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Background: Previously reported results from phase III KEYNOTE-048 demonstrated similar or improved overall survival (OS) with pembrolizumab or pembrolizumab-chemotherapy versus cetuximab-chemotherapy (EXTREME) in Japanese patients with recurrent/metastatic head and neck squamous cell carcinoma (R/M HNSCC). We report results in Japanese patients from KEYNOTE-048 after 5 years of follow-up. Methods: Patients with R/M HNSCC of the oropharynx, oral cavity, hypopharynx, or larynx were randomly assigned 1:1:1 to pembrolizumab, pembrolizumab-chemotherapy, or EXTREME. Primary endpoints were OS and progression-free survival. Efficacy was evaluated in the programmed cell death ligand 1 (PD-L1) combined positive score (CPS) ≥ 20, PD-L1 CPS ≥ 1, and total Japanese populations. Results: In Japan, 67 patients were enrolled (pembrolizumab, n = 23; pembrolizumab-chemotherapy, n = 25; EXTREME, n = 19). Median follow-up was 71.0 months (range, 61.2–81.5); data cutoff, February 21, 2022. 5-year OS rates with pembrolizumab versus EXTREME were 35.7% versus 12.5% (hazard ratio [HR] 0.38; 95% CI 0.13–1.05), 23.8% versus 12.5% (HR 0.70; 95% CI 0.34–1.45), and 30.4% versus 10.5% (HR 0.54; 95% CI 0.27–1.07) in the PD-L1 CPS ≥ 20, CPS ≥ 1, and total Japanese populations, respectively. 5-year OS rates with pembrolizumab-chemotherapy versus EXTREME were 20.0% versus 14.3% (HR 0.79; 95% CI 0.27–2.33), 10.5% versus 14.3% (HR 1.18; 95% CI 0.56–2.48), and 8.0% versus 12.5% (HR 1.11; 95% CI 0.57–2.16) in the PD-L1 CPS ≥ 20, CPS ≥ 1, and total Japanese populations, respectively. Conclusion: After 5 years of follow-up, pembrolizumab and pembrolizumab-chemotherapy showed long-term clinical benefits; results further support these treatments as first-line options for Japanese patients with R/M HNSCC. Clinical trial registration: NCT02358031. [ABSTRACT FROM AUTHOR]

The Flood Potential Portal (https://floodpotential.erams.com/) has been developed for the contiguous United States, as a practitioner‐focused tool that uses observational data (streamgages) to enhance understanding of how floods vary in space and time, and assist users in making more informed peak discharge predictions for infrastructure design and floodplain management. This capability is presented through several modules. The Mapping module provides tools to explore variability using multiple indices, and provides detailed information, figures, and algorithms describing and comparing flooding characteristics. The Cross‐Section Analysis module allows users to cut regional‐scale sections to interpret the role of topography in driving flood variability. The Watershed Analysis module provides multiple methods for quantifying expected peak discharge magnitudes and flood frequency relationships at user‐selected locations, including the integration of observed trends in flood magnitudes due to climate change and other sources of nonstationarity into decision making. The Streamgage Analysis module performs streamgage flood‐frequency analyses. These modules are based in part on the flood potential method, through the use of 207 zones of similar flood response defined using more than 8200 streamgages with watershed areas <10,000 km2. Regression models that define each zone had high explained variance (average R2 = 0.93). An example is provided to illustrate use of the Flood Potential Portal for the design of a hypothetical bridge replacement. [ABSTRACT FROM AUTHOR]

Future flood risk assessment has primarily focused on heavy rainfall as the main driver, with the assumption that projected increases in extreme rain events will lead to subsequent flooding. However, the presence of and changes in vegetation have long been known to influence the relationship between rainfall and runoff. Here, we extract historical (1850–1880) and projected (2070–2100) daily extreme rainfall events, the corresponding runoff, and antecedent conditions simulated in a prominent large Earth system model ensemble to examine the shifting extreme rainfall and runoff relationship. Even with widespread projected increases in the magnitude (78% of the land surface) and number (72%) of extreme rainfall events, we find projected declines in event‐based runoff ratio (runoff/rainfall) for a majority (57%) of the Earth surface. Runoff ratio declines are linked with decreases in antecedent soil water driven by greater transpiration and canopy evaporation (both linked to vegetation greening) compared to areas with runoff ratio increases. Using a machine learning regression tree approach, we find that changes in canopy evaporation is the most important variable related to changes in antecedent soil water content in areas of decreased runoff ratios (with minimal changes in antecedent rainfall) while antecedent ground evaporation is the most important variable in areas of increased runoff ratios. Our results suggest that simulated interactions between vegetation greening, increasing evaporative demand, and antecedent soil drying are projected to diminish runoff associated with extreme rainfall events, with important implications for society. Plain Language Summary: Climate change is leading to increases in the magnitude and number of extreme rainfall events. These increases in extreme rainfall events are often assumed to lead to an increase in extreme flooding events. However, using a climate model ensemble, our results indicate that changes in vegetation and atmospheric water demand may alter the relationship between extreme rainfall and extreme runoff. Notably, for a majority of the Earth surface, we find that projected changes in atmospheric aridity and vegetation lead to drier soil conditions prior to the extreme rainfall event that reduces the amount of hydrologic runoff generated. These findings have important implications for water resources management. Key Points: The number and magnitude of extreme rainfall events are projected to increase throughout the global land surfaceProjected declines in event‐based runoff ratio are found for a majority of the global land surfaceProjected runoff ratio declines are linked to decreased antecedent soil water from changes in individual evapotranspiration components [ABSTRACT FROM AUTHOR]

The magnitude and temporality of the yearly maxima water levels are key parameters for the characterization of the riverine flooding hazard and its impacts. Although the Amazon estuary, that conveys the largest river discharge to the world ocean, exhibits marked events of maxima of the water level every year, the contribution of the natural drivers to these yearly extreme water levels is not well quantified. In this study, we investigate the contributing factors to the yearly maxima water level events along the Amazon estuary using a high-resolution cross-scale hydrodynamic model that has been extensively validated against comprehensive in situ and satellite datasets. Our study shows that the oceanic tide plays a crucial role in the genesis of the yearly maxima, whose influence decays from the downstream part (accounting for 85% of the total water level) towards the upstream part (44% of the total water level) of the estuary. Conversely, the Amazon discharge during the peak flood season induces yearly maxima in the upstream part of the estuary (accounting for 41% of the total water level), but the riverine influence decays sharply towards downstream and remains minor in the region of the mouths (9% of the total water level). Additionally, the sporadic bursts of north-easterly trade winds result in a sizeable wind-setup in the estuary (typically accounting for 5% to 13% of the total water level). Our study underscores the need for considering compound forcing in the cross-scale modeling in Amazon and similar estuaries. At a time when the climatic extremes are becoming more frequent over the Amazon region, our study helps the interpretation of the imprint of these extremes on the water level variability along this estuary. [ABSTRACT FROM AUTHOR]

The article presents the spatio-temporal variability of the pluvial conditions in the West Pomeranian province in Poland as per 21 poviats1. The basic data for the study were monthly precipitation totals and maximum 24-hour period total for each month, obtained from 49 stations of the Institute of Meteorology and Water Management National Research Institute in 1991–2020. It was found that area averaged highest values of precipitation, on average, ranging from 71 to 100 mm, were recorded in July (with the exception of the Kołobrzeg and Sławno poviats), and the lowest, ranging from 29–38 mm, were recorded in April. Precipitation in the warm half-year (April–September), depending on a given poviat, ranged from 317 to 444 mm, which constitutes 52–58% of the annual total. Even higher variability was found with respect to the cold half-year (October–March) characterised by precipitation totals within the range of 234–404 mm. In the analysed multi-year period, statistically significant monthly precipitation totals were found only on several occasions: a positive trend was observed in January in the Kołobrzeg poviat, in July in Koszalin and Szczecinek poviats and in October in Myślibórz and Kołobrzeg poviats. The only instance of a marked decrease in monthly precipitation was identified for June in the Kamień Pomorski poviat. In all poviats of the voivodeship, there were nonsignificant tendency of an increase in precipitation in the cold half-year and reduction of the predominance of precipitation in the warm half-year over cold half-year.

