Duration Of Exposure Research Articles

Effects of climate change on seed germination may contribute to habitat homogenization in freshwater forested wetlands

AbstractClimate changes in temperate regions are expected to result in warmer, shorter winters in temperate latitudes. These changes may have consequences for germination of plant species that require a period of physiological dormancy. The effect of cold duration on seed germination has been investigated in a number of plant taxa, but has not been well studied in wetland and bottomland forest tree species, an ecosystem that is threatened by habitat homogenization. Our work sought to test the role of changing winter temperatures on seed germination in specialist (Nyssa aquatica and Taxodium distichum) and generalist (Acer rubrum and Liquidambar styraciflua) tree species within forested wetlands throughout the eastern U.S. The experiment was conducted in an environmental chamber in Norfolk, VA, USA. Seeds of T. distichum, N. aquatica, A. rubrum, and L. styraciflua were exposed to each of seven pre-germination cold exposure durations (0, 15, 30, 45, 60, 75, and 90 days) and observed for germination for 30 days. Cold stratification duration positively impacted total percent germination in N. aquatica (p < 0.0001) as well as A. rubrum (p = 0.0008) and T. distichum (p = 0.05). Liquidambar styraciflua seeds exhibited more rapid rates of germination with increasing cold exposure duration and greater percent germination compared to the others regardless of cold stratification duration. Our results provide insight into how community dynamics and biodiversity of wetland and bottomland trees may shift with a changing climate. Further, this work emphasizes the importance of understanding the role of plant functional traits in early life stages in community dynamics and has implications for management practices.

Investigating the impact of anthropogenic radiofrequency electromagnetic fields on animals and plants in the environment: analysis from a systematic map

ABSTRACT Radiofrequency electromagnetic fields (RF EMF) from anthropogenic sources have become ubiquitous in the environment. International guidelines have been set by expert scientific bodies to protect human health from excessive exposure. There are no specifically established exposure guidelines to protect plants and animals. A previous systematic map identified 334 studies investigating the effects of RF EMF exposure from anthropogenic sources on animals and plants. This study aimed to analyse the effect of RF EMF and its relationship to different exposure parameters and the quality of those studies. Statistically significant inverse relationships were found between effect size and exposure-level parameters for studies investigating effects in animals. The results indicated that quality score is more indicative of the magnitude of the effect size than exposure-level parameters or exposure duration. This highlights the need for further, high-quality research on the effects of RF EMF exposure on plants and animals.

Comparative analysis of circadian lighting models: melanopic illuminance vs. circadian stimulus

The influence of light exposure on human circadian rhythms has been widely recognized. This effect is mediated by a phototransduction process projected by the intrinsically photosensitive retinal ganglion cells (ipRGCs). The process also involves signal inputs from visual photoreceptors. However, the relative contributions of each photoreceptor to this process remain unclear; accordingly, two different types of circadian lighting models have been proposed: (i) the melanopic illuminance model based solely on ipRGC activation, including melanopic equivalent daylight D65 illuminance (m-EDI) and equivalent melanopic illuminance (EML), and (ii) the circadian stimulus (CS) model, which considers the participation of both ipRGC and visual photoreceptors. However, the two models can yield conflicting predictions. In this study, we assessed and compared the accuracies of these circadian lighting models by fitting a substantial amount of experimental data extracted from multiple laboratory studies. Upon evaluating the results across all exposure durations, data-fitting accuracy of the intricate CS model did not surpass that of the much simpler melanopic illuminance model. Consequently, the latter appears to be the more suitable model for lighting applications. Moreover, a recurring limitation of prior research was revealed: the lighting spectra were not tailored to effectively reflect the fundamental distinctions between the two types of models. Therefore, drawing clear conclusions regarding the accuracies of the models is challenging. To address this problem, we introduced a method for designing contrast-spectra pairs. This method can provide lighting spectra to highlight the difference in circadian illuminance based on one model while keeping the circadian illuminance of others constant.

