Average Tmax Research Articles

Phase I study of TQB3728 tablets, an oral inhibitor of apoptosis proteins in patients with advanced solid tumor.

e13104 Background: Apoptosis proteins are frequently upregulated in human cancers and are associated with resistance to therapeutic agents and poor outcomes. TQB3728 antagonizes the function of inhibitor of apoptosis proteins (IAPs), thereby inhibiting NF-кB signaling pathways and promoting cancer cell death. This first-in-human study aims to evaluate the maximum-tolerated dose (MTD), safety, pharmacokinetics, pharmacodynamics, and antitumor activity of TQB3728 in patients with advanced solid tumors after the failure of standard therapy. Methods: This study combined an accelerated dose titration design with a 3+3 dose escalation design. Three dosage schedules were explored. First of all, TQB3728 was given orally once a week, on a 28-day cycle (DS1). The starting dose of 25mg was escalated by 100% in a single patient until the third dose, then diverted to a 3+3 dose escalation design. The other two dosage schedules were TQB3728 given once daily on days 1-14 every 3 weeks (DS2) and daily every 4 weeks (DS3). The primary endpoint was safety, maximum tolerated or maximum administered dose (MTD), and the secondary endpoints were pharmacokinetics, pharmacodynamics, and tumor response per RECIST v1.1. Results: As of Dec 15, 2023, 23 patients (pts) received at least one dose of TQB3728 (dose range, 25 to 600mg). Based on the pharmacokinetics and safety of DS1, then DS2 (dose range, 100 to 200mg) and DS3 (dose range, 100 to 200mg) were investigated. The median follow-up period was 8.5m (range, 0.5 to 25m). No dose-limited toxicity and cytokine release syndrome were observed. The main treatment-related adverse events (TRAEs) were nausea (56.5%), lymphopenia (56.5%), dizziness (39.1%), hypersomnia (34.8%), increased aspartate aminotransferase (30.4%), increased alanine aminotransferase (26.1%), vomiting (26.1%), anemia (21.7%), decreased appetite (21.7%), and grade≥3 TRAE were lymphopenia (8.7%), anemia (4.4%). As for DS1, the average Tmax and t1/2 were 2 h and 9.6 h, respectively. The exposure did not increase with the dose above 150mg. Moreover, the average Tmax was about 2.3 h and 0.8 h, and t1/2 was 6.6 h and 7 h in DS2 and DS3, respectively. There was no significant accumulation with continuous medication. Additionally, Plasma MCP-1 increased at 3-6h postdose at high dose; cIAP-1 levels in PBMCs were undetected. Two pts (8.7%) had stable disease >6 weeks as the best treatment response. Conclusions: TQB3728 was well tolerated at doses up to 600mg but had limited anti-tumor activity in advanced solid tumor. According to the preliminary results, TQB3728 administered orally in combination with conventional chemo-radiotherapy is under exploration. Clinical trial information: NCT04523285 .

Exploring the potential of drill cuttings for reservoir characterization: A case study from the Volga-Ural basin, Russia

The research objectives are to assess the possibility of using drill cutting analysis to obtain information about the mineralogical and geochemical properties of the reservoir rocks. Drill cutting samples were collected from a vertical well that penetrated the Domanik sediments (Semiluksk Formation) in one of the oil fields in the Volga-Ural petroleum province. Thin sections from drill cuttings were examined using an optical polarizing microscope (Axio Imager A2). X-ray diffraction (XRD) analyses were performed using a Brucker D2 Phaser X-ray powder diffractometer. Thermophysical properties were studied using an STA 449 F3 Jupiter instrument. The pyrolytic studies were performed using the Rock-Eval method. Visual inspection showed that the studied sediments are alternations of carbonates and siliceous-carbonate rocks. Thin section examinations revealed that the carbonates are mainly limestone (mudstone and wackestone) and are characterized by a dense texture and up to 30 % organic residues. The siliceous-carbonate rocks are dominated by siliceous mudstones and are characterized by dark colours, layered structure, and an enrichment in organic matter. XRD analyses showed that the carbonate rocks are mainly composed of calcite, dolomite, quartz, feldspar, and mica, which are minor components. The siliceous-carbonate rocks are dominated by quartz, followed by calcite, although they also contain feldspars, mica, dolomite, and pyrite as impurities. According to the simultaneous thermal analysis, the average total hydrocarbon in the carbonate and siliceous-carbonate rocks is 13.6 % (for the core samples) and 11.5 % (for the drill cutting samples). The content of heavy hydrocarbons in the rocks is higher than the content of light hydrocarbons, indicating the immature nature of organic matter. Kerogen is found sporadically in siliceous-carbonate rocks. According to the pyrolytic studies, average S1 is 4.4 mg/g and average S2 is 19.8 mg/g (for the core samples); average S1 is 2.1 mg/g and average S2 is 17.8 mg/g (for the drill cutting samples), which indicated that the studied sediments have very good to excellent generation potential. The average Tmax of 425.7 °C (for the drill cutting samples) and 427.9 °C (for the core samples) indicate immature organic matter that generated only heavy oils. Comparing the results of the analysed drill cutting samples with the results of the analysed core analysis from the same reservoir interval in the neighbouring wells showed a good correlation, which proves that this technique is a valid tool that provides an alternative, cost-effective method to determine the rock's characteristics from drill cuttings.

