Moderate Events Research Articles

Long-Term Spatiotemporal Investigation of Various Rainfall Intensities over Central India Using EO Datasets

This study involved an investigation of the long-term seasonal rainfall patterns in central India at the district level during the period from 1991 to 2020, including various aspects such as the spatiotemporal seasonal trend of rainfall patterns, rainfall variability, trends of rainy days with different intensities, decadal percentage deviation in long-term rainfall patterns, and decadal percentage deviation in rainfall events along with their respective intensities. The central region of India was meticulously divided into distinct subparts, namely, Gujarat, Daman and Diu, Maharashtra, Goa, Dadra and Nagar Haveli, Madhya Pradesh, Chhattisgarh, and Odisha. The experimental outcomes represented the disparities in rainfall distribution across different districts of central India with the spatial distribution of mean rainfall ranges during winter (2.08 mm over Dadra and Nagar Haveli with an average of 24.19 mm over Odisha), premonsoon (6.65 mm over Gujarat to 132.89 mm over Odisha), monsoon (845.46 mm over Gujarat to 3188.21 mm over Goa), and post-monsoon (30.35 mm over Gujarat to 213.87 mm over Goa), respectively. Almost all the districts of central India displayed an uneven pattern in the percentage deviation of seasonal rainfall in all three decades for all seasons, which indicates the seasonal rainfall variability over the last 30 years. A noticeable variation in the percentage deviation of seasonal rainfall patterns has been observed in the following districts: Rewa, Puri, Anuppur, Ahmadabad, Navsari, Chhindwara, Devbhumi Dwarka, Amreli, Panch Mahals, Kolhapur, Kandhamal, Ratnagiri, Porbandar, Bametara, and Sabar Kantha. In addition, a larger number of rainy days of various categories occurred in the monsoon season in comparison to other seasons. A higher contribution of trace rainfall events was found in the winter season. The highest contributions of very light, light rainfall, moderate, rather high, and high events were found in the monsoon season in central India. The percentage of various categories of rainfall events has decreased over the last two decades (2001–2020) in comparison to the third decade (1991–2000), according to the mean number of rainfall events in the last 30 years. This spatiotemporal analysis provides valuable insights into the rainfall trends in central India, which represent regional disparities and the potential challenges impacted by climate patterns. This study contributes to our understanding of the changing rainfall dynamics and offers crucial information for effective water resource management in the region.

Impact of Atlantic multidecadal variability on rainfall intensity distribution and timing of the West African monsoon

Abstract. Previous studies agree on an impact of the Atlantic multidecadal variability (AMV) on the total seasonal rainfall amounts over the Sahel. However, whether and how the AMV affects the distribution of rainfall or the timing of the West African monsoon is not well known. Here we seek to explore these impacts by analyzing daily rainfall outputs from climate model simulations with an idealized AMV forcing imposed in the North Atlantic, which is representative of the observed one. The setup follows a protocol largely consistent with the one proposed by the Component C of the Decadal Climate Prediction Project (DCPP-C). We start by evaluating model's performance in simulating precipitation, showing that models underestimate it over the Sahel, where the mean intensity is consistently smaller than observations. Conversely, models overestimate precipitation over the Guinea coast, where too many rainy days are simulated. In addition, most models underestimate the average length of the rainy season over the Sahel; some are due to a monsoon onset that is too late and others due to a cessation that is too early. In response to a persistent positive AMV pattern, models show an enhancement in total summer rainfall over continental West Africa, including the Sahel. Under a positive AMV phase, the number of wet days and the intensity of daily rainfall events are also enhanced over the Sahel. The former explains most of the changes in seasonal rainfall in the northern fringe, while the latter is more relevant in the southern region, where higher rainfall anomalies occur. This dominance is connected to the changes in the number of days per type of event; the frequency of both moderate and heavy events increases over the Sahel's northern fringe. Conversely, over the southern limit, it is mostly the frequency of heavy events which is enhanced, thus affecting the mean rainfall intensity there. Extreme rainfall events are also enhanced over the whole Sahel in response to a positive phase of the AMV. Over the Sahel, models with stronger negative biases in rainfall amounts compared to observations show weaker changes in response to AMV, suggesting that systematic biases could affect the simulated responses. The monsoon onset over the Sahel shows no clear response to AMV, while the demise tends to be delayed, and the overall length of the monsoon season enhanced between 2 and 5 d with the positive AMV pattern. The effect of AMV on the seasonality of the monsoon is more consistent to the west of 10∘ W, with all models showing a statistically significant earlier onset, later demise, and enhanced monsoon season with the positive phase of the AMV. Our results suggest a potential for the decadal prediction of changes in the intraseasonal characteristics of rainfall over the Sahel, including the occurrence of extreme events.

