Average Concentration Research Articles

Spatial and Temporal Variability of Atmospheric Methane Concentrations in Bangladesh

We used 2019-2021 TROPOMI satellite observations of atmospheric methane in an analytical inversion to identify methane (CH4) emissions in Bangladesh from 2019 to 2021. Methane is considered as second most important greenhouse gas (GHG) contributor, with nearly 28 times more potential to global climate change next to carbon dioxide. Monitoring and predicting atmospheric methane concentrations is important in global efforts to mitigate and adapt to climate change. This study made an effort to detect existing concentrations of CH4 at the atmospheric level of Bangladesh, hot spot identification, and spatial-temporal pattern detection using remote sensing. The study used daily column-averaged dry air column methane mixing ratio (XCH4) data retrieved from TROPOMI measurements. Weekly/monthly average concentrations were extracted from Sentiniel-5P satellite images. The batch inverse Distance weighting (IDW) interpolation technique was conducted on raw images (excluding October months) to fill in missing values in the images. The emerging hot spot analysis tool (ArcGIS Pro) was applied to the weekly interpolated images to identify statistically significant spatiotemporal hotspots of CH4 concentrations. Results indicate that the persistent hot spot and intensifying hot spot of methane concentrations are prominent within the Dhaka Division. An intensifying hot spot of CH4 was found within the Dhaka district, which indicates that it is a hot spot for the study period. Source point detection and real-time monitoring can be more effective in identifying the methane emission reduction mechanism.

Distinctive dust weather intensities in North China resulted from two types of atmospheric circulation anomalies

Abstract. Dust weather in North China (NC; 34–42° N, 105–120° E) has worsened in recent years, posing adverse impacts on the environment, human health, and the economy. A super dust storm that occurred on 15 March 2021 raised Beijing's PM10 (particulate matter with a diameter less than 10 µm) concentrations above 7000 µg m−3, while 2023 witnessed the highest spring dust weather frequency in nearly a decade. Previous research has primarily focused on the role of the Mongolian cyclone in influencing dust weather in NC, with less attention given to other synoptic systems. Additionally, the differences in PM10 concentrations in NC caused by different synoptic systems have not yet been quantified. This study demonstrates that the Mongolian cyclone was responsible for 61.7 % of the dust weather in NC, while the remaining 38.3 % was primarily caused by the cold high. The dust intensity induced by the Mongolian cyclone was stronger than that of the cold high, with average maximum PM10 concentrations of 3076 and 2391 µg m−3, respectively. The three-dimensional structure of atmospheric circulation anomalies and related dynamic mechanisms of the two types were concluded. To comprehensively forecast the two types of dust weather, a common predictor was constructed based on the 500 hPa cyclonic anomaly and anticyclonic anomaly circulation systems. These findings contribute to enhancing the comprehension of dust weather in NC and offer insights for both dust weather forecasting and climate prediction.

A Novel LC-MS/MS Method for the Measurement of Elexacaftor, Tezacaftor and Ivacaftor in Plasma, Dried Plasma Spot (DPS) and Whole Blood in Volumetric Absorptive Microsampling (VAMS) Devices

Background: The combination of ivacaftor, tezacaftor and elexacaftor (ETI) is approved for patients with cystic fibrosis (CF) aged two years and older and at least one F508del mutation in the CFTR gene. Variability in ETI treatment response has been repeatedly reported, and its reasons are unclear and understudied. Objectives: We present a novel liquid chromatography–tandem mass spectrometry (LC–MS/MS) method for the rapid and simultaneous quantification of ETI in plasma, dried plasma spots (DPS), and whole blood volumetric absorptive microsampling (VAMS). Methods: The method utilizes a rapid extraction protocol with 200 μL methanol after the addition of deuterated internal standards. Chromatographic separation was achieved using a reversed-phase Hypersil Gold aQ column (Thermo Fisher Scientific). The method was validated according to ICH (International Council on Harmonisation) guidelines M10 for bioanalytical method validation, demonstrating linearity in the concentration range 0.020–12.000 µg/mL. It was also proved accurate and reproducible with no matrix effect. This method was applied to anonymized samples from patients undergoing ETI treatment: eight plasma and DPS and five VAMS samples were analyzed. Results: ETI concentrations measured in plasma and DPS were interchangeable, whereas ETI concentrations in VAMS were lower than in plasma, as expected for molecules with high plasma protein binding (99%). A correction factor based on the hematocrit value was used to calculate the equivalent plasma concentration from VAMS concentrations. Conclusions: This method is suitable for pharmacokinetic (PK) studies and could facilitate the centralization of samples to specialized laboratories, supporting multicenter studies.