Projection and Uncertainty Analysis of Future Temperature Change over the Yarlung Tsangpo-Brahmaputra River Basin Based on CMIP6

Accurate predictions of future climate change are significant to both human social production and development. Accordingly, the changes in the daily maximum (Tmax) and minimum temperatures (Tmin) in the Yarlung Tsangpo-Brahmaputra River Basin (YBRB), along with its three sub-regions (Tibetan Plateau—TP, Himalayan Belt—HB, and Floodplain—FP) were evaluated here using the Bayesian model average (BMA) results from nine climate models in the CMIP6 under four future scenarios, and the corresponding uncertainty of the projected results was analyzed. The results showed the following: (1) The BMA can simulate the Tmax and Tmin of the YBRB well. (2) Future Tmax and Tmin over the YBRB exhibited an overall fluctuating upward trend. Even under the most ideal sustainable development scenario examined (SSP126), the average Tmax (Tmin) over the YBRB was projected to increase by 3.53 (3.38) °C by the end of this century. (3) Although the future changes in the YBRB are predicted to fall below the global average, the future temperature difference in the YBRB will increase further. (4) The uncertainty increased with prediction time, while spatially, the regions with the uncertainty were the TP > HB > FP. These findings can provide a reference for the YBRB climate change adaptation strategies.

Source-rock evaluation of the Triassic – Jurassic interval of the Tanga Basin, coastal Tanzania

The Triassic-Jurassic interval is known to be the main source of oil and gas generation across the world. In the Tanga Basin of Tanzania, however, the potentiality of these strata for oil and gas generation has remained poorly understood. This study presents the organic geochemical analysis of the source rock within the Triassic-Jurassic interval of the Tanga Basin, integrating rock-eval pyrolysis, vitrinite reflectance and spore coloration analyses to assess the organic richness, quality and maturity for hydrocarbon generation. The results reveal that the Triassic and Jurassic shales are organically rich, with average total organic carbon (TOC) values of 1 wt % and 2 wt %, respectively. Triassic shales demonstrate the dominance of kerogen types II (oil), III (gas pone), II/III (gas with minor oil), and IV (inert) as indicated by hydrogen index values between 365 and 15 mg HC/g TOC. The hydrogen index (HI) values in the Jurassic interval range from 87 to 162 mg/HC/TOC, suggesting the dominance of kerogen type III (gas prone). Pyrolysis Tmax, vitrinite reflectance (Ro) and spore color index (SCI) indicate that the Triassic interval is thermally mature into a gas generation window, with average Tmax values of 450 °C, Ro ∼ 1.7% and SCI ∼8.5. The Jurassic interval is also revealed as thermally mature, with average values of Tmax ∼ 452 °C, Ro ∼ 0.7% and SCI ∼ 7.2, indicative of oil window. The positive findings of this study lay out an important foundation to follow up studies and extended exploration for hydrocarbon accumulations in the poorly explored Tanga Basin and across the coastal Tanzania in general.

Physiological changes and behavioral responses in heat-stressed goats under humid tropical environment.

