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In this study, a sensitivity analysis on a VECTRI dynamical model of malaria transmission is investigated to determine the relative importance of model parameters to disease transmission and prevalence. Apart from being most climatic prone, Odisha is a highly endemic state for malaria in India. The lack in sufficient modeling studies severely impacts the malarial process studies which further hinder the possibility of malaria early warning systems and preventive measures to be undertaken beforehand. Therefore, modeling studies and investigating the relationship between malaria transmission process studies and associated climatic factors are the need of the hour. Environmental conditions have pronounced effects on the malaria transmission dynamics and abundance of the poikilothermic vectors, but the exact relationship of sensitivity for these parameters is not well established. Sensitivity analysis is a useful tool for ascertaining model responses to different input variables. Therefore, in order to perform the requisite study, a dynamical model, VECTRI, is utilized. The study period ranges from 2000 to 2013, where several sensitivity tests are performed using different model parameters such as infiltration and evaporation rate loss of ponds, degree-days for parasite development, threshold temperature for parasite development, threshold temperature for egg development in the vector, and maximum and minimum temperature for larvae survival. The experiments suggest that the lower value of minimum temperature for larvae survival (rlarv_tmin), i.e., 16 °C, provides higher vector density and entomological inoculation rate (EIR) values. EIR reaches its maximum, when the threshold temperature for parasite development (rtsporo) is 22 °C and degree-days for parasite development (dsporo) is 8 degree-days. No change is observed in the vector density; even when rtsporo is 30 °C, values of EIR are close to 0. A successive increment of infiltration and evaporation rate loss of ponds (rwaterfrac evap126) values from 130 to 200 mm/day result in approximately 5% consistent decline in vector density and EIR. The study concludes that the most sensitive parameters are dsporo, rlarv_tmin, and rwaterfrac evap126. The VECTRI model is rather insensitive to maximum temperature for larvae survival (rlarv_tmin) for vector density and EIR variables. Further certain modifications and improvements are required in VECTRI to predict out variables like vector density and EIR more accurately in highly endemic region.
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Vidro , Malária , Animais , Prevalência , Malária/epidemiologia , Malária/prevenção & controle , Temperatura , Índia/epidemiologia , LarvaRESUMO
Imazethapyr is the most common herbicide used for weed management in pulses. A field trial was carried out with imazethapyr 10% SL formulation at 100 and 150 g a.i./ha application rates, as pre-and post-emergence, to study dissipation of imazethapyr in soil, persistence in urdbean plant, terminal residues in urdbean grains and effect on soil microbes. An acetate buffered- quick, easy, cheap, effective, rugged, and safe (QuEChERS) method in combination with high-performance liquid chromatography (HPLC) was validated for imazethapyr residue analysis. The half-life of imazethapyr in soil ranged from 15.12 to 18.02 days. The residues of imazethapyr persist up to 60 days in soil and up to 7-15 days in urdbean plant. Residues were not detected in grains at the time of harvest. Persistence of imazethapyr residues in soil significantly impact soil microbial populations depending on herbicide application rates and timing.
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Herbicidas , Ácidos Nicotínicos , Resíduos de Praguicidas , Microbiologia do Solo , Poluentes do Solo , Solo , Vigna , Herbicidas/análise , Poluentes do Solo/análise , Vigna/química , Ácidos Nicotínicos/análise , Resíduos de Praguicidas/análise , Solo/química , Cinética , Cromatografia Líquida de Alta Pressão , Meia-VidaRESUMO
Drought hampers global rice production. Abscisic acid (ABA) plays versatile roles under different environmental stresses. While the link between drought and ABA is known, its effect on ABA biosynthesis genes and metabolites is unclear. This study explored the impact of drought on various metabolites, namely beta-carotene, zeaxanthin, antheraxanthin, violaxanthin, neoxanthin, and candidate genes viz. zeaxanthin epoxidase (ZEP) and 9-cis epoxycarotenoid dioxygenase (NCED) of ABA biosynthesis pathway in rice cultivars (N22 and IR64) at anthesis {65 DAT (Days after transplanting)} with different stress levels. In stressed plants, zeaxanthin significantly increased (92%), while the concentration of beta-carotene, antheraxanthin, violaxanthin and neoxanthin decreased as drought stress progressed. The concentration of metabolites in roots was notably lower than in leaves in both genotypes. The ZEP expression was upregulated in roots (8.24-fold) under drought stress. Among five NCED isoforms, NCED3 showed significant upregulation (7.29-fold) in leaf and root tissue. NCED1 was significantly downregulated as stress progressed and was negatively correlated with ABA accumulation. NCED2, NCED4 and NCED5 showed no significant change in their expression. Drying and rolling of rice leaves was observed after imparting drought stress. The findings revealed that drought stress significantly influenced the expression of candidate genes and the concentration of metabolites of the ABA biosynthesis pathway. There was a significantly higher accumulation of ABA in N22 leaves (47%) and roots (30%) compared to IR64. The N22, a drought-tolerant genotype, exhibited significantly higher concentrations of intermediates and demonstrated increased expression of ZEP and NCED3, potentially contributing to its resilience against drought.
