and PM2.5 have not been investigated. Objectives: We examined whether previously reported association between PM2.5 exposure and lower white matter volume (WMV) differed between women whose usual diet during the last 3 months before baseline was more or less consistent with a Mediterranean–DASH Intervention for Neurodegenerative Delay (MIND)-like diet, a dietary pattern that may slow neurodegenerative changes. Methods: This study included 1,302 U.S. women who were 65–79 y old and free of dementia in the period 1996–1998 (baseline). In the period 2005–2006, structural brain magnetic resonance imaging (MRI) scans were performed to estimate normal-appearing brain volumes (excluding areas with evidence of small vessel ischemic disease). Baseline MIND diet scores were derived from a food frequency questionnaire. Three-year average PM2.5 exposure prior to MRI was estimated using geocoded participant addresses and a spatiotemporal model. Results: Average total and temporal lobe WMVs were 0.74 cm3 [95% confidence interval (CI): 0.001, 1.48) and 0.19 cm3 (95% CI: 0.002, 0.37) higher, respectively, with each 0.5-point increase in the MIND score and were 4.16 cm3 (95% CI: –6.99, –1.33) and 1.46 cm3 (95% CI: –2.16, –0.76) lower, respectively, with each interquartile range (IQR) (IQR=3.22 μg/m3) increase in PM2.5. The inverse association between PM2.5 per IQR and WMV was stronger (p-interaction

In this article I introduce a variety of social, political and economic collectivities to analyze ways in which their interactions are influenced by borders as the territorial delimitations of legal authority, or jurisdictions. The limits of authority within such collectivities are seen in the overlapping grants of authority that impact them. To the extent that borders delineate spheres of legitimate action by governments, they can be defensive of the rights of people within them as well as protective of the rights of governments to impinge on those same rights, or both simultaneously. Borders can thus be constraining of those who cannot easily pass across them, yet simultaneously unconstraining of international actors who may be predatory on those who expect their state to protect them. If we are to understand borders, boundaries and cognate phenomena, we need always to take both sets of relations into account.

Background Indices of multimorbidity and deficit accumulation (ie, frailty indices) have been proposed as markers of biological aging. If true, changes in these indices over time should predict downstream changes in cognition and physical function, and mortality. Methods We examined associations that 8-year changes in (i) a multimorbidity index comprised of 9 chronic diseases and (ii) a frailty index (FI) based on deficit accumulation in functional, behavioral, and clinical characteristics had with subsequent measures of cognitive and physical function over 10 years. We drew data from 3 842 participants in the Action for Health in Diabetes clinical trial. They were aged 45–76 years at baseline and at risk for accelerated biological aging due to overweight/obesity and type 2 diabetes mellitus. Results A total of 1 501 (39%) of the cohort had 8-year increases of 1 among the 9 diseases tracked in the multimorbidity index and 868 (23%) had increases of ≥2. Those with greatest increases in multimorbidity tended to be older individuals, males, and non-Hispanic Whites. Greater FI increases tended to occur among individuals who were older, non-Hispanic White, heavier, and who had more baseline morbidities. Changes in multimorbidity and FI were moderately correlated (r = 0.26; p < .001). Increases in both multimorbidity and FI were associated with subsequently poorer composite cognitive function and 400-m walk speed and increased risk for death (all p < .001). Conclusions Accelerated biological aging, as captured by multimorbidity and frailty indices, predicts subsequent reduced function and mortality. Whether intensive lifestyle interventions generally targeting multimorbidity and FI reduce risks for downstream outcomes remains to be seen. Clinical Trials Registration Number: NCT00017953

Objective: To evaluate changes in the prevalence of depressive symptoms, loneliness, and insomnia among older adults with type 2 diabetes from 2016 to 2020, and to assess risk factors for these conditions including demographics, multimorbidity, body mass index, treatment group, and pre-COVID-19 measure scores. Research Design and Methods: This was a prospective, observational study of participants from the Look AHEAD cohort study. Data were from two assessments before COVID-19 (Visit 1 (V1): April 2016-June 2018 and Visit 2 (V2): February 2018-February 2020), and one assessment during COVID-19 (Visit 3 (V3): July-December 2020). Surveys were administered to assess depressive symptoms, loneliness, and insomnia. Results: The study included 2829 adults (63.2% female, 60.6% white, mean [SD] age 75.6 [6.0] years). The prevalence of mild or greater depressive symptoms did not change significantly between the two pre-pandemic visits (p=0.88) but increased significantly from pre- to during COVID-19 (19.3% at V2 to 30.4% at V3 (p Conclusions: The prevalence of mild or greater depressive symptoms in older adults with diabetes was more than 1.6 times higher during COVID-19 than before the pandemic.

