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Crizanlizumab is an anti–P-selectin monoclonal antibody indicated to reduce the frequency/prevent recurrence of vaso-occlusive crises (VOCs) in patients with sickle cell disease (SCD) aged ≥16 years. This analysis of an ongoing phase 2, nonrandomized, open-label study reports the pharmacokinetics (PK), pharmacodynamics (PD), safety, and efficacy of crizanlizumab 5.0 mg/kg (N = 45) and 7.5 mg/kg (N = 12) in patients with SCD with a history of VOCs. The median treatment duration was 104.7 and 85.7 weeks in the 5.0 and 7.5 mg/kg groups, respectively. For both doses, serum crizanlizumab concentrations rose to near maximum levels shortly after infusion, and near complete and sustained ex vivo P-selectin inhibition was observed. Grade ≥3 adverse events (AEs) occurred in 48.9% and 33.3% of patients in the 5.0 and 7.5 mg/kg groups, respectively; only 1 event was deemed treatment-related (7.5 mg/kg group). No treatment-related serious AEs occurred. One infusion-related reaction was recorded (5.0 mg/kg, grade 2 “pain during infusion”), which resolved without treatment withdrawal. Infections occurred in 57.8% and 41.7% of patients in the 5.0 and 7.5 mg/kg groups, respectively; none were drug-related. No treatment-related bleeding events were reported. No patients developed immunogenicity. The median (range) absolute reduction from baseline in the annualized rate of VOCs leading to a health care visit was −0.88 (−14.7 to 13.3) and −0.93 (−2.0 to 0.4) in the 5.0 and 7.5 mg/kg groups, respectively. Results here demonstrate the PK/PD properties of crizanlizumab in patients with SCD and the potential sustained efficacy and long-term safety of the drug after >12 months’ treatment. This trial was registered at www.clinicaltrials.gov as #NCT03264989.

An efficient (C6F5)3B catalyzed method has been developed for the synthesis of benzo[b]cyclopenta[e][1,4]oxazin-2(1H)-one and thiazin-2(1H)-one derivatives from furan-2-yl(phenyl)methanol (1) and 2-aminophenol/thiophenol (2) under reflux in acetonitrile. This reaction proceeds through an aza-Piancatelli rearrangement/Michael reaction in one-pot. This strategy provides a facile and rapid access to benzo[b]cyclopenta[e][1,4]oxazin-2(1H)-one and thiazin-2(1H)-one derivatives (3a-l) in good to high yields under mild conditions. Several advantages, such as simple reaction procedure, low catalyst loading, broad substrate scope, easy product isolation, high functional group tolerance, and short reaction time make this strategy more attractive.

Lack of safe water prevents 42 percent of the world's population from accessing sanitation. In 2021, the WHO estimated that there would be 784 million people without access to safe drinking water. With a well-planned system, the group aims to cut the number of people in need of drinkable water by half by 2015. These methods improve saltwater, which makes up 97 percent of the world's water. In this regard, a model that simulates the work of groundwater treatment firms using natural resources and renewable energy has been developed. There was a lack of continuous wind energy throughout most of Oman, where this model was put, and the necessity for a reverse osmosis system for constant maintenance because these projects rely on renewable energy everywhere. This article aims to create an autonomous desalination plant powered by solar and wind energy. A simulator model based on renewable energy groundwater purification systems was created for this aim. To treat subterranean water in distant areas of Oman using two renewable technologies to create enough electricity to run the reverse water purification and water purification system at the lowest cost. A turbine mounted vertically with a height of 1.5 meters and a diameter of 1 meter will produce 2304 liters per day and 800000 liters per year

A series of oximinoethers of indanone/aryloxy indanone were synthesized and screened for its in vitro antileishmanial activity profile (in promastigote and amastigote models) against Leishmania donovani, the causative agent of leishmaniasis. Compounds 3a–d, 4a–d, 5a, 5b, 6a–d & 7a–d have shown 87–100% inhibition against promastigotes and 47–100% inhibition against amastigotes at a concentration of 05 μg/ml. compounds 3a, 4a–b, 6b–c, 7a–d and 4b, 4d, 6c–d exhibited 100% inhibition against promastigotes and amastigotes respectively.

In this paper, we introduce and study a new class k − ŨS s (a, c, µ, γ, t) of analytic functions in the open unit disc U with negative coefficients and obtain coefficient estimates, neighborhoods and partial sums for functions f belonging to this class.

The agricultural division is the highest consumer of water in Egypt, and it is facing crop yield reduction due to climate change. Irrigation technologies are a highly recommended adaptation option to meet the proposed change. Egypt`s financial resources allocated to climate change adaptation plans are limited. Therefore, determining the most vulnerable governorate in terms of Irrigation Water Requirements (IWR) to climate change is essential. This study aims to assess the vulnerability of IWR to climate change at the governorate level. Reference evapotranspiration and precipitation change were selected for exposure factors, sensitivity factors, soil type, and economic value of irrigation water. Finally, we identified education, poverty, and organizational capacity for adaptive capacity factors. Six climate model data were used under the shared socioeconomic pathway scenarios (SSP126, SSP245, SSP370, and SSP585) for the period (2040–2060). The results showed nine governorates (Al Minya, Asyut, Shamal Sina, Suhaj, Al Buhayrah, Al Fayyum, Al Isma`iliyah, Ash Sharqiyah, and Bani Suwayf) with the highest and high vulnerability degrees found in the country's middle and north region. Four governorates (Ad Daqahliyah, Aswan, Al Gharbiyah, Bur Sa`id) have the lowest vulnerability degree under the climate change scenarios (SSP126, SSP245, and SSP370), and one governorate (Aswan) has the lowest vulnerability degree under the SSP585 scenario. The study results help the decision-makers choose the best adaptation plans and support adapting effective mitigation strategies.