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Ácido Abscísico , Oryza , Ácido Abscísico/metabolismo , Oryza/genética , Oryza/metabolismo , beta Caroteno/metabolismo , Zeaxantinas/metabolismo , Secas , Vias Biossintéticas/genética , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Regulação da Expressão Gênica de Plantas , Estresse FisiológicoRESUMO
Water deficit is a significant impediment to enhancing rice yield. Genetic engineering tools have enabled agriculture researchers to develop drought-tolerant cultivars of rice. A common strategy to achieve this involves expressing drought-tolerant genes driven by constitutive promoters such as CaMV35S. However, the use of constitutive promoters is often limited by the adverse effects it has on the growth and development of the plant. Additionally, it has been observed that monocot-derived promoters are more successful in driving gene expression in monocots than in dicots. Substitution of constitutive promoters with stress-inducible promoters is the currently used strategy to overcome this limitation. In the present study, a 1514 bp AP2/ERF promoter that drives the expression of a transcription factor was cloned and characterized from drought-tolerant Indian rice genotype N22. The AP2/ERF promoter was fused to the GUS gene (uidA) and transformed in Arabidopsis and rice plants. Histochemical GUS staining of transgenic Arabidopsis plants showed AP2/ERF promoter activity in roots, stems, and leaves. Water deficit stress and ABA upregulate promoter activity in transformed Arabidopsis and rice. Quantitative PCR for uidA expression confirmed induced GUS activity in Arabidopsis and rice. This study showed that water deficit inducible Os-AP2/ERF-N22 promoter can be used to overcome the limitations of constitutive promoters. Transformants overexpressing Os-AP2/ERF-N22 showed higher relative water content, membrane stability index, total chlorophyll content, chlorophyll stability index, wax content, osmotic potential, stomatal conductance, transpiration rate, photosynthetic rate and radical scavenging activity. Drought tolerant (N22) showed higher expression of Os-AP2/ERF-N22 than the susceptible (MTU1010) cultivar. Supplementary Information: The online version contains supplementary material available at 10.1007/s12298-022-01246-9.
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BACKGROUND Our objectives were to evaluate geographic access to lung cancer treatment modalities in North Carolina and to characterize how practice patterns are changing over time. We hypothesized that rural patients would be less likely to undergo treatment compared to urban patients, with widening disparities over time.METHODS We identified patients with Stage I non-small cell lung cancer (NSCLC) from 2006 to 2015 using the North Carolina Central Cancer Registry linked with Medicaid, Medicare, and private insurance claims. The primary outcome was first-course treatment: surgery, radiation, or no treatment. Calendar years were split into earlier (2006-2010) and later (2011-2015) periods. We estimated the adjusted odds ratio (OR) of rural/urban status and time period with 1) surgery and 2) any treatment (surgery or radiation) using multivariable logistic regression.RESULTS Among 5504 patients, 3206 (58%) underwent surgery as initial therapy, 1309 (24%) received radiation as initial therapy, and 989 (18%) had no therapy. There were no rural-urban disparities in treatment patterns. For rural and urban patients, the odds of surgery decreased over time and the odds of radiation increased. We also found that only 48% of those receiving no treatment ever reached a surgeon or radiation oncologist.LIMITATIONS This was an insured, single-state population. Treatment preferences are unknown.CONCLUSIONS Among all treated patients, whether urban or rural, there was increasing use of radiation and decreasing use of surgery over time. Many patients without treatment never had a consultation with a surgeon/radiation oncologist, and this is an actionable target for improving treatment access for early-stage NSCLC.
