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To improve early intervention and personalise treatment for individuals early on the psychosis continuum, a greater understanding of symptom dynamics is required. We address this by identifying and evaluating the movement between empirically derived attenuated psychotic symptomatic substates—clusters of symptoms that occur within individuals over time.
Methods
Data came from a 90-day daily diary study evaluating attenuated psychotic and affective symptoms. The sample included 96 individuals aged 18–35 on the psychosis continuum, divided into four subgroups of increasing severity based on their psychometric risk of psychosis, with the fourth meeting ultra-high risk (UHR) criteria. A multilevel hidden Markov modelling (HMM) approach was used to characterise and determine the probability of switching between symptomatic substates. Individual substate trajectories and time spent in each substate were subsequently assessed.
Results
Four substates of increasing psychopathological severity were identified: (1) low-grade affective symptoms with negligible psychotic symptoms; (2) low levels of nonbizarre ideas with moderate affective symptoms; (3) low levels of nonbizarre ideas and unusual thought content, with moderate affective symptoms; and (4) moderate levels of nonbizarre ideas, unusual thought content, and affective symptoms. Perceptual disturbances predominantly occurred within the third and fourth substates. UHR individuals had a reduced probability of switching out of the two most severe substates.
Conclusions
Findings suggest that individuals reporting unusual thought content, rather than nonbizarre ideas in isolation, may exhibit symptom dynamics with greater psychopathological severity. Individuals at a higher risk of psychosis exhibited persistently severe symptom dynamics, indicating a potential reduction in psychological flexibility.
We evaluated sampling and detection methods for fungal contamination on healthcare surface materials, comparing the efficacy of foam sponges, flocked swabs, and Replicate Organism Detection And Counting (RODAC) plates alongside culture-based quantification and quantitative polymerase chain reaction (qPCR). Findings indicate that sponge sampling and qPCR detection performed best, suggesting a foundation for future studies aiming to surveillance practices for fungi.
The reward positivity (RewP) is an event-related potential that indexes reinforcement learning and reward system activation. The RewP has been shown to increase across adolescence; however, most studies have examined the RewP across two assessments, and no studies have examined within-person changes across adolescence into young adulthood. Moreover, the RewP has been identified as a neurobiological risk factor for adolescent-onset depression, but it is unclear whether childhood psychosocial risk factors might predict RewP development across adolescence. In a sample of 317 8- to 14-year-old girls (Mage = 12.4, SD = 1.8), the present study examined self-report measures of depression symptoms and stressful life events at baseline and the ΔRewP during the doors guessing task across three timepoints. Growth modeling indicated that, across all participants, the ΔRewP did not demonstrate linear change across adolescence. However, baseline anhedonia symptoms predicted within-person changes in the ΔRewP, such that individuals with low anhedonia symptoms demonstrated a linear increase in the ΔRewP, but individuals with high anhedonia symptoms had no change in the ΔRewP across adolescence. Similar patterns were observed for stressful life events. The present study suggests that childhood risk factors impact the development of reward-related brain activity, which might subsequently increase risk for psychopathology.
Pre-diagnostic stages of psychotic illnesses, including ‘clinical high risk’ (CHR), are marked by sleep disturbances. These sleep disturbances appear to represent a key aspect in the etiology and maintenance of psychotic disorders. We aimed to examine the relationship between self-reported sleep dysfunction and attenuated psychotic symptoms (APS) on a day-to-day basis.
Methods
Seventy-six CHR young people completed the Experience Sampling Methodology (ESM) component of the European Union Gene-Environment Interaction Study, collected through PsyMate® devices, prompting sleep and symptom questionnaires 10 times daily for 6 days. Bayesian multilevel mixed linear regression analyses were performed on time-variant ESM data using the brms package in R. We investigated the day-to-day associations between sleep and psychotic experiences bidirectionally on an item level. Sleep items included sleep onset latency, fragmentation, and quality. Psychosis items assessed a range of perceptual, cognitive, and bizarre thought content common in the CHR population.
Results
Two of the seven psychosis variables were unidirectionally predicted by previous night's number of awakenings: every unit increase in number of nightly awakenings predicted a 0.27 and 0.28 unit increase in feeling unreal or paranoid the next day, respectively. No other sleep variables credibly predicted next-day psychotic symptoms or vice-versa.
