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INTRODUCTION: Dementia often involves comorbid Alzheimer's and vascular pathology, but their combined impact warrants additional study. METHODS: We analyzed the Systolic Blood Pressure Intervention Trial and categorized white matter hyperintensity (WMH) volume into highest versus lowest/mid tertile and the amyloid beta (Aβ)42/40 ratio into lowest versus mid/highest ratio tertile. Using these binary variables, we created four exposure categories: (1) combined low risk, (2) Aβ risk, (3) WMH risk, and (4) combined high risk. RESULTS: In the cohort of 467 participants (mean age 69.7 ± 7.1, 41.8% female, 31.9% nonwhite or Hispanic) during 4.8 years of follow‐up and across the four exposure categories the rates of cognitive impairment were 5.3%, 7.8%, 11.8%, and 22.6%. Compared to the combined low‐risk category, the adjusted hazard ratio for cognitive impairment was 4.12 (95% confidence interval, 1.71 to 9.94) in the combined high‐risk category. DISCUSSION: This study emphasizes the potential impact of therapeutic approaches to dementia prevention that target both vascular and amyloid pathology. Highlights: White matter hyperintensity (WMH) and plasma amyloid (Aβ42/40) are additive risk factors for the development of cognitive impairment in the SPRINT MIND trial.Individuals in the high‐risk categories of both WMH and Aβ42/40 had a near fivefold increase in risk of cognitive impairment during 4.8 years of follow‐up on average.These findings suggest that treatment strategies targeting both vascular health and amyloid burden warrant further research. [ABSTRACT FROM AUTHOR]

This paper analyzes how ethnic diversity affects the provision of public goods in democratic and non‐democratic societies when political parties compete for voter support by offering a mix of private and public goods. Our model implies that increasing diversity that leads to more heterogeneous preferences for public goods decreases the provision of public goods in democracies, where political power is distributed equally among citizens, while there is a weaker or no effect in non‐democracies, where political power is distributed unequally among citizens. When measuring diversity by ethnic fractionalization and public good provision by either levels of government expenses, expenditures on health, or life expectancy, we indeed observe a negative association between diversity and the provision of public goods in democracies but no or only a weak association in non‐democracies. [ABSTRACT FROM AUTHOR]

Introduction Methods Results Conclusions The rapid adoption of electronic health record (EHR) systems has resulted in extensive archives of data relevant to clinical research, hospital operations, and the development of learning health systems. However, EHR data are not frequently available, cleaned, standardized, validated, and ready for use by stakeholders. We describe an in‐progress effort to overcome these challenges with cooperative, systematic data extraction and validation.A multi‐disciplinary team of investigators collaborated to create the Complete Inpatient Record Using Comprehensive Electronic Data (CIRCE) Project dataset, which captures EHR data from six hospitals within the University of Pennsylvania Health System. Analysts and clinical researchers jointly iteratively reviewed SQL queries and their output to validate desired data elements. Data from patients aged ≥18 years with at least one encounter at an acute care hospital or hospice occurring since 7/1/2017 were included. The CIRCE Project includes three layers: (1) raw data comprised of direct SQL query output, (2) cleaned data with errors removed, and (3) transformed data with standardized implementations of commonly used case definitions and clinical scores.Between July 1, 2017 and December 31, 2023, the dataset captured 1 629 920 encounters from 740 035 patients. Most encounters were emergency department only visits (n = 965 834, 59.3%), followed by inpatient admissions without an intensive care unit admission (n = 518 367, 23.7%). The median age was 46.9 years (25th–75th percentiles = 31.1–64.7) at the time of the first encounter. Most patients were female (n = 418 303, 56.5%), a significant proportion were of non‐White race (n = 272 018, 36.8%), and 54 625 (7.4%) were of Hispanic/Latino ethnicity.The CIRCE Project represents a novel cooperative research model to capture clinically validated EHR data from a large diverse academic health system in the greater Philadelphia region and is designed to facilitate collaboration and data sharing to support learning health system activities. Ultimately, these data will be de‐identified and converted to a publicly available resource. [ABSTRACT FROM AUTHOR]

Background: Men with fragile X‐associated tremor/ataxia syndrome (FXTAS) often develop executive dysfunction, characterized by disinhibition, frontal dyscontrol of movement, and working memory and attention changes. Although cross‐sectional studies have suggested that earlier executive function changes may precede FXTAS, the lack of longitudinal studies has made it difficult to address this hypothesis. Objective: To determine whether executive function deterioration experienced by premutation carriers (PC) in daily life precedes and predicts FXTAS. Methods: This study included 66 FMR1 PC ranging from 40 to 78 years (mean, 59.5) and 31 well‐matched healthy controls (HC) ages 40 to 75 (mean, 57.7) at baseline. Eighty‐four participants returned for 2 to 5 follow up visits over a duration of 1 to 9 years (mean, 4.6); 28 of the PC developed FXTAS. The Behavior Rating Inventory of Executive Function‐Adult Version (BRIEF‐A) was completed by participants and their spouses/partners at each visit. Results: Longitudinal mixed model regression analyses showed a greater decline with age in PC compared to HC on the Metacognition Index (MI; self‐initiation, working memory, organization, task monitoring). Conversion to FXTAS was associated with worsening MI and Behavioral Regulation Index (BRI; inhibition, flexibility, emotion modulation). For spouse/partner report, FXTAS conversion was associated with worsening MI. Finally, increased self‐report executive function problems at baseline significantly predicted later development of FXTAS. Conclusions: Executive function changes experienced by male PC represent a prodrome of the later movement disorder. © 2023 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society. [ABSTRACT FROM AUTHOR]

