Why does one trust? A 360-degree perspective on the role of position power in weighting trustworthiness factors.

The purpose of the current paper is to explore the influence of the perceived trustworthiness factors of ability, benevolence and integrity on general and specific trust across supervisors, subordinates and peers with the same focal referent. This study used a 360-degree approach to examine how positional power asymmetries influence the relationship between trustworthiness and trust for a general and situation-specific referent. Data were obtained from military supervisors (N = 200), peers (N = 123), and subordinates (N = 85). Measures of trustworthiness and trust of a common military officer were obtained. Supervisors and subordinates differed in their relative weighting of trustworthiness factors (i.e. ability, benevolence, and integrity) when evaluating general and specific trust. Peers evidenced no difference in the relative weighting of trustworthiness factors. The relationship between benevolence and specific trust was stronger for subordinates than for supervisors. One implication of our findings is that trust can develop differently in bottom-up versus top-down organizational relationships. This study provides evidence that supervisors and subordinates emphasize different aspects of trustworthiness when evaluating their trust of a focal officer, and this process was different for general versus specific trust referents. The study also extends previous research by replicating previous findings across raters.

Structure-activity relationship (SAR) studies on substituted N-(pyridin-3-yl)-2-amino-isonicotinamides as highly potent and selective glycogen synthase kinase-3 (GSK-3) inhibitors.

In our continuing efforts to explore structure-activity relationships around the novel class of potent, isonicotinamide-based GSK3 inhibitors described in our previous report, we extensively explored structural variations around both 4/5-pyridine substitutions and the amide group. Some analogs were found to have greatly improved pTau lowering potency while retaining high kinase selectivity. In contrast to previous active compounds 1a-c, a close analog 3h did not show in vivo efficacy in a triple-transgenic mouse Alzheimer's disease model. In general, these 2­pyridinyl amide derivatives were prone to amidase mediated hydrolysis in mouse plasma.

Development and Validation of the System Trustworthiness Scale.

OBJECTIVE: We created and validated a scale to measure perceptions of system trustworthiness. BACKGROUND: Several scales exist in the literature that attempt to assess trustworthiness of system referents. However, existing measures suffer from limitations in their development and validation. The current study sought to develop a scale based on theory and methodological rigor. METHOD: We conducted exploratory and confirmatory factor analyses on data from two online studies to develop the System Trustworthiness Scale (STS). Additional analyses explored the manipulation of the factors and assessed convergent and divergent validity. RESULTS: The exploratory factor analyses resulted in a three-factor solution that represented the theoretical constructs of trustworthiness: performance, purpose, and process. Confirmatory factor analyses confirmed the three-factor solution. In addition, correlation and regression analyses demonstrated the scale's divergent and predictive validity. CONCLUSION: The STS is a psychometrically valid and predictive scale for assessing trustworthiness perceptions of system referents. APPLICATIONS: The STS assesses trustworthiness perceptions of systems. Importantly, the scale differentiates performance, purpose, and process constructs and is adaptable to a variety of system referents.

Rimegepant, an Oral Calcitonin Gene-Related Peptide Receptor Antagonist, for Migraine.

