Quantifying the relative importance of genetics and environment on the comorbidity between mental and cardiometabolic disorders using 17 million Scandinavians.

Mental disorders are leading causes of disability and premature death worldwide, partly due to high comorbidity with cardiometabolic disorders. Reasons for this comorbidity are still poorly understood. We leverage nation-wide health records and near-complete genealogies of Denmark and Sweden (n = 17 million) to reveal the genetic and environmental contributions underlying the observed comorbidity between six mental disorders and 15 cardiometabolic disorders. Genetic factors contributed about 50% to the comorbidity of schizophrenia, affective disorders, and autism spectrum disorder with cardiometabolic disorders, whereas the comorbidity of attention-deficit/hyperactivity disorder and anorexia with cardiometabolic disorders was mainly or fully driven by environmental factors. In this work we provide causal insight to guide clinical and scientific initiatives directed at achieving mechanistic understanding as well as preventing and alleviating the consequences of these disorders.

Hysterectomy Techniques and Outcomes for Benign Large Uteri: A Systematic Review.

OBJECTIVE: To identify the optimal hysterectomy approach for large uteri in gynecologic surgery for benign indications from a perioperative morbidity standpoint. DATA SOURCES: PubMed and Embase databases were searched from inception through September 19, 2022. Meta-analyses were conducted as feasible. METHODS OF STUDY SELECTION: This review included studies that compared routes of hysterectomy with or without bilateral salpingo-oophorectomy for large uteri (12 weeks or more or 250 g or more) and excluded studies with any concurrent surgery for pelvic organ prolapse, incontinence, gynecologic malignancy, or any obstetric indication for hysterectomy. TABULATION, INTEGRATION, AND RESULTS: The review included 25 studies comprising nine randomized trials, two prospective, and 14 retrospective nonrandomized comparative studies. Studies were at high risk of bias. There was lower operative time for total vaginal hysterectomy compared with laparoscopically assisted vaginal hysterectomy (LAVH) (mean difference 39 minutes, 95% CI, 18-60) and total vaginal hysterectomy compared with total laparoscopic hysterectomy (mean difference 50 minutes, 95% CI, 29-70). Total laparoscopic hysterectomy was associated with much greater risk of ureteral injury compared with total vaginal hysterectomy (odds ratio 7.54, 95% CI, 2.52-22.58). There were no significant differences in bowel injury rates between groups. There were no differences in length of stay among the laparoscopic approaches. For LAVH compared with total vaginal hysterectomy, randomized controlled trials favored total vaginal hysterectomy for length of stay. When rates of blood transfusion were compared between these abdominal hysterectomy and robotic-assisted total hysterectomy routes, abdominal hysterectomy was associated with a sixfold greater risk of transfusion than robotic-assisted total hysterectomy (6.31, 95% CI, 1.07-37.32). Similarly, single studies comparing robotic-assisted total hysterectomy with LAVH, total laparoscopic hysterectomy, or total vaginal hysterectomy all favored robotic-assisted total hysterectomy for reduced blood loss. CONCLUSION: Minimally invasive routes are safe and effective and have few complications. Minimally invasive approach (vaginal, laparoscopic, or robotic) results in lower blood loss and shorter length of stay, whereas the abdominal route has a shorter operative time. SYSTEMATIC REVIEW REGISTRATION: PROSPERO, CRD42021233300.

Freeform generative design of complex functional structures.

Generative machine learning is poised to revolutionise a range of domains where rational design has long been the de facto approach: where design is practically a time consuming and frustrating process guided by heuristics and intuition. In this article we focus on the domain of flow chemistry, which is an ideal candidate for generative design approaches. We demonstrate a generative machine learning framework that optimises diverse, bespoke reactor elements for flow chemistry applications, combining evolutionary algorithms and a scalable fluid dynamics solver for in silico performance assessment. Experimental verification confirms the discovery of never-before-seen bespoke mixers whose performance exceeds the state of the art by 45%. These findings highlight the power of autonomous generative design to improve the operational performance of complex functional structures, with potential wide-ranging industrial applications.

