Disparities in all-cause mortality with potentially inappropriate medication use: Analysis of the Reasons for Geographic and Racial Differences in Stroke study.

OBJECTIVES: Health disparities across different socioeconomic subgroups have been reported in previous studies. Mortality with potentially inappropriate medication (PIM) use may be subject to similar disparities. We aimed to assess the association between PIM use and all-cause mortality and the effect of disparity parameters (sex, race, income, education, and location of residence) on this relationship. METHODS: This longitudinal cohort study included 26,399 U.S. adults aged 45 years and older from the Reasons for Geographic and Racial Differences in Stroke (REGARDS) study, of which 13,475 participants were aged 65 years and older (recruited 2003-2007). PIM use and drug-drug interactions (DDIs) were identified through the 2015 Beers Criteria and a clinically significant DDIs list by the American Family Physicians, respectively. Cox regression was used to assess disparities in mortality with PIM use, iteratively adjusting for disparity parameters and other covariates. The full models included interaction terms between PIM use and other covariates. A similar method was used for the analyses of disparities in mortality with DDIs. RESULTS: Approximately 87% of older adults used at least 1 drug listed in the Beers Criteria, and 3.8% of all participants used 2 or more drugs with DDIs. In the adjusted analysis, an increased risk of mortality was observed among whites with PIM use (hazard ratio [HR] = 1.27 [95% CI 1.10-1.47]). The higher mortality rate was observed among blacks without PIM use (1.34 [1.09-1.65]). Lower income and education were independent predictors for higher mortality. CONCLUSION: Racial differences in all-cause mortality with PIM use were observed. Further research is needed to better understand the contributing factors of such disparities to develop appropriate interventions.

Design and Numerical Analysis of a Graphene-Coated SPR Biosensor for Rapid Detection of the Novel Coronavirus.

In this paper, a highly sensitive graphene-based multiple-layer (BK7/Au/PtSe2/Graphene) coated surface plasmon resonance (SPR) biosensor is proposed for the rapid detection of the novel Coronavirus (COVID-19). The proposed sensor was modeled on the basis of the total internal reflection (TIR) technique for real-time detection of ligand-analyte immobilization in the sensing region. The refractive index (RI) of the sensing region is changed due to the interaction of different concentrations of the ligand-analyte, thus impacting surface plasmon polaritons (SPPs) excitation of the multi-layer sensor interface. The performance of the proposed sensor was numerically investigated by using the transfer matrix method (TMM) and the finite-difference time-domain (FDTD) method. The proposed SPR biosensor provides fast and accurate early-stage diagnosis of the COVID-19 virus, which is crucial in limiting the spread of the pandemic. In addition, the performance of the proposed sensor was investigated numerically with different ligand-analytes: (i) the monoclonal antibodies (mAbs) as ligand and the COVID-19 virus spike receptor-binding domain (RBD) as analyte, (ii) the virus spike RBD as ligand and the virus anti-spike protein (IgM, IgG) as analyte and (iii) the specific probe as ligand and the COVID-19 virus single-standard ribonucleic acid (RNA) as analyte. After the investigation, the sensitivity of the proposed sensor was found to provide 183.33°/refractive index unit (RIU) in SPR angle (θSPR) and 833.33THz/RIU in SPR frequency (SPRF) for detection of the COVID-19 virus spike RBD; the sensitivity obtained 153.85°/RIU in SPR angle and 726.50THz/RIU in SPRF for detection of the anti-spike protein, and finally, the sensitivity obtained 140.35°/RIU in SPR angle and 500THz/RIU in SPRF for detection of viral RNA. It was observed that whole virus spike RBD detection sensitivity is higher than that of the other two detection processes. Highly sensitive two-dimensional (2D) materials were used to achieve significant enhancement in the Goos-Hänchen (GH) shift detection sensitivity and plasmonic properties of the conventional SPR sensor. The proposed sensor successfully senses the COVID-19 virus and offers additional (1 + 0.55) × L times sensitivity owing to the added graphene layers. Besides, the performance of the proposed sensor was analyzed based on detection accuracy (DA), the figure of merit (FOM), signal-noise ratio (SNR), and quality factor (QF). Based on its performance analysis, it is expected that the proposed sensor may reduce lengthy procedures, false positive results, and clinical costs, compared to traditional sensors. The performance of the proposed sensor model was checked using the TMM algorithm and validated by the FDTD technique.