Abstract This study evaluates the use of simple linear or piecewise linear predictive models to predict extreme performance metrics in soccer matches, based on historical training and to match data of soccer players from RKS Raków Częstochowa football club. The data were collected from January to June 2023. The collected training and matched data average is 9000 records per month. A standard workweek at the RKS Academy consisted of 5 training units and at least 1 match. The best individual models found predict selected game performance metrics with a relative error of 2.3%, suggesting an excellent model fit between prediction and the actual value. This is illustrated by input data metric called “Metabolic Time Zone 5 and 6 Per Distance”, and output data by “Decelarations Total Distance in Zone 5 and 6 Per Distance”—calculated for in 3 min sliding window and characterized by the highest value of the generated parameter based on High Metabolic Load Distance (HMLD). The result concerns models run on aggregated performance metrics developed in APEX-PRO system using expert knowledge in soccer training, while raw GPS location-based models performing worse but still acceptably. Although we believe that the accuracy of the models still has limited reliability, their clarity and up-to-date quality make them useful in the daily planning of training activities and the management of workloads that affect player performance in the upcoming match, as well as the tactical decisions of the coach. More accurate predictions are given by individual models compared to aggregated models (player position), but there are exceptions where group models also perform very well. Adding a second metric to the input did not show a significant difference in the analyzed examples (the results are very similar). Our findings indicate that the model based on metrics from the last match also effectively predict extreme motor performances occurring in the game. In the case of the analyzed player, it was at the input “Accelerations Total Time Per Distance in Zone 6” at the output “Distance in Zone 6”. Specific training or match parameters can be key in predicting exceptional soccer performance, but they can also vary depending on the analyzed player. This confirms the need for further analysis of this issue.

The article presents the spatio-temporal variability of the pluvial conditions in the West Pomeranian province in Poland as per 21 poviats1. The basic data for the study were monthly precipitation totals and maximum 24-hour period total for each month, obtained from 49 stations of the Institute of Meteorology and Water Management National Research Institute in 1991-2020. It was found that area averaged highest values of precipitation, on average, ranging from 71 to 100 mm, were recorded in July (with the exception of the Kołobrzeg and Sławno poviats), and the lowest, ranging from 29-38 mm, were recorded in April. Precipitation in the warm half-year (April-September), depending on a given poviat, ranged from 317 to 444 mm, which constitutes 52-58% of the annual total. Even higher variability was found with respect to the cold half-year (October-March) characterised by precipitation totals within the range of 234-404 mm. In the analysed multi-year period, statistically significant monthly precipitation totals were found only on several occasions: a positive trend was observed in January in the Kołobrzeg poviat, in July in Koszalin and Szczecinek poviats and in October in Myślibórz and Kołobrzeg poviats. The only instance of a marked decrease in monthly precipitation was identified for June in the Kamień Pomorski poviat. In all poviats of the voivodeship, there were nonsignificant tendency of an increase in precipitation in the cold half-year and reduction of the predominance of precipitation in the warm half-year over cold half-year. [ABSTRACT FROM AUTHOR]

Southern Thailand has experienced significant shifts in precipitation patterns in recent years, exerting substantial impacts on regional water resources and infrastructure systems. This study aims to elucidate these changes and underlying factors based on daily precipitation observations from Nakhon Si Thammarat Province spanning 1980 to 2022. Additionally, data from the Coupled Model Intercomparison Project Phase 6 (CMIP6) is utilized to investigate projected changes in precipitation for 2015–2100 relative to the historical period (1980–2014), employing a comprehensive analysis considering two emissions scenarios (SSP245 and SSP585) across six models. Various precipitation indices are selected to assess trends and statistical significance using the Mann-Kendall test. Both observed and climate model data indicate an increasing precipitation trend in Southern Thailand, with a reduced association with the El Niño-Southern Oscillation (ENSO) under warming conditions. Extreme precipitation indices also exhibit an increasing trend, with total precipitation and the 95th percentile of daily precipitation (R95p) revealing very wet conditions in recent years, projected to continue increasing. Contrastingly, the number of dry days is also mounting, suggesting that both dry and wet extremes will impact Southern Thailand under a warmer climate. The findings from this study provide an early indication of future precipitation and extreme event scenarios, which can inform the development of measures to mitigate climate change-related hazards in the region. [ABSTRACT FROM AUTHOR]

Abstract Future flood risk assessment has primarily focused on heavy rainfall as the main driver, with the assumption that projected increases in extreme rain events will lead to subsequent flooding. However, the presence of and changes in vegetation have long been known to influence the relationship between rainfall and runoff. Here, we extract historical (1850–1880) and projected (2070–2100) daily extreme rainfall events, the corresponding runoff, and antecedent conditions simulated in a prominent large Earth system model ensemble to examine the shifting extreme rainfall and runoff relationship. Even with widespread projected increases in the magnitude (78% of the land surface) and number (72%) of extreme rainfall events, we find projected declines in event‐based runoff ratio (runoff/rainfall) for a majority (57%) of the Earth surface. Runoff ratio declines are linked with decreases in antecedent soil water driven by greater transpiration and canopy evaporation (both linked to vegetation greening) compared to areas with runoff ratio increases. Using a machine learning regression tree approach, we find that changes in canopy evaporation is the most important variable related to changes in antecedent soil water content in areas of decreased runoff ratios (with minimal changes in antecedent rainfall) while antecedent ground evaporation is the most important variable in areas of increased runoff ratios. Our results suggest that simulated interactions between vegetation greening, increasing evaporative demand, and antecedent soil drying are projected to diminish runoff associated with extreme rainfall events, with important implications for society.

Abstract Background Advanced head and neck squamous cell carcinoma (HNSCC) has a poor prognosis, and new treatment options are needed. Combining immunotherapies with differing mechanisms of action may enhance clinical benefits compared with single-agent immunotherapy. Epacadostat, an indoleamine 2,3 dioxygenase 1 inhibitor, plus pembrolizumab, a PD-1 inhibitor, showed promising activity in advanced HNSCC in the phase 1/2 KEYNOTE-037/ECHO-202 trial. Methods KEYNOTE-669/ECHO-304 is a randomized, open-label, phase 3 study evaluating the efficacy and safety of pembrolizumab plus epacadostat, pembrolizumab monotherapy, and the EXTREME regimen (cetuximab with a platinum [carboplatin or cisplatin] and 5-fluorouracil) in recurrent/metastatic (R/M) HNSCC. Participants had no prior systemic therapy for R/M HNSCC and were randomly assigned (2:1:2) to pembrolizumab 200 mg intravenously every 3 weeks plus epacadostat 100 mg orally twice daily, pembrolizumab monotherapy, or EXTREME. The primary endpoint was objective response rate (ORR; investigator assessment). Secondary endpoints were safety and tolerability. Change in serum kynurenine was an exploratory endpoint. Study enrollment was discontinued early as a strategic decision on May 2, 2018, and response assessment was discontinued after first on-study imaging assessment at week 9. Data cut-off was January 17, 2019. Results Between December 1, 2017, and May 2, 2018, 89 patients were randomly allocated to pembrolizumab plus epacadostat (n = 35), pembrolizumab monotherapy (n = 19), or EXTREME (n = 35). ORR (95% CI) was 31% (17%–49%) for pembrolizumab plus epacadostat, 21% (6%–46%) for pembrolizumab monotherapy, and 34% (19%–52%) for EXTREME. Treatment-related adverse events (TRAEs) occurred in 82% (n = 28) of patients receiving pembrolizumab plus epacadostat, 63% (n = 12) receiving pembrolizumab monotherapy, and 100% (n = 34) receiving EXTREME. Grade 3–4 TRAEs occurred in 24% (n = 8) of patients receiving pembrolizumab plus epacadostat, 16% (n = 3) receiving pembrolizumab monotherapy, and 82% (n = 28) receiving EXTREME. No deaths occurred due to AEs. Pembrolizumab plus epacadostat treatment reduced kynurenine levels but not to that of healthy subjects. Conclusions Pembrolizumab plus epacadostat and pembrolizumab monotherapy provided a similar response rate to EXTREME and demonstrated a manageable safety profile in patients with R/M HNSCC. Trial registration NCT03358472. Date of trial registration: November 30, 2017.