Kacang (K) and Kacang Etawah (KE) cross goats are the major goat breeds that are important for farming livelihood and income and recognized for their tolerance to hot and humid tropical climates. As global warming progresses, the daily maximum temperature (Tmax) is predicted to be continuously increased, which will challenge goat production in the future. The objective of this study was to evaluate the physiological and behavioral responses of the goats to the elevated Tmax. Six K and six KE female goats were housed in a normal environment (average Tmax: 33°C; temperature humidity index (THI): 76 to 86) for 6 weeks and then in a hot environment (average Tmax: 38°C; THI: 76 to 92) for 7 weeks. During hot conditions, rectal, rectal surface, and skin temperature, respiration rate, hemoglobin, and cholesterol increased (p < 0.05), whereas glucose blood levels decreased (p < 0.01). Dry matter (DM) intake was lowered (p < 0.01), and DM digestibility was elevated (p < 0.01), whereas drinking water and body water retention were lowered but varied (p < 0.05) during hot weeks. Lying time increased during the hot weeks in both breeds (p < 0.01), whereas lying and ruminating as well as total ruminating time was longer (p < 0.05) in KE goats compared to K goats, which explain the greater (p < 0.05) DM digestibility in KE goats. The effect of the elevated Tmax might be less severe since it also depends on the duration of the Tmax and the variation of daily THI.

Hydrothermally-altered coal from the Daqingshan Coalfield, Inner Mongolia, northern China: Evidence from stable isotopes of C within organic matter and C-O-Sr in associated carbonates

Igneous intrusions can bring hydrothermal fluids, metals, and ligands to the surrounding host sequences, changing their physical, textural and chemical features to some extent depending on the degree of thermal exposure. However, regarding hydrothermally-altered coals, previous studies have predominately focused on variations in coal quality, chemistry and mineralogy, despite the growing research on stable and radioactive isotopes within coal-bearing sequences.The Pennsylvanian coal from the Daqingshan Coalfield, Inner Mongolia, China, was thermally affected by a granitic intrusion in the eastern part of the coalfield during the Yanshanian Orogeny, between the Late Jurassic and Early Cretaceous. The investigated Hailiushu, Datanhao, and Adaohai mines in present study are distributed in Daqingshan Coalfield from west to east. The Adaohai Mine is located to the southwest of the intrusion point, at a distance of approximately 50 km. The Hailiushu and Adaohai mines are about10 km apart, and the Datanhao Mine is located between them. With decreasing distance to the intrusion, there is an increase in vitrinite reflectance values (from 0.84% through 1.17% to 1.58%) and a decrease in the volatile matter content (from 44.57% through 31.31% to 19.60%) in the studied three coal mines.The present study revealed that the westernmost Hailiushu coals have the most negative δ13Corg values (from −24.8 ‰ to −23.5 ‰; −24.3 ‰ on average). In contrast, with the distance from the intrusion decreases, the δ13Corg values of coals from the Datanhao mine range from −24.8 ‰ to −23.5 ‰ (−24.2 ‰ on average). The δ13Corg values of the easternmost Adaohai coals range from −23.8 ‰ to −22.8 ‰, (−23.3 ‰ on average), about 1 ‰ less negative than those in the Datanhao and Hailiushu coals. It is not just the maceral composition that causes the difference in organic carbon isotopes, but the loss of 12C-enriched volatiles due to the thermal effects associated with the igneous intrusion. This hypothesis was further supported by Rock-Eval analysis on the organic matter: the average Tmax of the Hailiushu, Datanhao, and Adaohai coals increases but generation of hydrocarbons and pyrolysable carbon decrease as approaching the intrusion. Moreover, fracture/cleat-filling carbonates are more abundant in the Adaohai coals than in the Datanhao and Hailiushu coals. The δ13CPDB (from −14.2 ‰ to 1.7 ‰) and δ18OPDB (from −16.9 ‰ to −7.0 ‰) of these vein carbonates all indicate a hydrothermal origin. Hydrothermal fluids derived from igneous intrusions is also responsible for the elevated 87Sr/86Sr ratios (0.711392–0.717643) in the carbonate mineral in the thermally altered coals.

Preclinical Pharmacokinetic Study on Caffeine as an Excipient for Monoclonal Antibody Formulations

Caffeine is a novel excipient that effectively reduces viscosity of high concentration mAb formulations intended for subcutaneous (SQ) delivery. Two preclinical studies were conducted in rats to evaluate pharmacokinetic (PK) parameters of caffeine as well as its effects on the PK profile of a model mAb, namely ipilimumab. Results show that SQ absorption and elimination of caffeine was rapid, with the average Tmax of 0.4 h and T1/2 of 1.6 h, administered with or without ipilimumab. Furthermore, caffeine did not affect ipilimumab SQ PK profiles. Independent of caffeine concentration, ipilimumab serum T1/2 was between 2 and 3 days, Tmax was between 3 and 4 days and SQ bioavailability was about 64%. In addition, SQ injection of caffeine at different dose levels showed no irritation at the injection site or adverse effects. Results from the current PK studies warrant further development of caffeine as a viscosity reducing excipient for mAb SQ formulations.