Comparisons of potentially inappropriate medications and outcomes in older adults admitted to intensive care unit: A retrospective cohort study.

OBJECTIVES: To comparatively assess potentially inappropriate medication (PIM) use and subsequent impact on clinical outcomes among older adults admitted to the intensive care unit (ICU) by means of 3 different screening criteria for PIMs. DESIGN: Retrospective cohort study. SETTING AND PARTICIPANTS: DCH Regional Medical Center ICU. Patients 65 years of age and older admitted to the medical ICU in 2014 (n = 346). MAIN OUTCOME MEASURES: PIMs were identified with the use of the Beers criteria (2015 and 2012 versions) and the Screening Tool of Older People's Potentially Inappropriate Prescriptions (STOPP). The proportions of PIM use at admission and discharge and proportions of in-hospital mortality and ICU and hospital readmission within 2014 among patients with PIM use were compared among the 3 criteria. Multivariable Poisson regression models assessed the associations of PIMs at admission with hospital and ICU length of stay (LOS). Statistical significance was considered to be indicated at P < 0.05. RESULTS: The proportions of patients with at least 1 PIM identified through 3 different criteria (2015 Beers, 2012 Beers, and STOPP, respectively; at admission: 68.5%, 58.1%, and 44.5%; at discharge: 77.4%, 63.6%, and 42.9%) were significantly different from each other (2012/2015 Beers vs. STOPP: P < 0.01). PIM use at admission as determined by STOPP was significantly associated with longer ICU stay (relative risk [RR] 1.24, 95% CI 1.11-1.38) and hospital LOS (RR 1.24, 95% CI 1.16-1.33). However, PIMs identified through the Beers criteria (2015 and 2012 versions) were associated with shorter ICU and hospital LOS. No differences were found in proportions of in-hospital mortality and ICU and hospital readmission among patients with PIM use identified through the 3 different criteria. CONCLUSION: Although the Beers criteria demonstrated the ability to identify PIMs more frequently in the ICU setting, PIM use identified by means of STOPP was associated with longer ICU and hospital LOS. Clinical interventions aiming to reduce PIMs identified by STOPP in inpatient or ICU settings may decrease patients' inpatient or ICU LOS.

Dipeptidyl Peptidase-4 Inhibitor-Associated Risk of Bleeding: An Evaluation of Reported Adverse Events.

BACKGROUND: Dipeptidyl peptidase-4 (DPP-4) inhibitors improve glycemic control, and sitagliptin has been associated with a reduction in cardiovascular events. In vivo data suggest reduced platelet activation, and aggregation may play a role, and therefore, increased bleeding risk is possible. OBJECTIVE: Comparatively assess bleeding risks associated with DPP-4 inhibitors against standard treatment. METHODS: Exploratory analyses of adverse event reports (AERs) from the US Food and Drug Administration Adverse Event Reporting System (FAERS) database (2004-2012 periods) were conducted. DPP-4 inhibitor-related bleeding was assessed with metformin as negative control, and aspirin, clopidogrel, and prasugrel illustrated positive comparators. Reporting odds ratios (RORs) and 95% CIs were calculated as a measure of disproportionality of reporting, and RORs were compared across drugs with the Breslow-Day statistics. RESULTS: From 2004 to 2012, 36 298, 4288, and 1202 AERs were found for sitagliptin, saxagliptin, and linagliptin, respectively, with 863, 102, and 14 bleeding complications. The relative reporting rate was not elevated with any DPP-4 inhibitor (sitagliptin: ROR = 0.71, 95% CI = 0.67-0.76; saxagliptin: ROR = 0.72, 95% CI = 0.59-0.87; linagliptin: ROR = 0.35, 95% CI = 0.20-0.59) or with metformin (ROR = 0.77; 95% CI = 0.75-0.78). Sitagliptin showed relatively higher reporting as compared with linagliptin ( P = 0.006) but not with saxagliptin ( P = 0.98). As positive references, antiplatelet drugs demonstrated relatively higher reporting compared with metformin (aspirin: ROR = 1.50, 95% CI = 1.48-1.51; clopidogrel: ROR = 2.28, 95% CI = 2.23-2.33; prasugrel: ROR = 5.09, 95% CI = 4.57-5.67). CONCLUSION: DPP-4 inhibitors were not associated with an undue increase in bleeding AERs in the FAERS database.

