Purpose We investigated the effect on outcome of measurable or minimal residual disease (MRD) status after each induction course to evaluate the extent of its predictive value for acute myeloid ...leukemia (AML) risk groups, including NPM1 wild-type (wt) standard risk, when incorporated with other induction response criteria. Methods As part of the NCRI AML17 trial, 2,450 younger adult patients with AML or high-risk myelodysplastic syndrome had prospective multiparameter flow cytometric MRD (MFC-MRD) assessment. After course 1 (C1), responses were categorized as resistant disease (RD), partial remission (PR), and complete remission (CR) or complete remission with absolute neutrophil count < 1,000/µL or thrombocytopenia < 100,000/μL (CRi) by clinicians, with CR/CRi subdivided by MFC-MRD assay into MRD+ and MRD-. Patients without high-risk factors, including Flt3 internal tandem duplication wt/- NPM1-wt subgroup, received a second daunorubicin/cytosine arabinoside induction; course 2 (C2) was intensified for patients with high-risk factors. Results Survival outcomes from PR and MRD+ responses after C1 were similar, particularly for good- to standard-risk subgroups (5-year overall survival OS, 27% RD v 46% PR v 51% MRD+ v 70% MRD-; P < .001). Adjusted analyses confirmed significant OS differences between C1 RD versus PR/MRD+ but not PR versus MRD+. CRi after C1 reduced OS in MRD+ (19% CRi v 45% CR; P = .001) patients, with a smaller effect after C2. The prognostic effect of C2 MFC-MRD status (relapse: hazard ratio HR, 1.88 95% CI, 1.50 to 2.36, P < .001; survival: HR, 1.77 95% CI, 1.41 to 2.22, P < .001) remained significant when adjusting for C1 response. MRD positivity appeared less discriminatory in poor-risk patients by stratified analyses. For the NPM1-wt standard-risk subgroup, C2 MRD+ was significantly associated with poorer outcomes (OS, 33% v 63% MRD-, P = .003; relapse incidence, 89% when MRD+ ≥ 0.1%); transplant benefit was more apparent in patients with MRD+ (HR, 0.72; 95% CI, 0.31 to 1.69) than those with MRD- (HR, 1.68 95% CI, 0.75 to 3.85; P = .16 for interaction). Conclusion MFC-MRD can improve outcome stratification by extending the definition of partial response after first induction and may help predict NPM1-wt standard-risk patients with poor outcome who benefit from transplant in the first CR.
IMPORTANCE: Despite guideline recommendations, many patients discontinue P2Y12 inhibitor therapy earlier than the recommended 1 year after myocardial infarction (MI), and higher-potency P2Y12 ...inhibitors are underutilized. Cost is frequently cited as an explanation for both of these observations. OBJECTIVE: To determine whether removing co-payment barriers increases P2Y12 inhibitor persistence and lowers risk of major adverse cardiovascular events (MACE). DESIGN, SETTING, AND PARTICIPANTS: Cluster randomized clinical trial among 301 hospitals enrolling adult patients with acute MI (June 5, 2015, through September 30, 2016); patients were followed up for 1 year after discharge (final date of follow-up was October 23, 2017), with blinded adjudication of MACE; choice of P2Y12 inhibitor was per clinician discretion. INTERVENTIONS: Hospitals randomized to the intervention (n = 131 6436 patients) provided patients with co-payment vouchers for clopidogrel or ticagrelor for 1 year (median voucher value for a 30-day supply, $137 25th-75th percentile, $20-$339). Hospitals randomized to usual care (n = 156 4565 patients) did not provide study vouchers. MAIN OUTCOMES AND MEASURES: Independent coprimary outcomes were patient-reported persistence with P2Y12 inhibitor (defined as continued treatment without gap in use ≥30 days) and MACE (death, recurrent MI, or stroke) at 1 year among patients discharged with a prescription for clopidogrel or ticagrelor. RESULTS: Among 11 001 enrolled patients (median age, 62 years; 3459 31% women), 10 102 patients were discharged with prescriptions for clopidogrel or ticagrelor (clopidogrel prescribed to 2317 36.0% in the intervention group and 2497 54.7% in the usual care group), 4393 of 6135 patients (72%) in the intervention group used the voucher, and follow-up data at 1 year were available for 10 802 patients (98.2%). Patient-reported persistence with P2Y12 inhibitors at 1 year was higher in the intervention group than in the control group (unadjusted rates, 5340/6135 87.0% vs 3324/3967 83.8%, respectively; P < .001; adjusted difference, 2.3% 95% CI, 0.4% to 4.1%; adjusted odds ratio, 1.19 95% CI, 1.02 to 1.40). There was no significant difference in MACE at 1 year between intervention and usual care groups (unadjusted cumulative incidence, 10.2% vs 10.6%; P = .65; adjusted difference, 0.66% 95% CI, −0.73% to 2.06%; adjusted hazard ratio, 1.07 95% CI, 0.93 to 1.25). CONCLUSIONS AND RELEVANCE: Among patients with MI, provision of vouchers to offset medication co-payments for P2Y12 inhibitors, compared with no vouchers, resulted in a 3.3% absolute increase in patient-reported persistence with P2Y12 inhibitors and no significant reduction in 1-year MACE outcomes. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02406677
