Spirituality, self-compassion, and anxiety among sexual minority men: a longitudinal mediation analysis.

BACKGROUND AND OBJECTIVE: Research related to anxiety among sexual minority men (SMM) typically focuses on risk factors. It has seldom examined factors that may be associated with lower levels of anxiety. This gap in the literature represents an opportunity to explore positive psychological factors that may be related to lower levels of anxiety among this group. Spirituality and self-compassion are two positive psychological factors that have been associated with reduced anxiety in general samples but have been understudied among SMM. This study aimed to determine the longitudinal associations between spirituality, self-compassion, and anxiety. DESIGN AND METHODS: Guided by an Afrocentric psychological framework, we conducted a secondary quantitative analysis with data from a racially and ethnically diverse sample of 697 U.S. SMM. RESULTS: Utilizing Hayes PROCESS Macro Model 4, we found that spirituality at baseline was positively associated with self-compassion at baseline, which in turn was inversely associated with anxiety at 12-month follow-up. CONCLUSIONS: Overall, our findings provide evidence that spirituality and self-compassion are two positive psychological factors that are inversely associated with anxiety among SMM.

Lexicase Selection for Multi-Task Evolutionary Robotics.

In Evolutionary Robotics, Lexicase selection has proven effective when a single task is broken down into many individual parameterizations. Evolved individuals have generalized across unique configurations of an overarching task. Here, we investigate the ability of Lexicase selection to generalize across multiple tasks, with each task again broken down into many instances. There are three objectives: to determine the feasibility of introducing additional tasks to the existing platform; to investigate any consequential effects of introducing these additional tasks during evolutionary adaptation; and to explore whether the schedule of presentation of the additional tasks over evolutionary time affects the final outcome. To address these aims we use a quadruped animat controlled by a feed-forward neural network with joint-angle, bearing-to-target, and spontaneous sinusoidal inputs. Weights in this network are trained using evolution with Lexicase-based parent selection. Simultaneous adaptation in a wall crossing task (labelled wall-cross) is explored when one of two different alternative tasks is also present: turn-and-seek or cargo-carry. Each task is parameterized into 100 distinct variants, and these variants are used as environments for evaluation and selection with Lexicase. We use performance in a single-task wall-cross environment as a baseline against which to examine the multi-task configurations. In addition, the objective sampling strategy (the manner in which tasks are presented over evolutionary time) is varied, and so data for treatments implementing uniform sampling, even sampling, or degrees of generational sampling are also presented. The Lexicase mechanism successfully integrates evolution of both turn-and-seek and cargo-carry with wall-cross, though there is a performance penalty compared to single task evolution. The size of the penalty depends on the similarity of the tasks. Complementary tasks (wallcross/turn-and-seek) show better performance than antagonistic tasks (wall-cross/cargo-carry). In complementary tasks performance is not affected by the sampling strategy. Where tasks are antagonistic, uniform and even sampling strategies yield significantly better performance than generational sampling. In all cases the generational sampling requires more evaluations and consequently more computational resources. The results indicate that Lexicase is a viable mechanism for multitask evolution of animat neurocontrollers, though the degree of interference between tasks is a key consideration. The results also support the conclusion that the naive, uniform random sampling strategy is the best choice when considering final task performance, simplicity of implementation, and computational efficiency.

Tracking Multiple Vehicles Constrained to a Road Network From a UAV with Sparse Visual Measurements.

Multiple-target tracking algorithms generally operate in the local frame of the sensor and have difficulty with track reallocation when targets move in and out of the sensor field-of-view. This poses a problem when an unmanned aerial vehicle (UAV) is tracking multiple ground targets on a road network larger than its field-of-view. To address this problem, we propose a Rao-Blackwellized Particle Filter (RBPF) to maintain individual target tracks and to perform probabilistic data association when the targets are constrained to a road network. This is particularly useful when a target leaves and then re-enters the UAV's field-of-view. The RBPF is structured as a particle filter of particle filters. The top level filter handles data association and each of its particles maintains a bank of particle filters to handle target tracking. The tracking particle filters incorporate both positive and negative information when a measurement is received. We implement two path planning controllers, receding horizon and deep reinforcement learning, and compare their ability to improve the certainty for multiple target location estimates. The controllers prioritize paths that reduce each target's entropy. In addition, we develop an algorithm that computes the upper bound on the filter's performance, thus facilitating an estimate of the number of UAVs needed to achieve a desired performance threshold.