Recent increases in extreme events, especially those near and beyond previous records, are a new index for Arctic and global climate change. They vary by type, location, and season. These record-shattering events often have no known historical analogues and suggest that other climate surprises are in store. Twenty-six unprecedented events from 2022, 2023, and early 2024 include record summer temperatures/heatwaves, storms, major Canadian wildfires, early continental snow melt, Greenland melt, sea temperatures of 5–7 °C above normal, drought in Iceland, and low northern Alaskan salmon runs. Collectively, such diverse extremes form a consilience, the principle that evidence from independent, unrelated sources converge as a strong indicator of ongoing Arctic change. These new behaviors represent emergent phenomenon. Emergence occurs when multiple processes interact to produce new properties, such as the interaction of Arctic amplification with the normal range of major weather events. Examples are typhon Merbok that resulted in extensive coastal erosion in the Bering Sea, Greenland melt, and record temperatures and melt in Svalbard. The Arctic can now be considered to be in a different state to before fifteen years ago. Communities must adapt for such intermittent events to avoid worst-case scenarios. [ABSTRACT FROM AUTHOR]

Background: Advanced head and neck squamous cell carcinoma (HNSCC) has a poor prognosis, and new treatment options are needed. Combining immunotherapies with differing mechanisms of action may enhance clinical benefits compared with single-agent immunotherapy. Epacadostat, an indoleamine 2,3 dioxygenase 1 inhibitor, plus pembrolizumab, a PD-1 inhibitor, showed promising activity in advanced HNSCC in the phase 1/2 KEYNOTE-037/ECHO-202 trial. Methods: KEYNOTE-669/ECHO-304 is a randomized, open-label, phase 3 study evaluating the efficacy and safety of pembrolizumab plus epacadostat, pembrolizumab monotherapy, and the EXTREME regimen (cetuximab with a platinum [carboplatin or cisplatin] and 5-fluorouracil) in recurrent/metastatic (R/M) HNSCC. Participants had no prior systemic therapy for R/M HNSCC and were randomly assigned (2:1:2) to pembrolizumab 200 mg intravenously every 3 weeks plus epacadostat 100 mg orally twice daily, pembrolizumab monotherapy, or EXTREME. The primary endpoint was objective response rate (ORR; investigator assessment). Secondary endpoints were safety and tolerability. Change in serum kynurenine was an exploratory endpoint. Study enrollment was discontinued early as a strategic decision on May 2, 2018, and response assessment was discontinued after first on-study imaging assessment at week 9. Data cut-off was January 17, 2019. Results: Between December 1, 2017, and May 2, 2018, 89 patients were randomly allocated to pembrolizumab plus epacadostat (n = 35), pembrolizumab monotherapy (n = 19), or EXTREME (n = 35). ORR (95% CI) was 31% (17%–49%) for pembrolizumab plus epacadostat, 21% (6%–46%) for pembrolizumab monotherapy, and 34% (19%–52%) for EXTREME. Treatment-related adverse events (TRAEs) occurred in 82% (n = 28) of patients receiving pembrolizumab plus epacadostat, 63% (n = 12) receiving pembrolizumab monotherapy, and 100% (n = 34) receiving EXTREME. Grade 3–4 TRAEs occurred in 24% (n = 8) of patients receiving pembrolizumab plus epacadostat, 16% (n = 3) receiving pembrolizumab monotherapy, and 82% (n = 28) receiving EXTREME. No deaths occurred due to AEs. Pembrolizumab plus epacadostat treatment reduced kynurenine levels but not to that of healthy subjects. Conclusions: Pembrolizumab plus epacadostat and pembrolizumab monotherapy provided a similar response rate to EXTREME and demonstrated a manageable safety profile in patients with R/M HNSCC. Trial registration: NCT03358472. Date of trial registration: November 30, 2017. [ABSTRACT FROM AUTHOR]

Indonesia experienced an increase in extreme poverty during the Covid-19 pandemic, rising from 9.22% in 2019 to 10.14% in 2020. In response to the target of reducing extreme poverty to 0% by 2024, Presidential Instruction Number 4 of 2022 on the Acceleration of Extreme Poverty Eradication was issued as the foundation for cooperation among policymakers at both the central and regional levels. The 2020-2024 Regional MediumTerm Development Plan (RPJMD) targets a reduction in the poverty rate in North Maluku to 6.19%. In reality, the poverty rate in North Maluku Province reached 6.39% in 2022, while in 2023, the poverty rate decreased to 6.25%. This indicates that the target set in the RPJMD is unlikely to be achieved, as 2024 is the final year of the current government’s term. The purpose of this study is to analyze the impact of economic growth, employment opportunities, the availability of economic infrastructure, human capital (HR), and financial inclusion on extreme poverty in the districts and cities of North Maluku. This study employs a quantitative analysis method (Structural Equation Modeling). The results of the study provide sufficient evidence that financial inclusion acts as a mediating variable in the relationship between employment opportunities, economic infrastructure, HR capacity, and basic infrastructure, which all have a significant positive impact on extreme poverty. Based on the findings, it is strongly explained that high economic growth in North Maluku Province does not significantly reduce extreme poverty. [ABSTRACT FROM AUTHOR]

Abstract Background This study evaluates the association of diuresis and hydration through a new monitoring indicator called $${U}_{sen}$$ U sen and the risk of acute kidney injury in patients treated with cisplatin based-EXTREME regimen. Methods We retrospectively reviewed all the cycles of patients with recurrent and/or metastatic head and neck cancer who received cisplatin based-EXTREME regimen from June 2008 to July 2022. Hydration regimen, urine output and concomitant treatments data were collected on the day of cisplatin infusion and the following day of each course received. Results Of the 110 courses received by 46 patients, 38 (34.5%) results in AKI. No patient characteristics showed a significant difference between AKI (70%) and non-AKI (30%) group. In univariate analysis, dose reduction of cisplatin (odds ratio = 0.166 [0.04; 0.75], p = 0.01)) and $${U}_{sen}$$ U sen >8 (odds ratio = 0.316 [0.133; 0.755], p = 0.015) and cardiac treatments (odds ratio = 3.24 [1.26; 8.52], p = 0.02) were significantly associated with AKI risk. In multivariate analysis, cisplatin dose reduction (odds ratio = 0.129 [0.0241; 0.687], p = 0.016) and $${U}_{sen}$$ U sen >8 (odds ratio = 0.184 [0.0648; 0.523], p = 0.0015) were associated with a risk reduction of cisplatin-related AKI. Concomitant administration of cardiac treatments (odds ratio = 3.18 [1.1; 9.22], p = 0.033) showed an increased risk of cisplatin-related AKI. Conclusion The combination of diuresis and i.v. hydration through the $${U}_{sen}$$ U sen composite score was shown to be associated with cisplatin-induced AKI risk in patients treated with cisplatin based EXTREME regimen. It could be used as a practical indicator to trigger specific clinical management to limit the risk of cisplatin induced AKI.

Abstract In the CheckMate 651 study, nivolumab plus ipilimumab versus EXTREME (cisplatin/carboplatin + cetuximab + fluorouracil) regimen was compared for effectiveness. It is not known whether these immunotherapy agents are cost-effective for recurrent or metastatic squamous cell carcinomas of the head and neck (R/M SCCHN). The purpose of this study was to compare the cost-effectiveness of nivolumab plus ipilimumab with EXTREME in the first-line setting from the standpoint of third-party payers in the United States. The projecting of costs and outcomes over 15 years was done using a three-state partitioned survival model discounted by 3% per year. Long-term extrapolation of CheckMate 651 was used to model progression-free survival and overall survival (OS). The incremental net health benefit (INHB), incremental net monetary benefit (INMB), quality-adjusted life years (QALYs), and incremental cost-effectiveness ratio (ICER) were calculated. The uncertainty and stability of the model were accounted for via one-way and probabilistic sensitivity analyses. As compared with nivolumab plus ipilimumab, EXTREME was associated with an increase of 0.154 life-years and 0.076 QALYs, as well as a cost increase of $572 per patient. The corresponding ICERs were $7545/QALY along with the values of INMB and INHB were $113,267 and 0.076 QALYs, respectively, at a willingness to pay (WTP) threshold of $150,000/QALY. The probability of nivolumab plus ipilimumab being cost-effective was > 99% in patients with combined positive score (CPS) ≥ 1, CPS 1–19, or CPS ≥ 20. Moreover, hazard ratio for OS and body weight were the most sensitive parameters for the model. According to sensitivity analyses, these results were generally robust. In overall populations with R/M SCCHN, the EXTREME regimen is cost-effective compared with nivolumab plus ipilimumab. Given a WTP threshold of $150,000 per QALY, the probability of the EXTREME regiment being cost-effective compared with nivolumab and ipilimumab, was 64%. Importantly, there was heterogeneity in the cost-effectiveness probabilities, based on primary sites and expression levels of PD-L1. Therefore, tailored treatment based on individual patient and clinical characteristics, remains important, and may impact the cost-effectiveness of the regimens under study.

