High Exposure Research Articles

Do they really return to early? Investigating the causal effect of rehab time on injury risk after return to play in elite football

In elite football, injury risk is considerable. Consequently, optimal rehabilitation and an adequate time point of return-to-play (RTP) are crucial. The elevated injury risk in the weeks after RTP (e.g. Orchard & Best, 2002; Wangensteen et al., 2016) and the time course of biological healing processes (Orchard & Best, 2002) nourished the speculation that players generally return to early. While the previously reported negative association between rehab time and injury risk after RTP (e.g. Beischer et al., 2020; Della Villa et al., 2021; Orchard & Best, 2002) points in the same direction, the truism “Correlation does not imply causation.” must be considered. To the best of our knowledge, the causal effect of rehab time on injury risk has not been investigated so far. This work aims to contribute towards closing this gap in knowledge. Specifically, to scrutinize if a reduction in injury risk may be expected when RTP is delayed. Previous time-loss injuries and match exposures of players currently playing in the European top leagues (Germany, Austria, France, Spain, Italy, Netherlands, United Kingdom) were collected from public sources and episodes (index injury-RTP-subsequent injury) constructed. Data analysis was conducted in R. Considering the time dependence of the excess injury risk after RTP, we analyzed injury occurrence after RTP within a fixed time frame (28 days). A robust scaling approach was used for making rehab time comparable between index injury diagnoses. Exposure within the 28-day period was adjusted for eventual time loss due to subsequent injury. The association between rehab time and injury was analyzed using logistic regression. Odds ratios (OR) were calculated from regression coefficients and adjusted for baseline probability to avoid overestimation of relative risk (RR). Two approaches were used to delineate a potential causal effect: (a) sensitivity analysis for the putative confounder (using Cornfield’s inequality) and (b) path analysis which due to the simple causal diagram could be implemented by including exposure in the logistic regression model. Eight thousand six hundred and forty-four episodes could be included among which 1,245 (14 %) had a subsequent injury within 28 days. There was a highly significant negative association between scaled rehab time and injury risk (RR 0,896), which was more pronounced for recurrences (RR 0,815). Cornfield’s inequality indicates that exposure would have to be lower by at least ~10% for every interquartile range of rehab time of the respective index injury to account for the observed association. While this is substantial, early return is in fact closely associated with higher exposure and this association accounts entirely for the observed association between rehab time and injury risk (Figure 1). Note that Figure 1 also shows that high exposures are observed exclusively after an early return. We conclude that the negative association between rehab time and injury risk is largely accounted for by higher exposures after early return. However, following from the limitations associated with predicting outside the range of previously observed values, the virtual absence of high exposures after long rehab (for the respective diagnosis) impedes on predicting the effect of prolonging rehab time.

Concentration-QTc analysis of soticlestat in healthy adults: An alternative to a thorough QT study.

This study aimed to examine the cardiac and overall safety and pharmacokinetic (PK) profiles of soticlestat (TAK-935), an oral, first-in-class selective cholesterol 24-hydroxylase inhibitor. Data came from a randomised, phase 1 study of soticlestat in 33 healthy Japanese adults (NCT04461483); 24 adults in Part 1 (single-dose soticlestat 200-1200 mg or placebo) and 9 in Part 2 (soticlestat 100-300 mg twice daily or placebo for 21 days). PK sample collection was paired with 12-lead electrocardiogram data from continuous Holter recordings. The concentration-QTc relationship was analysed using a linear mixed-effects model. QTc prolongation safety margins were determined for two scenarios of calculated high clinical exposures: scenario 1 (NCT05064449) involved coadministration of single-dose soticlestat 300 mg with itraconazole or mefenamic acid and scenario 2 (NCT05098054) involved single-dose soticlestat 300 mg administration in participants with mild/moderate hepatic impairment (implementing a 3-fold dose reduction for moderate severity). Based on concentration-QTc analysis, placebo-corrected change-from-baseline QT values (90% confidence intervals), corrected for heart rate (Fridericia's method), were 0.94 ms (-2.35, 4.23) for soticlestat and 0.63 ms (-3.15, 4.41) for its N-oxide metabolite plasma concentrations at therapeutic doses (soticlestat 300 mg twice daily); safety margins were >2-fold for scenarios of calculated high clinical exposures. No (Part 1) and five (83.3%; Part 2) participants experienced treatment-emergent adverse events (all mild). There was no evidence for QT prolongation with soticlestat at therapeutic doses or in two scenarios of high clinical exposures, which resulted in regulatory agencies waiving requirements of a thorough QT study. Safety/PK findings aligned with previous soticlestat clinical studies.

