The complement system drives local inflammatory tissue priming by metabolic reprogramming of synovial fibroblasts.

Arthritis typically involves recurrence and progressive worsening at specific predilection sites, but the checkpoints between remission and persistence remain unknown. Here, we defined the molecular and cellular mechanisms of this inflammation-mediated tissue priming. Re-exposure to inflammatory stimuli caused aggravated arthritis in rodent models. Tissue priming developed locally and independently of adaptive immunity. Repeatedly stimulated primed synovial fibroblasts (SFs) exhibited enhanced metabolic activity inducing functional changes with intensified migration, invasiveness and osteoclastogenesis. Meanwhile, human SF from patients with established arthritis displayed a similar primed phenotype. Transcriptomic and epigenomic analyses as well as genetic and pharmacological targeting demonstrated that inflammatory tissue priming relies on intracellular complement C3- and C3a receptor-activation and downstream mammalian target of rapamycin- and hypoxia-inducible factor 1α-mediated metabolic SF invigoration that prevents activation-induced senescence, enhances NLRP3 inflammasome activity, and in consequence sensitizes tissue for inflammation. Our study suggests possibilities for therapeutic intervention abrogating tissue priming without immunosuppression.

Prevalence of Cognitive and Manual Dexterity Disorders Among Men Following Artificial Urinary Sphincter Placement.

PURPOSE: Cognitive ability and manual dexterity sufficient to operate an artificial urinary sphincter (AUS) are critical for device function and safety. We aimed to define the incidence of cognitive and/or dexterity disorders among men after AUS. We secondarily aimed to assess for association between these disorders and postimplant complications. MATERIALS AND METHODS: This is a retrospective cohort study using the SEER (Surveillance, Epidemiology, and End Results)-Medicare linked database (2000-2018). We included men ≥ 66 years diagnosed with prostate cancer between 2001 to 2015 who subsequently underwent AUS placement. We excluded patients with < 1-year continuous fee-for-service Medicare enrollment or cognitive and/or manual dexterity disorder diagnoses prior to AUS implant. Subsequent cognitive/dexterity disorders and implant-related complications were queried using appropriate ICD (International Classification of Diseases)-9/10 and/or CPT (Current Procedural Terminology) codes. Associations between cognitive/dexterity disorders and postimplant complications were assessed using extended Cox proportional hazards modeling. Secondary analysis focused on serious complications (device revision/removal, Fournier's gangrene, urethral erosion). RESULTS: We identified 1560 men who underwent AUS who met inclusion criteria. Median age was 73.0 (IQR 70-77) years. Cumulative incidence function analysis estimated 44% and 17% incidence of cognitive and manual dexterity disorder, respectively, at 15 years post-AUS. Presence of cognitive with/without manual dexterity disorder was associated with increased hazard of any, but not serious, complication during follow-up. CONCLUSIONS: A significant proportion of patients develop cognitive and/or manual dexterity disorders following AUS. These data support the need for close longitudinal monitoring after implant.

Classification of hallux valgus deformity-is there a standard?

INTRODUCTION: Hallux valgus deformity severity is one determent for the surgical procedure for hallux valgus (HV) correction. HV deformities are usually classified into mild/moderate/severe. The aim was to investigate the cut-off criteria used to classify HV deformity. MATERIALS AND METHODS: The study was based on a previous living systematic review. Four common databases were searched for the last decade. All review-steps were conducted by two reviewers. Data assessed were the individual cut-off values used to classify HV deformity into mild/moderate/severe, and the referenced classification systems. RESULTS: 46 studies were included. 21/18 studies grade deformity based on the intermetatarsal angle (IMA)/ hallux valgus angle (HVA) with great heterogeneity throughout the different cut-off values. The most referenced classification systems were the Coughlin and Mann's and the Robinson classification. CONCLUSIONS: The currently used classification systems are heterogenic, and no standard could be defined. The community should define a uniform classification system. LEVEL OF EVIDENCE: Level I, systematic review of randomized controlled trials and prospective comparative studies.