As the world population and its dependency on energy is growing exponentially day by day, the existing energy generating resources are not enough to fulfill their needs. In the conventional grid ...system, most of the generated energy is wasted because of improper demand side management (DSM). This leads to a difficulty in keeping the equilibrium between the user need and electric power production. To overcome these difficulties, smart grid (SG) is introduced, which is composed of the integration of two-way communication between the user and utility. To utilize the existing energy resources in a better way, SG is the best option since a large portion of the generated energy is consumed by the educational institutes. Such institutes also need un-interrupted power supply at the lowest cost. Therefore, in this paper, we have taken a university campus load. We have not only applied two bio-inspired heuristic algorithms for energy scheduling—namely, the Firefly Algorithm (FA) and the Lion Algorithm (LA)—but also proposed a hybrid version, FLA, for more optimal results. Our main objectives are a reduction in both, that is, the cost of energy and the waiting time of consumers or end users. For this purpose, in our proposed model, we have divided all appliances into two categories—shiftable appliances and non-shiftable appliances. Shiftable appliances are feasible to be used in any of the time slots and can be planned according to the day-ahead pricing signal (DAP), provided by the utility, while non-shiftable appliances can be used for a specified duration and cannot be planned with the respective DAP signal. So, we have scheduled shiftable appliances only. We have also used renewable energy sources (RES) for achieving maximum end user benefits. The simulation results show that our proposed hybrid algorithm, FLA, has reduced the cost excellently. We have also taken into consideration the consumers’ waiting times, due to scheduling of appliances.
Recent earthquakes in Pakistan demonstrated that the region is highly seismic. Masonry buildings constructed with stones, concrete blocks, and fired-clay bricks and concrete buildings were damaged ...during the 8 October 2005 Kashmir earthquake. This paper presents the seismic behavior of reinforced concrete and masonry buildings in northern part of the North-West Frontier Province (NWFP) and Kashmir during the earthquake. Most of the buildings were observed to be nonengineered or semi-engineered. The paper presents an overview of the 1937 Quetta building code and the 1986 and 2007 building codes of Pakistan. Lessons learned during the earthquake are also presented.
During the COVID-19 outbreak, educational institutions were closed, and students worldwide were confined to their homes. In an educational environment, students depend on collaborative learning (CL) ...to improve their learning performance. This study aimed to increase the understanding of social media adoption among students during the COVID-19 pandemic for the purpose of CL. Social media provides a learning platform that enables students to easily communicate with their peers and subject specialists, and is conducive to students' CL. This study addresses the key concept of CL during the COVID-19 pandemic by assessing social media use among students in higher education. The relationship between social media use and students' performance is crucial to understanding the role of social media during a pandemic. This study is based on constructivism theory and the technology acceptance model. Structural equation modeling was used to analyze the conceptual model using SmartPLS. The research findings indicate that social media plays an important role during the pandemic because it provides opportunities for students to enhance CL under the aforementioned situations. This study makes noteworthy theoretical and practical contributions.
With the advancement in tissue engineering, researchers are working hard on new techniques to fabricate more advanced scaffolds from biocompatible polymers with enhanced porosity, appropriate ...mechanical strength, diverse shapes and sizes for potential applications in biomedical field in general and tissue engineering in particular. These techniques include electrospinning, solution blow spinning, centrifugal spinning, particulate leaching (salt leaching), freeze-drying, lithography, self-assembly, phase separation, gas foaming, melt molding, 3-D printing, fiber mesh and solvent casting. In this article we have summarized the scaffold’s fabrication techniques from biocompatible polymers that are reported so far, the recent advances in these techniques, characterization of the physicochemical properties of scaffolds and their potential applications in the biomedical field and tissue engineering. The article will help both newcomers and experts working in the biomedical implant fabrication to not only find their desired information in one document but also understand the fabrication techniques and the parameters that control the success of biocompatible polymeric scaffolds. Furthermore, a static analysis of the work published in all forms on the most innovative techniques is also presented. The data is taken from Scopus, restricting the search to biomedical fields and tissue engineering.