Current state of natural and artificial radiation in the Eastern Black Sea Coast of Türkiye (Trabzon–Rize–Artvin) 38 years after Chernobyl

Abstract The aim of this study was to evaluate the artificial and natural radiation dose levels in the coastal areas of Trabzon–Rize–Artvin provinces 38 years after the Chernobyl nuclear accident. Radioactive 232Th, 238U, 40K and 137Cs concentrations were determined in 49 soil samples by HPGe gamma spectrometry. Average concentrations were 12 Bqkg−1 for 238U, 15 Bqkg−1 for 232Th, 162 Bqkg−1 for 40K and 37 Bqkg−1 for 137Cs. Annual effective dose equivalents and excess lifetime cancer risk values are below the world average. This study also presents the average 137Cs value measured in the same area from 1990–2004–2024.

Voriconazole Steady-State Trough Concentrations and Clinical Outcomes in Patients with Talaromycosis.

Voriconazole (VRC) has been used as an alternative treatment for talaromycosis. However, there are few studies reporting the VRC plasma concentration in patients with talaromycosis. The purpose of this study was to analyze the correlations between VRC initial steady-state trough concentration and clinical outcomes. We prospectively enrolled patients who were diagnosed with talaromycosis and received VRC as initial antifungal treatment regime. Medical information, VRC initial steady-state trough concentration, clinical outcomes and adverse events (AEs) were recorded for analysis. This study included 69 patients with talaromycosis receiving VRC treatment, including 38 HIV-positive patients and 31 HIV-negative patients. The average age of the HIV-positive patients was 42years, and that of the HIV-negative patients was 51years. After 12 weeks of antifungal treatment, 55 patients achieved clinical remission, 3 patients were transferred to amphotericin B treatment because of persistent clinical symptoms, and 5 patients died, 2 patients discontinued VRC treatment due to AEs. Follow up to6 months,a total of 14 AEs were observed in 12 patients, and 3 patients discontinued VRC treatment due to AEs. The average VRC initial steady-state trough concentration was 5.26mg/L, with a range of 0.23-16.95mg/L, indicating high variability. No correlation was found between the VRC initial steady-state trough concentration and treatment failure (P = 0.079). A significant correlation between AEs and the VRC initial steady-state trough concentration was found (P = 0.048). The VRC initial steady-state trough concentration threshold for AEs was 5.88mg/L according to the ROC curve analysis. In addition, there was a significant correlation between mortality and the APACHE II score (P = 0.029). The risk of death significantly increased when the APACHE II score was > 10. Voriconazole is an effective antifungal drug for talaromycosis in patients with APACHE II scores < 10. VRC steady-state trough concentration may not be significantly correlated with poor prognosis. A high VRC trough concentration was significantly correlated with AEs, and it may promote the management of AEs.

