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Late-onset unexplained epilepsy (LoUE), defined as epilepsy starting after age 55 with no clearly identified cause, has emerged as a significant risk factor for dementia. Individuals presenting with LoUE have no prior history of dementia. Yet, LoUE is associated with a 2-3x increased risk of developing dementia, and up to 25% of individuals with LoUE develop dementia within 4 years after their first seizure. We have little understanding of the mechanisms that underlie development of dementia in LoUE. The ELUCID Study (Epilepsy of Late-onset Unknown etiology as a risk factor for Cognitive Impairment and Dementia) is a multi-center, prospective longitudinal observational study of LoUE, focused on understanding mechanisms and predicting outcomes of mild cognitive impairment and dementia in LoUE. ELUCID will enroll 600 participants with LoUE (and without dementia) across 7 study sites. Participants undergo a baseline evaluation with clinical history, cognitive testing, brain MRI, overnight scalp EEG, and blood draw, and are followed longitudinally with interval history every 6 months and annual cognitive testing. The primary outcomes are development of mild cognitive impairment and dementia. To date, 67 ELUCID participants have completed their initial study visit, with mean age of 67.9±7.2 years and 38.8% female. The sample includes 89.6% White, 3% Black, 1.5% Asian, 6% unreported race, and 1.5% Hispanic ethnicity. Mean level of education was 16.9±2.7 years. Vascular risk factors were common, including hypertension (51%), hyperlipidemia (58%), diabetes mellitus (6%), coronary artery disease (9%), and obstructive sleep apnea (28%). A family history of seizures was present in 23.9% of participants, and a family history of dementia in 58%. Cognitive test scores largely fell within normal range, including: MMSE: 28.7±1.5; Logical Memory Delayed: 11.9±3.4; FCSRT Free Recall: 31.6±6.4; Trails B: 94.3±54.4; Digit Symbol Substitution: 41.9±10.1; and Category Fluency (animals): 17.0±4.9. Subjectively, 32.8% of participants felt their memory had worsened compared to 6 months prior. The ELUCID Study is a large longitudinal study of LoUE that will define its relationship to Alzheimer's disease and related dementias. Here we describe the study protocol and provide an early report of the baseline demographic and clinical characteristics of the accruing ELUCID study population.

Background Late‐onset unexplained epilepsy (LoUE), defined as epilepsy starting after age 55 with no clearly identified cause, has emerged as a significant risk factor for dementia. Individuals presenting with LoUE have no prior history of dementia. Yet, LoUE is associated with a 2‐3x increased risk of developing dementia, and up to 25% of individuals with LoUE develop dementia within 4 years after their first seizure. We have little understanding of the mechanisms that underlie development of dementia in LoUE. Method The ELUCID Study (Epilepsy of Late‐onset Unknown etiology as a risk factor for Cognitive Impairment and Dementia) is a multi‐center, prospective longitudinal observational study of LoUE, focused on understanding mechanisms and predicting outcomes of mild cognitive impairment and dementia in LoUE. ELUCID will enroll 600 participants with LoUE (and without dementia) across 7 study sites. Participants undergo a baseline evaluation with clinical history, cognitive testing, brain MRI, overnight scalp EEG, and blood draw, and are followed longitudinally with interval history every 6 months and annual cognitive testing. The primary outcomes are development of mild cognitive impairment and dementia. Result To date, 67 ELUCID participants have completed their initial study visit, with mean age of 67.9±7.2 years and 38.8% female. The sample includes 89.6% White, 3% Black, 1.5% Asian, 6% unreported race, and 1.5% Hispanic ethnicity. Mean level of education was 16.9±2.7 years. Vascular risk factors were common, including hypertension (51%), hyperlipidemia (58%), diabetes mellitus (6%), coronary artery disease (9%), and obstructive sleep apnea (28%). A family history of seizures was present in 23.9% of participants, and a family history of dementia in 58%. Cognitive test scores largely fell within normal range, including: MMSE: 28.7±1.5; Logical Memory Delayed: 11.9±3.4; FCSRT Free Recall: 31.6±6.4; Trails B: 94.3±54.4; Digit Symbol Substitution: 41.9±10.1; and Category Fluency (animals): 17.0±4.9. Subjectively, 32.8% of participants felt their memory had worsened compared to 6 months prior. Conclusion The ELUCID Study is a large longitudinal study of LoUE that will define its relationship to Alzheimer's disease and related dementias. Here we describe the study protocol and provide an early report of the baseline demographic and clinical characteristics of the accruing ELUCID study population.