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Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Idoso , Carcinoma Pulmonar de Células não Pequenas/cirurgia , Humanos , Neoplasias Pulmonares/epidemiologia , Neoplasias Pulmonares/terapia , Medicaid , Medicare , População Rural , Estados Unidos/epidemiologia , População UrbanaRESUMO
Herbicides have proven to be a boon for agricultural fields. Their inherent property to kill weeds and unwanted vegetation makes them an essential biological tool for farmers and agricultural systems. Besides being capable of destroying weeds, they also exhibit certain effects on non-target crop plants. In the present study, a laboratory experiment was performed to assess the effect of glyphosate on Vigna mungo root meristem cells. Seeds of five different genotypes of V. mungo were treated with a series of concentrations of glyphosate ranging from 1 to 10 mM, and their effects on mitotic cell division were studied. Healthy and uniform-sized seeds were selected and were allowed to grow in Petri plates for 3 days, and all the doses were maintained in triplicates. Roots were fixed at day 3 after treatment (DAT) for cytological microscopic slide preparation. The results obtained indicate the dose-dependent reduction in the mitotic index in all the genotypes and an increase in the percentage of chromosomal aberrations (CAs) and relative abnormality rate (RAR). Most commonly observed chromosome aberrations at lower doses (< 6 mM) were fragments, stickiness, and disoriented metaphase, while at higher doses (6 to 10 mM) bridges, laggards, spindle disorientation, and clumping were obvious. The increase in the percentage of CAs and RAR indicates the inhibitory effect of glyphosate on cell cycle progression at various stages in root tip cells. The present study is a fine example of a biomarker-based genotoxic assessment of mitotic damage caused by glyphosate.
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Herbicidas , Vigna , Biomarcadores , Monitoramento Ambiental , Genótipo , Glicina/análogos & derivados , Herbicidas/toxicidade , Vigna/genética , GlifosatoRESUMO
BACKGROUND: Thromboprophylaxis for ambulatory patients with cancer is effective, although uncertainties remain on who should be targeted. Using D-dimer values from individuals enrolled to the AVERT trial, we sought to identify and validate a more efficient venous thromboembolism (VTE) risk threshold for thromboprophylaxis. MATERIALS AND METHODS: The AVERT trial compared thromboprophylaxis with apixaban with placebo among patients with cancer with a Khorana Risk Score ≥2. The D-dimer measured at randomization was used to calculate an individualized 6-month VTE risk using the validated CATScore. A modified intention-to-treat analysis was used to assess efficacy (VTE) and safety (major and overall bleeding) in the (a) complete cohort and (b) ≥8% and < 8% 6-month VTE risk thresholds. RESULTS: Five hundred seventy-four patients were randomized in the AVERT trial; 466 (81%) with baseline D-dimer were included in the study. Two hundred thirty-seven subjects received apixaban; 229 received placebo. In the complete cohort, there were 13 (5.5%) VTE events in the apixaban arm compared with 26 (11.4%) events in the placebo arm (adjusted hazard ratio [aHR] 0.49 [0.25-0.95], p < .05). Number needed to treat (NNT) to prevent one VTE = 17. Eighty-two (35%) and 72 (31%) patients in the apixaban and placebo arms, respectively, had a 6-month VTE risk ≥8%. In this subgroup, 7 (8.4%) VTE events occurred with apixaban and 19 (26.3%) events with placebo (aHR 0.33 [0.14-0.81], p < .05), NNT = 6. Individuals with a VTE risk <8% derived no benefit from apixaban thromboprophylaxis (aHR 0.89 [0.30-2.65), p = .84). Increased rates of overall bleeding were observed with apixaban in both the complete (aHR 2.11 [1.09-4.09], p < .05) and ≥ 8% predicted risk cohorts (aHR 2.87 [0.91-9.13], p = .07). CONCLUSION: A 6-month VTE risk threshold of ≥8% increases the efficiency of risk-targeted thromboprophylaxis in ambulatory patients with cancer. IMPLICATIONS FOR PRACTICE: Ambulatory patients with cancer receiving chemotherapy have an increased risk of venous thromboembolism (VTE). A Khorana Risk Score (KRS) ≥2 is currently the suggested threshold for thromboprophylaxis. Using baseline D-dimer values from individuals enrolled to the AVERT trial, this retrospective validation study identifies a 6-month VTE risk of ≥8% as a more efficient threshold for thromboprophylaxis. At this threshold, the number needed to treat to prevent one VTE is 6, compared with 17 when using a KRS ≥2. Conversely, individuals with a predicted risk of <8% derive no clinical benefit from thromboprophylaxis. Future prospective studies should validate this threshold for outpatient thromboprophylaxis.
