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Obsessive–compulsive disorder (OCD) is a neuropsychiatric disorder characterized by recurrent intrusive thoughts and ritualized behaviors, often aimed at reducing distress. OCD is heterogeneous in its presentation and many patients with OCD experience a variety of different symptoms throughout their course of illness. Efforts to understand symptom domains in OCD have typically identified three to five symptom domains, such as the domains of doubt/checking, contamination, superstitions/rituals, symmetry/hoarding, and taboo thoughts. Recent studies in the genetics of OCD have suggested a common OCD dimension may provide additional information above and beyond the previously identified symptom domains. Thus, we sought to test a hierarchical model of lifetime OCD symptoms and evaluate the utility of the inclusion of a common OCD dimension.
Methods
Participants included 999 individuals participating in the OCD Collaborative Genetics Study (OCGS) and an additional 2363 individuals participating in the OCD Genetic Association Study (OCGAS). We evaluated unidimensional, 5-factor, and hierarchical models of lifetime OCD symptom presentation using confirmatory factor analysis.
Results
Results suggested that the hierarchical model best fit the data. Further evaluation of these models using a Bayesian testlet response model showed that lifetime presence of specific OCD symptoms was differentially associated with lifetime OCD severity. Moreover, symptoms associated with greater lifetime severity were generally reported less frequently than symptoms present at lower levels of lifetime severity. Implications of these findings and future directions are discussed.
Background: Candida auris and methicillin-resistant Staphylococcus aureus (MRSA) are prevalent in nursing homes, and both are known to shed profusely from the skin. We evaluated the degree of differential shedding during caregiving activities versus at rest in nursing home residents. Methods: Residents at two nursing homes were screened for C. auris and MRSA using nares, axilla/groin, and peri-rectal swabs. Carriers of C. auris, some of whom also carried MRSA, were evaluated for proximal shed around their bed during rest and caregiving activities using chromogenic settle plates. Morning caregiving activities (e.g. hygiene care, linen/clothing change) were noted to generally take 12 minutes. For rest, settle plates were placed for a 12-minute period prior to the resident awakening in the morning. For caregiving, settle plates were placed for the 12-minute period of morning activity shortly after awakening. Twin rest-caregiving measurements were taken on three separate days per C. auris carrier. In addition, prior to caregiving, bilateral nares, hands, axilla, groin, and perirectal swabs were taken for C. auris and MRSA culture, along with an axilla/groin swab for measuring chlorhexidine concentration (CHG used for routine bathing). Logistic regression with person-level clustering analyzed associations between positive settle plates (“shedding”) and activity (caregiving versus rest), along with other adjusters. Results: The study included 23 C. auris carriers, 15 of whom carried MRSA. 65% were male, 91% had an indwelling device, 39% had wounds. Mean number of positive body sites was 2.3 for C. auris and 1.2 for MRSA. Median CHG concentration was 156 µg/mL (IQR=39-1250). Shedding occurred more frequently during caregiving versus rest for both C. auris (8/69 vs 1/69, P=0.02) and MRSA (15/69 vs 3/69, p=0.002). In multivariable models (Table), caregiving was associated with increased odds of shedding for both C. auris (OR: 9.25 (95% CI: 1.07-80.35), P=0.04) and MRSA (OR: 6.52 (95% CI: 1.72-24.78), P =0.01). Higher CHG concentrations were non-significantly associated with reduced shedding of both pathogens. Conclusion: C. auris and MRSA shedding increased significantly during caregiving activities, supporting CDC’s current recommendations for enhanced barrier precautions in nursing homes, which involve gown and glove use during high-contact care for carriers of multidrug-resistant organisms. Remarkably, shedding was readily detected within 12 minutes of morning caregiving, highlighting a rapid “plume effect” during resident care.
Patients with posttraumatic stress disorder (PTSD) exhibit smaller regional brain volumes in commonly reported regions including the amygdala and hippocampus, regions associated with fear and memory processing. In the current study, we have conducted a voxel-based morphometry (VBM) meta-analysis using whole-brain statistical maps with neuroimaging data from the ENIGMA-PGC PTSD working group.
Methods
T1-weighted structural neuroimaging scans from 36 cohorts (PTSD n = 1309; controls n = 2198) were processed using a standardized VBM pipeline (ENIGMA-VBM tool). We meta-analyzed the resulting statistical maps for voxel-wise differences in gray matter (GM) and white matter (WM) volumes between PTSD patients and controls, performed subgroup analyses considering the trauma exposure of the controls, and examined associations between regional brain volumes and clinical variables including PTSD (CAPS-4/5, PCL-5) and depression severity (BDI-II, PHQ-9).
