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Background: Exposure to fine particulate matter (PM 2.5 ) has been linked to an increased risk of atherosclerosis. However, it remains unclear whether specific compounds within PM 2.5 , rather than the overall mass, serve as a better indicator of adverse cardiovascular health outcomes associated with air pollution., Methods: In this cross-sectional study, we included 3257 participants (aged 37-51 years) from the Coronary Artery Risk Development in Young Adults (CARDIA) study. Exposure to PM 2.5 and its constituent compounds, black carbon (BC), ammonium, nitrate, organic matter, sulfate, mineral dust, and sea salt were included in the analyses. Carotid intima media thickness (cIMT; the average of common, bulb, and internal carotid) was measured by carotid ultrasonography. We assessed the cross-sectional associations of one-year exposure to PM 2.5 and its compounds with mean cIMT using linear regression models adjusting for participants' demographics, individual- and neighborhood-level socioeconomic status, behavioral components, and health conditions. We also adopted Bayesian kernel machine regression (BKMR) models to investigate the association between the PM 2.5 compound mixture and cIMT as well as the contribution of each compound to the association., Results: Greater exposure to BC was associated with higher cIMT (mm) (β =0.034, 95 % CI = 0.019-0.049, per IQR increase [0.56 μg/m 3 ] of BC) among participants with a mean age of 45.0, consisting of 45.9 % Black and 54.1 % White males and females. The association was generally consistent across participants' demographic characteristics. In our BKMR analysis, BC exhibited a dose-response association with cIMT with a high contribution to the association of cIMT with PM 2.5 compound as a mixture (posterior inclusion probability [PIP]: 1.00)., Conclusions: Our findings suggest that certain compounds of PM 2.5 , such as BC, may offer more reliable indications of the impact of air pollution on cardiovascular health., Competing Interests: Declaration of competing interest V. Murthy owns stock in General Electric, Cardinal Health, Viatris, Pfizer, Amgen, Merck and Johnson & Johnson and stock options in Ionetix. He is a paid consultant for INVIA Medical Imaging Solutions & Siemens Healthineers. V. Murthy has received research support through his institution from Siemens Healthineers., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Intimate partner violence (IPV) is a major global concern, and IPV victim-survivors are at an increased risk of brain injury (BI) due to the physical assaults. IPV-BI can encompass both mild traumatic brain injury (mTBI) and non-fatal strangulation (NFS), but IPV-BI often goes undetected and untreated due to a number of complicating factors. Therefore, the clinical care and support of IPV victim-survivors could be enhanced by BI screening and assessment in various settings (e.g., first responders, emergency departments, primary care providers, rehabilitation, shelters, and research). Further, appropriate screening and assessment for IPV-BI will support more accurate identifications, and prevalence estimates, improve understanding of health implications, and have the potential to inform policy decisions. Here we overview the seven available tools that have been used for IPV-BI screening and assessment purposes, including the BISA, BISQ-IPV, BAT-L/IPV, OSU TBI-ID, the HELPS, and the CHATS, and outline the advantages and disadvantages of these screening tools in the clinical, community, and research settings. Recommendations for further research to enhance the validity and utility of these tools are also included., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Instrumented mouthguards (iMGs) are widely applied to measure head acceleration event (HAE) exposure in sports. Despite laboratory validation, on-field factors including potential sensor skull-decoupling and spurious recordings limit data accuracy. Video analysis can provide complementary information to verify sensor data but lacks quantitative kinematics reference information and suffers from subjectivity. The purpose of this study was to develop a rigorous multi-stage screening procedure, combining iMG and video as independent measurements, aimed at improving the quality of on-field HAE exposure measurements. We deployed iMGs and gathered video recordings in a complete university men's ice hockey varsity season. We developed a four-stage process that involves independent video and sensor data collection (Stage I), general screening (Stage II), cross verification (Stage III), and coupling verification (Stage IV). Stage I yielded 24,596 iMG acceleration events (AEs) and 17,098 potential video HAEs from all games. Approximately 2.5% of iMG AEs were categorized as cross-verified and coupled iMG HAEs after Stage IV, and less than 1/5 of confirmed or probable video HAEs were cross-verified with iMG data during stage III. From Stage I to IV, we observed lower peak kinematics (median peak linear acceleration from 36.0 to 10.9 g; median peak angular acceleration from 3922 to 942 rad/s 2 ) and reduced high-frequency signals, indicative of potential reduction in kinematic noise. Our study proposes a rigorous process for on-field data screening and provides quantitative evidence of data quality improvements using this process. Ensuring data quality is critical in further investigation of potential brain injury risk using HAE exposure data., (© 2024. The Author(s) under exclusive licence to Biomedical Engineering Society.)

Intimate partner violence (IPV) is a significant, global public health concern. Women, individuals with historically underrepresented identities, and disabilities are at high risk for IPV and tend to experience severe injuries. There has been growing concern about the risk of exposure to IPV-related head trauma, resulting in IPV-related brain injury (IPV-BI), and its health consequences. Past work suggests that a significant proportion of women exposed to IPV experience IPV-BI, likely representing a distinct phenotype compared with BI of other etiologies. An IPV-BI often co-occurs with psychological trauma and mental health complaints, leading to unique issues related to identifying, prognosticating, and managing IPV-BI outcomes. The goal of this review is to identify important gaps in research and clinical practice in IPV-BI and suggest potential solutions to address them. We summarize IPV research in five key priority areas: (1) unique considerations for IPV-BI study design; (2) understanding non-fatal strangulation as a form of BI; (3) identifying objective biomarkers of IPV-BI; (4) consideration of the chronicity, cumulative and late effects of IPV-BI; and (5) BI as a risk factor for IPV engagement. Our review concludes with a call to action to help investigators develop ecologically valid research studies addressing the identified clinical-research knowledge gaps and strategies to improve care in individuals exposed to IPV-BI. By reducing the current gaps and answering these calls to action, we will approach IPV-BI in a trauma-informed manner, ultimately improving outcomes and quality of life for those impacted by IPV-BI.

Intimate partner violence is a serious, but underappreciated, issue that predominantly affects women and often results in concussion (i.e., mild traumatic brain injury). However, concussion in intimate partner violence is unique because it often involves a concomitant strangulation which may exacerbate or alter the physiology and clinical presentation of the brain injury. Therefore, here we conducted human and rodent studies to provide insight into knowledge gaps related to the detection, pathophysiology, and functional consequences of intimate partner violence-related brain injury. We conducted the first study to analyze blood biomarkers and symptoms of brain injury in intimate partner violence patients presenting to an emergency department within 72 h of concussion. Intimate partner violence concussion patients, some of whom had also experienced a concomitant strangulation, had elevated serum neurofilament light and worse brain injury symptoms compared to healthy control, orthopedic trauma, and non-intimate partner violence concussion groups. We also developed the first rat model of non-fatal strangulation and examined the consequences of strangulation and concussion in isolation and in combination on pathophysiology, blood biomarkers, and behavior at 2 h and 1wk post-injury. Rats exposed to combined strangulation and concussion had exacerbated motor and cognitive deficits, neuroinflammation, and serum glial fibrillary acidic protein levels compared with either injury in isolation. Taken together, these rodent findings demonstrate that a concomitant strangulation modifies and exacerbates concussion pathophysiology, biomarkers, and functional consequences. Overall, these findings provide novel insights into intimate partner violence-related brain injury and provides a foundation for future translational studies., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Purpose: In adults, intimate partner violence victimization and traumatic brain injuries, including concussion, are strongly connected. However, no prior research has explored this association among youth. This study explores the association between teen dating violence (TDV) and concussion to inform clinical care for these at-risk groups., Methods: We used data from ninth and 10th grade youth in the 2017/18 Health Behavior in School-Aged Children nationally representative Canadian dataset (N = 2,926). TDV in the past 12 months was measured using three items for victimization and three for perpetration. Youth were asked if they had been told by a doctor or nurse that they had had a concussion in the past 12 months and where they were and what they were doing when they had the concussion. We used coarsened exact matching to create equivalent groups of TDV victims and nonvictims, and then explored the association between TDV and concussion using doubly robust logistic regression models. We also explored effect modification by gender., Results: TDV was related to higher odds of concussion, both overall and when restricted to nonsport settings. In nonsport settings, youth who reported mutual TDV reported the highest odds of past-year concussion (adjusted odds ratio = 2.14, 95% confidence interval: 1.07, 4.28, p = .032). We also found that girls and nonbinary youth reported elevated risk of concussion in the context of TDV., Discussion: We found that TDV was associated with increased risk for concussion. Findings can be used to inform future research and may assist adolescent health providers who treat youth with concussion., (Copyright © 2024 Society for Adolescent Health and Medicine. Published by Elsevier Inc. All rights reserved.)