Human metabolism and excretion kinetics of the surfactant 2,4,7,9-tetramethyl-5-decyne-4,7-diol (TMDD) after oral and dermal administration.

2,4,7,9-Tetramethyl-5-decyne-4,7-diol (TMDD) is a non-ionic surfactant with a wide range of applications. TMDD is considered a high-production chemical and, due to its low biodegradation rate, possesses a potentially high prevalence in the environment. However, despite its widespread use, toxicokinetic data and data on internal exposure to TMDD in the general population are completely lacking. Hence, we developed a human biomonitoring (HBM) method for TMDD. Our approach included a metabolism study with four subjects, who were administered an oral dose of 75µg TMDD/kg body weight and a dermal dose of 750µg/kg body weight. Terminal methyl-hydroxylated TMDD (1-OH-TMDD) was previously identified as the main urinary metabolite in our lab. The results of the oral and dermal applications were used to determine the toxicokinetic parameters of 1-OH-TMDD as a biomarker of exposure. Finally, the method was applied to 50 urine samples from non-occupationally exposed volunteers. Results show that TMDD was rapidly metabolized, with an average tmax of 1.7h and a rapid and almost complete (96%) excretion of 1-OH-TMDD until 12h after oral dosage. Elimination was bi-phasic, with half-lives of 0.75-1.6h and 3.4-3.6h for phases 1 and 2, respectively. The dermal application resulted in a delayed urinary excretion of this metabolite with a tmax of 12h and complete excretion after about 48h. The excreted amounts of 1-OH-TMDD represented 18% of the orally administered TMDD dose. The data of the metabolism study demonstrated a fast oral as well as substantial dermal resorption of TMDD. Moreover, the results indicated an effective metabolism of 1-OH-TMDD, which is excreted rapidly and completely via urine. Application of the method to 50 urine samples revealed a quantification rate of 90%, with an average concentration of 0.19ng/mL (0.97nmol/g creatinine). With the urinary excretion factor (Fue) derived from the metabolism study, we estimated an average daily intake of 1.65µg TMDD from environmental and dietary sources. In conclusion, 1-OH-TMDD in urine is a suitable biomarker of exposure to TMDD and can be applied for biomonitoring of the general population.

Future climate projections using the LARS-WG6 downscaling model over Upper Indus Basin, Pakistan.

This study investigates the projections of precipitation and temperature at the local scale in the Upper Indus Basin (UIB) in Pakistan using six Regional Climate Models (RCMs) from CORDEX under two Representative Concentration Pathways (RCP 4.5 and RCP 8.5). For twenty-four stations spread across the study area, the Long Ashton Research Station Weather Generator, version six (LARS-WG6), was used to downscale the daily data from the six different RCMs for maximum temperature (Tmax), minimum temperature (Tmin), and precipitation (pr) at a spatial resolution of 0.44°. Investigations were made to predict changes in mean annual values of Tmax, Tmin, and precipitation during two future periods, i.e., the mid-century (2041-2070) and end-century (2071-2100). The model results from statistical and graphical comparison validated that the LARS-WG6 can simulate the temperature and the precipitation in the UIB. Each of the six RCMs and their ensemble revealed a continuously increased temperature projection in the basin; nevertheless, there is variation in projected magnitude across RCMs and between RCPs. The rise in average Tmax and Tmin was more significant under RCP 8.5 than RCP 4.5, possibly due to unmitigated greenhouse gas emissions (GHGs). The precipitation projections follow the non-uniform trend, i.e., not all RCMs agree on whether the precipitation will increase or decrease in the basin, and no orderly variations were detected during any future periods under any RCP. However, an overall increase in precipitation is projected by the ensemble of RCMs.

Predicted changes in future precipitation and air temperature across Bangladesh using CMIP6 GCMs