Land use/land cover (LULC) changes due to natural and anthropogenic interference have altered the hydrological processes of the Omo-Gibe basin, Ethiopia. In this study, hydrological modelling and r...

The Covid-19 pandemic has greatly affected the Indian education sector, especially the admissions and enrolments of university students. The increase in competition among higher education institutions for student admission and enrolment has led to the investment of large amounts of advertising expenditure in branding, advertising and Public Relations activities. This research paper highlights the impact of Digital Marketing Communication Strategies which helps in leveraging the Student Admission Decision Making Process, especially during the coronavirus pandemic. The increasing usage of the internet by students recommends that higher education institutions need to make use of digital media to reach out to prospective students for admission and enrolment by feeding in continuous and engaging user-generated content through text, images, infographics, videos, and podcasts. It is also noted that there is a drastic shift in traditional decision-making to digitalized decision-making. The article emphasizes that both prospective students and university marketers should effectively use digital marketing communication tools. The article suggests strategies and conclusions to manage the corona crisis and structuring a conceptual model to increase admissions by using digital marketing communications as the primary promotional tool.

The Current scientific work would be “Design, Progress and In-Vitro Categorization like Lansoprazole Delayed launch Capsules” indeed a categorization of proton pump inhibitor utilized during diagnosis like gastro esophagus acid reflux disease, erosional esophagitis as well as acid associated conditions. Lansoprazole would really an acid fragile opoid. That as well degrades with inside the acidic environment of it abdomen thereby resulting in therapeutic inefficacy. And thus will be essential to bypass an acidic nature of an abdomen. A current scientific task focus primarily on collection one of opoid would be Lansoprazole but also components like varied by HPC-L as well as eudragit L30 D55 have been also utilized even though enteric polymeric materials. An enteric coated granules seem to have been prepare through suspended layer-based particular method through fluidization processor. 10 compositions (F1 - F10) Lansoprazole enteric coated granules seem to have been ready wide variation a composers like drug loading, barrier coating as well as enteric covering. FT-IR has been manage to perform of about recognise this same suitability (compatibility) of some like the drug with assorted components various and SEM analysis had been done of about realize this same morphological characteristics of something like the pellets. In All 10 formulations were also maintained regarding Stability studies and done as three months there as 40°C/75 %RH but also 25°C/60 % RH as per ICH guidelines. A prepared formulations F 10 would be being shown advantageousin vitroacid as well as buffer release of drug in as during consistency timespan but also corresponding to a originator.

Groundnut shells (GNS) are renewable and sustainable sources that can reinforce polypropylene for composites intended for interior building and other applications. However, the hydrophilicity, low thermal and noise insulation of GNS reinforced polypropylene (PP) necessitate the use of additives to improve properties. In this work, non-coking bituminous coal was used as an additive to improve the properties of GNS-PP composites. Up to 30% of coal particles were included and the changes in tensile, flexural properties and noise and thermal insulation were studied. Morphological analysis showed limited interaction of coal with GNS or PP and consequently, there was only marginal improvement in the mechanical properties. However, moisture sorption of the composites decreased by 25% and the limited oxygen index increased to 27 from 24 without any coal. The presence of coal increases sound absorption and the noise absorption coefficient showed high absorption at specific frequencies. Coal is an abundantly available natural material which is suitable to improve the performance of composites.

In the present study, the rainfall-runoff modeling was carried out using MIKE 11 NAM model at the Shaya catchment in Ethiopia. The nine parameters of the model were optimized using observed rainfall, evaporation and observed streamflow during calibration (1990–2008) of the model. The validation of the model was done using an independent data for the period from 2009 to 2015. The model performance was evaluated using statistical performance indicators, such as correlation coefficient (R), Nash–Sutcliffe Efficiency coefficient (NSE), Root Mean Square Error (RMSE) and Percentage of Bias (PBAIS). The model performance was showed a good agreement between the observed and simulated runoff during the calibration (R = 0.93; NSE = 0.86; RMSE = 3.16 and PBIAS = − 1.58) and validation (R = 0.92; NSE = 0.83; RMSE = 4.04 and PBIAS = − 0.88). The results revealed that there is a very good agreement between the observed and computed runoff, particularly the low runoff compared to the high runoff in the Shaya catchment. High flow phenomena are often not caught by hydrological models but the low and average flows do. Therefore, this indicates that the model can be used for future hydrological modeling in the area successfully.

The main route of the transmission of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are through respiratory pathways and close contact of human-to-human. While information about other modes of transmission is comparatively less, some published literature supporting the likelihood of a fecal-oral mode of transmission has been accumulating. The diagnosis of SARS-COV-2 infected cases is based on the real-time reverse transcription-PCR (RT-PCR). The fecal excretion of SARS-COV-2 has been reported frequently, however, the role of fecal viral load with the severity of disease is not yet clear. Our study focused on the investigation of SARS-CoV-2 shedding in the fecal samples of patients with coronavirus disease 2019 (COVID-19). A total of 280 RT-PCR-positive patients were enrolled, among them 15.4% had gastrointestinal (GI) symptoms. It was shown that 62% of the patients were positive for SARS-CoV-2 RNA in fecal specimens. This positivity was not related to the presence of GI symptoms and the severity of disease. The next generation sequencing [NGS] of SARS-CoV-2 from fecal samples of patients was performed to analyze mutational variations. Findings from this study not only emphasized the potential presence of SARS-CoV-2 in feces, but also its continuing mutational changes and its possible role in fecal-oral transmission.

