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The prevalence rates and correlates of mental or physical disability among recently resettled refugees, who undergo strenuous journeys before arriving in the US, remain unknown, masking potential health disparities. Self-reported disability was measured by the 2018 Annual Survey of Refugees (ASR), and defined as having a physical, mental, or other health condition for more than 6 months that precluded one from working. Prevalence rates of self-reported disability and sample correlates were investigated using descriptive and logistic regression analyses. Of N = 4259 participating refugees in ASR (Mean Age = 28.2, SD = 17.2; 52.5% male), 2875 responded to the disability question and 21.4% reported disability. About 33.7% were born in the Middle East region, 29.5% had no formal education, and 35% had an income of less than $15,000. Age (OR = 1.06, 95% Confidence Interval (CI) [1.06,1.07], p < 0.001), region of birth (OR = 1.82, 95% CI [1.31, 2.51], p < 0.001), employment status (OR = 3.31, 95% CI [2.67, 4.11], p < 0.001), and receiving food stamps (OR = 2.09, 95% CI [1.66, 2.62], p < 0.001) were associated with self-reported disability. Disability levels among refugees recently resettled in the United States are comparable to national disability rates in the US. Our results suggest that multiple aspects of the refugee experience (i.e., demographics, socioeconomic status, contextual migration history) need to be considered to understand the risk for health outcomes. Future investigations of disabilities in diverse refugee populations over time and tailored public health interventions to mitigate potential risk factors are warranted to promote health equity.

UNLABELLED: Long-term physical functioning trajectories following distal forearm fracture are unknown. We found that women with versus those without distal forearm fracture were more likely to experience a 5-year decline in physical functioning, independent of initial physical functioning level. This association was most evident among women 80 years and older. INTRODUCTION: Physical functioning trajectory following lower arm or wrist fracture is not well understood. PURPOSE: This study is to evaluate physical functioning trajectory before vs. after lower arm or wrist fracture, stratified by age. METHODS: We performed a nested case-control study of prospective data from the Womens Health Initiative Study (n = 2097 cases with lower arm or wrist fracture, 20,970 controls). Self-reported fractures and the physical functioning subscale of the RAND 36-item Short-Form Health Survey were assessed annually. We examined three physical functioning trajectory groups: stable, improving, and declining. RESULTS: Mean (SD) number of physical functioning measurements was 5.2 (1.5) for cases and 5.0 (1.4) for controls. Declining physical functioning was observed among 20.4% of cases and 16.0% of controls. Compared to women without lower arm or wrist fracture, women with lower arm or wrist fracture were 33% more likely to experience declining physical functioning (adjusted odds ratio [aOR] 1.33 95% confidence interval [CI] 1.19-1.49, reference group stable or improving physical functioning trajectory). Associations varied by age: age ≥ 80 years aOR 1.56 (95% CI 1.29-1.88); age 70-79 years aOR 1.29 (95% CI 1.09-1.52); age < 70 years aOR 1.15 (95% CI 0.86-1.53) (pinteraction = 0.06). Associations between lower arm or wrist fracture and odds of declining physical functioning did not vary by baseline physical functioning or physical activity level. CONCLUSIONS: Women with lower arm or wrist fracture, particularly those aged 80 and older, were more likely to experien

Loneliness is a pervasive experience with adverse impacts on health and well-being. Despite its significance, notable gaps impede a full understanding of how loneliness changes across the adult life span and what factors influence these changes. To address this, we conducted a coordinated data analysis of nine longitudinal studies encompassing 128,118 participants ages 13 to 103 from over 20 countries. Using harmonized variables and models, we examined loneliness trajectories and predictors. Analyses revealed that loneliness follows a U-shaped curve, decreasing from young adulthood to midlife and increasing in older adulthood. These patterns were consistent across studies. Several baseline factors (i.e., sex, marital status, physical function, education) were linked to loneliness levels, but few moderated the loneliness trajectories. These findings highlight the dynamic nature of loneliness and underscore the need for targeted interventions to reduce social disparities throughout adulthood.

The gun assault case fatality rate measures the fraction of shooting victims who die from their wounds. Considerable debate has surrounded whether gun assault case fatality rates have changed over time and what factors may be involved. We use crime event data from Los Angeles to examine the victim and situational correlates of gun assault case fatality rates over time. We estimated log binomial regression models for the probability of death in each year from 2005 to 2021, conditioned on situational and victim characteristics of the crime. Case fatality rates increased by around 1.3% per year between 2005 and 2021 from around 15.9 to 19.7%. Baseline case fatality rates differed systematically by most situational and victim but followed similar temporal trends. Only victim age significantly covaried with the temporal trend in case fatality rates. An individual shot in Los Angeles in 2021 was 23.7% more likely to die than the equivalent victim in 2005. The steady increase in case fatality rates suggests that there were around 394 excess fatalities over what would have occurred if case fatality rates remained at the 2005 level. Increases in the average age of victims over time may contribute to the general temporal trend. We hypothesize that older victims are more likely to be shot indoors where lethal close-range wounds are more likely.

BACKGROUND: Premutations in the Fragile X Messenger Ribonucleoprotein 1 (FMR1) gene, defined as between 55 and 200 CGGs, have been implicated in fragile X-associated primary ovarian insufficiency (FXPOI). Only 20% of female premutation carriers develop early ovulatory dysfunction, the reason for this incomplete penetrance is unknown. This study validated the mathematical model in premutation alleles, after assigning each allele a score representing allelic complexity. Subsequently, allelic scores were used to investigate the impact of allele complexity on age at amenorrhea for 58 premutation cases (116 alleles) previously published. METHODS: The allelic score was determined using a formula previously described by our group. The impact of each allelic score on age at amenorrhea was analyzed using Pearsons test and a contour plot generated to visualize the effect. RESULTS: Correlation of allelic score revealed two distinct complexity behaviors in premutation alleles. No significant correlation was observed between the allelic score of premutation alleles and age at amenorrhea. The same lack of significant correlation was observed regarding normal-sized alleles, despite a nearly significant trend. CONCLUSIONS: Our results suggest that the use of allelic scores combination have the potential to explain female infertility, namely the development of FXPOI, or ovarian dysfunction, despite the lack of correlation with age at amenorrhea. Such a finding is of great clinical significance for early identification of females at risk of ovulatory dysfunction, enhancement of fertility preservation techniques, and increasing the probability for a successful pregnancy in females with premutations. Additional investigation is necessary to validate this hypothesis.

Neurocognitive aging researchers are increasingly focused on the locus coeruleus, a neuromodulatory brainstem structure that degrades with age. With this rapid growth, the field will benefit from consensus regarding which magnetic resonance imaging (MRI) metrics of locus coeruleus structure are most sensitive to age and cognition. To address this need, the current study acquired magnetization transfer- and diffusion-weighted MRI images in younger and older adults who also completed a free recall memory task. Results revealed significantly larger differences between younger and older adults for maximum than average magnetization transfer-weighted contrast (MTC), axial than mean or radial single-tensor diffusivity (DTI), and free than restricted multi-compartment diffusion (NODDI) metrics in the locus coeruleus; with maximum MTC being the best predictor of age group. Age effects for all imaging modalities interacted with sex, with larger age group differences in males than females for MTC and NODDI metrics. Age group differences also varied across locus coeruleus subdivision for DTI and NODDI metrics, and across locus coeruleus hemispheres for MTC. Within older adults, however, there were no significant effects of age on MTC or DTI metrics, only an interaction between age and sex for free diffusion. Finally, independent of age and sex, higher restricted diffusion in the locus coeruleus was significantly related to better (lower) recall variability, but not mean recall. Whereas MTC has been widely used in the literature, our comparison between the average and maximum MTC metrics, inclusion of DTI and NODDI metrics, and breakdowns by locus coeruleus subdivision and hemisphere make important and novel contributions to our understanding of the aging of locus coeruleus structure.

