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With urban developments and the aging of urban water distribution pipes their demand for repair and maintenance is rapidly grown. There are several factors that affect the performance and leakage in water and wastewater distribution networks (Ameyaw and Chan, 2016). By increasing the water leakage from pipes and wastewater depletion from houses to the injection wells, water level under the city ground is rising and saturation condition will be created near the underground infrastructures. In recent years, local uplifting of subsurface water level in metropolises created different challenges over water and wastewater systems with multiple damage effects (Baah et al., 2015;Qiu et al., 2016).İn recent two decades, the rising of groundwater table in Kerman city have caused several challanges over the water and wasetwaer infrustructures. İn the ancint zone of the Kerman city, water level come up to 3 meter under the groundsurface and is interacted with several underground structures and basment flooding. The rising water table have several destructive effects over the urban infrastructures. The main purpose of the present study is to investigate the effects of rising subsurface water level in Kerman city by using an AHP based damage prioritization to depict the relative importance or urgency of a damages of water level rising over infrastructures.

Models of rural development in the country, most of the imported versions, have been neglected by the "indigenous knowledge"of rural communities. Indigenous knowledge is a collection of skills and techniques, a knowledge that includes all the characteristics and sustainability of development. One of the most important rural organizations, is the "traditional irrigation system", which managed to manage the water resources of the centuries with the use of "indigenous knowledge". The main question is whether indigenous knowledge can be used as a sustainable model in the Conditions of the water crisis. This research has examined the local knowledge of traditional irrigation in the city of Bojistan by descriptive-analytical method. The method of data collection, field and library, and villages over 100 households in the city have been studied for the sustainability of water resources. The results of the research showed that the use of indigenous knowledge in water resources management has been able to minimize the problems caused by seasonal changes in temperature and its impact on the water resources deficit in the research area. This approach to water resources sustains the participation of villagers in traditional irrigation systems, and a network interconnected by human factors (agricultural council, Moallefan, kayyal, Joybanan, Moghanian and Motorban)and conventional irrigation organizations (changes in irrigation circuits throughout the year, spatial changes, and Time split and combination of triangular aqueducts). Research indicates that "indigenous knowledge"is a lost circle of sustainable rural development,which,if utilized with "modern knowledge",while empowering rural communities, provides the background for their partnership and development

Development literature show that the main concern of international organizations and scholars and scientific and research centers in the third millennium is human education and scientific development as an effective factor in development. This research aims to investigate the time series of the impact of science and technology on development. The type of this longitudinal research is time series and is intended to estimate, predict the time series of the impact and the trend of science and technology on development in the period 1980-2015 in 12 selected countries. The Selected countries have been selected in a targeted way the results of data analysis with R software show that by analyzing the significant difference between countries in the variable of human resources and education and technology variables by ANOVA, Significant differences between countries are confirmed. The results of dispersion graphs in all selected countries show upward trends. In general, the results indicate that growth and development during the 1980s to 2015 is on the rise and the trend of the impact of education and technology variables on development is on the upside, too.

Abstract In this research, physical, biometrical and chemical properties of Prosopis juliflora wood and then physical and mechanical properties of kraft pulp from aforesaid species were investigated and calculated. Dry and critical densities of Prosopis juliflora are 0.806 and 0.696 g/〖cm〗^3 respectively. Fiber length 895µm and cellulose 48.80%, lignin 23.66%, extractions 3.88%, ash 1.1% were measured. The preparation conditions of kraft pulp were included: effective alkaline 14, 16 and 18%, cooking time 120 and 180 min., temperature of cooking 170 and 180 ˚C and L/W ratio 5 to 1. After calculating the amounts of yield and kappa number of pulps, two treatments were determined. The freeness of two pulps was achieved approximately 400 (CSF) by refining. Then, physical and mechanical properties of the handsheets were calculated. Finally, statistical analysis of pulp and handsets data were performed by completely randomized factorial, duncan and T-test methods. The results showed that the handsheets resulted from produced kraft pulp under conditions: effective alkaline 18%, cooking time 120 min, cooking temperature 180 ˚C, had better mechanical properties. The investigation results showed that Prosopis juliflora of south zone of the country has suitable properties for kraft pulp preparation in comparison to other similar hard wood species and development of its planting, was recommended in the zone.