Atmospheric Estrogenic Semi-Volatile Compounds and PAH in PM2.5 in Mexico City

The quantification of semi-volatile organic compounds with potential endocrine-disrupting activity contained in fine atmospheric particles (PM2.5) is essential to understand their temporal behavior, identify their sources, and evaluate the health risks resulting from population exposure to said compounds. Since information and research outcomes regarding their presence in the atmosphere in developing countries are scarce, the main objective of this work was the development of a methodology devoted to extracting, characterizing, and quantifying, for the first time in Mexico, the concentration levels of three important groups of endocrine-disrupting compounds (EDCs) bonded to PM2.5 and collected during a year, namely: alkylphenols (4-n-nonylphenol (4NP) and 4-tert-octylphenol (4tOP)); bisphenols (bisphenol A (BPA) and bisphenol F (BPF)); natural and synthetic hormones (17β-estradiol (E2), estriol (E3) and 17α-ethinyl estradiol (EE2)). Further, priority polycyclic aromatic hydrocarbons (PAH) that also disrupt endocrine activity were analyzed. All compounds were determined by gas chromatography coupled to tandem mass spectrometry, and the concentration levels were analyzed for different climatic seasons. Cold-dry (CD) season displayed higher levels of 4NP, bisphenols, and hormones (between 0.71 (4NP) and 1860 pg m−3 (BPA)), as well as PAH concentrations (9.12 ng m−3). Regarding health effects, concentrations of alkylphenols, bisphenols, and hormones quantified had a value of estradiol equivalent concentration (EEQE2) between 0.07 and 0.17 ng m−3. PAH concentrations did not have carcinogenic and mutagenic risk with BaP(PEQ) &lt; 1 ng m−3. These results can be used by policymakers in the design of strategies for air pollution control.

Life Prediction of Penstock Based on Strength Simulation and Sediment Wear Test

A hydropower station, which has been in operation for over 50 years, has a penstock located in the plant’s open pipe section. Recently, concerns have been raised regarding the potential risks to the penstock’s safe operation due to wall thinning caused by abrasion. A series of stress tests, strength mathematical model analysis, and sediment erosion tests were performed on the penstock during turbine load rejection events. A stress and strain monitoring system for the steel pressure pipe was developed, enabling real-time monitoring and providing a warning function. The current wall thickness of the steel pressure pipe is about 28 mm. The results indicate that a pipe rupture is unlikely under any load rejection scenario. However, if the wall thickness is reduced to around 24 mm, the maximum equivalent stress of the pipe will approach the safety limit during load rejection. The sediment erosion test showed an erosion rate of 3.509 × 10–5 mm/h at an average sediment concentration of 0.63 kg/m3. Assuming no other factors, such as an increase in river sediment concentration, and based on the design specifications of the steel pressure pipe and the annual average sediment concentration of 0.63 kg/m3, it is projected that the open pipe section can be operated for about 19 years before the wall thickness reaches 24 mm. It is recommended that once the wall thickness reaches 24 mm due to erosion or other factors, the pipeline system undergoes maintenance or replacement. The findings provide significant guidance for the operation of similar power stations.

A Bioassay Analysis of Uranium and Lead in Urine Samples from a High Natural Background Radiation Area in Indonesia

Heavy metal pollution is a major environmental concern due to the high toxicity of heavy metals in humans. High natural background radiation areas (HNBRAs) contain high concentrations of the radioactive element 238U, which decays into 206Pb, in their soil, crops, and water. Concentrations of the heavy metals lead (Pb) and uranium (U) are, thus, correlated with HNBRAs. Mamuju in Indonesia is a recently studied HNBRA where high concentrations of Pb and U in the soil have been reported. The present study analyzes Mamuju residents’ exposure to Pb and U. Two zones in the study area were selected for comprehensive assessment. North Botteng was chosen to represent the HNBRA, and Topoyo was selected as the control zone, with 22 urine samples collected from each zone. The samples were analyzed using a quadrupole inductively coupled plasma mass spectrometer (ICP-MS). The average concentrations of Pb measured in the urine samples were 1.31 mg L−1 and 0.77 mg L−1 in North Botteng and Topoyo, respectively. These values are higher than the urine Pb reference value of 5 µg L−1. The urine Pb concentrations in both studied zones were alarmingly high, which may have serious health effects on the population and should warrant action to reduce Pb exposure in this area. The committed effective dose from the ingestion of 238U in North Botteng was higher than in Topoyo, measuring 36.0 mSv and 8.9 mSv, respectively. The area most affected by the ingestion of 238U was the red bone marrow, followed by the bone surface.

Seasonal variation of airborne fungal diversity and community structure in Urmia Lake, Iran.