State-of-the-art automotive fuel cells that operate at about 80 °C require large radiators and air intakes to avoid overheating. High-temperature fuel cells that operate above 100 °C under anhydrous conditions provide an ideal solution for heat rejection in heavy-duty vehicle applications. Here we report protonated phosphonic acid electrodes that remarkably improve the performance of high-temperature polymer electrolyte membrane fuel cells. The protonated phosphonic acids comprise tetrafluorostyrene-phosphonic acid and perfluorosulfonic acid polymers, where a perfluorosulfonic acid proton is transferred to the phosphonic acid to enhance the anhydrous proton conduction of fuel cell electrodes. By using this material in fuel cell electrodes, we obtained a fuel cell exhibiting a rated power density of 780 mW cm – 2 at 160 °C, with minimal degradation during 2,500 h of operation and 700 thermal cycles from 40 to 160 °C under load. High-temperature polymer electrolyte membrane fuel cells are promising for heavy-duty vehicle applications, but strides in performance are needed to improve their commercial viability. Here it is demonstrated that protonating phosphonic acid electrodes greatly enhances power density and durability.

Background In British Columbia Canada, a Daily Physical Activity (DPA) policy was mandated that requires elementary school teachers to provide students with opportunities to achieve 30 min of physical activity during the school day. However, the implementation of school-based physical activity policies is influenced by many factors. A theoretical examination of the factors that impede and enhance teachers’ implementation of physical activity policies is necessary in order to develop strategies to improve policy practice and achieve desired outcomes. This study used the Theoretical Domains Framework (TDF) to understand teachers’ barriers and facilitators to the implementation of the DPA policy in one school district. Additionally, barriers and facilitators were examined and compared according to how the teacher implemented the DPA policy during the instructional school day. Methods Interviews were conducted with thirteen teachers and transcribed verbatim. One researcher performed barrier and facilitator extraction, with double extraction occurring across a third of the interview transcripts by a second researcher. A deductive and inductive analytical approach in a two-stage process was employed whereby barriers and facilitators were deductively coded using TDF domains (content analysis) and analyzed for sub-themes within each domain. Two researchers performed coding. Results A total of 832 items were extracted from the interview transcripts. Some items were coded into multiple TDF domains, resulting in a total of 1422 observations. The most commonly coded TDF domains accounting for 75% of the total were Environmental context and resources ( ECR ; n  = 250), Beliefs about consequences ( n  = 225), Social influences ( n  = 193), Knowledge ( n  = 100), and Intentions ( n  = 88). Teachers who implemented DPA during instructional time differed from those who relied on non-instructional time in relation to Goals , Behavioural regulation , Social/professional role and identity , Beliefs about Consequences . Forty-one qualitative sub-themes were identified across the fourteen domains and exemplary quotes were highlighted. Conclusions Teachers identified barriers and facilitators relating to all TDF domains, with ECR , Beliefs about consequences , Social influences , Knowledge and Intentions being the most often discussed influencers of DPA policy implementation. Use of the TDF to understand the implementation factors can assist with the systematic development of future interventions to improve implementation.

The blood proteome holds great promise for precision medicine but poses substantial challenges due to the low abundance of most plasma proteins and the vast dynamic range of the plasma proteome. Here we address these challenges with NUcleic acid Linked Immuno-Sandwich Assay (NULISA™), which improves the sensitivity of traditional proximity ligation assays by ~10,000-fold to attomolar level, by suppressing assay background via a dual capture and release mechanism built into oligonucleotide-conjugated antibodies. Highly multiplexed quantification of both low- and high-abundance proteins spanning a wide dynamic range is achieved by attenuating signals from abundant targets with unconjugated antibodies and next-generation sequencing of barcoded reporter DNA. A 200-plex NULISA containing 124 cytokines and chemokines and other proteins demonstrates superior sensitivity to a proximity extension assay in detecting biologically important low-abundance biomarkers in patients with autoimmune diseases and COVID-19. Fully automated NULISA makes broad and in-depth proteomic analysis easily accessible for research and diagnostic applications. Unlocking the blood proteome requires exquisite sensitivity and multiplexing to detect low and high abundance proteins simultaneously. Here the authors describe a 200-plex immunoassay with attomolar sensitivity to detect important low abundance proteins in inflammatory diseases and COVID-19.