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Neoplasias , Tromboembolia Venosa , Anticoagulantes/efeitos adversos , Produtos de Degradação da Fibrina e do Fibrinogênio , Humanos , Neoplasias/complicações , Neoplasias/tratamento farmacológico , Estudos Prospectivos , Estudos Retrospectivos , Tromboembolia Venosa/prevenção & controleRESUMO
Background: Targeting low-dose computed tomography (LDCT) for lung cancer screening to persons at highest risk for lung cancer mortality has been suggested to improve screening efficiency. Objective: To quantify the value of risk-targeted selection for lung cancer screening compared with National Lung Screening Trial (NLST) eligibility criteria. Design: Cost-effectiveness analysis using a multistate prediction model. Data Sources: NLST. Target Population: Current and former smokers eligible for lung cancer screening. Time Horizon: Lifetime. Perspective: Health care sector. Intervention: Risk-targeted versus NLST-based screening. Outcome Measures: Incremental 7-year mortality, life expectancy, quality-adjusted life-years (QALYs), costs, and cost-effectiveness of screening with LDCT versus chest radiography at each decile of lung cancer mortality risk. Results of Base-Case Analysis: Participants at greater risk for lung cancer mortality were older and had more comorbid conditions and higher screening-related costs. The incremental lung cancer mortality benefits during the first 7 years ranged from 1.2 to 9.5 lung cancer deaths prevented per 10 000 person-years for the lowest to highest risk deciles, respectively (extreme decile ratio, 7.9). The gradient of benefits across risk groups, however, was attenuated in terms of life-years (extreme decile ratio, 3.6) and QALYs (extreme decile ratio, 2.4). The incremental cost-effectiveness ratios (ICERs) were similar across risk deciles ($75 000 per QALY in the lowest risk decile to $53 000 per QALY in the highest risk decile). Payers willing to pay $100 000 per QALY would pay for LDCT screening for all decile groups. Results of Sensitivity Analysis: Alternative assumptions did not substantially alter our findings. Limitation: Our model did not account for all correlated differences between lung cancer mortality risk and quality of life. Conclusions: Although risk targeting may improve screening efficiency in terms of early lung cancer mortality per person screened, the gains in efficiency are attenuated and modest in terms of life-years, QALYs, and cost-effectiveness. Primary Funding Source: National Institutes of Health (U01NS086294).