Estimation of Rainfall via IMERG-FR and Its Relationship with the Records of a Rain Gauge Network with Spatio-Temporal Variation, Case of Study: Mexican Semi-Arid Region

In the last few years, Satellite Precipitation Estimates (SPE) have been increasingly used for rainfall estimation applications. Their validity and accuracy are influenced by several factors related to the location where the SPEs are applied. The objective of this study is to evaluate the performance of the Integrated Multisatellite Retrievals for Global Precipitation Measurement Version 06 Half-Hour Temporal Resolution (IMERG-FR V06 HH) for rainfall estimation, as well as to determine its relationships with the hourly and daily rain gauge network data in a semiarid region during 2019–2021. The methodology contemplates the temporality, elevation, rainfall intensity, and rain gauge density variables, carrying out a point-to-pixel analysis using continuous, (Bias, r, ME, and RMSE), categorical (POD, FAR, and CSI), and volumetric (VHI, VFAR, and VCSI) statistical metrics to understand the different behaviors between the rain gauge and IMERG-FR V06 HH data. IMERG-FR greatly underestimated the heavy rainfall events in values of −63.54 to −23.58 mm/day and −25.29 to −11.74 mm/30 min; however, it overestimates the frequency of moderate rain events (1 to 25 mm/day). At making the correlation (r) between the temporal scales, the monthly temporal resolution was the one that better relates the measured and estimated data, as well as reported r values of 0.83 and 0.85, where records at shorter durations in IMERG-FR do not detect them. The weakness of this system, according to the literature and confirmed by the research findings, in the case of hydrological phenomena, is that recording or estimating short durations is essential for the water project, and therefore, the placement of rain gauges. The 1902–2101 m.a.s.l. range elevation has the best behavior between the data with the lowest error and best detection ability, of which IMERG-FR tended to overestimate the rain at higher altitudes. Considering that the r for two automated rain gauges per IMERG-FR pixel density was 0.74, this indicates that the automated rain gauges versus IMERG-FR have a better data fit than the rain gauges versus IMERG-FR. The distance to centroid and climatic evaluations did not show distinctive differences in the performance of IMERG. These findings are useful to improve the IMERG-FR algorithms, guide users about its performance at semiarid plateau regions, and assist in the recording of data for hydrological projects.

Observed failure modes in existing URM buildings after November 26, 2019 earthquake in Albania

This study explores the vulnerability of Unreinforced Masonry (URM) structures to seismic events, aiming to uncover the causes of failure and propose reconstruction strategies. Despite often being devastated in powerful earthquakes, URM buildings show damage even in mild to moderate seismic events. Field assessments after a magnitude 6.4 earthquake near Durres, Albania, in 2019, revealed severe damage in masonry buildings and adobe dwellings. Weak structural connections, insufficient roof support, and the absence of bond beams in load-bearing walls were identified as key contributors to the observed damage. The survival of masonry buildings post-earthquake does not guarantee seismic safety. The study recommends reinforcement techniques like shotcrete application, space reduction, and corner reinforcement, along with innovative methods such as Fiber Reinforced Polymer (FRP) use, for existing undamaged unreinforced buildings. These measures aim to prevent damage in the aftermath of destructive earthquakes, offering insights for the resilience of URM structures.

The Heat Budget of the Tropical Pacific Mixed Layer during Two Types of El Niño Based on Reanalysis and Global Climate Model Data

The heat budget of the equatorial Pacific mixed layer during El Niño formation was studied based on reanalysis (GLORYS2V4) and model data for the modern climate. The focus of the study is on the so-called El Niño diversity, i.e., the existence of different types of events that are characterized by different locations and intensities, as well as significantly different teleconnection all around the world. The analysis of the processes that participate in the formation of different El Niño types may serve for a better understanding of the El Niño dynamic and contribute to improving its forecast. Two classifications, based on the location and intensity of the events, were considered: strong/moderate and Eastern Pacific (EP)/Central Pacific (CP). The analysis did not reveal a significant difference in the heat budget of the mixed layer between strong and EP El Niño events, as well as between moderate and CP events. The major difference in the generation mechanism of strong (EP) and moderate (CP) El Niño events consists of the magnitude of heating produced by ocean heat budget components with higher heating rates for strong (EP) events. The evolution of sea surface temperature anomalies (SSTA) is governed primarily by oceanic advection. The vertical advection (due to the thermocline feedback) is the main contributor to SSTA growth in the eastern Pacific regardless of El Niño’s type. In the Central Pacific, horizontal advection is more important than vertical one, with a stronger impact of meridional processes for both strong and moderate regimes. Furthermore, the evaluation of the CMIP5 model’s skill in the simulation of the processes responsible for the formation of different El Niño types was carried out. The analysis of the heat budget of the mixed layer in the CMIP5 ensemble demonstrated that the most successful models are CCSM4, CESM1-BGC, CMCC-CMS, CNRM-CM5, GFDL-ESM2M, and IPSL-CM5B-LR. They are capable of reproducing the most important contribution of the advection terms in the SSTA tendency, keeping the major role of the thermocline feedback (and vertical advection) in the eastern Pacific, and do not overestimate the contribution of zonal advective feedback. These models are recommended to be used for the analysis of El Niño mechanism modification in the future climate.