The present study examines the trends of hydro-climatic parameters over the Black Volta Basin in Ghana. Trend analysis was carried at different time scales (i.e., monthly, seasonal, and annual) from 1961 to 2016. Modified Mann–Kendall (MMK) test, Sen’s slope estimates, and Pettit–Mann–Whitney test were applied to compute the existence of a trend, the degree of change, and probable change point, respectively. The results revealed that there are warming trends over the entire Black Volta Basin. Both temperature extremes, i.e., highest and lowest (annual, seasonal, and monthly scale), for upstream and downstream region revealed an increasing trend. The annual rainfall in the upstream region depicted a downward trend, while downstream showed an increasing trend in the Basin. The seasonal trend analysis for rainfall depicted a falling trend (@ Sen’s slopes − 0.47 and − 0.69) with a percentage change over the 56 years − 19.66% and − 19.30%, respectively, for upstream and downstream regions during the dry periods. While, the rainy season showed a decreasing rainfall trend (@ Sen’s slope − 0.71 and percentage change − 4.41%) for the upstream region and increasing (@ + 0.71 & 4.39%) for the downstream. However, annual rainfall for the sites in the Basin depicted a decreasing trend (@ − 0.88 and − 4.76%) for upstream and an increasing trend (@ + 0.16 with 0.81% change) for downstream region. Annual streamflow revealed an increasing trend (@ + 0.02 with a 1.53% change) over the 43 years for upstream and a decreasing trend (@—0.41 and − 15.04% change) for downstream region at Chache-Bole. Therefore, this study output will be helpful for different stakeholders and policymakers within the Black Volta Basin of the West African sub-region toward improving decisions on water resources management.

Behavioral responses of tadpoles of Duttaphrynus melanostictus (Anura: Bufonidae) to cues of starved and fed dragonfly larvae. Tadpoles of Duttaphrynus melanostictus use chemoreception to detect kairomonal cues and excretory metabolites from predatory anuran tadpoles (Hoplobatrachus tigerinus) that consume them. We describe here the behavioral responses of tadpoles of D. melanostictus to predatory dragonfly larvae (Pantala flavescens). The predator’s kairomones (water conditioned by the starved predator) or its diet-derived metabolites released in excreta of predator after consumption of conspecific prey tadpoles were used to simulate predation risk. The tadpoles of D. melanostictus had no behavioral response to predator kairomones. However, the larvae reduced swimming movements and overall time spent in swimming, and had a higher burst speed/swimming velocity in response to water borne cues released from the excreta of predators fed conspecific prey. Thus, just the presence of dragonfly larvae does not elicit defense behaviors in tadpoles of D. melanostictus, but when predation risk is recognized as real (i.e., when tadpoles are exposed to excretory metabolites of predators fed conspecific tadpoles), defense behaviors are activated.

In this work, we introduce and investigate a new class $ k- \widetilde{ U}S_s ( a, c , \gamma , t)$ of analytic functions in the open unit disc $U$ with negative coefficients. The object of the present paper is to determine coefficient estimates, neighborhoods and partial sums for functions $f$ belonging to this class.

In the present studies, activated carbon as an electrode material and polyvinyl- alcohol (PVA) as a polymer. Formic acid (FA) and potassium iodide-based electrolyte system have been synthesized for the fabrication of energy storage devices, supercapacitors. The diluted formic acid (CH2O2) in the double-distilled (DD) water has been optimized so that it exhibits maximum conductivity. The electrolyte system has also been prepared with PVA, redox additive (KI) with optimized formic acid (4.0 M). The redox additive concentration has also been identified that can have maximum conductivity. The selected system (PVA + FA + KI) shows the highest conductivity in the range ∼10−1 Scm−1. The banyan leaves (biomass) based carbon electrode (BAC) synthesized as an electrode material. The electric double layer capacitor (EDLC) has been fabricated using BAC as electrodes and (PVA + FA + KI) as electrolyte material. The result of (BAC) based EDLC cell has been compared with the cell fabricated using commercially available activated carbon (AC). The performance of cells has been determined by impedance spectroscopy (IS), Cyclic voltammetry (CV) and charge–discharge (CD) techniques. The overall capacitance of BAC / (PVA + FA + KI) / BAC and AC / FA (4.0 M) / AC have been found to be ∼356 mFcm−2 and ∼100 mFcm−2.

In the present work, the activated charcoal-dispersed with Copper Oxide (CuO) nanoparticles (NPs) electrode materials has been proposed as electrode materials for supercapacitor that is used as energy storage device. The CuO NPs have been synthesized using co-precipitation method and the nanocomposite has been with activated charcoal (AC) powder for its application in an electrochemical supercapacitor. CuO nanoparticles calcination has been carried out at three different temperatures (400, 500, and 600 °C). The optimized temperature for synthesis is 600 °C that resulted into better performance of electrode materials. The Synchrotron X-ray diffraction (SXRD) confirms the monoclinic structure with space group C2/c (15). Electrochemical properties of the prepared nanocomposite electrodes and fabricated supercapacitor cells have been characterized using a.c. impedance, cyclic voltammetry (CV) and charge discharge (CD) techniques by using 6 M KOH as an the electrolyte. The optimized composition is 1:1 (mass ratio) of CuO and activated charcoal. The specific capacitance of the supercapacitor cell is stable up to 2000 cycles at 100 mV cm−2, which show that the device has good electrochemical reversibility and cycle life with 6 M KOH electrolyte.

n this paper, we introduce and study a new subclass of meromorphic functions with positive coefficients involving the polylogaritham function and obtain coefficient estimates, growth and distortion theorem, radius of convexity, integral transforms, convex linear combinations and convolution properties for the class σ c,p (α, β, λ).