Results
PTSD patients exhibited smaller GM volumes across the frontal and temporal lobes, and cerebellum, with the most significant effect in the left cerebellum (Hedges’ g = 0.22, pcorrected = .001), and smaller cerebellar WM volume (peak Hedges’ g = 0.14, pcorrected = .008). We observed similar regional differences when comparing patients to trauma-exposed controls, suggesting these structural abnormalities may be specific to PTSD. Regression analyses revealed PTSD severity was negatively associated with GM volumes within the cerebellum (pcorrected = .003), while depression severity was negatively associated with GM volumes within the cerebellum and superior frontal gyrus in patients (pcorrected = .001).
Conclusions
PTSD patients exhibited widespread, regional differences in brain volumes where greater regional deficits appeared to reflect more severe symptoms. Our findings add to the growing literature implicating the cerebellum in PTSD psychopathology.
Almost 12 % of the human population have insufficient access to food and hence are at risk from nutrient deficiencies and related conditions, such as anaemia and stunting. Ruminant meat and milk are rich in protein and micronutrients, making them a highly nutritious food source for human consumption. Conversely, ruminant production contributes to methane (CH4) emissions, a greenhouse gas (GHG) with a global warming potential (GWP) 27–30 times greater than that of carbon dioxide (CO2). Nonetheless, ruminant production plays a crucial role in the circular bioeconomy in terms of upcycling agricultural products that cannot be consumed by humans, into valuable and nutritional food, whilst delivering important ecosystem services. Taking on board the complexities of ruminant production and the need to improve both human and planetary health, there is increasing emphasis on developing innovative solutions to achieve sustainable ruminant production within the ‘One Health’ framework. Specifically, research and innovation will undoubtedly continue to focus on (1) Genetics and Breeding; (2) Animal nutrition and (3) Animal Health, to achieve food security and human health, whilst limiting environmental impact. Implementation of resultant innovations within the agri-food sector will require several enablers, including large-scale investment, multi-actor partnerships, scaling, regulatory approval and importantly social acceptability. This review outlines the grand challenges of achieving sustainable ruminant production and likely research and innovation landscape over the next 15 years and beyond, specifically outlining the pathways and enablers required to achieve sustainable ruminant production within the One Health framework.
Objectives/Goals: Lung transplant is a life-saving surgery for patients with advanced lung diseases yet long-term survival remains poor. The clinical features and lung injury patterns of lung transplant recipients who die early versus those who survive longer term remain undefined. Here, we use cell-free DNA and rejection parameters to help elucidate this further. Methods/Study Population: Lung transplant candidacy prioritizes patients who have a high mortality risk within 2 years and will likely survive beyond 5 years. We stratified patients who died within 2 years of transplant as early death (n = 50) and those who survived past 5 years as long-term survivors (n = 53). Lung transplant recipients had serial blood collected as part of two prospective cohort studies. Cell-free DNA (cfDNA) was quantified using relative (% donor-derived cfDNA {%ddcfDNA}) and absolute (nuclear-derived {n-cfDNA}, mitochondrial-derived {mt-cfDNA}) measurements. As part of routine posttransplant clinical care, all patients underwent pulmonary function testing (PFT), surveillance bronchoscopy with bronchoalveolar lavage (BAL), transbronchial biopsy (TBBx), and donor-specific antibody testing (DSA). Results/Anticipated Results: Over the first 2 years after transplant, the number of episodes of antibody-mediated rejection (p) Discussion/Significance of Impact: Clinically, early-death patients perform worse on routine surveillance PFTs and experience a worse degree of CLAD. These patients also have higher levels of cfDNA as quantified by n-cfDNA and mt-cfDNA. These results provide preliminary evidence that early-death patients have worse allograft rejection, dysfunction, and molecular injury.
Powered equipment for patient handling was designed to alleviate Emergency Medical Service (EMS) clinician injuries while lifting patients. This project evaluated the organizational rationale for purchasing powered equipment and the outcomes from equipment use.
Methods:
This project analyzed secondary data obtained via an insurance Safety Intervention Grant (SIG) program in Ohio USA. These data were primarily in reports from EMS organizations. Investigators applied a mixed-methods approach, analyzing quantitative data from 297 grants and qualitative data from a sample of 64 grants. Analysts abstracted data related to: work-related injuries or risk of musculoskeletal-disorders (MSD), employee feedback regarding acceptance or rejection, and impact on quality, productivity, staffing, and cost.