Background: Identification of factors that may help to preserve cognitive function in late life could elucidate mechanisms and facilitate interventions to improve the lives of millions of people. However, the large number of potential factors associated with cognitive function poses an analytical challenge. Objective: We used data from the longitudinal Women’s Health Initiative Memory Study (WHIMS) and machine learning to investigate 50 demographic, biomedical, behavioral, social, and psychological predictors of preserved cognitive function in later life. Methods: Participants in WHIMS and two consecutive follow up studies who were at least 80 years old and had at least one cognitive assessment following their 80th birthday were classified as cognitively preserved. Preserved cognitive function was defined as having a score ≥39 on the most recent administration of the modified Telephone Interview for Cognitive Status (TICSm) and a mean score across all assessments ≥39. Cognitively impaired participants were those adjudicated by experts to have probable dementia or at least two adjudications of mild cognitive impairment within the 14 years of follow-up and a last TICSm score

When the transition temperature of a continuous phase transition is tuned to absolute zero, new ordered phases and physical behaviour emerge in the vicinity of the resulting quantum critical point. Sr3Ru2O7 can be tuned through quantum criticality with magnetic field at low temperature. Near its critical field Bc it displays the hallmark T-linear resistivity and a \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$T\,{{{{{{\mathrm{log}}}}}}}\,(1/T)$$\end{document}Tlog(1/T) electronic heat capacity behaviour of strange metals. However, these behaviours have not been related to any critical fluctuations. Here we use inelastic neutron scattering to reveal the presence of collective spin fluctuations whose relaxation time and strength show a nearly singular variation with magnetic field as Bc is approached. The large increase in the electronic heat capacity and entropy near Bc can be understood quantitatively in terms of the scattering of conduction electrons by these spin-fluctuations. On entering the spin-density-wave ordered phase present near Bc, the fluctuations become stronger suggesting that the order is stabilised through an “order-by-disorder” mechanism., Sr3Ru2O7 exhibits a quantum critical point tunable by magnetic field and has been widely used in the study of criticality. Here, by using inelastic neutron scattering, the authors measure collective magnetic excitations near the quantum critical point and relate them to thermodynamic properties and spin density wave order.

BACKGROUND Telehealth for emergency stroke care delivery (telestroke) has had widespread adoption, enabling many hospitals to obtain stroke center certification. Telehealth for pediatric emergency care has been less widely adopted. OBJECTIVE Our primary objective was to determine whether differences in policy or certification requirements contributed to differential uptake of telestroke versus pediatric telehealth. We hypothesized that differences in financial incentives, based on differences in patient volume, prehospital routing policy, and certification requirements, contributed to differential emergency department (ED) adoption of telestroke versus pediatric telehealth. METHODS We used the 2016 National Emergency Department Inventory–USA to identify EDs that were using telestroke and pediatric telehealth services. We surveyed all EDs using pediatric telehealth services (n=339) and a convenience sample of the 1758 EDs with telestroke services (n=366). The surveys characterized ED staffing, transfer patterns, reasons for adoption, and frequency of use. We used bivariate comparisons to examine differences in reasons for adoption and use between EDs with only telestroke services, only pediatric telehealth services, or both. RESULTS Of the 442 EDs surveyed, 378 (85.5%) indicated use of telestroke, pediatric telehealth, or both. EDs with both services were smaller in bed size, volume, and ED attending coverage than those with only telestroke services or only pediatric telehealth services. EDs with telestroke services reported more frequent use, overall, than EDs with pediatric telehealth services: 14.1% (45/320) of EDs with telestroke services reported weekly use versus 2.9% (8/272) of EDs with pediatric telehealth services (PP=.003). CONCLUSIONS In 2016, more US EDs had telestroke services than pediatric telehealth services; among EDs with the technology, consults were more frequently made for stroke than for pediatric patients. The most frequently indicated reason for adoption among all EDs was related to clinical care.