There is a common belief that antiosteoporosis medications are less effective in older adults. This study used data from randomized controlled trials (RCTs) to determine whether the anti-fracture efficacy of treatments and their effects on BMD differ in people ≥70 compared to those <70 yr. We used individual patient data from 23 RCTs of osteoporosis medications collected as part of the FNIH-ASBMR SABRE project. We assessed the following fractures: radiographic vertebral, non-vertebral, hip, all clinical, and all fractures. We used Cox proportional hazard regression to estimate treatment effect for clinical fracture outcomes, logistic regression for the radiographic vertebral fracture outcome, and linear regression to estimate treatment effect on 24-mo change in hip and spine BMD in each age subgroup. The analysis included 123 164 (99% female) participants; 43% being ≥70 yr. Treatment with anti-osteoporosis drugs significantly and similarly reduced fractures in both subgroups (eg, odds ratio [OR] = 0.47 and 0.51 for vertebral fractures in those below and above 70 yr, interaction P = .19; hazard ratio [HR] for all fractures: 0.72 vs 0.70, interaction P = .20). Results were similar when limited to bisphosphonate trials with the exception of hip fracture risk reduction which was somewhat greater in those <70 (HR = 0.44) vs ≥70 (HR = 0.79) yr (interaction P = .02). Allocation to anti-osteoporotic drugs resulted in significantly greater increases in hip and spine BMD at 24 mo in those ≥70 compared to those <70 yr. In summary, anti-osteoporotic medications similarly reduced the risk of fractures regardless of age, and the few small differences in fracture risk reduction by age were of uncertain clinical significance.

The articles in the June issue serve not only to inform senior care pharmacists on the importance of evidence-based approaches to reduce unnecessary aspirin use, but they also underscore the urgent need for the large and rapid increase in older adult representation in clinical trials and clinical research in general. A striking analysis performed in the United States that examined the trial populations used for Medicare coverage determinations found that while the average age of a Medicare enrollee was 70.8 years old (74.7 years old for older Medicare participants), the average age of the clinical trial population patients used in technology assessments for Medicare coverage determinations was 60.1 years. Hence, the US Medicare system, one of the largest national health care purchasers for older patients in the world, has relied on non-representative data to inform medical coverage decisions.

IntroductionPalbociclib is a widely used treatment for advanced breast cancer in older adults. However, the existing evidence regarding its safety and tolerability in this age group is inconsistent and limited to retrospective subgroup or pooled analyses.Materials and methodsWe conducted a prospective single-arm multicenter phase 2 study to evaluate the safety and tolerability of palbociclib in participants aged 70 years or older with advanced hormone receptor-positive breast cancer. Participants were given palbociclib in combination with their physician's choice of endocrine therapy (letrozole or fulvestrant). The primary endpoint was the incidence of grade 3+ adverse events (AEs) by six months. Secondary endpoints included AE-related dose delays, dose reductions, early discontinuations, and hospitalizations. Additionally, we compared these endpoints by age groups (70-74 and ≥ 75 years).ResultsOf the 90 participants (median age 74 years [70-87]) enrolled, 75.6% (95% confidence interval [CI], 65.4-84.0) had grade 3+ AEs by six months. The most frequent grade 3+ AEs were neutropenia (61%), fatigue (4%), and nausea (3%). Febrile neutropenia was uncommon (1.1%). Due to AEs, 36% had dose delays, 34% had dose reductions, 10% had early discontinuations, and 10% had hospitalizations. Compared to those aged 70-74 years, participants aged ≥75 years had higher rates of early discontinuations (5.9% vs 15.9%, a difference of 9.5% [95% CI 3.5%-22.5%]).DiscussionPalbociclib has an overall favorable safety profile in adults aged ≥70 with advanced breast cancer. However, adults ≥75 years had a trend toward higher rates of AE-related early discontinuations compared to those 70-74 years. Further research is needed to evaluate tolerability and improve the delivery of palbociclib in older adults.Clinicaltrialsgov:NCT03633331.

BACKGROUND: The incidence of breast and colorectal cancer (CRC) in younger-than-average-age patients is rising and poorly understood. This is the largest study on patients with both cancers who are less than 60 years old and aims to characterize demographic, clinicopathologic, and genetic features and describe therapeutic dilemmas and management strategies. MATERIALS AND METHODS: This is a retrospective medical records review of patients at the University of California San Francisco with both primary breast and CRC before age 60. RESULTS: Fifty-one patients were identified; 41 had detailed medical records. Median age of diagnosis with breast cancer was 43 (range 27-59) and CRC was 50 (28-59). Most were Caucasian (38, 74.5%) and never smokers (23, 56.1%); about half were current alcohol consumers (20, 48.8%) and about one-third had sedentary jobs (14, 34.1%). Average BMI was 25.8 (range: 14-49), and 30% were overweight or obese. Breast was the first cancer diagnosed in 36 patients (70.6%) and 44 (86.3%) had a metachronous CRC diagnosis. Breast cancer was early stage (0-2) in 32 (78.0%) patients whereas CRC was split between early stage (1-2) in 14 (34.1%) and later stage (3-4) in 19 (46.2%). Ten patients (24.3%) had a known germline mutation, although 23 (56.1%) had a family history of cancer in a first-degree relative. CONCLUSION: Younger patients with both breast and CRC are a unique cohort, often without known risk factors. Alcohol consumption and sedentary jobs were the most common risk factors, and about one-quarter had a known genetic predisposition. Comanagement of both cancers requires individualized, multidisciplinary care.

BACKGROUND // The most common cause of shoulder pain is clinical pictures related to rotator cuff problems. One of the most common treatments is arthroscopic surgery. The objective was to describe the clinical and epidemiological characteristics of patients undergoing this type of surgery in Spain. METHODS // A descriptive, observational and cross-sectional study with ninety participants was carried out. Data on age, sex, performance of work activity with overuse of upper limbs, body mass index (BMI), smoking habit, diagnosis of diabetes, performance of physical- sports activity and history of pre-surgical treatments were collected. Finally, a descriptive analysis of the variables and an analysis of correlations were carried out, using the Pearson and Spearman statistical test according to the type of variable. RESULTS // The mean age was 57.21 years with a standard deviation (SD) of 8.5 (95% CI, 55.41-59.00). Regarding their BMI, the mean was 28.49 with a SD of 4.9 (95% CI, 27.49-29.53), with 35.6% being obese (BMI greater than 30). The medical diagnosis of the subjects was 51.1% total rotator cuff tear. On the other hand, the intensity of physical activity was one hour or less per week in 87.8% of the sample. Finally, in relation to the previous physiotherapy treatment, 69.7% of the subjects had received some type of intervention.. CONCLUSIONS // The demographic and clinical characteristics found are consistent with those of other previously studied populations, and the association factors between them endorse the previously mentioned risk factors, with advanced age gaining special importance., FUNDAMENTOS // La causa más común de dolor de hombro son los cuadros clínicos relacionados con problemas del manguito rotador. Uno de los tratamientos más habituales es la cirugía artroscópica. El objetivo del estudio fue describir las características clínicas y epidemiológicas de los pacientes sometidos a este tipo de cirugías en España. MÉTODOS // Se realizó un estudio de tipo descriptivo, observacional y de corte transversal con noventa participantes. Se recogieron los datos de edad, sexo, realización de actividad laboral con sobreuso de miembros superiores (MMSS), índice de masa corporal (IMC), consumo de tabaco, diagnóstico de diabetes, realización de actividad física-deportiva y antecedentes de tratamientos prequirúrgicos. Finalmente, se realizó un análisis descriptivo de las variables y un análisis de correlaciones, mediante la prueba estadística de Pearson y Spearman según el tipo de variable. RESULTADOS // La media de edad fue de 57,21 años con una desviación estándar (DE) de 8,5 (Intervalo de Confianza [IC] del 95%, 55,41-59,00). En cuanto a su IMC, la media fue de 28,49 con una DE de 4,9 (IC del 95%, 27,49-29,53), siendo el 35,6% personas con obesidad (IMC mayor de 30). El diagnóstico médico de los sujetos fue en un 51,1% de rotura total del manguito rotador. Por otro lado, la intensidad de realización de actividad física fue de una hora o menos a la semana en el 87,8% de la muestra. Por último, en relación con el tratamiento previo de fisioterapia, el 69,7% de los sujetos habían recibido algún tipo de intervención. CONCLUSIONES // Las características demográficas y clínicas encontradas están en consonancia con las de otras poblaciones estudiadas previamente, y los factores de asociación entre ellas refrendan los factores de riesgo ya señalados previamente (edad, obesidad, sobreuso de MMSS), cobrando especial importancia la edad avanzada.