Continued Treatment With Tirzepatide for Maintenance of Weight Reduction in Adults With Obesity

The effect of continued treatment with tirzepatide on maintaining initial weight reduction is unknown. To assess the effect of tirzepatide, with diet and physical activity, on the maintenance of weight reduction. This phase 3, randomized withdrawal clinical trial conducted at 70 sites in 4 countries with a 36-week, open-label tirzepatide lead-in period followed by a 52-week, double-blind, placebo-controlled period included adults with a body mass index greater than or equal to 30 or greater than or equal to 27 and a weight-related complication, excluding diabetes. Participants (n = 783) enrolled in an open-label lead-in period received once-weekly subcutaneous maximum tolerated dose (10 or 15 mg) of tirzepatide for 36 weeks. At week 36, a total of 670 participants were randomized (1:1) to continue receiving tirzepatide (n = 335) or switch to placebo (n = 335) for 52 weeks. The primary end point was the mean percent change in weight from week 36 (randomization) to week 88. Key secondary end points included the proportion of participants at week 88 who maintained at least 80% of the weight loss during the lead-in period. Participants (n = 670; mean age, 48 years; 473 [71%] women; mean weight, 107.3 kg) who completed the 36-week lead-in period experienced a mean weight reduction of 20.9%. The mean percent weight change from week 36 to week 88 was -5.5% with tirzepatide vs 14.0% with placebo (difference, -19.4% [95% CI, -21.2% to -17.7%]; P < .001). Overall, 300 participants (89.5%) receiving tirzepatide at 88 weeks maintained at least 80% of the weight loss during the lead-in period compared with 16.6% receiving placebo (P < .001). The overall mean weight reduction from week 0 to 88 was 25.3% for tirzepatide and 9.9% for placebo. The most common adverse events were mostly mild to moderate gastrointestinal events, which occurred more commonly with tirzepatide vs placebo. In participants with obesity or overweight, withdrawing tirzepatide led to substantial regain of lost weight, whereas continued treatment maintained and augmented initial weight reduction. ClinicalTrials.gov Identifier: NCT04660643.

Inter-event and intra-event dynamics of microplastic emissions in an urban river during rainfall episodes

Urban rivers represent the major conduits for land-sourced microplastics in the global oceans, yet the real-time dynamics of their emissions in rivers during rainfall (and runoff) events are poorly understood. Herein, we report the results of high-frequency sampling of microplastic particles (MPs) and fibers (MPFs) in the surface water of an urban river in Japan over the course of three rainfall events (i.e., light, moderate, and heavy rainfalls). The event mean concentrations (EMCs) of MPs amounted to 35,000 items/m3, 929,000 items/m3, and 331,000 items/m3; and the corresponding total loads were 0.5 kg, 19.8 kg, and 35.0 kg for light, moderate and heavy rainfalls, respectively. The inter-event total loads of MPs correlate well with the total rainfall, while the concentrations were linked with the number of antecedent dry days. The dynamic trends show that <2000 μm MPs displayed first flush effects during light to moderate rainfall events (>50% mass discharged with the initial 20–40% of flow). Small-sized MPs (10–40 μm) mobilized rapidly at lower rainfall intensities, whereas MPs over 2000 μm discharged immediately after the peak rainfall intensity. Moreover, <70 μm MPs depicted a surge following heavy rainfall events due to turbulent flow conditions reverting the deposited MPs into suspension. Overall, the three events increased the loads by 4–110 folds, and EMCs by 10–350 folds compared to the concentrations during dry weather while portraying a significant impact on 300–1000 μm MPs. The dynamics of MPs were correlated with those of suspended solids in river water, and the characteristics were comparable to the same of road dust sampled in Japan. Although the dynamic trends between MPs and MPFs in river water were comparable, MPFs were relatively less impacted by rain, likely due to the intervention of separate sewer systems in the study area.

