Increasing the temperature stability of environmentally friendly drilling and completion fluids based on organic brine.

Formates provide an already superior system, designed to complement synthetic polymers and extend their temperature capabilities as drilling fluids. However, as HPHT drilling continues to move into more harsh environments with expected bottom-hole temperatures of over 300°C; further research is required to improve the temperature ceiling of eco-friendly formate drilling fluids. The overall aim of the project was to develop a well construction fluid capable of withstanding ultra and possibly extreme HPHT temperature measures. As a result of this research, a measured combination of polyglycol sacrificial agent and MagOx has been found to inhibit the degradation of xanthan gum in formate brine so it remains stable after 16 hours dynamic ageing at 200ºC without the use of any synthetic materials. However; a formate system comprised of xanthan gum and synthetic HE® polymer was proven to function incredibly well at ultra-HPHT temperatures in excess of 250ºC for >64 hours. Thus, through utilization of improved HPHT testing equipment, it is hypothesized that the formate system and HE® polymers will remain stable in extreme HPHT circumstances i.e. over 260ºC. Further, there has been some dissimilarity to the literature with regards to the solubility of biopolymers in formate solutions where it has been discovered that viscosity actually increases with even less water available for hydration. It was found that the highly alkaline environment and/or buffer effect was inhibiting viscous characteristics and not the extreme concentration of salts dissolved in formate solution. The present study has also confirmed that; the order of stabilizing effects of individual cations in formate solutions generally follows the Hofmeister series of cations; Li+, Cs+, Na+, K+ with the response becoming more pronounced at higher salt concentrations. Thus, increased temperature stability of polymers and other additives can easily be achieved through simple manipulation of the formate base brine. Additionally, a significant increase in xanthan Tm of 177ºC in 2.20g/cm3 caesium formate was measured in the current stock - 20ºC higher than original values recorded for the Formate Manual

Impacts of Time Restricted Feeding on Peak Volume of Oxygen Uptake and Substrate Utilization

Time Restricted Feeding (TRF) is a type of Intermittent Fasting, which refers to the finite time to intake calories during the day. TRF has become a dietary approach that is used for weight loss and overall health. Individuals that partake in TRF may experience a decrease in peak volume of oxygen uptake (VO2peak) due to minimization of glycolytic stores. To date, few studies have compared the impact of TRF on VO2peak. PURPOSE: The current study aimed to further investigate the metabolic impact of TRF. METHODS: Twenty one participants, ages 18-60, completed an eleven week longitudinal study to examine differences in VO2peak, substrate utilization crossover, and resting substrate utilization. Participants self-reported diet, exercise, sleep, and medications over two separate four week periods. The first four weeks were without TRF and the following four were with TRF. A maximal exercise test and a resting metabolic test were performed three times, four weeks apart from each other. A repeated measures ANOVA was performed to determine within subject differences. A post-hoc analysis was performed to determine the time effect. RESULTS: VO2peak was significantly lower after implementing TRF (phttps://openriver.winona.edu/urc2019/1012/thumbnail.jp

Distinguishing Binders from False Positives by Free Energy Calculations: Fragment Screening Against the Flap Site of HIV Protease

Molecular docking is a powerful tool used in drug discovery and structural biology for predicting the structures of ligand–receptor complexes. However, the accuracy of docking calculations can be limited by factors such as the neglect of protein reorganization in the scoring function; as a result, ligand screening can produce a high rate of false positive hits. Although absolute binding free energy methods still have difficulty in accurately rank-ordering binders, we believe that they can be fruitfully employed to distinguish binders from nonbinders and reduce the false positive rate. Here we study a set of ligands that dock favorably to a newly discovered, potentially allosteric site on the flap of HIV-1 protease. Fragment binding to this site stabilizes a closed form of protease, which could be exploited for the design of allosteric inhibitors. Twenty-three top-ranked protein–ligand complexes from AutoDock were subject to the free energy screening using two methods, the recently developed binding energy analysis method (BEDAM) and the standard double decoupling method (DDM). Free energy calculations correctly identified most of the false positives (≥83%) and recovered all the confirmed binders. The results show a gap averaging ≥3.7 kcal/mol, separating the binders and the false positives. We present a formula that decomposes the binding free energy into contributions from the receptor conformational macrostates, which provides insights into the roles of different binding modes. Our binding free energy component analysis further suggests that improving the treatment for the desolvation penalty associated with the unfulfilled polar groups could reduce the rate of false positive hits in docking. The current study demonstrates that the combination of docking with free energy methods can be very useful for more accurate ligand screening against valuable drug targets

Safety and immunogenicity of concomitant administration of COVID-19 vaccines (ChAdOx1 or BNT162b2) with seasonal influenza vaccines in adults in the UK (ComFluCOV): a multicentre, randomised, controlled, phase 4 trial

