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The association between cannabis and psychosis is established, but the role of underlying genetics is unclear. We used data from the EU-GEI case-control study and UK Biobank to examine the independent and combined effect of heavy cannabis use and schizophrenia polygenic risk score (PRS) on risk for psychosis.
Methods
Genome-wide association study summary statistics from the Psychiatric Genomics Consortium and the Genomic Psychiatry Cohort were used to calculate schizophrenia and cannabis use disorder (CUD) PRS for 1098 participants from the EU-GEI study and 143600 from the UK Biobank. Both datasets had information on cannabis use.
Results
In both samples, schizophrenia PRS and cannabis use independently increased risk of psychosis. Schizophrenia PRS was not associated with patterns of cannabis use in the EU-GEI cases or controls or UK Biobank cases. It was associated with lifetime and daily cannabis use among UK Biobank participants without psychosis, but the effect was substantially reduced when CUD PRS was included in the model. In the EU-GEI sample, regular users of high-potency cannabis had the highest odds of being a case independently of schizophrenia PRS (OR daily use high-potency cannabis adjusted for PRS = 5.09, 95% CI 3.08–8.43, p = 3.21 × 10−10). We found no evidence of interaction between schizophrenia PRS and patterns of cannabis use.
Conclusions
Regular use of high-potency cannabis remains a strong predictor of psychotic disorder independently of schizophrenia PRS, which does not seem to be associated with heavy cannabis use. These are important findings at a time of increasing use and potency of cannabis worldwide.
Product architecture decisions are made early in the product development process and have far-reaching effects. Unless anticipated through experience or intuition, many of these effects may not be apparent until much later in the development process, making changes to the architecture costly in time, effort and resources. Many researchers through the years have studied various elements of product architecture and their effects. By using a repeatable process for aggregating statements on the effects of architecture strategies from a selection of the literature on the topic and storing them in a systematic database, this information can then be recalled and presented in the form of a Product Architecture Strategy and Effect (PASE) matrix. PASE matrices allow for the identification, comparison, evaluation, and then selection of the most desirable product architecture strategies before expending resources along a specific development path. This paper introduces the PASE Database and matrix and describes their construction and use in guiding design decisions. This paper also provides metrics for understanding the robustness of this database.
From early on, infants show a preference for infant-directed speech (IDS) over adult-directed speech (ADS), and exposure to IDS has been correlated with language outcome measures such as vocabulary. The present multi-laboratory study explores this issue by investigating whether there is a link between early preference for IDS and later vocabulary size. Infants’ preference for IDS was tested as part of the ManyBabies 1 project, and follow-up CDI data were collected from a subsample of this dataset at 18 and 24 months. A total of 341 (18 months) and 327 (24 months) infants were tested across 21 laboratories. In neither preregistered analyses with North American and UK English, nor exploratory analyses with a larger sample did we find evidence for a relation between IDS preference and later vocabulary. We discuss implications of this finding in light of recent work suggesting that IDS preference measured in the laboratory has low test-retest reliability.
Incidence of first-episode psychosis (FEP) varies substantially across geographic regions. Phenotypes of subclinical psychosis (SP), such as psychotic-like experiences (PLEs) and schizotypy, present several similarities with psychosis. We aimed to examine whether SP measures varied across different sites and whether this variation was comparable with FEP incidence within the same areas. We further examined contribution of environmental and genetic factors to SP.
Methods
We used data from 1497 controls recruited in 16 different sites across 6 countries. Factor scores for several psychopathological dimensions of schizotypy and PLEs were obtained using multidimensional item response theory models. Variation of these scores was assessed using multi-level regression analysis to estimate individual and between-sites variance adjusting for age, sex, education, migrant, employment and relational status, childhood adversity, and cannabis use. In the final model we added local FEP incidence as a second-level variable. Association with genetic liability was examined separately.
Results
Schizotypy showed a large between-sites variation with up to 15% of variance attributable to site-level characteristics. Adding local FEP incidence to the model considerably reduced the between-sites unexplained schizotypy variance. PLEs did not show as much variation. Overall, SP was associated with younger age, migrant, unmarried, unemployed and less educated individuals, cannabis use, and childhood adversity. Both phenotypes were associated with genetic liability to schizophrenia.