BACKGROUND: Calcitonin gene-related peptide receptor has been implicated in the pathogenesis of migraine. Rimegepant is an orally administered, small-molecule, calcitonin gene-related peptide receptor antagonist that may be effective in acute migraine treatment. METHODS: In a multicenter, double-blind, phase 3 trial, we randomly assigned adults with at least a 1-year history of migraine and two to eight migraine attacks of moderate or severe intensity per month to receive rimegepant orally at a dose of 75 mg or matching placebo for the treatment of a single migraine attack. The primary end points were freedom from pain and freedom from the most bothersome symptom (other than pain) identified by the patient, both of which were assessed 2 hours after the dose of rimegepant or placebo was administered. RESULTS: A total of 1186 patients were randomly assigned to receive rimegepant (594 patients) or placebo (592 patients); of these, 537 patients in the rimegepant group and 535 patients in the placebo group could be evaluated for efficacy. The overall mean age of the patients evaluated for efficacy was 40.6 years, and 88.7% were women. In a modified intention-to-treat analysis, the percentage of patients who were pain-free 2 hours after receiving the dose was 19.6% in the rimegepant group and 12.0% in the placebo group (absolute difference, 7.6 percentage points; 95% confidence interval [CI], 3.3 to 11.9; P<0.001). The percentage of patients who were free from their most bothersome symptom 2 hours after the dose was 37.6% in the rimegepant group and 25.2% in the placebo group (absolute difference, 12.4 percentage points; 95% CI, 6.9 to 17.9; P<0.001). The most common adverse events were nausea and urinary tract infection. CONCLUSIONS: Treatment of a migraine attack with the oral calcitonin gene-related peptide receptor antagonist rimegepant resulted in a higher percentage of patients who were free of pain and free from their most bothersome symptom than placebo. (Funded by Biohaven Pharmaceuticals; ClinicalTrials.gov number, NCT03237845.).

Competitive Situations Requiring Mental Toughness in Women's Australian Rules Football.

In the last decade, mental toughness (MT) researchers have been interested in the behaviours exemplifying MT. Despite this interest, little attention has been paid to the competitive situations these behaviours occur in. Hence, the aim of the current study was to start addressing this gap by comprehensively focusing on the situations requiring MT in sport - specifically, the contextual demands linked to MT in women's Australian rules football. Focus groups and individual semi-structured interviews were conducted at two Australian rules football clubs after each competitive round of the 2020 season. Following analysis of participant responses, three broad situational categories were created, representing the psychological demands required by the player or team to successfully overcome in-game challenges. These categories were: context intelligence, attentional regulation, and emotional regulation. This study identified that situations requiring MT also required a degree of acceptance and commitment - alluding to a potential link between acceptance-commitment therapy (ACT) and MT. Conceptually, this view offers a new perspective on the psychological process of being mentally tough in competition. The link between ACT and MT also offers an avenue for MT development. Recommendations are made for incorporating these identified situations into regular training sessions following affective learning design principles.

The Effect of Asset Degradation on Trust in Swarms: A Reexamination of System-Wide Trust in Human-Swarm Interaction.

OBJECTIVE: The effects of asset degradation on trust in human-swarm interaction were investigated through the lens of system-wide trust theory. BACKGROUND: Researchers have begun investigating contextual features that shape human interactions with robotic swarms-systems comprising assets that coordinate behavior based on their nearest neighbors. Recent work has begun investigating how human trust toward swarms is affected by asset degradation through the lens of system-wide trust theory, but these studies have been marked by several limitations. METHOD: In an online study, the current work manipulated asset degradation and measured trust-relevant criteria in a within-subjects design and addressed the limitations of past work. RESULTS: Controlling for swarm performance (i.e., target acquisition), asset degradation and trust (i.e., reliance intentions) in swarms were negatively related. In addition, as degradation increased, perceptions of swarm cohesion, obstacle avoidance, target acquisition, and terrain exploration efficiency decreased, the latter two of which (coupled with the reliance intentions criterion) support the tenets of system-wide trust theory as well as replicate and extend past work on the effects of asset degradation on trust in swarms. CONCLUSION: Human-swarm interaction is a context in which system-wide trust is relevant, and future work ought to investigate how to calibrate human trust toward swarm systems. APPLICATIONS: Based on these findings, design professionals should prioritize ways to depict swarm performance and system health such that humans do not abandon trust in systems that are still functional yet not over-trust those systems which are indeed performing poorly.

Calcitonin gene-related peptide (CGRP) receptor antagonists: Heterocyclic modification of a novel azepinone lead.