Owing to the wavelength-dependent limits of the deep ultraviolet exposure process, the semiconductor industry introduced extreme ultraviolet (EUV) lithography operating at a 13.5 nm wavelength. Traditional photomasks employ pellicles for protection; however, EUV-specific pellicles are not widely applicable to commercial processes, requiring the development of a EUV photomask cleaning method. In this study, a wet cleaning method for Ta-based EUV photomasks at room temperature was systematically examined in terms of key parameters, including the pattern step height, surface topography, and particulate count, via atomic force microscopy and x-ray reflectivity. Post sulfuric acid-hydrogen peroxide mixture (SPM) treatment, the photomask exhibited a stable step height, indicating minimal pattern degradation. Additionally, discernible alterations in the surface roughness and a decrease in particle count were observed, further indicating to the effectiveness of SPM-mediated cleaning. Conversely, following standard clean-1 (SC-1) treatment, while the pattern step height remained relatively unchanged, a notable increase in surface irregularities and macroscopic particulates was observed, suggesting a suboptimal cleaning efficiency of the SC-1 solution despite its potential for pattern structure preservation. Our room temperature wet cleaning method efficiently reduces wear-out and successfully eliminates contaminants, potentially prolonging the EUV photomask's productivity and durability. [ABSTRACT FROM AUTHOR]

Let V n (d) denote the least number, such that every collection of n d-cubes with total volume 1 in d-dimensional (Euclidean) space can be packed parallelly into some d-box of volume V n (d) . We show that V 3 (d) = r 1 − d d if d ≥ 11 and V 3 (d) = 1 r + 1 r d + 1 r − r d + 1 if 2 ≤ d ≤ 10 , where r is the only solution of the equation 2 (d − 1) k d + d k d − 1 = 1 on 2 2 , 1 and (k + 1) d (1 − k) d − 1 d k 2 + d + k − 1 = k d d k d + 1 + d k d + k d + 1 on 2 2 , 1 , respectively. The maximum volume is achieved by hypercubes with edges x, y, z, such that x = 2 r d + 1 − 1 / d , y = z = r x if d ≥ 11 , and x = r d + (1 r − r) d + 1 − 1 / d , y = r x , z = (1 r − r) x if 2 ≤ d ≤ 10 . We also proved that only for dimensions less than 11 are there two different maximum packings, and for all dimensions greater than 10, the maximum packing has the same two smallest cubes. [ABSTRACT FROM AUTHOR]

Background: This study evaluates the association of diuresis and hydration through a new monitoring indicator called U sen and the risk of acute kidney injury in patients treated with cisplatin based-EXTREME regimen. Methods: We retrospectively reviewed all the cycles of patients with recurrent and/or metastatic head and neck cancer who received cisplatin based-EXTREME regimen from June 2008 to July 2022. Hydration regimen, urine output and concomitant treatments data were collected on the day of cisplatin infusion and the following day of each course received. Results: Of the 110 courses received by 46 patients, 38 (34.5%) results in AKI. No patient characteristics showed a significant difference between AKI (70%) and non-AKI (30%) group. In univariate analysis, dose reduction of cisplatin (odds ratio = 0.166 [0.04; 0.75], p = 0.01)) and U sen >8 (odds ratio = 0.316 [0.133; 0.755], p = 0.015) and cardiac treatments (odds ratio = 3.24 [1.26; 8.52], p = 0.02) were significantly associated with AKI risk. In multivariate analysis, cisplatin dose reduction (odds ratio = 0.129 [0.0241; 0.687], p = 0.016) and U sen >8 (odds ratio = 0.184 [0.0648; 0.523], p = 0.0015) were associated with a risk reduction of cisplatin-related AKI. Concomitant administration of cardiac treatments (odds ratio = 3.18 [1.1; 9.22], p = 0.033) showed an increased risk of cisplatin-related AKI. Conclusion: The combination of diuresis and i.v. hydration through the U sen composite score was shown to be associated with cisplatin-induced AKI risk in patients treated with cisplatin based EXTREME regimen. It could be used as a practical indicator to trigger specific clinical management to limit the risk of cisplatin induced AKI. [ABSTRACT FROM AUTHOR]

The pressing demand for novel compounds to address contemporary health challenges has prompted researchers to venture into uncharted territory, including extreme ecosystems, in search of new natural pharmaceuticals. Fungi capable of tolerating extreme conditions, known as extremophilic fungi, have garnered attention for their ability to produce unique secondary metabolites crucial for defense and communication, some of which exhibit promising clinical significance. Among these, halophilic fungi thriving in high-salinity environments have particularly piqued interest for their production of bioactive molecules. This review highlights the recent discoveries regarding novel compounds from halotolerant fungal strains isolated from various saline habitats. From diverse fungal species including Aspergillus, Penicillium, Alternaria, Myrothecium, and Cladosporium, a plethora of intriguing molecules have been elucidated, showcasing diverse chemical structures and bioactivity. These compounds exhibit cytotoxicity against cancer cell lines such as A549, HL60, and K-562, antimicrobial activity against pathogens like Escherichia coli, Bacillus subtilis, and Candida albicans, as well as radical-scavenging properties. Notable examples include variecolorins, sclerotides, alternarosides, and chrysogesides, among others. Additionally, several compounds display unique structural motifs, such as spiro-anthronopyranoid diketopiperazines and pentacyclic triterpenoids. The results emphasize the significant promise of halotolerant fungi in providing bioactive compounds for pharmaceutical, agricultural, and biotechnological uses. However, despite their potential, halophilic fungi are still largely unexplored as sources of valuable compounds. [ABSTRACT FROM AUTHOR]

Simple Summary: The welfare of purebred dogs and cats is being undermined by fashion trends that popularize extreme shapes. Official descriptions of breeds require their distinctive characteristics to be compatible with good health. Nevertheless, extremes within breeds that compromise health, referred to as hypertypes, have become trendy. For example, when flat faces are taken to the extreme, dogs and cats may be unable to breathe normally, which affects all aspects of their lives. Individuals such as breeders, owners and veterinarians, and organizations in the whole community surrounding purebred dogs and cats must collaborate to prevent the breeding of hypertypes. Fashion-fueled breeding of hypertypes, whether or not illegal, must also be tackled because its negative effects can extend beyond what is visible to unsuspecting owners choosing their puppy or kitten. The problem is complex, and the solution involves many bodies working together. However, the message is simple: health, temperament, and well-being must be prioritized over appearance. Putting this into practice will help protect the much-valued diversity of breeds. Fashions in the appearance of purebred dogs and cats are encouraged by celebrity culture, social media, and online impulse buying. The popularity of characteristics perceived as cute, quirky, and anthropomorphic has driven increasingly exaggerated breed features appealing to aesthetics rather than health. 'Hypertypes' of some breeds have emerged that take a breed's distinctive appearance to extremes beyond the intended interpretation of breed standards. This has severe, direct and indirect health and welfare consequences. Extreme conformations are associated with chronic health conditions including brachycephalic obstructive airway disorder, ocular, dental, skin, and musculoskeletal disorders. Puppy and kitten farms and illegal traders that meet the demand for hypertypes are associated with poor husbandry that neglects the physical, behavioral, and mental health of parents and offspring. A multidimensional approach involving collaboration between breeders, geneticists, owners, veterinarians, kennel clubs, cat fanciers' associations, animal charities, the academic and research communities, commercial enterprises, and governments is needed to safeguard breeds and tackle these challenges. There are many ongoing initiatives by national kennel clubs and global partnerships to educate pet owners and support responsible pet ownership and sustainable breeding. The resounding message is that health, temperament, and well-being must be prioritized over appearance. [ABSTRACT FROM AUTHOR]