A cross-sectional study on occupational hygiene in biowaste plants.

Recycling demands are increasing and new biowaste plants are established. The aim of this study is to obtain knowledge about occupational hygiene in biowaste pretreatment plants. At 6 plants, bioaerosol exposure, hand hygiene, and bioaerosol concentrations in work areas were investigated repeatedly. The total inflammatory potential (TIP) of exposures was measured using the human HL-60 cell line. Exposure to airborne bacteria, bacteria able to grow anaerobic, fungi(37°C), endotoxin, and TIP differed between plants and was lowest in a plant transporting waste in closed pipes compared to plants where waste was delivered on the receiving hall floor. Conversely, high exposures were measured in a plant that also processes compost. All microbial components had an impact on TIP of workers' exposure with main effects of fungi and endotoxin. Seasonality was found for several exposures and TIP, and they were lowest in the winter. Concentrations of bacteria and fungi on workers' hands at the end of the workday were 15 times higher for production than for nonproduction workers. In work areas, the concentrations of airborne fungi were highest in the waste-receiving area. Bacteria (3.2 µm) and anaerobic bacteria (4.0 µm) were present as larger airborne particles than fungi (2.8 µm), and bacteria were largest in the waste-receiving area. The microbial community compositions of exposures and work areas differed between plants and work areas. In conclusion, measures to reduce exposure should focus on the waste-receiving area and on the production workers. Differences in exposures and community compositions were found between seasons, work areas, work groups, and plants.

Discovery of a Potent, Orally Active, and Long-Lasting P2X7 Receptor Antagonist as a Preclinical Candidate for Delaying the Progression of Chronic Kidney Disease.

Chronic kidney disease (CKD) is a condition characterized by functional deterioration with sustained inflammation and progressive fibrosis of the kidneys affecting over 800 million people worldwide. The P2X7 receptor (P2X7R) plays a key role in CKD progression. Our previous P2X7R antagonists demonstrated good efficacy for treating kidney injury but were limited by low oral exposure and short half-life, restricting their application. This study reports the optimization of P2X7R antagonists for better oral pharmacokinetics. The candidate compound 13a with the respective IC50 of 34.86 and 25.28 nM against human and murine P2X7R, administered orally at 10 mg/kg in mice, exhibits a remarkably long half-life of 161.64 h, with a high exposure of 1,163,980.55 μg·h/L. Oral administration of 13a (0.3 or 1.0 mg/kg, twice weekly) significantly reduced renal injury and fibrosis in unilateral ureteral obstruction and adenine diet-induced mice models, highlighting its potential for delaying the progression of CKD.

Pharmacokinetics and pharmacodynamics of the factor XIa-inhibiting antibody osocimab in healthy male East Asian volunteers: Results from two phase 1 studies.

The pharmacokinetics, pharmacodynamics, immunogenicity, and safety of osocimab single doses in healthy Chinese and Japanese volunteers over 149 days were evaluated. Two phase 1 single-blinded, placebo-controlled studies with 27 Japanese and 50 Chinese participants were conducted. Osocimab was investigated with IV doses of 0.3, 1.25, and 2.5 mg/kg (Chinese study) and 0.3, 1.25, and 5.0 mg/kg (Japanese study), as well as SC doses of 3.0 and 6.0 mg/kg (Chinese study) and 6.0 mg/kg (Japanese study). The maximum plasma concentration was reached 1-3 h and 4-6 days after IV and SC administration, respectively. Osocimab exhibited a deviation from dose-proportional pharmacokinetics for AUC but not Cmax; higher doses had higher apparent clearance and disproportionately lower total exposure. A slightly lower exposure was observed in Japanese compared with Chinese volunteers after IV administration; conversely, relatively higher exposure in Japanese volunteers with SC dosing was identified. Osocimab was associated with a dose-dependent increase in activated partial thromboplastin time (aPTT). Maximal aPTT prolongations were observed 1-4 h and 2-6 days after IV and SC administration, respectively. Anti-drug antibodies of low titer were detected in 1/9 (11.1%) Japanese volunteers administered placebo and 26/40 (65.0%) Chinese volunteers administered osocimab. Adverse events were reported in 8/18 (44.4%) Japanese and 28/40 (70.0%) Chinese volunteers who received osocimab, as well as in 1/9 (11.1%) Japanese and 6/10 (60.0%) Chinese volunteers who received placebo. In conclusion, data did not suggest a clear dose-proportionality for osocimab within the investigated dose range. The effect of osocimab on aPTT was expected per its mechanism of action. Osocimab was generally well tolerated.