Droughts are the most spatially complex geohazard, which often lasts for years, thereby severely impacting socio-economic sectors. One of the critical aspects of drought studies is developing a reliable and robust forecasting model, which could immensely help drought management planners in adopting adequate measures. Further, the prediction of drought events are extremely challenging due to the involvement of several hydro-meteorological factors, which are further aggravated by the effect of climate change. Among the several techniques such as statistical, physical and data-driven that are used to forecast droughts, artificial neural networks provide one of the most robust approach. As droughts are inherently non-linear and multivariate in nature, the capability of neural networks to capture the dynamic relationship easily and efficiently has seen a rise in its use. Here we evaluate the most used architectures in the last two decades, using scientometric analysis. A general framework used in drought prediction studies is explained and examples from various continents are provided, thus exploring the topic in a global context. The findings show that using sophisticated input representation, the artificial intelligence-based solutions applied to drought prediction of hydro-meteorological variables have promising success, particularly in complex geographical scenarios. The future works need to focus on interpretable models, use of deep learning architectures for long lead time forecasting and use of neural networks to predict different drought characteristics like drought propagation and flash droughts. We also summarize the most widely used neural network approaches in spatial drought prediction, which would serve as a foundation for future research in drought prediction studies.

The transition processes from monogenetic volcanoes to composite volcanoes are poorly understood. The Late Pleistocene to Holocene intraplate monogenetic Wulanhada Volcanic Field (WVF) in northern China provides a snapshot of such a transition. Here we present petrographic observations, mineral chemistry, bulk rock major and trace element data, thermobarometry, and a partial melting model for the WVF to evaluate the lithology and partial melting degree of the mantle source, the crystallization conditions, and pre-eruptive magmatic processes occurring within the magma plumbing system. The far-field effect of India–Eurasia collision resulted in a relatively high degree (10 %–20 %) of partial melting of a carbonate-bearing eclogite (∼ 3 wt % carbonate; Gt/Cpx ≈ 2 : 8, where Gt denotes garnet and Cpx denotes clinopyroxene) followed by interaction with ambient peridotite. The primary melts ascended to the depth of the Moho (∼ 33–36 km depth), crystallized olivine, clinopyroxene and plagioclase at the temperature of 1100–1160 ∘C with the melt water contents of 1.1 wt %–2.3 wt %. Part of the primary melt interacted with the lithospheric mantle during ascent, resulting in an increase in the MgO contents and a decrease in the alkaline contents. The modified magma was subsequently directly emplaced into the middle crust (∼ 23–26 km depth) and crystallized olivine, clinopyroxene and plagioclase at the temperature of 1100–1160 ∘C. The primary melts from the same mantle sources migrated upward to the two-level magma reservoirs to form minerals with complex textures (including reverse and oscillatory zoning and sieve texture). Magma erupted along the NE–SW-striking basement fault and the NW–SE-striking Wulanhada–Gaowusu fault in response to the combined effects of regional tectonic stress and magma replenishment. The crustal magma reservoir in the WVF may represent a snapshot of the transition from monogenetic volcanoes to composite volcanoes. It is possible to form a composite volcano with large magma volumes and complex compositions if the magma is continuously supplied from the source and experiences assimilation and fractional crystallization processes in the magma plumbing system at crustal depth.

In the present work, a nanocomposite formed by dispersing vanadium oxide (VxOy) nanoparticles (NPs) in matrix activated charcoal for the purpose of electrode material in a supercapacitor. The synthesis of vanadium oxide (VxOy) has been carried out using cost effective method at room temperature. The starting materials vanadyl sulphate pentahydrate (VOSO4·xH2O) and sodium hydroxide (NaOH) have been dissolved to prepare stock solution and have been used to prepare vanadium oxide (VxOy) nanoparticles. The prepared nanoparticles have a size of approximately 26 nm, which has been determined from synchrotron X-ray diffraction data. The particle size distribution has been controlled through precipitation rate and calcination temperature. The final precipitates have been calcined at 400 °C and 500 °C temperatures to observe effect of temperature on particle size. The obtained nanopowder has been characterized by Synchrotron X-ray diffraction (SXRD), scanning electron microscopy (SEM) and Fourier transform infrared spectroscopy (FTIR). The XPS investigation provides different oxidation state of vanadium metal cations. The layer structure of oxide and different oxidation cations may have effect on charge transfer at interface between electrolyte and electrode. Further, the electrochemical characterization has been carried out to evaluate performance of nanopowder and activated charcoal composite as an electrode material in a supercapacitor. The specific capacitance of the cells containing electrolyte using 1 M H2SO4 and 6 M KOH and activated charcoal–vanadium oxide (VxOy), 1:1 mass ratio and 1:2 mass ratio electrodes in which vanadium oxide (VxOy) is prepared at 500 °C has resulted into better electrochemical performance. The specific capacitance of the supercapacitor cells is stable up to 2000 cycles at 100 mV cm−2, which shows that the device has good electrochemical reversibility and cycle life with 1 M H2SO4 and 6 M KOH electrolyte.