Conclusions
Schizotypy showed substantial between-sites variation, being more represented in areas where FEP incidence is higher. This supports the hypothesis that shared contextual factors shape the between-sites variation of psychosis across the spectrum.
The reactivity of colloidal particles is regulated by their surface properties. These properties affect the wettability, flocculation-dispersion characteristics, ion exchange, sorption capacities and transport of inorganic colloids. Most studies have focused on hydrophilic, charged-particle surfaces, often ignoring the alterations in surface properties produced by the adsorption of natural organic matter, surfactants and other compounds. Adsorption of these substances can potentially render a surface substantially more hydrophobic. Nevertheless, comparatively little is known about changes in surface properties and reactivity of minerals upon sorption of hydrophobic organic compounds. In this study, the properties of four minerals (kaolinite, pyrophyllite, montmorillonite and Min-U-Sil®) and two inorganic materials (X-ray amorphous Al hydroxide and X-ray amorphous Si oxide) were compared before and after treatment with the common silylating agent, trimethylchlorosilane (TMCS). The samples were characterized by measurements of total carbon, cation exchange capacity (CEC), particle size, specific surface area (SSA), electrophoretic mobility, contact angle, particle aggregation, and by X-ray diffraction and diffuse reflectance infrared spectroscopy. For the layer silicates, surface coverage was limited to ∼2% trimethyl silane (TMSi). TMSi covered 7.5% of the Min-U-Sil® surface and 33% of the X-ray amorphous Si oxide. Treatment did not affect the structure of the minerals but reduced the CEC, SSA and electrophoretic mobilities. Water contact angles increased to between 18 and 114° with treatment. While the apolar characteristic of the surfaces decreased minimally with treatment, the Lewis acid/base properties were substantially reduced and interfacial free energy shifted from positive to negative values indicating a more hydrophobic surface character. For all the samples except kaolinite, these changes affected the stability of the colloids in suspension depending upon solution pH. Although the grafting of TMSi altered colloidal mineral surface properties and increased their hydrophobicity, these changes were not sufficient to predict colloid aggregation behavior.
Mild traumatic brain injury (mTBI) is an important public health problem, due to its high incidence and the failure of at least 20% of patients to successfully recover from injury. Cognitive symptoms, in particular, are an important area of research in mTBI, due to their association with return to work and referral to neuropsychological services. Understanding the predictors of cognitive symptoms may help to improve outcomes after mTBI. This study explored female sex, psychological distress, coping style and illness perceptions as potential predictors of cognitive symptoms following adult civilian mTBI.
Participants and Methods:
Sixty-nine premorbidly healthy adults with mTBI (mean age = 36.7, SD = 14.7, range = 18-60; 15 females) were recruited from trauma wards at two public hospitals in Australia and assessed 6-12 weeks following injury. Cognitive complaint was measured using a comprehensive 30-item scale (CCAMCHI) assessing mTBI-specific symptoms in the domains of processing speed, attention, memory and executive function. Participants additionally completed the following measures: Brief-COPE, Illness Perceptions Questionnaire-Revised, Inventory of Depressive Symptomatology, Beck Anxiety Inventory, and PTSD Checklist for DSM-5. The latter three measures were combined to create an index of psychological distress.
Results:
Bivariate nonparametric correlational analyses indicated that female sex (r[67] = .26, 95% CI [.14, .55], p = .03) and psychological distress (r[66] = .54, 95% CI [.40, .72], p < .001) were each significantly associated with cognitive symptom reporting following mTBI. Additionally, while none of the three coping style factors were associated with cognitive symptom reporting, seven of the eight dimensions of illness perceptions were associated with symptom reporting (|r| = .25 - .58, p < 0.05). In a linear regression model assessing the combined effects of each variable, female sex, greater psychological distress, and overall negative illness perceptions were each significant independent predictors of increased cognitive complaint (adj. R2 = .47, F[4,63] = 15.59, p < .001).