Conclusion
In this study, the relationship between sleep disturbance and APS appears specific to the item in question. However, some APS, including perceptual disturbances, had low levels of endorsement amongst this sample. Nonetheless, these results provide evidence for a unidirectional relationship between sleep and some APS in this population.
The origins and timing of inpatient room sink contamination with carbapenem-resistant organisms (CROs) are poorly understood.
Methods:
We performed a prospective observational study to describe the timing, rate, and frequency of CRO contamination of in-room handwashing sinks in 2 intensive care units (ICU) in a newly constructed hospital bed tower. Study units, A and B, were opened to patient care in succession. The patients in unit A were moved to a new unit in the same bed tower, unit B. Each unit was similarly designed with 26 rooms and in-room sinks. Microbiological samples were taken every 4 weeks from 3 locations from each study sink: the top of the bowl, the drain cover, and the p-trap. The primary outcome was sink conversion events (SCEs), defined as CRO contamination of a sink in which CRO had not previously been detected.
Results:
Sink samples were obtained 22 times from September 2020 to June 2022, giving 1,638 total environmental cultures. In total, 2,814 patients were admitted to study units while sink sampling occurred. We observed 35 SCEs (73%) overall; 9 sinks (41%) in unit A became contaminated with CRO by month 10, and all 26 sinks became contaminated in unit B by month 7. Overall, 299 CRO isolates were recovered; the most common species were Enterobacter cloacae and Pseudomonas aeruginosa.
Conclusion:
CRO contamination of sinks in 2 newly constructed ICUs was rapid and cumulative. Our findings support in-room sinks as reservoirs of CRO and emphasize the need for prevention strategies to mitigate contamination of hands and surfaces from CRO-colonized sinks.
Unoccupied aerial application systems (UAAS) are gaining popularity for weed management to increase applicator safety and to deliver herbicide treatments where treatment sites limit ground-based spray equipment. Several studies have documented UAAS application strategies and procedures for weed control in terrestrial settings, yet literature describing remote spray technology for use in aquatics remains limited. Currently, applicators seek guidance for UAAS deployment for aquatic weed management to overcome site access restrictions, deal with environmental limitations, and improve ground-based applicator safety in hazardous treatment scenarios. In the present case studies, we evaluate a consumer-available UAAS to deliver the herbicide, florpyrauxifen-benzyl, as both foliar and directed in-water spray applications. The first case study showed that the invasive floating-leaved plant, yellow floating heart, was controlled 80% to 99% by 6 wk after treatment (WAT) following UAAS foliar herbicide treatments. The second case study demonstrated that UAAS directed in-water herbicide application reduced variable-leaf watermilfoil visible plant material by 94% at 5 WAT. Likewise, directed in-water applications from UAAS eliminated the need to deploy watercraft, which improved overall operational efficiency. Data from both case studies indicate that UAAS can provide an effective and efficient treatment strategy for floating-leaved and submersed plant control among common herbicide treatment scenarios. Future integration of UAAS in aquatic weed control programs is encouraged, especially among smaller treatment sites (≤4 ha) or where access limits traditional spray operations.
Recent theoretical models have posited that increases in self-injurious thoughts and behaviors (SITBs) during adolescence may be linked to failures in biological stress regulation in contexts of social stress. However, there is a lack of data examining this hypothesis during the transition to adolescence, a sensitive period of development characterized by changes across socioaffective and psychophysiological domains. Building on principles from developmental psychopathology and the RDoC framework, the present study used a longitudinal design in a sample of 147 adolescents to test whether interactions among experiences of social (i.e., parent and peer) conflict and cardiac arousal (i.e., resting heart rate) predicted adolescents’ engagement in SITBs (i.e., nonsuicidal self-injury, NSSI; and suicidal ideation; SI) across 1-year follow-up. Prospective analyses revealed that adolescents experiencing a combination of greater peer, but not family, conflict and higher cardiac arousal at baseline showed significant longitudinal increases in NSSI. In contrast, social conflict did not interact with cardiac arousal to predict future SI. Findings indicate that greater peer-related interpersonal stress in adolescents may increase risk for future NSSI among youth with physiological vulnerabilities (i.e., higher resting heart rate) that may be markers of maladaptive stress responses. Future research should examine these processes at finer timescales to elucidate whether these factors are proximal predictors of within-day SITBs.