Feasibility of safe outpatient treatment in pediatric patients following intraventricular radioimmunotherapy with 131I-omburtamab for leptomeningeal disease

BackgroundRadiolabeled antibody 131I-omburtamab was administered intraventricularly in patients with leptomeningeal disease under an institutionally approved study (#NCT03275402). Radiation safety precautions were tailored for individual patients, enabling outpatient treatment based on in-depth, evidence-based recommendations for such precautions. The imperative advancement of streamlined therapeutic administration procedures, eliminating the necessity for inpatient isolation and resource-intensive measures, holds pivotal significance. This development bears broader implications for analogous therapies within the pediatric patient demographic.MethodsIntraventricular radioimmunotherapy (RIT) with 925–1850 MBq (25–50 mCi) of 131I-omburtamab was administered via the Ommaya reservoir, in designated rooms within the pediatric ambulatory care center. Dosimeters were provided to staff involved in patient care to evaluate exposure during injection and post-administration. Post-administration exposure rate readings from the patient on contact, at 0.3 m, and at 1 m were taken within the first 30 min, and the room was surveyed after patient discharge. Duration of radiation exposure was calculated using standard U.S. Nuclear Regulatory Commission (US NRC) regulatory guidance recommendations combined with mean exposure rates and whole-body clearance estimates. Exposure rate measurements and clearance data provided patient-specific precautions for four cohorts by age: < 3 y/o, 3–10 y/o, 10–18 y/o, and 18+.ResultsPost-administration exposure rates for patients ranged from 0.16 to 0.46 µSv/hr/MBq at 0.3 m and 0.03–0.08 µSv/hr/MBq at 1 m. Radiation exposure precautions ranged from 1 to 10 days after release for the four evaluated cohorts. Based on the highest measured exposure rates and slowest whole-body clearance, the longest precautions were approximately 78% lower than the regulatory guidance recommendations. Radiation exposure to staff associated with 131I-omburtamab per administration was substantially below the annual regulatory threshold for individual exposure monitoring.Conclusion131I-omburtamab can be administered on an outpatient basis, using appropriate patient-based radiation safety precautions that employ patient-specific exposure rate and biological clearance parameters. This trial is registered with the National Library of Medicine’s ClinicalTrials.gov. The registration number is NCT03275402, and it was registered on 7 September 2017. The web link is included here. https://clinicaltrials.gov/study/NCT03275402.

FLIGHT HOURS AND BMI AGAINST TUC IN HYPOBARIC CHAMBER ALTITUDE 25.000 FEET

Background: Time of Useful Consciousness (TUC) is the time interval a person can survive carrying out flight duties due to a decrease in oxygen pressure and the point at which there is a decrease in the level of consciousness. The TUC time interval is influenced by various factors including Body Mass Index (BMI) and flying hours which affect the increase in the duration of the body's exposure to hypoxic conditions in pilots. Purpose: This research was conducted to determine the relationship between total flight hours and BMI on TUC. Method: This research employed observational analytic research with a cross-sectional method. Sampling was taken by simple random sampling technique. The sample for this research included active flight crew members from Lakespra dr. Saryanto 202 who met the inclusion criteria. Result: There were 53 research subjects, with the results showing that 48 subjects (90.6%) had a TUC &lt;4 minutes, and 5 subjects had a TUC &gt;4 minutes. There were 47 subjects (88.7%) with total flight hours &gt;1000 hours and 6 subjects (11.3%) with total flight hours &lt;1000 hours. In BMI, 37 subjects (69.8%) had an overweight BMI, and 16 subjects (30.2%) had a normal BMI. Conclusion: After examining 53 subjects, it was found that there was no relationship between total flight hours and TUC (p-value = 1.000) or BMI and TUC( p-value = 0.307) in the hypobaric chamber at an altitude of 25.000 feet.