An epidemiological study of season of birth, mental health, and neuroimaging in the UK Biobank.

Environmental exposures during the perinatal period are known to have a long-term effect on adult physical and mental health. One such influential environmental exposure is the time of year of birth which affects the amount of daylight, nutrients, and viral load that an individual is exposed to within this key developmental period. Here, we investigate associations between season of birth (seasonality), four mental health traits (n = 137,588) and multi-modal neuroimaging measures (n = 33,212) within the UK Biobank. Summer births were associated with probable recurrent Major Depressive Disorder (ß = 0.026, pcorr = 0.028) and greater mean cortical thickness in temporal and occipital lobes (ß = 0.013 to 0.014, pcorr<0.05). Winter births were associated with greater white matter integrity globally, in the association fibers, thalamic radiations, and six individual tracts (ß = -0.013 to -0.022, pcorr<0.05). Results of sensitivity analyses adjusting for birth weight were similar, with an additional association between winter birth and white matter microstructure in the forceps minor and between summer births, greater cingulate thickness and amygdala volume. Further analyses revealed associations between probable depressive phenotypes and a range of neuroimaging measures but a paucity of interactions with seasonality. Our results suggest that seasonality of birth may affect later-life brain structure and play a role in lifetime recurrent Major Depressive Disorder. Due to the small effect sizes observed, and the lack of associations with other mental health traits, further research is required to validate birth season effects in the context of different latitudes, and by co-examining genetic and epigenetic measures to reveal informative biological pathways.

Patterns of Care for Medicare Beneficiaries With Metastatic Prostate Cancer.

INTRODUCTION: Therapeutic options for men with metastatic prostate cancer have increased in the past decade. We studied recent treatment patterns for men with metastatic prostate cancer and how treatment patterns have changed over time. METHODS: Using the Surveillance, Epidemiology, and End Results‒Medicare database, we identified fee-for-service Medicare beneficiaries who either were diagnosed with metastatic prostate cancer or developed metastases following diagnosis, as indicated by the presence of claims with diagnoses codes for metastatic disease, between 2007 and 2017. We evaluated treatment patterns using claims. RESULTS: We identified 29,800 men with metastatic disease, of whom 4721 (18.8%) had metastatic disease at their initial diagnosis. The mean age was 77 years, and 77.9% of patients were non-Hispanic White. The proportion receiving antineoplastic agents within 3 years of the index date increased over time (from 9.7% in 2007 to 25.9% in 2017; P < .001). Opioid use within 3 years of prostate cancer diagnosis was stable during 2007 to 2013 (around 73%) but decreased through 2017 to 65.5% (P < .001). Patients diagnosed during 2015 to 2017 had longer median survival (32.6 months) compared to those diagnosed during 2007 to 2010 (26.6 months; P < .001). CONCLUSIONS: Most metastatic prostate cancer patients do not receive life-prolonging antineoplastic therapies. Improved adoption of effective cancer therapies when appropriate may increase length and quality of survival among metastatic prostate cancer patients.

Quantifying the Relative Importance of Genetics and Environment on the Comorbidity between Mental- and Cardiometabolic Disorders: A Comprehensive Analysis of National Register Data from 17 million Scandinavians.

Mental disorders (MDs) are leading causes of disability and premature death worldwide, partly due to high comorbidity with cardiometabolic disorders (CMDs). Reasons for this comorbidity are still poorly understood. We leverage nation-wide health records and complete genealogies of Denmark and Sweden (n=17 million) to reveal the genetic and environmental contributions underlying the observed comorbidity between six MDs and 14 CMDs. Genetic factors contributed about 50% to the comorbidity of schizophrenia, affective disorders, and autism spectrum disorder with CMDs, whereas the comorbidity of attention-deficit/hyperactivity disorder and anorexia with CMDs was mainly or fully driven by environmental factors. These findings provide causal insight to guide clinical and scientific initiatives directed at achieving mechanistic understanding as well as preventing and alleviating the consequences of these disorders.