Integrated crop and livestock systems increase both climate change adaptation and mitigation capacities

Integrated crop-livestock systems (ICLS) are proposed as key solutions to the various challenges posed to present-day agriculture which must guarantee high and stable yields while minimizing its impacts on the environment. Yet the complex relationships between crops, grasslands and animals on which they rely demand careful and precise management. In this study, from a 18-year ICLS field experiment in Brazil, that consists in annual no-till soybean-pastures grazed by beef cattle, we investigated the impacts of contrasted pastures grazing intensities (defined by sward heights of 10, 20, 30 and 40 cm, plus an ungrazed treatment) on the agroecosystem productivity and soil organic carbon (SOC) under both historical and future (2040–2070, RCP8.5) climatic conditions. We used an innovative methodology to model the ICLS with the STICS soil-crop model, which was validated with field observations. Results showed that the total system production increased along with grazing intensity because of higher stocking rates and subsequent live weight gains. Moderate and light grazing intensities (30 and 40 cm sward heights) resulted in the largest increase in SOC over the 18-year period, with all ICLS treatments leading to greater SOC contents than the ungrazed treatment. When facing climate change under future conditions, all treatments increased in productivity due to the CO2 fertilization effect and the increases in organic amendments that result from the larger stocking rate allowed by the increased pasture carrying capacity. Moderate grazing resulted in the most significant enhancements in productivity and SOC levels. These improvements were accompanied by increased resistance to both moderate and extreme climatic events, benefiting herbage production and live weight gain. Globally, our results show that adding a trophic level (i.e. herbivores) into cropping systems, provided that their carrying capacities are respected, proved to increase their ability to withstand climate change and to contribute to its mitigation.

Safety, tolerability, pharmacokinetics and pharmacodynamics of a single intravenous dose of SHR‐1707 in healthy adult subjects: two randomized, double‐blind, phase 1 studies

AbstractBackgroundSHR‐1707 is a novel humanized anti‐Aβ IgG1 monoclonal antibody that binds to Aβ fibrils and monomers to block the formation of Aβ plaques and to promote the microglial phagocytosis of Aβ. Preclinical studies in 5xFAD transgenic mice showed that SHR‐1707 reduced brain Aβ deposition and ameliorated memory deficits. Herein, we conducted two phase 1 studies to evaluate the safety, tolerability, pharmacokinetics (PK) and pharmacodynamics (PD) of a single intravenous dose of SHR‐1707 in healthy adult subjects.MethodTwo randomized, double‐blind, single‐ascending‐dose, phase 1 studies were conducted in China (Study CHN; NCT04973189) and Australia (Study AUS; NCT04745104). Study CHN consisted of 2 parts. In part 1, eligible healthy young adults (18‐45 years) were sequentially randomized 8:2 to receive SHR‐1707 (5 cohorts: 2, 6, 20, 40, and 60 mg/kg) or placebo in each cohort; in part 2, elderly subjects (55‐80 years) were randomized 8:4 to receive SHR‐1707 (20 mg/kg) or placebo. A similar design was used in Study AUS, but with only healthy young adults enrolled across 3 dosing cohorts (2, 20, and 60 mg/kg).Result62 (part 1/2, n = 50/12; mean age, 27.0/57.2 years) and 30 subjects (mean age, 26.1 years) were treated in Study CHN and Study AUS respectively. In Study CHN, across all dose levels, all TRAEs were mild in severity, with the most common being laboratory abnormalities. In Study AUS, TRAEs were mostly mild (1 moderate event each with SHR‐1707/placebo); the most common TRAEs with SHR‐1707 were dysgeusia and fatigue (8.3% each). In both studies, the exposure of SHR‐1707 increased in a slightly greater than dose‐proportional manner over the dose range of 2‐60 mg/kg in young adults; there was a dose‐dependent increase in plasma Aβ42 concentration following SHR‐1707 administration compared with the placebo group. The safety and PK/PD profiles of SHR‐1707 in the elderly subjects were consistent with the younger counterpart at the same dose level. No ethnic difference in safety and PK/PD of SHR‐1707 was observed.ConclusionA single intravenous dose of SHR‐1707 at 2‐60 mg/kg was safe and well tolerated in healthy young adult and elderly subjects. The PK/PD profiles are supportive of further clinical development.

Between-year and spatial variation in body condition across the breeding cycle in a pelagic seabird, the Red-billed Tropicbird.

Body condition in pelagic seabirds impacts key fitness-related traits such as reproductive performance and breeding frequency. Regulation of body condition can be especially important for species with long incubation periods and long individual incubation shifts between foraging trips. Here, we show that body condition of adult Red-billed Tropicbirds (Phaethon aethereus) at St Helena Island, South Atlantic Ocean, exhibited considerable variation between years (2013-2017) and between different stages of the breeding cycle. Females took the first incubation shift following egg laying, after which males and females alternated incubation shifts of varying length, ranging from <1 to 12 days. Body condition declined in both sexes during an incubation shift by an average of 22 g (2.83% of starting mass) per day and over the incubation period; mass loss was significantly greater during longer incubation shifts, later within a shift and later in the total incubation period. There was also significant differences in incubation behaviour and body condition between years; in 2015, coinciding with a moderate coastal warming event along the Angolan-Namibian coastlines, adults on average undertook longer incubation shifts than in other years and had lower body condition. This suggests that substantial between-year prey fluctuations in the Angola Benguela upwelling system may influence prey availability, in turn affecting incubation behaviour and regulation of body condition. Adults rearing chicks showed a significant reduction in body condition when chicks showed the fastest rate of growth. Chick growth rates during 2017 from two localities in the Atlantic Ocean: an oceanic (St Helena) versus neritic (Cabo Verde) population were similar, but chicks from St Helena were overall heavier and larger at fledging. Results from this multi-year study highlight that flexibility and adaptability in body condition regulation will be important for populations of threatened species to optimise resources as global climate change increasingly influences prey availability.