Background Telehealth for emergency stroke care delivery (telestroke) has had widespread adoption, enabling many hospitals to obtain stroke center certification. Telehealth for pediatric emergency care has been less widely adopted. Objective Our primary objective was to determine whether differences in policy or certification requirements contributed to differential uptake of telestroke versus pediatric telehealth. We hypothesized that differences in financial incentives, based on differences in patient volume, prehospital routing policy, and certification requirements, contributed to differential emergency department (ED) adoption of telestroke versus pediatric telehealth. Methods We used the 2016 National Emergency Department Inventory–USA to identify EDs that were using telestroke and pediatric telehealth services. We surveyed all EDs using pediatric telehealth services (n=339) and a convenience sample of the 1758 EDs with telestroke services (n=366). The surveys characterized ED staffing, transfer patterns, reasons for adoption, and frequency of use. We used bivariate comparisons to examine differences in reasons for adoption and use between EDs with only telestroke services, only pediatric telehealth services, or both. Results Of the 442 EDs surveyed, 378 (85.5%) indicated use of telestroke, pediatric telehealth, or both. EDs with both services were smaller in bed size, volume, and ED attending coverage than those with only telestroke services or only pediatric telehealth services. EDs with telestroke services reported more frequent use, overall, than EDs with pediatric telehealth services: 14.1% (45/320) of EDs with telestroke services reported weekly use versus 2.9% (8/272) of EDs with pediatric telehealth services (P Conclusions In 2016, more US EDs had telestroke services than pediatric telehealth services; among EDs with the technology, consults were more frequently made for stroke than for pediatric patients. The most frequently indicated reason for adoption among all EDs was related to clinical care.

Hall effect and quantum oscillation measurements on high temperature cuprate superconductors show that underdoped compositions have small Fermi surface pockets whereas when heavily overdoped, a single much larger pocket is found. The origin of this change in electronic structure has been unclear, but may be related to the high temperature superconductivity. Here we show that the clean overdoped single-layer cuprate Tl2Ba2CuO6+δ (Tl2201) displays CDW order with a remarkably long correlation length ξ ≈ 200 Å which disappears above a hole doping of pCDW ≈ 0.265. We show that the evolution of the electronic properties of Tl2201 as the doping is lowered may be explained by a Fermi surface reconstruction which accompanies the emergence of the CDW below pCDW. Our results demonstrate importance of CDW correlations in understanding the electronic properties of overdoped cuprates., The origin of the Fermi surface reconstruction that occurs in cuprate superconductors as hole doping increases remains unclear. Here, the authors observe long range charge density wave (CDW) order in the overdoped single-layer cuprate Tl2Ba2CuO6+δ, which then disappears above a hole concentration 0.265, suggesting a correlation between Fermi surface reconstruction and the emergence of the CDW.

Background Epigenetic age acceleration (AgeAccel), which indicates faster biological aging relative to chronological age, has been associated with lower cognitive function. However, the association of AgeAccel with mild cognitive impairment (MCI) or dementia is not well-understood. We examined associations of 4 AgeAccel measures with incident MCI and dementia. Methods This prospective analysis included 578 older women from the Women’s Health Initiative Memory Study selected for a case–cohort study of coronary heart disease (CHD). Women were free of CHD and cognitive impairment at baseline. Associations of AgeAccel measures (intrinsic AgeAccel [IEAA], extrinsic AgeAccel [EEAA], AgeAccelPheno, and AgeAccelGrim) with risks for incident adjudicated diagnoses of MCI and dementia overall and stratified by incident CHD status were evaluated. Results IEAA was not significantly associated with MCI (HR, 1.23; 95% CI, 0.99–1.53), dementia (HR, 1.10; 95% CI, 0.88–1.38), or cognitive impairment (HR, 1.18; 95% CI, 0.99–1.40). In stratified analysis by incident CHD status, there was a 39% (HR, 1.39; 95% CI, 1.07–1.81) significantly higher risk of MCI for every 5-year increase in IEAA among women who developed CHD during follow-up. Other AgeAccel measures were not significantly associated with MCI or dementia. Conclusions IEAA was not significantly associated with cognitive impairment overall but was associated with impairment among women who developed CHD. Larger studies designed to examine associations of AgeAccel with cognitive impairment are needed, including exploration of whether associations are stronger in the setting of underlying vascular pathologies.

Hirschsprung’s disease is primarily a disease of infancy, but in rare cases, adults with this condition require surgery. The aim of this study is to identify the types of operations and postoperative outcomes in adults with Hirschsprung’s disease on a national level. The National Surgical Quality Improvement Program database was used to perform a retrospective review of all adult patients diagnosed with Hirschsprung’s disease. Patients were divided into two groups depending on the type of operation: restoration of bowel continuity or diversion of fecal stream; clinicopathologic data and 30-day outcomes were compared between the two groups. A total of 32 patients were analyzed. Fourteen patients (43.8%) underwent diversion and 18 (56.2%) underwent restorative procedures. The median age was 49.5 years old for the diversion group and 23.5 years old for the reconstructive group (p = 0.001). The restorative surgery group was more likely to have an ASA 1–2 while the diversion group had a higher frequency of ASA 3–5 (p = 0.011). The median length of stay for the diversion surgery was 9.5 days and 5 days for the restoration group (p = 0.045). Complications occurred in 57% of patients in the diversion group and in 22% of patients in the restoration group (p = 0.049). There were otherwise no statistically significant differences in intraoperative data and postoperative complications. This is the first study using a national database to evaluate the surgical treatment of Hirschsprung’s disease in adult patients. Complications are common and were more frequent in the older, sicker diversion group, with restoration of continuity being better tolerated in the younger, healthier patient population.