Background: Reported associations between particulate matter with aerodynamic diameter ≤2.5 μm (PM 2.5 ) and cognitive outcomes remain mixed. Differences in exposure estimation method may contribute to this heterogeneity., Objectives: To assess agreement between PM 2.5 exposure concentrations across 11 exposure estimation methods and to compare resulting associations between PM 2.5 and cognitive or MRI outcomes., Methods: We used Visit 5 (2011-2013) cognitive testing and brain MRI data from the Atherosclerosis Risk in Communities (ARIC) Study. We derived address-linked average 2000-2007 PM 2.5 exposure concentrations in areas immediately surrounding the four ARIC recruitment sites (Forsyth County, NC; Jackson, MS; suburbs of Minneapolis, MN; Washington County, MD) using 11 estimation methods. We assessed agreement between method-specific PM 2.5 concentrations using descriptive statistics and plots, overall and by site. We used adjusted linear regression to estimate associations of method-specific PM 2.5 exposure estimates with cognitive scores (n = 4678) and MRI outcomes (n = 1518) stratified by study site and combined site-specific estimates using meta-analyses to derive overall estimates. We explored the potential impact of unmeasured confounding by spatially patterned factors., Results: Exposure estimates from most methods had high agreement across sites, but low agreement within sites. Within-site exposure variation was limited for some methods. Consistently null findings for the PM 2.5 -cognitive outcome associations regardless of method precluded empirical conclusions about the potential impact of method on study findings in contexts where positive associations are observed. Not accounting for study site led to consistent, adverse associations, regardless of exposure estimation method, suggesting the potential for substantial bias due to residual confounding by spatially patterned factors., Discussion: PM 2.5 estimation methods agreed across sites but not within sites. Choice of estimation method may impact findings when participants are concentrated in small geographic areas. Understanding unmeasured confounding by factors that are spatially patterned may be particularly important in studies of air pollution and cognitive or brain health., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests:Melinda Power reports financial support was provided by National Institutes of Health.Melinda Power reports a relationship with National Institutes of Health that includes: funding grants. Melinda Power reports a relationship with U.S. Department of Defense that includes: funding grants. Melinda Power reports a relationship with DC DEPARTMENT OF HEALTH that includes: funding grants. Melinda Power reports a relationship with Biogen that includes: consulting or advisory. Erin Bennett reports a relationship with Massachusetts General Hospital that includes: consulting or advisory. Eun Sug Park reports a relationship with National Institutes of Health that includes: funding grants. Jeff D. Yanosky reports a relationship with National Institutes of Health that includes: funding grants. Duanping Liao reports a relationship with National Institutes of Health that includes: funding grants. Joel D. Kaufman reports a relationship with National Institutes of Health that includes: funding grants. Joel D. Kaufman reports a relationship with U.S. Environmental Protection Agency that includes: funding grants. Lianne Sheppard reports a relationship with National Institutes of Health that includes: funding grants. Lianne Sheppard reports a relationship with Health Effects Institute that includes: funding grants. Adam Szpiro reports a relationship with National Institutes of Health that includes: funding grants. Adam Szpiro reports a relationship with Health Effects Institute that includes: funding grants. Adam Szpiro reports a relationship with Health Effects Institute that includes: consulting or advisory. Eric Whitsel reports a relationship with National Institutes of Health that includes: funding grants. Eric Whitsel reports a relationship with USFederal Aviation Administration that includes: funding grants.If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Currently available focal knee resurfacing implants (FKRIs) are fully or partially composed of metals, which show a large disparity in elastic modulus relative to bone and cartilage tissue. Although titanium is known for its excellent osseointegration, the application in FKRIs can lead to potential stress-shielding and metal implants can cause degeneration of the opposing articulating cartilage due to the high resulting contact stresses. Furthermore, metal implants do not allow for follow-up using magnetic resonance imaging (MRI).To overcome the drawbacks of using metal based FKRIs, a biomimetic and MRI compatible bi-layered non-resorbable thermoplastic polycarbonate-urethane (PCU)-based FKRI was developed. The objective of this preclinical study was to evaluate the mechanical properties, biocompatibility and osteoconduction of a novel Bionate® 75D - zirconium oxide (B75D-ZrO 2 ) composite material in vitro and the osseointegration of a B75D-ZrO 2 composite stem PCU implant in a caprine animal model. The tensile strength and elastic modulus of the B75D-ZrO 2 composite were characterized through in vitro mechanical tests under ambient and physiological conditions. In vitro biocompatibility and osteoconductivity were evaluated by exposing human mesenchymal stem cells to the B75D-ZrO 2 composite and culturing the cells under osteogenic conditions. Cell activity and mineralization were assessed and compared to Bionate® 75D (B75D) and titanium disks. The in vivo osseointegration of implants containing a B75D-ZrO 2 stem was compared to implants with a B75D stem and titanium stem in a caprine large animal model. After a follow-up of 6 months, bone histomorphometry was performed to assess the bone-to-implant contact area (BIC). Mechanical testing showed that the B75D-ZrO 2 composite material possesses an elastic modulus in the range of the elastic modulus reported for trabecular bone. The B75D-ZrO 2 composite material facilitated cell mediated mineralization to a comparable extent as titanium. A significantly higher bone-to-implant contact (BIC) score was observed in the B75D-ZrO 2 implants compared to the B75D implants. The BIC of B75D-ZrO 2 implants was not significantly different compared to titanium implants. A biocompatible B75D-ZrO 2 composite approximating the elastic modulus of trabecular bone was developed by compounding B75D with zirconium oxide. In vivo evaluation showed an significant increase of osseointegration for B75D-ZrO 2 composite stem implants compared to B75D polymer stem PCU implants. The osseointegration of B75D-ZrO 2 composite stem PCU implants was not significantly different in comparison to analogous titanium stem metal implants., (© 2024 The Authors. Journal of Biomedical Materials Research Part A published by Wiley Periodicals LLC.)

Global geophysical satellite-derived ambient fine particulate matter (PM 2.5 ) inference relies upon a geophysical relationship (η) from a chemical transport model to relate satellite retrievals of aerosol optical depth (AOD) to surface PM 2.5 . The resolution dependence of simulated η warrants further investigation. In this study, we calculate geophysical PM 2.5 with simulated η from the GEOS-Chem model in its high-performance configuration (GCHP) at cubed-sphere resolutions of C360 (∼25 km) and C48 (∼200 km) and satellite AOD at 0.01° (∼1 km). Annual geophysical PM 2.5 concentrations inferred from satellite AOD and GCHP simulations at ∼25 km and ∼200 km resolutions exhibit remarkable similarity ( R 2 = 0.96, slope = 1.03). This similarity in part reflects opposite resolution responses across components with population-weighted normalized mean difference (PW-NMD) increasing by 5% to 11% for primary species while decreasing by -30% to -5% for secondary species at finer resolution. Despite global similarity, our results also identify larger resolution sensitivities of η over isolated pollution sources and mountainous regions, where spatial contrast of aerosol concentration and composition is better represented at fine resolution. Our results highlight the resolution dependence of representing near-surface concentrations and the vertical distribution of chemically different species with implications for inferring ground-level PM 2.5 from columnar AOD., Competing Interests: The authors declare no competing financial interest., (© 2024 The Authors. Published by American Chemical Society.)

Background: Outdoor fine particulate air pollution, <2.5 µm (PM 2.5 ) mass concentrations can be constructed through many different combinations of chemical components that have varying levels of toxicity. This poses a challenge for studies interested in estimating the health effects of total outdoor PM 2.5 (i.e., how much PM 2.5 mass is present in the air regardless of composition) because we must consider possible confounders of the version of treatment-outcome relationships., Methods: We evaluated the extent of possible bias in mortality hazard ratios for total outdoor PM 2.5 by examining models with and without adjustment for sulfate and nitrate in PM 2.5 as examples of potential confounders of version of treatment-outcome relationships. Our study included approximately 3 million Canadians and Cox proportional hazard models were used to estimate hazard ratios for total outdoor PM 2.5 adjusting for sulfate and/or nitrate and other relevant covariates., Results: Hazard ratios for total outdoor PM 2.5 and nonaccidental, cardiovascular, and respiratory mortality were overestimated due to the confounding version of treatment-outcome relationships, and associations for lung cancer mortality were underestimated. Sulfate was most strongly associated with nonaccidental, cardiovascular, and respiratory mortality suggesting that regulations targeting this specific component of outdoor PM 2.5 may have greater health benefits than interventions targeting total PM 2.5 ., Conclusions: Studies interested in estimating the health impacts of total outdoor PM 2.5 (i.e., how much PM 2.5 mass is present in the air) need to consider potential confounders of the version of treatment-outcome relationships. Otherwise, health risk estimates for total PM 2.5 will reflect some unknown combination of how much PM 2.5 mass is present in the air and the kind of PM 2.5 mass that is present., (Copyright © 2024 The Authors. Published by Wolters Kluwer Health, Inc. on behalf of The Environmental Epidemiology. All rights reserved.)

At least one in three women experience intimate partner violence (IPV) in their lifetime. The most commonly sustained IPV-related brain injuries include strangulation-related alterations in consciousness (S-AICs) and traumatic brain injuries (TBIs). Moreover, survivors of IPV-related S-AICs and/or TBIs often demonstrate psychological distress such as depression, anxiety, and post-traumatic stress. However, the co-occurrence of S-AICs and TBIs, and whether such TBIs may be moderate to severe, has not been systematically examined, and most data have been collected from women in North America. The purpose of this study was to examine the co-occurrence of IPV-related S-AICs and TBIs across a range of geographical locations and to determine the extent to which these S-AICs are related to psychological distress. Women who had experienced physical IPV ( n = 213) were included in this secondary analysis of retrospectively collected data across four countries (Canada, the United States, Spain, and Colombia). The Brain Injury Severity Assessment (BISA) was used to assess IPV-related BI across all sites. Because various questionnaires were employed to assess levels of depression, anxiety, and post-traumatic stress disorder at each site, we created a standardized composite score by converting raw scores into Z -scores for analysis. Mann-Whitney U tests and chi-square tests were conducted to examine differences between women with and without experience of S-AICs and to discover if there was a relationship between the occurrence of S-AICs and TBIs. Analysis of variance and analysis of covariance (to control for the potential confounding effects of age, education, and non IPV-related TBI) were used to compare levels of psychological distress in women who had or had not experienced S-AICs. Approximately, 67% of women sustained at least one IPV-related BI (i.e., TBI and/or S-AIC). In a subsample of women who sustained at least one IPV-related BI, approximately 37% sustained both S-AICs and TBIs, 2% sustained only S-AICs (with no TBIs), and 61% sustained TBIs exclusively (with no S-AICs). Furthermore, women who had sustained S-AICs (with or without a TBI) were more likely to have experienced a moderate-to-severe BI than those who had not sustained an S-AIC (BISA severity subscale: U = 3939, p = 0.006). In addition, women who experienced S-AICs (with or without a TBI) reported higher levels of psychological distress compared with women who never experienced S-AICs, irrespective of whether they occurred once or multiple times. These data underscore the importance of assessing for S-AIC in women who have experienced IPV and when present, to also assess for TBIs and the presence of psychological distress. Unfortunately, there were methodological differences across sites precluding cross-site comparisons. Nonetheless, data were collected across four culturally and geographically diverse countries and, therefore, highlight IPV-related BIs as a global issue that needs to be aggressively studied with policies established and then implemented to address findings.