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Análise Custo-Benefício , Detecção Precoce de Câncer/economia , Neoplasias Pulmonares/diagnóstico por imagem , Programas de Rastreamento/economia , Tomografia Computadorizada por Raios X/economia , Idoso , Feminino , Humanos , Expectativa de Vida , Neoplasias Pulmonares/mortalidade , Masculino , Pessoa de Meia-Idade , Seleção de Pacientes , Anos de Vida Ajustados por Qualidade de Vida , Radiografia Torácica/economia , Risco , Fumantes , Estados Unidos/epidemiologiaRESUMO
AIM: To comparatively evaluate the status of fluoride in the body with thyroid activity in the pediatric population of endemic fluorosis areas. The present study also attempted to elucidate whether any correlation exists between fluoride and thyroid hormone derangement with delayed tooth eruption. MATERIALS AND METHODS: A total of 400 pediatric subjects were included in the present study. All the patients were divided into two broad groups; groups A and B. Group A included 200 subjects who belonged to the endemic fluorosis area while Group B included remaining 200 subjects, who belonged to the fluorosis non-endemic area. Group B subjects were taken as control. Group A subjects were further divided into two study groups as follows: Group A1: 100 Pediatric subjects with dental fluorosis, and Group A 2: A total of one hundred pediatric subjects without dental fluorosis. Dean's index of fluorosis was calculated in all the patients. Blood samples were collected and were sent to a laboratory for assessment of thyroid hormone levels. All the results were subjected to statistical analysis by Statistical Package for the Social Sciences (SPSS) software. RESULTS: Mean thyroid stimulating hormone (TSH), water fluoride levels, urine fluoride levels and serum fluoride levels of subjects in group 1 were found to be significantly higher than that of subjects of group 2. Delayed tooth eruption was absent in subjects of group B while it was present in 100 subjects of group A. Thyroid hormone level derangement was seen in 54 percent subjects of group B, while it was seen in 67.5% subjects of group A. CONCLUSION: Positive correlation exists between fluorosis and thyroid functional activity. However; the tooth eruption pattern is independent up on the thyroid hormone derangement. CLINICAL SIGNIFICANCE: Delayed tooth eruption and alteration in thyroid hormone levels can occur in subjects of the endemic fluoride areas. Therefore, adequate measures should be taken for controlling such adverse effects.
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Fluoretos/efeitos adversos , Fluoretos/metabolismo , Fluorose Dentária/metabolismo , Fluorose Dentária/fisiopatologia , Tireotropina/metabolismo , Erupção Dentária/efeitos dos fármacos , Criança , Pré-Escolar , Feminino , Fluoretos/análise , Humanos , Lactente , Masculino , Tireotropina/fisiologia , Erupção Dentária/fisiologia , Água/química , Abastecimento de ÁguaRESUMO
AIM: The present study was conducted to determine different bone markers in immediate loaded and nonloaded dental implants. MATERIALS AND METHODS: It comprised of 60 patients (males-30, females-30) which were divided into two groups of 30 each. Group I received immediate loaded dental implants, and group II received non-loaded dental implants. Modified bleeding on probing index, peri-implant sulcus depth was assessed in both groups at 1 month, 2 months, 3 months and 4 months. The crevicular fluid was obtained to determine bone markers levels such as transforming growth factor-alpha (TGF-a), osteocalcin (OCN), osteopontin (OPN), parathyroid hormone (PTH) and osteoprotegerin (OPG). RESULTS: Both groups revealed non-significant difference in modified bleeding on probing index and peri-implant sulcus depth (p > 0.05). Bone markers found to be elevated more in group I as compared to group II. However, the difference was non- significant (p > 0.05). CONCLUSION: Transforming growth factor alpha (TGF-a), OCN, OPN, OPG and PTH and parathyroid hormone (PTH) levels were higher in immediate loaded dental implants as compared to nonloaded dental implants. CLINICAL SIGNIFICANCE: Immediate loaded dental implants showed an increase in expression of bone markers such as TNF-a, OCN, OPN, PTH and OPG which may be useful in deciding future of immediate loaded dental implants.