BackgroundThe objectives were to assess (a) the association between poor oral health and mild cognitive impairment (MCI) in Hispanic/Latino immigrants and (b) potential modification effects on this association by age at immigration.MethodsData were from the Hispanic Community Health Study/Study of Latinos and its ancillary study-the Study of Latinos-Investigation of Neurocognitive Aging. MCI, a binary outcome variable, defined by the National Institute on Aging-Alzheimer's Association criteria. The main exposure was significant tooth loss (STL), defined as a loss of 8 or more teeth, and periodontitis, classified using the Centers for Disease Control and Prevention and American Academy of Periodontology case classification. Multiple logistic regression was used to assess the association between STL/periodontitis and MCI and test moderation effects of age at immigration. The analytical sample comprised 5 709 Hispanic/Latino adult immigrants.ResultsHispanic/Latino immigrants with STL (adjusted odds ratio [AOR] = 1.36, 95% confidence interval [CI]: 1.01-1.85) were more likely to have MCI than those with greater tooth retention. Overall, migration to the United States after age 18 was associated with greater odds of MCI than migration at a younger age. A significant interaction effect between STL and age at immigration revealed that the effect of STL on MCI is even higher in those who immigrated to the United States at ages 35-49 years.ConclusionsSTL is a significant risk factor for MCI and age at immigration had a modification effect on the association between STL and MCI. Better access to dental care, health education on risk factors of MCI, and promotion of good oral health may mitigate the burden of cognitive impairment in Hispanics/Latinos.

BackgroundAge-specific data on anal, and corresponding cervical, human papillomavirus (HPV) infection are needed to inform female anal cancer prevention.MethodsWe centrally reanalyzed individual-level data from 26 studies reporting HPV prevalence in paired anal and cervical samples by human immunodeficiency virus (HIV) status and age. For women with HIV (WWH) with anal high-grade squamous intraepithelial lesions or worse (HSIL+), we also investigated concurrent cervical cytopathology.ResultsIn HIV-negative women, HPV16 prevalence decreased significantly with age, both at anus (4.3% at 15-24 years to 1.0% at ≥55 years; ptrend = 0.0026) and cervix (7.4% to 1.7%; ptrend < 0.0001). In WWH, HPV16 prevalence decreased with age at cervix (18.3% to 7.2%; ptrend = 0.0035) but not anus (11.5% to 13.9%; ptrend = 0.5412). Given anal HPV16 positivity, concurrent cervical HPV16 positivity also decreased with age, both in HIV-negative women (ptrend = 0.0005) and WWH (ptrend = 0.0166). Among 48 WWH with HPV16-positive anal HSIL+, 27 (56%) were cervical high-risk HPV-positive, including 8 with cervical HPV16, and 5 were cervical HSIL+.ConclusionsAge-specific shifts in HPV16 prevalence from cervix to anus suggest that HPV infections in the anus persist longer, or occur later in life, than in the cervix, particularly in WWH. This is an important consideration when assessing the utility of cervical screening results to stratify anal cancer risk.

AIMS: The totality of atherosclerotic plaque derived from coronary computed tomography angiography (CCTA) emerges as a comprehensive measure to assess the intensity of medical treatment that patients need. This study examines the differences in age onset and prognostic significance of atherosclerotic plaque burden between sexes. METHODS AND RESULTS: From a large multi-center CCTA registry the Leiden CCTA score was calculated in 24 950 individuals. A total of 11 678 women (58.5 ± 12.4 years) and 13 272 men (55.6 ± 12.5 years) were followed for 3.7 years for major adverse cardiovascular events (MACE) (death or myocardial infarction). The age where the median risk score was above zero was 12 years higher in women vs. men (64-68 years vs. 52-56 years, respectively, P < 0.001). The Leiden CCTA risk score was independently associated with MACE: score 6-20: HR 2.29 (1.69-3.10); score > 20: HR 6.71 (4.36-10.32) in women, and score 6-20: HR 1.64 (1.29-2.08); score > 20: HR 2.38 (1.73-3.29) in men. The risk was significantly higher for women within the highest score group (adjusted P-interaction = 0.003). In pre-menopausal women, the risk score was equally predictive and comparable with men. In post-menopausal women, the prognostic value was higher for women [score 6-20: HR 2.21 (1.57-3.11); score > 20: HR 6.11 (3.84-9.70) in women; score 6-20: HR 1.57 (1.19-2.09); score > 20: HR 2.25 (1.58-3.22) in men], with a significant interaction for the highest risk group (adjusted P-interaction = 0.004). CONCLUSION: Women developed coronary atherosclerosis approximately 12 years later than men. Post-menopausal women within the highest atherosclerotic burden group were at significantly higher risk for MACE than their male counterparts, which may have implications for the medical treatment intensity.

INTRODUCTION: Bilingualism has historically been claimed to be a risk factor for developmental stuttering. The Early Childhood Longitudinal Study, Kindergarten Class of 2010-11 (ECLS-K:2011) ostensibly contains evidence to test that claim. METHODS: We analyze data from monolingual and bilingual children in Kindergarten through fifth grade in the ECLS-K:2011. RESULTS AND DISCUSSION: The prevalence, male/female ratio, and onset and recovery of reported stuttering in the ECLS are inconsistent with widely-accepted clinical reports of stuttering. We argue that the reported figures may be misleading. We discuss some factors that may inflate the reported prevalence, including a lack of awareness of the difference between stuttering vs. normal disfluencies, and the informal usage of the word stuttering on the part of teachers and parents to describe typical disfluencies.

BACKGROUND: The clinical high-risk (CHR) period offers a temporal window into neurobiological deviations preceding psychosis onset, but little attention has been given to regions outside the cerebrum in large-scale studies of CHR. Recently, the North American Prodrome Longitudinal Study (NAPLS)-2 revealed altered functional connectivity of the cerebello-thalamo-cortical circuitry among individuals at CHR; however, cerebellar morphology remains underinvestigated in this at-risk population, despite growing evidence of its involvement in psychosis. STUDY DESIGN: In this multisite study, we analyzed T1-weighted magnetic resonance imaging scans obtained from N = 469 CHR individuals (61% male, ages = 12-36 years) and N = 212 healthy controls (52% male, ages = 12-34 years) from NAPLS-2, with a focus on cerebellar cortex and white matter volumes separately. Symptoms were rated by the Structured Interview for Psychosis-Risk Syndromes (SIPS). The outcome by two-year follow-up was categorized as in-remission, symptomatic, prodromal-progression, or psychotic. General linear models were used for case-control comparisons and tests for volumetric associations with baseline SIPS ratings and clinical outcomes. STUDY RESULTS: Cerebellar cortex and white matter volumes differed between the CHR and healthy control groups at baseline, with sex moderating the difference in cortical volumes, and both sex and age moderating the difference in white matter volumes. Baseline ratings for major psychosis-risk dimensions as well as a clinical outcome at follow-up had tissue-specific associations with cerebellar volumes. CONCLUSIONS: These findings point to clinically relevant deviations in cerebellar cortex and white matter structures among CHR individuals and highlight the importance of considering the complex interplay between sex and age when studying the neuromaturational substrates of psychosis risk.