Objective: To determine the association between brain MRI abnormalities and incident epilepsy in older adults. Methods: Men and women (ages 45–64 years) from the Atherosclerosis Risk in Communities study were followed up from 1987 to 2018 with brain MRI performed between 2011 and 2013. We identified cases of incident late‐onset epilepsy (LOE) with onset of seizures occurring after the acquisition of brain MRI. We evaluated the relative pattern of cortical thickness, subcortical volume, and white matter integrity among participants with incident LOE after MRI in comparison with participants without seizures. We examined the association between MRI abnormalities and incident LOE using Cox proportional hazards regression. Models were adjusted for demographics, hypertension, diabetes, smoking, stroke, and dementia status. Results: Among 1251 participants with brain MRI data, 27 (2.2%) developed LOE after MRI over a median of 6.4 years (25–75 percentile 5.8–6.9) of follow‐up. Participants with incident LOE after MRI had higher levels of cortical thinning and white matter microstructural abnormalities before seizure onset compared to those without seizures. In longitudinal analyses, greater number of abnormalities was associated with incident LOE after controlling for demographic factors, risk factors for cardiovascular disease, stroke, and dementia (gray matter: hazard ratio [HR]: 2.3, 95% confidence interval [CI]: 1.0–4.9; white matter diffusivity: HR: 3.0, 95% CI: 1.2–7.3). Interpretation: This study demonstrates considerable gray and white matter pathology among individuals with LOE, which is present prior to the onset of seizures and provides important insights into the role of neurodegeneration, both of gray and white matter, and the risk of LOE. [ABSTRACT FROM AUTHOR]

Grasslands are globally distributed and naturally occurring; however, in Europe, most grasslands are anthropogenically created or altered by livestock grazing or mowing. Low‐intensity use and management have led to species‐rich communities in European grasslands. The intensification of crop production and livestock farming with stabling throughout the year has led to an abandonment of grasslands that are no longer economically profitable. In this study, we looked at the influence of grassland abandonment on biodiversity. We hypothesized that abandonment of grasslands decreases the overall biodiversity, but has different effects depending on the focal taxonomic group (i.e., vascular plants, insects, or birds). We also hypothesized that the type of management before abandonment, the type of grassland, and the time after abandonment would influence grassland biodiversity. We conducted a Web of Science search, with pre‐defined terms, to find articles that compared biodiversity of managed and abandoned grasslands in Europe. We screened the articles and included 39 studies in a subsequent meta‐analysis. We found that overall biodiversity was reduced after abandonment; however, the biodiversity reduction in the grasslands differed among taxonomic groups. Plant species diversity was significantly lower after abandonment (plant summary effect size: −0.25 [−0.34; −0.16]), whereas the diversity of insects and birds showed no significant trend, but a visual trend toward an increase. None of the other environmental variables (type of management, type of grassland, or the time after abandonment) had a significant influence on the biodiversity of the grasslands. We conclude that maintaining grassland management is crucial to support biodiversity conservation in European grasslands. [ABSTRACT FROM AUTHOR]

Objective: To compare different aspects of caregiving distress and experience in parents of patients with anorexia nervosa (AN) before and during the COVID‐19 pandemic. Methods: Three cohorts of parents of AN patients (cohort 1‐pre‐pandemic: N = 78, cohort 2‐first pandemic year: N = 51, cohort 3‐second pandemic year: N = 119) were recruited from child and adolescent psychiatry wards and cross‐sectionally assessed as part of the clinical routine. Quantitative measures of psychological distress, psychopathology, eating disorder (ED)‐related burden, expressed emotion and caregiver skills were obtained at the beginning of the child's inpatient or outpatient treatment. Results: Cohort 2 showed lower levels of anxiety and a tendency of lower emotional overinvolvement and higher caregiving skills compared to the pre‐pandemic cohort. In contrast, the levels of general psychological distress, depression, ED‐related burden and criticism observed in cohort 3 significantly exceeded pre‐pandemic levels. The prevalence of clinically relevant depression was higher in cohort 3 (41.5%) compared to cohorts 1 (24.4%) and 2 (21.6%). Discussion: The pandemic effects on parents seem to be time‐specific. Lower distress in the early phase of the pandemic may be associated with improvements in parent‐child‐relationships reported in previous studies. However, the pandemic may has negative consequences in the long‐term emphasising the need of ongoing parental support. Highlights: In the first year of the pandemic, parents of an offspring with anorexia nervosa showed lower anxiety levels and a tendency for higher caregiving skills.In the second pandemic year, the level of parental psychological distress, clinically relevant depression and eating disorder related burden and criticism were higher compared to the pre‐pandemic period.Frustration tolerance and emotional intelligence were aspects of caregiving skills that were particularly lower in parents of the second pandemic year compared to the pre‐pandemic period. [ABSTRACT FROM AUTHOR]

Background: The composition of the skin microbiome varies from infancy to adulthood and becomes most stable in adulthood. Adult acne patients harbour an 'acne microbiome' dominated by specific strains of Cutibacterium acnes. However, the precise timing of skin microbiome evolution, the development of the acne microbiome, and the shift to virulent C. acnes strain composition during puberty is unknown. Objectives: We performed a cross‐sectional pilot study in a paediatric population to understand how and when the skin microbiome composition transitions during puberty and whether a distinct 'acne microbiome' emerges in paediatric subjects. Methods: Forty‐eight volunteers including males and females, ages 7–17 years, with and without acne were enrolled and evaluated for pubertal development using the Tanner staging criteria. Sebum levels were measured, and skin microbiota were collected by sterile swab on the subject's forehead. DNA was sequenced by whole genome shotgun sequencing. Results: A significant shift in microbial diversity emerged between early (T1‐T2) and late (T3‐T5) stages of puberty, coinciding with increased sebum production on the face. The overall relative abundance of C. acnes in both normal and acne skin increased during puberty and individual C. acnes strains were uniquely affected by pubertal stage and the presence of acne. Further, an acne microbiome signature associated with unique C. acnes strain composition and metabolic activity emerges in late puberty in those with acne. This unique C. acnes strain composition is predicted to have increased porphyrin production, which may contribute to skin inflammation. Conclusions: Our data suggest that the stage of pubertal development influences skin microbiome composition. As children mature, a distinct acne microbiome composition emerges in those with acne. Understanding how both puberty and acne influence the microbiome may support novel therapeutic strategies to combat acne in the paediatric population. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the association of short‐term exposure to overall fine particulate matter of <2.5 μm (PM2.5) and wildfire‐specific PM2.5 with emergency department (ED) visits for headache. Background: Studies have reported associations between PM2.5 exposure and headache risk. As climate change drives longer and more intense wildfire seasons, wildfire PM2.5 may contribute to more frequent headaches. Methods: Our study included adult Californian members (aged ≥18 years) of a large de‐identified commercial and Medicare Advantage claims database from 2006 to 2020. We identified ED visits for primary headache disorders (subtypes: tension‐type headache, migraine headache, cluster headache, and "other" primary headache). Claims included member age, sex, and residential zip code. We linked daily overall and wildfire‐specific PM2.5 to residential zip code and conducted a time‐stratified case‐crossover analysis considering 7‐day average PM2.5 concentrations, first for primary headache disorders combined, and then by headache subtype. Results: Among 9898 unique individuals we identified 13,623 ED encounters for primary headache disorders. Migraine was the most frequently diagnosed headache (N = 5534/13,623 [47.6%]) followed by "other" primary headache (N = 6489/13,623 [40.6%]). For all primary headache ED diagnoses, we observed an association of 7‐day average wildfire PM2.5 (odds ratio [OR] 1.17, 95% confidence interval [CI] 0.95–1.44 per 10 μg/m3 increase) and by subtype we observed increased odds of ED visits associated with 7‐day average wildfire PM2.5 for tension‐type headache (OR 1.42, 95% CI 0.91–2.22), "other" primary headache (OR 1.40, 95% CI 0.96–2.05), and cluster headache (OR 1.29, 95% CI 0.71–2.35), although these findings were not statistically significant under traditional null hypothesis testing. Overall PM2.5 was associated with tension‐type headache (OR 1.29, 95% CI 1.03–1.62), but not migraine, cluster, or "other" primary headaches. Conclusions: Although imprecise, these results suggest short‐term wildfire PM2.5 exposure may be associated with ED visits for headache. Patients, healthcare providers, and systems may need to respond to increased headache‐related healthcare needs in the wake of wildfires and on poor air quality days. [ABSTRACT FROM AUTHOR]