Abstract B139: Redlining bias and progression of chronic health conditions in survivors of childhood cancer: A report from the St. Jude lifetime cohort study

Abstract Background/Aims: Racial health disparities have been linked to racial and residential segregation. Redlining bias is a special form of racial and residential segregation involving the systematic denial of mortgages, insurance, and other financial services to racial/ethnic minorities. This study examined associations between redlining bias and the progression of chronic health conditions (CHCs) in adult survivors of childhood cancer. Methods: We included 1,670 adult survivors of childhood cancer from the St. Jude Lifetime Cohort Study who had undergone two or more clinical assessments. Over 200 individual CHCs were graded using a modified CTCAE version and aggregated to determine the global CHC burden. CHC progression from baseline to follow-up evaluation was classified as either worsening over time (from Grade 2 to 3-5 or from Grade 3 to 4-5) or new-onset (from Grades 0-1 to 2-5). Survivors' home addresses at baseline (2007-2020) were linked to contemporary redlining bias data (2010-2017) created by Beyer et al. (J Clin Oncol, 2021). Redlining bias was defined as the odds ratio of a mortgage application denial for properties in a local area versus all metropolitan statistical areas and further classified as high (≥2.0), moderate (1.0-1.9), low (0.5-0.9), or least bias (<0.5). Multivariable logistic regression tested associations of risk for worsening/new-onset CHCs (vs. no progression) with redlining bias (high vs. moderate/low/least bias), adjusting for age, sex, treatment factors, personal socioeconomic status (SES; education and health insurance), and lifestyle factors. Joint effects of redlining bias and personal SES on CHC progression were also evaluated. Results: Survivors’ mean±SD age at baseline was 31.7±8.3 years; 17.5% lived in high and 19.5% in moderate redlining neighborhoods. The bivariate analysis found that living in a neighborhood classified as having high redlining bias (vs. moderate/low/least bias) increased the risk of progression of the global burden of CHCs (OR=1.32, 95% CI: 1.02-1.70). Multivariable analysis found significant associations of redlining bias with the risk of worsening/new-onset of individual CHCs such as cardiomyopathy (OR=1.63, 95% CI: 1.07-2.48), peripheral motor neuropathy (OR=1.56, 95% CI: 1.00-2.44), asthma (OR=1.85, 95% CI: 1.04-3.32), and restrictive pulmonary deficit (OR=1.79, 95% CI: 1.05-3.04). Considering joint effects, survivors enrolled in public insurance programs and living in a high redlining area had a higher risk of progression of the global burden of CHCs (OR=1.73, 95% CI: 1.05-2.87) and of worsening/new-onset in peripheral motor neuropathy (OR=3.18, 95% CI: 1.57-6.42) and restrictive pulmonary deficit (OR=5.29, 95% CI: 2.46-11.37) CHCs. Conclusions: The significant associations of redlining bias with the progression of CHCs among adult survivors of childhood cancer suggest an urgent need for interventions (typically social or healthcare policies) targeting neighborhoods with high discriminatory exposures to prevent CHC burden in this population. Citation Format: Jaesung Choi, Madeline R. Horan, Nickhill Bhakta, Deo Kumar Srivastava, Kirsten K. Ness, Gregory T. Armstrong, Melissa M. Hudson, I-Chan Huang. Redlining bias and progression of chronic health conditions in survivors of childhood cancer: A report from the St. Jude lifetime cohort study [abstract]. In: Proceedings of the 17th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2024 Sep 21-24; Los Angeles, CA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2024;33(9 Suppl):Abstract nr B139.

The AUREX cell: a versatile operando electrochemical cell for studying catalytic materials using X-ray diffraction, total scattering and X-ray absorption spectroscopy under working conditions.