BACKGROUND Recent data suggest that complications and death from coronavirus disease 2019 (Covid-19) may be related to high viral loads. METHODS In this ongoing, double-blind, phase 1-3 trial involving nonhospitalized patients with Covid-19, we investigated two fully human, neutralizing monoclonal antibodies against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike protein, used in a combined cocktail (REGN-COV2) to reduce the risk of the emergence of treatment-resistant mutant virus. Patients were randomly assigned (1:1:1) to receive placebo, 2.4 g of REGN-COV2, or 8.0 g of REGN-COV2 and were prospectively characterized at baseline for endogenous immune response against SARS-CoV-2 (serum antibody-positive or serum antibody-negative). Key end points included the time-weighted average change in viral load from baseline (day 1) through day 7 and the percentage of patients with at least one Covid-19-related medically attended visit through day 29. Safety was assessed in all patients. RESULTS Data from 275 patients are reported. The least-squares mean difference (combined REGN-COV2 dose groups vs. placebo group) in the time-weighted average change in viral load from day 1 through day 7 was -0.56 Iog10 copies per milliliter (95% confidence interval [CI], -1.02 to -0.11) among patients who were serum antibodynegative at baseline and -0.41 log10 copies per milliliter (95% CI, -0.71 to -0.10) in the overall trial population. In the overall trial population, 6% of the patients in the placebo group and 3% of the patients in the combined REGN-COV2 dose groups reported at least one medically attended visit; among patients who were serum antibody-negative at baseline, the corresponding percentages were 15% and 6% (difference, -9 percentage points; 95% CI, -29 to 11). The percentages of patients with hypersensitivity reactions, infusion-related reactions, and other adverse events were similar in the combined REGN-COV2 dose groups and the placebo group. CONCLUSIONS In this interim analysis, the REGN-COV2 antibody cocktail reduced viral load, with a greater effect in patients whose immune response had not yet been initiated or who had a high viral load at baseline. Safety outcomes were similar in the combined REGN-COV2 dose groups and the placebo group. (Funded by Regeneron Pharmaceuticals and the Biomedical and Advanced Research and Development Authority of the Department of Health and Human Services; ClinicalTrials.gov number, NCT04425629.). [ABSTRACT FROM AUTHOR]

Background: We evaluated the safety of SCB-2019, a protein subunit vaccine candidate containing a recombinant SARS-CoV-2 spike (S) trimer fusion protein, combined with CpG-1018/alum adjuvants., Methods: This ongoing phase 2/3, double-blind, placebo-controlled, randomized trial is being conducted in Belgium, Brazil, Colombia, the Philippines, and South Africa in participants ≥ 12 years of age. Participants were randomly assigned to receive 2 doses of SCB-2019 or placebo administered intramuscularly 21 days apart. Here, we present the safety results of SCB-2019 over the 6-month period following 2-dose primary vaccination series in all adult participants (≥18 years of age)., Results: A total of 30,137 adult participants received at least one dose of study vaccine (n = 15,070) or placebo (n = 15,067) between 24 March 2021 and 01 December 2021. Unsolicited adverse events, medically-attended adverse events, adverse events of special interest, and serious adverse events were reported in similar frequencies in both study arms over the 6-month follow-up period. Vaccine-related SAEs were reported by 4 of 15,070 SCB-2019 recipients (hypersensitivity reactions in two participants, Bell's palsy, and spontaneous abortion) and 2 of 15,067 placebo recipients (COVID-19, pneumonia, and acute respiratory distress syndrome in one participant and spontaneous abortion in the other one). No signs of vaccine-associated enhanced disease were observed., Conclusions: SCB-2019 administered as a 2-dose series has an acceptable safety profile. No safety concerns were identified during the 6-month follow-up after the primary vaccination., Clinical Trials Registration: NCT04672395; EudraCT: 2020-004272-17., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: RH, PA, IS, PL, HQ, CV, BH, and YH are employees of Clover Biopharmaceuticals and may own stocks in the company. CB is an employee of Clover Biopharmaceuticals and owns stocks in Clover Biopharmaceuticals, GSK, and Sanofi. PR was an employee of Clover Biopharmaceuticals at the time of the study conduct and owns stocks in the company., (Copyright © 2023. Published by Elsevier Ltd.)