Background: Transcranial Doppler (TCD) is a technique to assess blood flow velocity in the cerebral arteries. TCD is frequently used to monitor aneurysmal subarachnoid hemorrhage (aSAH) patients. This study compares TCD-criteria for vasospasm and its association with Delayed Cerebral Ischemia (DCI). An overall score based on flow velocities of various intracranial arteries was developed and evaluated., Methods: A retrospective diagnostic accuracy study was conducted between 1998 and 2017 with 621 patients included. Mean flow velocity (MFV) of the cerebral artery was measured between 2-5 days and between 6-9 days after ictus. Cutoff values from the literature, new cutoff values, and a new composite score (Combined Severity Score) were used to predict DCI. Sensitivity, specificity, and area under the curve (AUC) were determined, and logistic regression analysis was performed., Results: The Combined Severity Score showed an AUC 0.64 (95%CI 0.56-.71) at days 2-5, with sensitivity 0.53 and specificity 0.74. The Combined Severity Score had an adjusted Odds Ratio of 3.41 (95CI 1.86-6.32) for DCI. MCA-measurements yielded the highest AUC to detect DCI at day 2-5: AUC 0.65 (95%CI 0.58-0.73). Optimal cutoff MFV of 83 cm/s for MCA resulted in sensitivity 0.73 and specificity 0.50 at days 2-5., Conclusion: TCD-monitoring of aSAH patients may be a valuable strategy for DCI risk stratification. Lower cutoff values can be used in the early phase after the ictus (day 2-5) than are commonly used now. The Combined Severity Score incorporating all major cerebral arteries may provide a meaningful contribution to interpreting TCD measurements., (© 2024. The Author(s).)

Background: Numerous studies have linked fine particulate matter (PM2.5) to increased cardiovascular mortality. Less is known how the PM2.5-cardiovascular mortality association varies by use of cardiovascular medications. This study sought to quantify effect modification by statin use status on the associations between long-term exposure to PM2.5 and mortality from any cardiovascular cause, coronary heart disease (CHD), and stroke., Methods: In this nested case-control study, we followed 1.2 million community-dwelling adults aged ≥66 years who lived in Ontario, Canada from 2000 through 2018. Cases were patients who died from the three causes. Each case was individually matched to up to 30 randomly selected controls using incidence density sampling. Conditional logistic regression models were used to estimate odds ratios (ORs) for the associations between PM2.5 and mortality. We evaluated the presence of effect modification considering both multiplicative (ratio of ORs) and additive scales (the relative excess risk due to interaction, RERI)., Results: Exposure to PM2.5 increased the risks for cardiovascular, CHD, and stroke mortality. For all three causes of death, compared with statin users, stronger PM2.5-mortality associations were observed among non-users [e.g. for cardiovascular mortality corresponding to each interquartile range increase in PM2.5, OR = 1.042 (95% CI, 1.032-1.053) vs OR = 1.009 (95% CI, 0.996-1.022) in users, ratio of ORs = 1.033 (95% CI, 1.019-1.047), RERI = 0.039 (95% CI, 0.025-0.050)]. Among users, partially adherent users exhibited a higher risk of PM2.5-associated mortality than fully adherent users., Conclusions: The associations of chronic exposure to PM2.5 with cardiovascular and CHD mortality were stronger among statin non-users compared to users., (© The Author(s) 2024. Published by Oxford University Press on behalf of the International Epidemiological Association.)

Research in the field of intimate partner violence-caused brain injury (IPV-BI) has predominantly focused on heterosexual women, ignoring the unique needs of the Two Spirit, Lesbian, Gay, Bisexual, Transgender, Queer or Questioning (2S/LGBTQ) community. The purpose of this exploratory research was to better understand the prevalence of IPV and IPV-BI in 2S/LGBTQ relationships where IPV was defined as physical, psychological, financial, sexual, and/or identity-based abuse from a current of former intimate partner. This study used a cross sectional internet-based survey that ran from September to December of 2022. In addition to descriptive statistics, prevalence rates and their corresponding Wilson Score confidence intervals are reported to estimate the proportion of individuals who experienced IPV and IPV-BI. Finally, for both gender identity and sexual orientation, we tested whether participants with each identity had differing levels of brain injury severity compared to participants who did not hold that identity using Mann-Whitney U tests. In total, 170 2S/LGBTQ+ adults responded to the survey. Among the respondents, 54% identified as Two-Spirit, 24% identified as gay, 17% identified as queer, 14% identified as bisexual, and 8% identified as lesbian or pansexual, respectively. Respondents were predominantly multiracial, post-secondary educated, full-time employed, cisgender women (35%) or cisgender men (19%). The overwhelming majority reported lifetime prevalence of IPV at 98% ( n  = 166, 95% CI [94.11, 99.08]). Additionally, 68% ( n  = 115, 95% CI [60.29, 74.22]) of participants reported symptoms consistent with an IPV-BI. These results are consistent with the findings that the 2S/LGBTQ community are at heightened risk of experiencing physical IPV. These findings are the first to our knowledge to report a high rate of symptoms consistent with an IPV-BI in the 2S/LGBTQ population., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interests with respect to the authorship and/or publication of this article.

Background: Globally, approximately 1 in 3 women experience intimate partner violence (IPV) in their lifetime. Brain injury (BI) is a common, yet often unrecognized, consequence of IPV. BIs caused by IPV tend to be mild, occur repetitively over the course of months or years, are remote in time, and result in chronic symptoms. Similar to BI from other causes, therapeutic treatment for women with IPV-caused BI (IPV-BI) is crucial to help resolve any physical or cognitive impairments, enhance the quality of life (QoL), and minimize longer-term neurodegeneration., Objective: This study aims to investigate the feasibility and efficacy of a community support network (CSN) rehabilitation intervention regarding its impact on resiliency, QoL, and neurocognitive function., Methods: In this pre- and postexperimental design, women (aged 18 to 50 years) who are survivors of IPV and IPV-BI will be recruited from various community organizations serving survivors of IPV. Exclusion criteria will include current pregnancy and any diagnosed neurological disorder known to affect cerebrovascular, neurocognitive, or sensorimotor function. A CSN rehabilitation intervention that includes aerobic exercise, cognitive training, mindfulness meditation, and counseling will be administered. A trauma-informed approach will be integrated into the design and implementation of the program. Furthermore, the program will include a participant navigator who will provide trauma- and violence-informed advocacy and systems navigation support to participants, in addition to facilitating a monthly peer support group. The intervention will be provided for 2.5 hours a day and 2 days a week for 3 months. Participants will complete psychological assessments and provide clinic-demographic information in the first assessment. In the second (before intervention), third (after intervention), and fourth (at follow-up) sessions, they will complete tests of resiliency, QoL, and neurocognition. The estimated sample size is 100. The objective of this study will be accomplished by quantitatively measuring resiliency, QoL, and neurocognition before and immediately after the intervention. A follow-up assessment will occur 3 months after the completion of the intervention to evaluate the maintenance of any improvements in function. One-way ANOVAs will be used to evaluate the intervention outcome across the testing times. Relationships among various variables will be explored using regression analysis., Results: We anticipate that the CSN rehabilitation intervention will be effective in improving resiliency, QoL, and neurocognitive function in women who have experienced IPV-BI. Furthermore, we anticipate that this intervention will be feasible in terms of study recruitment, adherence, and retention., Conclusions: The CSN rehabilitation intervention will have a positive impact on resiliency, QoL, and neurocognitive functions in survivors of IPV-BI. Subsequently, a comparative study will be conducted by recruiting a control group receiving usual care., International Registered Report Identifier (irrid): PRR1-10.2196/54605., (©Shambhu Prasad Adhikari, Tori N Stranges, Setareh Nouri Zadeh Tehrani, Shaun Porter, Karen Mason, Paul van Donkelaar. Originally published in JMIR Research Protocols (https://www.researchprotocols.org), 24.05.2024.)