Understanding spatiotemporal variability in precipitation and temperature and their future projections is critical for assessing environmental hazards and planning long-term mitigation and adaptation. In this study, 18 Global Climate Models (GCMs) from the most recent Coupled Model Intercomparison Project phase 6 (CMIP6) were employed to project the mean annual, seasonal, and monthly precipitation, maximum air temperature (Tmax), and minimum air temperature (Tmin) in Bangladesh. The GCM projections were bias-corrected using the Simple Quantile Mapping (SQM) technique. Using the Multi-Model Ensemble (MME) mean of the bias-corrected dataset, the expected changes for the four Shared Socioeconomic Pathways (SSP1-2.6, SSP2-4.5, SSP3-7.0, and SSP5-8.5) were evaluated for the near (2015–2044), mid (2045–2074), and far (2075–2100) futures in comparison to the historical period (1985–2014). In the far future, the anticipated average annual precipitation increased by 9.48%, 13.63%, 21.07%, and 30.90%, while the average Tmax (Tmin) rose by 1.09 (1.17), 1.60 (1.91), 2.12 (2.80), and 2.99 (3.69) °C for SSP1-2.6, SSP2-4.5, SSP3-7.0, and SSP5-8.5, respectively. According to predictions for the SSP5-8.5 scenario in the distant future, there is expected to be a substantial rise in precipitation (41.98%) during the post-monsoon season. In contrast, winter precipitation was predicted to decrease most (11.12%) in the mid-future for SSP3-7.0, while to increase most (15.62%) in the far-future for SSP1-2.6. Tmax (Tmin) was predicted to rise most in the winter and least in the monsoon for all periods and scenarios. Tmin increased more rapidly than Tmax in all seasons for all SSPs. The projected changes could lead to more frequent and severe flooding, landslides, and negative impacts on human health, agriculture, and ecosystems. The study highlights the need for localized and context-specific adaptation strategies as different regions of Bangladesh will be affected differently by these changes.

Preliminary results of petroleum source rock evaluation of Mongolian Mesozoic oil shales

Jurassic and Cretaceous oil shale samples, collected from northern and central Mongolian basins, have been analyzed to determine their petroleum source rock potential. The contents of total organic carbon (TOC) and total sulfur, and source rock screening data were obtained by Rock-Eval pyrolysis. Cretaceous oil shales contain up to 17.4 wt.% TOC and Hydrogen Index (HI) values range from 638-957 mg HC/g TOC. Jurassic oil shale samples have similar TOC contents, ranging from 10.7 to 17.3 wt.%. HI values of Jurassic Tsagaan-Ovoo oil shale vary between 270-313 mg HC/g TOC. Average Tmax values of Cretaceous and Jurassic samples are 4370C and 4230C, respectively. This observed data indicates that both Jurassic and Cretaceous oil shales are excellent source rock. Cretaceous oil shales contain type I kerogen (highly oil prone), while Jurassic Tsagaan-Ovoo oil shale has mixed type II/III kerogen (mixed oil and gas prone). Based on Tmax and Production Index values, both Jurassic and Cretaceous oil shales are immature. Overall, the result of this study contributes organic geochemistry database of Mongolian oil shale and encourages source rock potential of both Jurassic and Cretaceous oil shale.

Analysis of Air Temperature and Precipitation Trends in Kandahar city, Afghanistan from 1990-2019

This study aims to analyze trends of three, annual average temperature, annual average T-max, annual average T-mini, and precipitation over the last 30 years 1990-2019 in Kandahar City, the western part of Afghanistan. For the purpose of analysis, available data from Afghanistan Meteorological Department (AMD) and Power Data Access Viewer dataset were used. First, daily average temperature and precipitation data were converted to monthly average data, then converted to annual average data for statistical calculation. The linear regression equation and trend magnitude was applied to identify the trend of temperature and precipitation. Analysis of the data demonstrated an upward trend in average temperature, average T-max, average T-mini, and downward precipitation, the most upward trend obtained in an annual average of T-mini and less upward trend in an annual average of T-max. Simultaneously, by increasing temperature, precipitation decreased which indicates dry and hot temperatures. The ongoing climate change affects various factors, especially agriculture, and socioeconomics. On this basis, it is recommended that the result could serve as a key in making plans and policies for those authorities involved in the planning. Further research is needed to identify other climatic parameters for a comprehensive understanding of the current and future climatic situation of the study area. Keywords: Air temperature, Precipitation, Climate change, Kandahar city, Trend line

A phase I/II study of arfolitixorin and 5-fluorouracil in combination with oxaliplatin (plus or minus bevacizumab) or irinotecan in metastatic colorectal cancer