Understanding the structure-property relationship in electrocatalysts under working conditions is crucial for the rational design of novel and improved catalytic materials. This paper presents the Aarhus University reactor for electrochemical studies using X-rays (AUREX) operando electrocatalytic flow cell, designed as an easy-to-use versatile setup with a minimal background contribution and a uniform flow field to limit concentration polarization and handle gas formation. The cell has been employed to measure operando total scattering, diffraction and absorption spectroscopy as well as simultaneous combinations thereof on a commercial silver electrocatalyst for proof of concept. This combination of operando techniques allows for monitoring of the short-, medium- and long-range structure under working conditions, including an applied potential, liquid electrolyte and local reaction environment. The structural transformations of the Ag electrocatalyst are monitored with non-negative matrix factorization, linear combination analysis, the Pearson correlation coefficient matrix, and refinements in both real and reciprocal space. Upon application of an oxidative potential in an Ar-saturated aqueous 0.1 M KHCO3/K2CO3 electrolyte, the face-centered cubic (f.c.c.) Ag gradually transforms first to a trigonal Ag2CO3 phase, followed by the formation of a monoclinic Ag2CO3 phase. A reducing potential immediately reverts the structure to the Ag (f.c.c.) phase. Following the electrochemical-reaction-induced phase transitions is of fundamental interest and necessary for understanding and improving the stability of electrocatalysts, and the operando cell proves a versatile setup for probing this. In addition, it is demonstrated that, when studying electrochemical reactions, a high energy or short exposure time is needed to circumvent beam-induced effects.

Frequency dependence and harmonic distortion of stapes displacement and intracochlear pressure in response to very high level sounds

Previous reports have suggested that intracochlear pressures (PIC) measured at the base of the cochlea increase directly proportionally with stapes displacement (DStap) in response to moderately high (<130 dB SPL) level sounds. Consistent with this assumption, we have reported that for low frequency sounds (<1 kHz), stapes displacement and intracochlear pressures increase linearly with sound pressure level (SPL) for moderately high levels (<130 dB SPL), but saturate at higher exposure levels (>130 dB SPL). However, the magnitudes of each response were found to be frequency dependent, thus the relationship between DStap and PIC may vary at higher frequencies or higher levels.In order to further examine this frequency and level dependence, measurements of DStap and PIC were made in cadaveric human temporal bones prepared with a mastoidectomy and extended facial recess to expose the ossicular chain. PIC was measured in scala vestibuli (PSV) and scala tympani (PST) simultaneously with SPL in the external auditory canal (PEAC) and laser Doppler vibrometry (LDV) measurements of stapes velocity (VStap). Consistent with prior reports, DStap and PSV increased proportionally with sound pressure level in the ear canal up to a frequency-dependent saturation point, above which both DStap and PSV showed a distinct deviation from proportionality with PEAC, suggesting that their relationship may remain constant at these high frequencies. Likewise, while the asymptotic value, and SPL at which saturation occurred were frequency dependent in both DStap and PSV, the reduction in gain with increasing SPL above this level was constant above this level at all frequencies, and the magnitude of responses at harmonics of the driving frequency increased with increasing level, consistent with harmonic distortion via peak clipping. Importantly, this nonlinear distortion shifts the energy arriving at the inner ear to higher frequencies than are present in incident stimulus, thus exposing the high frequency sensitive components of the auditory system to more noise than would be expected from measurement of that stimulus on its own. Overall, responses suggest that the cochlear representation of very high-level air conducted stimuli is limited by nonlinearities in the middle ear, and that this peak limiting leads to increased high frequency cochlear exposures than are present in the driving stimulus.

Identifying psychological risk and resilience in high-risk military personnel

IntroductionCombat exposure has been associated with the emergence of post-traumatic stress disorder (PTSD) symptoms in military personnel; however, not all veterans are negatively impacted by their operational experience. In many...

Thermal Comfort Conditions and Mortality in Brazil.

Conventional temperature-based approaches often overlook the intricate nature of thermal stress experienced by individuals. To address this limitation, climatologists have developed thermal indices-composite measures designed to reflect the complex interaction of meteorological factors influencing human perception of temperature. Our study focuses on Brazil, estimating the association between thermal comfort conditions and mortality related to respiratory and circulatory diseases. We examined four distinct thermal indices: the discomfort index (DI), net effective temperature (NET), humidex (H), and heat index (HI). Analyzing a comprehensive dataset of 2,872,084 deaths from 2003 to 2017, we found significant variation in relative risk (RR) based on health outcomes, exposure lag, percentile of exposure, sex/age groups, and specific thermal indices. For example, under high exposure conditions (99th percentile), we observed that the shorter lags (3, 5, 7, and 10) had the most robust effects on all-cause mortality. For example, under lag 3, the pooled national results for the overall population (all ages and sexes) indicate an increased risk of all-cause mortality, with an RR of 1.17 (95% CI: 1.13; 1.122) for DI, 1.15 (95% CI: 1.12; 1.17) for H, 1.15 (95% CI: 1.09; 1.21) for HI, and 1.18 (95% CI: 1.13; 1.22) for NET. At low exposure levels (1st percentile), all four distinct thermal indices were linked to an increase in all-cause mortality across most sex and age subgroups. Specifically, for lag 20, we observed an estimated RR of 1.19 (95% CI: 1.14; 1.23) for DI, 1.12 (95% CI: 1.08; 1.16) for H, 1.17 (95% CI: 1.12; 1.22) for HI, and 1.18 (95% CI: 1.14; 1.23) for NET. These findings have important implications for policymakers, guiding the development of measures to minimize climate change's impact on public health in Brazil.