Биохимические показатели мышц судака из Рыбинского водохранилища и оценка риска их потребления

Fish, as a food component, is very beneficial for human health. It is rich in protein, valuable fatty acids, vitamins and minerals. However, when consuming it, there is a risk of toxic substances entering the human body that ac-cumulate in the tissues of aquatic organisms, for example, heavy metals. The purpose of the work is to determine the biochemical parameters in the muscles of pike perch from the reaches of the Rybinsk reservoir, which differ in anthropogenic load, and to assess the risks of human consumption of this species. The amount of water, dry matter, lipids, protein, minerals and carbohydrates in muscle tissue was determined using standard methods. To assess the threat to human health associated with the potential duration of exposure to heavy metals from walleye consumption, target and cumulative hazard ratios were calculated. The assessment of carcinogenic risk to human health was determined using the target and general cancer risk index. Calculated indicators were obtained based on data on the content of heavy metals in the muscles of pike perch, established earlier. In the muscles of pike perch specimens from the Sheksninsky and Volzhsky reaches, no significant differences between biochemical parameters were found. According to the ratio of protein and lipids in muscle tissue, the studied individuals belong to category A, and according to the amount of lipids – to fish with a low-fat content. The estimated dietary intakes for weekly intakes of heavy metals from pike perch meat was below the reference values. The target and total hazard coefficient turned out to be less than one, which indicates that there is no potential non-carcinogenic risk for humans when consuming pike perch meat. The target cancer risk indices for Cd, Pb, Al and Cr are within acceptable ranges. The total risk of developing cancer for these metals is more than 1 in 100,000.

Four-Strata Risk Assessment in Patients with Pulmonary Arterial Hypertension Treated with Selexipag in Real-World Settings (EXPOSURE Study).

Risk assessment can aid management of pulmonary arterial hypertension (PAH) and clinical decision-making. This analysis describes characteristics, treatment patterns and outcomes of patients with PAH, categorised by risk status at time of treatment escalation with selexipag in clinical settings. Patients initiating selexipag in the ongoing multicentre, prospective EXPOSURE (EUPAS19085) study were grouped as low, intermediate-low, intermediate-high or high risk of 1-year mortality according to the ESC/ERS 4-strata method. As of November 2022, 77% (535/698) of patients initiating selexipag had data allowing for risk calculation; 14% (N = 76) were low, 31% (N = 168) intermediate-low, 34% (N = 182) intermediate-high and 20% (N = 109) high risk of 1-year mortality. Overall, patients were predominantly female (71%), with idiopathic/heritable PAH (56%) or PAH associated with connective tissue disease (CTD-PAH; 27%), median age of 60years and prevalent (2years) disease. From low to high risk, proportion of CTD-PAH and age increased (from 12%-40% and 46-68years, respectively); time from diagnosis decreased and presence of cardiovascular risk factors increased. Most patients across risk groups (74-81%) initiated selexipag as part of triple oral combination therapy. Overall median (Q1, Q3) selexipag exposure duration was 10.1 (3.5, 24.1) months. Proportions of hospitalised patients increased with increasing risk group (16-42% from low to high, respectively); more hospitalisations were PAH-related for the high risk (71%) versus other risk groups (47-54%). Kaplan-Meier survival estimates were 98%, 98%, 93% and 80% at 1-year and 98%, 92%, 81% and 67% at 2-years, from low to high risk, respectively. In clinical settings, selexipag is initiated across all risk groups, predominantly as triple therapy. Only 45% of patients being at low/intermediate-low risk at selexipag initiation suggests an opportunity for more frequent patient monitoring and earlier treatment escalation, given that 4-strata risk assessment was prognostic for hospitalisations and survival in this contemporary PAH cohort. A graphical abstract is available with this article.

Evaluation of the Impacts of Pesticides Exposure in Different Durations on the Neural System and Antioxidants in Iraqi Farmers

The objective of this research was to investigate the effects of pesticides in different durations on some neurotransmitters and oxidative parameters compared to controls. A total of 120 male farmers participated in this study, 30 not exposed to pesticides served as control group and 90 exposed to pesticides and were split into two groups based on their exposure durations (˂5 &amp; ≥5 years) and three age-groups (˂20, 20-40 and ≥41 years). Blood was collected to determine acetylcholinesterase (ACHE), serotonin (5-TH), dopamine (DA), reactive oxygen species (ROS), total antioxidant capacity (TAC) and malondialdehyde (MDA) levels using ELISA kits. The results of ACHE, serotonin, dopamine and TAC levels increased, whereas MDA and ROS levels decreased among farmers exposed to the pesticides. According to the exposure duration and farmers age, only 5-TH, DA and TAC levels were affected. It can be concluded that pesticides exposure may have an acute effect on acetylcholine and a chronic effect on the serotonin and dopamine via change in the antioxidant system which may play an important role in the neural diseases.