Fin-Bayes: A Multi-Objective Bayesian Optimization Framework for Soft Robotic Fingers.

Computational design is a critical tool to realize the full potential of Soft Robotics, maximizing their inherent benefits of high performance, flexibility, robustness, and safe interaction. Practically, computational design entails a rapid iterative search process over a parameterized design space, with assessment using (frequently) computational modeling and (more rarely) physical experimentation. Bayesian approaches work well for these expensive-to-analyze systems and can lead to efficient exploration of design space than comparative algorithms. However, such computational design typically entails weaknesses related to a lack of fidelity in assessment, a lack of sufficient iterations, and/or optimizing to a singular objective function. Our work directly addresses these shortcomings. First, we harness a sophisticated nonlinear Finite Element Modeling suite that explicitly considers geometry, material, and contact nonlinearity to perform rapid accurate characterization. We validate this through extensive physical testing using an automated test rig and printed robotic fingers, providing far more experimental data than that reported in the literature. Second, we explore a significantly larger design space than comparative approaches, with more free variables and more opportunity to discover novel, high performance designs. Finally, we use a multiobjective Bayesian optimizer that allows for the identification of promising trade-offs between two critical objectives, compliance and contact force. We test our framework on optimizing Fin Ray grippers, which are ubiquitous throughout research and industry due to their passive compliance and durability. Results demonstrate the benefits of our approach, allowing for the optimization and identification of promising gripper designs within an extensive design space, which are then 3D printed and usable in reality.

Starting fresh: a mixed method study of follower job satisfaction, trust, and views of their leader's behavior.

Introduction: The leadership literature has been dominated by the study of broad styles rather than the identification of specific key behaviors. To address this deficiency, a mixed method approach was utilized to explore how follower behavioral descriptions of their leaders would relate to potential outcomes of trust in that leader and job satisfaction. Methods: Data were collected from 273 hospital direct reports of 44 managers. They were asked to first describe the leadership approach of their managers in their own words, and then complete quantitative measures of the two potential outcomes. Results: The qualitative responses were coded into nine leadership behavior themes listed here in order from most to least often mentioned: Kindness, Supportive, Open to Input, Allow Autonomy, Engage with Team, Transparency, Fairness, Professionalism, Hold Accountable. All behavior themes related significantly to trust of the leader, with three themes relating significantly to job satisfaction (Transparency, Fairness, and Professionalism). Discussion: These results provide a more specific view of leader behavior than does the typical style approach.

Prospectively accelerated dynamic speech magnetic resonance imaging at 3 T using a self-navigated spiral-based manifold regularized scheme.

This work develops and evaluates a self-navigated variable density spiral (VDS)-based manifold regularization scheme to prospectively improve dynamic speech magnetic resonance imaging (MRI) at 3 T. Short readout duration spirals (1.3-ms long) were used to minimize sensitivity to off-resonance. A custom 16-channel speech coil was used for improved parallel imaging of vocal tract structures. The manifold model leveraged similarities between frames sharing similar vocal tract postures without explicit motion binning. The self-navigating capability of VDS was leveraged to learn the Laplacian structure of the manifold. Reconstruction was posed as a sensitivity-encoding-based nonlocal soft-weighted temporal regularization scheme. Our approach was compared with view-sharing, low-rank, temporal finite difference, extra dimension-based sparsity reconstruction constraints. Undersampling experiments were conducted on five volunteers performing repetitive and arbitrary speaking tasks at different speaking rates. Quantitative evaluation in terms of mean square error over moving edges was performed in a retrospective undersampling experiment on one volunteer. For prospective undersampling, blinded image quality evaluation in the categories of alias artifacts, spatial blurring, and temporal blurring was performed by three experts in voice research. Region of interest analysis at articulator boundaries was performed in both experiments to assess articulatory motion. Improved performance with manifold reconstruction constraints was observed over existing constraints. With prospective undersampling, a spatial resolution of 2.4 × 2.4 mm2 /pixel and a temporal resolution of 17.4 ms/frame for single-slice imaging, and 52.2 ms/frame for concurrent three-slice imaging, were achieved. We demonstrated implicit motion binning by analyzing the mechanics of the Laplacian matrix. Manifold regularization demonstrated superior image quality scores in reducing spatial and temporal blurring compared with all other reconstruction constraints. While it exhibited faint (nonsignificant) alias artifacts that were similar to temporal finite difference, it provided statistically significant improvements compared with the other constraints. In conclusion, the self-navigated manifold regularized scheme enabled robust high spatiotemporal resolution dynamic speech MRI at 3 T.