Premutation alleles with 55–200 CGG repeats in FMR1 can lead to fragile X‐associated tremor/ataxia syndrome (FXTAS). In this case study, we report uncontrolled gout in a 68‐year‐old male with FXTAS with multiple sites of involvement including a rare gouty tophus in the nasal region. [ABSTRACT FROM AUTHOR]

Objective: Knowledge on gut–brain interaction might help to develop new therapies for patients with anorexia nervosa (AN), as severe starvation‐induced changes of the microbiome (MI) do not normalise with weight gain. We examine the effects of probiotics supplementation on the gut MI in patients with AN. Method: This is a study protocol for a two‐centre double‐blind randomized‐controlled trial comparing the clinical efficacy of multistrain probiotic administration in addition to treatment‐as‐usual compared to placebo in 60 patients with AN (13–19 years). Moreover, 60 sex‐ and age‐matched healthy controls are included in order to record development‐related changes. Assessments are conducted at baseline, discharge, 6 and 12 months after baseline. Assessments include measures of body mass index, psychopathology (including eating‐disorder‐related psychopathology, depression and anxiety), neuropsychological measures, serum and stool analyses. We hypothesise that probiotic administration will have positive effects on the gut microbiota and the treatment of AN by improvement of weight gain, gastrointestinal complaints and psychopathology, and reduction of inflammatory processes compared to placebo. Conclusions: If probiotics could help to normalise the MI composition, reduce inflammation and gastrointestinal discomfort and increase body weight, its administration would be a readily applicable additional component of multi‐modal AN treatment. Key points: Patients with anorexia nervosa face profound alterations of the gut microbiome which does not normalise with weight gain.Alterations in the gut microbiome in patients with anorexia nervosa are linked to psychopathological symptoms and neurophysiological deficits, for example, related to the reward system.This is the first study examining the effects of probiotics administration in adolescents with anorexia nervosa using a randomized controlled trial design. [ABSTRACT FROM AUTHOR]

Background: Early life factors, such as birth weight (BW), may have long‐term health consequences, but the importance of these factors in dementia risk is poorly understood. Our objective was to prospectively examine the association of BW with dementia incidence over mid‐ to late‐adulthood in the ARIC study. We hypothesized that participants who report lower BW experience more incident dementia than participants who report normal BW, and this association may differ by race. Method: 10,789 participants who were dementia‐free at ARIC baseline (Visit 1: 1987‐1989; ages 45‐64) and followed through 2019 were included. Participants were asked their BW through standard interviews at Visit 4 (1996‐1998), but if unable to recall, they selected their BW category: low (<5.5 lbs.), medium (normal) (5.5‐9.0 lbs.), or high (>9.0 lbs.), and to identify if they were premature (yes/no). Adjudicated dementia cases from baseline through 2019 were classified using in‐person cognitive evaluations, informant interviews, and phone assessments as well as hospitalization codes and death certificate codes. The associations between having high or low (vs medium) BW and dementia, or premature birth status and dementia were investigated using Cox proportional hazards models, with testing for interaction by race. Result: Our overall population was 54 yo at baseline, 56% female, and 20% Black; 2,255 dementia cases were identified over a median of 28.2 years. Participants who reported a low BW had 1.2 times (95% CI 1.02, 1.41) increased risk of incident dementia compared to those with medium BW in demographic‐ and APOE‐adjusted models (Table 1). This association was no longer significant when the model additionally adjusted for vascular risk factors. The risk for dementia was not increased among participants who reported having been born premature (vs not premature). When stratified by race, the risk of incident dementia was elevated in Black participants reporting high (vs medium) BW, but not in White participants reporting high BW (p‐interaction = 0.006) (Table 2). Conclusion: In this cohort, low BW was associated with risk of dementia in minimally adjusted models. The association was attenuated after accounting for vascular risk factors. High BW was associated with risk of dementia in Black participants only. [ABSTRACT FROM AUTHOR]