The efficacy of mobile applications for reducing depression in adolescents and young adults: A meta-analysis of randomized control trials.

Mobile applications for mental health have the potential to aid people with mental health disorders, especially depression, by providing them with tools and coping mechanisms. Adolescents and young adults, being at risk of depressive symptoms and leading mobile users, are among the main targets of using mobile applications to alleviate symptoms. This study aimed to evaluate the impact of mobile application-based psychological interventions in reducing depression symptoms in adolescents and young adults compared to those not exposed to the intervention. We conducted a meta-analysis focusing on mobile applications for reducing depressive symptoms. We searched two databases: MEDLINE and EMBASE and included randomized controlled trials conducted in English among participants aged 18-35 years old who were assessed for depressive symptoms using a validated screening measure and used mobile applications-based psychological interventions. Two of six independent reviewers conducted study selection, data extraction, and bias assessment. A pooled mean standardized difference (Cohen's d) and 95% CI were calculated using random-effects meta-analysis. Risk of bias was assessed using I2 statistics and forest plot. Egger's test was used for assessing publication bias. After screening 740 references, we identified 12 trials with 1869 participants, with a mean age of participants ranging from 14.70 to 25.1 years. The interventions ranged from cognitive behavioral therapy (CBT)-based mobile apps to interactive story-telling apps and apps delivering a mix of CBT, interpersonal psychotherapy for adolescents, and dialectical behavior therapy elements. Control groups included information-only, waitlist, no intervention, and treatment as usual. Seven studies used Patient Health Questionnaire-9 (PHQ-9) to assess the severity of depressive symptoms, while the other five used different scales. There was no evidence of publication bias (p = 0.325). The mobile applications reduced depression score by 0.08 units of standardized difference more than the control, with a 95% CI of -0.19 to 0.03 (p = 0.294, I2 = 15.4%) using standardized mean difference (SMD) as the effect estimate. In a sensitivity analysis including only studies that used PHQ-9, we found a similar trend, SMD -0.72 (95%CI -1.48 to 0.03). However, both findings were not significant. Current evidence is insufficient to support mobile applications to relieve depression symptoms in adolescents and young adults. Further trials with larger sample size are needed to confirm our findings of a positive trend. With emerging technologies and the high exposure of apps in this population, mobile applications for depression hold promise for the future of treatment and awareness of mental health disorders in this population.

The Association between Aminoglycoside Exposure and Ototoxicity in Children with Cystic Fibrosis

Introduction: Pulmonary exacerbations increase the requirement of aminoglycoside (AG) antibiotics in people with cystic fibrosis (pwCF). Several studies have shown that AGs have a cumulative effect on ototoxicity. We aimed to investigate the relationship between AG exposure and ototoxicity by using 3 different methods in patients with CF. Materials/Methods: The multicenter study included 121 pwCF aged between 5 and 18 years with a history of parenteral AG exposure. Standard pure-tone audiometry, extended high-frequency pure-tone audiometry (EHF-PTA), and distortion-product otoacoustic emissions (DPOAE) tests were performed. Mitochondrial mutation analysis for m1555G>A was performed in 61 patients. Results: Median age was 12.85 years and 52.1% (n = 63) were male. 18.2% (n = 22) of the patients had received parenteral AGs more than 5 courses/lifetime. Ototoxicity was detected in at least one of the tests in 56.2% (n = 68) of the patients. Only 10.7% (n = 13) of the patients had reported a symptom indicating ototoxicity. 30.3% (n = 30) of the patients had ototoxicity in the low exposure group, while it was 45.5% (n = 10) in the high exposure group according to EHF-PTA (p > 0.05). Median number of parenteral amikacin courses was significantly higher in the ototoxic group (2 [1.25–5.75] vs. 2 [1–3]; p = 0.045). No m1555A>G mutation was detected in 61 patients who screened for mitochondrial mutation analysis. Conclusion: As AG ototoxicity occurs primarily at high frequencies, EHF-PTA is important in early detecting ototoxicity. EHF-PTA and DPOAE detected ototoxicity in some patients with normal PTA results. All pwCF with a history of AG exposure should be evaluated for hearing loss since symptoms may only be noticed in the late period.