Motivated by the recent tightening of the US annual standard of fine particulate matter (PM 2.5 ) concentrations from 12 to 9 μg/m 3 , there is a need to understand the spatial variation and drivers of historical PM 2.5 reductions. We evaluate and interpret the variability of PM 2.5 reductions across the contiguous US using high-resolution estimates of PM 2.5 and its chemical composition over 1998-2019, inferred from satellite observations, air quality modeling, and ground-based measurements. We separated the 3092 counties into four characteristic regions sorted by PM 2.5 trends. Region 1 (primarily Central Atlantic states, 25.9% population) exhibits the strongest population-weighted annual PM 2.5 reduction (-3.6 ± 0.4%/yr) versus Region 2 (primarily rest of the eastern US, -3.0 ± 0.3%/yr, 39.7% population), Region 3 (primarily western Midwest, -1.9 ± 0.3%/yr, 25.6% population), and Region 4 (primarily the Mountain West, -0.4 ± 0.5%/yr, 8.9% population). Decomposition of these changes by chemical composition elucidates that sulfate exhibits the fastest reductions among all components in 2720 counties (76% of population), mostly over Regions 1-3, with the 1998-2019 mean sulfate mass fraction in PM 2.5 decreasing from Region 1 (29.5%) to Region 4 (11.8%). Complete elimination of the remaining sulfate may be insufficient to meet the new standard for many regions in exceedance. Additional measures are needed to reduce other PM 2.5 sources and components for further progress., Competing Interests: The authors declare no competing financial interest., (© 2024 The Authors. Published by American Chemical Society.)

Prescribed fires (fires intentionally set for mitigation purposes) produce pollutants, which have negative effects on human and animal health. One of the pollutants produced from fires is fine particulate matter (PM 2.5 ). The Flint Hills (FH) region of Kansas experiences extensive prescribed burning each spring (March-May). Smoke from prescribed fires is often understudied due to a lack of monitoring in the rural regions where prescribed burning occurs, as well as the short duration and small size of the fires. Our goal was to attribute PM 2.5 concentrations to the prescribed burning in the FH. To determine PM 2.5 increases from local burning, we used low-cost PM 2.5 sensors (PurpleAir) and satellite observations. The FH were also affected by smoke transported from fires in other regions during 2022. We separated the transported smoke from smoke from fires in eastern Kansas. Based on data from the PurpleAir sensors, we found the 24-hr median PM 2.5 to increase by 3.0-5.3 μg m -3 (based on different estimates) on days impacted by smoke from fires in the eastern Kansas region compared to days unimpacted by smoke. The FH region was the most impacted by smoke PM 2.5 compared to other regions of Kansas, as observed in satellite products and in situ measurements. Additionally, our study found that hourly PM 2.5 estimates from a satellite-derived product aligned with our ground-based measurements. Satellite-derived products are useful in rural areas like the FH, where monitors are scarce, providing important PM 2.5 estimates., Competing Interests: The authors declare no conflicts of interest relevant to this study., (© 2024 The Authors. GeoHealth published by Wiley Periodicals LLC on behalf of American Geophysical Union.)

Global fine particulate matter (PM 2.5 ) assessment is impeded by a paucity of monitors. We improve estimation of the global distribution of PM 2.5 concentrations by developing, optimizing, and applying a convolutional neural network with information from satellite-, simulation-, and monitor-based sources to predict the local bias in monthly geophysical a priori PM 2.5 concentrations over 1998-2019. We develop a loss function that incorporates geophysical a priori estimates and apply it in model training to address the unrealistic results produced by mean-square-error loss functions in regions with few monitors. We introduce novel spatial cross-validation for air quality to examine the importance of considering spatial properties. We address the sharp decline in deep learning model performance in regions distant from monitors by incorporating the geophysical a priori PM 2.5 . The resultant monthly PM 2.5 estimates are highly consistent with spatial cross-validation PM 2.5 concentrations from monitors globally and regionally. We withheld 10% to 99% of monitors for testing to evaluate the sensitivity and robustness of model performance to the density of ground-based monitors. The model incorporating the geophysical a priori PM 2.5 concentrations remains highly consistent with observations globally even under extreme conditions (e.g., 1% for training, R 2 = 0.73), while the model without exhibits weaker performance (1% for training, R 2 = 0.51)., Competing Interests: The authors declare no competing financial interest., (© 2024 The Authors. Published by American Chemical Society.)

Introduction: Intimate partner violence (IPV) is a global health crisis with 30% of women over the age of 15 experiencing at least one event in their lifetime. Brain injury (BI) due to head impacts and/or strangulation is a common but understudied part of this experience. Previous research has shown BI from other injury mechanisms can disrupt neurovascular coupling (NVC). To gain further insight into whether similar changes occur in this population, we assessed NVC responses in women with a history of IPV-BI., Methods: NVC responses were measured for the middle and posterior cerebral arteries (MCA, PCA) using transcranial Doppler ultrasound while participants performed a complex visual search task. The lifetime history of previous exposure to IPV-BI was captured using the Brain Injury Severity Assessment (BISA) along with measures of post-traumatic stress disorder (PTSD), anxiety, depression, substance use, and demographic information. Initial analyses of NVC metrics were completed comparing participants who scored low vs. high on the BISA or did or did not experience non-fatal strangulation followed by a stepwise multiple regression to examine the impact of PTSD, anxiety, and depression on the relationship between the NVC metrics and IPV-BI., Results: Baseline and peak cerebral blood velocity were higher and the percentage increase was lower in the PCA in the low compared to the high BISA group whereas no differences between the groups were apparent in the MCA. In addition, those participants who had been strangled had a lower initial slope and area under the curve in the PCA than those who had not experienced strangulation. Finally, the stepwise multiple regression demonstrated the percentage increase in the PCA was significantly related to the BISA score and both depression and anxiety significantly contributed to different components of the NVC response., Conclusions: This preliminary study demonstrated that a lifetime history of IPV-BI leads to subtle but significant disruptions to NVC responses which are modulated by comorbid depression and anxiety. Future studies should examine cerebrovascular function at the acute and subacute stages after IPV episodes to shed additional light on this experience and its outcomes., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2024 Wallace, Smirl, Adhikari, Jones, Rieger, Rothlander and van Donkelaar.)

Contemporary biomechanical modeling of traumatic brain injury (TBI) focuses on either the global brain as an organ or a representative tiny section of a single axon. In addition, while it is common for a global brain model to employ real-world impacts as input, axonal injury models have largely been limited to inputs of either tension or compression with assumed peak strain and strain rate. These major gaps between global and microscale modeling preclude a systematic and mechanistic investigation of how tissue strain from impact leads to downstream axonal damage throughout the white matter. In this study, a unique subject-specific multimodality dataset from a male ice-hockey player sustaining a diagnosed concussion is used to establish an efficient and scalable computational pipeline. It is then employed to derive voxelized brain deformation, maximum principal strains and white matter fiber strains, and finally, to produce diverse fiber strain profiles of various shapes in temporal history necessary for the development and application of a deep learning axonal injury model in the future. The pipeline employs a structured, voxelized representation of brain deformation with adjustable spatial resolution independent of model mesh resolution. The method can be easily extended to other head impacts or individuals. The framework established in this work is critical for enabling large-scale (i.e., across the entire white matter region, head impacts, and individuals) and multiscale (i.e., from organ to cell length scales) modeling for the investigation of traumatic axonal injury (TAI) triggering mechanisms. Ultimately, these efforts could enhance the assessment of concussion risks and design of protective headgear. Therefore, this work contributes to improved strategies for concussion detection, mitigation, and prevention., Competing Interests: Declaration of competing interest None Declared., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Background: Ambient nitrogen dioxide ( NO 2 ) and fine particulate matter with aerodynamic diameter ≤ 2.5 μ m ( PM 2.5 ) threaten public health in the US, and systemic racism has led to modern-day disparities in the distribution and associated health impacts of these pollutants., Objectives: Many studies on environmental injustices related to ambient air pollution focus only on disparities in pollutant concentrations or provide only an assessment of pollution or health disparities at a snapshot in time. In this study, we compare injustices in NO 2 - and PM 2.5 -attributable health burdens, considering NO 2 -attributable health impacts across the entire US; document changing disparities in these health burdens over time (2010-2019); and evaluate how more stringent air quality standards would reduce disparities in health impacts associated with these pollutants., Methods: Through a health impact assessment, we quantified census tract-level variations in health outcomes attributable to NO 2 and PM 2.5 using health impact functions that combine demographic data from the US Census Bureau; two spatially resolved pollutant datasets, which fuse satellite data with physical and statistical models; and epidemiologically derived relative risk estimates and incidence rates from the Global Burden of Disease study., Results: Despite overall decreases in the public health damages associated with NO 2 and PM 2.5 , racial and ethnic relative disparities in NO 2 -attributable pediatric asthma and PM 2.5 -attributable premature mortality have widened in the US during the last decade. Racial relative disparities in PM 2.5 -attributable premature mortality and NO 2 -attributable pediatric asthma have increased by 16% and 19%, respectively, between 2010 and 2019. Similarly, ethnic relative disparities in PM 2.5 -attributable premature mortality have increased by 40% and NO 2 -attributable pediatric asthma by 10%., Discussion: Enacting and attaining more stringent air quality standards for both pollutants could preferentially benefit the most marginalized and minoritized communities by greatly reducing racial and ethnic relative disparities in pollution-attributable health burdens in the US. Our methods provide a semi-observational approach to track changes in disparities in air pollution and associated health burdens across the US. https://doi.org/10.1289/EHP11900.

Common genetic variation has been associated with multiple phenotypic features in Autism Spectrum Disorder (ASD). However, our knowledge of shared genetic factor structures contributing to this highly heterogeneous phenotypic spectrum is limited. Here, we developed and implemented a structural equation modelling framework to directly model genomic covariance across core and non-core ASD phenotypes, studying autistic individuals of European descent with a case-only design. We identified three independent genetic factors most strongly linked to language performance, behaviour and developmental motor delay, respectively, studying an autism community sample (N = 5331). The three-factorial structure was largely confirmed in independent ASD-simplex families (N = 1946), although we uncovered, in addition, simplex-specific genetic overlap between behaviour and language phenotypes. Multivariate models across cohorts revealed novel associations, including links between language and early mastering of self-feeding. Thus, the common genetic architecture in ASD is multi-dimensional with overarching genetic factors contributing, in combination with ascertainment-specific patterns, to phenotypic heterogeneity., (© 2024. The Author(s).)