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Implantação Dentária/métodos , Implantes Dentários , Líquido do Sulco Gengival/metabolismo , Carga Imediata em Implante Dentário , Osseointegração/genética , Osseointegração/fisiologia , Osteocalcina/análise , Osteopontina/análise , Osteoprotegerina/análise , Hormônio Paratireóideo/análise , Fator de Crescimento Transformador alfa/análise , Biomarcadores/análise , Biomarcadores/metabolismo , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Osteocalcina/metabolismo , Osteopontina/metabolismo , Osteoprotegerina/metabolismo , Hormônio Paratireóideo/metabolismo , Fatores de Tempo , Fator de Crescimento Transformador alfa/metabolismoRESUMO
γ-Tocopherol methyltransferase (γ-TMT) (EC 2.1.1.95) is the last enzyme in the tocopherol biosynthetic pathway and it catalyzes the conversion of γ-tocopherol into α-tocopherol, the nutritionally significant and most bioactive form of vitamin E. Although the γ-TMT gene has been successfully overexpressed in many crops to enhance their α-tocopherol content but still only few attempts have been made to uncover its structural, functional and regulation aspects at protein level. In this study, we have cloned the complete 909bp coding sequence of Glycine max γ-TMT (Gm γ-TMT) gene that encodes the corresponding protein comprising of 302 amino acid residues. The deduced Gm γ-TMT protein showed 74-87% sequence identity with other characterized plant γ-TMTs. Gm γ-TMT belongs to Class I Methyl Transferases that have a Rossmann-like fold which consists of a seven-stranded ß sheet joined by α helices. Heterologous expression of Gm γ-TMT in pET29a expression vector under the control of bacteriophage T7 promoter produced a 37.9 kDa recombinant Gm γ-TMT protein with histidine hexamer tag at its C-terminus. The expression of recombinant Gm γ-TMT protein was confirmed by western blotting using anti-His antibody. The recombinant protein was purified by Ni2+-NTA column chromatography. The purified protein showed SAM dependent methyltransferase activity. The α-tocopherol produced in the in-vitro reaction catalyzed by the purified enzyme was detected using reverse phase HPLC. This study has laid the foundation to unveil the biochemical understanding of Gm γ-TMT enzyme which can be further explored by studying its kinetic behaviour, substrate specificity and its interaction with other biomolecules.
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Glycine max/enzimologia , Metiltransferases/genética , gama-Tocoferol/metabolismo , Clonagem Molecular , Regulação da Expressão Gênica de Plantas , Metiltransferases/biossíntese , Metiltransferases/química , Plantas Geneticamente Modificadas , Sementes/genéticaRESUMO
This article presents and describes a dataset for the bills of materials for the buildings constructed with mass timber (MT), structural steel (SS), and reinforced concrete (RC), which are generated using Athena's Impact Estimator for Buildings (IE4B) software to conduct a whole building life-cycle assessment (WBLCA). These data are associated with the research article Environmental Impact Assessment of Mass Timber, Structural Steel, and Reinforced Concrete Buildings Based on the 2021 International Building Code Provisions [1]. This dataset was utilized to estimate their environmental impacts but can be used to estimate the costs of buildings constructed with MT, SS, and RC building materials. These data could be replicated using the same layout, system boundaries, reference study period (RSP), and building assemblies' information as used in the published work [1]. This dataset is related to conceptual design of a building with 11 apartment units per floor. However, a detailed design that includes the analysis of interior architectural finishes such as internal partitions within the units, kitchen and washroom fixtures, internal doors, flooring, and so on, could be developed and analyzed to obtain a more comprehensive estimates of life cycle assessment. This dataset was originally developed to compare the environmental impacts of structural materials selection for three common framing typologies.
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Nonresidential and mid- to high-rise multifamily residential structures in the United States currently use little wood per unit floor area installed, because earlier building codes lacked provisions for structural wood use in those types of buildings. However, revisions to the International Building Code allow for increased wood use in the form of mass timber, as structural and fire safety concerns have been addressed through new science-based design standards and through newly specified construction materials and measures. This study used multiple models to describe alternative futures for new construction, mass timber adoption rates, and the associated carbon benefits in higher than three-story buildings in the United States. The use of mass timber, in place of traditional constructions (i.e., structures dominated by concrete and steel), in projected new higher than three-story buildings was shown to provide combined carbon benefits (i.e., global warming mitigation benefits), including avoided embodied carbon emissions due to the substitution of non-wood alternatives and additional biogenic carbon storage in mass timber materials, of between 9.9 and 16.5 million t CO2e/yr spanning 50 years, 2020 to 2070. These carbon benefits equate to 12% to 20% of the total U.S. harvested wood products carbon storage for 2020. Future research is needed to understand how greater mass timber adoption leads to changes in forest product markets, land use, and total forest sector carbon.