Conclusions:
These findings implicate female sex, psychological distress, and illness perceptions as key factors associated with cognitive symptom reporting after mTBI. This research suggests that these factors may be useful in clinical practice when considering early identification of individuals at risk of poor recovery. Specifically, this research implicates females, individuals with high psychological distress, and individuals with negative illness perceptions as important to subgroups to consider for potential intervention after mTBI. Additionally, as psychological distress and illness perceptions are both potentially modifiable, this research suggests that these factors may be useful targets for intervention.
The COVID-19 pandemic accelerated the development of decentralized clinical trials (DCT). DCT’s are an important and pragmatic method for assessing health outcomes yet comprise only a minority of clinical trials, and few published methodologies exist. In this report, we detail the operational components of COVID-OUT, a decentralized, multicenter, quadruple-blinded, randomized trial that rapidly delivered study drugs nation-wide. The trial examined three medications (metformin, ivermectin, and fluvoxamine) as outpatient treatment of SARS-CoV-2 for their effectiveness in preventing severe or long COVID-19. Decentralized strategies included HIPAA-compliant electronic screening and consenting, prepacking investigational product to accelerate delivery after randomization, and remotely confirming participant-reported outcomes. Of the 1417 individuals with the intention-to-treat sample, the remote nature of the study caused an additional 94 participants to not take any doses of study drug. Therefore, 1323 participants were in the modified intention-to-treat sample, which was the a priori primary study sample. Only 1.4% of participants were lost to follow-up. Decentralized strategies facilitated the successful completion of the COVID-OUT trial without any in-person contact by expediting intervention delivery, expanding trial access geographically, limiting contagion exposure, and making it easy for participants to complete follow-up visits. Remotely completed consent and follow-up facilitated enrollment.
Since the initial publication of A Compendium of Strategies to Prevent Healthcare-Associated Infections in Acute Care Hospitals in 2008, the prevention of healthcare-associated infections (HAIs) has continued to be a national priority. Progress in healthcare epidemiology, infection prevention, antimicrobial stewardship, and implementation science research has led to improvements in our understanding of effective strategies for HAI prevention. Despite these advances, HAIs continue to affect ∼1 of every 31 hospitalized patients,1 leading to substantial morbidity, mortality, and excess healthcare expenditures,1 and persistent gaps remain between what is recommended and what is practiced.
The widespread impact of the coronavirus disease 2019 (COVID-19) pandemic on HAI outcomes2 in acute-care hospitals has further highlighted the essential role of infection prevention programs and the critical importance of prioritizing efforts that can be sustained even in the face of resource requirements from COVID-19 and future infectious diseases crises.3
The Compendium: 2022 Updates document provides acute-care hospitals with up-to-date, practical expert guidance to assist in prioritizing and implementing HAI prevention efforts. It is the product of a highly collaborative effort led by the Society for Healthcare Epidemiology of America (SHEA), the Infectious Disease Society of America (IDSA), the Association for Professionals in Infection Control and Epidemiology (APIC), the American Hospital Association (AHA), and The Joint Commission, with major contributions from representatives of organizations and societies with content expertise, including the Centers for Disease Control and Prevention (CDC), the Pediatric Infectious Disease Society (PIDS), the Society for Critical Care Medicine (SCCM), the Society for Hospital Medicine (SHM), the Surgical Infection Society (SIS), and others.
To model cognitive reserve (CR) longitudinally in a neurodiverse pediatric sample using a residual index approach, and to test the criterion and construct validity of this index.
Method:
Participants were N = 115 children aged 9.5–13 years at baseline (MAge = 10.48 years, SDAge = 0.61), and n = 43 (37.4%) met criteria for ADHD. The CR index represented variance in Matrix Reasoning scores from the WASI that was unexplained by MRI-based brain variables (bilateral hippocampal volumes, total gray matter volumes, and total white matter hypointensity volumes) or demographics (age and sex).
Results:
At baseline, the CR index predicted math computation ability (estimate = 0.50, SE = 0.07, p < .001), and word reading ability (estimate = 0.26, SE = 0.10, p = .012). Longitudinally, change in CR over time was not associated with change in math computation ability (estimate = −0.02, SE = 0.03, p < .513), but did predict change in word reading ability (estimate = 0.10, SE = 0.03, p < .001). Change in CR was also found to moderate the relationship between change in word reading ability and white matter hypointensity volume (estimate = 0.10, SE = 0.05, p = .045).