Background: Many approaches to quantifying air pollution exposures have been developed. However, the impact of choice of approach on air pollution estimates and health-effects associations remains unclear., Objectives: Our objective is to compare particulate matter with aerodynamic diameter ≤ 2.5 μ m ( PM 2.5 ) concentrations and resulting health effects associations using multiple estimation approaches previously used in epidemiologic analyses., Methods: We assigned annual PM 2.5 exposure estimates from 1999 to 2004 derived from 11 different approaches to Women's Health Initiative Memory Study (WHIMS) participant addresses within the contiguous US. Approaches included geostatistical interpolation approaches, land-use regression or spatiotemporal models, satellite-derived approaches, air dispersion and chemical transport models, and hybrid models. We used descriptive statistics and plots to assess relative and absolute agreement among exposure estimates and examined the impact of approach on associations between PM 2.5 and death due to natural causes, cardiovascular disease (CVD) mortality, and incident CVD events, adjusting for individual-level covariates and climate-based region., Results: With a few exceptions, relative agreement of approach-specific PM 2.5 exposure estimates was high for PM 2.5 concentrations across the contiguous US. Agreement among approach-specific exposure estimates was stronger near PM 2.5 monitors, in certain regions of the country, and in 2004 vs. 1999. Collectively, our results suggest but do not quantify lower agreement at local spatial scales for PM 2.5 . There was no evidence of large differences in health effects associations with PM 2.5 among estimation approaches in analyses adjusted for climate region., Conclusions: Different estimation approaches produced similar spatial patterns of PM 2.5 concentrations across the contiguous US and in areas with dense monitoring data, and PM 2.5 -health effects associations were similar among estimation approaches. PM 2.5 estimates and PM 2.5 -health effects associations may differ more in samples drawn from smaller areas or areas without substantial monitoring data, or in analyses with finer adjustment for participant location. Our results can inform decisions about PM 2.5 estimation approach in epidemiologic studies, as investigators balance concerns about bias, efficiency, and resource allocation. Future work is needed to understand whether these conclusions also apply in the context of other air pollutants of interest. https://doi.org/10.1289/EHP12995.

Background: Fine particulate matter (PM 2.5 ) exposure is a known risk factor for numerous adverse health outcomes, with varying estimates of component-specific effects. Populations with compromised health conditions such as diabetes can be more sensitive to the health impacts of air pollution exposure. Recent trends in PM 2.5 in primarily American Indian- (AI-) populated areas examined in previous work declined more gradually compared to the declines observed in the rest of the US. To further investigate components contributing to these findings, we compared trends in concentrations of six PM 2.5 components in AI- vs. non-AI-populated counties over time (2000-2017) in the contiguous US., Methods: We implemented component-specific linear mixed models to estimate differences in annual county-level concentrations of sulfate, nitrate, ammonium, organic matter, black carbon, and mineral dust from well-validated surface PM 2.5 models in AI- vs. non-AI-populated counties, using a multi-criteria approach to classify counties as AI- or non-AI-populated. Models adjusted for population density and median household income. We included interaction terms with calendar year to estimate whether concentration differences in AI- vs. non-AI-populated counties varied over time., Results: Our final analysis included 3108 counties, with 199 (6.4%) classified as AI-populated. On average across the study period, adjusted concentrations of all six PM 2.5 components in AI-populated counties were significantly lower than in non-AI-populated counties. However, component-specific levels in AI- vs. non-AI-populated counties varied over time: sulfate and ammonium levels were significantly lower in AI- vs. non-AI-populated counties before 2011 but higher after 2011 and nitrate levels were consistently lower in AI-populated counties., Conclusions: This study indicates time trend differences of specific components by AI-populated county type. Notably, decreases in sulfate and ammonium may contribute to steeper declines in total PM 2.5 in non-AI vs. AI-populated counties. These findings provide potential directives for additional monitoring and regulations of key emissions sources impacting tribal lands., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Objective: Near-infrared spectroscopy (NIRS) is a noninvasive tool to monitor cerebral regional oxygen saturation. Impairment of microvascular circulation with subsequent cerebral hypoxia during delayed cerebral ischemia (DCI) is associated with poor functional outcome after subarachnoid hemorrhage (SAH). Therefore, NIRS could be useful to predict the risk for DCI and functional outcome. However, only limited data are available on NIRS regional cerebral tissue oxygen saturation (rSO 2 ) distribution in SAH. The aim of this study was to compare the distribution of NIRS rSO 2 values in patients with nontraumatic SAH with the occurrence of DCI and functional outcome at 2 months. In addition, the predictive value of NIRS rSO 2 was compared with the previously validated SAFIRE grade (derived from Size of the aneurysm, Age, FIsher grade, World Federation of Neurosurgical Societies after REsuscitation)., Methods: In this study, the rSO 2 distribution of patients with and without DCI after SAH was compared. The optimal cutoff points to predict DCI and outcome were assessed, and its predictive value was compared with the SAFIRE grade., Results: Of 41 patients, 12 developed DCI, and 9 had unfavorable outcome at 60 days. Prediction of DCI with NIRS had an area under the curve of 0.77 (95% confidence interval 0.62-0.92; P = 0.0028) with an optimal cutoff point of 65% (sensitivity 1.00; specificity 0.45). Prediction of favorable outcome with NIRS had an area under the curve of 0.86 (95% confidence interval 0.74-0.98; P = 0.0003) with an optimal cutoff point of 63% (sensitivity 1.00; specificity 0.63). Regression analysis showed that NIRS rSO 2 score is complementary to the SAFIRE grade., Conclusions: NIRS rSO 2 monitoring in patients with SAH may improve prediction of DCI and clinical outcome after SAH., (Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.)

Ambient fine particulate matter (PM 2.5 ) is the world's leading environmental health risk factor. Quantification is needed of regional contributions to changes in global PM 2.5 exposure. Here we interpret satellite-derived PM 2.5 estimates over 1998-2019 and find a reversal of previous growth in global PM 2.5 air pollution, which is quantitatively attributed to contributions from 13 regions. Global population-weighted (PW) PM 2.5 exposure, related to both pollution levels and population size, increased from 1998 (28.3 μg/m 3 ) to a peak in 2011 (38.9 μg/m 3 ) and decreased steadily afterwards (34.7 μg/m 3 in 2019). Post-2011 change was related to exposure reduction in China and slowed exposure growth in other regions (especially South Asia, the Middle East and Africa). The post-2011 exposure reduction contributes to stagnation of growth in global PM 2.5 -attributable mortality and increasing health benefits per µg/m 3 marginal reduction in exposure, implying increasing urgency and benefits of PM 2.5 mitigation with aging population and cleaner air., (© 2023. Springer Nature Limited.)

Current regenerative cartilage therapies are associated with several drawbacks such as dedifferentiation of chondrocytes during expansion and the formation of fibrocartilage. Optimized chondrocyte expansion and tissue formation could lead to better clinical results of these therapies. In this study, a novel chondrocyte suspension expansion protocol that includes the addition of porcine notochordal cell-derived matrix was used to self-assemble human chondrocytes from osteoarthritic (OA) and nondegenerate (ND) origin into cartilage organoids containing collagen type II and proteoglycans. Proliferation rate and viability were similar for OA and ND chondrocytes and organoids formed had a similar histologic appearance and gene expression profile. Organoids were then encapsulated in viscoelastic alginate hydrogels to form larger tissues. Chondrocytes on the outer bounds of the organoids produced a proteoglycan-rich matrix to bridge the space between organoids. In hydrogels containing ND organoids some collagen type I was observed between the organoids. Surrounding the bulk of organoids in the center of the gels, in both OA and ND gels a continuous tissue containing cells, proteoglycans and collagen type II had been produced. No difference was observed in sulphated glycosaminoglycan and hydroxyproline content between gels containing organoids from OA or ND origin after 28 days. It was concluded that OA chondrocytes, which can be harvested from leftover surgery tissue, perform similar to ND chondrocytes in terms of human cartilage organoid formation and matrix production in alginate gels. This opens possibilities for their potential to serve as a platform for cartilage regeneration but also as an in vitro model to study pathways, pathology, or drug development., (© 2023 The Authors. Journal of Orthopaedic Research® published by Wiley Periodicals LLC on behalf of Orthopaedic Research Society.)

