The twisted fourth moment of the Riemann zeta function

We compute the asymptotics of the fourth moment of the Riemann zeta function times an arbitrary Dirichlet polynomial of length $T^{{1/11} - \epsilon}$Comment: 28 pages. v2: added reference

Usability, Acceptability, and Effectiveness of Web-Based Conversational Agents to Facilitate Problem Solving in Older Adults: Controlled Study.

BACKGROUND: The usability and effectiveness of conversational agents (chatbots) that deliver psychological therapies is under-researched. OBJECTIVE: This study aimed to compare the system usability, acceptability, and effectiveness in older adults of 2 Web-based conversational agents that differ in theoretical orientation and approach. METHODS: In a randomized study, 112 older adults were allocated to 1 of the following 2 fully automated interventions: Manage Your Life Online (MYLO; ie, a chatbot that mimics a therapist using a method of levels approach) and ELIZA (a chatbot that mimics a therapist using a humanistic counseling approach). The primary outcome was problem distress and resolution, with secondary outcome measures of system usability and clinical outcome. RESULTS: MYLO participants spent significantly longer interacting with the conversational agent. Posthoc tests indicated that MYLO participants had significantly lower problem distress at follow-up. There were no differences between MYLO and ELIZA in terms of problem resolution. MYLO was rated as significantly more helpful and likely to be used again. System usability of both the conversational agents was associated with helpfulness of the agents and the willingness of the participants to reuse. Adherence was high. A total of 12% (7/59) of the MYLO group did not carry out their conversation with the chatbot. CONCLUSIONS: Controlled studies of chatbots need to be conducted in clinical populations across different age groups. The potential integration of chatbots into psychological care in routine services is discussed

Acceptability and Effectiveness of NHS-Recommended e-Therapies for Depression, Anxiety, and Stress: Meta-Analysis.

BACKGROUND: There is a disconnect between the ability to swiftly develop e-therapies for the treatment of depression, anxiety, and stress, and the scrupulous evaluation of their clinical utility. This creates a risk that the e-therapies routinely provided within publicly funded psychological health care have evaded appropriate rigorous evaluation in their development. OBJECTIVE: This study aims to conduct a meta-analytic review of the gold standard evidence of the acceptability and clinical effectiveness of e-therapies recommended for use in the National Health Service (NHS) in the United Kingdom. METHODS: Systematic searches identified appropriate randomized controlled trials (RCTs). Depression, anxiety, and stress outcomes at the end of treatment and follow-up were synthesized using a random-effects meta-analysis. The grading of recommendations assessment, development, and evaluation approach was used to assess the quality of each meta-analytic comparison. Moderators of treatment effect were examined using subgroup and meta-regression analysis. Dropout rates for e-therapies (as a proxy for acceptability) were compared against controls. RESULTS: A total of 24 studies evaluating 7 of 48 NHS-recommended e-therapies were qualitatively and quantitatively synthesized. Depression, anxiety, and stress outcomes for e-therapies were superior to controls (depression: standardized mean difference [SMD] 0.38, 95% CI 0.24 to 0.52, N=7075; anxiety and stress: SMD 0.43, 95% CI 0.24 to 0.63, n=4863), and these small effects were maintained at follow-up. Average dropout rates for e-therapies (31%, SD 17.35) were significantly higher than those of controls (17%, SD 13.31). Limited moderators of the treatment effect were found. CONCLUSIONS: Many NHS-recommended e-therapies have not been through an RCT-style evaluation. The e-therapies that have been appropriately evaluated generate small but significant, durable, beneficial treatment effects. TRIAL REGISTRATION: International Prospective Register of Systematic Reviews (PROSPERO) registration CRD42019130184; https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=130184

Dynamics Impact Tolerance of Shuttle RCC Leading Edge Panels Using LS-DYNA

This paper describes a research program conducted to enable accurate prediction of the impact tolerance of the shuttle Orbiter leading-edge wing panels using physics-based codes such as LS-DYNA, a nonlinear, explicit transient dynamic finite element code. The shuttle leading-edge panels are constructed of Reinforced-Carbon-Carbon (RCC) composite material, which is used because of its thermal properties to protect the shuttle during reentry into the Earth's atmosphere. Accurate predictions of impact damage from insulating foam and other debris strikes that occur during launch required materials characterization of expected debris, including strain-rate effects. First, analytical models of individual foam and RCC materials were validated. Next, analytical models of foam cylinders impacting 6- in. x 6-in. RCC flat plates were developed and validated. LS-DYNA pre-test models of the RCC flat plate specimens established the impact velocity of the test for three damage levels: no-detectable damage, non-destructive evaluation (NDE) detectable damage, or visible damage such as a through crack or hole. Finally, the threshold of impact damage for RCC on representative Orbiter wing panels was predicted for both a small through crack and for NDE-detectable damage

Mechanical properties of α-tricalcium phosphate-based bone cements incorporating regenerative biomaterials for filling bone defects exposed to low mechanical loads