Adolescence is an important developmental period associated with increased risk for excessive alcohol use, but also high rates of recovery from alcohol use-related problems, suggesting potential resilience to long-term effects compared to adults. The aim of this systematic review is to evaluate the current evidence for a moderating role of age on the impact of chronic alcohol exposure on the brain and cognition. We searched Medline, PsycInfo, and Cochrane Library databases up to February 3, 2021. All human and animal studies that directly tested whether the relationship between chronic alcohol exposure and neurocognitive outcomes differs between adolescents and adults were included. Study characteristics and results of age-related analyses were extracted into reference tables and results were separately narratively synthesized for each cognitive and brain-related outcome. The evidence strength for age-related differences varies across outcomes. Human evidence is largely missing, but animal research provides limited but consistent evidence of heightened adolescent sensitivity to chronic alcohol's effects on several outcomes, including conditioned aversion, dopaminergic transmission in reward-related regions, neurodegeneration, and neurogenesis. At the same time, there is limited evidence for adolescent resilience to chronic alcohol-induced impairments in the domain of cognitive flexibility, warranting future studies investigating the potential mechanisms underlying adolescent risk and resilience to the effects of alcohol. The available evidence from mostly animal studies indicates adolescents are both more vulnerable and potentially more resilient to chronic alcohol effects on specific brain and cognitive outcomes. More human research directly comparing adolescents and adults is needed despite the methodological constraints. Parallel translational animal models can aid in the causal interpretation of observed effects. To improve their translational value, future a

BackgroundLife-course approaches to identify and help improve modifiable risk factors, particularly in midlife, may mitigate cognitive aging.ObjectiveWe examined how midlife self-rated physical functioning and health may predict cognitive health in older age.MethodsWe used data from the Health and Retirement Study (1998-2016; unweighted-N = 4,685). We used survey multinomial logistic regression and latent growth curve models to examine how midlife (age 50-64 years) activities of daily living (ADL), physical function, and self-reported health affect cognitive trajectories and cognitive impairment not dementia (CIND) and dementia status 18 years later. Then, we tested for sex and racial/ethnic modifications.ResultsAfter covariates-adjustment, worse instrumental ADL (IADL) functioning, mobility, and self-reported health were associated with both CIND and dementia. Hispanics were more likely to meet criteria for dementia than non-Hispanic Whites given increasing IADL impairment.ConclusionMidlife health, activities limitations, and difficulties with mobility are predictive of dementia in later life. Hispanics may be more susceptible to dementia in the presence of midlife IADLs. Assessing midlife physical function and general health with brief questionnaires may be useful for predicting cognitive impairment and dementia in later life.

Cancer is often called a disease of aging. There are numerous ways in which cancer epidemiology and behaviour change with the age of the patient. The molecular bases for these relationships remain largely underexplored. To characterise them, we analyse age-associations in the nuclear and mitochondrial somatic mutational landscape of 20,033 tumours across 35 tumour-types. Age influences both the number of mutations in a tumour (0.077 mutations per megabase per year) and their evolutionary timing. Specific mutational signatures are associated with age, reflecting differences in exogenous and endogenous oncogenic processes such as a greater influence of tobacco use in the tumours of younger patients, but higher activity of DNA damage repair signatures in those of older patients. We find that known cancer driver genes such as CDKN2A and CREBBP are mutated in age-associated frequencies, and these alter the transcriptome and predict for clinical outcomes. These effects are most striking in brain cancers where alterations like SUFU loss and ATRX mutation are age-dependent prognostic biomarkers. Using three cancer datasets, we show that age shapes the somatic mutational landscape of cancer, with clinical implications.

Indicators based a fixed “old” age threshold have been widely used for assessing socioeconomic disparities in mortality at older ages. Interpretation of long-term trends and determinants of these indicators is challenging because mortality above a fixed age that in the past would have reflected old age deaths is today mixing premature and old-age mortality. We propose the modal (i.e., most frequent) age at death, M, an indicator increasingly recognized in aging research, but which has been infrequently used for monitoring mortality disparities at older ages. We use mortality and population exposure data by occupational class over the 1971-2017 period from Finnish register data. The modal age and life expectancy indicators are estimated from mortality rates smoothed with penalized B-splines. Over the 1971-2017 period, occupational class disparities in life expectancy at 65 and 75 widened while disparities in M remained relatively stable. The proportion of the group surviving to the modal age was constant across time and occupational class. In contrast, the proportion surviving to age 65 and 75 has roughly doubled since 1971 and showed strong occupational class differences. Increasing socioeconomic disparities in mortality based on fixed old age thresholds may be a feature of changing selection dynamics in a context of overall declining mortality. Unlike life expectancy at a selected fixed old age, M compares individuals with similar survival chances over time and across occupational classes. This property makes trends and differentials in M easier to interpret in countries where old-age survival has improved significantly.

BACKGROUND: Hospitalized patients with SARS-CoV2 develop acute kidney injury (AKI) frequently, yet gaps remain in understanding why adults seem to have higher rates compared to children. Our objectives were to evaluate the epidemiology of SARS-CoV2-related AKI across the age spectrum and determine if known risk factors such as illness severity contribute to its pattern. METHODS: Secondary analysis of ongoing prospective international cohort registry. AKI was defined by KDIGO-creatinine only criteria. Log-linear, logistic and generalized estimating equations assessed odds ratios (OR), risk differences (RD), and 95% confidence intervals (CIs) for AKI and mortality adjusting for sex, pre-existing comorbidities, race/ethnicity, illness severity, and clustering within centers. Sensitivity analyses assessed different baseline creatinine estimators. RESULTS: Overall, among 6874 hospitalized patients, 39.6% (n = 2719) developed AKI. There was a bimodal distribution of AKI by age with peaks in older age (≥60 years) and middle childhood (5-15 years), which persisted despite controlling for illness severity, pre-existing comorbidities, or different baseline creatinine estimators. For example, the adjusted OR of developing AKI among hospitalized patients with SARS-CoV2 was 2.74 (95% CI 1.66-4.56) for 10-15-year-olds compared to 30-35-year-olds and similarly was 2.31 (95% CI 1.71-3.12) for 70-75-year-olds, while adjusted OR dropped to 1.39 (95% CI 0.97-2.00) for 40-45-year-olds compared to 30-35-year-olds. CONCLUSIONS: SARS-CoV2-related AKI is common with a bimodal age distribution that is not fully explained by known risk factors or confounders. As the pandemic turns to disproportionately impacting younger individuals, this deserves further investigation as the presence of AKI and SARS-CoV2 infection increases hospital mortality risk.

BackgroundOzone effects on lung function are particularly important to understand in the context of the air pollution-health outcomes epidemiologic literature, given the complex relationships between ozone and other air pollutants with known lung function effects.Research questionWhat has been learned about the association between ozone exposures and lung function from epidemiology studies published from 2013 through 2020?Study design and methodsOn March 18, 2018, and September 8, 2020, PubMed was searched using the terms health AND ozone, filtering to articles in English and about humans, from 2013 or later. An additional focused review searching for ozone AND (lung function OR FEV1OR FVC) was performed June 26, 2021. Articles were selected for this review if they reported a specific relationship between a lung function outcome and ozone exposure.ResultsOf 3,271 articles screened, 53 ultimately met criteria for inclusion. A systematic review with assessment of potential for bias was conducted, but a meta-analysis was not carried out because of differences in exposure duration and outcome quantification. Consistent evidence exists of small decreases in children's lung function, even associated with very low levels of short-term ozone exposure. The effects on adult lung function from exposure to low-level, short-term ozone are less clear, although ozone-associated decrements may occur in the elderly. Finally, long-term ozone exposure decreases both lung function and lung function growth in children, although few new studies have examined long-term ozone and lung function in adults.InterpretationMuch of this literature involves concentrations below the current US Environmental Protection Agency's National Ambient Air Quality Standard of 70 parts per billion over an 8-h averaging time, suggesting that this current standard may not protect children adequately from ozone-related decrements in lung function.