The Influence of Social Media on Adolescent Sexual Behavior: A Retrospective Analysis

In this modern era, the internet has become an essential part of basic human needs. Social media, as one of the most widely used platforms, offers various benefits, such as a means of communication and self-expression. However, behind these benefits, there are various negative impacts, especially for teenagers and minors. One of them is access to pornographic content that can influence premarital sexual behavior. This study aims to analyze the influence of social media on adolescent sexual behavior. The research method used is a literature study, by collecting and reviewing theories from various relevant literatures. Based on an analysis of seven international articles, it was found that adolescents have a very high exposure to negative content on social media, including pornography. This exposure increases the risk of unhealthy sexual behavior, where the more often adolescents are exposed to information and experiences related to sexual behavior, the stronger the stimulus to imitate the behavior. One significant impact of unhealthy social media use is the increase in promiscuous sex among adolescents. The implications of this study emphasize the importance of supervision and education for adolescents in using social media to minimize these negative impacts.

Environmental high temperature affects pre-implantation embryo development by impairing the DNA repair ability

Environmental high temperature poses a significant threat to human health, however, limited information is available for understanding the relationship between the hot weather and infertility. This study aims to assess the adverse effect of the hot weather to early embryonic cells. Our results indicated that environmental high temperature exposure could cause the decline of early embryo quality and implantation ability. In detail, it led to early embryonic development retardation, embryo degeneration rate increased, the rate of blastocyst and hatching decreased, and reduced the number of implants. And the finding also the impairment of environmental high temperature on early embryonic cells may be due to oxidative damage of DNA caused by ROS, while BER repair ability is decreased, failing to repair oxidative damage of DNA in time, resulting in a large number of early embryonic apoptosis. The work underscored that pregnant women should stay away from high-temperature environments.

English Vowel Perception in Spanish-English Bilingual Preschoolers: Multiple-Talker Input Is Only Beneficial for Children With High Language Exposure Levels.

This study examines English vowel perception in Spanish-English bilingual preschoolers, comparing bilinguals' perception patterns to those of monolinguals and examining how child internal (age) and external variables (input quantity and input diversity) predict perceptual performance. Sixty children between 3;6 and 5;6 (years;months) of age participated in the study, 28 of whom were Spanish-English bilinguals and 32 English monolinguals. Perception was assessed through a forced-choice minimal-pair identification task in which children heard synthesized audio stimuli (i.e., "sheep" and "ship") that varied systematically along the /i-ɪ/ continuum and were asked to match them with one of two pictures. The data were analyzed with Bayesian mixed-effects logistic regression analyses, modeling responses as a function of continuum step, language background (monolingual or bilingual), age, English exposure (i.e., input quantity), and number of English input providers (i.e., input diversity). The results indicate that, despite displaying nonnative English stop voicing perception in a previous study, the same bilingual children showed English /i-ɪ/ perception patterns that did not differ from those of monolinguals. While age did not predict vowel perception, input quantity and diversity jointly interacted to moderate how well children perceived the /i-ɪ/ contrast. Specifically, diverse input promoted perceptual performance in children who received high levels of English exposure-and who presumably had more advanced English language skills, whereas it limited perceptual performance in children with more limited English exposure and skills. This study shows that bilingual children can show monolingual-like perception patterns for some sounds while displaying nontarget perception for others. This is the first study to demonstrate that language exposure mediates the role of input diversity on speech sound development, suggesting that varied input can be more or less beneficial for speech sound development based on the learner's language learning stage.

Exposure Assessment of Benzotriazole Ultraviolet Absorbers in Plastic Sports Field Dust and Indoor Dust: Are Plastic Sports Fields High Exposure Scenarios?