A study conducted around Urmia Lake, Iran, investigated the impact of dust storms on fungal concentrations in the air. Researchers collected samples over a year, analyzing fungal variations during dusty and normal days. The average fungal concentration was found to be 436.2 CFU/m3, with Cladosporium cladosporioides, Penicillium chrysogenum, and Cladosporium iridis being the most prevalent species. Notably, fungal concentrations during dust days averaged 967.65 CFU/m3, which is 3.6 times higher than on normal days (267.10 CFU/m3). A total of 61 species were detected on normal days, compared to 45 on dusty days, with Aspergillus and Cladosporium spp. dominating both conditions. The study also linked environmental factors like temperature, humidity, and wind speed to fungal concentrations. Additionally, the distribution of dust was analyzed using the HYSPLIT model and MODIS satellite imagery, highlighting the health risks associated with high fungal concentrations and changing mycobiota due to dust disturbances.

Identification of particulate matter (PM10 and PM2.5) sources using bivariate polar plots and k-means clustering in a South American megacity: Metropolitan Area of Lima-Callao, Peru.

The identification of different air pollution sources is essential to effectively control atmospheric pollution, particularly in megacities of emerging countries with rapid economic development, such as the Metropolitan Area of Lima-Callao (MALC). The objective of this research was to identify the main sources of particulate matter pollution by applying bivariate polar plots and the k-means clustering algorithm. These statistical techniques were applied to hourly in situ data of four variables collected over a 5-year period (2015-2019) by the Automatic Air Quality Monitoring Network of the MALC: wind direction, wind speed, PM10, and PM2.5 concentrations. Average PM10 concentrations ranged from 34μgm-3 (CDM station) to 126.7μgm-3 (VMT station), while average PM2.5 concentrations ranged from 16.8μgm-3 (CDM station) to 41.2μgm-3 (ATE station). The diurnal variation of PM presented two peaks, one in the morning (from 0800 to 1000h) and the other at night (from 1900 to 2300h), with the highest concentrations of PM10 recorded at the ATE (0800h: 155.8μgm-3) and VMT (2100h: 154.6μgm-3) stations, and PM2.5 at the ATE station (0800h: 60.3μgm-3 and 2300h: 37.5μgm-3). The results showed that the contributions of PM10 are directly related to emissions from industrial activities, automotive fleet, construction, demolition, wind erosion, and the suspension and resuspension of particulates from unpaved roads. Meanwhile, high concentrations of PM2.5 are mainly attributed to vehicle exhaust emissions, industrial emissions, secondary particulate formation, and drag by the action of the winds. The major source of particulate matter contamination is the vehicle fleet, and within this, automobiles, station wagons, combi vans, and 2 and 3-wheel motorcycles are those that have the greatest contribution. These results were supported by non-parametric statistical tests such as Kruskal-Wallis and Mann-Whitney U and validated by the conditional bivariate probability function. The findings of this work may help to implement pollution prevention and control strategies in the future within this South American megacity.

Unprecedented Summer Phytoplankton Bloom in the Ross Sea

AbstractHigh‐resolution glider sampling in the southwestern Ross Sea revealed an extensive phytoplankton bloom in austral summer 2022–2023 that persisted for over one month and extended through the upper 100 m of the water column. The temporal mean euphotic‐zone chlorophyll concentration was 20.38.5 , six to nine times higher than average summer Ross Sea concentrations. The bloom was likely initially dominated by Phaeocystis, favored over diatoms due to low light and high iron availability. Our observations are consistent with an ice‐edge bloom likely fueled by iron supply and enhanced stratification from late sea‐ice melt during an anomalously high ice‐covered summer. Photoacclimation to particularly low light conditions might have enhanced Chl‐a fluorescence. In the Ross Sea, the most productive region in the Southern Ocean, understanding the drivers of this extreme bloom is crucial for predicting potential impacts of the changing climate on primary production rates and carbon sequestration.