Background: The open-label RECOVERY study reported improved survival in hospitalized, SARS-CoV-2 seronegative patients treated with casirivimab and imdevimab (CAS + IMD)., Methods: In this phase 1/2/3, double-blind, placebo-controlled trial conducted prior to widespread circulation of Delta and Omicron, hospitalized COVID-19 patients were randomized (1:1:1) to 2.4 g or 8.0 g CAS + IMD or placebo, and characterized at baseline for viral load and SARS-CoV-2 serostatus., Results: In total, 1336 patients on low-flow or no supplemental (low-flow/no) oxygen were treated. The primary endpoint was met in seronegative patients, the least-squares mean difference (CAS + IMD versus placebo) for time-weighted average change from baseline in viral load through day 7 was -0.28 log10 copies/mL (95% confidence interval [CI], -.51 to -.05; P = .0172). The primary clinical analysis of death or mechanical ventilation from day 6 to 29 in patients with high viral load had a strong positive trend but did not reach significance. CAS + IMD numerically reduced all-cause mortality in seronegative patients through day 29 (relative risk reduction, 55.6%; 95% CI, 24.2%-74.0%). No safety concerns were noted., Conclusions: In hospitalized COVID-19 patients on low-flow/no oxygen, CAS + IMD reduced viral load and likely improves clinical outcomes in the overall population, with the benefit driven by seronegative patients, and no harm observed in seropositive patients., Clinical Trials Registration: NCT04426695., Competing Interests: Potential conflicts of interest. S. S.-K., S. A., Y. Sun, R. B., J. Mei, J. Miller, E. F.-N., C. P., V. P., Y. Z., A. M., J. D. D., Y. K., A. C., B. K., Y. Soo, A. T. D., G. P. G., L. L., N. B., and D. M. W. are employees/stockholders of Regeneron Pharmaceuticals, Inc, and report grants from Biomedical Advanced Research and Development Authority (BARDA). E. M. reports payments to his institution received from National Institutes of Health (NIH)/National Institute of Allergy and Infectious Diseases, NIH/National Institute of General Medical Sciences, SciClone Pharmaceuticals, Regeneron Pharmaceuticals, Inc, Pfizer, Chemic Labs/KODA Therapeutics, Cidara, and Leidos Biomedical Research Inc/NCI. V. P. M. and J. C. W. report grants from BARDA. S. S. is an Excision BioTherapeutics employee/stockholder and former Regeneron Pharmaceuticals, Inc, employee and current stockholder, and reports grants from BARDA. L. C. is a Regeneron Pharmaceuticals, Inc employee and reports grants from BARDA. A. T. H. is a Regeneron Pharmaceuticals, Inc employee/stockholder, a former Pfizer employee and current stockholder, has a patent pending with Regeneron Pharmaceuticals, Inc and reports grants from BARDA. J. D. H., K. C. T., and G. A. H. are employees/stockholders of Regeneron Pharmaceuticals, Inc and have a patent pending, which has been licensed and receiving royalties, with Regeneron Pharmaceuticals, Inc. R. H. is a former employee and current stockholder of Regeneron Pharmaceuticals, Inc, and reports grants from BARDA. N. S. and G. D. Y. are employees/stockholders of Regeneron Pharmaceuticals, Inc, and have issued patents (US Patent Nos. 10 787 501, 10 954 289, and 10 975 139) and pending patents, which have been licensed and receiving royalties, with Regeneron Pharmaceuticals, Inc, and reports grants from BARDA. Funding to pay the Open Access publication charges for this article was provided by Regeneron Pharmaceuticals, Inc., (© The Author(s) 2022. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)