Orally Bioavailable Small-Molecule CD73 Inhibitor (OP-5244) Reverses Immunosuppression through Blockade of Adenosine Production.

The adenosinergic pathway represents an attractive new therapeutic approach in cancer immunotherapy. In this pathway, ecto-5-nucleotidase CD73 has the unique function of regulating production of immunosuppressive adenosine (ADO) through the hydrolysis of AMP. CD73 is overexpressed in many cancers, resulting in elevated levels of ADO that correspond to poor patient prognosis. Therefore, reducing the level of ADO via inhibition of CD73 is a potential strategy for treating cancers. Based on the binding mode of adenosine 5'-(α,ß-methylene)diphosphate (AOPCP) with human CD73, we designed a series of novel monophosphonate small-molecule CD73 inhibitors. Among them, OP-5244 (35) proved to be a highly potent and orally bioavailable CD73 inhibitor. In preclinical studies, 35 completely inhibited ADO production in both human cancer cells and CD8+ T cells. Furthermore, 35 lowered the ratio of ADO/AMP significantly and reversed immunosuppression in mouse models, indicating its potential as an in vivo tool compound for further development.

Probing Trends in Enantioinduction via Substrate Design: Palladium-Catalyzed Decarboxylative Allylic Alkylation of α-Enaminones.

Herein, we report the palladium-catalyzed decarboxylative asymmetric allylic alkylation of α-enaminones. In addition to serving as valuable synthetic building blocks, we exploit the α-enaminone scaffold and its derivatives as probes to highlight structural and electronic factors that govern enantioselectivity in this asymmetric alkylation reaction. Utilizing the (S)-t-BuPHOX ligand in a variety of nonpolar solvents, the alkylated products are obtained in up to 99% yield and 99% enantiomeric excess.

Tips for pandemic response planning for Internal Medicine training programs.

This article was migrated. The article was marked as recommended. The current Coronavirus Disease 2019 (COVID-19) pandemic has strained hospital systems and training programs across the world. As capacity issues mount and trainees are called upon to provide frontline medical care, programs and institutions have had to rapidly evolve to redefine the trainee experience. To that end, there is a paucity of literature regarding how healthcare training programs should operate during a global pandemic. Here, we aim to describe twelve evidence-based recommendations for coordinating a cohesive, systematic approach to pandemic response planning for Internal Medicine residency training programs. These tips encompass inpatient and outpatient practices, provider safety, resuscitation, virtual education programming and resident wellbeing. Though many of these considerations or recommendations were not described during the COVID-19 pandemic, these tips have been described previously in the literature, are applicable to the current pandemic and could be easily extrapolated to future crises.

Exploring Bipedal Hopping through Computational Evolution.

Bipedal hopping is an efficient form of locomotion, yet it remains relatively rare in the natural world. Previous research has suggested that the tail balances the angular momentum of the legs to produce steady state bipedal hopping. In this study, we employ a 3D physics simulation engine to optimize gaits for an animat whose control and morphological characteristics are subject to computational evolution, which emulates properties of natural evolution. Results indicate that the order of gene fixation during the evolutionary process influences whether a bipedal hopping or quadrupedal bounding gait emerges. Furthermore, we found that in the most effective bipedal hoppers the tail balances the angular momentum of the torso, rather than the legs as previously thought. Finally, there appears to be a specific range of tail masses, as a proportion of total body mass, wherein the most effective bipedal hoppers evolve.

AI for Not Bad.