Electron transfer reactions of candidate tumor suppressor 101F6 protein, a cytochrome b561 homologue, with ascorbate and monodehydroascorbate radical.

The candidate tumor suppressor 101F6 protein is a homologue of adrenal chromaffin granule cytochrome b561, which is involved in the electron transfer from cytosolic ascorbate to intravesicular monodehydroascorbate radical. Since the tumor suppressor activity of 101F6 was enhanced in the presence of ascorbate, it was suggested that 101F6 might utilize a similar transmembrane electron transfer reaction. Detailed kinetic analyses were conducted on the detergent-solubilized recombinant human 101F6 for its electron transfer reactions with ascorbate and monodehydroascorbate radical by stopped-flow and pulse radiolysis techniques. The reduction of oxidized 101F6 with ascorbate was found to be independent of pH in contrast to those observed for chromaffin granule and Zea mays cytochromes b561 in which both cytochromes exhibited very slow rates at pH 5.0 but faster at pH 6.0 and 7.0. The absence of the inhibition for the electron acceptance from ascorbate upon the treatment with diethyl pyrocarbonate suggested that 101F6 might not utilize a "concerted proton/electron transfer mechanism". The second-order rate constant for the electron donation from the ascorbate-reduced 101F6 to the pulse-generated monodehydroascorbate radical was found to be 5.0 × 10(7) M(-1 )s(-1), about 2-fold faster than that of bovine chromaffin granule cytochrome b561 and about five times faster than that of Zea mays cytochrome b561, suggesting that human 101F6 is very effective for regenerating ascorbate from monodehydroascorbate radical in cells. Present observations suggest that 101F6 employs distinct electron transfer mechanisms on both sides of the membranes from those of other members of cytochrome b561 protein family.

Experimental Investigation of a Self-adaptive Thickening Polymer Performance under High-Temperature-High-Salinity Reservoir Conditions.

A polymer flooding workflow was developed to diminish polymer degradation and minimize formation damage under high-temperature-high-salinity reservoir conditions by using a shear-thickening polymer (SAP) prepared in engineered waters. First, rock characterization, fluid-fluid analysis, and formation damage tests were conducted to shortlist the potential formulations of polymer solutions based on higher viscosity and less formation damage. Second, polymer core flooding experiments were conducted under reservoir conditions to investigate the performance of candidate polymer solutions on oil displacement efficiency (DE). For the first time, the compatibility between SAP and engineered water was systematically tested. The factors affecting bulk rheology, polymer retention, and oil DE, including polymer concentration, polymer type, salinity, and hardness, were experimentally investigated and compared with regular partially hydrolyzed polyacrylamide (HPAM). Results showed that compared with HPAM, the SAP solution led to lower formation damage and overall higher oil DE, especially in the first 0.4 pore volume of polymer injection. When using SAP prepared in twice-diluted and hardness-stripped seawater under low-salinity formation brine conditions, the DE was the highest (69.04%). The formation damage was reduced when the salinity and hardness of the base fluid were lower, whereas stripping the hardness had a more pronounced effect on reducing formation damage. The improved oil recovery potential due to the shear-thickening feature of SAP solutions and their better compatibility with engineered water compared to regular HPAM has been proven in this study. It was also found that the lower salinity and hardness of the engineered water further stimulated the enhanced oil recovery potential of SAP solutions. The contribution of this work relies on revealing how SAP prepared in different engineered waters affects incremental oil DE under harsh reservoir conditions based on experimental evidence and mechanism analysis. The novelty of this work lays the foundation for investigating the potential application of SAP on a pilot scale.

Standardization of Particle Size for Floating Particle Wettability Measurement for Carbonate Rocks.