BackgroundAge and ethnicity are among several factors that influence overall survival (OS) in ovarian cancer. The study objective was to determine whether ethnicity and age were of prognostic significance in women enrolled in a clinical trial evaluating the addition of bevacizumab to front-line therapy.MethodsWomen with advanced stage ovarian, primary peritoneal, or fallopian tube cancer were enrolled in a phase III clinical trial. All women had surgical staging and received adjuvant chemotherapy with one of three regimens. Cox proportional hazards models were used to evaluate the relationship between OS with age and race/ethnicity among the study participants.ResultsOne-thousand-eight-hundred-seventy-three women were enrolled in the study. There were 280 minority women and 328 women over the age of 70. Women age 70 and older had a 34% increase risk for death when compared to women under 60 (HR = 1.34; 95% CI 1.16-1.54). Non-Hispanic Black women had a 54% decreased risk of death with the addition of maintenance bevacizumab (HR = 0.46, 95% CI:0.26-0.83). Women of Asian descent had more hematologic grade 3 or greater adverse events and a 27% decrease risk of death when compared to non-Hispanic Whites (HR = 0.73; 95% CI: 0.59-0.90).ConclusionsNon-Hispanic Black women showed a decreased risk of death with the addition of bevacizumab and patients of Asian ancestry had a lower death rate than all other minority groups, but despite these clinically meaningful improvements there was no statistically significant difference in OS among the groups.

Background: The aim of this study was to investigate the factors that associate the decayed, missing due to caries, and filled teeth (DMFT) index of patients with dental anxiety during dental treatment discontinuation. Methods: A total of 110 patients who complained of fear and anxiety toward dental treatments and who re-visited following treatment discontinuation were enrolled in the study. Patient and dental data considered to be related to caries were digitally collected from medical and dental records. The decayed (D), missing (M), and filled (F) scores, and the DMFT index before and after discontinuation were compared using Wilcoxon signed-rank tests, and the associated factors were evaluated using the Poisson and multiple regression analyses. Results: The D score and DMFT index augmented significantly during the discontinuation period, and the F score reduced. There was no significant change in the M score. The change in the D score was associated by the pre-discontinuation D score and the number of experiences of intravenous sedation, and the change in the F score was associated by the duration of treatment discontinuation, the DMFT index before discontinuation, and the number of experiences of intravenous sedation. The upsurge in the DMFT index was associated by the experience of intravenous sedation, the D and M scores, and the DMFT index before discontinuation. Conclusion: Discontinuation of dental treatment was proven to be associated with the incidence of caries in dentally-fearful patients., Acta medica Nagasakiensia, 65(3), pp.95−101; 2022

Insulin sensitivity progressively declines with age. Currently, the mechanism underlying age-associated insulin resistance remains unknown. Here, we identify membrane-bound matrix metalloproteinase 14 (MT1-MMP/MMP14) as a central regulator of insulin sensitivity during ageing. Ageing promotes MMP14 activation in insulin-sensitive tissues, which cleaves Insulin Receptor to suppress insulin signaling. MT1-MMP inhibition restores Insulin Receptor expression, improving insulin sensitivity in aged mice. The cleavage of Insulin Receptor by MT1-MMP also contributes to obesity-induced insulin resistance and inhibition of MT1-MMP activities normalizes metabolic dysfunctions in diabetic mouse models. Conversely, overexpression of MT1-MMP in the liver reduces the level of Insulin Receptor, impairing hepatic insulin sensitivity in young mice. The soluble Insulin Receptor and circulating MT1-MMP are positively correlated in plasma from aged human subjects and non-human primates. Our findings provide mechanistic insights into regulation of insulin sensitivity during physiological ageing and highlight MT1-MMP as a promising target for therapeutic avenue against diabetes.

BackgroundThe cost-effectiveness of screening mammography beyond age 75 years remains unclear.ObjectiveTo estimate benefits, harms, and cost-effectiveness of extending mammography to age 80, 85, or 90 years according to comorbidity burden.DesignMarkov microsimulation model.Data sourcesSEER (Surveillance, Epidemiology, and End Results) program and Breast Cancer Surveillance Consortium.Target populationU.S. women aged 65 to 90 years in groups defined by Charlson comorbidity score (CCS).Time horizonLifetime.PerspectiveNational health payer.InterventionScreening mammography to age 75, 80, 85, or 90 years.Outcome measuresBreast cancer death, survival, and costs.Results of base-case analysisExtending biennial mammography from age 75 to 80 years averted 1.7, 1.4, and 1.0 breast cancer deaths and increased days of life gained by 5.8, 4.2, and 2.7 days per 1000 women for comorbidity scores of 0, 1, and 2, respectively. Annual mammography beyond age 75 years was not cost-effective, but extending biennial mammography to age 80 years was ($54 000, $65 000, and $85 000 per quality-adjusted life-year [QALY] gained for women with CCSs of 0, 1, and ≥2, respectively). Overdiagnosis cases were double the number of deaths averted from breast cancer.Results of sensitivity analysisCosts per QALY gained were sensitive to changes in invasive cancer incidence and shift of breast cancer stage with screening mammography.LimitationNo randomized controlled trials of screening mammography beyond age 75 years are available to provide model parameter inputs.ConclusionAlthough annual mammography is not cost-effective, biennial screening mammography to age 80 years is; however, the absolute number of deaths averted is small, especially for women with comorbidities. Women considering screening beyond age 75 years should weigh the potential harms of overdiagnosis versus the potential benefit of averting death from breast cancer.Primary funding sourceNational Cancer Institute and Nation

PurposeWe evaluated whether combining a humanized antidisialoganglioside monoclonal antibody (hu14.18K322A) throughout therapy improves early response and outcomes in children with newly diagnosed high-risk neuroblastoma.Patients and methodsWe conducted a prospective, single-arm, three-stage, phase II clinical trial. Six cycles of induction chemotherapy were coadministered with hu14.18K322A, granulocyte-macrophage colony-stimulating factor (GM-CSF), and low-dose interleukin-2 (IL-2). The consolidation regimen included busulfan and melphalan. When available, an additional cycle of parent-derived natural killer cells with hu14.18K322A was administered during consolidation (n = 31). Radiation therapy was administered at the end of consolidation. Postconsolidation treatment included hu14.18K322A, GM-CSF, IL-2, and isotretinoin. Early response was assessed after the first two cycles of induction therapy. End-of-induction response, event-free survival (EFS), and overall survival (OS) were evaluated.ResultsSixty-four patients received hu14.18K322A with induction chemotherapy. This regimen was well tolerated, with continuous infusion narcotics. Partial responses (PRs) or better after the first two chemoimmunotherapy cycles occurred in 42 of 63 evaluable patients (66.7%; 95% CI, 55.0 to 78.3). Primary tumor volume decreased by a median of 75% (range, 100% [complete disappearance]-5% growth). Median peak hu14.18K322A serum levels in cycle one correlated with early response to therapy (P = .0154, one-sided t-test). Sixty of 62 patients (97%) had an end-of-induction partial response or better. No patients experienced progressive disease during induction. The 3-year EFS was 73.7% (95% CI, 60.0 to 83.4), and the OS was 86.0% (95% CI, 73.8 to 92.8), respectively.ConclusionAdding hu14.18K322A to induction chemotherapy improved early objective responses, significantly reduced tumor volumes in most patients, improved end-of-induction response rates, and yielded an encouraging 3-year

Background: Soft tissue sarcomas (STS) are a heterogeneous group of tumors whose management benefits from a multidisciplinary therapeutic approach. Published data suggest that cancer treatment at a specialized cancer center (SCC) can improve survival in other cancers. Therefore, we examined the impact of the location of treatment on survival in children and adolescents and young adults (AYAs) with STS. Methods: We performed a population-based analysis of children and AYAs hospitalized within 1 year of diagnosis with first primary STS (2000-2014) using the California Cancer Registry linked with hospitalization data. Patients were categorized based on receiving all inpatient treatments at a SCC versus part/none. Multivariable Cox proportional hazards regression identified factors associated with overall and STS-specific survival by age group. Results are presented as adjusted hazard ratios (HRs) and 95% confidence intervals (CIs). Results: Of the 1,674 patients with STS, 142 were children (0-14) and 1,532 were AYAs (15-39) and 89.4% and 40.4% received all inpatient treatments at a SCC, respectively. Overall, the 5-year survival was improved for patients who received all inpatient care at a SCC (59.8% vs. those who received part/none, 50.7%). Multivariable regression analysis found that having all treatments at a SCC was associated with better overall survival (HR, 0.79, CI: 0.65-0.95) in AYAs, but not in children. Conclusions: Our findings demonstrate that treatment for STS at a SCC is associated with better survival in AYAs. Eliminating barriers to treatment of AYAs with STS at SCCs could improve survival in this population.