Enabling Technologies for Gynecologic Vaginal Surgery: A Systematic Review.

OBJECTIVE: To systematically review the literature to evaluate clinical and surgical outcomes for technologies that facilitate vaginal surgical procedures. DATA SOURCES: We systematically searched MEDLINE, EMBASE, and ClinicalTrials.gov from January 1990 to May 2022. METHODS OF STUDY SELECTION: Comparative and single-arm studies with data on contemporary tools or technologies facilitating intraoperative performance of vaginal gynecologic surgical procedures for benign indications were included. Citations were independently double screened, and eligible full-text articles were extracted by two reviewers. Data collected included study characteristics, technology, patient demographics, and intraoperative and postoperative outcomes. Risk of bias for comparative studies was assessed using established methods, and restricted maximum likelihood model meta-analyses were conducted as indicated. TABULATION, INTEGRATION, AND RESULTS: The search yielded 8,658 abstracts, with 116 eligible studies that evaluated pedicle sealing devices (n=32), nonrobotic and robotic vaginal natural orifice transluminal endoscopic surgery (n=64), suture capture devices (n=17), loop ligatures (n=2), and table-mounted telescopic cameras (n=1). Based on 19 comparative studies, pedicle sealing devices lowered vaginal hysterectomy operative time by 15.9 minutes (95% CI, -23.3 to -85), blood loss by 36.9 mL (95% CI, -56.9 to -17.0), hospital stay by 0.2 days (95% CI, -0.4 to -0.1), and visual analog scale pain scores by 1.4 points on a subjective 10-point scale (95% CI, -1.7 to -1.1). Three nonrandomized comparative studies and 53 single-arm studies supported the feasibility of nonrobotic vaginal natural orifice transluminal endoscopic surgery for hysterectomy, adnexal surgery, pelvic reconstruction, and myomectomy. Data were limited for robotic vaginal natural orifice transluminal endoscopic surgery, suture capture devices, loop ligatures, and table-mounted cameras due to few studies or study heterogeneity. CONCLUSION: Pedicle sealing devices lower operative time and blood loss for vaginal hysterectomy, with modest reductions in hospital stay and pain scores. Although other technologies identified in the literature may have potential to facilitate vaginal surgical procedures and improve outcomes, additional comparative effectiveness research is needed. SYSTEMATIC REVIEW REGISTRATION: PROSPERO, CRD42022327490.

Variation in State-Level Mammography Use, 2012 and 2020.