Hype surrounds the promotions, aspirations, and notions of "artificial intelligence (AI) for social good" and its related permutations. These terms, as used in data science and particularly in public discourse, are vague. Far from being irrelevant to data scientists or practitioners of AI, the terms create the public notion of the systems built. Through a critical reflection, I explore how notions of AI for social good are vague, offer insufficient criteria for judgement, and elide the externalities and structural interdependence of AI systems. Instead, the field known as "AI for social good" is best understood and referred to as "AI for not bad."

The role of lifetime anxiety history in the course of bipolar spectrum disorders.

Individuals with bipolar spectrum disorder (BSD) frequently meet criteria for comorbid anxiety disorders, and anxiety may be an important factor in the etiology and course of BSDs. The current study examined the association of lifetime anxiety disorders with prospective manic/hypomanic versus major depressive episodes. Participants were 244 young adults (aged 17-26) with milder forms of BSDs (i.e., bipolar-II, cyclothymia, BD-NOS). First, bivariate analyses assessed differences in baseline clinical characteristics between participants with and without DSM-IV anxiety diagnoses. Second, negative binomial regression analyses tested whether lifetime anxiety predicted number of manic/hypomanic or major depressive episodes developed during the study. Third, survival analyses evaluated whether lifetime anxiety predicted time to onset of manic/hypomanic and major depressive episodes. Results indicated that anxiety history was associated with greater illness severity at baseline. Over follow-up, anxiety history predicted fewer manic/hypomanic episodes, but did not predict number of major depressive episodes. Anxiety history also was associated with longer time to onset of manic/hypomanic episodes, but shorter time to onset of depressive episodes. Findings corroborate past studies implicating anxiety disorders as salient influences on the course of BSDs. Moreover, results extend prior research by indicating that anxiety disorders may be linked with reduced manic/hypomanic phases of illness.

Enantioselective Construction of Acyclic Quaternary Carbon Stereocenters: Palladium-Catalyzed Decarboxylative Allylic Alkylation of Fully Substituted Amide Enolates.

We report a divergent and modular protocol for the preparation of acyclic molecular frameworks containing newly created quaternary carbon stereocenters. Central to this approach is a sequence composed of a (1) regioselective and -retentive preparation of allyloxycarbonyl-trapped fully substituted stereodefined amide enolates and of a (2) enantioselective palladium-catalyzed decarboxylative allylic alkylation reaction using a novel bisphosphine ligand.

Evolution of Joint-Level Control for Quadrupedal Locomotion.

We investigate a hierarchical approach to robot control inspired by joint-level control in animals. The method combines a high-level controller, consisting of an artificial neural network (ANN), with joint-level controllers based on digital muscles. In the digital muscle model (DMM), morphological and control aspects of joints evolve concurrently, emulating the musculoskeletal system of natural organisms. We introduce and compare different approaches for connecting outputs of the ANN to DMM-based joints. We also compare the performance of evolved animats with ANN-DMM controllers with those governed by only high-level (ANN-only) and low-level (DMM-only) controllers. These results show that DMM-based systems outperform their ANN-only counterparts while also exhibiting less complex ANNs in terms of the number of connections and neurons. The main contribution of this work is to explore the evolution of artificial systems where, as in natural organisms, some aspects of control are realized at the joint level.

Reward and punishment sensitivity and disordered eating behaviors in men and women.

BACKGROUND: Reward and punishment sensitivities have been identified as potential contributors to binge eating and compensatory behaviors, though few studies have examined gender differences in these behaviors. METHOD: A college-aged sample (N = 1,022) completed both the Eating Disorders Diagnostic Scale (EDDS) and Sensitivity to Punishment/Sensitivity to Reward Questionnaire (SPSRQ). RESULTS: Rates of binge eating were similar in males and females. Among those reporting compensatory behaviors, women reported engaging in compensatory behaviors more frequently than men. Sensitivity to reward and sensitivity to punishment were both positively associated with binge eating frequency in both genders. In contrast, women with high reward sensitivity reported engaging in compensatory behaviors more frequently. CONCLUSIONS: Rates of binge eating and compensatory weight control behaviors were similar between college-aged males and females, though females who engaged in compensatory behaviors did so more frequently than males. Sensitivity to punishment was greater in females, whereas sensitivity to reward was greater in males. Reward and punishment sensitivity were each positively associated with binge eating in both males and females, while only reward sensitivity was positively associated with compensatory behaviors in females.