The comparative vulnerability of two co-existing tadpole species (Indosylvirana temporalis and Clinotarsus curtipes) to their common predator, water scorpions (Laccotrephes sp.; Hemiptera: Nepidae), and the importance of refugia in predator avoidance were studied in the laboratory. In a total of 60 experimental trials, 10 tadpoles each of I. temporalis and C. curtipes of comparable body sizes were exposed to water scorpions (starved for 48 h). Thirty trials included refugia while 30 did not. The results of this study showed that in both the absence and the presence of refugia C. curtipes tadpoles fell prey to water scorpions more frequently than I. temporalis tadpoles. A main difference between the two species is the speed of swimming; Vmax of C. curtipes (24.73 cm/s) tadpoles is lower than that of I. temporalis (30.78 cm/s) tadpoles. This is likely to be the reason why more C. curtipes tadpoles were preyed upon than were I. temporalis tadpoles. Predation risk of tadpoles of both species was affected significantly by the presence of refuge sites. The vulnerability of both tadpole species was lower where refuge sites were available. The present study clearly shows that I. temporalis tadpoles avoid predation by water scorpions more effectively than do C. curtipes tadpoles.

Groundwater is an important component of the hydrologic cycle and its significance is quite high due to the lack of surface water and is an important source of fresh water. The amount of surface water alone is not enough to meet the demands of increasing population and increased needs for different purposes due to technological advances. Hence, the need of the hour is to increase groundwater sources and manage them effectively for their sustainable growth. Therefore, the main objective of this study is to map groundwater potential (GWP) zones of the Shipra river basin in India using advanced machine learning and geospatial techniques. Nine factors were used as effective factors such as slope degree, altitude, plan curvature, topographic wetness index (TWI), profile curvature, topographic factor, drainage density, slope aspect, and land use/land cover. The models adopted in this study were classification and regression tree (CART), boosted regression tree (BRT), and random forest (RF). The integrated results of GIS and machine learning techniques were proved to be effective and successful in predicting GWP zones. The area under the curve (AUC) of three models namely BRT, CART, and RF came out to be 0.841, 0.880, and 0.899, respectively. This indicates that all the models are giving a good performance for the GWP zone mapping (>0.80). This study also found that the best technique for prediction is random forest followed by CART and BRT in the case of Shipra river basin. Therefore, this study outcome can prove to be beneficial for effective management, protection, and exploration of groundwater prospects for the different stakeholders.