The Hierarchical Taxonomy of Psychopathology (HiTOP) has emerged out of the quantitative approach to psychiatric nosology. This approach identifies psychopathology constructs based on patterns of co-variation among signs and symptoms. The initial HiTOP model, which was published in 2017, is based on a large literature that spans decades of research. HiTOP is a living model that undergoes revision as new data become available. Here we discuss advantages and practical considerations of using this system in psychiatric practice and research. We especially highlight limitations of HiTOP and ongoing efforts to address them. We describe differences and similarities between HiTOP and existing diagnostic systems. Next, we review the types of evidence that informed development of HiTOP, including populations in which it has been studied and data on its validity. The paper also describes how HiTOP can facilitate research on genetic and environmental causes of psychopathology as well as the search for neurobiologic mechanisms and novel treatments. Furthermore, we consider implications for public health programs and prevention of mental disorders. We also review data on clinical utility and illustrate clinical application of HiTOP. Importantly, the model is based on measures and practices that are already used widely in clinical settings. HiTOP offers a way to organize and formalize these techniques. This model already can contribute to progress in psychiatry and complement traditional nosologies. Moreover, HiTOP seeks to facilitate research on linkages between phenotypes and biological processes, which may enable construction of a system that encompasses both biomarkers and precise clinical description.
Studying phenotypic and genetic characteristics of age at onset (AAO) and polarity at onset (PAO) in bipolar disorder can provide new insights into disease pathology and facilitate the development of screening tools.
Aims
To examine the genetic architecture of AAO and PAO and their association with bipolar disorder disease characteristics.
Method
Genome-wide association studies (GWASs) and polygenic score (PGS) analyses of AAO (n = 12 977) and PAO (n = 6773) were conducted in patients with bipolar disorder from 34 cohorts and a replication sample (n = 2237). The association of onset with disease characteristics was investigated in two of these cohorts.
Results
Earlier AAO was associated with a higher probability of psychotic symptoms, suicidality, lower educational attainment, not living together and fewer episodes. Depressive onset correlated with suicidality and manic onset correlated with delusions and manic episodes. Systematic differences in AAO between cohorts and continents of origin were observed. This was also reflected in single-nucleotide variant-based heritability estimates, with higher heritabilities for stricter onset definitions. Increased PGS for autism spectrum disorder (β = −0.34 years, s.e. = 0.08), major depression (β = −0.34 years, s.e. = 0.08), schizophrenia (β = −0.39 years, s.e. = 0.08), and educational attainment (β = −0.31 years, s.e. = 0.08) were associated with an earlier AAO. The AAO GWAS identified one significant locus, but this finding did not replicate. Neither GWAS nor PGS analyses yielded significant associations with PAO.
Conclusions
AAO and PAO are associated with indicators of bipolar disorder severity. Individuals with an earlier onset show an increased polygenic liability for a broad spectrum of psychiatric traits. Systematic differences in AAO across cohorts, continents and phenotype definitions introduce significant heterogeneity, affecting analyses.
Introduction. Individuals with psychotic-spectrum disorders may smoke due to the ameliorating effect of nicotine on the cognitive deficits that accompany these illnesses. Metacognitive remediation therapy (MCR) has been shown to produce improvements in cognitive functioning among individuals with psychotic-spectrum disorders and provides a foundation for a novel smoking cessation intervention for this population. Aims. To complete an open investigation of pharmacotherapy and a modified version of MCR [MCR to Quit (MCR-Q)] in promoting smoking cessation among individuals with psychotic-spectrum disorders. Methods. Forty-nine individuals with a psychotic-spectrum disorder and who currently smoke cigarettes participated in MCR-Q while also receiving evidence-based smoking cessation pharmacotherapy. Tobacco use was assessed as follows: (i) prior to MCR-Q, (ii) immediately after completing MCR-Q, and (iii) six weeks after completion of MCR-Q. Results/Findings. During participation in MCR-Q, nearly 80% of participants made a 24-hour quit attempt. Following the completion of MCR-Q, participants experienced reductions in level of nicotine dependency and exhaled carbon monoxide, with reductions in nicotine dependency sustained six weeks after completion of MCR-Q. Over the course of their participation in MCR-Q, participants reported strong therapeutic alliance with their MCR-Q therapist and high levels of intrinsic motivation with regard to completing MCR-Q exercises. Conclusions. The results from the current study suggest cautious optimism with regard to the use of MCR-Q in combination with medication for individuals with psychotic-spectrum disorders who want to quit smoking.