Oxidized Low-Density Lipoprotein Immune Complex Priming of the Nlrp3 Inflammasome Involves TLR and FcγR Cooperation and Is Dependent on CARD9.

Oxidized low-density lipoprotein (oxLDL) is known to activate inflammatory responses in a variety of cells, especially macrophages and dendritic cells. Interestingly, much of the oxLDL in circulation is complexed to Abs, and these resulting immune complexes (ICs) are a prominent feature of chronic inflammatory disease, such as atherosclerosis, type-2 diabetes, systemic lupus erythematosus, and rheumatoid arthritis. Levels of oxLDL ICs often correlate with disease severity, and studies demonstrated that oxLDL ICs elicit potent inflammatory responses in macrophages. In this article, we show that bone marrow-derived dendritic cells (BMDCs) incubated with oxLDL ICs for 24 h secrete significantly more IL-1ß compared with BMDCs treated with free oxLDL, whereas there was no difference in levels of TNF-α or IL-6. Treatment of BMDCs with oxLDL ICs increased expression of inflammasome-related genes Il1a, Il1b, and Nlrp3, and pretreatment with a caspase 1 inhibitor decreased IL-1ß secretion in response to oxLDL ICs. This inflammasome priming was due to oxLDL IC signaling via multiple receptors, because inhibition of CD36, TLR4, and FcγR significantly decreased IL-1ß secretion in response to oxLDL ICs. Signaling through these receptors converged on the adaptor protein CARD9, a component of the CARD9-Bcl10-MALT1 signalosome complex involved in NF-κB translocation. Finally, oxLDL IC-mediated IL-1ß production resulted in increased Th17 polarization and cytokine secretion. Collectively, these data demonstrate that oxLDL ICs induce inflammasome activation through a separate and more robust mechanism than oxLDL alone and that these ICs may be immunomodulatory in chronic disease and not just biomarkers of severity.

Targeting quinolone- and aminocoumarin-resistant bacteria with new gyramide analogs that inhibit DNA gyrase.

Bacterial DNA gyrase is an essential type II topoisomerase that enables cells to overcome topological barriers encountered during replication, transcription, recombination, and repair. This enzyme is ubiquitous in bacteria and represents an important clinical target for antibacterial therapy. In this paper we report the characterization of three exciting new gyramide analogs-from a library of 183 derivatives-that are potent inhibitors of DNA gyrase and are active against clinical strains of gram-negative bacteria (Escherichia coli, Shigella flexneri, and Salmonella enterica; 3 of 10 wild-type strains tested) and gram-positive bacteria (Bacillus spp., Enterococcus spp., Staphylococcus spp., and Streptococcus spp.; all 9 of the wild-type strains tested). E. coli strains resistant to the DNA gyrase inhibitors ciprofloxacin and novobiocin display very little cross-resistance to these new gyramides. In vitro studies demonstrate that the new analogs are potent inhibitors of the DNA supercoiling activity of DNA gyrase (IC50s of 47-170 nM) but do not alter the enzyme's ATPase activity. Although mutations that confer bacterial cells resistant to these new gyramides map to the genes encoding the subunits of the DNA gyrase (gyrA and gyrB genes), overexpression of GyrA, GyrB, or GyrA and GyrB together does not suppress the inhibitory effect of the gyramides. These observations support the hypothesis that the gyramides inhibit DNA gyrase using a mechanism that is unique from other known inhibitors.

Enantioconvergent catalysis.