Bundled climate-smart agricultural solutions for smallholder farmers in Sri Lanka

Smallholder farmers are among the most vulnerable to climate shocks in Sri Lanka. Lack of education and technical skills, poverty, risks inherent to agricultural investments, limited assets, and financial capital are major reasons for low investments in enhancing adaptive capacity. The study explores the use of agricultural technologies in improving smallholder resilience to water-related disasters and their opportunities for recovery. We tested four bundled services to promote climate-smart agriculture practices namely weather index insurance (WII), agronomic advisories dissemination via SMS, weather services, and climate-resilient seeds of maize and rice. The integrated solutions are referred to as Bundled Solutions of Index Insurance with Climate Information and Seed Systems (BICSA) to manage agricultural risks in Sri Lanka. The study conducted the bundled solutions in three agroecological regions spread over five districts and covering more than 2,500 farmers in three cropping periods ofMahaandYalaseasons. The results demonstrate that providing bundled solutions significantly protects smallholders against moderate drought events. The satellite-based weather index insurance can offset the long-term consequences of severe yield losses and mitigate the long-term drop in farm productivity. Our findings demonstrate the importance of bundled insurance to mitigate financial risks associated with extreme weather events and enhance resilience to climate change among vulnerable smallholders. It is evident from the study promoting a viable business model among seed companies, insurance companies, and technological partners, along with public institutions such as agricultural extension services can help production-level improvements and develop strategies at both the farm and policy levels that will support a transition to a more resilient farming system.

Resistance of freshwater sediment bacterial communities to salinity disturbance and the implication for industrial salt discharge and climate change-based salinization

The impact of salinization on freshwater ecosystems became apparent during the 2022 ecological disaster in the Oder River, located in Poland and Germany, which was caused by salt discharge from mining activities. How bacterial communities respond to salinization caused by industrial salt discharge, or climate change-driven events, depends on the sensitivity of these complex bacterial communities. To investigate the sensitivity of bacterial communities to pulse salinization, we performed an experiment in the salinity range from 0.2 to 6.0. In addition, we sampled similar salinities in the littoral zone of the Baltic Sea where the bacterial communities are permanently exposed to the aforementioned salinities. To simulate a major disturbance, we included an ampicillin/streptomycin treatment in the experiment. Although the addition of antibiotics and increase in salinity had a significant impact on the water bacterial richness and community composition, only antibiotics affected the sediment bacterial community in the experiment. In contrast, sediment bacterial communities from the Baltic Sea littoral zone clustered according to salinity. Hence, sediment bacterial communities are more resistant to pulse changes in salinity than water bacteria but are able to adapt to a permanent change without loss in species richness. Our results indicate that moderate pulse salinization events such as industrial salt discharge or heavy storms will cause changes in the water bacterial communities with unknown consequences for ecosystem functioning. Sediment bacterial communities, however, will probably be unaffected in their ecosystem functions depending on the disturbance strength. Long-term disturbances, such as sea level rise or constant salt discharge, will cause permanent changes in the sediment bacterial community composition.

Limitations in the use of Sentinel-1 data for morphological change detection in rivers

ABSTRACT The identification of morphological changes occurring along river channels is essential to support river process understanding, assess sediment budgets and evaluate the effectiveness of river management. Among available remote sensing techniques, space-borne synthetic aperture radar (SAR) could potentially provide a powerful complement to optical imagery for this task. However, very few studies have been carried out on the use of SAR datasets to study erosion and deposition processes in river channels. In this work, we investigate the potential of change detection analysis based on Sentinel-1 data, by comparing variations of radar backscattering to river morphology changes identified through high-resolution drone acquisitions. We considered a time series of two years of Sentinel-1 data relative to a period where, despite a moderate fluvial event occurred, morphological changes have been significantly detected in multitemporal drone point clouds. Satellite optical imagery (planet.com) and hydro-meteorological data were used to support the analysis and interpret results. The results show that the spatial and temporal resolution of Sentinel-1 is currently not suitable for accurate discrimination of morphological changes related to river dynamics at local scale. Other spaceborne sensors with sub-metric ground sampling distance and/or daily revisit time would be probably suitable; however, so far, this option would need the use of commercial solutions with a consistent increase of the costs of the investigation.