Background Given the potential impact school-based daily physical activity (DPA) policies can have on the health outcomes of Canadian children, it is surprising that such little research has examined the implementation and student-level effectiveness of these policies, and that even less have used theory to understand the barriers and facilitators affecting uptake of this policy by teachers. This review descriptively summarizes the implementation status, approaches used to implement DPA, and the effectiveness of DPA at increasing the physical activity of children at school. In addition, the Theoretical Domains Framework (TDF) was used to explore the barriers and facilitators to DPA implementation. Methods A scoping review of English articles using ERIC, CINAHL, and Google Scholar (2005 to 2016) was conducted. Only studies that evaluated the implementation and/or student-level effectiveness of DPA policies in Canadian elementary schools were included. Only articles that examined DPA implementation barriers and facilitators by teachers, principals, and/or administration were eligible for the TDF analysis. Data on study characteristics and major findings regarding implementation status, implementation approach used, and impact on student’s physical activity were extracted and were summarized descriptively, including study quality indicators. Two coders extracted and categorized implementation barriers and facilitators into TDF domains. Results The search resulted in 66 articles being retrieved and 38 being excluded for not meeting the eligibility criteria, leaving 15 eligible for review (10 of which examined barriers and facilitators to implementation from DPA deliverers’ perspective). Eleven of 15 studies examined the Ontario DPA policy, and 2 studies were from both Alberta and British Columbia. Thirteen studies examined implementation, and only two examined effectiveness. DPA implementation status, approaches to delivery, and effectiveness on student’s PA levels are inconsistent across the three provinces. A total of 203 barriers/facilitators were extracted across the ten implementation studies, most of which related to the environmental context and resources ( ECR; n  = 86; 37.4%), beliefs about consequences ( n  = 41; 17.8%), and social influences ( n  = 36; 15.7%) TDF domains. Conclusions With the limited research examining the DPA policy in Canada, the current status and approaches used to implement DPA and the student-level effectiveness is not well understood; however, this review revealed that DPA deliverers often report many barriers to DPA implementation. Most importantly, in conducting a TDF-based analysis of the barriers/facilitators affecting implementation, this review provides a theoretical basis by which researchers and policy-makers can design interventions to better target these problems in the future. Registration A protocol for this review was not registered.

Outdoor air pollution is classified as a Group 1 carcinogen based primarily on evidence of associations with lung cancer. It has increasingly been associated with a higher incidence of other cancers, including breast and uterine cancers. Ovarian cancer, which shares a hormonal etiology with breast and uterine cancers, is the deadliest gynecologic cancer among women, contributing to ~12,740 deaths in the United States (US) in 2024.6 The literature on outdoor air pollution and ovarian cancer is sparse, with most studies evaluating mortality rather than incidence. The few studies investigating disease etiology utilize cross-sectional or ecologic designs focusing on area-level observations. A 2023 ecologic study using registry data across >700 US counties reported a positive association between county-level estimates of ambient particulate matter =2:5 lm in aerodynamic diameter (PM2:5) and ovarian cancer incidence. Our study expands upon the existing literature by investigating the association between individual-level residential estimates of air pollution [nitrogen dioxide (NO2), PM2:5, and ozone (O3)] and incident ovarian cancer in a large, nationwide prospective cohort.

The hair bundle of auditory and vestibular hair cells converts mechanical stimuli into electrical signals through mechanoelectrical transduction (MET). The MET apparatus is built around a tip link that connects neighboring stereocilia that are aligned in the direction of mechanosensitivity of the hair bundle. Upon stimulation, the MET channel complex responds to changes in tip-link tension and allows a cation influx into the cell. Ca 2+ influx in stereocilia has been used as a signature of MET activity. Using genetically encoded Ca 2+ sensors (GCaMP3, GCaMP6s) and high-performance fluorescence confocal microscopy, we detect spontaneous Ca 2+ transients in individual stereocilia in developing and fully formed hair bundles. We demonstrate that this activity is abolished by MET channel blockers and thus likely originates from putative MET channels. We observe Ca 2+ transients in the stereocilia of mice in tissue explants as well as in vivo in zebrafish hair cells, indicating this activity is evolutionarily conserved. Within stereocilia, the origin of Ca 2+ transients is not limited to the canonical MET site at the stereocilia tip but is also present along the stereocilia length. Remarkably, we also observe these Ca 2+ transients in the microvilli-like structures on the hair cell surface in the early stages of bundle development, prior to the onset of MET. Ca 2+ transients are also present in the tallest rows of stereocilia in auditory hair cells, structures not traditionally thought to contain MET channels. We hypothesize that this newly described activity may reflect stochastic and spontaneous MET channel opening. Localization of these transients to other regions of the stereocilia indicates the presence of a pool of channels or channel precursors. Our work provides insights into MET channel assembly, maturation, function, and turnover. .

