Simultaneous Escalation Research Articles

Effect of Mn-HA on ARGs and MRGs in nitrogen-culturing sludge

The simultaneous escalation in ARGs (antibiotic resistance genes) and MRGs (metal resistance genes) further complicates the intricate network of factors contributing to the proliferation of microbial resistance. Manganese, which has been reported to affect the resistance of bacteria to antibiotics and metals, plays a vital role in microbial nitrogen metabolism. Moreover, nitrifying and denitrifying populations are potential hosts for ARGs. In this study, manganese was introduced in its prevalent organic chelated form in the environment (Manganese humus chelates, Mn-HA) to a N metabolism sludge to explore the effect of manganese on MRGs and ARGs dissemination. Metagenomics results revealed that manganese availability enhances nitrogen metabolism, while a decrease in ARGs was noted which may be attributed to the inhibition of horizontal gene transfer (HGT), reflected in the reduced integrase -encoded gene int. Population analysis revealed that nitrifier and denitrifier genus harbor MRGs and ARGs, indicating that nitrifier and denitrifier are hosts of MRGs and ARGs. This raises the question of whether the prevalence of ARGs is always increased in metal-contained environments.

The Venezuelan Humanitarian Crisis, Out-Migration, and Household Change Among Venezuelans in Venezuela and Abroad

International migration is increasingly characterized by the need to evade threats to survival. Nevertheless, demographic understandings of how families—rather than individuals alone—decide to migrate or separate in response to threats remain limited. Focusing on the recent humanitarian crisis in Venezuela, we analyze 2012–2016 data on Venezuelans in Venezuela and 2018–2020 data on UNHCR (United Nations High Commissioner for Refugees)-registered Venezuelans in nine receiving countries to illuminate the evolution of threats Venezuelans sought to evade, how threat evasion transformed households away from previous norms, the selection of migrants into different receiving countries and household structures, and demographic disparities in migrants’ odds of reporting changes to their household because of specific migration-related processes (e.g., leaving someone in Venezuela, leaving someone in another country). Results underscore a simultaneous escalation of economic, safety, and political concerns that informed Venezuelans’ increasing intentions to out-migrate. Where Venezuelans migrated and who ended up in their households abroad varied by demographic background and migration experiences. Among UNHCR-registered Venezuelans, 43% left family members in Venezuela, and more than 10% left or were left behind by members in another country. Such household separations, however, were unevenly distributed across factors such as age, gender, and country of reception.

Effect of Nitrogen on Growth and Optical Properties of Single-Crystal Diamond Synthesized by Chemical Vapor Deposition.

Concurrently achieving high growth rate and high quality in single-crystal diamonds (SCDs) is significantly challenging. The growth rate of SCDs synthesized by microwave plasma chemical vapor deposition (MPCVD) was enhanced by introducing N2 into the typical CH4-H2 gas mixtures. The impact of nitrogen vacancy (NV) center concentration on growth rate, surface morphology, and lattice binding structure was investigated. The SCDs were characterized through Raman spectroscopy, photoluminescence (PL) spectroscopy, and X-ray photoelectron spectroscopy. It was found that the saturation growth rate was increased up to 45 μm/h by incorporating 0.8-1.2% N2 into the gas atmosphere, which is 4.5 times higher than the case without nitrogen addition. Nitrogen addition altered the growth mode from step-flow to bidimensional nucleation, leading to clustered steps and a rough surface morphology, followed by macroscopically pyramidal hillock formation. The elevation of nitrogen content results in a simultaneous escalation of internal stress and defects. XPS analysis confirmed chemical bonding between nitrogen and carbon, as well as non-diamond carbon phase formation at 0.8% of nitrogen doping. Furthermore, the emission intensity of NV-related defects from PL spectra changed synchronously with N2 concentrations (0-1.5%) during diamond growth, indicating that the formation of NV centers activated the diamond lattice and facilitated nitrogen incorporation into it, thereby accelerating chemical reaction rates for achieving high-growth-rate SCDs.

Trends in ferritin measurements in children and adolescents: AFinnish 9-year observational study.

AimA lack of stored iron, indicated by low serum ferritin, has been associated with various clinical symptoms. There are no longitudinal data on the frequency of ferritin measurements in children and adolescents.MethodsA total of 2834 children aged <18 years with serum ferritin and other anaemia‐related blood parameters taken during an outpatient visit between 2012 and 2019 were investigated. Patients with acute infections were excluded. Nationwide temporal and regional variations and correlations with public information searches through Google were analysed.ResultsA significant increase in the frequency of ferritin measurements was seen starting in 2018, with a 47‐fold rise in 2019 compared to 2012. A simultaneous escalation in Google Search activity was seen. Deficiency of stored iron was relatively common: 21.6% of children with normal haemoglobin and 14.9% of non‐anaemic children with normal red cell indices exhibited ferritin levels below 15 μg/L.ConclusionFerritin measurement has increased greatly among children and adolescents. Our results suggest that public interest and popular trends can significantly influence health care practices. This calls for further investigation into the causes and consequences of such a phenomenon. Prospective randomised intervention studies are needed to evaluate the utility of iron supplementation in patients with low iron storage levels.