Conclusions:
Evidence for the criterion validity of this CR index is encouraging, but somewhat mixed, while construct validity was evidenced through interaction between CR, brain, and word reading ability. Future research would benefit from optimization of the CR index through careful selection of brain variables for a pediatric sample.
The U.S. Department of Agriculture–Agricultural Research Service (USDA-ARS) has been a leader in weed science research covering topics ranging from the development and use of integrated weed management (IWM) tactics to basic mechanistic studies, including biotic resistance of desirable plant communities and herbicide resistance. ARS weed scientists have worked in agricultural and natural ecosystems, including agronomic and horticultural crops, pastures, forests, wild lands, aquatic habitats, wetlands, and riparian areas. Through strong partnerships with academia, state agencies, private industry, and numerous federal programs, ARS weed scientists have made contributions to discoveries in the newest fields of robotics and genetics, as well as the traditional and fundamental subjects of weed–crop competition and physiology and integration of weed control tactics and practices. Weed science at ARS is often overshadowed by other research topics; thus, few are aware of the long history of ARS weed science and its important contributions. This review is the result of a symposium held at the Weed Science Society of America’s 62nd Annual Meeting in 2022 that included 10 separate presentations in a virtual Weed Science Webinar Series. The overarching themes of management tactics (IWM, biological control, and automation), basic mechanisms (competition, invasive plant genetics, and herbicide resistance), and ecosystem impacts (invasive plant spread, climate change, conservation, and restoration) represent core ARS weed science research that is dynamic and efficacious and has been a significant component of the agency’s national and international efforts. This review highlights current studies and future directions that exemplify the science and collaborative relationships both within and outside ARS. Given the constraints of weeds and invasive plants on all aspects of food, feed, and fiber systems, there is an acknowledged need to face new challenges, including agriculture and natural resources sustainability, economic resilience and reliability, and societal health and well-being.
The National Pediatric Cardiology Quality Improvement Collaborative (NPC-QIC) lacks a rigorous enrollment audit process, unlike other collaborative networks. Most centers require individual families to consent to participate. It is unknown whether there is variation across centers or biases in enrollment.
Methods:
We used the Pediatric Cardiac Critical Care Consortium (PC4) registry to assess enrollment rates in NPC-QIC for those centers participating in both registries using indirect identifiers (date of birth, date of admission, gender, and center) to match patient records. All infants born 1/1/2018–12/31/2020 and admitted 30 days of life were eligible. In PC4, all infants with a fundamental diagnosis of hypoplastic left heart or variant or who underwent a surgical or hybrid Norwood or variant were eligible. Standard descriptive statistics were used to describe the cohort and center match rates were plotted on a funnel chart.
Results:
Of 898 eligible NPC-QIC patients, 841 were linked to 1,114 eligible PC4 patients (match rate 75.5%) in 32 centers. Match rates were lower in patients of Hispanic/Latino ethnicity (66.1%, p = 0.005), and those with any specified chromosomal abnormality (57.4%, p = 0.002), noncardiac abnormality (67.8%, p = 0.005), or any specified syndrome (66.5%, p = 0.001). Match rates were lower for patients who transferred to another hospital or died prior to discharge. Match rates varied from 0 to 100% across centers.
Conclusions:
It is feasible to match patients between the NPC-QIC and PC4 registries. Variation in match rates suggests opportunities for improvement in NPC-QIC patient enrollment.
While cannabis use is a well-established risk factor for psychosis, little is known about any association between reasons for first using cannabis (RFUC) and later patterns of use and risk of psychosis.
Methods
We used data from 11 sites of the multicentre European Gene-Environment Interaction (EU-GEI) case–control study. 558 first-episode psychosis patients (FEPp) and 567 population controls who had used cannabis and reported their RFUC.
We ran logistic regressions to examine whether RFUC were associated with first-episode psychosis (FEP) case–control status. Path analysis then examined the relationship between RFUC, subsequent patterns of cannabis use, and case–control status.