In our efforts to identify orally bioavailable CGRP receptor antagonists, we previously discovered a novel series of orally available azepinone derivatives that unfortunately also exhibited the unwanted property of potent time-dependent human CYP3A4 inhibition. Through heterocyclic replacement of the indazole ring, we discovered a series of heterocycle derivatives as high-affinity CGRP receptor antagonists. Some of them showed reasonable oral exposures, and the imidazolone derivatives that showed good oral exposure also exhibited substantially reduced time-dependent CYP3A4 inhibition. Several compounds showed strong in vivo efficacy in our marmoset facial blood flow assay with up to 87% inhibition of CGRP-induced activity. However, oral bioavailability generally remained low, emphasizing the challenges we and others encountered in discovering clinical development candidates for this difficult Class B GPCR target.

Azepino-indazoles as calcitonin gene-related peptide (CGRP) receptor antagonists.

Calcitonin gene-related peptide (CGRP) receptor antagonists have been shown clinically to be effective treatments for migraine. Zavegepant (BHV-3500, BMS-742413) is a high affinity antagonist of the CGRP receptor (hCGRP Ki = 0.023 nM) that has demonstrated efficacy in the acute treatment of migraine with intranasal delivery in a Phase 2/3 trial, despite showing low oral bioavailability in rats (FPO = 1.7%). Using zavegepant as a template, we sought to improve oral bioavailability through a series of azepinones which were designed in an attempt to reduce the number of rotatable bonds. These efforts led to the discovery of compound 21 which was able to mostly maintain high affinity binding (hCGRP Ki = 0.100 nM) and in vivo efficacy in the marmoset facial blood flow assay, while greatly improving oral bioavailability (rat FPO = 17%).

Aspiration fuels willpower: Evidence from the addiction literature.

Ainslie identifies two possible motivational sources for resolve: "thinking categorically" and "intertemporal bargaining." Ainslie opts for intertemporal bargaining, adding that thinking categorically has no motivational power. The most researched instance of willpower is remission from addiction. This literature shows that aspirations for a more desirable identity and comfortable lifestyle motivate remission. In other words, "thinking categorically" drives willpower.

Machine-Learning-Assisted Synthesis of Polar Racemates.

Racemates have recently received attention as nonlinear optical and piezoelectric materials. Here, a machine-learning-assisted composition space approach was applied to synthesize the missing M = Ti, Zr members of the Δ,Λ-[Cu(bpy)2(H2O)]2[MF6]2·3H2O (M = Ti, Zr, Hf; bpy = 2,2'-bipyridine) family (space group: Pna21). In each (CuO, MO2)/bpy/HF(aq) (M = Ti, Zr, Hf) system, the polar noncentrosymmetric racemate (M-NCS) forms in competition with a centrosymmetric one-dimensional chain compound (M-CS) based on alternating Cu(bpy)(H2O)22+ and MF62- basic building units (space groups: Ti-CS (Pnma), Zr-CS (P1̅), Hf-CS (P2/n)). Machine learning models were trained on reaction parameters to gain unbiased insight into the underlying statistical trends in each composition space. A human-interpretable decision tree shows that phase selection is driven primarily by the bpy:CuO molar ratio for reactions containing Zr or Hf, and predicts that formation of the Ti-NCS compound requires that the amount of HF present be decreased to raise the pH, which we verified experimentally. Predictive leave-one-metal-out (LOO) models further confirm that behavior in the Ti system is distinct from that of the Zr and Hf systems. The chemical origin of this distinction was probed via fluorine K-edge X-ray absorption spectroscopy. Pre-edge features in the F1s X-ray absorption spectra reveal the strong ligand-to-metal π bonding between Ti(3d - t2g) and F(2p) states that distinguishes the TiF62- anion from the ZrF62- and HfF62- anions.

Potential clinical utility of ERC-2 yeast phase lysate antigen for antibody detection in dogs with blastomycosis.