Misrepresentation of the wettability of a reservoir can lead to potentially low ultimate hydrocarbon recovery resulting in substantial economic losses. At the same time, it is impossible to determine the wettability of a reservoir across its length and breadth on a continuous basis using standard procedures. This work presents the development and standardization of a quick, easy, and low-cost wettability measurement method using the adherence tendency of rock particles in the oil or aqueous phase. The most important aspect of this study was establishing the optimum particle size for sustained floatation and balancing the buoyancy and gravity effect. The results show that the particles sink with a larger than optimum particle size because of the gravity effect. Similarly, the particles would float if they are smaller than optimum due to buoyancy and viscosity advantages. A new scale is designed, and the midpoint analysis shows that a 63-90 µm particle size is the ideal size range for the carbonate reservoir's wettability measurements, as the midpoint of the size distribution coincides with the standard Amott-Harvey (A-H) index. However, this size range is found to be wider for oil-wet particles. The floating particle method has several advantages over the established methods once standardized against a reliable process. Not only is the process fast but it can be performed with basic laboratory tools and does not require a high skill set. Most importantly, reliable wettability information can be obtained from drill cuttings and core fragments, enabling the determination of reservoir wettability on a continuum basis and not as a point basis, thus providing a more reliable average value, particularly for heterogeneous and unconsolidated reservoirs.

Exploring Prognostic Biomarkers of Acute Myeloid Leukemia to Determine Its Most Effective Drugs from the FDA-Approved List through Molecular Docking and Dynamic Simulation.

Acute myeloid leukemia (AML) is a blood cancer caused by the abnormal proliferation and differentiation of hematopoietic stem cells in the bone marrow. The actual genetic markers and molecular mechanisms of AML prognosis are unclear till today. This study used bioinformatics approaches for identifying hub genes and pathways associated with AML development to uncover potential molecular mechanisms. The expression profiles of RNA-Seq datasets, GSE68925 and GSE183817, were retrieved from the Gene Expression Omnibus (GEO) database. These two datasets were analyzed by GREIN to obtain differentially expressed genes (DEGs), which were used for performing the Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway, protein-protein interaction (PPI), and survival analysis. The molecular docking and dynamic simulation were performed to identify the most effective drug/s for AML from the drug list approved by the Food and Drug Administration (FDA). By integrating the two datasets, 238 DEGs were identified as likely to be affected by AML progression. GO enrichment analyses exhibited that the upregulated genes were mainly associated with inflammatory response (BP) and extracellular region (CC). The downregulated DEGs were involved in the T-cell receptor signalling pathway (BP), an integral component of the lumenal side of the endoplasmic reticulum membrane (CC) and peptide antigen binding (MF). The pathway enrichment analysis showed that the upregulated DEGs were mainly associated with the T-cell receptor signalling pathway. Among the top 15 hub genes, the expression levels of ALDH1A1 and CFD were associated with the prognosis of AML. Four FDA-approved drugs were selected, and a top-ranked drug was identified for each biomarker through molecular docking studies. The top-ranked drugs were further confirmed by molecular dynamic simulation that revealed their binding stability and confirmed their stable performance. Therefore, the drug compounds, enasidenib and gilteritinib, can be recommended as the most effective drugs against the ALDH1A1 and CFD proteins, respectively.

Mapping out the vulnerabilities of migrant women in the informal sector: A qualitative investigation in Dhaka city.

The current study seeks to explore the vulnerabilities typically encountered by female migrants in the informal sector in Dhaka city. It used a qualitative research approach, purposively selecting four areas from Dhaka city. Twenty-five semi-structured in-depth interviews during eight months of participant observation were conducted to accomplish the study objective. The authors used the capability approach theory to elucidate the phenomenon of vulnerability experienced by female migrants in the informal sector. The thematic data analyses were performed using the Granheim approach and NVivo 12 software. The findings of this study suggest that migrant women who work on the street face a number of significant challenges. These challenges include sexual assault and harassment, social stigma and cultural barriers, financial obstacles, and extortion and bribery. The authors recommend that governments provide access to state credits, social security, health insurance, and other forms of social protection for informal sector workers. The finding revealed that informal workers are often excluded from these essential benefits, making it difficult for such workers to expand their businesses or have a safety net in case of illness, unemployment, or other shocks.