Background: Autism Spectrum Disorder (ASD) risk is highly heritable, with potential additional non-genetic factors, such as prenatal exposure to ambient particulate matter with aerodynamic diameter < 2.5 µm (PM 2.5 ) and maternal immune activation (MIA) conditions. Because these exposures may share common biological effect pathways, we hypothesized that synergistic associations of prenatal air pollution and MIA-related conditions would increase ASD risk in children., Objectives: This study examined interactions between MIA-related conditions and prenatal PM 2.5 or major PM 2.5 components on ASD risk., Methods: In a population-based pregnancy cohort of children born between 2001 and 2014 in Southern California, 318,751 mother-child pairs were followed through electronic medical records (EMR); 4,559 children were diagnosed with ASD before age 5. Four broad categories of MIA-related conditions were classified, including infection, hypertension, maternal asthma, and autoimmune conditions. Average exposures to PM 2.5 and four PM 2.5 components, black carbon (BC), organic matter (OM), nitrate (NO 3 - ), and sulfate (SO 4 2- ), were estimated at maternal residential addresses during pregnancy. We estimated the ASD risk associated with MIA-related conditions, air pollution, and their interactions, using Cox regression models to adjust for covariates., Results: ASD risk was associated with MIA-related conditions [infection (hazard ratio 1.11; 95% confidence interval 1.05-1.18), hypertension (1.30; 1.19-1.42), maternal asthma (1.22; 1.08-1.38), autoimmune disease (1.19; 1.09-1.30)], with higher pregnancy PM 2.5 [1.07; 1.03-1.12 per interquartile (3.73 μg/m 3 ) increase] and with all four PM 2.5 components. However, there were no interactions of each category of MIA-related conditions with PM 2.5 or its components on either multiplicative or additive scales., Conclusions: MIA-related conditions and pregnancy PM 2.5 were independently associations with ASD risk. There were no statistically significant interactions of MIA conditions and prenatal PM 2.5 exposure with ASD risk., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Recent studies have identified inequality in the distribution of air pollution attributable health impacts, but to our knowledge this has not been examined in Canadian cities. We evaluated the extent and sources of inequality in air pollution attributable mortality at the census tract (CT) level in seven of Canada's largest cities. We first regressed fine particulate matter (PM 2.5 ) and nitrogen dioxide (NO 2 ) attributable mortality against the neighborhood (CT) level prevalence of age 65 and older, low income, low educational attainment, and identification as an Indigenous (First Nations, Métis, Inuit) or Black person, accounting for spatial autocorrelation. We next examined the distribution of baseline mortality rates, PM 2.5 and NO 2 concentrations, and attributable mortality by neighborhood (CT) level prevalence of these characteristics, calculating the concentration index, Atkinson index, and Gini coefficient. Finally, we conducted a counterfactual analysis of the impact of reducing baseline mortality rates and air pollution concentrations on inequality in air pollution attributable mortality. Regression results indicated that CTs with a higher prevalence of low income and Indigenous identity had significantly higher air pollution attributable mortality. Concentration index, Atkinson index, and Gini coefficient values revealed different degrees of inequality among the cities. Counterfactual analysis indicated that inequality in air pollution attributable mortality tended to be driven more by baseline mortality inequalities than exposure inequalities. Reducing inequality in air pollution attributable mortality requires reducing disparities in both baseline mortality and air pollution exposure., Competing Interests: The authors declare no conflicts of interest relevant to this study., (© 2023 His Majesty the King in Right of Canada and The Authors. Reproduced with the permission of the Minister of Health Canada.)

Frictional properties of cartilage resurfacing implants should be sufficiently low to limit damaging of the opposing cartilage during articulation. The present study determines if native lubricious molecule proteoglycan 4 (PRG4) can adsorb onto a layer-by-layer bioinspired coating composed of poly-l-lysine (PLL) and dopamine modified hyaluronic acid (HADN) and thereby can reduce the friction between implant and articular cartilage. An ELISA was developed to quantify the amount of immobilized human recombinant (rh)PRG4 after exposure to the PLL-HADN coating. The effect on lubrication was evaluated by comparing the coefficient of friction (CoF) of bare polycaprolactone (PCL) disks to that of PLL-HADN coated PCL disks while articulated against cartilage using a ring-on-disk geometry and a lubricant solution consisting of native synovial fluid components including rhPRG4. The PLL-HADN coating effectively immobilized rhPRG4. The surface roughness of PCL disks significantly increased while the water contact angle significantly decreased after application of the coating. The average CoF measured during the first minute of bare PCL against cartilage exceeded twice the CoF of the PLL-HADN coated PCL against cartilage. After 60 min, the CoF reached equilibrium values which were still significantly higher for bare PCL compared to coated PCL. The present study demonstrated that PCL can effectively be coated with PLL-HADN. Additionally, this coating reduces the friction between PCL and cartilage when a PRG4-rich lubricant is used, similar to the lubricating surface of native cartilage. This makes PLL-HADN coating a promising application to improve the clinical success of PCL-based cartilage resurfacing implants., (© 2023 The Authors. Journal of Biomedical Materials Research Part B: Applied Biomaterials published by Wiley Periodicals LLC.)

Fine particulate matter (PM 2.5 ) exposure is a leading mortality risk factor in India and the surrounding region of South Asia. This study evaluates the contribution of emission sectors and fuels to PM 2.5 mass for 29 states in India and 6 surrounding countries (Pakistan, Bangladesh, Nepal, Bhutan, Sri Lanka, and Myanmar) by combining source-specific emission estimates, stretched grid simulations from a chemical transport model, high resolution hybrid PM 2.5 , and disease-specific mortality estimates. We find that 1.02 (95% Confidence Interval (CI): 0.78-1.26) million deaths in South Asia attributable to ambient PM 2.5 in 2019 were primarily from three leading sectors: residential combustion (28%), industry (15%), and power generation (12%). Solid biofuel is the leading combustible fuel contributing to the PM 2.5 -attributable mortality (31%), followed by coal (17%), and oil and gas (14%). State-level analyses reveal higher residential combustion contributions (35%-39%) in states (Delhi, Uttar-Pradesh, Haryana) with high ambient PM 2.5 (>95 μg/m 3 ). The combined mortality burden associated with residential combustion (ambient) and household air pollution (HAP) in India is 0.72 million (95% CI:0.54-0.89) (68% attributable to HAP, 32% attributable to residential combustion). Our results illustrate the potential to reduce PM 2.5 mass and improve population health by reducing emissions from traditional energy sources across multiple sectors in South Asia.

A HydroSpacer implant, that is, a swelling hydrogel confined by a spacer fabric, was developed to repair focal cartilage defects and to prevent progression into osteoarthritis. The present study evaluated the effect of implant placement height in an osteochondral (OC) plug on wear of the opposing and adjacent cartilage. Three-dimensional warp-knitted spacer fabrics, polycaprolactone with poly(4-hydroxybutyrate) pile yarns, were filled with a hyaluronic acid methacrylate and chondroitin sulfate methacrylate hydrogel. After polymerization of the hydrogel, these HydroSpacers were implanted in OC defects (ø 6 mm) created in bovine OC plugs (ø 10 mm) and allowed to swell to equilibrium. A custom-made pin-on-plate wear apparatus was used to apply simultaneous compression and sliding against bovine cartilage. Cartilage damage, visualized with Indian ink, was only seen for the group in which the HydroSpacer was placed flush with the surrounding cartilage. A significant increase on average surface roughness of the sliding path compared to the adjacent cartilage confirmed surface damage for this group. When the implants were recessed (with and without extra hydrogel layer on top of the implant), this damage was not observed, but the cartilage surrounding the implants was compressed (without damage) indicating substantial load sharing with the implant. Furthermore, it was shown that all defects treated with a HydroSpacer implant resulted in shear forces comparable to intact cartilage. Clinical significance: The present study suggests that placing a HydroSpacer implant recessed into the surrounding cartilage would decrease wear of the opposing cartilage. Altogether, this study supports the development of textile-constraining hydrogels for cartilage replacement., (© 2022 The Authors. Journal of Orthopaedic Research® published by Wiley Periodicals LLC on behalf of Orthopaedic Research Society.)

Low haemoglobin (Hb) concentrations and anaemia in children have adverse effects on development and functioning, some of which may have consequences in later life. Exposure to ambient air pollution is reported to be associated with anaemia, but there is little evidence specific to low- and middle-income countries (LMICs), where childhood anaemia prevalence is greatest. We aimed to determine if long-term ambient fine particulate matter (≤2.5 μm in aerodynamic diameter [PM 2.5 ]) exposure was associated with Hb levels and the prevalence of anaemia in children aged <5 years living in 36 LMICs. We used Demographic and Health Survey data, collected between 2010 and 2019, which included blood Hb measurements. Satellite-derived estimates of annual average PM 2.5 was the main exposure variable, which was linked to children's area of residence. Anaemia was defined according to standard World Health Organization guidelines (Hb < 11 g/dL). The association of PM 2.5 with Hb levels and anaemia prevalence was examined using multivariable linear and logistic regression models, respectively. We examined whether the effects of ambient PM 2.5 were modified by a child's sex and age, household wealth index, and urban/rural place of residence. Models were adjusted for relevant covariates, including other outdoor pollutants and household cooking fuel. The study included 154,443 children, of which 89,904 (58.2%) were anaemic. The country-level prevalence of anaemia ranged from 15.8% to 87.9%. Mean PM 2.5 exposure was 33.0 (±21.6) μg/m 3 . The adjusted model showed that a 10 μg/m 3 increase in annual PM 2.5 concentration was associated with greater odds of anaemia (OR = 1.098 95% CI: 1.087, 1.109). The same increase in PM 2.5 was associated with a decrease in average Hb levels of 0.075 g/dL (95% CI: 0.081, 0.068). There was evidence of effect modification by household wealth index and place of residence, with greater adverse effects in children from lower wealth quintiles and children in rural areas. Exposure to annual PM 2.5 was cross-sectionally associated with decreased blood Hb levels, and greater risk of anaemia, in children aged <5 years living in 36 LMICs., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Aerosol therapies with vented facemasks are considered a risk for nosocomial transmission of viruses such as severe acute respiratory syndrome coronavirus 2. The transmission risk can be decreased by minimizing aerosol leakage and filtering the exhaled air. Objective: In this study, we determined which closed facemask designs show the least leakage. Methods: Smoke leakage was quantified during in- and exhalation in a closed system with expiration filter for three infant, six child, and six adult facemasks (three times each mask), using age-appropriate anatomical face models and breathing patterns. To assess leakage, smoke release was recorded and cumulative average pixel intensity (cAPI) was calculated. Results: In the adult group, aircushion edges resulted in less leakage than soft edges (cAPI: 407 ± 250 vs. 774 ± 152) ( p  = 0.004). The Intersurgical ® Economy 5 mask (cAPI: 146 ± 87) also released less smoke than the Intersurgical ® Clearlite 5 (cAPI: 748 ± 68) mask with the same size, but different geometry and edge type ( p -value <0.05). Moreover, mask size had an effect, as there was a difference between Intersurgical ® Economy 4 (cAPI: 708 ± 346) and 5, which have the same geometry but a different size ( p -value <0.05). Finally, repositioning masks increased the standard deviations. Mask leakage was not dependent on breathing patterns within the child group. Conclusions: Mask leakage can be minimized by using a closed system with a well-fitting mask that is appropriately positioned. To decrease leakage, and therewith minimize potential viral transmission, selecting a well-fitting mask with an aircushion edge is to be recommended.