Does sunlight exposure predict next-night sleep? A daily diary study among U.S. adults.

Poor sleep is becoming increasingly prevalent and is associated with adverse health outcomes. Sunlight exposure may improve sleep by regulating circadian rhythms, increasing vitamin D, and influencing melatonin production. However, research on the sunlight-sleep association is limited, especially outside of cross-sectional designs. This study examined associations between daily self-reported sunlight exposure and next-night sleep quality in 103 adults for up to 70 days. The timing of sunlight exposure predicted next-night sleep quality. Specifically, morning sunlight exposure, relative to no sunlight, predicted better sleep quality based on responses to the brief Pittsburg Sleep Quality Index. Duration of sunlight exposure was generally not associated with sleep quality. Morning sunlight may regulate circadian rhythms, subsequently improving sleep. Findings have potential implications for sleep interventions and daylight savings time policies. Future research should test whether morning sunlight exposure can enhance the effectiveness of sleep interventions.

Uses of antiseizure medication among pregnant women with epilepsy and risk of adverse obstetric outcomes: A group-based trajectory analysis.

This study was undertaken to examine the association between different patterns of antiseizure medication (ASM) use during pregnancy and adverse obstetric outcomes (preterm birth, low birth weight [LBW], and small for gestational age [SGA]). This retrospective cohort study used the Birth Certificate Application and National Health Insurance data in Taiwan (January 1, 2004 through December 31, 2018). We retrieved weekly ASM among pregnant women with epilepsy who were prepregnancy chronic users and used group-based trajectory modeling to identify distinct patterns of use. Logistic regressions were adopted to examine the association between patterns of ASM use and risk of preterm birth, LBW, and SGA. In addition, we revealed postnatal ASM utilization pattern among these prepregnancy chronic users as an exploratory study. Of 2175 pregnant women with epilepsy, we identified four patterns of ASM use during pregnancy: frequent and continuous (64.87%), frequent but discontinuous (7.08%), intermittent (19.72%), and intermittent and discontinuous users (8.32%). Compared to frequent and continuous users, the adjusted odds ratios for preterm birth in frequent but discontinuous, intermittent, and intermittent and discontinuous users were .83 (95% confidence interval [CI] = .47-1.48), .71 (95% CI = .47-1.05), and .88 (95% CI = .52-1.49), respectively. Similar results were observed for LBW and SGA. In the exploratory study, we found that most of our study subjects maintained the same patterns before and after delivery. After considering duration and timing of exposure, our study did not find an association between four distinct patterns of ASM use and adverse obstetric outcomes among women with epilepsy. The findings suggested that optimal seizure control could be received for pregnant women with epilepsy after evaluating the risks and benefits.

Lead Contamination in Pangasius Djambal in the Dam of Kalitidu District, Bojonegoro District: An Environmental Health Risk Study

Introduction: One of the areas passed by the Bengawan Solo River is Bojonegoro. Many Bojonegoro people find fish at the point of Bendung Gerak, Ngringinrejo Village. One of the fish that is often caught is Pangasius djambal. At this location, the dominant waste contamination comes from agricultural and domestic waste. Lead can contaminate water and enter through the food chain in fish which are later eaten by humans. The purpose of this study was to analyze the environmental health risk of lead (Pb) content in Pangasius djambal in Bendung Gerak Ngringinrejo Village, Kalitidu District, Bojonegoro Regency. Methods: This research used field environmental health risk analysis method. The total sampling of the community was 50 respondents and was taken using accidental sampling. Community sample criteria are those who consume Pangasius djambal within 1 year. Environmental samples are Pangasius djambal taken at 3 points and analyzed using the Atomic Absorption Spectrophotometry (AAS) method. Results and Discussion: The results showed lead intakes at points A, B, and C were 0.0018 mg/kg/day, 0.0639 mg/kg/day, and 0.0012 mg/kg.day, respectively. The results show the RQ value of point B RQ&gt;1 (unsafe), while points A and C are RQ≤1 (safe). It can be caused by several factors such as body weight, intake rate, consumption frequency, exposure duration, and lead concentration. Conclusion: Based on these results, it is necessary to do risk management at point B.