OBJECTIVES: Mammography is a screening tool for early detection of breast cancer. Uptake in screening use in states can be influenced by Medicaid coverage and eligibility policies, public health outreach efforts, and the Centers for Disease Control and Prevention-funded National Breast and Cervical Cancer Early Detection Program. We described state-specific mammography use in 2020 and changes as compared with 2012. METHODS: We estimated the proportion of women aged ≥40 years who reported receiving a mammogram in the past 2 years, by age group, state, and demographic and socioeconomic characteristics, using 2020 Behavioral Risk Factor Surveillance System data. We also compared 2020 state estimates with 2012 estimates. RESULTS: The proportion of women aged 50-74 years who received a mammogram in the past 2 years was 78.1% (95% CI, 77.4%-78.8%) in 2020. Across measures of socioeconomic status, mammography use was generally lower among women who did not have health insurance (52.0%; 95% CI, 48.3%-55.6%) than among those who did (79.9%; 95% CI, 79.3%-80.6%) and among those who had a usual source of care (49.4%; 95% CI, 46.1%-52.7%) than among those who did not (81.0%; 95% CI, 80.4%-81.7%). Among women aged 50-74 years, mammography use varied across states, from a low of 65.2% (95% CI, 61.4%-69.0%) in Wyoming to a high of 86.1% (95% CI, 83.8%-88.3%) in Massachusetts. Four states had significant increases in mammography use from 2012 to 2020, and 8 states had significant declines. CONCLUSION: Mammography use varied widely among states. Use of evidence-based interventions tailored to the needs of local populations and communities may help close gaps in the use of mammography.

Reading for Meaning: The Influence of Reader Characteristics on Paragraph Understanding in Aphasia.

PURPOSE: The study improves our understanding of the reading comprehension difficulties seen in people with aphasia. It investigates the influence of reader characteristics, including personal demographic variables, and linguistic and wider cognitive skills, on text comprehension. METHOD: Seventy-five people with aphasia and 87 neurologically typical readers completed a test of paragraph comprehension. People with aphasia also completed background tests of language, attention, recognition memory, and executive functions. The influence of demographic variables (age, gender, and level of education) was analyzed separately in the group of people with aphasia and the typical readers using analyses of variance. In the people with aphasia, the relationship between paragraph comprehension and the language and cognitive tests was explored using correlational analyses. RESULTS: In the typical readers, there was a significant effect of gender and level of education and a significant three-way interaction. For the people with aphasia, there were no significant effects of demographic variables. Significant positive correlations were found between performance on paragraph comprehension and each of the language tests and with tests of auditory attention, executive functions, and recognition memory for words. CONCLUSIONS: In people with aphasia, the effects of demographic variables were overshadowed by the effect of their language difficulties. The association seen across language measures reflects the shared semantic representations across single-word, sentence, and text levels, across modalities. The study emphasizes the importance of attention, executive functions, and short-term memory in the comprehension of and memory for what we read. The contribution of both language difficulties and wider cognitive skills needs to be considered when planning intervention. SUPPLEMENTAL MATERIAL: https://doi.org/10.23641/asha.24695451.

Cost-Effectiveness Analysis of Screening for Pancreatic Cancer Among High-Risk Populations.

PURPOSE: We evaluated the potential cost-effectiveness of combined magnetic resonance imaging (MRI) and endoscopic ultrasound (EUS) screening for pancreatic ductal adenocarcinoma (PDAC) among populations at high risk for the disease. METHODS: We used a microsimulation model of the natural history of PDAC to estimate the lifetime health benefits, costs, and cost-effectiveness of PDAC screening among populations with specific genetic risk factors for PDAC, including BRCA1 and BRCA2, PALB2, ATM, Lynch syndrome, TP53, CDKN2A, and STK11. For each high-risk population, we simulated 29 screening strategies, defined by starting age and frequency. Screening included MRI with follow-up EUS in a subset of patients. Costs of tests were based on Medicare reimbursement for MRI, EUS, fine-needle aspiration biopsy, and pancreatectomy. Cancer-related cost by stage of disease and phase of treatment was based on the literature. For each high-risk population, we performed an incremental cost-effectiveness analysis, assuming a willingness-to-pay (WTP) threshold of $100,000 US dollars (USD) per quality-adjusted life year (QALY) gained. RESULTS: For men with relative risk (RR) 12.33 (CDKN2A) and RR 28 (STK11), annual screening was cost-effective, starting at age 55 and 40 years, respectively. For women, screening was only cost-effective for those with RR 28 (STK11), with annual screening starting at age 45 years. CONCLUSION: Combined MRI/EUS screening may be a cost-effective approach for the highest-risk populations (among mutations considered, those with RR >12). However, for those with moderate risk (RR, 5-12), screening would only be cost-effective at higher WTP thresholds (eg, $200K USD/QALY) or with once-only screening.