Results:
A total of $16.67 million (2018 adjusted USD) was spent from 2005 through 2018 for powered cots, powered loading systems, powered stair chairs, and non-patient handling equipment (eg, chest compression system, powered roller). Organizations purchased equipment to accommodate staff demographics (height, age, sex) and patient characteristics (weight, impairments). Grantees were fire departments (n = 254) and public (n = 19) and private (n = 24) EMS organizations consisting of career (45%), volunteer (20%), and a combination of career and volunteer (35%) staff. Powered equipment reduced reported musculoskeletal injuries, and organizations reported it improved EMS clinicians’ safety. Organization feedback was mostly positive, and no organization indicated outright rejection of the purchased equipment. Analyst-identified design advantages for powered cots included increased patient weight capacity and hydraulic features, but the greater weight of the powered cot was a disadvantage. The locking mechanism to hold the cot during transportation was reported as an advantage, but it was a disadvantage for older cots without a compatibility conversion kit. Around one-half of organizations described a positive impact on quality of care and patient safety resulting from the new equipment.
Conclusion:
Overall, organizations reported improved EMS clinicians’ safety but noted that not all safety concerns were addressed by the new equipment.
Since the 1950s, the United Nations (UN) has designated days (e.g., World Wetland Day), years (e.g., Year of the Gorilla) and decades (e.g., Decade on Biodiversity) with a commonly stated goal to raise awareness and funding for conservation-oriented initiatives, and these Days, Years and Decades of ‘…’ (hereafter ‘DYDOs’) continue. However, the effectiveness of these initiatives to achieve their stated objectives and to contribute to positive conservation outcomes is unclear. Here we used a binary analysis change model to evaluate the effectiveness of UN conservation-oriented DYDOs observed between 1974 and 2020. We also examined four case studies to understand the different strategies employed to meet specified conservation goals. We found that DYDOs apparently contributed to positive conservation outcomes when they were tied to social media campaigns and/or when they were strategically situated in current events or global discourse. Although the outcomes of DYDOs were varied, those with longer timescales and those that engaged local communities were more likely to be successful. We suggest that DYDO organizers should identify all possible paths of action through the lens of the change model outlined in this paper to strengthen the value and effectiveness of these initiatives in the future. Using this approach could help ensure that resources are used efficiently and effectively, and that initiatives yield positive conservation outcomes that benefit people and nature.
Each day a venous catheter is retained poses unnecessary safety risks. In a retrospective evaluation of central/peripheral lines in nursing home residents receiving antibiotics, 80% were retained beyond antibiotic treatment end and nearly one third were retained longer than a week. Interventions for timely catheter removal are urgently needed.
Fast glacier motion is facilitated by slip at the ice-bed interface. For slip over rigid beds, areas of ice-bed separation (cavities) can exert significant control on slip dynamics. Analytic models of these systems assume that cavities instantaneously adjust to changes in slip and effective pressure forcings, but recent studies indicate transient forcings violate this—and other—underlying assumptions. To assess these incongruities, we conducted novel experiments emulating hard-bedded slip with ice-bed separation under periodic effective pressure transients. We slid an ice-ring over a sinusoidal bed while varying the applied overburden stress to emulate subglacial effective pressure cycles observed in nature and continuously recorded mechanical and geometric system responses. We observed characteristic lags and nonlinearities in system responses that were sensitive to forcing periodicity and trajectory. This gave rise to hysteresis not predicted in analytic theory, which we ascribed to a combination of geometric, thermal and rheologic processes. This framework corroborates other studies of transient glacier slip and we used it to place new constraints on transient phenomena observed in the field. Despite these divergences, average system responses converged toward model predictions, suggesting that analytic theory remains applicable for modeling longer-term behaviors of transiently forced slip with ice-bed separation.
To evaluate the impact of a mobile-app-based central line-associated bloodstream infection (CLABSI) prevention program in nursing home residents with peripherally inserted central catheters (PICCs).
Design:
Pre-post prospective cohort study with baseline (September 2015–December 2016), phase-in (January 2017–April 2017), and intervention (May 2017–December 2018). Generalized linear mixed models compared intervention with baseline frequency of localized inflammation/infection, dressing peeling, and infection-related hospitalizations. Cox proportional hazards models compared days-to-removal of lines with localized inflammation/infection.
Setting:
Six nursing homes in Orange County, California.
Patients:
Adult nursing home residents with PICCs.