Background: SCD is an inherited blood disorder characterized by hemolytic anemia, endothelial damage and acutely painful VOCs that cause chronic and potentially life-threatening complications. P-selectin is an adhesion protein that plays a key role in the multicellular interactions leading to a VOC. The Phase II SUSTAIN study showed that crizanlizumab (SelG1), a humanized monoclonal anti-P-selectin antibody, reduced the annualized rate of VOCs leading to a healthcare visit by 45.3% vs placebo (P=0.01) in SCD patients (pts) [Ataga K et al. N Engl J Med 2017]. Aims: To evaluate the pharmacokinetics (PK) and pharmacodynamics (PD; ex vivo P-selectin inhibition) of crizanlizumab (SEG101), as well as safety and efficacy in SCD pts with a history of VOCs. Methods: SOLACE-adults is a Phase II, multicenter, open-label PK-PD study that enrolled SCD pts aged 16-70 years who had experienced ≥1 VOC in the 12 months prior to study start (NCT03264989). Pts received crizanlizumab by intravenous infusion over 30 minutes at 5.0 mg/kg or 7.5 mg/kg on: Week 1, Day 1 (Wk1D1); Wk3D1; and then on D1 of every 4-wk cycle. PK and PD assessments were performed in all pts pre- and post-dose on days 1, 2, 4, 8, and 15 of the first dose (Wk1D1) and then on days 1, 2, 4, 8, 15, 22 and 29 of the fifth dose (Wk15D1). Adverse events (AEs) were evaluated based on MedDRA v22.1 and AE severity based on CTCAE v5.0. Pts were continuously monitored for VOCs, with the relevant medical and treatment information collected in case of occurrence. Results: A total of 57 pts were enrolled: 45 received crizanlizumab 5.0 mg/kg (female, n=25 [56%]; mean [SD] age, 32 [13] years) for a median of 65 (range, 6-90) wks and 12 received 7.5 mg/kg (female, n=6 [50%]; mean [SD] age, 27 [12] years) for a median of 43 (range, 9-49) wks. In the 5.0 and 7.5 mg/kg arms, respectively, 6 (13%) and 2 (17%) pts discontinued treatment, primarily because of patient decision (n=4; 9%) in the 5.0 mg/kg arm and because of death and AE (both n=1; 8%) in the 7.5 mg/kg arm. The most common AEs were headache (5.0 mg/kg, n=11 [24%]; 7.5 mg/kg, n=3 [25%]) and pyrexia (5.0 mg/kg, n=9 [20%]; 7.5 mg/kg, n=2 [17%]). Grade ≥3 AEs occurred in 18 (40%) pts in the 5.0 mg/kg arm and in 2 pts (17%) in the 7.5 mg/kg arm. Serious AEs were reported in 11 pts (24%) in the 5.0 mg/kg arm and in 1 pt (8%) in the 7.5 mg/kg arm; none were deemed drug-related. One pt in each of the 5.0 (2%) and 7.5 mg/kg (8%) arms discontinued treatment because of AEs. Infections, infusion-related reactions (IRR), bleeding events, and immunogenicity were AEs of special interest. Infections were reported in 20 (44%) and 3 (25%) pts in the 5.0 and 7.5 mg/kg arms, respectively; none were considered drug-related. Signs and symptoms indicative of IRRs were reported in 15 (33%) and 2 (17%) pts in the 5.0 and 7.5 mg/kg arms, respectively; none were grade 3/4 severity or led to treatment withdrawal. Bleeding events were rare, and none were deemed serious. No pts developed immunogenicity. For both doses, serum crizanlizumab concentrations increased to nearly maximum levels (Cmax) at the end of the 30-minute infusion, remaining steady for 6 hours post-infusion (Figure). For each dose, Cmax at wks 1 and 15 were similar (Table), indicating a lack of accumulation. The increase in exposure to crizanlizumab in the 5.0 and 7.5 mg/kg arms was almost dose-proportional. Ex vivo inhibition of P-selectin binding to its receptor was complete throughout the dosing interval for both crizanlizumab doses (Figure). Pre-dose PK and PD were consistent and stable throughout the study. The median (range) annualized rate of VOCs leading to a healthcare visit in the 5.0 mg/kg arm was 4.0 (1.0-25.0) at baseline and 2.8 (0.0-21.7) on treatment (median [range] absolute change from baseline, -0.97 [-14.4 to 17.7]). In the 7.5 mg/kg arm, the corresponding rates were 2.0 (1.0-9.0) and 1.8 (0.0-7.0) [median (range) absolute change from baseline, -0.80 (-3.7 to 1.0)]. Seven pts (16%) in the 5.0 mg/kg arm and 4 pts (33%) in the 7.5 mg/kg arm were VOC-free during the treatment period. Conclusions: No new safety signals were identified in this SCD population treated with crizanlizumab, with no apparent differences between the 5.0 and 7.5 mg/kg doses in the frequency and severity of AEs. For both doses, serum crizanlizumab concentrations rose to a near maximum level shortly after infusion. Consistent with results from the SUSTAIN trial, crizanlizumab reduced from baseline the annualized rate of VOCs leading to a healthcare visit. Disclosures Smith-Whitley: Global Blood Therapeutics: Membership on an entity's Board of Directors or advisory committees; Novartis: Membership on an entity's Board of Directors or advisory committees; Prime: Other: Education material; Celgene: Membership on an entity's Board of Directors or advisory committees. Brown:Global Blood Therapeutics: Membership on an entity's Board of Directors or advisory committees, Research Funding; Imara, Inc: Consultancy, Research Funding; Novartis: Consultancy, Research Funding; Forma Therapeutics: Research Funding. Shah:Alexion: Speakers Bureau; Novartis: Consultancy, Research Funding, Speakers Bureau; Global Blood Therapeutics: Consultancy, Research Funding, Speakers Bureau; CSL Behring: Consultancy; Bluebird Bio: Consultancy. Tanaka:Novartis Institute for Biomedical Research: Current Employment, Current equity holder in publicly-traded company. Sanchez-Olle:NOVARTIS PHARMA AG: Current Employment. Albers:Novartis Pharma AG: Current Employment, Current equity holder in publicly-traded company. Kanter:Guidepoint Global: Honoraria; GLG: Honoraria; Jeffries: Honoraria; Cowen: Honoraria; Wells Fargo: Honoraria; NHLBI Sickle Cell Advisory Board: Membership on an entity's Board of Directors or advisory committees; SCDAA Medical and Research Advisory Board: Membership on an entity's Board of Directors or advisory committees; AGIOS: Membership on an entity's Board of Directors or advisory committees; BEAM: Membership on an entity's Board of Directors or advisory committees; Novartis: Consultancy; bluebird bio, inc: Consultancy, Honoraria; Sanofi: Consultancy; Medscape: Honoraria.

Purpose The purpose of this paper is to propose and develop PA2200-based composite powder containing 0-15 Wt.% magnesium oxide before directly using it in selective laser sintering (SLS) machine to produce end-use products for low-volume production in the engineering applications with keen focus to meet the functional requirements which rely on material properties. Design/methodology/approach The methodology reported emphasises PA2200-based composite powder containing 0-15 Wt.% magnesium oxide development for SLS process which starts with preparation and characterisation of composite material, thermal and rheological study of composite material to decide optimum process parameters for SLS process machine to get optimal part properties. Further, to verify composite material properties, a conventional casting methodology is used. The composition of composite materials those possessing good properties are further selected for processing in SLS process under optimal processing parameters. Findings The process parameters of SLS machine are material-dependent. The effect of temperature in X-ray diffraction profile is negligible in the case of magnesium oxide reinforced PA2200 composite material. The cyclic heating of material increases melting point temperature, this grounds to modify part bed temperature of material every time before processing on SLS machine to uphold build part properties, as well as material. With the rise in temperature, the Melt flow index and rheological property of materials change. The magnesium oxide reinforced PA2200 composite material has high thermal stability than pure PA2200 material. By the addition of small quantity of magnesium oxide, most of the mechanical property and flammability property improves while elongation at break (percentage) decreases significantly. Practical implications The proposed PA2200-based composite powder containing 0-15 Wt.% magnesium oxide material development system and casting metrology to verify developed material properties will be very useful to develop new composite material for SLS process with use of less material. The developed methodology has proven, especially in the case where non-experts or student need to develop composite material for SLS process according to the property requirement of applications. Originality/value Unlike earlier composite material development methodology, the projected methodology of polymer-based composite material and confirmation of material properties instead of commencing SLS process provides straight forward means for SLS process composite materials development with less use of the material and period of time.

