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Cannabis is one of the most widely used recreational drugs among people with clinical psychosis, after nicotine and alcohol. There has been a debate in psychiatry about whether or not we can infer a cause-and-effect relationship between the use of cannabis and psychotic disorders. In this editorial, we first present and critically discuss the evidence to date of the association between heavy cannabis use and psychosis. We argue that while the biological mechanisms underlying individual susceptibility to develop a psychotic disorder following heavy cannabis use are still unknown, heavy cannabis use remains the most modifiable risk factor for the onset of psychotic disorders and for its clinical and functional outcome. This demands a clear move towards both primary and secondary prevention intervention to reduce the impact of heavy cannabis use on the incidence and prevalence of psychotic disorders.
For centuries, paleontologists have sought functional explanations for the uniquely complex internal walls (septa) of ammonoids, extinct shelled cephalopods. Ammonoid septa developed increasingly complex fractal margins, unlike any modern shell morphologies, throughout more than 300 million years of evolution. Some have suggested these morphologies provided increased resistance to shell-crushing predators. We perform the first physical compression experiments on model ammonoid septa using controlled, theoretical morphologies generated by computer-aided design and 3D printing. These biomechanical experiments reveal that increasing complexity of septal margins does not increase compression resistance. Our results raise the question of whether the evolution of septal shape may be tied closely to the placement of the siphuncle foramen (anatomic septal hole). Our tests demonstrate weakness in the centers of uniformly thick septa, supporting work suggesting reinforcement by shell thickening at the center of septa. These experiments highlight the importance of 3D reconstruction using idealized theoretical morphologies that permit the testing of long-held hypotheses of functional evolutionary drivers by recreating extinct morphologies once rendered physically untestable by the fossil record.
In recent years, a variety of efforts have been made in political science to enable, encourage, or require scholars to be more open and explicit about the bases of their empirical claims and, in turn, make those claims more readily evaluable by others. While qualitative scholars have long taken an interest in making their research open, reflexive, and systematic, the recent push for overarching transparency norms and requirements has provoked serious concern within qualitative research communities and raised fundamental questions about the meaning, value, costs, and intellectual relevance of transparency for qualitative inquiry. In this Perspectives Reflection, we crystallize the central findings of a three-year deliberative process—the Qualitative Transparency Deliberations (QTD)—involving hundreds of political scientists in a broad discussion of these issues. Following an overview of the process and the key insights that emerged, we present summaries of the QTD Working Groups’ final reports. Drawing on a series of public, online conversations that unfolded at www.qualtd.net, the reports unpack transparency’s promise, practicalities, risks, and limitations in relation to different qualitative methodologies, forms of evidence, and research contexts. Taken as a whole, these reports—the full versions of which can be found in the Supplementary Materials—offer practical guidance to scholars designing and implementing qualitative research, and to editors, reviewers, and funders seeking to develop criteria of evaluation that are appropriate—as understood by relevant research communities—to the forms of inquiry being assessed. We dedicate this Reflection to the memory of our coauthor and QTD working group leader Kendra Koivu.1
Understanding place-based contributors to health requires geographically and culturally diverse study populations, but sharing location data is a significant challenge to multisite studies. Here, we describe a standardized and reproducible method to perform geospatial analyses for multisite studies. Using census tract-level information, we created software for geocoding and geospatial data linkage that was distributed to a consortium of birth cohorts located throughout the USA. Individual sites performed geospatial linkages and returned tract-level information for 8810 children to a central site for analyses. Our generalizable approach demonstrates the feasibility of geospatial analyses across study sites to promote collaborative translational research.
During the last fifteen years there has been a paradigm shift in the continuum modelling of granular materials; most notably with the development of rheological models, such as the $\mu (I)$-rheology (where $\mu$ is the friction and I is the inertial number), but also with significant advances in theories for particle segregation. This paper details theoretical and numerical frameworks (based on OpenFOAM) which unify these currently disconnected endeavours. Coupling the segregation with the flow, and vice versa, is not only vital for a complete theory of granular materials, but is also beneficial for developing numerical methods to handle evolving free surfaces. This general approach is based on the partially regularized incompressible $\mu (I)$-rheology, which is coupled to the gravity-driven segregation theory of Gray & Ancey (J. Fluid Mech., vol. 678, 2011, pp. 353–588). These advection–diffusion–segregation equations describe the evolving concentrations of the constituents, which then couple back to the variable viscosity in the incompressible Navier–Stokes equations. A novel feature of this approach is that any number of differently sized phases may be included, which may have disparate frictional properties. Further inclusion of an excess air phase, which segregates away from the granular material, then allows the complex evolution of the free surface to be captured simultaneously. Three primary coupling mechanisms are identified: (i) advection of the particle concentrations by the bulk velocity, (ii) feedback of the particle-size and/or frictional properties on the bulk flow field and (iii) influence of the shear rate, pressure, gravity, particle size and particle-size ratio on the locally evolving segregation and diffusion rates. The numerical method is extensively tested in one-way coupled computations, before the fully coupled model is compared with the discrete element method simulations of Tripathi & Khakhar (Phys. Fluids, vol. 23, 2011, 113302) and used to compute the petal-like segregation pattern that spontaneously develops in a square rotating drum.