Generation of force and torque during joining of AZ91C plates by FSW under distinctive tool tilt angle and their impact on mechanical strength and micro-structure

Joint characteristics of friction stir welded AZ91C Mg alloy flat plates in terms of mechanical strength and micro-structural attributed have been investigated by varying the tool tilt angles for two distinctive tapered tool pin geometries without and with threaded structures (TP and TPWT). Spindle torque and distinctive forces acting longitudinally, vertically (termed as X and Y – force respectively) generated at the interface of the tool and flat plates were measured and analyzed to understand the impact of employed tool tilt angles. It was revealed that the spindle torque and forces relevant to FSW escalates with the increase in tool tilt angle. Spindle torque (15.1 Nm) and Y–force (6.4 kN) generated by TPWT are higher than that of TP tool (11 Nm and 2 kN), whereas X – force associated with TPWT (0.74 kN) tool was found to be lower when compared to that of the TP tool (0.98 kN). Inconsistencies in forces have escalated with a simultaneous escalation in the tool tilt angle for the TP tool and the TPWT tool has exhibited a reversed behavior. Enhanced flow of plasticized metal induced by tool pin geometry with threaded structures have contributed to the formations of onion ring type features and these structures cannot be visualized in the joints fabricated by the TP tool. The largest value of tensile strength of 227 MPa was exhibited by joint fabricated at 0° tool tilt angle using TPWT tool.

Software modernization to embrace quantum technology

Quantum Computing is becoming an increasingly mature area, with a simultaneous escalation of investment in many sectors. Quantum technology will revolutionize all the engineering fields. For example, companies will need to add quantum computing progressively to some or all of their daily operations. It is clear that all existing classical information systems cannot be done away with. Rather than that occurring, it is expected that some quantum algorithms will be added, so that they can work alongside classical information systems. There has been no systematic solution offered to deal with this challenge so far. This research proposes a software modernization approach (model-driven reengineering) designed to restructure classical systems to work in conjunction with quantum systems, thereby providing target environments that combine both of these computational paradigms. The approach proposed is systematic, and based on existing software engineering standards like the Knowledge Discovery Metamodel and the Unified Modelling Language. It could therefore be applied in industry in a way that complies with the existing software evolution processes. The independence of this proposal with respect to quantum programming environments is also guaranteed, making its application feasible in the changing environment in today's quantum industry. The main implication of this approach is technical, but also economic, since it enables the reuse of the knowledge embedded in legacy systems, while at the same time the new quantum-based projects are speeded up.

A phase I study of milademetan in combination with quizartinib in patients (pts) with newly diagnosed (ND) or relapsed/refractory (R/R) FLT3-ITD acute myeloid leukemia (AML).

TPS7067 Background: Fms -like tyrosine kinase 3 internal tandem duplication ( FLT3-ITD) mutations occur in ≈ 25% of pts with AML and are associated with poor prognosis. Quizartinib is a highly potent, selective, next-generation type II FLT3 inhibitor. In the phase 3 QuANTUM-R trial, quizartinib prolonged overall survival vs salvage chemotherapy in pts with R/R FLT3-ITD AML. MDM2 downregulates the p53 tumor suppressor and is upregulated in pts with AML. Targeting MDM2 may restore p53 activity in pts with wild-type p53 AML. Milademetan, a novel and specific MDM2 inhibitor, showed activity in an ongoing phase 1 trial in pts with AML or myelodysplastic syndromes (MDS). Preclinical studies have shown that quizartinib plus milademetan may act synergistically to target FLT3-ITD and restore p53 activity in FLT3-ITD/ TP53 wild-type AML [Andreeff et al. ASH 2018, abstract 2720]. Methods: This open-label phase 1 study (NCT03552029) has 2 parts: dose escalation (part 1) followed by dose expansion (part 2), with 2 planned cohorts. Key inclusion criteria include FLT3-ITD AML (primary or secondary to MDS) and adequate renal, hepatic, and clotting functions. Key exclusion criteria include acute promyelocytic leukemia, prior treatment with a MDM2 inhibitor, QTcF interval &gt; 450 ms, significant cardiovascular disease, and unresolved toxicities from prior therapies. Dose escalation and expansion cohort 1 includes R/R pts. Expansion cohort 2 includes ND pts unfit for intensive chemotherapy. During dose escalation, quizartinib will be administered once daily in 28-day cycles, with 3 proposed levels (30, 40, and 60 mg). Milademetan will be administered on days 1-14 of each 28-day cycle, with 3 proposed levels (90, 120, and 160 mg). The quizartinib dose will be escalated first, followed by the milademetan dose with no simultaneous escalation, guided by modified continual reassessment with overdose control. Primary objectives are safety and tolerability, optimum dosing schedule, maximum tolerated dose, recommended dosing for the expansion cohort, and phase 2 dosing. Secondary objectives are pharmacokinetics and preliminary efficacy. This study is recruiting. Clinical trial information: NCT03552029.