Adhesion and Cohesion of Silica Surfaces with Quartz Cement: A Molecular Simulations Study.

This study focuses on developing an adhesive and cohesive molecular modeling approach to study the properties of silica surfaces and quartz cement interfaces. Atomic models were created based on reported silica surface configurations and quartz cement. For the first time, molecular dynamics (MD) simulations were conducted to investigate the cohesion and adhesion properties by predicting the interaction energy and the adhesion pressure at the cement and silica surface interface. Results show that the adhesion pressure depends on the area density (per nm2) and degree of ionization, and van der Waals forces are the major contributor to the interactions between the cement and silica surfaces. Moreover, it is shown that adhesion pressure could be the actual rock failure mechanism in contrast to the reported literature which considers cohesion as the failure mechanism. The bonding energy factors for both "dry" and "wet" conditions were used to predict the water effect on the adhesion pressure at the cement-surface interface, revealing that H2O can cause a significant reduction in adhesion pressure. In addition, relating the adhesion pressure to the dimensionless area ratio of the cement to silica surfaces resulted in a good correlation that could be used to distribute the adhesion pressure in a rock system based on the area of interactions between the cement and the surface. This study shows that MD simulations can be used to understand the chemomechanics relationship fundamental of cement-surfaces of a reservoir rock at a molecular/atomic level and to predict the rock mechanical failure for sandstones, limestones, and shales.

Perspective Review of Polymers as Additives in Water-Based Fracturing Fluids.

After successful implementation for more than 6 decades by the oil and gas industry, hydraulic fracturing remains the pioneer well stimulation method to date. Polymers are one of the additives in fracturing fluids that play a significant role. Polymers are used as friction reducers and viscosifiers to provide a transport medium for proppants in fracturing fluids. There are many polymer-based fracturing fluid systems, but choosing the most appropriate type and system depends on the type of application and a wide range of parameters. Currently, there is no complete review study that gives a reference and hence a perspective for researchers on the use of polymers in hydraulic fracturing. This paper summarizes the published literature on polymers used in fracturing fluids and discusses the current research issues, efforts, and trends in the field, aiming to provide an overview of the polymer applications in slick-water and cross-linked gel systems. The mechanism and limitation of polymer use such as polymer degradation, fracture conductivity reduction, and polymer adsorption are also reviewed in this paper. The reviewed literature suggested that polymers are important additives in fracturing fluids not only to provide adequate transportation of proppants but also to determine the width of the fracture whereby higher viscosities yield wider fractures. The development of synthetic polymers and associative polymers in fracturing fluids showed a remarkable potential to improve the stability of fracturing fluids in unconventional reservoirs under reservoir conditions, which makes it an interesting topic for future studies.

Optimization of Drying Parameters for Total Phenolic Content of Papaya Using Response Surface Methodology.

An optimum condition of the drying process can minimize nutrient losses and maximize the shelf life of food products. Thus, this study is aimed at developing an optimized system for the process conditions to determine the total phenolic content (TPC) of oven-dried papaya slices. The response surface method and central composite design were used to design the experiment, and it was found that the drying conditions had a significant impact on the total phenolic content of papaya slices. TPC was determined in relation to their interactions with the independent variables that include time, temperature, sample thickness, and stage of ripeness. The optimum drying conditions are those with the maximum content of TPC. In order to fit the experimental data, a quadratic polynomial model is created for the output variable, and an analysis of variance is carried out to determine whether or not the model is compatible to determine the optimal drying conditions. Time (10 h), temperature (62.02°C), thickness (9.75 mm) and stages (ripe) were found to be the optimal drying conditions. It was found that temperature had more effect on the amount of TPC than other factors. The numerical findings showed a good agreement with experimental data, with R 2 = 0.9237. It is hoped that the findings will make a contribution to the process of drying food.

Investigation of Hybrid Nanoparticle-Acid Fluids (HNAFs): Influence of Wettability and Interfacial Tension Mechanisms in Harsh Carbonate Reservoirs for Improved Oil Recovery.