The skin microbiome plays an important role in maintaining skin homeostasis by controlling inflammation, providing immune education and maintaining host defense. However, in many inflammatory skin disorders the skin microbiome is disrupted. This dysbiotic community may contribute to disease initiation or exacerbation through the induction of aberrant immune responses in the absence of infection. Hidradenitis suppurativa (HS) is a complex, multifaceted disease involving the skin, innate and adaptive immunity, microbiota and environmental stimuli. Herein, we discuss the current state of HS skin microbiome research and how microbiome components may activate pattern recognition receptor (PRR) pathways, metabolite sensing pathways and antigenic receptors to drive antimicrobial peptide, cytokine, miRNA and adaptive immune cell responses in HS. We highlight the major open questions that remain to be addressed and how antibiotic therapies for HS likely influence both microbial burden and inflammation. Ultimately, we hypothesize that the two‐way communication between the skin microbiome and host immune response in HS skin generates a chronic positive feed‐forward loop that perpetuates chronic inflammation, tissue destruction and disease exacerbation. [ABSTRACT FROM AUTHOR]

Introduction: Head injury is associated with significant morbidity and mortality. Long‐term associations of head injury with dementia in community‐based populations are less clear. Methods: Prospective cohort study of 14,376 participants (mean age 54 years at baseline, 56% female, 27% Black, 24% with head injury) enrolled in the Atherosclerosis Risk in Communities (ARIC) Study. Head injury was defined using self‐report and International Classification of Diseases, Ninth/Tenth Revision (ICD‐9/10) codes. Dementia was defined using cognitive assessments, informant interviews, and ICD‐9/10 and death certificate codes. Results: Head injury was associated with risk of dementia (hazard ratio [HR] = 1.44, 95% confidence interval [CI] = 1.3‐1.57), with evidence of dose‐response (1 head injury: HR = 1.25, 95% CI = 1.13‐1.39, 2+ head injuries: HR = 2.14, 95% CI = 1.86‐2.46). There was evidence for stronger associations among female participants (HR = 1.69, 95% CI = 1.51‐1.90) versus male participants (HR = 1.15, 95% CI = 1.00‐1.32), P‐for‐interaction <.001, and among White participants (HR = 1.55, 95% CI = 1.40‐1.72) versus Black participants (HR = 1.22, 95% CI = 1.02‐1.45), P‐for‐interaction =.008. Discussion: In this community‐based cohort with 25‐year follow‐up, head injury was associated with increased dementia risk in a dose‐dependent manner, with stronger associations among female participants and White participants. [ABSTRACT FROM AUTHOR]

Atypical responses to fearful stimuli and the presence of various forms of anxiety are commonly seen in children with autism spectrum disorder (ASD). The fear potentiated startle paradigm (FPS), which has been studied both in relation to anxiety and as a probe for amygdala function, was carried out in 97 children aged 9–14 years including 48 (12 female) with ASD and 49 (14 female) with typical development (TD). In addition, exploratory analyses were conducted examining the association between FPS and amygdala volume as assessed with magnetic resonance imaging in a subset of the children with ASD with or without an anxiety disorder with available MRI data. While the startle latency was increased in the children with ASD, there was no group difference in FPS. FPS was not significantly associated with traditional Diagnostic and Statistical Manual (DSM) or "autism distinct" forms of anxiety. Within the autism group, FPS was negatively correlated with amygdala volume. Multiple regression analyses revealed that the association between FPS and anxiety severity was significantly moderated by the size of the amygdala, such that the association between FPS and anxiety was significantly more positive in children with larger amygdalas than smaller amygdalas. These findings highlight the heterogeneity of emotional reactivity associated with ASD and the difficulties in establishing biologically meaningful probes of altered brain function. Lay summary Many children with autism spectrum disorder (ASD) have additional problems such as anxiety that can greatly impact their lives. How these co‐occurring symptoms develop is not well understood. We studied the amygdala, a region of the brain critical for processing fear and a laboratory method called fear potentiated startle for measuring fear conditioning, in children with ASD (with and without an anxiety disorder) and typically developing children. Results showed that the connection between fear conditioning and anxiety is dependent on the size of the amygdala in children with ASD. [ABSTRACT FROM AUTHOR]

The pollution caused by polymer waste is becoming a serious problem, because many petrochemical polymers persist in the environment and pollute it. In contrast to non‐degradable polymers, natural polymers derived from renewable sources are environment‐friendly and sustainable. Bacterial cellulose (BC) is an abundant and reproducible biopolymer that is biocompatible and biodegradable and has a wide range of applications in different industrial segments. In order to evaluate the degradation behavior of BC, wet membranes are exposed to different environmental conditions. BC membranes are synthesized by Komagataeibacter hansenii and purified in NaOH solution. The degradation of the membranes are evaluated at different times in soil (SO), estuarine environment (EE), natural weathering (NW), and accelerated aging chamber (AAC). The samples are examined by visual analysis (VA), Fourier transform infrared spectroscopy with attenuated total reflectance (FTIR/ATR) and thermogravimetric (TGA) analysis. In general, in the soil and estuary environment, degradation is more intense, facilitating the presence of microorganisms in the media that promote microbial attack. The TGA and FTIR analyses, together with a VA, allowed the kinetics of membrane degradation to occur in the following order: SO > EE > NW > AAC. [ABSTRACT FROM AUTHOR]

Background: Fragile X–associated tremor and ataxia syndrome (FXTAS) is a late‐onset neurodegenerative disorder linked to the FMR1 premutation. Objectives: FXTAS in women is far less common than in men, and this study represents the largest sample reported to date. Methods: A total of 53 female premutation carriers with FXTAS (meanage, 66.83 years; FXTAS stages 2–5) and 55 age‐matched and demographic background–matched control participants (meanage, 61.94 years) underwent a comprehensive molecular, physiological, neuropsychological, and psychiatric assessment. Results: The large sample of female premutation carriers showed a wide range of variability of clinical signs and symptom progression. The imaging results showed a middle cerebellar peduncles sign in only 6 patients; another symptom included high‐signal intensity in the splenium of the corpus callosum, and diffuse cerebral deep white matter changes (e.g., in the pons) are more common. The rate of psychiatric disorders, especially depression, is higher than in the general population. There is a clear impairment in executive functioning and fine motor skills in connection with a higher FXTAS stage. Conclusions: The manifestation of FXTAS symptoms in female carriers can be diverse with a milder phenotype and a lower penetrance than those observed in male premutation carriers. The middle cerebellar peduncles sign is present in only a small percentage of the sample, and we propose that the imaging criteria for FXTAS in women need to be expanded. [ABSTRACT FROM AUTHOR]