Results
Controls (86.1%) and FEPp (75.63%) were most likely to report ‘because of friends’ as their most common RFUC. However, 20.1% of FEPp compared to 5.8% of controls reported: ‘to feel better’ as their RFUC (χ2 = 50.97; p < 0.001). RFUC ‘to feel better’ was associated with being a FEPp (OR 1.74; 95% CI 1.03–2.95) while RFUC ‘with friends’ was associated with being a control (OR 0.56; 95% CI 0.37–0.83). The path model indicated an association between RFUC ‘to feel better’ with heavy cannabis use and with FEPp-control status.
Conclusions
Both FEPp and controls usually started using cannabis with their friends, but more patients than controls had begun to use ‘to feel better’. People who reported their reason for first using cannabis to ‘feel better’ were more likely to progress to heavy use and develop a psychotic disorder than those reporting ‘because of friends’.
The intent of this document is to highlight practical recommendations in a concise format designed to assist acute-care hospitals in implementing and prioritizing their surgical-site infection (SSI) prevention efforts. This document updates the Strategies to Prevent Surgical Site Infections in Acute Care Hospitals published in 2014.1 This expert guidance document is sponsored by the Society for Healthcare Epidemiology of America (SHEA). It is the product of a collaborative effort led by SHEA, the Infectious Diseases Society of America (IDSA), the Association for Professionals in Infection Control and Epidemiology (APIC), the American Hospital Association (AHA), and The Joint Commission, with major contributions from representatives of a number of organizations and societies with content expertise.
Body size is an important trait with implications for energy use and ecology as well as generation time and evolutionary rates. Turritelline gastropods are widely distributed through geologic time and space, making them an excellent group for evaluating macroevolutionary patterns. To evaluate the pattern of body-size change in turritelline gastropods, we compiled a dataset of shell lengths of 316 species of turritelline gastropods spanning the Jurassic to Recent. Type specimens were almost always significantly larger than specimen distributions from the same species. We found that turritelline gastropod size was inversely correlated with latitude, a trend likely driven by the Neogene–Recent diversification of small-bodied Southern Hemisphere taxa. A time series model was applied to distinguish among three possible macroevolutionary patterns: unbiased random walk (no directional trend), biased random walk (directional trend), and stasis (no net change). We determined that turritelline gastropods have experienced stasis in body size throughout their evolutionary history, adding to the growing literature documenting directionless body-size trends in marine invertebrate clades. Stasis of geographically widespread clades may be the result of ecological variability across the environmental range occupied by the group or differential diversification into opposing environments. Turritelline life-history patterns, especially their reproductive strategy that combines a short life span and decline in growth rate around 1 year of age to reallocate energy to reproduction, might circumvent selection for longevity and larger size, while further decrease in minimum size is likely limited by feeding efficiency and anti-predatory defense. The expectation that species or clades should continue to evolve to occupy larger size classes conflicts with the evolutionary advantages of small size, which in turritelline gastropods include high generational turnover and larger population sizes that yield opportunities for genetic variance.
Cognitive symptoms are associated with return to work, healthcare use and quality of life after mild traumatic brain injury (mTBI). Additionally, while overall ‘post-concussion’ symptoms are often present at similar levels in mTBI and control groups, cognitive complaints may be specifically elevated in mTBI. A systematic review and meta-analysis was conducted to investigate the frequency and extent of cognitive complaints following adult civilian mTBI, and compare it to the frequency and extent of complaints in control populations (PROSPERO: CRD42020151284).
Method:
This review included studies published up to March 2022. Thirteen studies were included in the systematic review, and six were included in the meta-analysis. Data extraction and quality assessment were conducted by two independent reviewers.
Results:
Cognitive complaints are common after mTBI, although reported rates differed greatly across studies. Results suggested that mTBI groups report cognitive complaints to a significantly greater extent than control groups (Hedges’ g = 0.85, 95% CI 0.31–1.40, p = .0102). Heterogeneity between studies was high (τ2 = 0.20, 95% CI 0.04–1.58; I2 = 75.0%, 95% CI 43.4%–89.0%). Between-group differences in symptom reporting were most often found when healthy rather than injured controls were employed.