Prevalence and associated factors of myopia among adolescents aged 12–15 in Shandong Province, China: a cross-sectional study

Myopia is a growing concern worldwide, especially among adolescents. This study aimed to investigate the prevalence and associated factors of myopia in adolescents aged 12–15 in Shandong Province, China. This cross-sectional study adhered to the Strengthening the Reporting of Observational Studies in Epidemiology guidelines and involved stratified random cluster sampling of 128,678 students from 186 middle schools across 17 cities in Shandong Province. Data collection was conducted from March to April 2024. We excluded students with organic eye diseases, abnormal binocular vision functions, or a history of eye injuries or surgeries. Myopia was assessed using the standard logarithmic visual acuity chart and autorefractor without inducing ciliary muscle paralysis. A comprehensive questionnaire survey was conducted to gather demographic characteristics and daily life behaviors. With the chi-squared test for univariable analysis and multivariable logistic regression for identifying significant factors. This study included 126,375 participants, with a gender distribution of 51.02% male and 48.98% female. The overall prevalence of myopia was 71.34%. Higher prevalence was observed in girls (72.26%) compared to boys (70.45%), and the prevalence increased with age, peaking at 73.12% in 15-year-olds. Urban residents had a higher prevalence (71.86%) than rural (70.39%). Factors such as increased frequency of eye usage while lying down or leaning forward, frequent use of eyes while walking or riding in a car, prolonged screen time, and extended homework duration were associated with higher odds of developing myopia. Conversely, higher frequency of outdoor exercise, maintaining proper posture during reading and writing, greater distance from eyes to screen, and longer sleep duration were associated with lower odds. Additionally, female gender, older age, urban residence, and parental history of myopia increased the risk. The high prevalence of myopia among adolescents in Shandong Province was influenced by a combination of demographic, behavioral, and environmental factors. The study highlighted the importance of lifestyle modifications, such as increasing outdoor activities and maintaining proper visual habits, limiting the duration of screen exposure and homework sessions, and extending sleep duration, to mitigate the risk of developing myopia. These findings underscored the need for targeted public health interventions and educational campaigns to address this significant public health issue.

Evaluating Antibiotic De-escalation for Autologous Stem Cell Transplant Patients With Febrile Neutropenia in a Real-World Clinical Setting

Febrile neutropenia (FN) is a complication in approximately 90% of autologous stem cell transplant (SCT) patients. Guidelines support early broad-spectrum antibiotics (BSA) to prevent morbidity and mortality. However, in patients who are clinically stable and deemed to have a fever of unknown origin, the optimal duration of BSA is unknown. Accumulating evidence suggests that de-escalation of BSA in select patients may decrease duration of BSA exposure without compromising clinical outcomes such as infection, recurrent fever, and readmission. With this, a de-escalation protocol was implemented at Vanderbilt University Medical Center (VUMC) to identify autologous SCT patients who may benefit from early de-escalation of BSA. The objectives of this study were to analyze the impact of early empiric antibiotic de-escalation on the duration of BSA as well as its impact on the incidence of recurrent fever and documented infection in autologous SCT patients. This was a single-center, retrospective study evaluating patients older than 18 years of age who underwent autologous SCT and experienced an episode of FN from January 2018 to December 2022 at VUMC (N = 195). The protocol was initiated on January 1, 2020, to de-escalate BSA back to prophylaxis in stable neutropenic patients determined to have a fever of unknown origin. The primary outcome was the number of BSA days within 30 days. Secondary clinical outcomes included recurrent fever, documented infection, readmission, 30-day mortality, and 90-day non-relapsed mortality (NRM). Outcomes were compared across pre- and post-protocol groups with a Wilcoxon rank sum test, Pearson chi-square test, or regression analysis as appropriate. The median BSA duration was 4.7 and 2.7 days in the pre- and post-protocol groups, respectively (p <0.001). Recurrent fever (14.2% vs. 16.0%, p = 0.726), documented infection (1.7% vs. 6.7%, p = 0.068), and readmission (13.3% vs. 22.7%, p = 0.091) within 30 days were not significantly different between the two groups. Neither 30-day mortality (0.8% vs. 1.3%, p = 0.736) nor 90-day NRM (0.8% vs. 1.3%, p = 0.736) differed. The implementation of an early de-escalation protocol for autologous SCT patients who develop FN was associated with a reduction in duration of BSA compared to the pre-protocol group without a significant difference in readmission, recurrent fevers, and documented infections. This study adds to existing evidence that early de-escalation of BSA in FN patients with a fever of unknown origin who are afebrile and clinically stable is safe and reduces unnecessary antibiotic use.