The authors are leading a multinational effort to understand the effects of "hybrid" warfare on international commercial negotiation. The start‐up process is itself essentially a negotiation, among about forty individual practitioners and scholars with very diverse backgrounds, over whether and how they will work together. In a pandemic, a key risk is that the necessary cooperation and trust will be harder to build, particularly among professionals who are dealing with security‐sensitive issues and who have never met each other. This article discusses the current necessity of replacing the in‐person model for eliciting such cooperation which the authors had developed previously for large collaborative projects, and describes a "remote convening" replacement process. [ABSTRACT FROM AUTHOR]

Background: Acute on chronic liver failure (ACLF) has been identified as a distinct syndrome due to acute decompensation of liver cirrhosis accompanied by extra‐hepatic organ failure, primarily caused by an overwhelming systemic immune response. Therapeutic plasma exchange (TPE) has been demonstrated in a randomized controlled trial to improve transplant free survival in acute liver failure. Here we investigated if TPE might have comparable beneficial effects in patients with ACLF. Methods: Thirty‐one patients with ACLF that were treated with TPE were enrolled into this retrospective analysis and 1:1 matched to an ACLF cohort treated with standard medical therapy (SMT) only. Results: Patients considered for a bridge to recovery (n = 21 each group) approach had a 30‐day mortality >90% that was not improved by TPE (P =.185). Deaths occurred in the SMT group at significant earlier time points compared to the patients treated with TPE (mortality at 5 days: 33.3% for TPE and 66.7% for SMT, P =.048). However, patients who received TPE as a bridge to transplant strategy (n = 10) survived in 60% of cases and demonstrated 24 hours after study inclusion a stabilization of organ dysfunction (organ failures at inclusion: 4 (3‐5) vs 24 hours after inclusion: 3 (2‐4), P =.031 and CLIF‐C‐ACLF score: 64 (49‐76) vs 54 (49‐66), P =.043) not seen in SMT patients. Conclusions: Although these retrospective data need to be interpreted with caution, they suggest that TPE in ACLF patients is feasible but not suitable as a bridge to recovery strategy. In selected patients TPE might assist as bridge to transplant. [ABSTRACT FROM AUTHOR]

OBJECTIVES: Understanding how dementia risk is impacted by timing of smoking cessation has public health implications for prevention efforts. We investigated the relationship of cigarette smoking and cessation with dementia risk and cognitive decline in the Atherosclerosis Risk in Communities (ARIC) study. DESIGN: Ongoing prospective cohort study. SETTING: Begun in 1987‐1989, ARIC was conducted in four US communities. PARTICIPANTS: A total of 13 002 men and women (25% African American) aged 52 to 75 years. MEASUREMENTS: All‐cause dementia was defined using standardized algorithms incorporating longitudinal cognitive data, proxy report, and hospital and death certificate dementia codes. Cognitive decline was measured using a composite cognitive score created from three tests measured at two time points (1996‐1998 and 2011‐2013). Smoking and cessation status were defined by self‐report using data from 1987‐1989 (visit 1) and 1996‐1998 (visit 4). Incident dementia risk and differences in cognitive change by smoking status were estimated with Cox proportional hazards and linear regression models, respectively. To address smoking‐related attrition, cognitive scores were imputed for living participants with incomplete cognitive testing. RESULTS: The proportion of never, former, and current smokers was 44%, 41%, and 14%; 79% of former smokers quit 9 years or more before baseline. A total of 1347 participants developed dementia. After adjustment, compared with never smoking, the hazard ratio for all‐cause dementia for current smoking was 1.33 (95% confidence interval [CI] = 1.12‐1.59) and for recent quitting (<9 y before baseline) was 1.24 (95% CI = 1.01‐1.52). Quitting 9 years or more before baseline was not associated with dementia. We found no differences in rates of cognitive decline by smoking status. CONCLUSION: Although quitting at any time suggested benefit, dementia risk depended on time since smoking cessation. Our study highlights the importance of early midlife cessation to decrease dementia risk. J Am Geriatr Soc 68:337–345, 2020 [ABSTRACT FROM AUTHOR]

Socioeconomic status (SES) is a multi‐faceted theoretical construct associated with stroke risk and outcomes. Knowing which SES measures best correlate with population stroke metrics would improve its accounting in observational research and inform interventions. Using the Centers for Disease Control and Prevention's (CDC) Population Level Analysis and Community Estimates (PLACES) and other publicly available databases, we conducted an ecological study comparing correlations of different United States county‐level SES, health care access and clinical risk factor measures with age‐adjusted stroke prevalence. The prevalence of adults living below 150% of the federal poverty level most strongly correlated with stroke prevalence compared to other SES and non‐SES measures (correlation coefficient = 0.908, R2 = 0.825; adjusted partial correlation coefficient: 0.589, R2 = 0.347). ANN NEUROL 2024 [ABSTRACT FROM AUTHOR]

The human integument and gastrointestinal tract host unique microbial ecosystems. Within the last decade, research has focused on understanding the contributions of the microbiota to human health and disease. The majority of skin microbiome studies involve adults. This review focuses on key studies conducted within the pediatric population and provides a framework for future skin microbiome work in this ever‐expanding field. This article begins by exploring the skin microbiome at birth and reviews the impact of delivery mode on infant skin colonization. How skin microbial colonization evolves from infancy to adulthood and normal development impacts the abundance of skin commensals such as Streptococcus, Staphylococcus, and Cutibacterium is also highlighted. Finally, several skin microbiome research studies in common pediatric skin conditions are reviewed, including body odor, atopic dermatitis (AD), and acne. The bacteria involved in metabolizing sweat, the impact on body odor, and how this process evolves from childhood to adulthood is outlined. In AD, different bacteria genera that predominate in children and adults and the impact of current AD therapies on skin microbiota are explored. Finally, in acne, the understanding of how Cutibacterium acnes contributes to acne pathogenesis and how acne therapies impact the skin microbial communities is reviewed. [ABSTRACT FROM AUTHOR]