There is increasing evidence linking long-term fine particulate matter (PM 2.5 ) exposure to negative health effects. However, the relative influence of each component of PM 2.5 on health risk is poorly understood. In a cohort study in the contiguous United States between 2000 and 2017, we examined the effect of long-term exposure to PM 2.5 main components and all-cause mortality in older adults who had to be at least 65 years old and enrolled in Medicare. We estimated the yearly mean concentrations of six key PM 2.5 compounds, including black carbon (BC), organic matter (OM), soil dust (DUST), nitrate (NO 3 - ), sulfate (SO 4 2- ), and ammonium (NH 4 + ), using two independently sourced well-validated prediction models. We applied Cox proportional hazard models to evaluate the hazard ratios for mortality and penalized splines for assessing potential nonlinear concentration-response associations. Results suggested that increased exposure to PM 2.5 mass and its six main constituents were significantly linked to elevated all-cause mortality. All components showed linear concentration-response relationships in the low exposure concentration ranges. Our research indicates that long-term exposure to PM 2.5 mass and its essential compounds are strongly connected to increased mortality risk. Reductions of fossil fuel burning may yield significant air quality and public health benefit.

High-resolution simulations are essential to resolve fine-scale air pollution patterns due to localized emissions, nonlinear chemical feedbacks, and complex meteorology. However, high-resolution global simulations of air quality remain rare, especially of the Global South. Here, we exploit recent developments to the GEOS-Chem model in its high-performance implementation to conduct 1-year simulations in 2015 at cubed-sphere C360 (∼25 km) and C48 (∼200 km) resolutions. We investigate the resolution dependence of population exposure and sectoral contributions to surface fine particulate matter (PM 2.5 ) and nitrogen dioxide (NO 2 ), focusing on understudied regions. Our results indicate pronounced spatial heterogeneity at high resolution (C360) with large global population-weighted normalized root-mean-square difference (PW-NRMSD) across resolutions for primary (62-126%) and secondary (26-35%) PM 2.5 species. Developing regions are more sensitive to spatial resolution resulting from sparse pollution hotspots, with PW-NRMSD for PM 2.5 in the Global South (33%), 1.3 times higher than globally. The PW-NRMSD for PM 2.5 for discrete southern cities (49%) is substantially higher than for more clustered northern cities (28%). We find that the relative order of sectoral contributions to population exposure depends on simulation resolution, with implications for location-specific air pollution control strategies.

Background: Numerous epidemiological studies have documented the adverse health impact of long-term exposure to fine particulate matter [particulate matter ≤ 2.5 μ m in aerodynamic diameter ( PM 2.5 )] on mortality even at relatively low levels. However, methodological challenges remain to consider potential regulatory intervention's complexity and provide actionable evidence on the predicted benefits of interventions. We propose the parametric g-computation as an alternative analytical approach to such challenges., Method: We applied the parametric g-computation to estimate the cumulative risks of nonaccidental death under different hypothetical intervention strategies targeting long-term exposure to PM 2.5 in the Canadian Community Health Survey cohort from 2005 to 2015. On both relative and absolute scales, we explored the benefits of hypothetical intervention strategies compared with the natural course that a ) set the simulated exposure value at each follow-up year to a threshold value if exposure was above the threshold ( 8.8   μ g / m 3 , 7.04   μ g / m 3 , 5   μ g / m 3 , and 4   μ g / m 3 ), and b ) reduced the simulated exposure value by a percentage (5% and 10%) at each follow-up year. We used the 3-y average PM 2.5 concentration with 1-y lag at the postal code of respondents' annual mailing addresses as their long-term exposure to PM 2.5 . We considered baseline and time-varying confounders, including demographics, behavior characteristics, income level, and neighborhood socioeconomic status. We also included the R syntax for reproducibility and replication., Results: All hypothetical intervention strategies explored led to lower 11-y cumulative mortality risks than the estimated value under the natural course without intervention, with the smallest reduction of 0.20 per 1,000 participants (95% CI: 0.06, 0.34) under the threshold of 8.8   μ g / m 3 , and the largest reduction of 3.40 per 1,000 participants (95% CI: - 0.23 , 7.03) under the relative reduction of 10% per interval. The reductions in cumulative risk, or numbers of deaths that would have been prevented if the intervention was employed instead of maintaining the status quo, increased over time but flattened toward the end of the follow-up period. Estimates among those ≥ 65 years of age were greater with a similar pattern. Our estimates were robust to different model specifications., Discussion: We found evidence that any intervention further reducing the long-term exposure to PM 2.5 would reduce the cumulative mortality risk, with greater benefits in the older population, even in a population already exposed to low levels of ambient PM 2.5 . The parametric g-computation used in this study provides flexibilities in simulating real-world interventions, accommodates time-varying exposure and confounders, and estimates adjusted survival curves with clearer interpretation and more information than a single hazard ratio, making it a valuable analytical alternative in air pollution epidemiological research. https://doi.org/10.1289/EHP11095.

Introduction: This systematic review aims to provide an overview of predictors for failure of treatment of displaced femoral neck fracture (dFNF) with internal fixation and quantify their risk of fixation failure in a meta-analysis., Patients and Methods: PubMed, Embase, Web of Science, Cochrane Library, and EMCare were searched for original studies published from January 2000, including adult patients with an internally fixated dFNF, that reported data on predictors for fixation failure defined as revision surgery due to non-union, avascular femoral head necrosis or cut-out of implant. RevMan version 5 software was used to pool univariable Odds Ratio's (OR) for predictors of fixation failure by means of a random effects model., Results: This review included 16 articles (15 articles cohort studies and one randomised trial). Twenty-four predictors for fixation failure were identified and analysed, 16 of which were evaluated in just one study. Data of 7 predictors were pooled in a meta-analysis. Female sex (OR 1.78, 95% confidence interval [CI] 1.26-2.52), smoking (OR 3.64, 95% CI 1.68-7.91), age >50 years (OR 3.64, 95% CI 1.68-7.91), inadequate fracture reduction (OR 2.28, 95% CI 1.62-3.22), fixation with cannulated screws (CS) or pins compared to fixed angle devices (OR 2.16, 95% CI 1.03-4.54) were identified as significant predictors for fixation failure., Conclusion: This study can help surgeons to choose the preferred treatment for patients with a dFNF and substantiate future algorithms and guidelines for treatment of FNF., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Exposure to ambient air pollution may affect cognitive functioning and development in children. Unfortunately, there is little evidence available for low- and middle-income countries (LMICs), where air pollution levels are highest. We analysed the association between exposure to ambient fine particulate matter (≤2.5 μm [PM 2.5 ]) and cognitive development indicators in a cross-sectional analysis of children (aged 3-4 years) in 12 LMICs. We linked Demographic and Health Survey data, conducted between 2011 and 2018, with global estimates of PM 2.5 mass concentrations to examine annual average exposure to PM 2.5 and cognitive development (literacy-numeracy and learning domains) in children. Cognitive development was assessed using the United Nations Children's Fund's early child development indicators administered to each child's mother. We used multivariable logistic regression models, adjusted for individual- and area-level covariates, and multi-pollutant models (including nitrogen dioxide and surface-level ozone). We assessed if sex and urban/rural status modified the association of PM 2.5 with the outcome. We included 57,647 children, of whom, 9613 (13.3%) had indicators of cognitive delay. In the adjusted model, a 5 μg/m 3 increase in annual all composition PM 2.5 was associated with greater odds of cognitive delay (OR = 1.17; 95% CI: 1.13, 1.22). A 5 μg/m 3 increase in anthropogenic PM 2.5 was also associated with greater odds of cognitive delay (OR = 1.05; 95% CI: 1.00, 1.10). These results were robust to several sensitivity analyses, including multi-pollutant models. Interaction terms showed that urban-dwelling children had greater odds of cognitive delay than rural-dwelling children, while there was no significant difference by sex. Our findings suggest that annual average exposure to PM 2.5 in young children was associated with adverse effects on cognitive development, which may have long-term consequences for educational attainment and health., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Studies examining long-term effects of ambient air pollution exposure, measured as annual averages, on pulmonary tuberculosis (TB) incidence are scarce, particularly in endemic, rural settings. We performed a small-area study in Ningxia Hui Autonomous Region (NHAR), a high TB-burden area in rural China, using township-level (n = 358 non-overlapping townships) annual TB notification data (2005-2017). We aimed to determine if annual average concentrations of ambient air pollution (particulate matter <2·5 μm [PM 2·5 ], nitrogen dioxide [NO 2 ] ozone [O 3 ]) were associated with TB notification rates (as a proxy for incidence). Air pollution effects on TB notification rates at township-level were estimated as incidence rate ratios (IRR), fitted using a generalised estimating equation (GEE) adjusted for covariates (age, sex, occupation, education, ethnicity, remoteness [urban or rural], household crowding and solid fuel use). A total of 38,942 TB notifications were reported in NHAR between 2005 and 2017. The mean annual TB notification rate was 67 (standard deviation [SD]; 7) per 100,000 people. Median concentrations of PM 2·5 , NO 2 , and O 3 were 42 μg/m 3 (interquartile range [IQR]; 38-48 μg/m 3 ), 15 ppb (IQR; 12-16 ppb), and 56 ppb (IQR; 56-57 ppb), respectively. In single pollutant models, adjusted for covariates, an interquartile range (IQR) increase (10 μg/m 3 ) in PM 2·5 was significantly associated with higher TB notification rates (IRR: 1∙35; 95% CI: 1·25-1·48). Comparable effects on notifications of TB were observed for increases in NO 2 exposure (IRR: 1·20 per IQR (4 ppb) increase; 95% CI: 1·08-1·31). Ground-level ozone was not associated with TB notification rate in any models. The observed effects were consistent over time, in multi-pollutant models, and appeared robust to additional adjustment for indicators of household crowding, solid fuel use and remoteness. More rigorous study designs are needed to understand if improving air quality has population-level benefits on TB disease incidence in endemic settings., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