Background: Concomitant administration of COVID-19 and influenza vaccines could reduce burden on health-care systems. We aimed to assess the safety of concomitant administration of ChAdOx1 or BNT162b2 plus an age-appropriate influenza vaccine.Methods: In this multicentre, randomised, controlled, phase 4 trial, adults in receipt of a single dose of ChAdOx1 or BNT162b2 were enrolled at 12 UK sites and randomly assigned (1:1) to receive concomitant administration of either an age-appropriate influenza vaccine or placebo alongside their second dose of COVID-19 vaccine. 3 weeks later the group who received placebo received the influenza vaccine, and vice versa. Participants were followed up for 6 weeks. The influenza vaccines were three seasonal, inactivated vaccines (trivalent, MF59C adjuvanted or a cellular or recombinant quadrivalent vaccine). Participants and investigators were masked to the allocation. The primary endpoint was one or more participant-reported solicited systemic reactions in the 7 days after first trial vaccination(s), with a difference of less than 25% considered non-inferior. Analyses were done on an intention-to-treat basis. Local and unsolicited systemic reactions and humoral responses were also assessed. The trial is registered with ISRCTN, ISRCTN14391248.Findings: Between April 1 and June 26, 2021, 679 participants were recruited to one of six cohorts, as follows: 129 ChAdOx1 plus cellular quadrivalent influenza vaccine, 139 BNT162b2 plus cellular quadrivalent influenza vaccine, 146 ChAdOx1 plus MF59C adjuvanted, trivalent influenza vaccine, 79 BNT162b2 plus MF59C adjuvanted, trivalent influenza vaccine, 128 ChAdOx1 plus recombinant quadrivalent influenza vaccine, and 58 BNT162b2 plus recombinant quadrivalent influenza vaccine. 340 participants were assigned to concomitant administration of influenza and a second dose of COVID-19 vaccine at day 0 followed by placebo at day 21, and 339 participants were randomly assigned to concomitant administration of placebo and a second dose of COVID-19 vaccine at day 0 followed by influenza vaccine at day 21. Non-inferiority was indicated in four cohorts, as follows: ChAdOx1 plus cellular quadrivalent influenza vaccine (risk difference for influenza vaccine minus placebo –1·29%, 95% CI –14·7 to 12·1), BNT162b2 plus cellular quadrivalent influenza vaccine (6·17%, –6·27 to 18·6), BNT162b2 plus MF59C adjuvanted, trivalent influenza vaccine (–12·9%, –34·2 to 8·37), and ChAdOx1 plus recombinant quadrivalent influenza vaccine (2·53%, –13·3 to 18·3). In the other two cohorts, the upper limit of the 95% CI exceeded the 0·25 non-inferiority margin (ChAdOx1 plus MF59C adjuvanted, trivalent influenza vaccine 10·3%, –5·44 to 26·0; BNT162b2 plus recombinant quadrivalent influenza vaccine 6·75%, –11·8 to 25·3). Most systemic reactions to vaccination were mild or moderate. Rates of local and unsolicited systemic reactions were similar between the randomly assigned groups. One serious adverse event, hospitalisation with severe headache, was considered related to the trial intervention. Immune responses were not adversely affected.Interpretation: Concomitant vaccination with ChAdOx1 or BNT162b2 plus an age-appropriate influenza vaccine raises no safety concerns and preserves antibody responses to both vaccines. Concomitant vaccination with both COVID-19 and influenza vaccines over the next immunisation season should reduce the burden on health-care services for vaccine delivery, allowing for timely vaccine administration and protection from COVID-19 and influenza for those in need

Association study of human leukocyte antigen (HLA) variants and idiopathic pulmonary fibrosis

IntroductionIdiopathic pulmonary fibrosis (IPF) is a chronic interstitial pneumonia marked by progressive lung fibrosis and a poor prognosis. Recent studies have highlighted the potential role of infection in the pathogenesis of IPF and a prior association of theHLA-DQB1gene with idiopathic fibrotic interstitial pneumonia (including IPF) has been reported. Due to the important role that the Human Leukocyte Antigen (HLA) region plays in the immune response, here we evaluated if HLA genetic variation was associated specifically with IPF risk.MethodsWe performed a meta-analysis of associations of the HLA region with IPF risk in individuals of European ancestry from seven independent case-control studies of IPF (comprising a total of 5159 cases and 27 459 controls, including the prior study of fibrotic interstitial pneumonia). Single nucleotide polymorphisms, classical HLA alleles and amino acids were analysed and signals meeting a region-wide association thresholdp<4.5×10−4and a posterior probability of replication >90% were considered significant. We sought to replicate the previously reportedHLA-DQB1association in the subset of studies independent of the original report.ResultsThe meta-analysis of all seven studies identified four significant independent single nucleotide polymorphisms associated with IPF risk. However, none met the posterior probability for replication criterion. TheHLA-DQB1association was not replicated in the independent IPF studies.ConclusionVariation in the HLA region was not consistently associated with risk in studies of IPF. However, this does not preclude the possibility that other genomic regions linked to the immune response may be involved in the aetiology of IPF

Impact of Time Restricted Feeding on Muscular Strength Within a Healthy Adult Population.