OBJECTIVES: Cardiac troponin T, measured using a high‐sensitive assay (hs‐cTnT), and N‐terminal pro‐B‐type natriuretic peptide (NT‐proBNP) are associated with increased stroke risk and perhaps with cognitive decline. However, few well‐designed prospective studies with extended follow‐up have been conducted. We aimed to estimate the association of hs‐cTnT and NT‐proBNP with 15‐year cognitive change in the Atherosclerosis Risk in Communities (ARIC) study. DESIGN: Prospective cohort study. SETTING: Four US communities. PARTICIPANTS: A total of 9114 and 9108 participants from the Atherosclerosis Risk in Communities study for analyses of hs‐cTnT and NT‐proBNP, respectively. MEASUREMENTS: We examined association of hs‐cTnT and NT‐proBNP with 15‐year change (1996‐1998 to 2011‐2013) in three cognitive tests of executive function (Digit Symbol Substitution Test), verbal learning memory (Delayed Word Recall Test), and semantic fluency (Word Fluency Test), and an overall score combining the three tests using multivariable linear mixed effect models. We conducted several sensitivity analyses including multiple imputations to address bias due to missing data and attrition, and we compared associations within groups combining hs‐cTnT and NT‐proBNP into a three‐level categorical variable. RESULTS: At baseline (1996‐1998), mean age was 63.4 (standard deviation [SD] = 5.7) years; 56.4% were women, and 17.5% were black. The hs‐cTnT at baseline was not associated with cognitive change in any measure. Some evidence indicated accelerated decline in verbal learning and memory when comparing those in the highest with the lowest NT‐proBNP quintiles; however, this association was not replicated when considering clinically relevant cutoffs or deciles of exposure in survivors. Sensitivity analyses were consistent with our primary analyses. There was little evidence to support effect modification by any considered factors. People with highest levels of both biomarkers had excessive decline in global z scores vs people with lowest levels (−.34; 95% confidence interval = −.63 to −.04). CONCLUSION: Markers of myocardial injury and stretch were not associated with cognitive decline following 15 years among survivors, but when combined together they were suggestive in post hoc analysis. Whether this represents targets of intervention should be examined in the future. J Am Geriatr Soc 67:2353–2361, 2019 [ABSTRACT FROM AUTHOR]

Background: Multi‐organ dysfunction in acute liver failure (ALF) has been attributed to a systemic inflammatory response directly triggered by the injured liver. High‐volume therapeutic plasma exchange (HV‐TPE) has been demonstrated in a large randomized controlled trial to improve survival. Here, we investigated if a more cost‐/ resource effective low‐volume (LV) TPE strategy might have comparable beneficial effects. Methods: This retrospective study evaluated the effect of LV‐TPE on remote organ failure, hemodynamical and biochemical parameters as well as on survival in patients with ALF. Twenty patients treated with LV‐TPE in addition to standard medical therapy (SMT) were identified and 1:1 matched to a historical ALF cohort treated with SMT only. Clinical and biochemical parameters were recorded at admission to the intensive care unit and the following 7 days after LV‐TPE. Results: Mean arterial pressure increased following first LV‐TPE treatments (d0: 68 [61‐75] mm Hg vs d7: 88 [79‐98] mm Hg, P =.003) and norepinephrine dose was reduced (d0: 0.264 [0.051‐0.906] μg/kg/min vs d3: 0 [0‐0.024] μg/kg/min, P =.016). Multi‐organ dysfunction was significantly diminished following LV‐TPE (CLIF‐SOFA d0: 17 [13‐20] vs d7: 7 [3‐11], P =.001). Thirty‐day in‐hospital survival was 65% in the LV‐TPE cohort and 50% in the SMT cohort (Hazard‐ratio for TPE: 0.637; 95% CI: 0.238‐1.706, P =.369). Conclusions: Patients treated with LV‐TPE showed improved surrogate parameters comparable with the effects reported with HV‐TPE. These data need to be interpreted with caution due to their retrospective character. Future controlled studies are highly desirable. [ABSTRACT FROM AUTHOR]

When a region successfully attracts a firm by offering subsidies, the firm often commits itself to performance targets in terms of employment. In this paper, we interpret these firm‐specific targets as a consequence of incomplete information. We analyze a model of two regions that compete for a firm, assuming that the firm's productivity is ex ante unknown. We show that performance targets often induce overemployment in high‐productivity firms, and that tax credits are often superior to lump‐sum payments. Moreover, when regions differ in wage rates, the low‐wage region wins the bid and has a higher surplus than under complete information. Finally, we show that, under incomplete information, bidding might not lead to efficient firm location. [ABSTRACT FROM AUTHOR]

The article discusses the use of problem-solving approach in teaching negotiation and dealing with difficult individuals. Topics mention including the difficult bargaining tactics and strategies, negotiation strategy of U.S. President Donald Trump and recognizing the uniqueness of the leverage and power of the American presidency.

Introduction: The interplay between midlife vascular risk factors and midlife cognitive function with later life mild cognitive impairment (MCI) and dementia (DEM) is not well understood. Methods: In the Atherosclerosis Risk in Communities Study, cardiovascular risk factors and cognition were assessed in midlife, ages 45–64 years. In 2011–2013, 20–25 years later, all consenting Atherosclerosis Risk in Communities participants underwent a cognitive and neurological evaluation and were given adjudicated diagnoses of cognitively normal, MCI, or DEM. Results: In 5995 participants with complete covariate data, midlife diabetes, hypertension, obesity, and hypercholesterolemia were associated with late‐life MCI and DEM. Low midlife cognition function was also associated with greater likelihood of late‐life MCI or DEM. Both midlife vascular risk factors and midlife cognitive function remained associated with later life MCI or DEM when both were in the model. Discussion: Later life MCI and DEM were independently associated with midlife vascular risk factors and midlife cognition. [ABSTRACT FROM AUTHOR]

Abstract: We analyze optimal business tax policy when some firms are able to escape taxation by moving abroad. In contrast to the existing literature, we assume that the true number of mobile firms is ex ante unknown. While the government may learn from the firms' location responses to past tax rate changes, firms may anticipate this and adjust their choices accordingly. We find that incomplete information on mobility substantially affects the properties and the implications of equilibrium policy choices. First, the government may find it optimal to set a tax rate that triggers partial firm migration but full revelation of the true number of mobile firms. Second, we show that, if the firms' outside option is attractive (i.e., relocation cost and foreign tax rates are low), expected tax rates and expected firm migration are higher if the degree of mobility is unknown. Third, there is a positive value of learning, i.e., commitment on future tax rates cannot increase the government's expected revenue. However, if the government can commit to a rule‐based learning mechanism, i.e., credibly tie its future tax policy to present policy outcomes, it may obtain a Pareto improvement. [ABSTRACT FROM AUTHOR]