TPS9589 Background: The treatment of melanoma has improved markedly with the emergence of new immune therapies, and both anti-PD-1 monotherapy and the combination of the anti-PD-1 antibody nivolumab and anti-CTLA-4 therapy ipilimumab are now considered standard-of-care in the unresectable or metastatic (advanced) melanoma setting. However, many patients have primary or acquired resistance to these therapies, thereby underpinning the need for more effective approaches. IO102-IO103 is a potentially first-in-class, dual-antigen, immune-modulatory therapy targeting the key cancer immune resistance pathways mediated by IDO and PD-L1. The ability of IO102 and IO103 to respectively activate the specific T cells that recognize these checkpoint molecules and directly modulate immune regulation has previously been demonstrated both preclinically and in human clinical trials. A synergistic anti-tumor response upon treatment against both IDO and PD-L1 has also previously been demonstrated in a preclinical model where IDO and PD-L1 were expressed by different cells in the tumor microenvironment. Due to the distinctive mechanisms of action of IO102-IO103 and anti-PD-1 antibodies, there may be a further synergistic effect when treatment is combined. A previous Phase 1/2 trial investigating the use of IO102-IO103 plus nivolumab in patients with anti-PD-1-naïve metastatic melanoma has demonstrated promising anti-tumor activity with an overall response rate (ORR) of 80%, median progression-free survival (PFS) of 26 months and a manageable safety profile (NCT03047928; Kjeldsen et al, Nat Med 2021). Methods: This is a Phase 3, multicenter, open-label, randomized, 2-arm trial investigating the efficacy and safety of IO102-IO103 plus pembrolizumab versus pembrolizumab alone (EudraCT: 2021-004594-32; ClinicalTrials.gov No: NCT05155254). Inclusion criteria include: adult patients with untreated, unresectable (Stage III), or metastatic (Stage IV) melanoma; > 6 months since last dose of (neo)adjuvant treatment with targeted or immune therapy (in those previously treated); and ≥1 measurable lesion by RECIST v1.1. Primary endpoint is PFS by blinded independent central review. Secondary endpoints include ORR, durable response rate, complete response rate, duration of response, time to response, disease control rate, overall survival, and safety/tolerability. Target enrollment is 300 patients at > 100 sites in 20 countries. Patients are randomized 1:1 to receive either pembrolizumab 200 mg intravenously (IV) every 3 weeks up to 2 years or pembrolizumab 200 mg IV every 3 weeks up to 2 years with dual-antigen IO103-IO102 85-85 µg and Montanide adjuvant subcutaneously on Day 1 and 8 of cycle 1 and 2 and on Day 1 of each cycle thereafter. Enrolment for the study is ongoing. Clinical trial information: EudraCT: 2021-004594-32; ClinicalTrials.gov No: NCT05155254.

The present study was carried out to identify the extent of flood hazard on the Fogera floodplain in the Ribb catchment of the Blue Nile River basin in Ethiopia. A coupled 1 dimensional (D) and 2D hydrodynamic model (i.e., MIKE FLOOD) was used to simulate the flood inundation extent and flooding depth under climate change scenario in the study area. MIKE FLOOD coupled with a SWAT was used to simulate the floods hazard maps under short-term (2030s) and long-term (the 2060s) future climate projections for the RCP4.5 scenario. The results were revealed that the future minimum and maximum temperature can be increased to 1.99 °C and 2.65 °C, respectively. The average annual rainfall can be increased in the future. The dimensionless inflow hydrograph was best fitted with Gumbel distribution for the 100 years return period. This was derived from an output of the hydrological model and then fed into MIKE FLOOD to generate the flood hazard maps. The intensity of annual floods was indicated an increasing trend under the RCP4.5 scenario. The model was calibrated using the historical hydro-meteorological data, measured River cross-section data, and Lake Tana water level. The result of flood frequency analysis showed that a flow value of 100 year return period can be expected to 290 m3/s, 346 m3/s, and 367 m3/s for historical, short-term, and long-term time periods, respectively. The prepared flood hazard map indicated that the flooded area can be expected to 57.72 km2, 59.3 km2, and 61.01 km2 for the base period, 2030s, and 2060s, respectively, while the depth of inundated flood flow in the study area may be anticipated to a depth of 4.23 m, 4.68 m, and 4.96 m for similar time periods, respectively. Therefore, this study will be helpful for the decision makers to take the decision about the planning for the flood mitigation measures in the study region.

Corona Virus Disease 2019 (COVID-19) caused by the novel coronavirus, results in an acute respiratory condition coronavirus 2 (SARS-CoV-2) and is highly infectious. The recent spread of this virus has caused a global pandemic. Currently, the transmission routes of SARS-CoV-2 are being established, especially the role of environmental transmission. Here we review the environmental transmission routes and persistence of SARS-CoV-2. Recent studies have established that the transmission of this virus may occur, amongst others, in the air, water, soil, cold-chain, biota, and surface contact. It has also been found that the survival potential of the SARS-CoV-2 virus is dependent on different environmental conditions and pollution. Potentially important pathways include aerosol and fecal matter. Particulate matter may also be a carrier for SARS-CoV-2. Since microscopic particles can be easily absorbed by humans, more attention must be focused on the dissemination of these particles. These considerations are required to evolve a theoretical platform for epidemic control and to minimize the global threat from future epidemics La enfermedad del coronavirus 2019 (COVID-19) causada por el nuevo coronavirus, da como resultado una enfermedad respiratoria aguda padece el coronavirus 2 (SARS-CoV-2) y es altamente infeccioso. La reciente propagación de este virus ha provocado una pandemia mundial. Actualmente, se están estableciendo las rutas de transmisión del SARS-CoV-2, especialmente el papel de la transmisión ambiental. Aquí revisamos las rutas de transmisión ambiental y la persistencia del SARS-CoV-2. Estudios recientes han establecido que la transmisión de este virus puede ocurrir, entre otros, en el aire, el agua, el suelo, la cadena de frío, la biota y el contacto con la superficie. También se ha encontrado que El potencial de supervivencia del virus SARS-CoV-2 depende de diferentes condiciones ambientales y contaminación. Las vías potencialmente importantes incluyen aerosoles y materia fecal. El material particulado también puede ser portador del SARS-CoV-2. Dado que las partículas microscópicas pueden ser absorbidas fácilmente por los seres humanos, se debe prestar más atención a la diseminación de estas partículas. Estas consideraciones son necesarias para evolucionar una plataforma teórica para el control de epidemias y para minimizar la amenaza global de futuras epidemias