Provider Perspectives on Diagnosis and Management of Acute Chest Syndrome

Introduction: Acute chest syndrome (ACS) is the leading cause of mortality, accounting for 25% of all deaths among individuals with sickle cell disease (SCD). The etiologies and clinical manifestations of ACS are variable, with a lack of clear risk stratification guidelines for the practicing clinician. Management of ACS is based on limited evidence and is currently guided primarily by expert opinion. Based on this gap in the diagnosis and management of ACS, we created a multicenter ACS work group in March 2022 that included pediatric and adult hematologists, and transfusion medicine physicians. We hypothesized that the risk stratification and management of ACS is significantly variable among providers involved in the care of SCD individuals. Methods: The ACS work group created a survey to determine how providers from different subspecialty groups diagnose and manage ACS. The survey was anonymous. Five ACS diagnostic features had to be rated from 1 to 5 in addition to 3 case scenarios to reflect mild, moderate, or severe ACS events as determined by the work group. The study was IRB approved and distributed through RedCap to providers from adult and pediatric hematology/oncology, transfusion medicine, emergency medicine, critical care and pulmonology during a one-month period in June to July, 2023. Results: Out of 465 providers who have received the survey to date, 161 providers have responded (34.6%). Of these, 103 (64%) reported caring for over 50 SCD individuals while 38 (24%) reported caring for &amp;gt;200 SCD individuals in the year prior. Most providers (68%) were from pediatric specialties (110/161) while 20% (32/161) were from solely adult specialties. One hundred and twenty-four (77%) of respondents were hematologists. Sixty-four percent (n= 103) of the providers rated a new pulmonary infiltrate as one of the top 2 criteria to diagnose ACS. However no other criteria for ACS such as hypoxia, lobar pneumonia, fevers, drop in hemoglobin of more than 2 g/dL from baseline, were rated as the top 2 criteria by more than 40% of the providers. For the case scenarios, the case deemed moderate ACS by the work group received the most discordant results about its stratification and management. Although most respondents considered it ACS (93%), 42% graded it as mild ACS (63/150) and 31% graded it as moderate ACS (46/150). For the management of this case, transfusion practices varied with 28 providers choosing 10-15 mL/kg packed red blood cells (pRBCs), 67 choosing pRBCs to goal hemoglobin of 9-10 g/dL and 10 providers choosing RBC exchange transfusion (RBCX). For all the case scenarios, a mean of 37 providers (24%) selected that grading for ACS is not important as the patient had ACS regardless of the grading. In the case deemed mild ACS, transfusions were selected by 4% (n = 6) of the providers choosing 10-15 mL/kg of pRBCs, and 7.5% (n =12) providers choosing pRBCs to goal hemoglobin of 9-10 g/dL. Conclusion: We conclude that diagnosis and management of ACS is highly variable, even among experienced specialty providers. Further research is needed to improve standardization of ACS risk stratification and management to optimize care for individuals with SCD.

Phase 1 Trial of Dendritic Cell/AML Fusion Cell Vaccine after Allogeneic Stem Cell Transplant in Acute Myeloid Leukemia