Representational level matters for tone-word recognition: Evidence from form priming.

In a form priming experiment with a lexical decision task, we investigated whether the representational structure of lexical tone in lexical memory impacts spoken-word recognition in Mandarin. Target monosyllabic words were preceded by five types of primes: (1) the same real words (/lun4/-/lun4/), (2) real words with only tone contrasts (/lun2/-/lun4/), (3) unrelated real words (/pie3/-/lun4/), (4) pseudowords with only tone contrasts (*/lun3/-/lun4/), and (5) unrelated pseudowords (*/tai3/-/lun4/). We found a facilitation effect in target words with pseudoword primes that share the segmental syllable but contrast in tones (*/lun3/-/lun4/). Moreover, no evident form priming effect was observed in target words primed by real words with only tone contrasts (/lun2/-/lun4/). These results suggest that the recognition of a tone word is influenced by the representational level of tone accessed by the prime word. The distinctive priming patterns between real-word and pseudoword primes are best explained by the connectionist models of tone-word recognition, which assume a hierarchical representation of lexical tone.

Hospital ownership and admission rates from the emergency department, evidence from Florida.

OBJECTIVE: In light of Department of Justice investigations of for-profit chains for over-admitting patients, we sought to evaluate whether for-profit hospitals are more likely to admit patients from the emergency department. DATA SOURCES: We used statewide visit-level inpatient and emergency department records from Florida's Agency for Healthcare Administration for 2007-2019. STUDY DESIGN: We calculated differences in admission rates between for-profit and other hospitals, adjusting for patient and hospital characteristics. We also estimated instrumental variables models using differential distance to a for-profit hospital as an instrument. DATA COLLECTION/EXTRACTION METHODS: Our main analysis focuses on patients ages 65 and older treated in hospitals that primarily serve adults. PRINCIPAL FINDINGS: Adjusted admission rates among patients ages 65 and older were 7.1 percentage points (95% CI: 5.1-9.1) higher at for-profit hospitals in 2019 (or 18.8% of the sample mean of 37.8%). Differences in admission rates have remained constant since 2009. CONCLUSION: Our results are consistent with allegations that for-profit hospitals maintain lower admission thresholds to increase occupancy levels.

Contributions of Polygenic Risk and Disease Status to Gray Matter Abnormalities in Major Depression.

BACKGROUND: Gray matter (GM) abnormalities in depression are potentially attributable to some combination of trait, state, and illness history factors. Here, we sought to determine the contributions of polygenic risk for depression, depressive disease status, and the interaction of these factors to these GM abnormalities. METHODS: We conducted a cross-sectional comparison using a 2 × 3 factorial design examining effects of polygenic risk for depression (lower vs. upper quartile) and depression status (never depressed, currently depressed, or remitted depression) on regional GM concentration and GM volume. Participants were a subset of magnetic resonance imaging-scanned UK Biobank participants comprising 2682 people (876 men, 1806 women) algorithmically matched on 16 potential confounders. RESULTS: In women but not men, we observed that elevated polygenic risk for depression was associated with reduced cerebellar GM volume. This deficit occurred in salience and dorsal attention network regions of the cerebellum and was associated with poorer performance on tests of attention and executive function but not fluid intelligence. Moreover, in women with current depression compared to both women with remitted depression and women who never had depression, we observed GM reductions in ventral and medial prefrontal, insular, and medial temporal regions. These state-related abnormalities remained when accounting for antidepressant medication status. CONCLUSIONS: Neuroanatomical deficits attributed broadly to major depression are more likely due to an aggregation of independent factors. Polygenic risk for depression accounted for cerebellar structural abnormalities that themselves accounted for cognitive deficits observed in this disorder. Medial and ventral prefrontal, insular, and temporal cortex deficits constituted a much larger proportion of the aggregate deficit and were attributable to the depressed state.