Background Postoperative inflammation is a common consequence of surgery and the ensuing stress response. Local anesthetics have anti-inflammatory properties. The primary aim of this study was to evaluate if LA administrated intraperitoneally perioperatively might inhibit expression of inflammatory cytokines. Methods This was a, randomized, double blind, placebo-controlled study (ClinicalTrial.gov reg no: NCT02256228) in patients undergoing surgery for ovarian cancer. Patients were randomized to receive: intraperitoneal ropivacaine (Group IPLA) or saline (Group P) perioperatively. Except for study drug, patients were treated similarly. At the end of surgery, a multi-port catheter was inserted intraperitoneally, and ropivacaine 2 mg/mL or 0.9% saline, 10 mL was injected intermittently every other hour during 72 hours postoperatively. Systemic expression of cytokines and plasma ropivacaine were determined before and 6, 24, and 48 hours after surgery. Stress response was measured by serum glucose, cortisol, and insulin. Results Forty patients were recruited, 20 in each group. There was no statistical significant difference in systemic cytokine between the groups at any time point. Serum cortisol was significantly lower in the IPLA group at 6 hours, median 103 nmol/L (IQR 53-250) compared to placebo, median 440 nmol/L (IQR 115-885), P = 0.023. Serum glucose and insulin were similar between the groups. Total and free serum concentrations of ropivacaine were well below toxic concentrations. Conclusion In this small study, perioperative intraperitoneal ropivacaine did not reduce the systemic inflammatory response associated with major abdominal surgery. Total and free ropivacaine concentrations were below known toxic concentrations in humans.

Background Sex may be an important modifier of brain health in response to risk factors. We compared brain structure and function of older overweight and obese women and men with type 2 diabetes mellitus. Methods Cross-sectional cognitive assessments and magnetic resonance images were obtained in 224 women and 95 men (mean age 69 years) with histories of type 2 diabetes mellitus and overweight or obesity. Prior to magnetic resonance images, participants had completed an average of 10 years of random assignment to either multidomain intervention targeting weight loss or a control condition of diabetes support and education. Total (summed gray and white) matter volumes, white matter hyperintensity volumes, and cerebral blood flow across five brain regions of interest were analyzed using mixed-effects models. Results After covariate adjustment, women, compared with men, averaged 10.9 [95% confidence interval 3.3, 18.5; ≈1%] cc greater summed region of interest volumes and 1.39 [0.00002, 2.78; ≈54%] cc greater summed white matter hyperintensity volumes. Sex differences could not be attributed to risk factor profiles or intervention response. Their magnitude did not vary significantly with respect to age, body mass index, intervention assignment, or APOE-ε4 genotype. Sex differences in brain magnetic resonance images outcomes did not account for the better levels of cognitive functioning in women than men. Conclusions In a large cohort of older overweight or obese adults with type 2 diabetes mellitus, differences in brain volumes and white matter disease were apparent between women and men, but these did not account for a lower prevalence of cognitive impairment in women compared with men in this cohort. Trial registration NCT00017953.

ObjectiveTo examine the relationship between blood pressure (BP) variability (BPV), brain volumes, and cognitive functioning in postmenopausal women with few modifiable cardiovascular risk factors.MethodsStudy participants consisted of postmenopausal women enrolled in the Women's Health Initiative Memory MRI study (WHIMS-MRI) without cardiovascular disease, diabetes mellitus, hypertension, or current smoking at baseline (1996–1999). BP readings were taken at baseline and each annual follow-up visit. BPV was defined as the SD associated with a participant's mean BP across visits and the SD associated with the participant's regression line with BP regressed across visits. Brain MRI scans were performed between 2004 and 2006. Cognitive functioning was assessed at baseline and annually thereafter with the Modified Mini-Mental State Examination (3MSE) scoring until 2008. The final sample consisted of 558 women (mean age 69 years, median follow-up time [interquartile range] 8 [0.8] years).ResultsIn adjusted models including mean systolic BP, women in the highest tertile of systolic BPV had lower hippocampal volumes and higher lesion volumes compared to women in the lowest tertile. No relationship between BPV and 3MSE scoring was detected.ConclusionsIn postmenopausal women with few modifiable cardiovascular risk factors, greater visit-to-visit systolic BPV was associated with reductions in hippocampal volume and increases in lesion volumes at later life. These data add evidence to the emerging importance of BPV as a prognostic indicator even in the absence of documented cardiovascular risk factors.