Over the past few years, there has been significant interest in the potential of hybrid nanoparticle-acid fluid (HNAFs) for improved oil recovery. This comprehensive study investigates the effects of nanoparticles and acid on interfacial tension (IFT) to establish a relationship between brine properties and the oil/brine IFT. This investigation is one of the first regional studies conducted utilizing candidate field data from the Middle East. Based on the literature review and screening studies conducted, a seawater (SW)-based HNAF was formulated with nanoparticles (SiO2, Al2O3, and ZnO) and HCl to measure their effect on IFT. A total of 48 formulations of HNAFs, nanofluids with and without acid, were analyzed with crude oil from a candidate field. IFT measurements were subsequently conducted using the pendant drop method under ambient conditions and in a high-pressure, high-temperature reservoir environment. Results showcased that IFT reduction was observed by increasing the acid concentration with SiO2 and Al2O3, although a reverse trend was observed with ZnO. Moreover, it was observed that IFT varied with increasing concentrations of nanoparticles, and at certain acid concentrations, IFT reduced significantly with higher nanoparticle concentrations. From the Amott studies, a clear signature was achieved, with ZnO exhibiting a total of 31.4% oil recovery, followed by SiO2 (27.3%) and Al2O3 (23.7%). The results of this study may assist in defining a screening criterion for future displacement (oil recovery) studies involving the presented nanoparticles. The results also reveal further the mechanisms involved in IFT reduction by hybrid nano-acid fluids and their potential for significant applications in the Middle East.

Hydraulic Fracturing Design Considerations and Optimal Usage of Water Resources for Middle Eastern Tight Gas Reservoirs.

Over the past few decades, hydraulic fracturing, a well-stimulation technique commonly used for extracting hydrocarbons within unconventional reservoirs, has played a significant role in transforming the energy industry. Multiple studies and field trials have proven that an effective, efficient, and economical approach is critical for such operations. However, even after numerous fracturing jobs conducted across the globe, they are still related with high risk. Moreover, the exploitation of such reservoirs is water- and resource-intensive as compared to conventional reservoirs. This is crucial, especially in offshore operations and arid regions. A comprehensive investigation through a traditional fracture design process was conducted for a candidate Middle Eastern reservoir. Through the construction of strategically constrained cases in the presence of complex natural fracture sets, this novel investigation allowed the model to successfully isolate and characterize the key fracture design parameters that influenced fracture geometry for the candidate field and in turn the requirements with respect to water usage and resource consumption. The results indicate that for the given field conditions, fluid and proppant optimization is critical to achieving maximum recovery. The influence of natural fracture is highly critical and greatly influences the overall productivity. Simulations further indicate water requirements for the candidate field ranging from 3.5 to 5.8 million gallons of water per operation, which is significant in water-scarce regions. The findings of this study and the proposed workflow can assist to better understand the distinct contributions of key fracture design and operational parameters that are critical under the current volatile market conditions.

Novel Mathematical Model for Transient Pressure Analysis of Multifractured Horizontal Wells in Naturally Fractured Oil Reservoirs.

Multifractured horizontal wells have gained significant attention within the petroleum industry for commercial development. Despite considerable developments of transient pressure analysis or flow rate behaviors for horizontal wells in naturally fractured reservoirs, some significant problems are yet to be resolved, including high heterogeneity of reservoirs, pressure sensitivity of hydraulic fractures, and non-Darcy flow effect, which may occur during the production life. This paper presents a more pragmatic mathematical model for multifractured horizontal wells in naturally fractured reservoirs based on the fractal system, the theory of permeability modulus, and the time-fractional calculus correspondingly as an extension of the classic trilinear flow model. This new model comprises three modules: high heterogeneity of the reservoir based on the fractal system, the permeability modulus typically showing the pressure sensitivity of hydraulic fractures, and the anomalous diffusion describing non-Darcy flow turbulence. This investigation evaluates a trilinear dual-permeability dual-porosity flow model, with the dual-porosity model for the unstimulated outer reservoir flow region, the dual-permeability model for the stimulated inner reservoir flow region, and the permeability modulus for the flow region of hydraulic fractures. The comprehensive sensitivity analysis conducted indicates how the key parameters, such as fractal dimension, hydraulic fracture permeability modulus and conductivity, interporosity flow coefficient, storativity ratio, etc., affect the transient pressure behaviors, along with their reasons for the change in behavior. Application to a field case study further demonstrates the validity of the mathematical model, and the results presented may play a guiding role in well test interpretation.