An enantioconvergent catalytic process has the potential to convert a racemic starting material to a single highly enantioenriched product with a maximum yield of 100%. Three mechanistically distinct approaches to effecting enantioconvergent catalysis are identified, and recent examples of each are highlighted. These processes are compared to related, non-enantioconvergent methods.

Leadership for All: An Internal Medicine Residency Leadership Development Program.

BACKGROUND: Developing effective leadership skills in physicians is critical for safe patient care. Few residency-based models of leadership training exist. OBJECTIVE: We evaluated residents' readiness to engage in leadership training, feasibility of implementing training for all residents, and residents' acceptance of training. METHODS: In its fourth year, the Leadership Development Program (LDP) consists of twelve 90-minute modules (eg, Team Decision Making and Bias, Leadership Styles, Authentic Leadership) targeting all categorical postgraduate year (PGY) 1 residents. Modules are taught during regularly scheduled educational time. Focus group surveys and discussions, as well as annual surveys of PGY-1s assessed residents' readiness to engage in training. LDP feasibility was assessed by considering sustainability of program structures and faculty retention, and resident acceptance of training was assessed by measuring attendance, with the attendance goal of 8 of 12 modules. RESULTS: Residents thought leadership training would be valuable if content remained applicable to daily work, and PGY-1 residents expressed high levels of interest in training. The LDP is part of the core educational programming for PGY-1 residents. Except for 2 modules, faculty presenters have remained consistent. During academic year 2014-2015, 45% (13 of 29) of categorical residents participated in at least 8 of 12 modules, and 72% (21 of 29) participated in at least 7 of 12. To date, 125 categorical residents have participated in training. CONCLUSIONS: Residents appeared ready to engage in leadership training, and the LDP was feasible to implement. The attendance goal was not met, but attendance was sufficient to justify program continuation.

Assessment and Treatment of Bipolar Spectrum Disorders in Emerging Adulthood: Applying the Behavioral Approach System Hypersensitivity Model.

Bipolar disorder is associated with a host of negative physical and interpersonal outcomes including suicide. Emerging adulthood is an age of risk for the onset of bipolar spectrum disorders (BSD) and there has been increased effort to focus on early identification and subsequent intervention for BSDs during this developmental period. Recent research on the behavioral approach system (BAS) hypersensitivity model of bipolar disorder may have implications for the assessment and treatment of BSD in emerging adulthood. We summarize relevant findings on the BAS hypersensitivity model that support the use of reward sensitivity in the early identification of BSDs and suggest evidence-based strategies for clinical work with emerging adults with bipolar spectrum disorders.

Acute Systolic Heart Failure Associated with Complement-Mediated Hemolytic Uremic Syndrome.

Complement-mediated hemolytic uremic syndrome (otherwise known as atypical HUS) is a rare disorder of uncontrolled complement activation that may be associated with heart failure. We report the case of a 49-year-old female with no history of heart disease who presented with microangiopathic hemolytic anemia, thrombocytopenia, and acute kidney injury. Given her normal ADAMSTS13 activity, evidence of increased complement activation, and renal biopsy showing evidence of thrombotic microangiopathy, she was diagnosed with complement-mediated HUS. She subsequently developed acute hypoxemic respiratory failure secondary to pulmonary edema requiring intubation and mechanical ventilation. A transthoracic echocardiogram showed evidence of a Takotsubo cardiomyopathy with an estimated left ventricular ejection fraction of 20%, though ischemic cardiomyopathy could not be ruled out. Treatment was initiated with eculizumab. After several failed attempts at extubation, she eventually underwent tracheotomy. She also required hemodialysis to improve her uremia and hypervolemia. After seven weeks of hospitalization and five doses of eculizumab, her renal function and respiratory status improved, and she was discharged in stable condition on room air and independent of hemodialysis. Our case illustrates a rare association between acute systolic heart failure and complement-mediated HUS and highlights the potential of eculizumab in stabilizing even the most critically-ill patients with complement-mediated disease.