Uterine fibroids disproportionately affect Black women, and exposure to chemicals from hair relaxers or straighteners (\"straighteners\") may contribute to fibroid development. We examined the association between straightener use and prevalent young-onset uterine fibroids (diagnosed before age 36 y), as well as incident fibroids (diagnosed age 36-60 y), with a focus on Black women. We also examined differences in associations across birth cohorts as proxies for formulation changes. Data from 4,162 Black women in the Sister Study, a prospective cohort of women 35-74 y of age (enrolled 2003-2009), were analyzed. We used logistic regression to estimate odds ratios (ORs) for the association of straightener use at 10-13 y of age and self-reported young-onset fibroids. We used Cox regression to assess hazard ratios (HRs) for straightener use (age 10-13 y and in 12 months before enrollment) and incident fibroids among 779 premenopausal Black women. Similar analyses were conducted in 40,782 non-Hispanic White women. Over 70% of Black women used straighteners. In comparison with no use, any [ ; 95% confidence interval (CI): 0.96, 1.36] and frequent use ( ; 95% CI: 0.99, 1.42) of straighteners at 10-13 y of age were associated with young-onset fibroids. This association was most apparent among those born between 1928 and 1945 ( ; 95% CI: 1.15, 2.74) and 1965-1974 ( ; 95% CI: 0.82, 3.29). Fibroid incidence from 36 to 60 y of age was modestly associated with use of straighteners at 10-13 y of age [hazard ratio ; 95% CI: 0.81, 1.63] and in the 12 months prior to enrollment ( ; 95% CI: 0.88, 2.00). Among non-Hispanic White women, straightener use at 10-13 y of age was similarly associated with young-onset fibroids ( ; 95% CI: 1.03, 1.47) despite lower use ( ) of straighteners. Sensitivity analyses indicated a potential for bias due to fibroid misclassification, with an overestimation of the effect likely if nulliparous women or women from households with lower education reported their fibroid status less accurately. Hair straightener use may be positively associated with fibroid risk. https://doi.org/10.1289/EHP14493.

Some personal care products (PCPs) contain endocrine-disrupting chemicals that may affect breast cancer (BC) risk. Patterns of use vary by race and ethnicity. Use often starts in adolescence, when rapidly developing breast tissue may be more susceptible to environmental carcinogens. Few studies have examined associations of BC with PCP use during this susceptible window. We characterized race and ethnicity-specific patterns of PCP use at 10-13 years of age and estimated associations of use with incident BC. At enrollment (2003-2009), Sister Study participants ( Black, 2,104 Latina, and 39,312 White women) 35-74 years of age reported use of 37 \"everyday\" PCPs during the ages of 10-13 y (did not use, sometimes, or frequently used). We conducted race and ethnicity-specific latent class analyses to separately identify groups of women with similar patterns of beauty, hair, and skincare/hygiene product use. We estimated hazard ratios (HRs) and 95% confidence intervals (CIs) for associations of identified PCP classes and single products with incident BC using Cox proportional hazards regression. During a mean follow-up time of 10.8 y, 280 Black, 128 Latina, and 3,137 White women were diagnosed with BC. Classes of adolescent PCP use were not clearly associated with BC diagnosis among Black, Latina, or White women. HRs were elevated but imprecise for frequent nail product and perfume use in Black women ( 1.34; 95% CI: 0.85, 2.12) and greater hair product use in Black ( 1.28; 95% CI: 0.91, 1.80) and Latina ( 1.42; 95% CI: 0.81, 2.48) women compared with lighter use. In single-product models, we observed higher BC incidence associated with frequent use of lipstick, nail products, pomade, perfume, makeup remover, and acne/blemish products in at least one group. This work provides some support for the hypothesis that PCP use during puberty is associated with BC risk. More research is needed to confirm these novel findings. https://doi.org/10.1289/EHP13882.