Conclusions:
Cognitive complaints are consistently reported after mTBI, and are present at greater levels in mTBI patients than in controls. Despite the importance of these complaints, including in regards to return to work, healthcare use and quality of life, there has been limited research in this area, and heterogeneity in research methodology is common.
This article is a clinical guide which discusses the “state-of-the-art” usage of the classic monoamine oxidase inhibitor (MAOI) antidepressants (phenelzine, tranylcypromine, and isocarboxazid) in modern psychiatric practice. The guide is for all clinicians, including those who may not be experienced MAOI prescribers. It discusses indications, drug-drug interactions, side-effect management, and the safety of various augmentation strategies. There is a clear and broad consensus (more than 70 international expert endorsers), based on 6 decades of experience, for the recommendations herein exposited. They are based on empirical evidence and expert opinion—this guide is presented as a new specialist-consensus standard. The guide provides practical clinical advice, and is the basis for the rational use of these drugs, particularly because it improves and updates knowledge, and corrects the various misconceptions that have hitherto been prominent in the literature, partly due to insufficient knowledge of pharmacology. The guide suggests that MAOIs should always be considered in cases of treatment-resistant depression (including those melancholic in nature), and prior to electroconvulsive therapy—while taking into account of patient preference. In selected cases, they may be considered earlier in the treatment algorithm than has previously been customary, and should not be regarded as drugs of last resort; they may prove decisively effective when many other treatments have failed. The guide clarifies key points on the concomitant use of incorrectly proscribed drugs such as methylphenidate and some tricyclic antidepressants. It also illustrates the straightforward “bridging” methods that may be used to transition simply and safely from other antidepressants to MAOIs.
In this chapter we will describe how Parkinson’s disease (PD) affects patients’ eye movements, both bedside and laboratory, preceded by brief review of the anatomo-physiological substrate of eye movements. We will provide a practical summary of how to use the eye movement examination to aid the differential diagnosis of the parkinsonian syndromes, in particular idiopathic PD from multiple system atrophy (MSA), progressive supranuclear palsy (PSP), and corticobasal syndrome (CBS). A sub-section will describe how deep brain stimulation (DBS) also influences eye movements in PD. Despite a plethora of eye movement laboratory studies in PD it is still relatively unknown what the eye movements of these patients are like in real life. Given that the eyes move in order to see better, does the akinesia of PD impose visual deprivation or delays during ecological whole-body movements?.
Schizophrenia (SZ), bipolar disorder (BD) and depression (D) run in families. This susceptibility is partly due to hundreds or thousands of common genetic variants, each conferring a fractional risk. The cumulative effects of the associated variants can be summarised as a polygenic risk score (PRS). Using data from the EUropean Network of national schizophrenia networks studying Gene-Environment Interactions (EU-GEI) first episode case–control study, we aimed to test whether PRSs for three major psychiatric disorders (SZ, BD, D) and for intelligent quotient (IQ) as a neurodevelopmental proxy, can discriminate affective psychosis (AP) from schizophrenia-spectrum disorder (SSD).
Methods
Participants (842 cases, 1284 controls) from 16 European EU-GEI sites were successfully genotyped following standard quality control procedures. The sample was stratified based on genomic ancestry and analyses were done only on the subsample representing the European population (573 cases, 1005 controls). Using PRS for SZ, BD, D, and IQ built from the latest available summary statistics, we performed simple or multinomial logistic regression models adjusted for 10 principal components for the different clinical comparisons.
Results
In case–control comparisons PRS-SZ, PRS-BD and PRS-D distributed differentially across psychotic subcategories. In case–case comparisons, both PRS-SZ [odds ratio (OR) = 0.7, 95% confidence interval (CI) 0.54–0.92] and PRS-D (OR = 1.31, 95% CI 1.06–1.61) differentiated AP from SSD; and within AP categories, only PRS-SZ differentiated BD from psychotic depression (OR = 2.14, 95% CI 1.23–3.74).
Conclusions
Combining PRS for severe psychiatric disorders in prediction models for psychosis phenotypes can increase discriminative ability and improve our understanding of these phenotypes. Our results point towards the potential usefulness of PRSs in specific populations such as high-risk or early psychosis phases.