This paper examines the welfare effects of powerful labour unions when the government levies a uniform tax rate - as is currently the case in most OECD countries - and firms are heterogeneous with respect to productivity. I show that an increase in the bargaining power of labour unions can decrease the welfare loss generated by restriction of the tax policy and provide conditions under which powerful labour unions decrease the likelihood that firms will move abroad. I also reproduce the well-known effect whereby powerful labour unions decrease corporate tax rates if firms are mobile. [ABSTRACT FROM AUTHOR]

The recent discovery of methane seeps in the Arctic region requires a better understanding of the fate of methane in marine sediments if we are to understand the contributions of methane to Arctic ecosystems and climate change. To this goal, we analyze pore water data from five sites along eastern Vestnesa Ridge, a sediment drift off-north-west Svalbard, to quantify the consumption of dissolved methane across the sulfate-methane-transition-zone which are 3-5 m below seafloor from the investigated sites. We use transport-reaction models to quantify the hydrology as well as the carbon mass balance in the sediments. Pore water profiles and our model results demonstrate that hydrological, microbial, and geochemical processes/reactions efficiently remove methane carbon from fluid over different time scales. We interpret the nonsteady-state behavior of the first 50-70 cm of our pore water profiles from the active sites as an annual scale downward fluid flow due to a seepage-related pressure imbalance. Such downward flow supplies sulfate which enhances methane consumption through anaerobic oxidation of methane (AOM) within this depth range. Our steady-state modeling confirms the efficiency of AOM in consuming dissolved methane in the upper 0.8-1.2 m of sediments. Based on the phosphate profiles, we estimate that AOM at the active pockmarks may have been operating for the last two to four centuries. Precipitation of authigenic carbonate removes more than a quarter of the dissolved inorganic carbon produced by AOM and fixes it as authigenic carbonate in the sediments, a process that sequestrates methane carbon over geological time. [ABSTRACT FROM AUTHOR]

Introduction The impact of blood pressure on brain volumes may be time-dependent or pattern-dependent. Methods Of 1678 participants from the Atherosclerosis Risk in Communities Neurocognitive Study, we quantified the association between measures and patterns of blood pressure over three time points (∼24 or ∼15 years prior and concurrent with neuroimaging) with late life brain volumes. Results Higher diastolic blood pressure ∼24 years prior, higher systolic and pulse pressure ∼15 years prior, and consistently elevated or rising systolic blood pressure from ∼15 years prior to concurrent with neuroimaging, but not blood pressures measured concurrent with neuroimaging, were associated with smaller volumes. The pattern of hypertension ∼15 years prior and hypotension concurrent with neuroimaging was associated with smaller volumes in regions preferentially affected by Alzheimer's disease (e.g., hippocampus: −0.27 standard units, 95% CI: −0.51, −0.03). Discussion Hypertension 15 to 24 years prior is relevant to current brain volumes. Hypertension followed by hypotension appears particularly detrimental. [ABSTRACT FROM AUTHOR]

Fragile X syndrome (FXS) affects individuals with more than 200 CGG repeats (full mutation) in the fragile X mental retardation 1 ( FMR1) gene. Those born with FXS experience cognitive and social impairments, developmental delays, and some features of autism spectrum disorders. Carriers of a premutation (55-200 CGG repeats) are generally not severely affected early in life; however, are at high risk of developing the late onset neurodegenerative disorder, Fragile X-associated Tremor/Ataxia Syndrome (FXTAS), or Fragile X-associated Primary Ovarian Insufficiency (FXPOI), and may have other medical conditions such as developmental delay, autism spectrum disorders, hypertension, anxiety, and immune-mediated disorders. Here we present a case of a 58-year-old man with a borderline IQ, average memory skills, and executive function deficits. He met criteria for multiple psychiatric diagnoses and presented with tremor and ataxia, meeting criteria for FXTAS. Molecular testing unveiled a completely unmethylated FMR1 full mutation in peripheral blood mononucleated cells with elevated FMR1 mRNA and premutation alleles of different sizes in two other tissues (primary fibroblasts and sperm), indicating the presence of allele instability based on both inter- and intra-tissue mosaicism. The observation of FXTAS in this case of a full mutation mosaic man suggests that the pathogenic mechanism underlying this disorder is not observed exclusively in premutation carriers as it was originally thought. The concomitant presence of features of FXS and late onset neurological deterioration with probable FXTAS likely result from a combined molecular pathology of elevated FMR1 mRNA levels, a molecular hallmark of FXTAS and low FMRP expression that leads to FXS. © 2015 Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]

The fragile X-associated tremor ataxia syndrome (FXTAS) is caused by the premutation in FMR1 gene. Recent reports of environmental toxins appear to worsen the progression of FXTAS. Here we present a case of male adult with FXTAS and a long history of methadone use. The patient shows a faster progression in both symptoms of disease and MRI changes compared to what is typically seen in FXTAS. There has been no research regarding the role of narcotics in onset, progression, and severity of FXTAS symptoms. However, research has shown that narcotics can have a negative impact on several neurodegenerative diseases, and we hypothesize that in this particular case, methadone may have contributed to a faster progression of FXTAS as well as exacerbating white matter disease through RNA toxicity seen in premutation carriers. © 2015 Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]