Background5-fluorouracil (5-FU) combined with a folate remains an essential treatment component for metastatic colorectal cancer (mCRC). Leucovorin is the folate most often used, but requires intracellular conversion to a reduced folate, and has high pharmacokinetic variability and limited bioavailability in patients with low folate pathway gene expression. Arfolitixorin is an immediately active form of folate, [6R]-5,10-methylenetetrahydrofolate ([6R]-MTHF), and may improve outcomes.Patients and methodsThis open-label, multicenter, phase I/II study in patients with mCRC (NCT02244632) assessed the tolerability and efficacy of first- or second-line arfolitixorin (30, 60, 120, or 240 mg/m2 intravenous) with 5-FU alone, or in combination with oxaliplatin (plus or minus bevacizumab) or irinotecan, every 14 days. Safety, efficacy, and pharmacokinetics were assessed before and after four cycles (8 weeks) of treatment.ResultsIn 105 treated patients, investigators reported 583 adverse events (AEs) in 86 patients (81.9%), and 256 AEs (43.9%) were potentially related to arfolitixorin and 5-FU. Dose adjustments were required in 16 patients (15.2%). At 8 weeks, 9 out of 57 patients assessed for efficacy achieved an objective response (15.8%), and all 9 achieved a partial response. Six of these nine patients had received arfolitixorin as a first-line treatment. A further 33 patients (57.9%) achieved stable disease. Pharmacokinetics were assessed in 35 patients. The average tmax was 10 min, and area under the plasma concentration–time curve from time 0 to 1 h increased linearly between 30 and 240 mg/m2. No accumulation was observed for [6R]-MTHF following repeated administration, and there were no major pharmacokinetic differences between cycle 1 and cycle 4 at any dose.ConclusionsArfolitixorin is a well-tolerated moderator of 5-FU activity. It is suitable for further investigation in mCRC and has the potential to improve treatment outcomes in patients with low folate pathway gene expression. Arfolitixorin can easily be incorporated into current standard of care, requiring minimal changes to chemotherapy regimens.

Development, characterization and optimization of a new bone cement based on calcium–strontium aluminates and chitosan-glycerin solution

Bioceramic bone cements are increasingly studied, developed, and improved to become a viable alternative to polymethyl methacrylate (PMMA)-based cements. In this regard, we aimed to develop a new cement composed of calcium aluminate (C12A7) and strontium aluminate (S3A) powders obtained via solution combustion synthesis (SCS) and chitosan/glycerin solution. The cement properties were optimized through a design of experiments. The approach used in the optimization process was the 2k factorial experimental design with insertion of 3 repetitions of the central point, which resulted in 11 compositions. All compositions were tested to determine the liquid/powder ratio (L/P), final setting time (ST), maximum hydration temperature (Tmax), compressive strength and radiopacity. The results were statistically evaluated by analyzing the effects, Pareto diagram, ANOVA analysis and response surface plot. The models obtained in this study could precisely predict three responses: Tmax, compressive strength, and radiopacity. An optimized composition for possible application as bone cement had an average Tmax of 40.34 °C, compressive strength of 7.75 MPa and radiopacity of 3.76 mm Al, all above the standard requirements.

Modeling the response of sesame (Sesamum indicum L.) growth and development to climate change under deficit irrigation in a semi-arid region

The future climate outlook was based on a combination of CCMs based on three Representative Concentration Pathway (RCP) scenarios including RCP 2.6, RCP 4.5 and RCP 8.5 for the future period of 2021–2051. The results showed an increase of the average Tmax in June, July and August (averaged by 1.8°C compared to the observed period) and a decrease in rainfall in May to September (averaged by 30.76 mm compared to the observed period under all three scenarios. Estimation of phenological stages of sesame under different scenarios showed that with increasing Tmax in April and May, the beginning of flowering, grain filling and physiological maturity was accelerated, also with increasing temperature from June to August the duration of the phenological stages was decreased. The effect of deficit irrigation (DI, supplying of 50% plant water requirement) on sesame phenological stages was not significantly different from full irrigation (FI). Simulation of canopy cover evolution (CC) and dry matter accumulation using the AquaCrop model revealed that the length of the late-season and the mid-season stages, have the greatest liability to be changed under the future climate change. Under the studied scenarios, the beginning of sesame growing season will accelerate from 9 to 11 days, which makes possible delayed sowing of sesame. The average of biomass (B) produced under three scenarios in DI and FI conditions were 17920 and 17241 kg ha-1, and the average of grain yield (GY) was 2905 and 3429 kg ha-1, respectively, which shows an increase by 31.5% and 28.7% of B, 18.4% and 39.5% of GY, compared to the observations (year 2016). The results revealed that under the future climate (except for RCP8 scenario), DI strategy can be used without reducing the GY of sesame due to the very little reduction (1.2%) in GY under DI compared to FI.

A phase I/II study of first-in-human trial of JAB-21822 (KRAS G12C inhibitor) in advanced solid tumors.