Environmental and health risk assessment of polycyclic aromatic hydrocarbons and toxic elements in the red sea using Monte Carlo simulation

This research evaluates the environmental and health risks linked to potentially toxic elements (PTEs) and PAHs along the western coast of the Gulf of Suez, Egypt. This study investigated the concentration of 16 PAH compounds in the Suez Gulf, revealing significantly higher levels than the EU (0.20 µg/L) and US (0.030 µg/L) standards. The average total PAH concentration across eight locations was significantly higher, with the Suez area having the highest concentration at 479 µg/L. Pyrene (Pyr) was the dominant PAH with a concentration of 443 µg/L in Suez, while acenaphthylene (Ace) had the lowest concentration at 0.120 µg/L in Northern Zaafarana. Carcinogenic PAHs (CAR) ranged from 8.67 µg/L at Ras Gharib to 29.62 µg/L at Suez, highlighting the urgent need for regulatory measures. Confirmatory ratios pointed to industrial and shipping influences as petrogenic sources. Elevated total organic carbon (TOC) levels in Suez Bay indicated aggravated organic pollution, exacerbated by oil rigs and refineries. The ecological risk assessment highlighted substantial risks, particularly in Suez, necessitating immediate interventions to combat PAH contamination and preserve the environmental balance of the Red Sea. The dominant metals in water samples were arranged in descending order as follows: Pb > Fe > Cr > Cu > Zn > Mn > Cd > Ni. The study evaluated environmental and human health risks using a multifaceted approach, including cluster analysis, principal component analysis, and various indices (HPI, RI, MI, HQ, HI, and CR). Most water samples exhibited high pollution risks, surpassing permissible limits for HPI (> 100) and MI (> 6). Notably, HI oral values indicated significant non-carcinogenic risks for adults and children. While HI values for adults suggested low-risk dermal contact, those for children showed a substantial proportion in the high-risk category. Most water samples displayed CR values exceeding 1 × 10–4 for Cd, Cr, and Pb, indicating vulnerability to carcinogenic effects in both age groups. Monte Carlo simulations reinforced these findings, revealing a significant carcinogenic impact on children and adults. The identified clusters, reflective of industrial, petroleum-related, and urban runoff contamination sources, were consistently validated and clarified through PCA, enhancing the reliability of the findings. In light of these results, urgent and comprehensive water treatment measures are imperative to mitigate carcinogenic and non-carcinogenic health risks. These insights provide a foundation for implementing targeted management strategies to effectively address the challenges of heavy metal contamination in the Red Sea.

Innovative strategies for pollution assessment in Northern Bangladesh: Mapping pollution areas and tracing metal(loid)s sources in various soil types.

This study assessed the risks of soil pollution by heavy metals in Chilmari Upazila, northern Bangladesh, using the static environmental resilience (Pi) model of soil. Geostatistical modeling and self-organizing maps (SOM) identified pollution areas and spatial patterns, while a positive matrix factorization (PMF) model revealed pollution sources. The results showed that the average concentrations of Cr, Pb and As were well above background levels. Agricultural and industrial soils were mainly contaminated with Cr, Pb and As according to the Nemerow Pollution Index (NPI), Ecological Risk (ER) and Pi Index. Over 70% of the sites were contaminated with Pb and Cr, while co-contamination was particularly high. A one-way ANOVA showed significant correlations between Pb, Cu and Zn levels and human activities. The PMF analysis revealed that industrial effluents, agrochemicals and lithogenic sources were the main contributors to soil contamination with 16%, 41% and 43%, respectively. The SOM analysis revealed three distinct spatial patterns (Pb-Zn, Cr-Cu-Ni and Co-Mn-As), which are consistent with the PMF results. These results emphasize the need for stringent measures to reduce industrial emissions and remediate soil contamination in order to improve soil quality and food security.

Spatiotemporal occurrence, distribution, and risk of steroid hormones along the coast of Guangdong, China

IntroductionSteroid hormones are widely present in the environment and pose potential risks to organisms. Previous studies of steroid hormones have predominantly focused on terrestrial environments, with few studies conducted in marine environments.MethodsIn this study, we analyzed the occurrence of 44 steroid hormones in seawater, sediment, and marine organisms collected from the coast of Guangdong, China.ResultsTotal concentration of steroid hormones ranged from 0.11 to 30.15 ng/L in seawater, ND to 8.58 ng/g (dw) in sediments, and ND to 80.52 ng/g (ww) in organisms. The highest average concentrations of steroid hormones detected in seawater, sediments, and marine organisms were progestins, estrogens, and glucocorticoids, respectively. Steroid hormone concentrations in seawater were significantly higher during the dry season than the rainy season. The concentrations of steroid hormones in Guanghai Bay, the Pearl River Estuary, Daya Bay, and Zhelin Bay were significantly higher than those in other bays.DiscussionNegative correlations were observed between steroid hormones and salinity, indicating a potential continental input. Risk assessment results indicated that 17α-ethinylestradiol in Zhelin Bay posed high risks. Nevertheless, the consumption of seafood does not pose a significant health risk to humans. To the best of our knowledge, this is the first study to concurrently analyze androgens, glucocorticoids, progestins, and estrogens in water, sediment, and organisms from diverse marine environments.