Objective To characterize the prevalence of nonalcoholic fatty liver disease (NAFLD) by race in a nationally representative sample of the U.S. population and to investigate potential explanatory factors for racial disparities. Design and Methods Cross-sectional study of 4,037 non-Hispanic white, 2,746 non-Hispanic black, and 2,892 Mexican-American adults in the Third National Health and Nutrition Examination Survey. NAFLD was defined using ultrasound and with elevated aminotransferases. Results Age-adjusted prevalence of NAFLD was highest in Mexican-Americans (21.2%), followed by non-Hispanic whites (12.5%), and was lowest in non-Hispanic blacks (11.6%). Even after adjustment for demographic, lifestyle, adiposity, and metabolic factors, compared to non-Hispanic whites, Mexican-Americans were more likely to have NAFLD (OR: 1.67, 95% CI: 1.26, 2.22). Non-Hispanic blacks were significantly less likely to have NAFLD with elevated aminotransferases (OR: 0.51, 95% CI: 0.27, 0.97). Racial differences were attenuated among those with normal BMI and among 'never drinkers.' Conclusion In this representative sample of the U.S. population, we found significant racial differences in the prevalence of ultrasound-defined NAFLD (with and without elevated liver enzymes). The racial differences were not fully explained by lifestyle, adiposity, and metabolic factors. More works is needed to identify potential contributors. [ABSTRACT FROM AUTHOR]

Cognitive and behavioral correlates of molecular variations related to the FMR1 gene have been studied rather extensively, but research about the long-term outcome in individuals with fragile X spectrum disorders remains sparse. In this review, we present an overview of aging research and recent findings in regard to cellular and clinical manifestations of aging in fragile X syndrome, and the FMR1 premutation. © 2013 Wiley Periodicals, Inc. Dev Disabil Res Rev 2013;18:68-74. [ABSTRACT FROM AUTHOR]

Objective To investigate the nature of cognitive impairments and underlying brain mechanisms in older female fragile X premutation carriers with and without fragile X-associated tremor/ataxia syndrome (FXTAS). Methods Extensive neuropsychological testing and cognitive event-related brain potentials (ERPs; particularly, the auditory P300) were examined in 84 female participants: 33 fragile X premutation carriers with FXTAS (mean age = 62.8 years), 25 premutation carriers without FXTAS (mean age = 55.4 years), and 26 normal healthy controls (mean age = 59.3 years). Results Both premutation groups exhibited executive dysfunction on the Behavioral Dyscontrol Scale, with subtle impairments in inhibition and performance monitoring in female carriers without FXTAS, and more substantial deficits in FXTAS women. However, the female carrier group without FXTAS showed more pronounced deficiencies in working memory. Abnormal ERPs were recorded over the frontal lobes, where FXTAS patients showed both P300 amplitude reduction and latency prolongation, whereas only decreased frontal P300 amplitudes were found in carriers without FXTAS. These frontal P300 measures correlated with executive function and information processing speed. Interpretation The neuropsychological testing and ERP results of the present study provide support for the hypothesis that executive dysfunction is the primary cognitive impairment among older female premutation carriers both with and without FXTAS, although these deficits are relatively mild compared to those in FXTAS males. These findings are consistent with a synergistic effect of the premutation and aging on cognitive impairment among older female fragile X premutation carriers, even in those without FXTAS symptoms. Ann Neurol 2013;74:275-283 [ABSTRACT FROM AUTHOR]

Our research suggests that a true norm of ethical negotiation behavior exists within the legal profession. This conclusion is tempered, however, with the knowledge that a large minority of our research respondents - at times approaching one-third of them - engaged in unethical and even fraudulent behavior. Additionally, the survey respondents were not saddled with the pressures that practicing attorneys typically confront (pressures likely to make people behave less, rather than more, ethically). In an attempt to understand the reasons for such a high frequency of unethical negotiation, we have identified three major contributing factors: too many lawyers have only a superficial understanding of rules that are more complicated than they appear; lawyers frequently take their 'zealous advocate' role too far, thereby placing client loyalty above other important values such as respect for truth and justice; and the practice of law and the people who are drawn to it are highly competitive. To address these factors, we suggest approaching the problem from several different angles. In the classroom, we suggest a focus on the relevant legal standards, including a focus on the often misunderstood law of fraudulent misrepresentations. Because many students fail to appreciate the differences between 'ethical' behavior, the floor of socially acceptable conduct, and the expectations that others have for how they will be treated, we also suggest that lawyer training programs focus on the important role that personal relationships and one's reputation play in the legal profession, and how falling short in these areas can decrease one's negotiation effectiveness. For the profession itself, we also suggest clarifying the attorney rules of conduct and provide a number of tactics and strategies to defend against lying and deception during negotiation. Finally, we recognize there are certain psychological factors at play that can cause people to engage in behavior inconsistent with their personal sense of ethics. We believe the only way to avoid these lapses is to integrate conscious and reflective practices that can bring ethical concerns to the forefront of lawyers' decision-making and thought processes. [ABSTRACT FROM AUTHOR]

The offers the author's insights on professor Roger Fisher's lessons on work and conduct of life. The author tells that Roger accepted that illustrations makes ideas more cxomprehendable and concrete and enable readers to view a theory in action. He tells that Roger also recommends individuals to focus on making sure of the product along with its purpose. He adds that Roger believed that his ideas grew when they were tested and shared with others.

The indication for mandatory screening colonoscopies in liver transplant candidates is controversial. Since the introduction of MELD-based allocation, patients with advanced liver disease and often severe comorbidities are prioritized for liver transplantation ( LT). This study evaluated safety and outcome of colonoscopy in this high-risk patient group. During a two-yr period, we performed 243 colonoscopies in potential LT candidates. Endoscopic findings were registered in a standardized form, and correlations with biochemical or clinical parameters were analyzed using Mann- Whitney U-test and chi-square test. Only 57 patients (23.5%) had an endoscopically normal colon. Main findings were polyps (45.7%), hypertensive colopathy (24.3%), diverticulosis (21%), rectal varices (19.8%), and hemorrhoids (13.6%). In 21% of all patients, the removed polyps were diagnosed as adenomas. The prevalence of neoplastic polyps increased significantly with age: 13.6% (patients <50 yr) vs. 25% (patients ≥50 yr) (p = 0.03). Advanced neoplasia was found only in patients older than 40 yr. No major complications were observed; post-interventional hemorrhage was observed in 1.7% and controlled by clipping or injection therapy. In conclusion, lower gastrointestinal endoscopy is safe and effective in LT candidates. Due to the age dependency of neoplastic polyps, a screening colonoscopy should be performed in LT candidates older than 40 yr or with symptoms or additional risk factors. [ABSTRACT FROM AUTHOR]