Four Blastomyces antigens ERC-2 (B. gilchristii, dog, Wisconsin), B5929 (human, Minnesota), 597 (human, Wisconsin), and T-27 (polar bear, Tennessee) were tested against 31 serum specimens from dogs with blastomycosis and 19 from healthy dogs. All antigens detected antibody; efficacy varied. ERC-2 showed the highest ELISA mean absorbance value of 3.00 followed by T-27. Test performance varied by sample geographic origin. Further study is needed to determine if ERC-2 antigens may be clinically useful, and whether the combination of the particular fungal species as antigen source, host animal, and the species and geographic location of the patient being tested is important for optimum test characteristics.

Blastomyces dermatitidis Antibody and Antigen Detection: Comparison of Four Lysate Antigens and Antibodies Prepared from Human Isolates from a Blastomycosis Outbreak.

Blastomycosis is a systemic fungal disease of humans and other animals produced by the thermally dimorphic fungal organism, Blastomyces dermatitidis. Recent studies have focused on the utilization of antibody and antigen detection in the development of immunoassays for the diagnosis of blastomycosis. This study was designed to evaluate four B. dermatitidis yeast lysate antigenic preparations from human isolates (591, 592, 597, 598) from an outbreak of blastomycosis in Eagle River, Wisconsin. The indirect enzyme-linked immunosorbent assay (ELISA) was used to compare these four antigens for their ability to detect antibodies in 28 serum specimens from immunized rabbits and in 18 sera from dogs with blastomycosis. This study also compared antibodies prepared from each of the four B. dermatitidis lysate antigens for their ability to detect antigen using the competitive enzyme-linked immunosorbent assay in 18 urine specimens from the same dogs as above with blastomycosis. All four reagents proved to be immunoreactive and were able to detect antibody in the rabbit and dog sera and antigen in each of the urine specimens with only slight variations in the mean absorbance values evidenced. Antibody detection, mean absorbance values with the four lysates, ranged from 1.522 (592 antigen) to 2.047 (597 antigen) in the rabbit sera and from 1.504 (591 antigen) to 1.878 (597 antigen) in the dog sera. Antigen detection, sensitivity values obtained with the antibodies prepared from the four lysates, ranged from 89% (598 serum) to 100% (591 and 592 serum specimens).

Control of Size and Composition of Colloidal Nanocrystals of Manganese Oxide.

A comprehensive study on the effects of experimental parameters on the composition and size of manganese oxide nanocrystals was completed using colloidal chemistry. The reactions studied involved the thermolysis of Mn2+ acetate and Mn3+ acetylacetonate in oleylamine. Temperature was found to be the dominant factor affecting the composition and size of the products. Reactions completed below 200 °C favored the formation of nanocrystals smaller than 20 nm, with the presence of even impurity amounts of oxidizing agents leading to the formation of Mn3O4. Nanocrystals of MnO could only be synthesized below 200 °C if Mn2+ acetate was used, and the reaction was carefully controlled to have no O2 and H2O contamination. In turn, particle growth was rapid above this temperature. In this case, regardless of the oxidizing agents used or oxidation state of the Mn precursor, nanocrystals of MnO formed after annealing for at least 1 h at temperatures higher than 200 °C. This finding suggests the role of oleylamine as solvent, surfactant, and reducing agent at sufficiently high annealing temperatures. These results increase the understanding of redox stability of manganese during the colloidal synthesis of semiconductor metal oxide nanocrystals.

Effects of Sprint Interval Training With Active Recovery vs. Endurance Training on Aerobic and Anaerobic Power, Muscular Strength, and Sprint Ability.