Moisture stress in rainfed areas has significant adverse impacts on plant growth and yield. Plant growth promoting rhizobacteria (PGPR) plays an important role in the revegetation and rehabilitation ...of rainfed areas by modulating plant growth and metabolism and improving the fertility status of the rhizosphere soils. The current study explored the positive role of PGPR and salicylic acid (SA) on the health of the rhizosphere soil and plants grown under rainfed conditions. Maize seeds of two different varieties, i.e., SWL-2002 (drought tolerant) and CZP-2001 (drought sensitive), were soaked for 4 h prior to sowing in 24-h old culture of
strain P1 (accession no. MF616408) and
strain P2 (accession no. MF616406). The foliar spray of SA (150 mg/L) was applied on 28-days old seedlings. The combined treatment of the consortium of PGPR and SA not only alleviated the adverse effects of low moisture stress of soil in rainfed area but also resulted in significant accumulation of leaf chlorophyll content (40% and 24%), chlorophyll fluorescence (52% and 34%) and carotenoids (57% and 36%) in the shoot of both the varieties. The PGPR inoculation significantly reduced lipid peroxidation (33% and 23%) and decreased the proline content and antioxidant enzymes activities (32% and 38%) as compared to plants grown in rainfed soil. Significant increases (>52%) were noted in the contents of Ca, Mg, K Cu, Co, Fe and Zn in the shoots of plants and rhizosphere of maize inoculated with the PGPR consortium. The soil organic matter, total nitrogen and C/N ratio were increased (42%), concomitant with the decrease in the bulk density of the rhizosphere. The PGPR consortium, SA and their combined treatment significantly enhanced the IAA (73%) and GA (70%) contents but decreased (55%) the ABA content of shoot. The rhizosphere of plants treated with PGPR, SA and consortium showed a maximum accumulation (>50%) of IAA, GA and ABA contents, the sensitive variety had much higher ABA content than the tolerant variety. It is inferred from the results that rhizosphere soil of treated plants enriched with nutrients content, organic matter and greater concentration of growth promoting phytohormones, as well as stress hormone ABA, which has better potential for seed germination and establishment of seedlings for succeeding crops.
Wandering spleen and gastric volvulus are two of the rarely encountered conditions occurring together with or without other congenital and acquired defects. These potentially fatal conditions ...originate from a shared cause, i.e. the defect of intraperitoneal ligaments resulting in a failure to withhold these organs at their anatomical position and alignment. This can come to attention in both childhood and/or adulthood, and the diagnosis calls for a high degree of suspicion and a failure to diagnose can culminate in death of both the organs, i.e. the spleen and stomach. We are presenting the case of a 20-year-old girl who underwent an emergency laparotomy for gastric volvulus and wandering spleen.
The preceding climate change demonstrates overwintering of pathogens that lead to increased incidence of insects and pest attack. Integration of ecological and physiological/molecular approaches are ...imperative to encounter pathogen attack in order to enhance crop yield. The present study aimed to evaluate the effects of two plant growth promoting rhizobacteria (Bacillus endophyticus and Pseudomonas aeruginosa) on the plant physiology and production of the secondary metabolites in tomato plants infested with Spodoptera litura (Fabricius) (Lepidoptera: Noctuidae). The surface sterilized seeds of tomato were inoculated with plant growth promoting rhizobacteria (PGPR) for 3–4 h prior to sowing. Tomato leaves at 6 to 7 branching stage were infested with S. litura at the larval stage of 2nd instar. Identification of secondary metabolites and phytohormones were made from tomato leaves using thin-layer chromatography (TLC) and high performance liquid chromatography (HPLC) and fourier-transform infrared spectroscopy (FTIR). Infestation with S. litura significantly decreased plant growth and yield. The PGPR inoculations alleviated the adverse effects of insect infestation on plant growth and fruit yield. An increased level of protein, proline and sugar contents and enhanced activity of superoxide dismutase (SOD) was noticed in infected tomato plants associated with PGPR. Moreover, p-kaempferol, rutin, caffeic acid, p-coumaric acid and flavonoid glycoside were also detected in PGPR inoculated infested plants. The FTIR spectra of the infected leaf samples pre-treated with PGPR revealed the presence of aldehyde. Additionally, significant amounts of indole-3-acetic acid (IAA), salicylic acid (SA) and abscisic acid (ABA) were detected in the leaf samples. From the present results, we conclude that PGPR can promote growth and yield of tomatoes under attack and help the host plant to combat infestation via modulation in IAA, SA, ABA and other secondary metabolites.
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