A reciprocal perspective on the differential associations between personality traits and multiple indicators of academic achievement.

OBJECTIVE: This study aims to explore the reciprocal associations between personality traits (conscientiousness and openness to experience) and academic achievement in adolescents, using the Personality Achievement Saturation Hypothesis (PASH). BACKGROUND: Personality traits, especially conscientiousness, and openness, have been identified as strong predictors of academic achievement. The PASH provides a framework for understanding these relationships but has mainly been studied from a unidirectional perspective. This study extends the PASH to examine reciprocal associations and how they vary with different achievement indicators. METHODS: Using large-scale panel data (N = 6482) of secondary school students in Germany, we applied cross-lagged panel models and latent change score models to examine the differential reciprocal associations between personality traits (conscientiousness/openness) and academic achievement (school grades/achievement test scores) in language and math over two years from grades 7 to 9. RESULTS: In line with the PASH, initial levels of conscientiousness were more strongly associated with school grades than with achievement test scores over two years. Simultaneously, prior school grades were more strongly associated with conscientiousness over two years. However, initial levels of openness did not show differential associations with either school grades or achievement test scores over two years. Similarly, prior school grades and achievement test scores were also not differentially associated with openness over two years. CONCLUSIONS: Our findings introduce an innovative lens through which we observe how the PASH can be leveraged to explain the differential reciprocal associations between conscientiousness and academic achievement. Further research is needed to examine if PASH could be similarly extended to disentangle the associations between openness and academic achievement.

The effect of stress on rates of asexual reproduction in an invasive planarian.

Animal reproduction under stressful conditions is often reduced, with current survival and future reproduction being generally traded off against current reproductive activity. This study examines the impacts of physical and chemical stressors on the rates of asexual reproduction of the invasive planarian Girardia tigrina. 320 wild-caught planaria (mixed size class) were kept individually in Petri dishes such that their individual rates of fission through fragmentation could be easily monitored. Four treatment groups were compared, one chemical (5 mg/L ammonia) and one physical (decapitation), in comparison to a negative control (animals were starved of food) and a positive control where the animals were given an abundance of food. The two treatment groups immediately began reproducing asexually and accumulated the highest number of fissions over the course of the 12-day investigation period, while the positive control only began to fission after 7 days. We propose that the reproductive response observed here is an adaptive one to stressful conditions, whereby the likelihood of survival through numerical abundance is enhanced, although the size and vulnerability of resulting fragments may impose a balancing cost. The response may play a role in the invasiveness of G. tigrina by making it able to colonize environments where adverse conditions prevail.

Nonverbal Synchrony: An Indicator of Clinical Communication Quality in Racially-Concordant and Racially-Discordant Oncology Interactions.

OBJECTIVES: The aim of this cross-sectional study was to apply a novel software to measure and compare levels of nonverbal synchrony, as a potential indicator of communication quality, in video recordings of racially-concordant and racially-discordant oncology interactions. Predictions include that the levels of nonverbal synchrony will be greater during racially-concordant interactions than racially-discordant interactions, and that levels of nonverbal synchrony will be associated with traditional measures of communication quality in both racially-concordant and racially-discordant interactions. DESIGN: This is a secondary observational analysis of video-recorded oncology treatment discussions collected from 2 previous studies. SETTING: Two National Cancer Institute-designated Comprehensive Cancer Centers and another large urban cancer center. PARTICIPANTS: Participants from Study 1 include 161 White patients with cancer and 11 White medical oncologists. Participants from Study 2 include 66 Black/African-American patients with cancer and 17 non-Black medical oncologists. In both studies inclusion criteria for patients was a recent cancer diagnosis; in Study 2 inclusion criteria was identifying as Black/African American. MAIN OUTCOME MEASURES: Nonverbal synchrony and communication quality. RESULTS: Greater levels of nonverbal synchrony were observed in racially-discordant interactions than in racially-concordant interactions. Levels of nonverbal synchrony were associated with indicators of communication quality, and these associations were more consistently found in racially-discordant interactions. CONCLUSION: This study advances clinical communication and disparities research by successfully applying a novel approach capturing the unconscious nature of communication, and revealing differences in communication in racially-discordant and racially-concordant oncology interactions. This study highlights the need for further exploration of nonverbal aspects relevant to patient-physician interactions.