Sökmen, B, Witchey, RL, Adams, GM, and Beam, WC. Effects of sprint interval training with active recovery vs. endurance training on aerobic and anaerobic power, muscular strength, and sprint ability. J Strength Cond Res 32(3): 624-631, 2018-This study compared sprint interval training with active recovery (SITAR) to moderate-intensity endurance training (ET) in aerobic and anaerobic power, muscular strength, and sprint time results. Forty-two recreationally active adults were randomly assigned to a SITAR or ET group. Both groups trained 3× per week for 10 weeks at 75% of V[Combining Dot Above]O2max for 30 minutes weeks 1-4, with duration increasing to 35 minutes weeks 5-7 and 40 minutes weeks 8-10. While ET ran on a 400-m track without rest for the full training session, SITAR sprinted until the 200-m mark and recovered with fast walking or light jogging the second 200 m to the finish line in 3× original sprint time. Maximal oxygen consumption (V[Combining Dot Above]O2max), anaerobic treadmill run to exhaustion at 12.5 km·h at 20% incline, isokinetic leg extension and flexion strength at 60 and 300°·s, and 50 m sprint time were determined before and after training. Results showed a significant improvement (p ≤ 0.05) in absolute and relative V[Combining Dot Above]O2max, anaerobic treadmill run, and sprint time in both groups. Only SITAR showed significant improvements in isokinetic leg extension and flexion at 300°·s and decreases in body mass (p ≤ 0.05). SITAR also showed significantly greater improvement (p ≤ 0.05) over ET in anaerobic treadmill run and 50 m sprint time. These data suggest that SITAR is a time-efficient strategy to induce rapid adaptations in V[Combining Dot Above]O2max comparable to ET with added improvements in anaerobic power, isokinetic strength, and sprint time not observed with ET.

The effect of propensity to trust and perceptions of trustworthiness on trust behaviors in dyads.

Research on trust has burgeoned in the last few decades. Despite the growing interest in trust, little is known about trusting behaviors in non-dichotomous trust games. The current study explored propensity to trust, trustworthiness, and trust behaviors in a new computer-mediated trust relevant task. We used multivariate multilevel survival analysis (MMSA) to analyze behaviors across time. Results indicated propensity to trust did not influence trust behaviors. However, trustworthiness perceptions influenced initial trust behaviors and trust behaviors influenced subsequent trustworthiness perceptions. Indeed, behaviors fully mediated the relationship of trustworthiness perceptions over time. The study demonstrated the utility of MMSA and the new trust game, Checkmate, as viable research methods and stimuli for assessing the loci of trust.

Degradation Mechanisms of Magnesium Metal Anodes in Electrolytes Based on (CF3SO2)2N- at High Current Densities.

The energy density of rechargeable batteries utilizing metals as anodes surpasses that of Li ion batteries, which employ carbon instead. Among possible metals, magnesium represents a potential alternative to the conventional choice, lithium, in terms of storage density, safety, stability, and cost. However, a major obstacle for metal-based batteries is the identification of electrolytes that show reversible deposition/dissolution of the metal anode and support reversible intercalation of ions into a cathode. Traditional Grignard-based Mg electrolytes are excellent with respect to the reversible deposition of Mg, but their limited anodic stability and compatibility with oxide cathodes hinder their applicability in Mg batteries with higher voltage. Non-Grignard electrolytes, which consist of ethereal solutions of magnesium(II) bis(trifluoromethanesulfonyl)imide (Mg(TFSI)2), remain fairly stable near the potential of Mg deposition. The slight reactivity of these electrolytes toward Mg metal can be remedied by the addition of surface-protecting agents, such as MgCl2. Hence, ethereal solutions of Mg(TFSI)2 salt with MgCl2 as an additive have been suggested as a representative non-Grignard Mg electrolyte. In this work, the degradation mechanisms of a Mg metal anode in the TFSI-based electrolyte were studied using a current density of 1 mA cm-2 and an areal capacity of ∼0.4 mAh cm-2, which is close to those used in practical applications. The degradation mechanisms identified include the corrosion of Mg metal, which causes the loss of electronic pathways and mechanical integrity, the nonuniform deposition of Mg, and the decomposition of TFSI- anions. This study not only represents an assessment of the behavior of Mg metal anodes at practical current density and areal capacity but also details the outcomes of interfacial passivation, which was detected by simple cyclic voltammetry experiments. This study also points out the absolute absence of any passivation at the electrode-electrolyte interface for the premise of developing electrolytes compatible with a metal anode.