Calcium phosphate-based cements with enhanced regenerative potential are promising biomaterials for the healing of bone defects. With a view to the use of such cements for low load bearing applications such as sinus augmentation or filling extraction sites, we have prepared α-tricalcium phosphate (α-TCP)-based bone cements including materials that we would expect to improve their regenerative potential, and describe the mechanical properities of the resulting formulations herein. Formulations incorporated α-TCP, hydroxyapatite, biopolymer-thickened wetting agents, sutures, and platelet poor plasma. The mechanical properties of the composites were composition dependent, and optimized formulations had clinically relevant mechanical properties. Such calcium phosphate-based cements have potential as replacements for cements such as those based on polymethylmethacrylate (PMMA)

Dynamic Impact Tolerance of Shuttle RCC Leading Edge Panels using LS-DYNA

This paper describes a research program conducted to enable accurate prediction of the impact tolerance of the shuttle Orbiter leading-edge wing panels using 'physics-based- codes such as LS-DYNA, a nonlinear, explicit transient dynamic finite element code. The shuttle leading-edge panels are constructed of Reinforced-Carbon-Carbon (RCC) composite material, which issued because of its thermal properties to protect the shuttle during re-entry into the Earth's atmosphere. Accurate predictions of impact damage from insulating foam and other debris strikes that occur during launch required materials characterization of expected debris, including strain-rate effects. First, analytical models of individual foam and RCC materials were validated. Next, analytical models of individual foam cylinders impacting 6-in. x 6-in. RCC flat plates were developed and validated. LS-DYNA pre-test models of the RCC flat plate specimens established the impact velocity of the test for three damage levels: no-detectable damage, non-destructive evaluation (NDE) detectable damage, or visible damage such as a through crack or hole. Finally, the threshold of impact damage for RCC on representative Orbiter wing panels was predicted for both a small through crack and for NDE-detectable damage

Alginate/Chitosan Particle-Based Drug Delivery Systems for Pulmonary Applications

Cystic fibrosis (CF) is a complex, potentially life-threatening disease that is most effectively treated through the administration of antibiotics (e.g., colistimethate sodium). Chronic infection with Pseudomonas aeruginosa is one of the most significant events in the pathogenesis of cystic fibrosis, and tobramycin is the treatment of choice for those patients with chronic P. aeruginosa infection who are deteriorating despite regular administration of colistimethate sodium. Effective treatment can be challenging due to the accumulation of thickened mucus in the pulmonary environment, and here we describe the results of our investigation into the development of alginate/chitosan particles prepared via precipitation for such environments. Tobramycin loading and release from the alginate/chitosan particles was investigated, with evidence of both uptake and release of sufficient tobramycin to inhibit P. aeruginosa in vitro. Functionalisation of the alginate/chitosan particles with secretory leukocyte protease inhibitor (SLPI) was shown to help inhibit the inflammatory response associated with lung infections (via inhibition of neutrophil elastase activity) and enhance their interaction with cystic fibrosis mucus (assayed via reduction of the depth of particle penetration into the mucus) in vitro, which have prospects to enhance their efficacy in vivo

A Summary of the Slush Hydrogen Technology Program for the National Aero-Space Plane

Slush hydrogen, a mixture of solid and liquid hydrogen, offers advantages of higher density (16 percent) and higher heat capacity (18 percent) than normal boiling point hydrogen. The combination of increased density and heat capacity of slush hydrogen provided a potential to decrease the gross takeoff weight of the National Aero-Space Plane (NASP) and therefore slush hydrogen was selected as the propellant. However, no large-scale data was available on the production, transfer and tank pressure control characteristics required to use slush hydrogen as a fuel. Extensive testing has been performed at the NASA Lewis Research Center K-Site and Small Scale Hydrogen Test Facility between 1990 and the present to provide a database for the use of slush hydrogen. This paper summarizes the results of this testing

A key role for peroxynitrite-mediated inhibition of cardiac ERG (Kv11.1) K+ channels in carbon monoxide–induced proarrhythmic early afterdepolarizations

Exposure to carbon monoxide (CO) causes early afterdepolarization arrhythmias. Previous studies in rats indicated arrhythmias arose due to augmentation of the late Na+ current. The purpose of the present study was to examine the basis of CO-induced arrhythmias in guinea pig myocytes in which action potentials more closely resemble those of human myocytes. Whole-cell current- and voltage-clamp recordings were made from isolated guinea pig myocytes and also from HEK293 cells expressing wild-type or a C723S mutant form of Kv11.1 (ERG). We also monitored formation of peroxynitrite (ONOO-) in HEK293 cells fluorimetrically. CO, applied as the CO releasing molecule, CORM-2, prolonged action potentials and induced early after-depolarizations (EADs) in guinea pig myocytes. In HEK293 cells CO inhibited wild-type but not C723S mutant Kv11.1 K+ currents. Inhibition was prevented by an antioxidant, mitochondrial inhibitors or inhibition of nitric oxide formation. CO also raised ONOO- levels, an effect reversed by the ONOO- scavenger, FeTPPS which also prevented CO inhibition of Kv11.1 currents, and abolished the effects of CO on Kv11.1 tail currents and action potentials in guinea pig myocytes. Our data suggest that CO induces arrhythmias in guinea pig cardiac myocytes via ONOO--mediated inhibition of Kv11.1 K+ channel