In the CheckMate 651 study, nivolumab plus ipilimumab versus EXTREME (cisplatin/carboplatin + cetuximab + fluorouracil) regimen was compared for effectiveness. It is not known whether these immunotherapy agents are cost-effective for recurrent or metastatic squamous cell carcinomas of the head and neck (R/M SCCHN). The purpose of this study was to compare the cost-effectiveness of nivolumab plus ipilimumab with EXTREME in the first-line setting from the standpoint of third-party payers in the United States. The projecting of costs and outcomes over 15 years was done using a three-state partitioned survival model discounted by 3% per year. Long-term extrapolation of CheckMate 651 was used to model progression-free survival and overall survival (OS). The incremental net health benefit (INHB), incremental net monetary benefit (INMB), quality-adjusted life years (QALYs), and incremental cost-effectiveness ratio (ICER) were calculated. The uncertainty and stability of the model were accounted for via one-way and probabilistic sensitivity analyses. As compared with nivolumab plus ipilimumab, EXTREME was associated with an increase of 0.154 life-years and 0.076 QALYs, as well as a cost increase of $572 per patient. The corresponding ICERs were $7545/QALY along with the values of INMB and INHB were $113,267 and 0.076 QALYs, respectively, at a willingness to pay (WTP) threshold of $150,000/QALY. The probability of nivolumab plus ipilimumab being cost-effective was > 99% in patients with combined positive score (CPS) ≥ 1, CPS 1–19, or CPS ≥ 20. Moreover, hazard ratio for OS and body weight were the most sensitive parameters for the model. According to sensitivity analyses, these results were generally robust. In overall populations with R/M SCCHN, the EXTREME regimen is cost-effective compared with nivolumab plus ipilimumab. Given a WTP threshold of $150,000 per QALY, the probability of the EXTREME regiment being cost-effective compared with nivolumab and ipilimumab, was 64%. Importantly, there was heterogeneity in the cost-effectiveness probabilities, based on primary sites and expression levels of PD-L1. Therefore, tailored treatment based on individual patient and clinical characteristics, remains important, and may impact the cost-effectiveness of the regimens under study. [ABSTRACT FROM AUTHOR]

Various jobs, indoors and outdoors, are subjected to severe cold temperatures during daily activities. Extremely low-temperature exposure and work intensity affect health, safety, and occupational performance. This work aimed to assess the physiological and thermal sensation responses before, during, and following a 60 min exposure to cold (−20 °C), during which occupational activities were developed. Using ingestible telemetric temperature pills, eight skin temperature sensors, blood pressure equipment, and the Thermal Sensation Questionnaire, experiments were conducted with 11 healthy male volunteers wearing highly insulating cold protective clothing. The most notorious alterations were reported in mean skin temperatures and thermal sensation responses during the first 20 min of cold exposure. Among the eight skin temperature points, the forehead and left hand showed a higher sensitivity to cold. The mean core temperature reported significant variations throughout the protocol, with decreases during the initial 10 min of cold exposure and posterior increases despite the cold environment. Blood pressure showed slight increases from the initial to the recovery period. Overall, outcomes contribute to current scientific knowledge on physiological and perception responses in extremely cold environments while describing the influence of protective clothing and occupational activities on these responses. Future research should be developed with additional skin temperature measurements in the extremities (fingers, face, and toes) and the analysis of thermal sensation potential associations with performance changes, which can also be of great significance for future thermal comfort models. [ABSTRACT FROM AUTHOR]

Previous evaluations of coupled climate models have indicated that under the influence of global warming precipitation extremes, including those over Indonesia, are expected to intensify. Here, we examine the most recent future projections of extreme rainfall in Indonesia using 24 global climate models from the Coupled Model Intercomparison Project Phase 6, consisting of 11 low resolution (LR) and 13 medium resolution (MR) models. The performance of these models is evaluated against Climate Hazards Group InfraRed Precipitation with Station data observations and realistically reproduce Indonesia's mean climatology over the period assessed (1987–2014). Overall, both LR and MR multi‐model ensemble means (MMEM) outperform individual models. Interestingly, extreme rainfall projections vary across different seasons, time periods, spatial resolutions and climate change scenarios. The LR and MR MMEMs project a continuous increase in wet extremes (R95p and Rx5d) during the wet season across most of Indonesia over the 21st century. Conversely, dry extremes (consecutive dry days [CDD]) are projected to increase (decrease) over the south (north) during the wet season but increase countrywide during the dry season. We show that future extreme wet and dry events are projected to be more frequent and intense, with upper extreme values surpassing historical records. The MR models project smaller changes in extreme wet indices than the LR models but simulate a more prolonged extreme dry index. Key findings here indicate that forthcoming instances of extreme rainfall present substantial hazards, necessitating the implementation of adequate preventative measures by policymakers, particularly within densely inhabited regions, such as Java. [ABSTRACT FROM AUTHOR]

The most intense thunderstorms on Earth were surveyed using the comprehensive meteorological instrumentation on the Tropical Rainfall Measuring Mission (TRMM) satellite. Expansive land‐based Mesoscale Convective Systems (MCSs) were consistently identified among the Earth's most intense thunderstorms, with their organization into many convective cells spanning a large areal extent permitting exceptional overall flash rates for these storms. In this study, we identify a new class of extreme thunderstorm. Lightning‐dense thunderstorms are relatively compact convective storms whose concentrated lightning activity hinders our ability to accurately measure their flash rates. The top storms have a flash rate of one flash spanning many seconds, as there is insufficient separation to distinguish one flash from another. While any particularly active convective cell could be capable of producing high lightning densities, we find that thunderstorms with the greatest lightning densities on Earth are found in maritime thunderstorms that have not been appreciated in prior work due to the inaccurate flash rate measurements. These storms that are mostly found throughout the Gulf of Mexico and east of South Africa (among other coastal and oceanic regions) have measured TRMM proxies for convective intensity that rival the top MCS thunderstorms, but their horizontal and vertical dimensions are small by comparison. Thus, the necessary microphysical elements for electrification processes are more highly concentrated, enabling the observed extreme lightning densities. Plain Language Summary: Using lightning flash rates as a measurement of thunderstorm intensity is complicated by the fact that thunderstorms produce lightning in different ways based on how they are organized. Isolated thunderstorms might consist of a single convective cell with all of the measured lightning coming from that one cell. Meanwhile, a Mesoscale Convective System (MCS) moving across the central United States would be comprised of many convective cells across a line spanning up to thousands of kilometers. All of the flashes produced by all of the cells count toward the total flash rate of the organized MCS. Due to this advantage, studies that assess the highest flash rate thunderstorms on Earth identify MCSs as their top storms. In this study, we ask a different but related question: where are the thunderstorms with the greatest lightning densities on Earth? Answering this question allows us to identify particularly active convection regardless of whether it describes an isolated thunderstorm or one of the cells in a broader MCS. We find that the storms with the greatest lightning densities are not organized MCSs over land, but rather smaller maritime thunderstorms. Key Points: Certain intense thunderstorms produce extraordinary amounts of lightning concentrated in one areaLightning‐dense thunderstorms are comparable in intensity to the top flash rate storms over land, but are smaller maritime stormsMeasured flash rates are inaccurate for these lightning‐dense thunderstorms, adversely impacting weather forecasting and physical research [ABSTRACT FROM AUTHOR]

In this paper, we will prove a theorem for a functional where we prove that the necessary condition for the extreme of a functional is that the variation of a functional is equal to zero and we will give an example of its application to the catenary problem. [ABSTRACT FROM AUTHOR]