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Carbono , Conservação dos Recursos Naturais , Estados Unidos , Florestas , Madeira , Materiais de ConstruçãoRESUMO
On September 2, 2022, the Food and Drug Administration (FDA) approved durvalumab in combination with cisplatin and gemcitabine, for the treatment of patients with unresectable or metastatic biliary tract cancers (BTC). On October 31, 2023, the FDA approved pembrolizumab in combination with cisplatin and gemcitabine for the same indication. Approvals were based on two randomized, multiregional, placebo-controlled trials that randomly allocated patients to receive durvalumab (TOPAZ-1) or pembrolizumab (KEYNOTE-966) in combination with chemotherapy or placebo in combination with chemotherapy. Overall survival (OS) was the primary endpoint in both studies. In both studies, a statistically significant and clinically meaningful improvement in OS was demonstrated. In the TOPAZ-1 trial, the median OS of patients receiving durvalumab was 12.8 months [95% confidence interval (CI), 11.1-14.0] and 11.5 months (95% CI, 10.1-12.5) in patients receiving placebo [hazard ratio (HR), 0.80 (95% CI, 0.66-0.97)]. In the KEYNOTE-966 trial, the median OS of patients receiving pembrolizumab was 12.7 months (95% CI, 11.5-13.6) and 10.9 months (95% CI, 9.9-11.6) in patients receiving placebo [HR, 0.83 (95% CI, 0.72-0.95)]. The addition of checkpoint inhibitors to standard of care chemotherapy for this indication did not reveal any new adverse event signals, and the safety profile was generally consistent with the known clinical experience with durvalumab, pembrolizumab, and the backbone chemotherapy regimen. The approvals of durvalumab and pembrolizumab in combination with standard of care cisplatin and gemcitabine for the treatment of unresectable or metastatic BTC add two new therapeutic options for these patients.
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Anticorpos Monoclonais Humanizados , Anticorpos Monoclonais , Protocolos de Quimioterapia Combinada Antineoplásica , Neoplasias do Sistema Biliar , Aprovação de Drogas , Inibidores de Checkpoint Imunológico , United States Food and Drug Administration , Humanos , Anticorpos Monoclonais Humanizados/uso terapêutico , Anticorpos Monoclonais Humanizados/efeitos adversos , Anticorpos Monoclonais Humanizados/administração & dosagem , Anticorpos Monoclonais/uso terapêutico , Anticorpos Monoclonais/administração & dosagem , Anticorpos Monoclonais/efeitos adversos , Estados Unidos , Neoplasias do Sistema Biliar/tratamento farmacológico , Neoplasias do Sistema Biliar/patologia , Inibidores de Checkpoint Imunológico/uso terapêutico , Inibidores de Checkpoint Imunológico/efeitos adversos , Inibidores de Checkpoint Imunológico/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Masculino , Feminino , Idoso , Pessoa de Meia-Idade , Ensaios Clínicos Controlados Aleatórios como Assunto , Gencitabina , AdultoRESUMO
The present experiment was conducted to evaluate the metribuzin-induced stress response in Vigna radiata and to explore the ameliorative role of exogenous application of plant growth regulators (PGRs) against metribuzin toxicity by assessing important biochemical and yield parameters. Prior to the field experiment, dose standardization experiments were performed, and EC50 was calculated for metribuzin. On day 21, field grown V. radiata plants were treated with graded concentrations of metribuzin (0-1000 mg [Formula: see text]). Plants treated with 600 mg [Formula: see text] (EC50) and 1000 mg [Formula: see text] (highest dose) of metribuzin were co-treated individually and simultaneously with gibberellic acid-3 (GA), indole-3 acetic acid (IAA), and salicylic acid (SA). After 7 days of treatment, leaf tissues were analyzed for biochemical parameters, whereas those related to yield were recorded during harvest. The result of this study indicated that metribuzin treatment to V. radiata resulted in increase in lipid peroxidation and reduce chlorophyll and carotenoid contents as well as yield parameters. However, metribuzin-treated plants induced proline accumulation and activity of antioxidant enzymes. Exogenous application of GA, IAA, and SA significantly reduced lipid peroxidation and increased contents of photosynthetic pigments, proline, and antioxidant enzymes thereby increasing yield parameters. It was observed that during metribuzin stress, SA exhibited a better ameliorative response out of the three exogenously applied PGRs, while the combined use of all PGRs exhibited much improved ameliorative response on biochemical and yield parameters of plants.