Kurtosis as a Decisive Topographic Parameter for Pitting Attack of AISI 304L Stainless Steel

ABSTRACTThe effects of the centerline average (Ra), kurtosis (Rku), and Cr concentration at the surface on the pitting corrosion resistance of AISI 304L stainless steel were studied based on the modification of the corroding surface by mechanical polishing and electropolishing routes. The values of EP − Ecorr, EP − Erp, and iP were devised as the quantitative measures of pitting resistance, where EP is the pitting potential, Erp is the repassivation potential, Ecorr is the corrosion potential, and iP is the passive current density. Preliminary, the improved resistance against pitting corrosion was associated with the reduced Ra and the elevated Cr concentration on the surface. However, more intense analysis revealed that the samples with Rku &lt; ~3 (platykurtic distribution) exhibited a good resistance to pitting attack, irrespective of the values of Ra and Cr content. Accordingly, the importance of the Rku as a decisive topographic parameter for pitting attack was established.

Changes in dust concentration in a gas-dust cloud during blasting in an iron ore pit

In open-pit extraction of minerals emit large amounts of harmful dust fractions and gas into the atmosphere. This leads to atmospheric pollution in open pit and sanitary protection zones. The largest dust emissions are observed during blasting operations in open pits. This is especially the cases when unfavorable meteorological conditions occur, means of dust sup-pression are not sufficiently effective, blasting technology was violated. Dust particles are known to be able to propagate long distances from the source of the explosion. Dust fractions up to 10 µm diameter are the most dangerous, as they are the main risk factor for the devel-opment of chronic respiratory diseases. In particular, according to European standards, the average daily concentration of dust particles with a diameter between 2.5 and 10 µm should not exceed 0.05 mg/m3. The paper estimates mass concentrations of dust fractions in the gas-dust cloud at the dynamic stage of its formation after a mass explosion in an iron ore open pit. The following assumptions were made in the calculations: no influence of the temperature factor (ejected air flows); dust particles are spherical; flow of dust fractions by the gas flow follows the Stokes law. The ranges of variation of ascent height and mass concentrations of dust fractions at the dynamic stage of gas-dust cloud formation are established. In particular, the lift height of the dust fraction is directly proportional to the value of the dynamic impulse. The differ-ence in mass concentrations of dust fractions in the gas-dust cloud is due to the physical and mechanical properties of rocks destroyed by boreholes explosive substance charge. When de-termining the mass concentrations of dust fractions, the results of experimental studies were used, which were carried out in the open pit of Ingulec Mining and Processing Combine. The graphical dependence of average mass concentrations of dust fractions depending on the height of their ascent at the dynamic stage of gas-dust cloud formation is presented, the re-gression equation in the form of a degree function is obtained. The results of calculations have shown that the greatest intensity of mass concentration increase in the gas-dust cloud at the dynamic stage of its formation is characteristic of dust fractions with diameter up to 31 μm. The intensity of growth of mass concentrations of larger dust fractions decreases markedly.

Alternative dosing regimens of tislelizumab proposed using modeling and simulation.