3089 Background: KRAS G12C mutation occurs in approximately 4% of non-small cell lung cancer (NSCLC), 1-2% of colorectal cancer (CRC) and other solid tumors in China. JAB-21822 (Jacobio, Beijing, PRC) is a highly selective, covalent oral inhibitor of KRAS G12C. Methods: NCT05009329 is an ongoing first-in-human, open label phase I/II study of JAB-21822 in patients with advanced solid tumors. The primary objective is to evaluate the safety and tolerability of JAB-21822. Other objectives include preliminary efficacy, pharmacokinetics, and biomarkers. Here we report the results from the dose escalation phase of the trial. Results: As of January 28th, 2022, 53 patients with a median age of 62 years (39-79) were enrolled in 5 different dose levels: 200mg QD, 400mg QD, 800mg QD, 400mg BID and 400mg TID. Most patients (55%) had ≥ 2 prior lines of therapy. No dosing-limiting toxicities were observed. Two treatment-related adverse events (TRAEs) were G4 neutropenia (1 in 400mg BID and 1 in 400mg TID). The most common TRAEs (≥ 10%) included anemia (24.5%), total bilirubin increase (20.8%), direct bilirubin increase (15.1%), proteinuria (13.2%) and indirect bilirubin increase (11.3%). Only Grade 1 and 2 TRAEs were observed in the QD cohorts. A total of 33 patients (22 NSCLC, 9 CRC and 2 pancreatic cancer) had at least 1 post-baseline tumor assessment; in the 800mg QD cohort, overall response rate (ORR) and disease control rate (DCR) were 50% (5/10) and 100% (10/10), respectively, including 4 non-confirmed partial response (PR); in the 400mg QD cohort had an ORR and DCR of 80% (4/5) and 100% (5/5) respectively, including 2 non-confirmed PR. Patients with NSCLC (400mg QD and 800mg QD), the ORR and DCR were 70% (7/10) and 100% (10/10), respectively, including 5 non-confirmed PR. With respect to the pharmacokinetics analysis, JAB-21822 was rapidly absorbed with an average Tmax of 2 hr and reached higher plasma exposures (Cmax and AUC0-24h) after a single dose and multiple doses at C1D8. Conclusions: JAB-21822 was well tolerated with impressive preliminary efficacy in patients with heavily treated solid tumors harboring KRAS G12C mutation. The study is enrolling patients in the expansion phase. Multiple JAB-21822-based combination trials are also ongoing. Clinical trial information: NCT05009329.

Climate Change Induced Major Livelihood Changes on Char Dwellers in Northern Regions of Bangladesh

Bangladesh is one of the most vulnerable to climate change due to its geographic position and socio-economic context. The newly emerged land in the river channel is called char. The northern region especially Lalmonirhat, Kurigram, Gaibandha is most vulnerable. The study was carried out based on a questionnaire interview, focus group discussion, and secondary data sources from Bangladesh Meteorological Department (BMD). Climatic factors such as temperature (seasonal Tmax and Tmini, daily average Tmax and Tmini), rainfall, sunshine, relative humidity, solar radiation intensity, sea level pressure and wind speed, etc. were detailed (how much change between before 2000s’and after the 2000s’) studied in these areas. These are the main drivers that influence the vulnerability dimensions resulting in livelihood strategies and access to food, water, agricultural practices, income and overall livelihood, and leads to a vicious cycle of poverty. The study helps to understand the impacts of climate change, and natural disaster-related threats in the northern char area. Also suggested that if providing necessary institutional and organizational supports for strengthening the livelihood capitals, assets, and strategy to combat or mitigate impacts of climate change aspects in Bangladesh. SAARC J. Agric., 19(2): 317-330 (2021)