Background: Open-label platform trials and a prospective meta-analysis suggest efficacy of anti-interleukin (IL)-6R therapies in hospitalized patients with coronavirus disease 2019 (COVID-19) receiving corticosteroids. This study evaluated the efficacy and safety of sarilumab, an anti-IL-6R monoclonal antibody, in the treatment of hospitalized patients with COVID-19., Methods: In this adaptive, phase 2/3, randomized, double-blind, placebo-controlled trial, adults hospitalized with COVID-19 received intravenous sarilumab 400 mg or placebo. The phase 3 primary analysis population included patients with critical COVID-19 receiving mechanical ventilation (MV). The primary outcome was proportion of patients with ≥1-point improvement in clinical status from baseline to day 22., Results: There were 457 and 1365 patients randomized and treated in phases 2 and 3, respectively. In phase 3, patients with critical COVID-19 receiving MV (n = 298; 28.2% on corticosteroids), the proportion with ≥1-point improvement in clinical status (alive, not receiving MV) at day 22 was 43.2% for sarilumab and 35.5% for placebo (risk difference, +7.5%; 95% confidence interval [CI], -7.4 to 21.3; P =.3261), a relative risk improvement of 21.7%. In post hoc analyses pooling phase 2 and 3 critical patients receiving MV, the hazard ratio for death for sarilumab vs placebo was 0.76 (95% CI, .51 to 1.13) overall and 0.49 (95% CI, .25 to .94) in patients receiving corticosteroids at baseline., Conclusions: This study did not establish the efficacy of sarilumab in hospitalized patients with severe/critical COVID-19. Post hoc analyses were consistent with other studies that found a benefit of sarilumab in patients receiving corticosteroids., Clinical Trials Registration: NCT04315298., (© The Author(s) 2022. Published by Oxford University Press for the Infectious Diseases Society of America.)

Background: A range of safe and effective vaccines against SARS CoV 2 are needed to address the COVID 19 pandemic. We aimed to assess the safety and efficacy of the COVID-19 vaccine SCB-2019., Methods: This ongoing phase 2 and 3 double-blind, placebo-controlled trial was done in adults aged 18 years and older who were in good health or with a stable chronic health condition, at 31 sites in five countries (Belgium, Brazil, Colombia, Philippines, and South Africa). The participants were randomly assigned 1:1 using a centralised internet randomisation system to receive two 0·5 mL intramuscular doses of SCB-2019 (30 μg, adjuvanted with 1·50 mg CpG-1018 and 0·75 mg alum) or placebo (0·9% sodium chloride for injection supplied in 10 mL ampoules) 21 days apart. All study staff and participants were masked, but vaccine administrators were not. Primary endpoints were vaccine efficacy, measured by RT-PCR-confirmed COVID-19 of any severity with onset from 14 days after the second dose in baseline SARS-CoV-2 seronegative participants (the per-protocol population), and the safety and solicited local and systemic adverse events in the phase 2 subset. This study is registered on EudraCT (2020-004272-17) and ClinicalTrials.gov (NCT04672395)., Findings: 30 174 participants were enrolled from March 24, 2021, until the cutoff date of Aug 10, 2021, of whom 30 128 received their first assigned vaccine (n=15 064) or a placebo injection (n=15 064). The per-protocol population consisted of 12 355 baseline SARS-CoV-2-naive participants (6251 vaccinees and 6104 placebo recipients). Most exclusions (13 389 [44·4%]) were because of seropositivity at baseline. There were 207 confirmed per-protocol cases of COVID-19 at 14 days after the second dose, 52 vaccinees versus 155 placebo recipients, and an overall vaccine efficacy against any severity COVID-19 of 67·2% (95·72% CI 54·3-76·8), 83·7% (97·86% CI 55·9-95·4) against moderate-to-severe COVID-19, and 100% (97·86% CI 25·3-100·0) against severe COVID-19. All COVID-19 cases were due to virus variants; vaccine efficacy against any