Time restricted feeding (TRF) has been shown to produce several health benefits. Muscular strength and nutritional intake have been strongly researched prior to this study. Little research exists investigating the impacts of TRF on muscular strength in human subjects. PURPOSE: This study was to identify the potential impacts of TRF on muscular strength. METHODS: Participants tracked caloric intake, sleep duration, sleep quality, exercise, and medications for two, four-week periods. Statistical analyses quantifying within subject effects were performed with a repeated measures ANOVA. Post-hoc analyses were performed to elicit differences between testing periods. RESULTS: Mean torque flexion at 60 degrees/second (MTF 60) (83.92 Nm ± 29.53Nm vs. 95.63 Nm ± 28.95 Nm) and mean torque flexion at 180 degrees/second (MTF 180) (66.75 Nm ± 25.9 Nm vs. 69.01 Nm ± 21.29 Nm vs. 75.55 Nm ± 23.9 Nm; 50 F = 7.920 Nm) had an increase from pre-test to TRF, and non-TRF to TRF. Post-hoc testing revealed differences between pre-test and TRF MTF 60 increased (p-value=0.001). Similar results were found for MTF 180 as well (p-value=0.037). When observing respiratory quotient (RQ) at rest (0.716±0.077 vs. 0.73 ±0.077 vs. 0.08±0.79; F = 8.352) showed increase from pre-test to TRF (p-value=0.008), and non-TRF to TRF (p-value=0.034). Analyzing total strength training days from non-TRF to TRF (8.11 days ± 1.18 vs. 5.22 days ± 1.48), CONCLUSION: Post TRF, participants showed an increase in muscular strength and resting RQ despite a decrease in strength training. Future studies are needed to identify physiological mechanisms behind these findings

Effects of time restricted feeding on metabolism, depression, and circadian rhythms

Introduction: Time restricted feeding (TRF) is a form of intermittent fasting limiting the time to intake calories throughout the day. TRF has been shown to affect substrate concentration and utilization at rest and exercise. Changing patterns in substrate availability and utilization can have effects on metabolism, cognitive functioning and circadian rhythms. Purpose: The purpose of this study was to evaluate the effects of TRF on overall physiological functioning, specifically sleep, resting energy expenditure (REE), resting respiratory quotient (RQ), and likelihood of depression. Methods: A longitudinal design was used to examine physiological changes associated with four weeks of TRF among 34 healthy adults between the ages of 18-60 years. Sleep was evaluated via self-report logs given to participants at testing sessions. REE and RQ were measured using a metabolic cart while subjects were in a fasted state. The Brief Anxiety and Depression Survey was administered, and each subject was given a score indicating their likelihood of depression at each testing session. Variable differences within subjects were determined using a repeated measures ANOVA or a paired samples T-test. Results: A significant decrease in total sleep (p = 0.034) and BADS scores (p=.046) occurred between non-TRF and TRF. Analysis revealed that resting RQ values experienced a significant increase (p=.002) between testing non-TRF and TRF testing periods (p=.034) and pre-test and TRF testing sessions (p=.008). Direct correlations were found between BADS, total sleep and resting RQ. Conclusion: TRF may influence glucose utilization during rest. Past studies have shown that different forms of intermittent fasting, such as TRF, enable an organism to create more regulated circadian rhythms, allowing less reliance on glucose, resulting in benefits in prevention and treatment of various diseases. The results of the present study are in opposition of previous literature and may provide insight into how glucose utilization affects other physiological processes. Increased glucose utilization may have been a factor in the decrease in total sleep and depression in the patients in the study. Future research is needed to verify if increased utilization of carbohydrates at rest influences changes of circadian rhythms and depression occurrence

A Scoping Review of Mental Health Programs for Parents of Children with Complex Medical Conditions

Parents of children with complex medical conditions (CMC) are at-risk of mental health concerns but have few mental health interventions available. This study summarized extant research on mental health interventions for parents of children with CMC. Searches of PsycINFO, Medline, CINAHL, Web of Science, PubMED, and Social Services Abstracts databases occurred, and articles were screened using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines as well as the Arksey and O’Malley’s five-stage method for scoping reviews. Screening eligibility included being peer-reviewed and written in English, assessing a parent/caregiver of a child aged 0-12 with a CMC who received a mental health intervention, and published between January 1, 2000 to May 19, 2020. Nine studies were included, each assessing mental health, process, and/or feasibility outcomes. Reduced depression, anxiety, stress, and an increase in quality of life, psychological flexibility, mindfulness, coping skills, and shared management were found; however, results were mixed. Parental support/education and parent education/child developmental supports are important for treating stress and quality of life, respectively. Stress interventions are most effective when provided close to CMC diagnosis. Findings highlight the need to improve mental health for parents of children with CMC