394 Background: Tislelizumab (TIS; BGB-A317) is approved for the treatment of multiple solid tumors, administered at 200 mg every 3 weeks (Q3W), and has demonstrated a flat exposure–response relationship across a wide range of doses. We evaluated alternative dosing regimens of TIS at 150 mg every 2 weeks (Q2W), 300 mg every 4 weeks (Q4W), and 400 mg every 6 weeks (Q6W) using a model-based approach with the aim of alleviating patient burden by providing longer dosing intervals and/or treatment flexibility compatible with background chemotherapy to meet the needs of patients and healthcare practitioners. Methods: A previously developed population pharmacokinetic (PK) model was used for simulating PK exposure of the alternative regimens, which were selected by exposure-matching to the reference dose of 200 mg Q3W. PK-based criteria (peak concentration [C max ] within 25% and trough concentration [C trough ] within 20% of the reference dose) were also used. Alternative dosing regimen exposures in the first least common time interval and at steady state were compared with the reference. Deviations from PK-based criteria were bridged using appropriate safety and efficacy references and exposure–response analyses using data from four phase 1, 2, and 3 clinical trials of TIS in patients with solid tumors, including gastric cancer and esophageal squamous cell carcinoma. Results: Simulations at steady state shown here demonstrate that the TIS alternative dosing regimens of 150 mg Q2W, 300 mg Q4W, and 400 mg Q6W produce comparable exposures to the 200 mg Q3W reference regimen. Although the simulated C max at 300 mg Q4W and 400 mg Q6W were higher than with the 200 mg Q3W reference dose, these were below the C max of the 5 mg/kg Q3W safety reference (Table). And while the C trough for the 400 mg Q6W dosing regimen was lower than with the 200 mg Q3W reference dose, it was 10.7% higher compared with the 2 mg/kg efficacy reference dose; therefore, it was within the concentration range where a flat exposure–efficacy relationship of TIS has previously been established. Conclusions: TIS alternative dosing regimens of 150 mg Q2W, 300 mg Q4W, and 400 mg Q6W are expected to result in similar safety and efficacy profiles as the 200 mg Q3W reference dosing regimen and may be used interchangeably for indications where 200 mg Q3W is approved. Clinical trial information: NCT04716634 , NCT05014828 , NCT04379635 , NCT02407990 , NCT04068519 , NCT03430843 and NCT03358875 . Steady-state PK exposure metrics for alternative TIS doses vs reference doses. Parameter 150 mg Q2W vs 200 mg Q3W 300 mg Q4Wvs 200 mg Q3W 300 mg Q4Wvs 5 mg/kg Q3W a 400 mg Q6Wvs 200 mg Q3W 400 mg Q6Wvs 5 mg/kg Q3W a 400 mg Q6Wvs 2 mg/kg Q3W b C max −5.8 (Yes) 31.4 (No) −18.7 (Yes) 52.2 (No) −5.8 (Yes) – C average 12.3 (Yes) 12.6 (Yes) – 0.4 (Yes) – – C trough 27.2 (Yes) 0.1 (Yes) – −28.4 (No) – 10.7 (Yes) Data are presented as difference (% = [GM test − GM reference /GM reference ] × 100) vs the 200 mg Q3W reference, a safety reference, or b efficacy reference (meets regulatory criteria, Yes/No). C average , average concentration; GM, geometric mean.

Normal levels of Cu and Zn contamination present in swine manure increase the antibiotic resistance gene abundances in composting products

Cu and Zn are abundant heavy metals in swine manure. Heavy metals are not readily biodegradable and can continuously drive the co-selection of antibiotic resistance. Thus, to simulate the effects of different concentrations of heavy metals detected in swine manure on antibiotic resistance genes (ARGs), normal (L) and high (H) concentrations of Cu and Zn were added during composting. Compared with the control (CK), the total relative abundances (RAs) of ARGs in the composting products increased by 0.26–0.28 logs under CuL and ZnL. The total RAs of ARGs decreased by 0.84 logs under ZnH, and the RAs of sul1, tetX, and sul2 were 0.51–1.87 logs lower than those under CK (P < 0.05). Network analysis indicated that intI1 and ISCR1 were associated with the co-occurrence of ARGs and metal resistance genes. After composting, the abundances of intI1 were significantly higher under CuL and ZnL than CK (4.2–8.4 times), and normal concentrations of Cu and Zn promoted the horizontal transfer of ARGs. Moreover, the responses of the potential hosts to Cu and Zn affected the abundances of ARGs during composting. Overall, normal concentrations of heavy metals (CuL and ZnL) increased the ecological risk of ARGs in composting products.

Prenatal exposure to per- and polyfluoroalkyl substances (PFAS) from contaminated water and risk of childhood cancer in California, 2000-2015.