Excavators working in a ceremonial plaza group in the Classic period Lowland Maya city of Caracol, Belize, encountered thousands of pieces of chert and obsidian scattered above a royal tomb. A recent analysis of the chert from this context confirms that the assemblage included pieces from each stage of reduction in the production of blades. Taken together, the quantity of both chert and obsidian makes it the largest reported collection of lithic debitage found at the site and provides insight into the techniques of lithic crafters at Caracol. In this article, we consider the sequence of actions involved in the burial of a high-ranking individual and suggest that the layering of flaked stone above the tomb is reminiscent of other reported above-tomb contexts in the Maya Lowlands. Further, a technological analysis of this collection produced results similar to analyses of assemblages typically found in crafting-intensive residential groups. This finding suggests that lithic crafters throughout the city of Caracol donated flaked stone material for funerary events, providing a protective layer and sealing the grave below.
An intermediate-depth (1751 m) ice core was drilled at the South Pole between 2014 and 2016 using the newly designed US Intermediate Depth Drill. The South Pole ice core is the highest-resolution interior East Antarctic ice core record that extends into the glacial period. The methods used at the South Pole to handle and log the drilled ice, the procedures used to safely retrograde the ice back to the National Science Foundation Ice Core Facility (NSF-ICF), and the methods used to process and sample the ice at the NSF-ICF are described. The South Pole ice core exhibited minimal brittle ice, which was likely due to site characteristics and, to a lesser extent, to drill technology and core handling procedures.
Research has demonstrated that chronic stress exposure early in development can lead to detrimental alterations in the orbitofrontal cortex (OFC)–amygdala circuit. However, the majority of this research uses functional neuroimaging methods, and thus the extent to which childhood trauma corresponds to morphometric alterations in this limbic-cortical network has not yet been investigated. This study had two primary objectives: (i) to test whether anatomical associations between OFC–amygdala differed between adults as a function of exposure to chronic childhood assaultive trauma and (ii) to test how these environment-by-neurobiological effects relate to pathological personality traits.
Participants were 137 ethnically diverse adults (48.1% female) recruited from the community who completed a clinical diagnostic interview, a self-report measure of pathological personality traits, and anatomical MRI scans.
Findings revealed that childhood trauma moderated bilateral OFC–amygdala volumetric associations. Specifically, adults with childhood trauma exposure showed a positive association between medial OFC volume and amygdalar volume, whereas adults with no childhood exposure showed the negative OFC–amygdala structural association observed in prior research with healthy samples. Examination of the translational relevance of trauma-related alterations in OFC–amygdala volumetric associations for disordered personality traits revealed that trauma exposure moderated the association of OFC volume with antagonistic and disinhibited phenotypes, traits characteristic of Cluster B personality disorders.
The OFC–amygdala circuit is a potential anatomical pathway through which early traumatic experiences perpetuate emotional dysregulation into adulthood and confer risk for personality pathology. Results provide novel evidence of divergent neuroanatomical pathways to similar personality phenotypes depending on early trauma exposure.
To conduct a pilot study implementing combined genomic and epidemiologic surveillance for hospital-acquired multidrug-resistant organisms (MDROs) to predict transmission between patients and to estimate the local burden of MDRO transmission.
Pilot prospective multicenter surveillance study.
The study was conducted in 8 university hospitals (2,800 beds total) in Melbourne, Australia (population 4.8 million), including 4 acute-care, 1 specialist cancer care, and 3 subacute-care hospitals.