CONTEXT: COVID-19 morbidity and mortality are increased in type 1 diabetes (T1D), but few data focus on age-based outcomes. OBJECTIVE: This work aimed to quantify the risk for COVID-19-related hospitalization and adverse outcomes by age in people with T1D. METHODS: For this observational, multisite, cross-sectional study of patients with T1D and laboratory-confirmed COVID-19 from 56 clinical sites in the United States, data were collected from April 2020 to March 2021. The distribution of patient factors and outcomes across age groups (0-18, 19-40, and > 40 years) was examined. Descriptive statistics were used to describe the study population, and multivariate logistic regression models were used to analyze the relationship between age, adverse outcomes, and hospitalization. The main outcome measure was hospitalization for COVID-19. RESULTS: A total of 767 patients were analyzed. Fifty-four percent (n = 415) were aged 0 to 18 years, 32% (n = 247) were aged 19 to 40 years, and 14% (n = 105) were older than 40 years. A total of 170 patients were hospitalized, and 5 patients died. Compared to the 0- to 18-years age group, those older than 40 years had an adjusted odds ratio of 4.2 (95% CI, 2.28-7.83) for hospitalization after adjustment for sex, glycated hemoglobin A1c, race, insurance type, and comorbidities. CONCLUSION: Age older than 40 years is a risk factor for patients with T1D and COVID-19, with children and younger adults experiencing milder disease and better prognosis. This indicates a need for age-tailored treatments, immunization, and clinical management of individuals affected by T1D.

Introduction: With the prolongation of life expectancy, an increasing number of elderly patients are evaluated for pancreatic surgery. However, the influence of increasing age on outcomes after pancreaticoduodenectomy (PD) is still unclear, especially in octogenarians. Aim of this study is to evaluate the perioperative characteristics and outcomes of octogenarians undergoing PD. Methods: Data for 812 patients undergoing PD between 2019 and 2020 in 10 referral centers in Italy were reviewed. Patients aged 80 years or older were matched based on nearest neighbor propensity scores in a 1:1 ratio to patients younger than 80 years. Propensity scores were calculated using 7 perioperative variables including gender, ASA score, neoadjuvant treatment (NAT), biliary stent positioning, type of surgical approach (open, laparoscopic, robot-assisted), associated vascular resections, type of lesion. Perioperative characteristics and short-term postoperative outcomes were compared before and after matching. Results: Overall, 81 (10%) patients had 80 years or more. Before matching, octogenarians had a higher rate of ASA score≥ 3 (n = 35, 43.2% vs. n = 207, 28.3%; p = 0.005) and less frequently underwent NAT (n = 11, 13.6% vs. n = 213, 29.1%; p = 0.003). Matching was successfully performed for 70 octogenarians. After matching, no differences in preoperative and intraoperative characteristics were found. Postoperatively, ICU admission was more frequent in octogenarians (50% vs 30%; p = 0.01). Although in-hospital mortality was higher in octogenarians before matching (7.4% vs 2.9% in the younger cohort; p = 0.03), no difference was noted between the matched cohorts (p = 0.36). Postoperative morbidity was comparable between groups in the whole and selected populations. At the multivariate analysis, chronological age was not recognized as a prognostic factor for cumulative major complications, while ASA ≥3 was the only confirmed influencing feature (OR 2.98; 95%CI: 1.6–6.8; p = 0.009). C

Purpose To evaluate the changes in pupil diameter in women and men after cataract surgery. The correlation of pupillary changes with the variables age and anterior chamber depth will be analyzed. Methods The values of 109 randomized eyes who underwent cataract surgery were obtained and divided into two groups, 71 women and 38 men. Pupil diameter was measured preoperatively and 3-months postoperatively using the pupillometer software of the Topolyzer Vario (Wavelight Laser Technologie AG). Anterior chamber depth was obtained with Pentacam® (Oculus). Differences in pupillary diameters were investigated and correlations with age and anterior chamber depth were analyzed. Results For mesopic pupils, the male group had greater reduction in their postoperative pupillary diameter, -0.56 mm (-12.4%), than the female group, -0.38 mm (-8.2%), P = 0.025. Photopic postoperative pupils reduced to a lesser extent, yet more in men than in women (-0.11mm [-4.5%] vs. -0.04 [-1.6%], P = 0.048). Weak significant negative correlation was found between photopic pupillary changes in women with age (r = -0.24, P = 0.041), and positive correlation for mesopic pupillary changes in men with age (r = +0.34, P = 0.039). Conclusions Patients experience pupil reduction after cataract surgery in general, but more in men than in women and for both photopic and mesopic lighting conditions. The differences are statistically significant and have moderate clinical relevance. Concerning pupillary changes, weak but opposite sign correlations were found between male/female gender and age., This work was supported by the Spanish Ministerio de Economía y Competitividad and FEDERfunds under project Ref. DPI2016-76019-R, Peer Reviewed, Postprint (author's final draft)

The role of school-based contacts in the epidemiology of SARS-CoV-2 is incompletely understood. We use an age-structured transmission model fitted to age-specific seroprevalence and hospital admission data to assess the effects of school-based measures at different time points during the COVID-19 pandemic in the Netherlands. Our analyses suggest that the impact of measures reducing school-based contacts depends on the remaining opportunities to reduce non-school-based contacts. If opportunities to reduce the effective reproduction number (Re) with non-school-based measures are exhausted or undesired and Re is still close to 1, the additional benefit of school-based measures may be considerable, particularly among older school children. As two examples, we demonstrate that keeping schools closed after the summer holidays in 2020, in the absence of other measures, would not have prevented the second pandemic wave in autumn 2020 but closing schools in November 2020 could have reduced Re below 1, with unchanged non-school-based contacts.

Vietnamese Americans have a higher rate of cervical and colorectal cancer (CRC) compared to other ethnicities. Increasing CRC screening, Pap testing, and HPV vaccination is critical to preventing disproportionate cancer burden among Vietnamese families. To describe the successes and challenges of implementing a novel intergenerational family group chat intervention that encourages CRC screening, Pap testing, and HPV vaccination. Young adult Family Health Advocates (FHAs) were trained to facilitate online family group chat conversations to encourage cancer screenings. Ten families participated in a 4-week intervention. Data collection included screenshot data of family group chat conversations, family member surveys, and post-intervention FHA interviews. Intervention implementation successes included (a) cultural and language brokering, (b) active co-facilitation by family members to follow up on cancer screenings, (c) high levels of family group chat engagement, (d) high acceptability of intervention among families, and (e) accessibility of intervention curriculum. FHA challenges to implement the intervention included (a) sustaining cancer prevention conversations, (b) comfort with navigating family conversations around cancer screening, (c) relevance for all family members, and (d) missed opportunities for correcting misinformation. Researcher challenges included family recruitment and retention. The intervention made cancer-screening messages more accessible and was well accepted by Vietnamese families. Scaling up the intervention will require (a) training FHAs to monitor family conversations and build confidence in sharing medical accurate messages, (b) segmenting group chats by age and gender, and (c) employing multiple family engagement strategies.