Asymmetric Synthesis of the Major Metabolite of a Calcitonin Gene-Related Peptide Receptor Antagonist and Mechanism of Epoxide Hydrogenolysis.

An asymmetric synthesis of the major metabolite of the calcitonin gene-related peptide recepotor antagonist BMS-846372 is presented. The variously substituted cyclohepta[b]pyridine ring system represents an underexplored ring system and showed some unexpected chemistry. Reactivities of epoxide and ketone functional groups on the cycloheptane ring were extensively controlled by a remote bulky TIPS group. The rate difference of the hydrogenolysis between two diastereomeric epoxide intermediates shed some light on the mechanism of epoxide hydrogenolysis, and further, deuterium labeling studies revealed more mechanistic details on this well-known chemical transformation for the first time.

Methods for simulating nutritional requirement and response studies with all organisms to increase research efficiency.

Nutritional requirements and responses of all organisms are estimated using various models representing the response to different dietary levels of the nutrient in question. To help nutritionists design experiments for estimating responses and requirements, we developed a simulation workbook using Microsoft Excel. The objective of the present study was to demonstrate the influence of different numbers of nutrient levels, ranges of nutrient levels and replications per nutrient level on the estimates of requirements based on common nutritional response models. The user provides estimates of the shape of the response curve, requirements and other parameters and observation to observation variation. The Excel workbook then produces 1-1000 randomly simulated responses based on the given response curve and estimates the standard errors of the requirement (and other parameters) from different models as an indication of the expected power of the experiment. Interpretations are based on the assumption that the smaller the standard error of the requirement, the more powerful the experiment. The user can see the potential effects of using one or more subjects, different nutrient levels, etc., on the expected outcome of future experiments. From a theoretical perspective, each organism should have some enzyme-catalysed reaction whose rate is limited by the availability of some limiting nutrient. The response to the limiting nutrient should therefore be similar to enzyme kinetics. In conclusion, the workbook eliminates some of the guesswork involved in designing experiments and determining the minimum number of subjects needed to achieve desired outcomes.

Synthesis and SAR of calcitonin gene-related peptide (CGRP) antagonists containing substituted aryl-piperazines and piperidines.

Calcitonin gene-related peptide (CGRP) is a potent neuropeptide implicated in the pathophysiology of migraine. In the course of seeking CGRP antagonists with improved oral bioavailability, metabolic stability, and pharmacokinetic properties, lower molecular weight, structurally simpler piperidine and piperazine analogs of BMS-694153 were prepared. Several were found to have nM binding affinity in vitro. The synthesis and SAR of these substituted piperidine and piperazine CGRP antagonists are discussed.

Mayer-Rokitansky-Kuster-Hauser syndrome accompanied by invasive ductal carcinoma: a case report.

Milllerian agenesis and the absence of organs of Millerian canal origin are referred to as Mayer-Rokitansky-Kuster-Hauser (MRKH) syndrome. Invasive ductal carcinoma constitutes 47-75% of all breast carcinomas and is the most common type. The authors report the first case of invasive ductal carcinoma associated with MRKH syndrome in the literature to their knowledge. A 25-year-old woman with a palpable mass in her right breast for three months presented to the presented clinic. On physical examination a mobile, firm mass measuring 2x2 cm was detected in right breast, at a region close to axilla. A fine needle aspiration biopsy from the lesion revealed malignant cells and thus a segmental mastectomy operation was performed. All genital tract and endocrinological system should be thoroughly examined before administering hormone replacement therapy to patients presenting with primary amenorrhea.The co-occurrence MRKH syndrome of with invasive ductal carcinoma is regarded as coincidental. Confirming the absence of a common etiology, however, requires further genetic studies.