All clinical and screening isolates from hospital inpatients (April 24 to June 18, 2017) were collected for 6 MDROs: vanA VRE, MRSA, ESBL Escherichia coli (ESBL-Ec) and Klebsiella pneumoniae (ESBL-Kp), and carbapenem-resistant Pseudomonas aeruginosa (CRPa) and Acinetobacter baumannii (CRAb). Isolates were analyzed and reported as routine by hospital laboratories, underwent whole-genome sequencing at the central laboratory, and were analyzed using open-source bioinformatic tools. MDRO burden and transmission were assessed using combined genomic and epidemiologic data.
In total, 408 isolates were collected from 358 patients; 47.5% were screening isolates. ESBL-Ec was most common (52.5%), then MRSA (21.6%), vanA VRE (15.7%), and ESBL-Kp (7.6%). Most MDROs (88.3%) were isolated from patients with recent healthcare exposure.
Combining genomics and epidemiology identified that at least 27.1% of MDROs were likely acquired in a hospital; most of these transmission events would not have been detected without genomics. The highest proportion of transmission occurred with vanA VRE (88.4% of patients).
Genomic and epidemiologic data from multiple institutions can feasibly be combined prospectively, providing substantial insights into the burden and distribution of MDROs, including in-hospital transmission. This analysis enables infection control teams to target interventions more effectively.
Commonsense morality seems to feature both agent-neutral and agent-relative elements. For a long time, the core debate between consequentialists and deontologists was which of these features should take centerstage. With the introduction of the consequentializing project and agent-relative value, however, agent-neutrality has been left behind. While I likewise favor an agent-relative view, agent-neutral views capture important features of commonsense morality.
This article investigates whether an agent-relative view can maintain what is attractive about typical agent-neutral views. In particular, I argue that the agent-relative reasons-wielding deontologist is ultimately able to capture those features ordinarily associated with agent-neutral views, while the agent-relative value wielding consequentialist is left with a dilemma. The consequentializer either succumbs to the concerns of her agent-neutral opponents or else abandons the distinctive and attractive features of her view. Either way, I conclude that agent-relative value is best left behind.
Evidence is limited on how to synthesize and incorporate the views of stakeholders into a multisite pragmatic trial and how much academic teams change study design and protocol in response to stakeholder input. This qualitative study describes how stakeholders contributed to the design, conduct, and dissemination of findings of a multisite pragmatic clinical trial, the COMprehensive Post-Acute Stroke Services (COMPASS) Study. We engaged stakeholders as integral research partners by embedding them in study committees and community resource networks that supported local sites. Data stemmed from formal focus groups and continuous participation in working groups. Guided by Grounded Theory, we extracted themes from focus group and meeting notes. These were discussed as a team and with other stakeholder groups for feasibility. A consensus approach was used. Stakeholder input changed many aspects of the study including: the care model that treated stroke as a chronic condition after hospital discharge, training for hospital-based providers who often lacked awareness of the barriers to recovery that patients face, support for caregivers who were essential for stroke patients’ recovery, and for community-based health and social service providers whose services can support recovery yet often go underutilized. Stakeholders brought value to both pragmatic research and health service delivery. Future studies should test the impact of elements of study implementation informed by stakeholders vs those that are not.
Telemedicine visits are an increasingly popular method of care for mild infectious complaints, including uncomplicated urinary tract infections (UTIs), and they are an important target for antimicrobial stewardship programs (ASPs) to evaluate quality of prescribing. In this study, we compared antimicrobial prescribing in a primary care network for uncomplicated UTIs treated through virtual visits and at in-office visits.
Retrospective cohort study comparing guideline-concordant antibiotic prescribing for uncomplicated UTI between virtual visits and office visits.
Primary care network composed of 44 outpatient sites and a single virtual visit platform.
Adult female patients diagnosed with a UTI between January 1 and December 31, 2018.
Virtual visit prescribing was compared to office visit prescribing, including agent, duration, and patient outcomes. The health system ASP provides annual education to all outpatient providers regarding local antibiogram trends and prescribing guidelines. Guideline-concordant therapy was assessed based on the network’s ASP guidelines.
In total, 350 patients were included, with 175 per group. Patients treated for a UTI through a virtual visit were more likely to receive a first-line antibiotic agent (74.9% vs 59.4%; P = .002) and guideline-concordant duration (100% vs 53.1%; P < .001). Patients treated through virtual visits were also less likely to have a urinalysis (0% vs 97.1%; P < .001) or urine culture (0% vs 73.1%; P < .001) ordered and were less likely to revisit within 7 days (5.1% vs 18.9%; P < .001).