Intervention:
CLABSI prevention program consisting of an actionable scoring system for identifying insertion site infection/inflammation coupled with a mobile-app enabling photo-assessments and automated physician alerting for remote response.
Results:
We completed 8,131 assessments of 817 PICCs in 719 residents (baseline: 4,865 assessments, 422 PICCs, 385 residents; intervention: 4,264 assessments, 395 PICCs, 334 residents). The intervention was associated with 57% lower odds of peeling dressings (OR 0.43, 95% CI 0.28–0.64, P < .001), 73% lower local inflammation/infection (OR = 0.27, 95% CI: 0.13–0.56, P < .001), and 41% lower risk of infection-related hospitalizations (OR = 0.59, 95% CI: 0.42–0.83, P = .002). Physician mobile-app alerting and response enabled 62% lower risk of lines remaining in place after inflammation/infection was identified (HR 0.38, CI: 0.24–0.62, P < .001) and 95% faster removal of infected lines from mean (SD) 19 (20) to 1 (2) days.
Conclusions:
A mobile-app-based CLABSI prevention program decreased the frequency of inflamed/infected central line insertion sites, improved dressing integrity, increased speed of removal when inflammation/infection were found, and reduced infection-related hospitalization risk.
We compared the Institute for Clinical and Economic Review’s (ICER) ratings of comparative clinical effectiveness with the German Federal Joint Committee’s (G-BA) added benefit ratings, and explored what factors, including the evidence base, may explain disagreement between the two organizations.
Methods
Drugs were included if they were assessed by ICER under its 2020–2023 Value Assessment Framework and had a corresponding assessment by G-BA as of March 2023 for the same indication, patient population, and comparator drug. To compare assessments, we modified ICER’s proposed crosswalk between G-BA and ICER benefit ratings to account for G-BA’s extent and certainty ratings. We also determined whether each assessment pair was based on similar or dissimilar evidence. Assessment pairs exhibiting disagreement based on the modified crosswalk despite a similar evidence base were qualitatively analyzed to identify reasons for disagreement.
Results
We identified 15 assessment pairs and seven out of fifteen were based on similar evidence. G-BA and ICER assessments disagreed for each of these drugs. For 4/7 drugs, G-BA (but not ICER) determined the evidence was unsuitable for assessment: for 2/4 drugs, G-BA concluded the key trials did not appropriately assess the comparator therapy; for 1/4, G-BA did not accept results of a before-and-after study due to non-comparable study settings; for 1/4, G-BA determined follow-up in the key trial was too short. Among assessment pairs where both organizations assessed the evidence, reasons for disagreement included concerns about long-term safety, generalizability, and study design.
Conclusions
This study underscores the role of value judgments within assessments of clinical effectiveness. These judgments are not always transparently presented in assessment summaries. The lack of clarity regarding these value-based decisions underscores the need for improvements in transparency and communication, which are essential for promoting a more robust health technology assessment process and supporting transferability of assessments across jurisdictions.
The reliable change index has been used to evaluate the significance of individual change in health-related quality of life. We estimate reliable change for two measures (physical function and emotional distress) in the Patient-Reported Outcomes Measurement Information System (PROMIS®) 29-item health-related quality of life measure (PROMIS-29 v2.1). Using two waves of data collected 3 months apart in a longitudinal observational study of chronic low back pain and chronic neck pain patients receiving chiropractic care, and simulations, we compare estimates of reliable change from classical test theory fixed standard errors with item response theory standard errors from the graded response model. We find that unless true change in the PROMIS physical function and emotional distress scales is substantial, classical test theory estimates of significant individual change are much more optimistic than estimates of change based on item response theory.
The new software package OpenMx 2.0 for structural equation and other statistical modeling is introduced and its features are described. OpenMx is evolving in a modular direction and now allows a mix-and-match computational approach that separates model expectations from fit functions and optimizers. Major backend architectural improvements include a move to swappable open-source optimizers such as the newly written CSOLNP. Entire new methodologies such as item factor analysis and state space modeling have been implemented. New model expectation functions including support for the expression of models in LISREL syntax and a simplified multigroup expectation function are available. Ease-of-use improvements include helper functions to standardize model parameters and compute their Jacobian-based standard errors, access to model components through standard R $ mechanisms, and improved tab completion from within the R Graphical User Interface.
Persistent discrimination and identity threats contribute to adverse health outcomes in minoritized groups, mediated by both structural racism and physiological stress responses.