Benzotriazole ultraviolet absorbers (BUVs), as emerging contaminants of extensive use, especially in plastic sports fields, have aroused increasing concern due to their potential human and environmental impacts. However, BUV exposure from plastic sports field dust is still unknown. This study compared BUVs in plastic sports field dust and indoor dust for the first time. The order of the geometric mean concentrations of the total BUVs (ΣBUVs) in plastic sports field dust was indoor badminton courts (11023 ng g-1) > basketball courts (4777 ng g-1) > plastic tracks (3779 ng g-1) > synthetic turf (1920 ng g-1) > tennis courts (689 ng g-1). The geometric mean concentrations of ΣBUVs in indoor dust (1150 ng g-1) were lower than those in most plastic sports field dust. The dominant BUV was 2-hydroxy-4-(octyloxy)benzophenone (UV-531) in plastic sports field dust, while 2,2'-methylenebis[4-(1,1,3,3-tetramethylbutyl)-6-2H-benzotriazole-2-yl)phenol] (UV-360) was the dominant BUV in indoor dust. Releases from plastic track materials, sneaker soles, and friction between them might be important BUV sources in plastic track dust. The average estimated daily intakes of ΣBUVs from plastic sports field dust for general exercisers were lower than those from indoor dust, but those for exercisers with long time or professional athletes might be higher, potentially posing health risks.

Multimedia and Full-Life-Cycle Monitoring Discloses the Dynamic Accumulation Rules of PFAS and Underestimated Foliar Uptake in Wheat near a Fluorochemical Industrial Park.

The escalating concern of perfluoroalkyl and polyfluoroalkyl substances (PFAS), particularly at contaminated sites, has prompted extensive investigations. In this study, samples of multimedia including air, rhizosphere soil, and tissues of wheat at various growing stages were collected near a mega fluorochemical industrial park in China. Perfluorooctanoic acid (PFOA) was predominant in both air and soil with a strong correlation, highlighting air deposition as an important source in the terrestrial system. PFAS concentrations in wheat decreased in the stem and ear but increased in the leaves as wheat matured. Specifically, perfluorobutanoic acid (PFBA) dominated in the aboveground tissues in the full-life-cycle, except that PFOA surpassed and became predominant in leaves during the filling and maturing stages, hinting at an airborne source. For all PFAS, both bioaccumulation factors and translocation factors (TFs) were inversely correlated with the carbon chain length during the full-life-cycle. The obtained TF values were considerably higher than those obtained from ambient sites reported previously, further suggesting an unneglectable foliar uptake from air, which was estimated to be 25% for PFOA. Moreover, spray irrigation remarkably enhanced the absorption of PFAS in wheat via foliar uptake relative to flood irrigation. The estimated daily intake of PFBA via wheat consumption and air inhalation was 0.50 μg/kg/day for local residents, at least one magnitude higher than the corresponding threshold, suggesting an alarmingly high exposure risk.

Safe concentration, unsafe effects: Impact of BPA on antioxidant function in the hepatopancreas and ovarian gene expression in oriental river prawns (Macrobrachium nipponense)

This study investigated the effects of Bisphenol A (BPA), a common endocrine-disrupting chemical, on the antioxidant enzyme activities in the hepatopancreas and the expression of genes related to ovarian development in oriental river prawns (Macrobrachium nipponense). The 24hLC50 and 48hLC50 values for BPA were 80.59 mg/L and 63.90 mg/L, respectively, with a safe concentration of 12.06 mg/L. Prawns were exposed to low (4.85 mg/L), safe (12.06 mg/L), and high (30.00 mg/L) concentrations of BPA for 10 days to measure enzyme activities, and for 20 days followed by 7 days in BPA-free water to measure gene expression.Short-term exposure (12 h, 1d, 3d) to low concentration BPA did not significantly affect superoxide dismutase (SOD) activity in the hepatopancreas (P > 0.05), but long-term exposure (6d, 10d) significantly reduced SOD activity (P < 0.05). Catalase (CAT) activity showed no significant changes throughout the low concentration exposure period (P > 0.05). At safe and high concentrations, SOD and CAT activities significantly decreased after 12 h of exposure (P < 0.05).BPA affected heat shock protein 90 (HSP90) expression in the ovary, with low concentration BPA significantly upregulating HSP90 after 1 day (P < 0.05), but returning to normal levels after 10 and 20 days. At the safe concentration, HSP90 was significantly upregulated at all three sampling points (1d, 10d, 20d) (P < 0.05), while high concentration exposure led to significant upregulation only on day 10 (P < 0.05).Low concentration BPA had no significant effect on Cathepsin B (CB) and Cathepsin L (CL) gene expression in the ovaries (P > 0.05). However, safe concentration exposure promoted CB expression on days 1, 10, and 20 (P < 0.05), while high concentration exposure significantly increased CB expression on day 1 (P < 0.05), with levels returning to normal on days 10 and 20. CL expression significantly increased after 20 days of exposure to both safe and high concentrations (P < 0.05). Gene expression levels in the ovaries returned to normal after transfer to BPA-free water, with HSP90 and CB normalizing by day 1, and CL by day 7.These results indicate that even safe concentrations of BPA impose stress on the hepatopancreas and increase the expression of HSP90, CB, and CL genes in the ovaries, affecting ovarian development. And, these effects are reversible within a certain period after the removal of BPA.