Prosocial activities, such as volunteering, predict better mental and physical health in late adulthood, but their proximal links to well-being in daily life are largely unknown. The current study examined day-to-day associations of prosocial activities with emotional and physical well-being, and whether these associations differ with age. We used daily diary data from the National Study of Daily Experiences (NSDE) II (n = 2,016; ages 33-84) and NSDE Refresher Study (n = 774; ages 25-75). Participants completed telephone interviews on 8 consecutive evenings regarding their prosocial activities (formal volunteering, providing unpaid assistance, providing emotional support), well-being (negative affect, stressors, positive events), and physical symptoms. On days when individuals participated in more formal volunteering or provided more unpaid assistance than usual, they experienced more stressors and positive events but no difference in the number of physical symptoms. Negative affect was reduced on volunteering days for older adults but increased for younger adults (NSDE Refresher). Providing emotional support was associated with higher same-day negative affect, more stressors, more positive events, and elevated physical symptoms. Compared to younger and middle-aged adults, older adults experienced less of an increase in stressors and positive events (NSDE II) and negative affect (NSDE Refresher) on days when they provided more emotional support than usual. These findings demonstrate that prosocial activities are associated with both costs (negative affect, stressors, physical symptoms) and benefits (positive events) for same-day well-being. Older age may protect against negative ramifications associated with prosocial activities. (PsycInfo Database Record (c) 2021 APA, all rights reserved).

DNAJC3, also known as P58IPK, is an Hsp40 family member that interacts with and inhibits PKR-like ER-localized eIF2α kinase (PERK). Dnajc3 deficiency in mice causes pancreatic β-cell loss and diabetes. Loss-of-function mutations in DNAJC3 cause early-onset diabetes and multisystemic neurodegeneration. The aim of our study was to investigate the genetic cause of early-onset syndromic diabetes in two unrelated patients, and elucidate the mechanisms of β-cell failure in this syndrome., info:eu-repo/semantics/published

SARS-CoV-2 is transmitted primarily through close, person-to-person interactions. Physical distancing policies can control the spread of SARS-CoV-2 by reducing the amount of these interactions in a population. Here, we report results from four waves of contact surveys designed to quantify the impact of these policies during the COVID-19 pandemic in the United States. We surveyed 9,743 respondents between March 22 and September 26, 2020. We find that interpersonal contact has been dramatically reduced in the US, with an 82% (95%CI: 80%-83%) reduction in the average number of daily contacts observed during the first wave compared to pre-pandemic levels. However, we find increases in contact rates over the subsequent waves. We also find that certain demographic groups, including people under 45 and males, have significantly higher contact rates than the rest of the population. Tracking these changes can provide rapid assessments of the impact of physical distancing policies and help to identify at-risk populations.

Stereotypes linking Black Americans with guns can have life-altering outcomes, making it important to identify factors that shape such weapon identification biases and how they do so. We report 6 experiments that provide a mechanistic account of how category salience affects weapon identification bias elicited by male faces varying in race (Black, White) and age (men, boys). Behavioral analyses of error rates and response latencies revealed that, when race was salient, faces of Black versus White males (regardless of age) facilitated the classification of objects as guns versus tools. When a category other than race was salient, racial bias in behavior was reduced, though not eliminated. In Experiments 1-4, racial bias was weaker when participants attended to a social category besides race (i.e., age). In Experiments 5 and 6, racial bias was weaker when participants attended to an applicable, yet nonsubstantive category (i.e., the color of a dot on the face). Across experiments, process analyses using diffusion models revealed that, when race was salient, seeing Black versus White male faces led to an initial bias to favor the "gun" response. When a category besides race (i.e., age, dot color) was salient, racial bias in the relative start point was reduced, though not eliminated. These results suggest that the magnitude of racial bias in weapon identification may differ depending on what social category is salient. The collective findings also highlight the utility of diffusion modeling for elucidating how category salience shapes processes underlying racial biases in behavior. (PsycInfo Database Record (c) 2021 APA, all rights reserved).

ImportanceColorectal cancer is the third leading cause of cancer death for both men and women, with an estimated 52 980 persons in the US projected to die of colorectal cancer in 2021. Colorectal cancer is most frequently diagnosed among persons aged 65 to 74 years. It is estimated that 10.5% of new colorectal cancer cases occur in persons younger than 50 years. Incidence of colorectal cancer (specifically adenocarcinoma) in adults aged 40 to 49 years has increased by almost 15% from 2000-2002 to 2014-2016. In 2016, 26% of eligible adults in the US had never been screened for colorectal cancer and in 2018, 31% were not up to date with screening.ObjectiveTo update its 2016 recommendation, the US Preventive Services Task Force (USPSTF) commissioned a systematic review to evaluate the benefits and harms of screening for colorectal cancer in adults 40 years or older. The review also examined whether these findings varied by age, sex, or race/ethnicity. In addition, as in 2016, the USPSTF commissioned a report from the Cancer Intervention and Surveillance Modeling Network Colorectal Cancer Working Group to provide information from comparative modeling on how estimated life-years gained, colorectal cancer cases averted, and colorectal cancer deaths averted vary by different starting and stopping ages for various screening strategies.PopulationAsymptomatic adults 45 years or older at average risk of colorectal cancer (ie, no prior diagnosis of colorectal cancer, adenomatous polyps, or inflammatory bowel disease; no personal diagnosis or family history of known genetic disorders that predispose them to a high lifetime risk of colorectal cancer [such as Lynch syndrome or familial adenomatous polyposis]).Evidence assessmentThe USPSTF concludes with high certainty that screening for colorectal cancer in adults aged 50 to 75 years has substantial net benefit. The USPSTF concludes with moderate certainty that screening for colorectal cancer in adults aged 45 to 49 years has mode

Increased cerebrospinal fluid neurofilament light (NfL) is a recognized biomarker for neurodegeneration that can also be assessed in blood. Here, we investigate plasma NfL as a marker of neurodegeneration in 13 neurodegenerative disorders, Down syndrome, depression and cognitively unimpaired controls from two multicenter cohorts: King's College London (n = 805) and the Swedish BioFINDER study (n = 1,464). Plasma NfL was significantly increased in all cortical neurodegenerative disorders, amyotrophic lateral sclerosis and atypical parkinsonian disorders. We demonstrate that plasma NfL is clinically useful in identifying atypical parkinsonian disorders in patients with parkinsonism, dementia in individuals with Down syndrome, dementia among psychiatric disorders, and frontotemporal dementia in patients with cognitive impairment. Data-driven cut-offs highlighted the fundamental importance of age-related clinical cut-offs for disorders with a younger age of onset. Finally, plasma NfL performs best when applied to indicate no underlying neurodegeneration, with low false positives, in all age-related cut-offs.

BackgroundExisting evidence suggests that there is an association between body size and prevalent Benign Prostatic Hyperplasia (BPH)-related outcomes and nocturia. However, there is limited evidence on the association between body size throughout the life-course and incident BPH-related outcomes.MethodsOur study population consisted of men without histories of prostate cancer, BPH-related outcomes, or nocturia in the intervention arm of the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial (PLCO) (n = 4710). Associations for body size in early- (age 20), mid- (age 50) and late-life (age ≥ 55, mean age 60.7 years) and weight change with incident BPH-related outcomes (including self-reported nocturia and physician diagnosis of BPH, digital rectal examination-estimated prostate volume ≥ 30 cc, and prostate-specific antigen [PSA] concentration > 1.4 ng/mL) were examined using Poisson regression with robust variance estimation.ResultsMen who were obese in late-life were 25% more likely to report nocturia (Relative Risk (RR): 1.25, 95% Confidence Interval (CI): 1.11-1.40; p-trendfor continuous BMI < 0.0001) and men who were either overweight or obese in late-life were more likely to report a prostate volume ≥ 30 cc (RRoverweight: 1.13, 95% CI 1.07-1.21; RRobese: 1.10, 95% CI 1.02-1.19; p-trendfor continuous BMI = 0.017) as compared to normal weight men. Obesity at ages 20 and 50 was similarly associated with both nocturia and prostate volume ≥ 30 cc. Considering trajectories of body size, men who were normal weight at age 20 and became overweight or obese by later-life had increased risks of nocturia (RRnormal to overweight: 1.09, 95% CI 0.98-1.22; RRnormal to obese: 1.28, 95% CI 1.10-1.47) and a prostate volume ≥ 30 cc (RRnormal to overweight: 1.12, 95% CI 1.05-1.20). Too few men were obese early in life to examine the independent effect of early-life body size. Later-life body size modified the association between physica