Objective:
This study aims to evaluate the feasibility of recruiting African American volunteers for a pilot study of race-based stress, the acceptability of a mindfulness intervention designed to reduce racism-induced stress, and to evaluate preliminary associations between race-based stress and clinical, psychosocial, and biological measures.
Methods:
A convenience sample of African Americans aged 18–50 from New York City’s Tri-state area underwent assessments for racial discrimination using the Everyday Discrimination Scale (EDS) and Race-Based Traumatic Stress Symptom Scale. Mental health was evaluated using validated clinical scales measuring depression, anxiety, stress, resilience, mindfulness, resilience, sleep, interpersonal connection, and coping. Biomarkers were assessed through clinical laboratory tests, allostatic load assessment, and blood gene expression analysis.
Results:
Twenty participants (12 females, 8 males) completed assessments after consent. Elevated EDS scores were associated with adverse lipid profiles, including higher cholesterol/high-density lipoprotein (HDL) ratios and lower HDL levels, as well as elevated inflammatory markers (NF-kB activity) and reduced antiviral response (interferon response factor). Those with high EDS reported poorer sleep, increased substance use, and lower resilience. Mindfulness was positively associated with coping and resilience but inversely to sleep disturbance. 90% showed interest in a mindfulness intervention targeting racism-induced stress.
Conclusions:
This study demonstrated an association between discrimination and adverse health effects among African Americans. These findings lay the groundwork for further research to explore the efficacy of mindfulness and other interventions on populations experiencing discrimination.
Introduction to Probability and Statistics for Data Science provides a solid course in the fundamental concepts, methods and theory of statistics for students in statistics, data science, biostatistics, engineering, and physical science programs. It teaches students to understand, use, and build on modern statistical techniques for complex problems. The authors develop the methods from both an intuitive and mathematical angle, illustrating with simple examples how and why the methods work. More complicated examples, many of which incorporate data and code in R, show how the method is used in practice. Through this guidance, students get the big picture about how statistics works and can be applied. This text covers more modern topics such as regression trees, large scale hypothesis testing, bootstrapping, MCMC, time series, and fewer theoretical topics like the Cramer-Rao lower bound and the Rao-Blackwell theorem. It features more than 250 high-quality figures, 180 of which involve actual data. Data and R are code available on our website so that students can reproduce the examples and do hands-on exercises.
This chapter treats love, desire and eroticism, arguing that eros and philotes serve as metapoetic structuring principles of epic narrative. It begins with a preliminary survey of the foundational texts, focusing on the scene of Helen at the loom as she weaves a tapestry of warriors in battle, essentially a figuration of the Iliad as an artistic product of sexual longing. The chapter then moves forward to consider how these same erotic structuring principles play out in imperial Greek epic, which absorbs Homer’s models through the filter of romantic fiction. Smith focuses on the first three books of Quintus of Smyrna’s Posthomerica – the events surrounding Penthesileia, Memnon, and the death of Achilles – reading them as flirtatious manipulations that intensify readerly anticipation, and then turns to Nonnus’ Dionysiaca, specifically the tendril imagery in the Ampelos episode and its sequel, the romance of Calamus and Carpus. These episodes serve as exemplars of the regenerative powers of epic desire.
What are the origins and effects of legal ambiguity in authoritarian regimes? Using a detailed case study of nationality rights in Jordan – which draws from interviews with 210 Jordanian political officials, judges, lawyers, activists, and citizens/residents – we develop a framework for understanding how legal ambiguity emerges, and how it matters, under authoritarianism. We first conceptualize four discrete forms in which legal ambiguity manifests: lexical ambiguity (in legal texts); substantive ambiguity (in status as law); conflictual ambiguity (between contradictory legal rules); and operational ambiguity (in enforcement processes). We then scrutinize the emergence and effects of legal ambiguity in Jordanian nationality policy by integrating historical process tracing, detailed interview evidence, and a content analysis of archival documents, laws, and court verdicts pertaining to nationality rights. Our findings contribute to scholarship on legal ambiguity, authoritarian legality, and discretionary state authority by showing that (1) crisis junctures make the emergence of legal ambiguity more likely; (2) legal ambiguity takes a variety of different forms that warrant conceptual disaggregation; and (3) different forms of legal ambiguity often have disparate effects on how authoritarian state power is organized and experienced in public life.
In Chapter 3 we learned how to do basic probability calculations and even put them to use solving some fairly complicated probability problems. In this chapter and the next two, we generalize how we do probability calculations, where we will transition from working with sets and events to working with random variables.