This retrospective cohort study examined associations of autism spectrum disorder (ASD) with prenatal exposure to major fine particulate matter (PM 2.5 ) components estimated using two independent exposure models. The cohort included 318 750 mother-child pairs with singleton deliveries in Kaiser Permanente Southern California hospitals from 2001 to 2014 and followed until age five. ASD cases during follow-up ( N = 4559) were identified by ICD codes. Prenatal exposures to PM 2.5 , elemental (EC) and black carbon (BC), organic matter (OM), nitrate (NO 3 - ), and sulfate (SO 4 2- ) were constructed using (i) a source-oriented chemical transport model and (ii) a hybrid model. Exposures were assigned to each maternal address during the entire pregnancy, first, second, and third trimester. In single-pollutant models, ASD was associated with pregnancy-average PM 2.5 , EC/BC, OM, and SO 4 2- exposures from both exposure models, after adjustment for covariates. The direction of effect estimates was consistent for EC/BC and OM and least consistent for NO 3 - . EC/BC, OM, and SO 4 2- were generally robust to adjustment for other components and for PM 2.5 . EC/BC and OM effect estimates were generally larger and more consistent in the first and second trimester and SO 4 2- in the third trimester. Future PM 2.5 composition health effect studies might consider using multiple exposure models and a weight of evidence approach when interpreting effect estimates.

Growing evidence suggests that fine particulate matter (PM 2.5 ) likely increases the risks of dementia, yet little is known about the relative contributions of different constituents. Here, we conducted a nationwide population-based cohort study (2000 to 2017) by integrating the Medicare Chronic Conditions Warehouse database and two independently sourced datasets of high-resolution PM 2.5 major chemical composition, including black carbon (BC), organic matter (OM), nitrate (NO 3 - ), sulfate (SO 4 2- ), ammonium (NH 4 + ), and soil dust (DUST). To investigate the impact of long-term exposure to PM 2.5 constituents on incident all-cause dementia and Alzheimer's disease (AD), hazard ratios for dementia and AD were estimated using Cox proportional hazards models, and penalized splines were used to evaluate potential nonlinear concentration-response (C-R) relationships. Results using two exposure datasets consistently indicated higher rates of incident dementia and AD for an increased exposure to PM 2.5 and its major constituents. An interquartile range increase in PM 2.5 mass was associated with a 6 to 7% increase in dementia incidence and a 9% increase in AD incidence. For different PM 2.5 constituents, associations remained significant for BC, OM, SO 4 2- , and NH 4 + for both end points (even after adjustments of other constituents), among which BC and SO 4 2- showed the strongest associations. All constituents had largely linear C-R relationships in the low exposure range, but most tailed off at higher exposure concentrations. Our findings suggest that long-term exposure to PM 2.5 is significantly associated with higher rates of incident dementia and AD and that SO 4 2- , BC, and OM related to traffic and fossil fuel combustion might drive the observed associations.

Cartilage defects occur frequently and can lead to osteoarthritis. Hydrogels are a promising regenerative strategy for treating such defects, using their ability of mimicking the native extracellular matrix. However, commonly used hydrogels for tissue regeneration are too soft to resist load-bearing in the joint. To overcome this, an implant is being developed in which the mechanical loadbearing function originates from the osmotic pressure generated by the swelling potential of a charged hydrogel, which is restricted from swelling by a textile spacer fabric. This study aims to quantify the relationship between the swelling potential of the hydrogel and the compressive stiffness of the implant., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Women who experience physical intimate partner violence (IPV) are at high risk of suffering a brain injury (BI) due to head impacts and/or strangulation. Currently, most staff at women's shelters tend not to be aware of IPV-caused BIs. The objective of this study was to address this by developing a new online module within the Concussion Awareness Training Tool (cattonline.com) specifically focused on IPV-caused BI, and measuring its effectiveness in increasing BI awareness and knowledge among staff members at women's shelters. A mixed-methods approach was used which included (i) a survey to measure participant knowledge before and after completing the module; (ii) a 1-on-1 interview 6 months post-training to better understand participants' perceptions of what effect the training had on how they worked with women in their job; and (iii) an evaluation of the content of the module using behavior change techniques. About 81 participants recruited from staff at women's shelters completed the pre/post survey. The average BI knowledge score increased significantly from the pre-survey ( M  = 8.12/12, SD = 1.05) to the post-survey ( M  = 9.72/12, SD = 1.62), t (80) = 9.12, P  < .001, d  = 1.01). Analysis of the interviews with 9 participants highlighted 3 main themes arising from the module: knowledge, mindfulness, and advocacy. All participants felt their knowledge of IPV-caused BIs had increased and said they would recommend the training to their co-workers. Analysis of the module content revealed the most frequent behavior change techniques were related to instructions on how to perform screening and accommodation for IPV-caused BI. The results showed the module was effective in increasing knowledge of IPV-caused BIs amongst women's shelter staff as well as improving how they advocate for, and are mindful of, their clients with BIs. This online training may help improve the care women with IPV-caused BIs receive, and ultimately improve their quality of life.

In native articular cartilage, chondrocytes (Chy) are completely capsulated by a pericellular matrix (PCM), together called the chondron (Chn). Due to its unique properties (w.r.t. territorial matrix) and importance in mechanotransduction, the PCM and Chn may be important in regenerative strategies. The current gold standard for the isolation of Chns from cartilage dates from 1997. Although previous research already showed the low cell yield and the heterogeneity of the isolated populations, their compositions and properties have never been thoroughly characterized. This study aimed to compare enzymatic isolation methods for Chy and Chns and characterizes the isolation efficiency and quality of the PCM. Bovine articular cartilage was digested according to the 5-h (5H) gold standard Chn isolation method (0.3% dispase +0.2% collagenase II), an overnight (ON) Chn isolation (0.15% dispase +0.1% collagenase II), and an ON Chy isolation (0.15% collagenase II +0.01% hyaluronidase). Type VI collagen staining, fluorescence-activated cell sorting (FACS) analysis, specific cell sorting, and immunohistochemistry were performed using a type VI collagen staining, to study their isolation efficiency and quality of the PCM. These analyses showed a heterogeneous mixture of Chy and Chns for all three methods. Although the 5H Chn isolation resulted in the highest percentage of Chns, the cell yield was significantly lower compared to the other isolation methods. FACS, based on the type VI collagen staining, successfully sorted the three identified cell populations. To maximize Chn yield and homogeneity, the ON Chn enzymatic digestion method should be combined with type VI collagen staining and specific cell sorting. Impact statement Since chondrocytes are highly dependent on their microenvironment for maintaining phenotypic stability, it is hypothesized that using chondrons results in superior outcomes in cartilage tissue engineering. This study reveals the constitution of cell populations obtained after enzymatic digestion of articular cartilage tissue and presents an alternative method to obtain a homogeneous population of chondrons. These data can improve the impact of studies investigating the effect of the pericellular matrix on neocartilage formation.

Emissions of fine particulate matter (PM 2.5 ) from human activities have been linked to substantial disease burdens, but evidence regarding how reducing PM 2.5 at its sources would improve public health is sparse. We followed a population-based cohort of 2.7 million adults across Canada from 2007 through 2016. For each participant, we estimated annual mean concentrations of PM 2.5 and the fractional contributions to PM 2.5 from the five leading anthropogenic sources at their residential address using satellite observations in combination with a global atmospheric chemistry transport model. For each source, we estimated the causal effects of six hypothetical interventions on 10-y nonaccidental mortality risk using the parametric g-formula, a structural causal model. We conducted stratified analyses by age, sex, and income. This cohort would have experienced tangible health gains had contributions to PM 2.5 from any of the five sources been reduced. Compared with no intervention, a 10% annual reduction in PM 2.5 contributions from transportation and power generation, Canada's largest and fifth-largest anthropogenic sources, would have prevented approximately 175 (95%CI: 123-226) and 90 (95%CI: 63-117) deaths per million by 2016, respectively. A more intensive 50% reduction per year in PM 2.5 contributions from the two sources would have averted 360 and 185 deaths per million, respectively, by 2016. The potential health benefits were greater among men, older adults, and low-income earners. In Canada, where PM 2.5 levels are among the lowest worldwide, reducing PM 2.5 contributions from anthropogenic sources by as little as 10% annually would yield meaningful health gains.