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Reguladores de Crescimento de Plantas , Vigna , Reguladores de Crescimento de Plantas/farmacologia , Antioxidantes , ProlinaRESUMO
Waste collection in developing nations faces multi-fold challenges, such as resource constraints and real-time changes in waste values, while finding the optimal routes. This paper attempts to address these challenges by modeling real-time waste values in smart bins and Collection Vehicles (CV). Further, waste value prioritized routes for coordinated CV, during various time intervals are modeled in a multi-agent environment for finding good routes. The CV, as agents, implement the formulated linear program to maximize the collected waste while minimizing the distance to the central depot. The city of Chandigarh, India, was divided into regions and the model was implemented to achieve significantly better performance in terms of waste collected in less distance and total bins covered when compared to the existing scenario. The stakeholders can use the outcomes to effectively plan the resources for better collection practices, which will have a positive impact on the environment.
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BACKGROUND: Liposuction, the most common body sculpting surgical procedure known today is associated with the risk of numerous complications. A safer and more noninvasive approach involves the use of high-intensity focused ultrasonography (HIFU) lasers, which work by selectively damaging fat tissue through apoptosis or necrosis induction of fat cells. The authors' systematic review was designed to identify the effectiveness of HIFU for nonsurgical facial and body contouring. METHODS: An exhaustive literature search was conducted of the PubMed/MEDLINE, Cochrane Central, Scopus, and EBSCO electronic databases for the period from November of 2005 to July of 2020. The full text of selected articles was reviewed for possible study inclusion, and articles fulfilling the inclusion criteria were recruited. Characteristics of the included studies were noted, and outcomes were assessed. Assessment of quality and risk of bias was performed for all the studies using the RevMan tool and the methodological index for nonrandomized studies. RESULTS: The initial search revealed a total of 4584 citations, of which only 11 were included in the present review: nine used HIFU for recontouring of the abdomen and only two used HIFU over the face and neck. Studies evaluated either the efficacy of HIFU or the safety of its use. The average total energy ranged from 140 to 248 J/cm 2 for the abdominal region and 0.3 to 1.2 J/cm 2 for the face and neck. The focal depth ranged from 1.1 to 1.8 cm. All the studies showed promising results with the use of HIFU. CONCLUSION: HIFU therapy is safe, effective, and minimally invasive, with predictable results when used for body and facial recontouring.
Assuntos
Contorno Corporal , Técnicas Cosméticas , Tratamento por Ondas de Choque Extracorpóreas , Ablação por Ultrassom Focalizado de Alta Intensidade , Humanos , Ablação por Ultrassom Focalizado de Alta Intensidade/métodos , Estudos Prospectivos , UltrassonografiaRESUMO
BACKGROUND: Since the outbreak of the pandemic, the release of the COVID (Corona Virus Disease)-19 vaccine was highly anticipated. Nevertheless, vaccine availability does not symbolize the end of pandemic due to ongoing vaccine hesitancy and anti-vaccination movements. The objective of this study is to evaluate COVID-19 vaccine acceptance among pregnant and lactating individuals in Maharashtra state, India. MATERIALS AND METHODS: A descriptive cross-sectional study was conducted via a hybrid approach using various digital portals such as Whatsapp, telegram, and physical distribution to those who did not have access to smartphone devices. A probability proportional sampling strategy was deployed. A pre-validated structured self-administered questionnaire tool designed by Freeman et al. 2020 (Oxford COVID-19 vaccine hesitancy scale) was used, which consisted of seven close-ended targeted and focused questions. Analysis of several survey items and vaccine acceptance was conducted using the Chi-square test. RESULTS: Analysis revealed that 58% of individuals were willing to take vaccines after government approval and 26% of individuals showed hesitancy toward vaccination. When compared, lactating individuals showed less vaccine hesitancy (22%) than pregnant individuals (27%). The maximum vaccine hesitancy was observed in the third trimester of pregnancy (29.5%). CONCLUSIONS: Trust in vaccines is a crucial factor and is dependent on the ability of the government in promoting vaccines through effective communication; this can be one of the reasons for the high level of acceptance and awareness toward COVID-19 vaccination in this study.