UTI care through a virtual visit was associated with more appropriate antimicrobial prescribing compared to office visits and decreased utilization of diagnostic and follow-up resources.
Alzheimer’s disease (AD) studies are increasingly targeting earlier (pre)clinical populations, in which the expected degree of observable cognitive decline over a certain time interval is reduced as compared to the dementia stage. Consequently, endpoints to capture early cognitive changes require refinement. We aimed to determine the sensitivity to decline of widely applied neuropsychological tests at different clinical stages of AD as outlined in the National Institute on Aging – Alzheimer’s Association (NIA-AA) research framework.
Amyloid-positive individuals (as determined by positron emission tomography or cerebrospinal fluid) with longitudinal neuropsychological assessments available were included from four well-defined study cohorts and subsequently classified among the NIA-AA stages. For each stage, we investigated the sensitivity to decline of 17 individual neuropsychological tests using linear mixed models.
1103 participants (age = 70.54 ± 8.7, 47% female) were included: n = 120 Stage 1, n = 206 Stage 2, n = 467 Stage 3 and n = 309 Stage 4. Neuropsychological tests were differentially sensitive to decline across stages. For example, Category Fluency captured significant 1-year decline as early as Stage 1 (β = −.58, p < .001). Word List Delayed Recall (β = −.22, p < .05) and Trail Making Test (β = 6.2, p < .05) became sensitive to 1-year decline in Stage 2, whereas the Mini-Mental State Examination did not capture 1-year decline until Stage 3 (β = −1.13, p < .001) and 4 (β = −2.23, p < .001).
We demonstrated that commonly used neuropsychological tests differ in their ability to capture decline depending on clinical stage within the AD continuum (preclinical to dementia). This implies that stage-specific cognitive endpoints are needed to accurately assess disease progression and increase the chance of successful treatment evaluation in AD.
This study investigated the latent factor structure of the NIH Toolbox Cognition Battery (NIHTB-CB) and its measurement invariance across clinical diagnosis and key demographic variables including sex, race/ethnicity, age, and education for a typical Alzheimer’s disease (AD) research sample.
The NIHTB-CB iPad English version, consisting of 7 tests, was administered to 411 participants aged 45–94 with clinical diagnosis of cognitively unimpaired, dementia, mild cognitive impairment (MCI), or impaired not MCI. The factor structure of the whole sample was first examined with exploratory factor analysis (EFA) and further refined using confirmatory factor analysis (CFA). Two groups were classified for each variable (diagnosis or demographic factors). The confirmed factor model was next tested for each group with CFA. If the factor structure was the same between the groups, measurement invariance was then tested using a hierarchical series of nested two-group CFA models.
A two-factor model capturing fluid cognition (executive function, processing speed, and memory) versus crystalized cognition (language) fit well for the whole sample and each group except for those with age < 65. This model generally had measurement invariance across sex, race/ethnicity, and education, and partial invariance across diagnosis. For individuals with age < 65, the language factor remained intact while the fluid cognition was separated into two factors: (1) executive function/processing speed and (2) memory.
The findings mostly supported the utility of the battery in AD research, yet revealed challenges in measuring memory for AD participants and longitudinal change in fluid cognition.
Background: A prolonged outbreak of carbapenemase-producing Serratia marcescens (CPSM) was identified in our quaternary healthcare center over a 2-year period from 2015 through 2017. A reservoir of IMP-4–producing S. marcescens in sink drains of clinical hand basins (CHB) was implicated in propagating transmission, supported by evidence from whole-genome sequencing (WGS). We assessed the impact of manual bioburden reduction intervention on further transmission of CPSM. Methods: Environmental sampling of frequently touched wet and dry areas around CPSM clinical cases was undertaken to identify potential reservoirs and transmission pathways. After identifying CHB as a source of CPSM, a widespread annual CHB cleaning intervention involving manual scrubbing of sink drains and the proximal pipes was implemented. Pre- and postintervention point prevalence surveys (PPS) of CHB drains performed to assess for CPSM colonization. Surveillance for subsequent transmission was conducted through weekly screening of patients and annual screening of CHB in transmission areas, and 6-monthly whole-hospital PPS of patients. All CPSM isolates were assessed by WGS. Results: In total, 6 patients were newly identified with CPSM from 2015 to 2017 (4.3 transmission events per 100,000 surveillance bed days [SBD]; 95% CI, 1.6–9.4). All clinical CPSM isolates were linked to CHB isolates by WGS. The CHB cleaning intervention resulted in a reduction in CHB colonization with CPSM in transmission areas from 72% colonization to 28% (ARR, 0.44; 95% CI, 0.25–0.63). A single further clinical case of CPSM linked to the CHB isolates was detected over 2 years of surveillance from 2017 to 2019 following the implementation of the annual CHB cleaning program (0.7 transmissions per 100,000 SBD; 95% CI, 0.0–3.9). No transmissions were linked to undertaking the cleaning intervention. Conclusions: A simple intervention targeted at reducing the biological burden of CPSM in CHB drains at regular intervals was effective in preventing transmission of carbapenemase-producing Enterobacterales from the hospital environment to patients over a prolonged period of intensive surveillance. These findings highlight the importance of detailed cleaning for controlling the spread of multidrug-resistant organisms from healthcare environments.