Investigating Spatial Effects through Machine Learning and Leveraging Explainable AI for Child Malnutrition in Pakistan

While socioeconomic gradients in regional health inequalities are firmly established, the synergistic interactions between socioeconomic deprivation and climate vulnerability within convenient proximity and neighbourhood locations with health disparities remain poorly explored and thus require deep understanding within a regional context. Furthermore, disregarding the importance of spatial spillover effects and nonlinear effects of covariates on childhood stunting are inevitable in dealing with an enduring issue of regional health inequalities. The present study aims to investigate the spatial inequalities in childhood stunting at the district level in Pakistan and validate the importance of spatial lag in predicting childhood stunting. Furthermore, it examines the presence of any nonlinear relationships among the selected independent features with childhood stunting. The study utilized data related to socioeconomic features from MICS 2017–2018 and climatic data from Integrated Contextual Analysis. A multi-model approach was employed to address the research questions, which included Ordinary Least Squares Regression (OLS), various Spatial Models, Machine Learning Algorithms and Explainable Artificial Intelligence methods. Firstly, OLS was used to analyse and test the linear relationships among selected variables. Secondly, Spatial Durbin Error Model (SDEM) was used to detect and capture the impact of spatial spillover on childhood stunting. Third, XGBoost and Random Forest machine learning algorithms were employed to examine and validate the importance of the spatial lag component. Finally, EXAI methods such as SHapley were utilized to identify potential nonlinear relationships. The study found a clear pattern of spatial clustering and geographical disparities in childhood stunting, with multidimensional poverty, high climate vulnerability and early marriage worsening childhood stunting. In contrast, low climate vulnerability, high exposure to mass media and high women’s literacy were found to reduce childhood stunting. The use of machine learning algorithms, specifically XGBoost and Random Forest, highlighted the significant role played by the average value in the neighbourhood in predicting childhood stunting in nearby districts, confirming that the spatial spillover effect is not bounded by geographical boundaries. Furthermore, EXAI methods such as partial dependency plot reveal the existence of a nonlinear relationship between multidimensional poverty and childhood stunting. The study’s findings provide valuable insights into the spatial distribution of childhood stunting in Pakistan, emphasizing the importance of considering spatial effects in predicting childhood stunting. Individual and household-level factors such as exposure to mass media and women’s literacy have shown positive implications for childhood stunting. It further provides a justification for the usage of EXAI methods to draw better insights and propose customised intervention policies accordingly.

Secondhand smoke exposure among adolescents in the gulf cooperation council countries: analysis of global youth tobacco surveys

This study aimed to analyze patterns and predictors of secondhand smoke (SHS) exposure among adolescents (12–16 years old) in Bahrain, Kuwait, Oman, Qatar, Saudi Arabia, and the United Arab Emirates. Nationally representative data from the most recent Global Youth Tobacco Survey in each country were analyzed (N = 17,220). SHS exposure at home, in public places, and at school was assessed. Descriptive statistics summarized exposure prevalence overall and by sex. Multivariable logistic regression examined factors associated with each SHS exposure’s outcome. The results showed that SHS exposure was high overall, with exposure at home and school ranging from 12.7 to 20.7%, respectively, in Oman to 39.4% and 36.7%, respectively, in Kuwait. Almost half of the adolescents reported exposure to SHS in public places, with a prevalence of 40.8% in Saudi Arabia to 65.9% in Kuwait. The prevalence of exposure varied between countries, with the highest rates occurring in Kuwait. Girls had higher exposure at home, while boys had higher exposure in public and at school. Factors associated with higher exposure included parental smoking, friend smoking, and tobacco advertising. The belief that SHS is harmful was associated with lower home exposure. In conclusion, adolescents in the Gulf Cooperation Council countries are exposed to concerning levels of SHS, especially in public places. These findings underscore the urgent need for stronger tobacco control policies, including comprehensive smoke-free laws covering all public venues, to protect youth from SHS exposure. Additionally, the results support the development of targeted interventions promoting smoke-free homes and social norms against smoking.