severity COVID-19 due to the three predominant variants was 78·7% (95% CI 57·3-90·4) for delta, 91·8% (44·9-99·8) for gamma, and 58·6% (13·3-81·5) for mu. No safety issues emerged in the follow-up period for the efficacy analysis (median of 82 days [IQR 63-103]). The vaccine elicited higher rates of mainly mild-to-moderate injection site pain than the placebo after the first (35·7% [287 of 803] vs 10·3% [81 of 786]) and second (26·9% [189 of 702] vs 7·4% [52 of 699]) doses, but the rates of other solicited local and systemic adverse events were similar between the groups., Interpretation: Two doses of SCB-2019 vaccine plus CpG and alum provides notable protection against the entire severity spectrum of COVID-19 caused by circulating SAR-CoV-2 viruses, including the predominating delta variant., Funding: Clover Biopharmaceuticals and the Coalition for Epidemic Preparedness Innovations., Competing Interests: Declaration of interests IS, HHH, PLi, RH, CB, BH, and JL are full-time employees of Clover Biopharmaceuticals. FR is a statistical adviser for Clover Biopharmaceuticals. RC, DA, PR, and GS are scientific advisers for Clover Biopharmaceuticals. All other authors declare no competing interests., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Background: In the phase 1-2 portion of an adaptive trial, REGEN-COV, a combination of the monoclonal antibodies casirivimab and imdevimab, reduced the viral load and number of medical visits in patients with coronavirus disease 2019 (Covid-19). REGEN-COV has activity in vitro against current severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants of concern., Methods: In the phase 3 portion of an adaptive trial, we randomly assigned outpatients with Covid-19 and risk factors for severe disease to receive various doses of intravenous REGEN-COV or placebo. Patients were followed through day 29. A prespecified hierarchical analysis was used to assess the end points of hospitalization or death and the time to resolution of symptoms. Safety was also evaluated., Results: Covid-19-related hospitalization or death from any cause occurred in 18 of 1355 patients in the REGEN-COV 2400-mg group (1.3%) and in 62 of 1341 patients in the placebo group who underwent randomization concurrently (4.6%) (relative risk reduction [1 minus the relative risk], 71.3%; P<0.001); these outcomes occurred in 7 of 736 patients in the REGEN-COV 1200-mg group (1.0%) and in 24 of 748 patients in the placebo group who underwent randomization concurrently (3.2%) (relative risk reduction, 70.4%; P = 0.002). The median time to resolution of symptoms was 4 days shorter with each REGEN-COV dose than with placebo (10 days vs. 14 days; P<0.001 for both comparisons). REGEN-COV was efficacious across various subgroups, including patients who were SARS-CoV-2 serum antibody-positive at baseline. Both REGEN-COV doses reduced viral load faster than placebo; the least-squares mean difference in viral load from baseline through day 7 was -0.71 log 10 copies per milliliter (95% confidence interval [CI], -0.90 to -0.53) in the 1200-mg group and -0.86 log 10 copies per milliliter (95% CI, -1.00 to -0.72) in the 2400-mg group. Serious adverse events occurred more frequently in the placebo group (4.0%) than in the 1200-mg group (1.1%) and the 2400-mg group (1.3%); infusion-related reactions of grade 2 or higher occurred in less than 0.3% of the patients in all groups., Conclusions: REGEN-COV reduced the risk of Covid-19-related hospitalization or death from any cause, and it resolved symptoms and reduced the SARS-CoV-2 viral load more rapidly than placebo. (Funded by Regeneron Pharmaceuticals and others; ClinicalTrials.gov number, NCT04425629.)., (Copyright © 2021 Massachusetts Medical Society.)