Introduction We have developed a vaccine in which patient-derived AML cells are fused with donor-derived dendritic cells (DCs). Vaccination after initial remission and consolidation was shown to elicit leukemia-specific immune responses. We hypothesized that donor-derived DC/AML vaccination post-transplant would elicit the durable expansion of leukemia-specific T cells within the donor T cell repertoire to effectively protect against disease relapse. We report updated results of a phase 1 clinical trial (NCT03679650) evaluating the use of DC/AML fusion vaccine following allogeneic transplant. Methods DC/AML fusion vaccine was generated with patient leukemia blasts, cryopreserved at the time of diagnosis, and donor-derived DCs, from leukapheresis of patients who achieved hematopoietic recovery and remained in CR 25-90 days after an allogeneic transplant. DCs were differentiated via culture of adherent mononuclear cells in the presence of GM-CSF, IL-4 and TNFa. Vaccine was administered starting day 70-100 post-transplant as long as the patient did not have active GVHD requiring therapy. Two doses of the vaccine were given subcutaneously at 3 week intervals, in conjunction with 100 mcg GMCSF daily at the vaccine site for 4 days. A booster vaccine was given 30-60 days following the taper of immune suppression, in the absence of GVHD. Longitudinal profiling of the immune landscape by single cell RNA sequencing and CyTOF from peripheral blood samples obtained before and after vaccination is underway. Immunologic response of leukemia-specfic T cells is being evaluated via IFN-gamma expression following stimulation with autologous tumor lysate. OS was calculated using Kaplan Meier Curve. Results 27 participants have been enrolled with median age 59 years (range 23-74). 15 patients were transplanted with a matched unrelated donor, 10 with a matched sibling donor and two with a haplo-identical donor. One patient relapsed prior to leukapheresis and was ineligible. The median yield of leukemia cells was 218x10 6 (range 62-818x10 6)and mean viability was 97%. The median yield of DCs was 106x10 6 (range 19-182x10 6) and mean viability 81%. Fusion vaccine was successfully generated in 25 of 26 patients who underwent leukapheresis; one patient had insufficient DC. Mean fusion efficiency was 47% with viability of 79%. Mean fusion vaccine dose was 3.8 x10 6 cells. 6 patients from whom vaccine was generated did not meet eligibility to initiate vaccination due to GVHD or COVID19 infection. 19 participants initiated vaccine administration and are evaluable for toxicity and immunologic response. The most common side effects were vaccine site reactions (n=10 grade 1, n=2 grade 2). 5 patients developed GVHD that was attributed as possibly related to vaccination, at a median time of 17 days after vaccination (range 5-70 days). Acute GVHD included two events of skin grade 2, one GI grade 2, one liver and skin grade 3. Chronic GVHD included a moderate event affecting 3 organs and severe event affecting 4 organs. There were 10 additional GVHD events with a median time of 108 days post vaccination (range 7-126 days), assessed as unlikely related or unrelated to vaccine based on pre-existing GVHD and timing of onset. Median time of follow-up is 23 months post-transplant (range 11-59 months). Amongst 19 vaccinated patients, 14 remained in CR and median overall survival estimate is 49 months post transplant. 3 died of relapsed disease, 2 died of GVHD and/or infection, and 1 died of unknown cause. Preliminary results of PB CyTOF from 4 patients in remission and 1 patient that relapsed indicate higher proportions of T cells and DCs in patients in CR. Interferon expression was higher in a patient with durable remission while absent from a patient with early relapse. Conclusions Vaccination using host-derived leukemia cells and donor derived DC was safe and feasible. Adverse events post vaccination have included injection site reactions as well as acute and chronic graft versus host disease. Vaccination may be a promising strategy to reduce relapse as 14 of 19 vaccinated patients remain relapse free. Albeit this approach is limited to patients who have not had early relapse or early GVHD. Immunologic response by interferon release upon lysate stimulation, CyTOF and single cell RNA sequencing of the immune milieu will be reported.

Relationship between the diagnosis of food protein-induced enterocolitis syndrome and postemetic procalcitonin levels.

There are no reports on the relationship between food protein-induced enterocolitis syndrome (FPIES) diagnosis and procalcitonin levels. Our study sought to demonstrate a correlation between the presence or absence and severity of FPIES symptoms and postemetic procalcitonin levels. The subjects were 53 patients with FPIES (44 with hen's egg allergy, 4 with milk allergy, 4 with wheat allergy, and 3 with soy allergy), who collectively underwent a total of 75 oral food challenges (OFCs). Procalcitonin levels at 5 hours after antigen ingestion were compared between patients with a positive OFC result and those with a negative OFC result and between patients who experienced mild or moderate events and those who experienced severe events. At 5 hours after ingestion of the causative food, the median procalcitonin levels in patients with a negative OFC result, patients who experienced a mild or moderate event, and patients who experienced a severe event were 0.02, 0.03, and 0.16 ng/mL, respectively. The procalcitonin level was significantly higher in the groups with a positive OFC result than in the groups with a negative OFC result (P< .001), and it was significantly higher in those who experienced severe events than in those who experienced mild or moderate events (P= .012). Measurement of procalcitonin levels has the potential to provide a quantitative and objective assessment of FPIES diagnosis and severity.

Metabolic regulation reduces the oxidative damage of arid lizards in response to moderate heat events.

Climate warming poses a significant threat to species worldwide, particularly those inhabiting arid and semi-arid regions where extreme temperatures are increasingly prevalent. However, empirical studies investigating how moderate heat events affect the physiological processes of arid and semi-arid animals are largely scarce. To address this knowledge gap, we used an arid and semi-arid lizard species (Phrynocephalus przewalskii) as a study system. We manipulated thermal environments to simulate moderate heat events (43.5 ± 0.3°C during the heating period) for lizards and examined physiological and biochemical traits related to survival, metabolism, locomotion, oxidative stress, and telomere length. We found that the body condition and survival of the lizards were not significantly affected by moderate heat events, despite an increase in body temperature and a decrease in locomotion at high test temperatures were detected. Mechanistically, we found that the lizards exhibited down-regulated metabolic rates and enhanced activities of antioxidative enzymes, resulting in reduced oxidative damage and stable telomere length under moderate heat events. Based on these findings, which indicated a beneficial regulation of fitness by physiological and biochemical processes, we inferred that moderate heat events did not have a detrimental effect on the toad-headed agama, P. przewalskii. Overall, our research contributes to understanding the impacts of moderate heat events on arid and semi-arid species and highlights the adaptive responses and resilience exhibited by the toad-headed agama in the face of climate warming.