The 2021 International Society on Thrombosis and Haemostasis' (ISTH) recommends standard doses of apixaban and rivaroxaban regardless of high body mass index (BMI) and weight, but had not compare DOACs head-to-head in obesity or address underweight patients. Our aim is to evaluate the safety and efficacy of DOACs in underweight and obese patients compared to warfarin. The primary endpoints include incidence of thromboembolic and bleeding events. Descriptive statistics was used for continuous variables. The Kruskal-Wallis test was used to compare the four-groups for continuous measures and the chi-square test or Fisher's exact test was used to analyze categorical data. The chi-square test or Fisher's exact test, was used for categorical variables, and the Mann-Whitney test (the non-parametric counterpart to the two-sample t -test) for continuous data. Of 2940 patients receiving anticoagulation for venous thromboembolism (VTE) treatment or atrial fibrillation (AF), 492 met eligibility criteria. Within each group, 248 patients received warfarin, 101 received apixaban, 100 received rivaroxaban and 43 received dabigatran. Patients were characterized in 4 body mass index (BMI) categories, in which 80 were underweight and 412 were obese. When each DOAC was compared to warfarin in rates of VTE, apixaban showed statistically significant lower rate of VTE (p = 0.0149). However, no statistical significance was identified in the rate of VTE between DOACs combined vs. warfarin (p = 0.1529). When each DOAC was compared to warfarin, apixaban showed the lowest rate of overall bleeding (p = 0.0194). However, no statistical difference in the rate of bleeding was observed between DOACs combined vs. warfarin (p = 0.3284). Patients with extreme body weights requiring anticoagulation for VTE and AF may safety benefit from DOAC therapy. This evaluation showed apixaban with the lowest rate of VTE and bleeding compared to warfarin, rivaroxaban, and dabigatran. These results provide experience for the clinician to use DOACs, particularly apixaban, in underweight and obese populations. • What is the new aspect of your work? The new aspect of our work is to evaluate the safety and efficacy of oral anticoagulants in patients who are underweight or obese, since direct oral anticoagulants (DOACs) are fixed-dose and may have increased bleeding in underweight populations, but reduced efficacy in obese populations. • What is the central finding of your work? In underweight patients with BMI <18.5, DOACs have similar efficacy and safety to vitamin k antagonist (warfarin), p =0.1179 in the 4-group analysis and p =0.5658 in the 2-group analysis. When reviewed individually, apixaban has statistically significant less risk of bleeding in patients with BMI < 18.5, apixaban 1 (10%), rivaroxaban 5 (38.46%), dabigatran 5 (50%), and warfarin 7 (14.89%), p =0.0322. In obese patients with BMI > 40, there rate of VTE was lowest in the apixaban 0 (0%) and warfarin groups 0 (0%), followed by dabigatran 1 (12.5%), then rivaroxaban 3 (13.64%), p =0.0104 in the 4-group analysis and p =0.0346 in the 2-group analysis. In BMI > 40, the risk of bleeding was not statistically significant among the 4-group analysis, p=0.3417. • What is (or could be) the specific relevance of your work? The relevance of our work is DOACs may be safe and efficacious, compared to vitamin k agonist (warfarin), in patient with extreme weights. Monitoring DOAC plasma levels in extreme weights may be of utility. [ABSTRACT FROM AUTHOR]

Recurring floods, droughts, heatwaves, and other hydro-meteorological extreme events are likely to be increased under the climate change scenarios. The increased risk of these extreme events might have more exposure to the population; thus, it is important to discuss such extreme events and their projected behavior under a changing climate scenario. In the present study, we have computed the extreme precipitation and temperature indices over the 10 agro-climatic zones falling under the Ganga River Basin (GRB)utilizing a high-resolution daily gridded temperature and precipitation multi-model ensembled CMIP6 dataset (0.25° × 0.25°) under global warming levels of 1.5 °C, 2 °C, and 3 °C. We found that the annual daily minimum temperature (TNN) showed a higher rise of about 67% than the maximum temperature (TXX) of 48% in GRB. The basin also experiences a greater increase in the frequency of warm nights (TN90P) of about 67.71% compared to warm days (TX90P) of 29.1% for the 3 °C global warming level. Along with extreme indices, the population exposed due to the impact of the extreme maximum temperature has also been analyzed for progressive warming levels. Population exposure to extreme temperature event (TXX) has been analyzed with 20-year return period using GEV distribution method. The study concludes that the exposed population to extreme temperature event experienced an increase from 46.99 to 52.16% for the whole Ganga Basin. Consecutive dry days (CDD) and consecutive wet days (CWD) both show a significant increasing trend, but CWD has a significant increase in the majority of the zones, while CDD shows a significant decreasing trend for some of the zones for three warming levels periods. Extreme climate indices help to understand the frequency and intensity of extreme weather events such as heavy rainfall, droughts, and heatwaves to develop early warning systems and adaptation strategies to mitigate such events. [ABSTRACT FROM AUTHOR]

Global warming alters the inherent variability of climate variables and induces more frequent extremes of hydroclimatic compound events with substantial impacts. The concurrence of hydrological drought and saltwater intrusion in the estuary can have devastating effects on agricultural production, water security, and ecological health. In this study, the compound drought and saltwater intrusion extreme indices, including the Blend Drought and Saltwater intrusion Index (BDSI), the Compound drought and Saltwater intrusion Index (CDSI) and the Standardized Drought and Saltwater intrusion Index (SDSI), were constructed to monitor compound extremes in the critical zone of Pearl River Estuary during the dry season from 1999 to 2016. The results reveal that the three compound indices can effectively depict different aspects of compound drought and saltwater intrusion extreme events in the critical zone of Pearl River Estuary. Among the three indices, the SDSI performed best in depicting compound drought‐saltwater intrusion events, while the BDSI outperformed the other indices in depicting high value of Standardized Runoff Index (SRI) and Standardized Saltwater intrusion Index (SSI), and the CDSI outperformed the other indices in depicting low values of SRI and SSI. Using those developed compound indices, we found that the frequency of abnormal and moderate compound drought‐saltwater intrusion events increased from 9.26% to 12.03% during the period of 1999–2016, while severe, extreme and exceptional compound drought‐saltwater intrusion events were rare. [ABSTRACT FROM AUTHOR]

The question has long been asked whether there is an ideology called „Putinism” and whether it can be assimilated to fascism. The premise of this article is that Putinism exists, it is an ideology in formation, „thin centered”, like populism. The article presents the dispute between „eternal fascism” and „the defascination of fascism”, as well as the most important positions of some authors in the field regarding the possibility of equating Putinism with fascism. The article concludes that Putinism is a new phenomenon, an ideological DIY specific to Russia today, the result of the symbiosis between nationalism, fascism and ideas specific to the far left, to which is added a form of messianism that transcends political regimes and ideologies in Russia. Putinism has not reached the stage of ideology but is manifested by extreme violence (the war in Ukraine), a sign of political radicalism.

Introduction: The goal of this study is to provide analysis of statistics and dynamics of extreme heatwaves over two areas of Europe, France and Scandinavia, while comparing and contrasting the representation in climate models and reanalysis.Methods: The 1000 year long datasets are generated using respectively two climate models of different complexity. The composite maps of the heatwaves found in these datasets are compared to the ones observed in reanalysis by estimating significance of such patterns. We also employ time series analysis, in particular compare return time plots and use Gaussian stochastic processes to model the temporal correlations for rare events.Results: Our investigation reveals that recurrent wavenumber three teleconnection patterns distinctly underpin heatwaves in France and Scandinavia. These patterns manifest in both surface temperature and mid-tropospheric geopotential height. For heatwaves of return times of 4 years such patterns are robustly represented across diverse models of complexity and reanalysis data. For longer return times, reanalysis records are too short to give statistically significant results, while models confirm the relevance of these large scale patterns for the most extreme heatwaves. Moreover, A time series analysis shows that heatwave indices defined at synoptic scale are fairly well described by Gaussian stochastic processes, and that these Gaussian processes reproduce well return time plots even for very rare events.Discussion: These results suggest that extreme heatwaves over different areas of Europe show recurrent typical behaviours in terms of long-range spatial correlations and subseasonal-scale temporal correlations. These properties are consistently represented among models of different complexity and observations, thus suggesting their relevance for a better understanding of the drivers and causes of the occurrence of extreme midlatitude heatwaves and their predictability.