Investigation on electromagnetic and heat transfer coupling of heating susceptor for selective microwave hybrid soldering: 3D multi-physics simulation and experiment

The utilization of microwave hybrid heating as an emerging technique in the field of low-temperature joining presents a notable benefit of delivering both selective and rapid heating, a feature that is not commonly observed in traditional soldering methods. However, due to the complex multi-physical coupling problem, the factors and mechanisms affecting the heating effect of the susceptors have not been clearly explained. To examine the effect of susceptor shape, size, and process parameters on heating efficiency, a numerical model of electromagnetic and thermal coupling was created to analyze silicon carbide susceptor heating under microwave action. The response surface method examined how microwave frequency, power, and exposure time affect susceptor heating efficiency. The model’s three process parameters are used to selectively heat Cu/SAC305/Cu joints, and the connection mechanism is studied. The results reveal that cylindrical susceptors heat more efficiently and uniformly than cubic ones. The heating efficiency is the highest when the height of the susceptor is 30 mm. Moreover, the heating effect is optimum at 2.45 GHz. Microwave power and exposure period positively linked with susceptor heating efficiency. The finite element simulation model shows that energy consumption at 2.45 GHz\\2 kW210 s is 78.38 % of that at 2.45 GHZ\\1 kW370 s, and the maximum temperature difference is 73.44 % of that at 2.45 GHz\\3k W\\90 s. MHS experiments show that as exposure duration increases, Cu6Sn5 grew and the growth orientation becomes consistent and perpendicular to the {0 0 0 1} family of crystal planes. Under process settings of 2.45 GHz \\ 2 kW \\ 210 s, the joint can achieve 16.55 MPa shear tensile strength. The results can serve as references for the study on selective microwave hybrid soldering and provide a new idea for selective and efficient soldering.

A New Approach Refined Probabilistic Health Risk Assessment of Shaoguan Smelter Based on Microenvironment - Guangdong Province, China, 2021.

This study introduces a novel method for developing an advanced exposure conceptual model tailored for health risk assessment, focusing on microenvironments. The research was conducted at a major smelter in China to assess the health risks associated with trace metals (TMs) pollutants in the facility and the surrounding soil. Deterministic risk assessment indicated that cobalt, cadmium, antimony, manganese, arsenic, plumbum, and mercury (Co, Cd, Sb, Mn, As, Pb, and Hg) necessitated further evaluation through probabilistic risk assessment to assess potential health risks to residents. The 95% quantile concentrations of other TMs were found to be within acceptable health risk limits. For the probabilistic risk assessment, exposure parameters such as body weight, respiration rate, and exposure duration were collected using a questionnaire. This targeted assessment of the residential microenvironment revealed it as the site of the highest carcinogenic (CR) and non-carcinogenic risks (NCR), with values ranging from 2.84×10-5 to 6.7×10-5 and 1.59 to 5.57, respectively. The primary contaminants posing the greatest health risks in residential and industrial areas have been identified as As, Pb, and Mn. The probabilistic health risk model, which focuses on microenvironmental factors, yields more precise results and offers a valuable tool for managing soil health risks.