Hydraulic Fracture Propagation and Analysis in Heterogeneous Middle Eastern Tight Gas Reservoirs: Influence of Natural Fractures and Well Placement.

Hydraulic fracturing is a stimulation process, most frequently used in tight and unconventional reservoirs for successful and economical hydrocarbon production. This study deals with the propagation behavior of induced hydraulic fractures (HFs) in naturally fractured formations within heterogeneous Middle Eastern tight gas reservoirs. Local sensitivity analysis was conducted for a Middle East candidate reservoir by varying fracture design parameters to investigate the fracture propagation behavior. After a comprehensive evaluation, a discrete fracture network-based simulator was used to introduce multiple sets of natural fractures (NFs) into the model to further analyze their interactions. Furthermore, simplistic wellbore placement analysis was also conducted. It is observed that production in tight reservoirs is governed by the presence of NFs and their distribution. This investigation analyzes HF propagation behavior and its correlated effects in the presence of NFs. Further assessment in terms of varying fracture geometry, NF sets, wellbore placement, and their effects on the conductivity are also presented. The introduced NF sets further illustrate the significance of the NF properties in this assessment. Additionally, variations in well placement demonstrate how effective the treatment can be in the presence of complex NF sets when properly located. The study is unique as it is one of its kind based on field data within the Middle East region and offers an insight into the potential concerns that may assist future fracturing operations within the region. The outcomes from this research validate the significance of NF orientation and its subsequent effects on the final HF geometry and network. Additionally, it further highlights the criticality of well placement and design strategies during hydraulic fracturing treatment design. Results describe how a minor modification with respect to the well placement can significantly affect hydraulic fracturing operations and subsequently the productivity and feasibility.

Effect of Silica Nanoparticles on Polymer Adsorption Reduction on Marcellus Shale.

Polymers play a major role in developing rheology of fracturing fluids for multistage hydraulic fracturing horizontal wells in unconventional reservoirs. Reducing the amount of polymer adsorbed in the shale formation is essential to maintain the polymer efficiency. In this study, the ability of silica nanoparticles to minimize polymer adsorption in Marcellus shale formation at reservoir temperature was investigated. Partially hydrolyzed polyacrylamide polymers of varying molecular weights (1-12 MD), salinities (2500-50,000 ppm), polymer concentrations (100-2000 ppm), and silica nanoparticle concentrations (0.01-0.1 w/w) were used in the static adsorption experiments. Adsorption of the polymer in the Marcellus shale samples was contrasted with and without the silica nanoparticles at a Marcellus formation reservoir temperature of 65 °C, showing a significant polymer adsorption reduction of up to 50%. The adsorption and adsorption reduction were more sensitive to the variation of the polymer concentration than to the variation of the salinity within the tested conditions. The highest adsorptions were reported at the higher molecular weight of 10-12 MD. In addition, silica nanoparticles significantly improved polymer rheology at elevated temperatures. The results indicate that nanoparticles can play a significant role in reducing polymer adsorption in the fracturing fluid and improve its rheological properties and its efficiency, which will reduce the number of issues caused by the polymers in the fracturing fluid and making it more cost effective.

Disparities in Cognitive Impairment With Anticholinergic Drug Use: A Population-Based Study.