Introduction: The Food and Drug Administration (FDA) Adverse Event Reporting System (FAERS) and VigiBase ® are two established databases for safety monitoring of medicinal products, recently complemented with the EudraVigilance Data Analysis System (EVDAS)., Objective: Signals of disproportionate reporting (SDRs) can characterize the reporting profile of a drug, accounting for the distribution of all drugs and all events in the database. This study aims to quantify the redundancy among the three databases when characterized by two disproportionality-based analyses (DPA)., Methods: SDRs for 100 selected products were identified with two sets of thresholds (standard EudraVigilance SDR criteria for all vs Bayesian approach for FAERS and VigiBase ® ). Per product and database, the presence or absence of SDRs was determined and compared. Adverse events were considered at three levels: MedDRA ® Preferred Term (PT), High Level Term (HLT), and HLT combined with Standardized MedDRA ® Query (SMQ). Redundancy was measured in terms of recall (SDRs in EVDAS divided by SDRs from any database) and overlap (SDRs in EVDAS and at least one other database, divided by SDRs in EVDAS). Covariates with potential impact on results were explored with linear regression models., Results: The median overlap between EVDAS and FAERS or VigiBase ® was 85.0% at the PT level, 94.5% at the HLT level, and 97.7% at the HLT or SMQ level. The corresponding median recall of signals in EVDAS as a percentage of all signals generated in all three databases was 59.4%, 74.1%, and 87.9% at the PT, HLT, and HLT or SMQ levels, respectively. The overlap difference is partially explained by the relative number of EU cases in EudraVigilance and the ratio of EVDAS cases and FAERS cases, presumably due to differences in marketing authorizations, or market penetration in different regions. Products with few cases in EVDAS (< 1500) also display limited recall of signals relative to FAERs/VigiBase ® . Time-on-market does not predict signal redundancy between the three databases. The choice of the DPA has an expected but somewhat small effect on redundancy., Conclusions: Organizations typically consider regulatory expectations, operating performance (e.g., positive predictive value), and procedural complexity when selecting databases for signal management. As SDRs can be seen as a proxy of general reporting characteristics identifiable in a systematic screening process, our results indicate that, for most products, these characteristics are largely similar in each of the databases.

Background: REGN3470-3471-3479 is a co-formulated cocktail of three human monoclonal antibodies targeting three non-overlapping epitopes on Ebola virus. We investigated safety, tolerability, pharmacokinetics, and anti-drug antibodies in healthy adults., Methods: This randomised, double-blind, placebo-controlled, dose-escalation study was done at a phase 1 unit in the USA. Healthy adults, aged 18-60 years, with a body-mass index of 18·0-30·0 kg/m 2 were randomly assigned (3:1) to receive a single intravenous dose of REGN3470-3471-3479 or placebo on day 1 (baseline) in one of the four sequential ascending intravenous dose cohorts (3 mg/kg, 15 mg/kg, 60 mg/kg, and 150 mg/kg). Site investigators and participants were masked to the treatment assignment, whereas designated personnel at the site who prepared and generated the study medication were aware of the randomisation treatment assignments. The primary outcome was safety and the secondary outcomes were the pharmacokinetic profiles and immunogenicity. Study assessments were done the day before study drug administration, on the day of drug administration, on day 2 (before discharge), on days 3, 4, 8, 15, 29, 57, 85, 113, and 141, and at the end of study on day 169. The safety analysis included all randomised participants who received study drug. This trial is registered with ClinicalTrials.gov, number NCT002777151., Findings: Between May 18, 2016, and October 27, 2016, 70 adults were screened and 24 participants were enrolled in the study. 18 participants were assigned to and received REGN3470-3471-3479, and six participants were assigned to and received placebo as a single intravenous infusion. 19 treatment-emergent adverse events occurred in the combined REGN3470-3471-3479 treatment groups, and four treatment-emergent adverse events occurred in combined placebo groups. Adverse events were transient and mild-to-moderate in severity. The most common treatment-emergent adverse event was headache (six [33%] of 18 participants in the combined REGN3470-3471-3479 group vs none of six participants in the placebo group. Headaches were mild-to-moderate in severity, with onset between 2 h and 27 days after start of study drug infusion. There were no deaths, serious adverse events, or adverse events that led to study discontinuation. The pharmacokinetics of each antibody was linear, with mean half-lives of 27·3 days for REGN3471, 21·7 days for REGN3470, and 23·3 days for REGN3479. No participants tested positive for anti-REGN3470, anti-REGN3471, or anti-REGN3479 antibodies., Interpretation: REGN3470-3471-3479 was well tolerated, displayed linear pharmacokinetics, and did not lead to detectable immunogenicity. These data support further clinical development of REGN3470-3471-3479 as a single-dose therapeutic drug for acute Ebola virus infection., Funding: The Department of Health and Human Services, the Office of the Assistant Secretary for Preparedness and Response, and the Biomedical Advanced Research and Development Authority., (Copyright © 2018 Elsevier Ltd. All rights reserved.)