The Future Strikes Back: Using Future Treatments to Detect and Reduce Hidden Bias.

Conventional advice discourages controlling for postoutcome variables in regression analysis. By contrast, we show that controlling for commonly available postoutcome (i.e., future) values of the treatment variable can help detect, reduce, and even remove omitted variable bias (unobserved confounding). The premise is that the same unobserved confounder that affects treatment also affects the future value of the treatment. Future treatments thus proxy for the unmeasured confounder, and researchers can exploit these proxy measures productively. We establish several new results: Regarding a commonly assumed data-generating process involving future treatments, we (1) introduce a simple new approach and show that it strictly reduces bias, (2) elaborate on existing approaches and show that they can increase bias, (3) assess the relative merits of alternative approaches, and (4) analyze true state dependence and selection as key challenges. (5) Importantly, we also introduce a new nonparametric test that uses future treatments to detect hidden bias even when future-treatment estimation fails to reduce bias. We illustrate these results empirically with an analysis of the effect of parental income on children's educational attainment.

Shedding light on the effects of supportive techniques on nonverbal synchrony and their moderators in psychotherapy for depression.

Objective: Accumulating research demonstrates the importance of utilizing supportive techniques in psychotherapy; however, little is known about therapeutic processes that are set in motion following the use of supportive techniques. The present study examined the effects of supportive techniques on nonverbal synchrony, both at the sample level and at the individual differences level.Method: The sample consisted of 86 patients from a randomized controlled trial for treatment of depression. Supportive techniques were rated by patients and therapists after every session, and nonverbal synchrony was quantified by motion energy analysis (MEA) for each session. The ability of supportive techniques to predict subsequent nonverbal synchrony was examined using polynomial regression and response surface analysis.Results: The findings suggest that, at the sample level, greater use of supportive techniques was a significant predictor of subsequent higher levels of nonverbal synchrony. At the individual differences level, this effect was significant for patients with low levels of depression severity and personality disorders, yet not significant for patients with high levels.Conclusion: The present study demonstrates that greater use of supportive techniques in treatment may facilitate a process that manifests as higher levels of synchrony, especially for patients with lower levels of personality disorders and depression.

Electron-Hole Crossover in Gate-Controlled Bilayer Graphene Quantum Dots.

Electron and hole Bloch states in bilayer graphene exhibit topological orbital magnetic moments with opposite signs, which allows for tunable valley-polarization in an out-of-plane magnetic field. This property makes electron and hole quantum dots (QDs) in bilayer graphene interesting for valley and spin-valley qubits. Here, we show measurements of the electron-hole crossover in a bilayer graphene QD, demonstrating opposite signs of the magnetic moments associated with the Berry curvature. Using three layers of top gates, we independently control the tunneling barriers while tuning the occupation from the few-hole regime to the few-electron regime, crossing the displacement-field-controlled band gap. The band gap is around 25 meV, while the charging energies of the electron and hole dots are between 3 and 5 meV. The extracted valley g-factor is around 17 and leads to opposite valley polarization for electrons and holes at moderate B-fields. Our measurements agree well with tight-binding calculations for our device.

rMEA: An R package to assess nonverbal synchronization in motion energy analysis time-series.