OBJECTIVES: We aim to evaluate the association between anticholinergic drug (ACH) use and cognitive impairment and the effect of disparity parameters (sex, race, income, education, and rural or urban areas) on this relationship. METHODS: The analyses included 13,623 adults aged ≥65 years from the REasons for Geographic And Racial Differences in Stroke study (recruited 2003-2007). The ACH use was defined by the 2015 Beers Criteria, and cognitive impairment was measured by the Six-Item Cognitive Screener. Multivariable logistic regression models assessed disparities in cognitive impairment with ACH use, iteratively adjusting for disparity parameters and other covariates. The full models included interaction terms between ACH use and other covariates. A similar approach was used for class-specific ACH exposure and cognitive impairment analyses. RESULTS: Approximately 14% of the participants used at least 1 ACH listed in the Beers Criteria. Antidepressants were the most frequently prescribed ACH class. A significant sex-race interaction illustrated that females compared with males (in Blacks: odds ratio [OR] = 1.28, 95% confidence interval [CI] 1.10-1.49 and in Whites: OR = 1.96, 95% CI 1.74-2.20), especially White females (Black vs White: OR = 0.71, 95% CI 0.64-0.80), were more likely to receive ACHs. Higher odds of cognitive impairment were observed among ACH users compared with the nonusers (OR = 1.26, 95% CI 1.01-1.58). In our class-level analyses, only antidepressant users (OR = 1.60, 95% CI 1.14-2.25) showed a significant association with cognitive impairment in the fully adjusted model. CONCLUSIONS: We observed demographic and socioeconomic differences in ACH use and in cognitive impairment, individually.

Morpho-physiological retardations due to iron toxicity involve redox imbalance rather than photosynthetic damages in tomato.

Iron (Fe) toxicity is a major nutritional disorder that affects growth and yield in plants. Understanding the responses or damages due to Fe-toxicity may provide useful knowledge to improve tomato varieties. This study investigates the physiological and molecular responses in Fe-toxic tomato plants. The tomato plants were grown in separate hydroponic containers with two concentrations of Fe-EDTA (25 µM and 5 mM) in addition to the other nutrient elements. Fe-toxicity showed a severe reduction in growth parameters, which was accompanied by the increased electrolyte leakage and cell death in tomato. However, the SPAD score, quantum efficiency of PSII, and photosynthesis performance index did not show any changes in leaves, suggesting that damages due to Fe-toxicity are not related to the photosynthetic disturbance in tomato. The FCR (ferric chelate reductase) activity in root along with the Fe concentration in root and shoot significantly increased, being consistent with the upregulation of Fe-related genes (SlNramp1 and SlFRO1) in roots. It suggests that inefficiency to cope with elevated Fe is closely linked to Fe mobilization and uptake in roots of tomato. Consequently, this sensitive genotype was more prone to oxidative damages because of the inefficient antioxidant defense linked to antioxidant enzymes and metabolites. In conclusion, the growth retardation in Fe-toxic tomato is not related to photosynthetic inefficiency but highly associated with oxidative injuries in cells. These findings could be targeted in breeding or transgenic program to improve tomato plants sensitive to Fe toxicity.

Arbuscular mycorrhizal fungi alleviate Fe-deficiency symptoms in sunflower by increasing iron uptake and its availability along with antioxidant defense.

Iron (Fe)-deficiency causes chlorosis and growth inhibition in sunflower, an important commercial crop. This study examines whether and how arbuscular mycorrhizal fungi (AMF) ameliorate Fe-deficiency symptoms in Fe-deficiency sensitive sunflower plants. AMF supplementation showed a significant improvement in plant biomass, chlorophyll score, Fv/Fm (quantum efficiency of photosystem II), and Pi_ABS (photosynthesis performance index), suggesting its beneficial effect under Fe deficiency. This AM-driven amelioration of Fe deficiency was further supported by the improvement of biochemical stress indicators, such as cell death, electrolyte leakage, superoxide anion, and hydrogen peroxide. In this study, the AMF supplementations resulted in significant improvement in Fe as well as Zn concentrations in root and shoot of sunflower under Fe deficiency. One of the primary Strategy-I responses, ferric reductase activity along with the expression of its respective gene (HaFRO1), significantly increased in roots due to AMF ensuring Fe availability in the rhizosphere under Fe deficiency. Our qPCR analysis also showed a significant upregulation of HaIRT1, HaNramp1, and HaZIP1 in roots of sunflower in the presence of AMF, suggesting that Fe and Zn transporters are concurrently involved with AMF-mediated alleviation of Fe deficiency. Further, AMF accelerates the activities of CAT and SOD, predominantly in roots to protect sunflower plants from Fe-deficiency reactive oxygen species (ROS). This study unveils the mechanistic basis of AMF to limit Fe deficiency retardation in sunflower.