During the COVID-19 pandemic, social distancing measures often result in individual isolation, which can lead to adverse mental outcomes. We collected online questionnaires from 3,952 US adults to examine the impact of "shelter-in-place" guidelines on mental health, and to explore potential disparities and modifiable factors. Self-reported anxiety, depression, and PTSD symptoms were associated with more restrictive quarantine. Younger adults, women, those with lower income, more insecurity, more media exposure, reduced physical activity, or worsened family relationships were particularly affected. Targeted prevention on susceptible subpopulations, including young adults and lower SES groups, might help mitigate disparities in COVID-19-related mental health problems.

Polygenic hazard score (PHS) models are associated with age at diagnosis of prostate cancer. Our model developed in Europeans (PHS46) showed reduced performance in men with African genetic ancestry. We used a cross-validated search to identify single nucleotide polymorphisms (SNPs) that might improve performance in this population. Anonymized genotypic data were obtained from the PRACTICAL consortium for 6253 men with African genetic ancestry. Ten iterations of a 10-fold cross-validation search were conducted to select SNPs that would be included in the final PHS46+African model. The coefficients of PHS46+African were estimated in a Cox proportional hazards framework using age at diagnosis as the dependent variable and PHS46, and selected SNPs as predictors. The performance of PHS46 and PHS46+African was compared using the same cross-validated approach. Three SNPs (rs76229939, rs74421890 and rs5013678) were selected for inclusion in PHS46+African. All three SNPs are located on chromosome 8q24. PHS46+African showed substantial improvements in all performance metrics measured, including a 75% increase in the relative hazard of those in the upper 20% compared to the bottom 20% (2.47-4.34) and a 20% reduction in the relative hazard of those in the bottom 20% compared to the middle 40% (0.65-0.53). In conclusion, we identified three SNPs that substantially improved the association of PHS46 with age at diagnosis of prostate cancer in men with African genetic ancestry to levels comparable to Europeans.

Background & aimsIn patients with chronic liver disease (CLD) with or without cirrhosis, existing studies on the outcomes with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection have limited generalizability. We used the National COVID Cohort Collaborative (N3C), a harmonized electronic health record dataset of 6.4 million, to describe SARS-CoV-2 outcomes in patients with CLD and cirrhosis.MethodsWe identified all patients with CLD with or without cirrhosis who had SARS-CoV-2 testing in the N3C Data Enclave as of July 1, 2021. We used survival analyses to associate SARS-CoV-2 infection, presence of cirrhosis, and clinical factors with the primary outcome of 30-day mortality.ResultsWe isolated 220,727 patients with CLD and SARS-CoV-2 test status: 128,864 (58%) were noncirrhosis/negative, 29,446 (13%) were noncirrhosis/positive, 53,476 (24%) were cirrhosis/negative, and 8941 (4%) were cirrhosis/positive patients. Thirty-day all-cause mortality rates were 3.9% in cirrhosis/negative and 8.9% in cirrhosis/positive patients. Compared to cirrhosis/negative patients, cirrhosis/positive patients had 2.38 times adjusted hazard of death at 30 days. Compared to noncirrhosis/positive patients, cirrhosis/positive patients had 3.31 times adjusted hazard of death at 30 days. In stratified analyses among patients with cirrhosis with increased age, obesity, and comorbid conditions (ie, diabetes, heart failure, and pulmonary disease), SARS-CoV-2 infection was associated with increased adjusted hazard of death.ConclusionsIn this study of approximately 221,000 nationally representative, diverse, and sex-balanced patients with CLD; we found SARS-CoV-2 infection in patients with cirrhosis was associated with 2.38 times mortality hazard, and the presence of cirrhosis among patients with CLD infected with SARS-CoV-2 was associated with 3.31 times mortality hazard. These results provide an additional impetus for increasing vaccination uptake and further research regar

Diffusion imaging studies have observed age-related degradation of white matter that contributes to cognitive deficits separately in younger-old (ages 65-89) and oldest-old (ages 90+) adults. But it remains unclear whether these age effects are magnified in advanced age groups, which may reflect disease-related pathology. Here, we tested whether age-related differences in white matter microstructure followed linear or nonlinear patterns across the entire older adult lifespan (65-98 years), these patterns were influenced by oldest-old adults at increased risk of dementia (cognitive impairment no dementia, CIND), and they explained age effects on episodic memory. Results revealed nonlinear microstructure declines across fiber classes (medial temporal, callosal, association, projection and/or thalamic) that were largest for medial temporal fibers. These patterns remained after excluding oldest-old participants with CIND, indicating that aging of white matter microstructure cannot solely be explained by pathology associated with early cognitive impairment. Moreover, finding that the effect of age on episodic memory was mediated by medial temporal fiber microstructure suggests it is essential for facilitating memory-related neural signals across the older adult lifespan.

Multimodal T cell profiling can enable more precise characterization of elusive cell states underlying disease. Here, we integrated single-cell RNA and surface protein data from 500,089 memory T cells to define 31 cell states from 259 individuals in a Peruvian tuberculosis (TB) progression cohort. At immune steady state >4 years after infection and disease resolution, we found that, after accounting for significant effects of age, sex, season and genetic ancestry on T cell composition, a polyfunctional type 17 helper T (TH17) cell-like effector state was reduced in abundance and function in individuals who previously progressed from Mycobacterium tuberculosis (M.tb) infection to active TB disease. These cells are capable of responding to M.tb peptides. Deconvoluting this state-uniquely identifiable with multimodal analysis-from public data demonstrated that its depletion may precede and persist beyond active disease. Our study demonstrates the power of integrative multimodal single-cell profiling to define cell states relevant to disease and other traits.

Health systems are struggling to manage a fluctuating volume of critically ill patients with COVID-19 while continuing to provide basic surgical services and expand capacity to address operative cases delayed by the pandemic. As we move forward through the next phases of the pandemic, we will need a decision-making system that allows us to remain nimble as clinicians to meet our patient's needs while also working with a new framework of healthcare operations. Here, we present our quality improvement process for the adaptation and application of the Medically Necessary Time-Sensitive (MeNTS) toolto gynecologic surgical services beyond the initial COVID response and into recovery of surgical services; with analysis of the reliability of the modified-MeNTS tool in our multi-site safety net hospital network. This multicenter study evaluated the gynecology surgical case volume at three tertiary acute care safety net institutions within the LA County Department of Health Services: Harbor-UCLA (HUMC), Olive View Medical Center (OVMC), and Los Angeles County + University of Southern California (LAC+USC). We describe our modified-Delphi approach to adapt the MeNTS tool in a structured fashion and its application to gynecologic surgical services. Blinded reviewers engaged in a three-round iterative adaptation and final scoring utilizing the modified tool. The cohort consisted of 392 female consecutive gynecology patients across three Los Angeles County Hospitals awaiting scheduled procedures in the surgical queue.The majority of patients were Latina (74.7%) and premenopausal (67.1%). Over half (52.4%) of the patients had cardiovascular disease, while 13.0% had lung disease, and 13.8% had diabetes. The most common indications for surgery were abnormal uterine bleeding (33.2%), pelvic organ prolapse (19.6%) and presence of an adnexal mass (14.3%). Minimally invasive approaches via laparoscopy, robotic-assisted laparoscopy, or vaginal surgery was the predominant planned surgical