Potential Contamination Sources on Fresh Produce Associated with Food Safety

The health benefits associated with consumption of fresh produce have been clearly demonstrated and encouraged by international nutrition and health authorities. However, since fresh produce is usually minimally processed, increased consumption of fresh fruits and vegetables has also led to a simultaneous escalation of foodborne illness cases. According to the report by the World Health Organization (WHO), 1 in 10 people suffer from foodborne diseases and 420,000 die every year globally. In comparison to other processed foods, fresh produce can be easily contaminated by various routes at different points in the supply chain from farm to fork. This review is focused on the identification and characterization of possible sources of foodborne illnesses from chemical, biological, and physical hazards and the applicable methodologies to detect potential contaminants. Agro-chemicals (pesticides, fungicides and herbicides), natural toxins (mycotoxins and plant toxins), and heavy metals (mercury and cadmium) are the main sources of chemical hazards, which can be detected by several methods including chromatography and nano-techniques based on nanostructured materials such as noble metal nanoparticles (NMPs), quantum dots (QDs) and magnetic nanoparticles or nanotube. However, the diversity of chemical structures complicates the establishment of one standard method to differentiate the variety of chemical compounds. In addition, fresh fruits and vegetables contain high nutrient contents and moisture, which promote the growth of unwanted microorganisms including bacterial pathogens (Salmonella, E. coli O157: H7, Shigella, Listeria monocytogenes, and Bacillus cereus) and non-bacterial pathogens (norovirus and parasites). In order to detect specific pathogens in fresh produce, methods based on molecular biology such as PCR and immunology are commonly used. Finally, physical hazards including contamination by glass, metal, and gravel in food can cause serious injuries to customers. In order to decrease physical hazards, vision systems such as X-ray inspection have been adopted to detect physical contaminants in food, while exceptional handling skills by food production employees are required to prevent additional contamination.

The Plant Simulator as viable means to prevent and manage risk through competencies management: Experiment results

Making decisions and managing competences in complex systems is a challenging task to accomplish. Specifically, the process industry is known for its complexity and sensitivity to critical procedures. Recent disasters like the “Deepwater Horizon” (2010, 11 fatalities), BP Texas City (2005, 15 fatalities), and AZF Toulouse (2001, 29 fatalities), clearly showed the risk to which we are all exposed. The increasing complexity of processes, due to the simultaneous escalation of automation, optimisation and intensification processes (followed to face globalisation challenges), are moving the attention to the management of abnormal situations, which are even more complex in nature and frequent. This increasing complexity, coupled with the fact that abnormal situations may lead to irreversible losses, is imposing the adoption of adequate approaches and tools that allow for better learning and properly managing abnormal situations. The paper presents a simulation-enabled, experiment-based approach that can be used to prevent and manage risk through competencies management. More specifically, the paper presents the results of the first experiment campaign performed in a Plant Simulator (PS), the first known in the process industry domain, and shows the efficacy of using Immersive Virtual Environments (IVE) both to make decisions and to train teams (not just single operators).The experiment results presented in the paper show the effectiveness of IVE to increase the competencies and train operators and managers. In addition, they explain how conveniently the data collected by means of the PS can be used for making daily decisions to better prevent and manage risks.

Nitrogen-induced surface area and conductivity modulation of carbon nanohorn and its function as an efficient metal-free oxygen reduction electrocatalyst for anion-exchange membrane fuel cells.