Introduction. Motion Energy Analysis (MEA) is a procedure that allows to automatically assess the amount of persons' movement from video recordings. Recent studies used MEA to investigate nonverbal synchrony, i.e., the occurrence of simultaneous movement, suggesting the existence of an association with relationship quality. In patient-therapist dyads, synchrony predicted therapeutic alliance, empathy, as well as treatment outcome. Package description. The article presents rMEA, an open-source R package that allows to import, filter, and visualize dyadic time-series of nonverbal behaviour generated by other MEA software. The package includes a fast, state-of-the-art, moving window cross-correlation algorithm with lag analysis, which provides a user-friendly interface for the assessment of nonverbal synchrony. Through the analysis of a motivating example (40 psychotherapy intake interviews split between dropouts and good cases) the article provides an in-depth description of the package main functions and a tutorial for a typical analysis in this field, requiring only the most basic knowledge of the R language and environment. The rich visualization capabilities of the software provide powerful tools for the various steps involved in the diagnostics, analysis, interpretation and publication of these data. Conclusions. Overall, the paper aims to empower psychotherapy researchers and other interaction scientists to investigate nonverbal synchrony in their own dyads.

Observation of the Spin-Orbit Gap in Bilayer Graphene by One-Dimensional Ballistic Transport.

We report on measurements of quantized conductance in gate-defined quantum point contacts in bilayer graphene that allow the observation of subband splittings due to spin-orbit coupling. The size of this splitting can be tuned from 40 to 80 µeV by the displacement field. We assign this gate-tunable subband splitting to a gap induced by spin-orbit coupling of Kane-Mele type, enhanced by proximity effects due to the substrate. We show that this spin-orbit coupling gives rise to a complex pattern in low perpendicular magnetic fields, increasing the Zeeman splitting in one valley and suppressing it in the other one. In addition, we observe a spin polarized channel of 6e^{2}/h at high in-plane magnetic field and signatures of interaction effects at the crossings of spin-split subbands of opposite spins at finite magnetic field.

Motion energy analysis (MEA): A primer on the assessment of motion from video.

Nonverbal behavior is a central factor influencing the therapeutic relationship. Despite broad agreement on its importance, empirical studies assessing nonverbal behavior in counseling and psychotherapy are relatively scarce and often limited to few cases. One restraining factor may be the resources needed when assessing nonverbal behavior. Movement dynamics are an exemplary aspect of nonverbal behavior that can be captured with computer vision-a discipline concerned with the automated analysis of footage captured on video. One of the simplest methods requiring no special detectors, devices, or markers on patients or therapists is based on the assessment of differences in sequences of pictures (frames) found in video recordings. Algorithms of so-called frame-differencing methods may be implemented on commonly available computers, and they provide a good, straightforward assessment of, for example, patients' and therapists' movement dynamics in counseling and therapy sessions. Frame-differencing methods in psychology date back 36 years, but their use in counseling and psychotherapy research is only recently gaining momentum. In this introductory article, the use of one specific application suitable for the assessment of human motion from archival video material is presented. Motion energy analysis (MEA) is a procedure particularly appropriate for clinicians and researchers who have access to recordings of sessions or who wish to record their own video material. Focusing on the phenomenon of nonverbal synchrony-the coordination of movement between patient and therapist-a step-by-step demonstration of the stages involved in a successful application of MEA in psychotherapy research is provided. (PsycInfo Database Record (c) 2020 APA, all rights reserved).

Innovative approaches to exploring processes of change in counseling psychology: Insights and principles for future research.

In recent years, innovative approaches have been implemented in counseling and psychotherapy research, creating new and exciting interdisciplinary subfields. The findings that emerged from the implementation of these approaches demonstrate their potential to deepen our understanding of therapeutic change. This article serves as an introduction to the "Innovative Approaches to Exploring Processes of Change in Counseling Psychology" special issue. The special issue includes articles representing several of the most promising approaches. Each article seeks to serve as a sourcebook for implementing a given approach in counseling research, in such areas as the assessment of coregulation processes, language processing, physiology, motion synchrony, event-related potentials, hormonal measures, and sociometric signals captured by a badge. The studies included in this special issue represent some of the most promising pathways for future studies and provide valuable resources for researchers, as well as clinicians interested in implementing such approaches and/or being educated consumers of empirical findings based on such approaches. This introduction synthesizes the articles in the special issue and proposes a list of guidelines for conducting and consuming research that implements new approaches for studying the process of therapeutic change. We believe that we are not far from the day when these approaches will be instrumental in everyday counseling practice, where they can assist therapists and patients in their collaborative efforts to reduce suffering and increase thriving. (PsycInfo Database Record (c) 2020 APA, all rights reserved).