Cognitive behavior therapy (CBT) is effective for most patients with a social anxiety disorder (SAD) but a substantial proportion fails to remit. Experimental and clinical research suggests that enhancing CBT using imagery-based techniques could improve outcomes. It was hypothesized that imagery-enhanced CBT (IE-CBT) would be superior to verbally-based CBT (VB-CBT) on pre-registered outcomes.
A randomized controlled trial of IE-CBT v. VB-CBT for social anxiety was completed in a community mental health clinic setting. Participants were randomized to IE (n = 53) or VB (n = 54) CBT, with 1-month (primary end point) and 6-month follow-up assessments. Participants completed 12, 2-hour, weekly sessions of IE-CBT or VB-CBT plus 1-month follow-up.
Intention to treat analyses showed very large within-treatment effect sizes on the social interaction anxiety at all time points (ds = 2.09–2.62), with no between-treatment differences on this outcome or clinician-rated severity [1-month OR = 1.45 (0.45, 4.62), p = 0.53; 6-month OR = 1.31 (0.42, 4.08), p = 0.65], SAD remission (1-month: IE = 61.04%, VB = 55.09%, p = 0.59); 6-month: IE = 58.73%, VB = 61.89%, p = 0.77), or secondary outcomes. Three adverse events were noted (substance abuse, n = 1 in IE-CBT; temporary increase in suicide risk, n = 1 in each condition, with one being withdrawn at 1-month follow-up).
Group IE-CBT and VB-CBT were safe and there were no significant differences in outcomes. Both treatments were associated with very large within-group effect sizes and the majority of patients remitted following treatment.
Over the course of the 2014/15 and 2015/16 austral summer seasons, the South Pole Ice Core project recovered a 1751 m deep ice core at the South Pole. This core provided a high-resolution record of paleoclimate conditions in East Antarctica during the Holocene and late Pleistocene. The drilling and core processing were completed using the new US Intermediate Depth Drill system, which was designed and built by the US Ice Drilling Program at the University of Wisconsin–Madison. In this paper, we present and discuss the setup, operation, and performance of the drill system.
To evaluate the effect of the burden of Staphylococcus aureus colonization of nursing home residents on the risk of S. aureus transmission to healthcare worker (HCW) gowns and gloves.
Multicenter prospective cohort study.
Setting and participants:
Residents and HCWs from 13 community-based nursing homes in Maryland and Michigan.
Residents were cultured for S. aureus at the anterior nares and perianal skin. The S. aureus burden was estimated by quantitative polymerase chain reaction detecting the nuc gene. HCWs wore gowns and gloves during usual care activities; gowns and gloves were swabbed and then cultured for the presence of S. aureus.
In total, 403 residents were enrolled; 169 were colonized with methicillin-resistant S. aureus (MRSA) or methicillin-sensitive S. aureus (MSSA) and comprised the study population; 232 were not colonized and thus were excluded from this analysis; and 2 were withdrawn prior to being swabbed. After multivariable analysis, perianal colonization with S. aureus conferred the greatest odds for transmission to HCW gowns and gloves, and the odds increased with increasing burden of colonization: adjusted odds ratio (aOR), 2.1 (95% CI, 1.3–3.5) for low-level colonization and aOR 5.2 (95% CI, 3.1–8.7) for high level colonization.
Among nursing home patients colonized with S. aureus, the risk of transmission to HCW gowns and gloves was greater from those colonized with greater quantities of S. aureus on the perianal skin. Our findings inform future infection control practices for both MRSA and MSSA in nursing homes.