Nitrogen-doped carbon morphologies have been proven to be better alternatives to Pt in polymer-electrolyte membrane (PEM) fuel cells. However, efficient modulation of the active sites by the simultaneous escalation of the porosity and nitrogen doping, without affecting the intrinsic electrical conductivity, still remains to be solved. Here, a simple strategy is reported to solve this issue by treating single-walled carbon nanohorn (SWCNH) with urea at 800 °C. The resulting nitrogen-doped carbon nanohorn shows a high surface area of 1836 m2 g(-1) along with an increased electron conductivity, which are the pre-requisites of an electrocatalyst. The nitrogen-doped nanohorn annealed at 800 °C (N-800) also shows a high oxygen reduction activity (ORR). Because of the high weight percentage of pyridinic nitrogen coordination in N-800, the present catalyst shows a clear 4-electron reduction pathway at only 50 mV overpotential and 16 mV negative shift in the half-wave potential for ORR compared to Pt/C along with a high fuel selectivity and electrochemical stability. More importantly, a membrane electrode assembly (MEA) based on N-800 provides a maximum power density of 30 mW cm(-2) under anion-exchange membrane fuel cell (AEMFC) testing conditions. Thus, with its remarkable set of physical and electrochemical properties, this material has the potential to perform as an efficient Pt-free electrode for AEMFCs.

Simultaneous modulated accelerated radiation therapy for esophageal cancer: A feasibility study

To establish the feasibility of simultaneous modulated accelerated radiation therapy (SMART) in esophageal cancer (EC). Computed tomography (CT) datasets of 10 patients with upper or middle thoracic squamous cell EC undergoing chemoradiotherapy were used to generate SMART, conventionally-fractionated three-dimensional conformal radiotherapy (3DCRT) and intensity-modulated radiation therapy (cf-IMRT) plans, respectively. The gross target volume (GTV) of the esophagus, positive regional lymph nodes (LN), and suspected lymph nodes (LN ±) were contoured for each patient. The clinical target volume (CTV) was delineated with 2-cm longitudinal and 0.5- to 1.0-cm radial margins with respect to the GTV and with 0.5-cm uniform margins for LN and LN(±). For the SMART plans, there were two planning target volumes (PTVs): PTV66 = (GTV + LN) + 0.5 cm and PTV54 = CTV + 0.5 cm. For the 3DCRT and cf-IMRT plans, there was only a single PTV: PTV60 = CTV + 0.5 cm. The prescribed dose for the SMART plans was 66 Gy/30 F to PTV66 and 54 Gy/30 F to PTV54. The dose prescription to the PTV60 for both the 3DCRT and cf-IMRT plans was set to 60 Gy/30 F. All the plans were generated on the Eclipse 10.0 treatment planning system. Fulfillment of the dose criteria for the PTVs received the highest priority, followed by the spinal cord, heart, and lungs. The dose-volume histograms were compared. Clinically acceptable plans were achieved for all the SMART, cf-IMRT, and 3DCRT plans. Compared with the 3DCRT plans, the SMART plans increased the dose delivered to the primary tumor (66 Gy vs 60 Gy), with improved sparing of normal tissues in all patients. The Dmax of the spinal cord, V20 of the lungs, and Dmean and V50 of the heart for the SMART and 3DCRT plans were as follows: 38.5 ± 2.0 vs 44.7 ± 0.8 (P = 0.002), 17.1 ± 4.0 vs 25.8 ± 5.0 (P = 0.000), 14.4 ± 7.5 vs 21.4 ± 11.1 (P = 0.000), and 4.9 ± 3.4 vs 12.9 ± 7.6 (P = 0.000), respectively. In contrast to the cf-IMRT plans, the SMART plans permitted a simultaneous dose escalation (6 Gy) to the primary tumor while demonstrating a significant trend of a lower irradiation dose to all organs at risk except the spinal cord, for which no significant difference was found. SMART offers the potential for a 6 Gy simultaneous escalation in the irradiation dose delivered to the primary tumor of EC and improves the sparing of normal tissues.

Urgent Need to Orient Public Health Response to Rapid Nutrition Transition

India is currently undergoing a rapid transition on economic, demographic, epidemiologic, nutrition, and sociological fronts. There is evidence of a decline in undernutrition with a simultaneous escalation in overnutrition and associated non-communicable diseases (NCDs). However, the current concern and national policy response for tackling malnutrition in India is still primarily restricted to undernutrition diagnosed on the basis of body size (anthropometry). A complex range of interacting factors have been linked to the rising trend of overnutrition and associated NCDs from a global perspective. The burden of overnutrition and associated morbidities is rapidly escalating to alarming proportions, particularly in urban areas and high socio-economic status groups. The poor are not spared from this transition. It is predicted that a more rapid transition may occur amongst poor populations in future with higher economic development. The need of the hour is to launch an integrated public health response to the dual burden beginning from pregnancy and early life. This will obviously require careful deliberation of the strategy and interventions, and a multi-sectoral approach, especially involving the health, women and child development, nutrition, education, agriculture, food processing, trade, architecture, water supply and sanitation, community and non-governmental organizations.