Exploring the evolution of nonverbal synchrony in psychotherapy: The idiographic perspective provides a different picture.

Objectives: A methodological obstacle for the assessment of psychotherapy process concerns the compatibility between nomothetic versus idiographic approaches. Using quantitative methodology at an idiographic level, we seek to narrow this gap for the special case of nonverbal synchrony in psychotherapy dyads.Methods: Using quantitative idiographic process analysis (QUIPA), we combined the assessments of nonverbal synchrony-the coordination of patient's and therapist's body-movement-quantified with motion energy analysis (MEA), patient- and therapist session-reports, and patient's self-reports of symptomatology into multivariate time-series of psychotherapy process across the course of N = 12 dyadic psychotherapies with a total of N = 150 sessions. Adopting both mixed models as well as vector auto regressive models (VAR) to time-series, we aimed to extend previous results assessed in a randomized sample by exploring the evolution of nonverbal synchrony in psychotherapy dyads across time.Results: Aggregated idiographic data revealed that nonverbal synchrony was different from findings based on a previously reported nomothetic account: Associations with session-level outcome were weaker and did not replicate cross-sectional analyses.Conclusions: The application of idiographic assessments may help broadening our conception of synchrony in psychotherapy and also reminds us that ergodicity is not necessarily the usual case, but one of many possibilities.

Missing information in statewide and national cancer databases: Correlation with health risk factors, geographic disparities, and outcomes.

OBJECTIVE: The objectives of this study were to analyze factors associated with outcomes and missing data in women with epithelial ovarian cancer using institutional, state and national databases. METHODS: Data were abstracted from the University of Virginia cancer registry, Virginia Department of Health (VDH) database, and Surveillance, Epidemiology, and End Results (SEER) Program and analyzed for correlations with demographics, cancer characteristics, and outcomes. Statewide spatial associations between health risk factors such as smoking, obesity, and missing grade/stage were evaluated using bivariate LiSA in Geoda. RESULTS: There were 524 institutional, 3544 VDH, and 44,464 SEER cases of epithelial ovarian cancer. Institutional cases were younger, most often of white race, had increased grade 1, and decreased unknown grade and stage (all p < 0.001). Significant predictors of unknown grade were non-white race, older age, no surgery, unknown stage/stage IV, and unknown histology/adenocarcinoma. Unknown grade correlated with a significant survival disadvantage. Missing stage and grade correlated with county-level obesity and smoking, as rural regions in Southwest and Southside Virginia had high rates of health risk factors and missing stage/grade compared to urban, affluent regions in Northern Virginia. CONCLUSIONS: Over a third of nationally reported cases have an unknown grade and 10-20% have an unknown stage which correlates with the worst survival. Predictors of unknown grade include insurance, age, race, smoking status, obesity, and rural setting. Missing data may represent geographical differences or disparities in cancer care available as significantly fewer cases had an unknown grade/stage at a tertiary academic medical center compared to VDH and SEER.

Growing Wealth Gaps in Education.

Prior research on trends in educational inequality has focused chiefly on changing gaps in educational attainment by family income or parental occupation. In contrast, this contribution provides the first assessment of trends in educational attainment by family wealth and suggests that we should be at least as concerned about growing wealth gaps in education. Despite overall growth in educational attainment and some signs of decreasing wealth gaps in high school attainment and college access, I find a large and rapidly increasing wealth gap in college attainment between cohorts born in the 1970s and 1980s, respectively. This growing wealth gap in higher educational attainment co-occurred with a rise in inequality in children's wealth backgrounds, although the analyses also suggest that the latter does not fully account for the former. Nevertheless, the results reported here raise concerns about the distribution of educational opportunity among today's children who grow up in a context of particularly extreme wealth inequality.