The Eastern Pontides Orogenic Belt (EPOB) in northeastern Turkey is a continental arc that is part of the Himalayan-Alpine orogeny. Late Cretaceous magmatism in this belt is dominated by high-K calc-alkaline, shoshonitic, and alkaline rocks that occur over an area of -600 km (E-W) and -200 km (N-S). We present new geochemical data (whole rock major and trace element analyses, mineral compositions, U-Pb zircon and titanite ages, zircon trace element data, and Sr-Nd-Pb isotopic analyses) for 153 samples, with compiled data for an additional 265 samples. Magmatism is diachronous across the arc. In the north, Cycle-I (92-84 Ma) commenced with tholeiitic and calc-alkaline basalts and andesites, and continued with felsic extrusive rocks. Cycle-II (84-70 Ma) includes mainly intermediate and felsic extrusive rocks. Over time, the low-K granitoids progressively give way to calc-alkaline granitoids in the north. In the south, Cycle-I (84-78 Ma) includes high-K trachyandesites, trachytes and felsic extrusive rocks. Cycle-II (78-65 Ma) comprises leucitites, trachybasalts, and other K-rich rocks. Shoshonitic granitoids in the south show ages between 80 and 65 Ma. Clinopyroxene compositions in trachyandesites and leucitites indicate initial crystallization at -38 km depth and 1120 degrees C. Amphibole joins the phase assemblage at -8 km depth and T < 950 degrees C. All samples have LILE and LREE enrichments and negative Nb, Ta, and Ti, and positive Pb anomalies, consistent with their subduction-related origin. Isotopic data indicate mixing between magmas from heterogeneous, enriched subcontinental mantle sources and those from a range of crustal sources. Mantle-derived and crustally-derived magmas are clearly separated by (Gd/Yb)N. Chemical zoning of the EPOB, from tholeiitic and calc-alkaline rocks to high-K calc-alkaline, shoshonitic, and alkaline rocks, from north to south, and the timing of magmatism younging southward, are consistent with a model of southward subduction in the Late Cretaceous. (c) 2021 International Association for Gondwana Research. Published by Elsevier B.V. All rights reserved.

The impact of land use/land cover (LULC) change on the stream flow of the Shaya catchment was assessed by employing the MIKE SHE hydrological model. The digital elevation model, soil, LULC, climate, and stream flow data were used as model inputs. The LULC was analyzed from different years of satellite imageries using ERDAS IMAGINE software package and its accuracy was verified following the standard procedures. Trend and shift detection analysis were also conducted to study the effect of rainfall on stream flow using the Mann–Kendall (MK) and Pettit tests, respectively. The result showed that there is a significant expansion of settlement and agricultural area, while there was a decrease of bare land, forest, and bush land in the catchment. In contrary, rangeland was increased from the year 1987 to 2000 and then decreased from 2000 to 2015. The performance of the MIKE SHE hydrological model was very good both during model calibration and validation periods. It has been observed that rainfall did not show any significant trends and shifts, but the stream flow was increased significantly in the two decades. In this study, the effects of LULC change on the stream flow in the study area have been distinguished: the mean monthly stream flow was increased during the wet season, while it was decreased during the dry season. Therefore, we recommend concerned bodies to monitor and take appropriate control of the LULC changes, especially settlement and deforestation, before it makes acute problems of the hydrologic imbalance in the catchment.

Hepatic vena cava syndrome (HVCS) is a bacterial infection-induced obliterative disease of the inferior vena cava at the site of the hepatic vein openings that causes chronic liver disease with a high incidence of liver cirrhosis and a moderate incidence of hepatocellular carcinoma (HCC). HVCS typically manifests clinically as recurrent mild jaundice and/or a mild elevation of transaminases or ascites as a result of hepatic venous outflow obstruction. This study is an investigation of the complications and treatment results of a large cohort of HVCS patients with an emphasis on splenomegaly and hypersplenism.A total of 1935 (1335 male and 600 female) patients with HVCS seen between 2004 and 2019 for splenomegaly and hypersplenism were enrolled in this retrospective study. The incidence of splenomegaly, ascites, cirrhosis, HCC, and other complications was measured and analyzed.Long-term follow-up of a large study group seen over several years indicated that 16% had mild splenomegaly, and 50% of these developed cytopenia commonly thrombocytopenia and/or leucopenia.The development of hypersplenism was related to recurrent or prolonged acute exacerbation of HVCS. This resulted in an increased incidence of ascites and cirrhosis as well as complications, such as hepatic encephalopathy, gastrointestinal or mucosal bleeding, or mortality.