Beyond the 3+3 method: expanded algorithms for dose- escalation in Phase I oncology trials of two agents

The number of published Phase I trials for determining a maximum tolerated combination of two agents is increasing, with a majority of those trials suffering from poor study design. A recent editorial proposed a 3+3+3 design, which takes the traditional 3+3 design used for one-agent dose-finding and adds an additional possible cohort of three patients. To investigate the utility and performance of the 3+3+3, and more generally, A+B+C algorithmic designs, in Phase I trials of two-agent combinations and to discuss the issues related to such designs. Operating characteristics for an A+B+C design can be computed exactly in the statistical software package R using publicly available functions created by the authors. Using those functions, six different A+B+C designs are compared in six different settings with respect to the dose-limiting toxicity rate of combinations that each design selects as the maximum tolerated combination, as well as the average total number of patients required by each design and the average number of patients assigned to each combination. Allowing for simultaneous escalation of doses of both agents does not increase patients' exposure to overly toxic combinations, yet increases the probability of identifying the maximum tolerated combination when it occurs at higher doses of either agent, than a design that forbids simultaneous escalation. Designs in which A ≤ 3 tend to target combinations with dose-limiting toxicity rates higher than designs in which A ≥ 4. The implicitly targeted dose-limiting toxicity rate of any given algorithmic design is not transparent, requiring computation of results under a variety of settings to help understand the operating characteristics of that design. Thus, the appropriate A+B+C design will vary from trial to trial. A+B+C designs also have 'short memory', as escalation decisions are based primarily on the most recent cohort of patients. Algorithmic A+B+C designs are potentially useful in the design of Phase I trials of combinations of two agents. However, a head-to-head comparison to model-based designs is needed to warrant their general use.

Just Food: Obesity Trends Demand System Strategies

Food and health are at the core of human existence and serve as common indicators of economic and social well-being. The simultaneous escalation in obesity rates and evidence of a food system marked by a lack of access and sustainability suggest the need for comprehensive systematic approaches to understanding, evaluating, and transforming both these complex and interrelated entities. This article reviews obesity trends and food system forces that may contribute to excessive caloric intake and food inequality. Given that obesity and food insecurity share many of the same etiologies, comprehensive evidence-based strategies designed to address shared causes may leverage the impact of shared solutions. The potential benefits of promoting healthy sustainable food systems to build healthy just communities are briefly explored to encourage more in-depth discussion.

Nanocrystalline silicon prepared at high growth rate using helium dilution

Growth and optimization of the nanocrystalline silicon (nc-Si: H) films have been studied by varying the electrical power applied to the helium diluted silane plasma in RF glow discharge. Wide optical gap and conducting intrinsic nanocrystalline silicon network of controlled crystalline volume fraction and oriented crystallographic lattice planes have been obtained at a reasonably high growth rate from helium diluted silane plasma, without using hydrogen. Improving crystallinity in the network comprising ∼ 10 nm Si-nanocrystallites and contributing optical gap widening, conductivity ascending and that obtained during simultaneous escalation of the deposition rate, promises significant technological impact.

A Human Cell-Based Assay to Evaluate the Effects of Alterations in the MLH1 Mismatch Repair Gene

We describe a new approach to investigate alterations in the human MLH1 mismatch repair (MMR) gene. This is based on complementation of the phenotype of a MLH1-defective subclone of the ovarian carcinoma A2780 cells by transfection of vectors encoding altered MLH1 proteins. Measurements of resistance (tolerance) to methylating agents, mutation rate at HPRT, microsatellite instability (MSI), and steady-state levels of DNA 8-oxoguanine were used to define the MMR status of transfected clones. The approach was validated by transfecting cDNA of wild-type (WT) MLH1, cDNAs bearing two previously identified polymorphisms (I219V and I219L) and two with confirmed hereditary nonpolyposis colorectal cancer (HNPCC) syndrome mutations (G224D and G67R). A low-level expression of two MLH1 polymorphisms partially reversed methylation tolerance and the mutator phenotype, including MSI. Higher levels of I219V resulted in full restoration of these properties to WT. Increased expression of I129L did not fully complement the MLH1 defect, because there was a simultaneous escalation in the level of oxidative DNA damage. The findings confirmed the important relationship between deficient MMR and increased levels of oxidative DNA damage. Mutations from Italian HNPCC families (G224D, G67R, N635S, and K618A) were all ineffective at reversing the phenotype of the MLH1-defective A2780 cells. One (K618A) was identified as a low penetrance mutation based on clinical and genetic observations.