Few studies have investigated associations between per- and polyfluoroalkyl substances (PFAS) and childhood cancers. Detectable levels of PFAS in California water districts were reported in the Third Unregulated Contaminant Monitoring Rule for 2013-2015. Geocoded residences at birth were linked to corresponding water district boundaries for 10,220 California-born children (aged 0-15 years) diagnosed with cancers (2000-2015) and 29,974 healthy controls. A pharmacokinetic model was used to predict average steady-state maternal serum concentrations of perfluorooctanesulfonic acid (PFOS) and perfluorooctanoic acid (PFOA) from contaminated drinking water. Adjusted odds ratios (AORs) and 95% confidence intervals (CIs) per doubling of background exposure were calculated for cancers with at least 90 cases. Predicted PFOS and PFOA maternal serum concentrations ranged from background (5 ng/ml PFOS and 2 ng/ml PFOA) to 22.89 ng/ml and 6.66 ng/ml, respectively. There were suggestive associations between PFOS and nonastrocytoma gliomas (n = 268; AOR = 1.26; 95% CI: 0.99, 1.60), acute myeloid leukemia (n = 500; AOR = 1.14; 95% CI: 0.94, 1.39), Wilms tumors (n = 556, AOR = 1.15; 95% CI: 0.96, 1.38), and noncentral system embryonal tumors (n = 2,880; AOR = 1.07; 95% CI: 0.98, 1.17), and between PFOA and non-Hodgkin lymphoma (n = 384; AOR = 1.19; 95% CI: 0.95, 1.49). Among children of Mexico-born mothers, there was increased risk of Wilms tumor (n = 101; AORPFOS = 1.52; 95% CI: 1.06, 2.18; AORPFOA = 1.59, 95% CI: 1.12, 2.24) and noncentral system embryonal tumors (n = 557; AORPFOS = 1.24, 95% CI: 1.03, 1.50; AORPFOA = 1.19, 95% CI: 0.98, 1.45). Results suggest associations between predicted prenatal maternal PFAS serum concentrations and some childhood cancers. Future analyses are warranted.

Redox-induced phosphorus release from critical source areas following rainfall events in New Zealand.

Critical source areas (CSAs) can act as a source of phosphorus (P) during intermittent rainfall events and contribute to dissolved P loss via runoff. Dissolved forms of P are readily accessible for plant and algal uptake; hence it is a concern in terms of the eutrophication of freshwater bodies. The potential of CSAs to release dissolved P to surface runoff upon intermittent short-term submergence caused by different rainfall events has not been studied at a field-scale in New Zealand previously. A field study was conducted to investigate the potential of two different pastoral soil CSAs (Recent and Pallic soil) to release soil P over five rainfall events during winter and to explore the mechanisms of P release in these soils. Ten sampling stations were installed within each CSA in an area of 6×2m2. Each sampling station had two porewater samplers installed at two depths (2 and 10cm) below the soil surface. Two platinum half-cell electrodes were installed at the same two depths. Porewater and floodwater samples were collected following five rainfall events. Redox potentials were measured in-situ. Dissolved reactive phosphorus (DRP), pH, dissolved organic carbon, cations, anions, and alkalinity of the water samples were measured. Soil chemical P fractions were assessed at the beginning, middle and end of the experiment. Thermodynamic modelling was used to infer dissolution and formation of P and P-associated minerals. The average porewater DRP at the two depths during the rainfall events of the Recent and Pallic soils were 0.32-1.3mgL-1 and 0.26-2.31mgL-1, respectively. The average floodwater DRP concentrations of the Recent and Pallic soils were 35 and 43-fold higher than the target DRP concentration (0.01mgL-1) for the Manawatū River. The study highlights the substantial risk of P loss from CSAs to surface water, driven primarily by the reductive dissolution of Fe and Mn oxy(hydr)oxides. The findings underscore the importance of targeted management strategies to mitigate dissolved P runoff, particularly in high-risk CSAs frequent submerged during rainfall events. This study developed an effective method for monitoring soil porewater P and redox conditions, offering valuable insights and practical tools for resource managers seeking to reduce P contamination.