Efficacy and safety of zuranolone co-initiated with an antidepressant in adults with major depressive disorder: results from the phase 3 CORAL study

Major depressive disorder (MDD) is a mental health disorder that can cause disability and functional impairment that standard-of-care (SOC) antidepressant therapies (ADTs) can take weeks to treat. Zuranolone is a neuroactive steroid and positive allosteric modulator of synaptic and extrasynaptic γ-aminobutyric acid (GABA) type A receptors approved as an oral, once-daily, 14-day treatment course in adults with postpartum depression and under investigation in adults with MDD. The phase 3 CORAL Study (NCT04476030) evaluated the efficacy and safety of zuranolone 50 mg co-initiated with SOC ADT (zuranolone+ADT) vs placebo co-initiated with SOC ADT (placebo+ADT) in adults with MDD. Patients were randomized 1:1 to once-daily, blinded zuranolone+ADT or placebo+ADT for 14 days, then continued open-label SOC ADT for 28 more days. The primary endpoint was change from baseline (CFB) in the 17-item Hamilton Rating Scale for Depression (HAMD-17) total score at Day 3. Among 425 patients in the full analysis set, CFB in HAMD-17 total score at Day 3 was significantly improved with zuranolone+ADT vs placebo+ADT (least squares mean [standard error], −8.9 [0.39] vs −7.0 [0.38]; p = 0.0004). The majority of patients receiving zuranolone+ADT that experienced treatment-emergent adverse events (TEAEs) reported mild or moderate events. The most common TEAEs present in ≥10% of patients in either zuranolone+ADT or placebo+ADT groups were somnolence, dizziness, headache, and nausea. These results demonstrate that zuranolone+ADT provided more rapid improvement in depressive symptoms compared with placebo+ADT in patients with MDD, with a safety profile consistent with previous studies. Clinical trial registration: ClinicalTrials.gov identifier: NCT04476030.

Reappraisal of the 1926, Jersey earthquake source parameters

The Cotentin peninsula is a region located on the northeastern edge of the Armorican Massif (France) that hosts several nuclear and radioactive waste facilities. A recent publication raised some issues regarding the source parameters of the 1926, Jersey earthquake, one of the key reference earthquakes for assessing the seismic hazard at the nuclear sites. In this study, we performed in-depth analyses on both the instrumental and macroseismic data to reappraise the source parameters. While the instrumental epicentral location was fairly well constrained at about mid-distance between the Jersey Island and the Cotentin peninsula, the focal depth could not be retrieved due to the resolution limits associated with a sparse seismological network and to the uncertainties on the phase picking. Different MS formulations applicable for moderate magnitude events recorded at regional distances were implemented to better account for the epistemic uncertainties, resulting in an estimation of MS equal to 5.1 ± 0.3. Regarding the moment magnitude MW, we performed a broad series of waveform modeling accounting for a broad set of source parameterizations and signal processing techniques. The magnitude MW of the Jersey earthquake is estimated to 5.4 ± 0.3 although these evaluations are strongly influenced by the period range adopted to fit the observations. We also carried out the evaluation of both MS and MW magnitudes by modeling the macroseismic field with results (MS = 5.1 ± 0.3; Mw = 5.3 ± 0.3) that are consistent with the instrumental estimates. Regarding the focal depth, the macroseismic analyses shed light on this parameter, even though the results depend on the assumption made on the presumed epicentral intensity (∼18 km for I0 = VI-VII and ∼ 12 km for I0 = VII).

Compound drought and heat waves variation and association with SST modes across China

Compound drought and heatwaves (CDH) have garnered increasing attention because concurrent extreme events can exacerbate the harmful impacts caused by univariate extremes. However, various severities in CDH events and their relationships with sea surface temperature (SST) variations in China remain little understood. Here, we accurately identify CDH events and multi-aspect of characteristics using the standardized precipitation evapotranspiration index (SPEI) and the excess heat factor (EHF) during the extended summer (May–September) of 1961–2017. The evolution of multifaceted characteristics of CDH and their association with SST variation are further explored. The results suggest that the number, frequency, duration and intensity of regional CDH events show heterogeneous spatial patterns, with a significant increasing trend. A consistent abrupt transition in CDH characteristics averaged over China occurred in the period of 1993–1996. Mild and moderate CDHs occur more commonly in Northwest and North China, whereas severe CDHs are mainly found in central and eastern regions. Mild and moderate CDHs are more susceptible to SST modes than severe CDH, and there are strong positive correlations between mild and moderate CDH characteristics and SST variations in the northwest and northern regions. Compared to El Niño-Southern Oscillation (ENSO), Indian Ocean Dipole (IOD) plays a dominant role in the intensifications of mild and moderate CDH events. Regionally, the northwest and north have experienced longer, more frequent and severe CDH events during the positive phase of IOD. These findings reveal the divergent evolutions in CDH characteristics with various severities and inconsistent impacts of different SST modes on the compound events.