We plot the surface temperatures at LVi and LVa for three temperature minimums including the extreme cold event of 14 July 2018. Keywords: climate; extreme; meteorology; temperature; weather EN climate extreme meteorology temperature weather 120 123 4 05/16/23 20230401 NES 230401 Introduction The McMurdo Dry Valleys in East Antarctica represents the largest ice-free area on the continent. It is notable that LVi and VV stations show very similar temperature trends in 2018, providing more confidence in the LVi numbers. Results During a long calm period on 14 July 2018 at 01h00 local time (13 July at 12h00 GMT), the LVi 3 m temperature sensor measured a record low temperature for the entire McMurdo Dry Valley meteorological dataset of -69.1°C (Fig. [Extracted from the article]

Burrowing mammals strongly impact plant communities. One of the main effects is accelerating nutrient cycling and thus promoting plant growth. This mechanism is well‐studied in grasslands and alpine habitats, but less is known about this phenomenon in arid, cold mountain environments. We studied ecosystem engineering by long‐tailed marmots (Marmota caudata) by measuring the content of plant nitrogen and phosphorus, as well as nitrogen stable isotopes in plant biomass and marmot feces in a distance gradient up to 20 m from marmot burrows in an extremely arid glacier valley in Eastern Pamir, Tajikistan. We also captured aerial images of the area inhabited by marmots to study the spatial distribution of vegetation. There was a weak relationship between the presence of burrows and vegetation cover on soil not covered by burrow material. Burrow mounds were not colonized by plants, as opposed to other studies, where mounds are often microhabitats that enhance plant diversity. A significant increase in N and P in aboveground green plant biomass in the proximity of burrows was found in one out of six studied plant species. Contrary to our expectations, stable N isotopes did not give further insight into N routing. We assume that plant growth is strongly limited by water availability, which prevents them from utilizing the local increase in nutrients, certainly provided by marmot activity. The results are contrary to numerous studies, which showed that the role of burrowing animals as ecosystem engineers increases with increasing abiotic stress, including aridity. This shows a lack of this type of study at the end of the gradient of abiotic factors. The presence of marmots and their burrows has surprisingly little effect on plant nutrient content and on vegetation cover in an extremely arid, cold mountain habitat. Burrow mounds are no microhabitats, as there is no plant succession on them. The results are contrary to previous studies on the effect size of ecosystem engineering in arid environments. [ABSTRACT FROM AUTHOR]

In a rapidly changing environment, healthcare systems in polar regions face increasing pressures imposed by climate change, burgeoning tourism, and potential ramifications for future space exploration. The urgency to reevaluate health stewardship and governance in these areas is driven by unique challenges, including geographical barriers and scarce resources. Further accentuated by the ongoing COVID-19 pandemic and the anticipated boom in the polar tourism industry, the need for robust emergency, trauma, and surgical care is highlighted. The objective of this paper is to address these challenges and advocate for a unified health governance approach. Adopting measures like artificial intelligence, telemedicine, and advanced technologies is suggested to promote the effectiveness of remote care, considering the distinct limitations of these regions. Moreover, research focused on the human health impact of these extreme conditions is paramount for formulating adequate responses, thereby improving the overall readiness and resilience of the healthcare systems in these regions.

Various jobs, indoors and outdoors, are subjected to severe cold temperatures during daily activities. Extremely low-temperature exposure and work intensity affect health, safety, and occupational performance. This work aimed to assess the physiological and thermal sensation responses before, during, and following a 60 min exposure to cold (−20 °C), during which occupational activities were developed. Using ingestible telemetric temperature pills, eight skin temperature sensors, blood pressure equipment, and the Thermal Sensation Questionnaire, experiments were conducted with 11 healthy male volunteers wearing highly insulating cold protective clothing. The most notorious alterations were reported in mean skin temperatures and thermal sensation responses during the first 20 min of cold exposure. Among the eight skin temperature points, the forehead and left hand showed a higher sensitivity to cold. The mean core temperature reported significant variations throughout the protocol, with decreases during the initial 10 min of cold exposure and posterior increases despite the cold environment. Blood pressure showed slight increases from the initial to the recovery period. Overall, outcomes contribute to current scientific knowledge on physiological and perception responses in extremely cold environments while describing the influence of protective clothing and occupational activities on these responses. Future research should be developed with additional skin temperature measurements in the extremities (fingers, face, and toes) and the analysis of thermal sensation potential associations with performance changes, which can also be of great significance for future thermal comfort models.

Fire weather indices are one of the basic components of any fire danger early warning system. The Canadian Fire Weather Index (FWI) was developed to indicate the danger due to wildfires in boreal and temperate forests in Canada in the second half of the 20th century. Over time, the FWI has been adapted all over the world and is considered the most widely used fire weather index. This study provides a comprehensive review and meta-analysis of 750 research papers, generalizing the adoption of the FWI across 18 global environmental zones. The objective was to determine FWI values for various fire danger classes worldwide, from very low to extreme. The values of FWI and hydrometeorological variables were compared with wildfire occurrence. Key findings indicate that in drier and warmer climates, higher FWI values (around 50) correspond to high fire danger, whereas in cooler and moister climates, lower FWI values (around 25) signify extreme danger. The analysis of hydrometeorological variables reveals that relative humidity, aridity index, and vapor pressure deficit are significant factors influencing extreme minimum FWI, while average solar radiation has minimal impact. These insights have critical implications for developing effective wildfire prevention and management strategies tailored to specific environmental conditions. By establishing new fire danger classes reflective of regional meteorological and hydroclimatic characteristics, this study enhances the global applicability of the FWI. The ability to quickly adapt the FWI for fire danger forecasting in new areas is particularly beneficial for regions with previously low study coverage. The results underscore the importance of integrating regional climate variables into fire danger assessment frameworks to improve early warning systems and mitigate wildfire risks. The conclusions highlights the effectiveness of the FWI in diverse geographic contexts and its potential to enhance fire danger forecasting globally, thereby aiding in the prevention and management of wildfires.

Extreme rainfall events drive the amount and spatial distribution of rainfall in the Amazon and are a key driver of forest dynamics across the basin. This study investigates how the 3-hourly predictions in the High Resolution Model Intercomparison Project (HighResMIP, a component of the recent Coupled Model Intercomparison Project, CMIP6) represent extreme rainfall events at annual, seasonal, and sub-daily time scales. TRMM 3B42 (Tropical Rainfall Measuring Mission) 3 h data were used as observations. Our results showed that eleven out of seventeen HighResMIP models showed the observed association between rainfall and number of extreme events at the annual and seasonal scales. Two models captured the spatial pattern of number of extreme events at the seasonal and annual scales better (higher correlation) than the other models. None of the models captured the sub-daily timing of extreme rainfall, though some reproduced daily totals. Our results suggest that higher model resolution is a crucial factor for capturing extreme rainfall events in the Amazon, but it might not be the sole factor. Improving the representation of Amazon extreme rainfall events in HighResMIP models can help reduce model rainfall biases and uncertainties and enable more reliable assessments of the water cycle and forest dynamics in the Amazon.