Durability of partially cured GFRP reinforcing bars in alkaline environments with or without sustained tensile load

Corrosion of steel reinforcing bars (rebars) in reinforced concrete structures can be addressed by using corrosion-resistant materials like Fiber-Reinforced Polymers (FRP). However, in France, FRP rebars are primarily restricted to temporary applications due to lack of comprehensive durability data. While numerous studies have explored FRP durability in alkaline environments, understanding the combined effect of alkali ions and sustained loading remains limited. Furthermore, the impact of incomplete matrix curing on the long-term performance of FRP rebars is limited.Accordingly, this paper investigates the durability of Glass FRP (GFRP) rebars exposed to alkali environments at varying temperatures. A batch of partially cured rebars was selected for this study, with part of them undergoing post-curing to investigate the effect of curing state on the ageing behaviour. Additionally, some partially cured specimens were subjected to combined sustained tensile loading at 20 % and 40 % of ultimate strength. Mechanical, physico-chemical and microstructural characterizations were conducted after various exposure durations. Results revealed that incomplete curing minimally impacted long-term tensile properties but significantly affected the interlaminar shear strength of aged rebars. Moreover, applying a combined load had little influence on residual properties at 20°C but led to rapid reduction in GFRP residual tensile strength at higher ageing temperatures (40 and 60°C).

Ruxolitinib for pediatric patients with treatment-naïve and steroid-refractory acute graft-versus-host disease: the REACH4 study

AbstractIn REACH4, a phase 1/2, open-label, single-arm, multicenter study, the pharmacokinetics (PK), efficacy, and safety of ruxolitinib were evaluated in treatment-naïve and steroid-refractory pediatric patients with grade 2 to 4 acute graft-versus-host disease (aGVHD; n = 45). Ruxolitinib dosing was based on age and targeted the exposure in adults receiving 10 mg twice daily; group 1 (aged ≥12 to <18 years) received 10 mg twice daily and preliminary starting doses for groups 2 (aged ≥6 to <12 years) and 3 (aged ≥2 to <6 years) were 5 mg twice daily and 4 mg/m2 twice daily, respectively. The phase 1 primary objective was to assess ruxolitinib PK parameters and define an age-appropriate recommended phase 2 dose (RP2D) for patients aged <12 years. The phase 2 primary objective was to measure the activity of ruxolitinib as assessed by overall response rate (ORR) at day 28; the key secondary objective was to assess the durable ORR at day 56. Ruxolitinib exposure was comparable across age groups; starting doses were confirmed as the RP2D. The median duration of ruxolitinib exposure was 3.8 months (range, 0.3-11.2). ORR in all patients was 84.4% (90% confidence interval [CI], 72.8-92.5) at day 28, with a durable ORR at day 56 of 66.7% (90% CI, 53.4-78.2); high response rates were observed across age groups and in both treatment-naïve and steroid-refractory subgroups. Adverse events were consistent with those expected in patients with aGVHD (anemia, decreased neutrophil and leukocyte count) treated with ruxolitinib. In pediatric patients with aGVHD, ruxolitinib showed clinically meaningful efficacy with no new safety signals. This trial was registered at www.ClinicalTrials.gov as #NCT03491215.

Characterization of emissions from rubber modified asphalt and their impact on environmental burden: Insights into composition variability and hazard assessment

Rubber modified asphalt (RMA) is a promising avenue for recycling waste tires but faces concerns over hazardous fumes emission during production and construction. This study employs a specialized apparatus to analyze RMA's emission behavior, focusing on crumb rubber size variations under thermal conditions. Ozone Formation Potential (OFP) and Secondary Organic Aerosol Formation Potential (SOAFP) were quantified to evaluate the environmental burden. Results indicate distinct periods of emission behavior for different pollutants, with H2S emissions primarily occurring within the initial 150 min while volatile organic compounds (VOCs) dominate within the first 270 min. The size of rubber particles and thermal exposure duration influence the VOCs microscopic emission characteristics and environmental burdens. Polycyclic aromatic hydrocarbons (PAHs) emerge as the primary contributors to OFP and SOAFP, accounting for nearly 65 % and 25 %−60 %, respectively. High molecular weight aliphatic hydrocarbons (ALHs) also significantly contribute to SOAFP, with PAHs dominating throughout, while ALHs peak during the middle stage. H2S emissions likely stem from rubber, while early VOC emissions originate from rubber, transitioning to petroleum asphalt during the middle and late stages. Asphalt fractions influence emission behavior and property evolution. These findings inform emission suppression strategies and highlight the need for tailored approaches to mitigate emissions effectively.