Grand Advantage: Family Wealth and Grandchildren's Educational Achievement in Sweden.

We study the role of family wealth for children's educational achievement using novel and unique Swedish register data. In particular, we focus on the relationship between grandparents' wealth and their grandchildren's educational achievement. Doing so allows us to reliably establish the independent role of wealth in contributing to long-term inequalities in opportunity. We use regression models with rich controls to account for observed socioeconomic characteristics of families, cousin fixed effects to net out potentially unobserved grandparental effects, and marginal structural models to account for endogenous selection. We find substantial associations between grandparents' wealth and their grandchildren's grade point averages (GPA) in the 9th grade that are only partly mediated by the socioeconomic characteristics and wealth of parents. Our findings indicate that family wealth inequality - even in a comparatively egalitarian context like Sweden - has profound consequences for the distribution of opportunity across multiple generations. We posit that our estimates of the long-term consequences of wealth inequality may be conservative for nations other than Sweden, like the United States, where family wealth - in addition to its insurance and normative functions - allows the direct purchase of educational quality and access.

Self-navigation under non-steady-state conditions: Cardiac and respiratory self-gating of inversion recovery snapshot FLASH acquisitions in mice.

PURPOSE: An algorithm is presented to enable cardiac and respiratory self-gating in combination with Inversion Recovery Look-Locker read-outs. METHODS: A radial inversion recovery snapshot FLASH sequence was adapted for retrospective cardiac T1 measurements in mice. Cardiac and respiratory data were extracted from the k-space center of radial projections and an adapted method for retrospective cardiac synchronization is introduced. Electrocardiogram (ECG) data was acquired concurrently for validation of the proposed self-gating technique. T1 maps generated by the proposed technique were compared with maps reconstructed with the ECG reference. RESULTS: Respiratory gating and cardiac trigger points could be obtained for the whole time course of the relaxation dynamic and correlate very well to the ECG signal. T1 maps reconstructed with the self-gating technique are in very good agreement with maps reconstructed with the external reference. CONCLUSION: The proposed method extends "wireless" cardiac MRI to non-steady-state inversion recovery measurements. T1 maps were generated with a quality comparable to ECG based reconstructions. As the method does not rely on an ECG trigger signal it provides easier animal handling. Magn Reson Med 76:1887-1894, 2016. © 2016 International Society for Magnetic Resonance in Medicine.

GPI-anchored carbonic anhydrase IV displays both intra- and extracellular activity in cRNA-injected oocytes and in mouse neurons.

Soluble cytosolic carbonic anhydrases (CAs) are well known to participate in pH regulation of the cytoplasm of mammalian cells. Membrane-bound CA isoforms--such as isoforms IV, IX, XII, XIV, and XV--also catalyze the reversible conversion of carbon dioxide to protons and bicarbonate, but at the extracellular face of the cell membrane. When human CA isoform IV was heterologously expressed in Xenopus oocytes, we observed, by measuring H(+) at the outer face of the cell membrane and in the cytosol with ion-selective microelectrodes, not only extracellular catalytic CA activity but also robust intracellular activity. CA IV expression in oocytes was confirmed by immunocytochemistry, and CA IV activity measured by mass spectrometry. Extra- and intracellular catalytic activity of CA IV could be pharmacologically dissected using benzolamide, the CA inhibitor, which is relatively slowly membrane-permeable. In acute cerebellar slices of mutant mice lacking CA IV, cytosolic H(+) shifts of granule cells following CO(2) removal/addition were significantly slower than in wild-type mice. Our results suggest that membrane-associated CA IV contributes robust catalytic activity intracellularly, and that this activity participates in regulating H(+) dynamics in the cytosol, both in injected oocytes and in mouse neurons.