Climate change can be traced in any given region by searching for changes in climatic elements' characteristics. Extreme precipitation, for example, is a characteristic of precipitation whose changes, especially in recent years, can be attributed to global warming and climate change. This study aimed to investigate possible changes in extreme precipitation in Iran by analysing the frequency of extreme rainy days duration. To this end, gridded precipitation datasets from the hydrological years 1971–1972 to 2015–2016 were used, and days associated with extreme precipitation were extracted by using thresholds of 90th, 95th, and 99th percentiles (as heavy, very heavy, and extremely heavy precipitation, respectively). Latitude and longitude showed the most significant correlation with precipitation characteristics in the spatial distribution during the study period. In addition, heavy (HP), very heavy, and extremely heavy precipitation experienced durations of 1–8, 1–7, and 1–4 days, respectively. At all extremes, the 1‐day duration covered more areas and had more repetition, while the longer duration had the lowest tempo–spatial repetition. According to the results of the present study, the one‐day duration of HP contributed more significantly to the annual precipitation. The proportion of this type of precipitation has been more significant in the southern and central regions of the country. Furthermore, it was revealed that the frequency of durations of short‐term HP increased during the study period, whereas the duration of long‐term HP declined. [ABSTRACT FROM AUTHOR]

Variational calculus studied methods for finding maximum and minimum values of functional. It has its inception in 1696 year by Johan Bernoulli with its glorious problem of the brachistochrone: to find a curve connecting two points A and B, which does not lie in a vertical, so that the heavy point descends along this curve from position A to reach position B in the shortest time. In functional analysis, variational calculus takes the same space, as well as the theory of maximum and minimum intensity in the classic analysis. We will prove a theorem for functional where we prove that the necessary condition for the extreme of the functional is the variation of functional to be equal to zero. We describe the solution of the equation of Euler with an example of application, such as the problem of brachistochrone, and its generalization that has the potential to completely revolutionize transportation. [ABSTRACT FROM AUTHOR]

In this paper, we will prove a theorem for a functional where we prove that the necessary condition for the extreme of a functional is the variation of the functional to be equal to zero and we will give an example of its application, the problem of the Plateau. [ABSTRACT FROM AUTHOR]

The EXTREME regimen is the standard for recurrent and/or metastatic head and neck squamous cell carcinoma (HNSCC). However, many patients have a poor performance status and/or comorbidities, making them unfit for this regimen. We have treated them with carboplatin and cetuximab (simplified EXTREME regimen) since 2007. Our aim was to assess the efficacy and tolerance of this regimen in this frail population. A retrospective chart review of all patients treated with the simplified EXTREME regimen for recurrent and/or metastatic HNSCC in three academic hospitals between 2007 and 2017 was carried out. The primary end point was overall survival. Secondary end points were progression-free survival (PFS), overall response rate (ORR) and toxicity. One hundred and three patients were included. The median age was 63 years, 40% had performance status 2–3. The median follow-up was 30.2 months. The median overall survival and PFS were 7.2 and 3.7 months, respectively. The median overall survival was 10.1 months in patients with performance status 0–1 versus 4.6 months in patients with performance status 2–3 (P = 0.01). ORR was 39%. Acute grade 3–4 haematological and non-haematological toxicity rates were 25.2% and 27.2%, respectively. Patients with grade 1 or more skin toxicity had a higher ORR (hazard ratio = 3.44; P = 0.03), a prolonged overall survival (hazard ratio = 0.37; P < 0.0001) and PFS (hazard ratio = 0.29; P < 0.0001). During treatment, 29% of patients had pain reduction, 13.5% had weight gain and 17.2% had an improvement in performance status. This is the largest cohort of patients treated with simplified EXTREME for HNSCC. It was well tolerated, with a high ORR. Interestingly, skin toxicity correlated with treatment efficacy. • Carboplatin and cetuximab (simplified EXTREME) is used in patients unfit for EXTREME. • It is well tolerated with 25% acute grade 3–4 haematological toxicity. • Median overall survival was 7.2 months, ORR was 39%. • Median overall survival was 10.1 months in patients with performance status 0–1. • Patients with grade 1 or more skin toxicity had a higher ORR and a prolonged overall survival. [ABSTRACT FROM AUTHOR]

Building efficient sampling procedures to provide more accurate results with small sample sizes is one of the main goals in sampling surveys. The ranked set sampling (RSS) is a well-known procedure for selecting representative samples and improving parametric estimation by employing ranking on observations. In order to have a more efficient sampling procedure, new sampling procedures are proposed and investigated in this article. The main focus of this article is to enhance the mean estimation of the study population using the proposed RSS procedures. The performance of the proposed sampling procedures is compared with their competitors in RSS, double RSS (DRSS), extreme RSS (ERSS), and double extreme RSS (DERSS) by conducting simulation studies for numerous (symmetric and asymmetric) distributions. An application to a real dataset is also considered to exemplify the achievement of the proposals. Numerical simulations show that the new modified estimators are unbiased for the population mean for symmetric distributions and they outperform their competitors in most of the cases investigated in this article. [ABSTRACT FROM AUTHOR]

This document is an editorial published in Frontiers in Marine Science titled "Impact of oceans on extreme weather events (tropical cyclones)." The editorial discusses the significant damage caused by extreme weather events, specifically tropical cyclones, to global coastlines. It emphasizes the need for reliable predictions of these events and highlights recent progress made by the research community in model improvements, data assimilation, and the use of physical and biogeochemical marine observations. The document also outlines future directions for research and development, including improved numerical modeling, integrated observing networks, advances in data assimilation techniques, risk-based decision support systems, resilience strategies, and stakeholder engagement. The authors stress the importance of interdisciplinary approaches to understanding and mitigating the impacts of extreme weather events on coastal areas. [Extracted from the article]

Introduction: The shortcomings of standardized sunscreen testing have been discussed in recent years, noting differences between how sunscreens perform in indoor clinical (in vivo) laboratory testing compared with real-life conditions. We previously developed an outdoor clinical method for ranking sunscreens by performance level. We used this method to test the performance of a new broad-spectrum sunscreen against International Organization for Standardization (ISO) reference products P3, P5 and P8. Methods: Sixty-five healthy volunteers with individual typology angle (ITA) ≥ 28° (light to intermediate skin colour) participated in an outdoor study in Mauritius. Test areas were marked on their backs, which were treated with the different products: one commercially available broad-spectrum sun protection factor (SPF) 50 sunscreen [investigational product (IP)] and the three reference products P3 (SPF 15), P5 (SPF 30) and P8 (SPF 50+) from ISO norm 24444:2019 for SPF testing. The test areas were exposed for 2–3 h, depending on the baseline skin colour. They were also compared with an unprotected positive control area and a non-exposed negative control area. Clinical and colorimetry assessment of erythema and pigmentation were performed at 24 h and 8 days, respectively. Results: Overall, according to this outdoor clinical testing method, the sunscreens' efficacy was ranked in an appropriate order given their established SPF levels, with higher SPFs giving greater protection against erythema and pigmentation. Between the different levels of SPF, the differences were statistically significant, for both clinical and colorimetry assessments. The new broad-spectrum SPF 50 IP performed similarly to the SPF 50+ (P8) reference product. Even the highest SPF products, SPF 50 and SPF 50+, had some instances of photoprotection failure. Conclusion: These findings confirm the feasibility of this outdoor clinical testing method in ranking sunscreens and provide further evidence, in addition to standardized SPF and UVA protection factor (UVAPF) testing, on how this new broad-spectrum SPF 50 sunscreen performs in extreme outdoor solar exposure: in line with reference product P8 (SPF 50+). Trial Registration No.: ISRCTN95394014. [ABSTRACT FROM AUTHOR]

Everyday evil is seen in a broad range of scenarios of intended behaviors that are often not violations of criminal law, but nevertheless cause significant and enduring personal and emotional harm. For this reason, the manifestations of everyday evil have pressing psychiatric import. Here, we propose the Welner Inventory of Everyday Extreme and Outrageous (WIEEO) for use as a screening inventory in clinical settings. The WIEEO contains 14 items within four categories: Physical and Emotional Damage, Exploitation, Extending Damage, and Extinguishing Goodness. Five items of "Physical and Emotional Damage" account for enduring life impact from said damage, and material effects that amplify emotional impact as well. Three items of "Exploitation" highlight the significance of not merely the actor's exploitation itself, but also the defenseless vulnerability of the victim. Four items that comprise the "Extending Suffering" category lengthen the impact, involve unusual dimensions, reflect creative social deviance in intent, or extend to additional parties. The two items of "Extinguishing Goodness" focus on the impact of decaying the otherwise prosocial or benevolent character of another and spawning everyday outrageousness in someone who would not have otherwise acted as such. These items have assumed relevance to the WIEEO through research and clinical settings that reveal their significant impact and psychological morbidity. The WIEEO serves as a marker for behaviors that warrant closer clinical attention to intervene, treat and detoxify such situations and the motivations of such malignant behavior before it further traumatizes or damages others. [ABSTRACT FROM AUTHOR]