1033. Skin Surface Thermal Imaging to Differentiate Cellulitis and Pseudocellulitis in the Emergency Department

Abstract Background Cellulitis is misdiagnosed in up to 30% of cases, resulting in overuse of antibiotics. This represents a threat to patient safety and public health. Surface thermal imaging has been proposed as a tool to reduce errors in diagnosing cellulitis. The study objective was to compare skin surface temperature measurements between patients with cellulitis and pseudocellulitis. Methods We prospectively enrolled patients presenting to the emergency department (ED) with dermatologic lower extremity complaints that involved visible erythema. Using a thermal imaging camera, the maximum temperature value (Tmax) for the affected area of skin and corresponding area on an unaffected limb were captured. The Tmax gradient between the affected and unaffected limb was calculated. Gold standard diagnosis (cellulitis versus pseudocellulitis) was determined by consensus of a blinded, multidisciplinary physician review panel (two infectious disease, two dermatologists and two emergency medicine). Differences in temperature variables (Tmax and Tmax gradient) between cellulitis and pseudocellulitis were compared using t-tests. Results The sample included 204 participants, 59% male with an average age of 57 years. Based on expert panel consensus diagnosis, 92 (45%) of the participants had cellulitis. The cellulitis group had an average Tmax of 33.2°C and 30.2°C for affected and unaffected skin respectively, which was a significant difference of 2.9°C (CI: 2.5 to 3.6; p&amp;lt; 0.001). The difference in the Tmax gradients between patients with cellulitis and pseudocellulitis was 2.08°C (CI: 1.46-2.70; p&amp;lt; 0.001). Conclusion This represents the largest validation study of skin surface temperature differences between cellulitis and pseudocellulitis. Significant difference in temperature gradients between cases of cellulitis and pseudocellulitis suggests thermal imaging could be a useful diagnostic adjunct that can help differentiate these conditions. Such a modality could be particularly helpful in the ED setting where providers must balance diagnostic uncertainty with antimicrobial stewardship principles. Future work will identify the best performing temperature variables and determine optimal cutoff values for use in diagnostic algorithms. Disclosures All Authors: No reported disclosures

Hydrocarbon source rock potential of the Lower Eocene carbonates from the Abu Darag sub-basin, Gulf of Suez, Egypt: Integrated organic geochemical and petrographic analyses

Twenty-four subsurface samples from the Lower Eocene Thebes Formation in the north Gulf of Suez underwent organic geochemical and petrographic analyses. The aim is to evaluate the hydrocarbon source rock potential and understand the organic facies composition of this pre-rift formation, which received little attention. The Thebes Formation is a potential hydrocarbon source rock in the area of the GS 24–1 well with an average TOC of 1.52 wt% (range 0.51–4.23 wt%). The organic geochemical (HI/OI and Pr/Ph vs Pr/n-C17) and petrographic analyses revealed that the organic matter of this conventionally known marine source rock is made up of both marine and terrestrial sources in the Abu Darag sub-basin. The predominant kerogen type II is comprised mainly of liptinitic (dinoflagellate cysts and amorphous organic matter: AOM) and subordinate vitrinitic macerals, which produced mixed cyclo and normal alkanes and some aromatics when subjected to pyrochromatography. The average Tmax value of 428 °C and UV fluorescence of the palynomorphs and AOM indicate that the organic matter has entered the early oil-window stage. The tectonostratigraphic evolution of the Abu Darag sub-basin affected the Thebes Formation source rock quality. More exploration activities across this sub-basin are needed to fully explore the organic facies composition and hydrocarbon potential of the Thebes Formation.

Projected temperature and precipitation changes using the LARS‐WG statistical downscaling model in the Shire River Basin, Malawi

AbstractThis study analyzes local‐scale temperature and precipitation projections in the Shire River Basin (SRB) in Malawi using 10 global circulation models (GCMs) available in the coupled model intercomparison project phase 5 (CMIP5), under two representative concentration pathways (RCP 4.5 and RCP 8.5). For nine stations in the study area, large‐scale maximum temperature (Tmax), minimum temperature (Tmin) and precipitation data from the selected GCMs were downscaled by the sixth version of the Long Ashton Research Station Weather Generator (LARS‐WG6). The mean seasonal and annual change projections for Tmax, Tmin and precipitation during two future periods, that is, the middle future (2041–2070) and late future (2071–2100) periods were analyzed. Modelling results demonstrated that the LARS‐WG model is capable of simulating temperature more accurately than precipitation in the SRB. All 10 GCMs revealed that continually rising temperatures are anticipated in the study area; however, the projected magnitude of change varied across GCMs and between RCPs. Generally, the increase in average Tmax and Tmin was observed to be higher under RCP 8.5 compared with RCP 4.5 due to unmitigated greenhouse gas emissions (GHGs). Future precipitation change results showed more complexity and uncertainty than for temperature; not all GCMs agree on whether there will be positive or negative changes in precipitation and no systematic variations under RCP4.5 and RCP8.5 were observed during the two future time period, illustrating that both GCMs and RCPs are important sources of the relatively large uncertainties in future precipitation projections in the SRB. Thus, this study indicated that uncertainties constrained by both GCMs and RCPs are crucial and need to always be considered when executing climate impact studies and adaptation, particularly at river basin level.