Asbestos Surveillance Program Aachen (ASPA): Cancer mortality among asbestos exposed power industry workers

BackgroundThe time between initial asbestos exposure and asbestos-related disease can span several decades. The Asbestos Surveillance Program aims to detect early asbestos-related diseases in a cohort of 8,565 power industry workers formerly exposed to asbestos. Research questionHow does asbestos exposure patterns affect cancer mortality and the duration of latency until death? MethodsA mortality follow-up was conducted with available vital status for 8,476 participants (99 %) and available death certificates for 89.9 % of deceased participants. Standardised mortality ratios (SMR) were calculated for asbestos-related cancers. The SMR of mesothelioma and lung cancer were stratified by exposure duration, cumulative asbestos exposure and smoking. The effect of age at first exposure, cumulative asbestos exposure and smoking on the duration of latency until death was examined using multiple linear regression analysis. ResultsThe mortality risk of mesothelioma (n = 104) increased with cumulative asbestos exposure but not with exposure duration; the highest mortality (SMR: 23.20; 95 % CI: 17.62–29.99) was observed in participants who performed activities with short extremely high exposures (steam turbine revisions). Lung cancer mortality (n = 215) was not increased (SMR: 1.03; 95 % CI: 0.89–1.17). Median latency until death was 46 (15–63) years for mesothelioma and 44 (15–70) years for lung cancer and deaths occurred between age 64 and 82 years. Latency until death was not influenced by age at first exposure, cumulative exposure, or smoking. ConclusionCumulative dose seems to be more appropriate than exposure duration for estimating the risk of mesothelioma death. Additionally, exposure with high cumulative doses in short time should be considered. Since only lung cancer mortality, not incidence, was recorded in this study, lung cancer risk associated with asbestos exposure could not be assessed and the lung cancer mortality was lower than expected probably due to screening effects and improved treatments. The critical time window of death from asbestos-related cancer is between the seventh and ninth decade of life. Future studies should further explore the concept of latency, especially since large ranges are reported throughout the literature.

Performance assessment of firefighter protective clothing under different thermal environments: Impact of the variation of thickness in inter-layer airgap and microclimate

Personal protective equipment for firefighters can effectively prevent skin burns and ensure firefighters' safety. Considering a variety of fire environments faced by a firefighter, the present study is devoted to showing the role of the inter-layer fabric airgap and its variation in thickness on skin burns under high intensity heat flux. The present numerical model is formulated by considering a coupled conduction and radiation heat interaction in the porous fabric medium and the Pennes bioheat transfer model for the multi-layered skin. The study considers the effect of variation in airgap thickness, variation in heat transfer coefficient, and duration of exposure on the thermal damage of the firefighter's skin subjected to different harsh thermal environments. The results found that increasing the thickness of AG1 and AG2 does not yield a significant impact during the exposure time. Conversely, AG3 and AG4 lead to considerable temperature reductions at the basal layer, with AG3 causing a decrease of 2.6 °C to 2.9 °C and AG4 causing a decrease of 11.9 °C to 17.0 °C under all exposure conditions. Additionally, when the heat transfer coefficient increases during post-exposure, temperature drops of 9.17 °C to 10.72 °C, 9.81 °C to 11.46 °C, 10.0 °C to 11.64 °C, and 8.68 °C to 10.07 °C are observed for AG1, AG2, AG3, and AG4, respectively, across all exposure conditions. However, both the airgaps have a substantial effect on thermal protection during the post exposure period. In addition, the nature of the variation of stored and transmitted energy in fabric assembly shows an opposite trend during both the exposure and post exposure period in contrast to the third and fourth airgaps for all the considered thermal environments.