Elective surgical patients routinely bathe with chlorhexidine gluconate (CHG) at home days prior to their procedures. However, the impact of home CHG bathing on surgical site CHG concentration is unclear. We examined 3 different methods of applying CHG and hypothesized that different application methods would impact resulting CHG skin concentration.
Two randomized, controlled trials of L-methylfolate augmentation of SSRIs for major depressive disorder (MDD) were conducted using a novel study design (sequential parallel comparison design- SPCD).
Objectives/aims
To evaluate the efficacy of L-methylfolate augmentation using the Hamilton Depression Rating Scale.
Methods
In study one (TRD-1), 148 outpatients with SSRI-resistant MDD were enrolled in a 60-day, SPCD study, divided into two 30-day periods (phases 1 and 2). Patients were randomized 2:3:3 to receive L-methylfolate (7.5mg/d in phase 1, 15mg/d in phase 2), placebo in phase 1 followed by L-methylfolate 7.5mg/d in phase 2, or placebo for both phases. Study two (TRD-2) involved 75 patients and was identical in design to TRD-1 except for the dose of L-methylfolate (15mg only).
Results
In the TRD-1 Study, L-methylfolate 7.5 mg/d was not found to be more effective than placebo. In phase 1 of the TRD-2 Study, 37% of patients on L-methylfolate 15mg/d responded and 18% of placebo patients responded, while in phase 2 among placebo non-responders, the response rates were 28% on L-methylfolate 15mg/d and 9.5% on placebo. When phases 1 and 2 were pooled according to the SPCD model, the difference in response rates was statistically significant in favor of L-methylfolate (p = 0.0399). The rates of spontaneously reported AEs and rates of study discontinuation appear r comparable between L-methylfolate and placebo in both studies. Rates of study discontinuation were also comparable
Conclusions
These studies suggest that L-methylfolate 15 mg/d may be a safe and effective augmentation strategy for inadequate response to SSRIs.
The COllaborative project of Development of Anthropometrical measures in Twins (CODATwins) project is a large international collaborative effort to analyze individual-level phenotype data from twins in multiple cohorts from different environments. The main objective is to study factors that modify genetic and environmental variation of height, body mass index (BMI, kg/m2) and size at birth, and additionally to address other research questions such as long-term consequences of birth size. The project started in 2013 and is open to all twin projects in the world having height and weight measures on twins with information on zygosity. Thus far, 54 twin projects from 24 countries have provided individual-level data. The CODATwins database includes 489,981 twin individuals (228,635 complete twin pairs). Since many twin cohorts have collected longitudinal data, there is a total of 1,049,785 height and weight observations. For many cohorts, we also have information on birth weight and length, own smoking behavior and own or parental education. We found that the heritability estimates of height and BMI systematically changed from infancy to old age. Remarkably, only minor differences in the heritability estimates were found across cultural–geographic regions, measurement time and birth cohort for height and BMI. In addition to genetic epidemiological studies, we looked at associations of height and BMI with education, birth weight and smoking status. Within-family analyses examined differences within same-sex and opposite-sex dizygotic twins in birth size and later development. The CODATwins project demonstrates the feasibility and value of international collaboration to address gene-by-exposure interactions that require large sample sizes and address the effects of different exposures across time, geographical regions and socioeconomic status.
Hill (Twin Research and Human Genetics, Vol. 21, 2018, 84–88) presented a critique of our recently published paper in Cell Reports entitled ‘Large-Scale Cognitive GWAS Meta-Analysis Reveals Tissue-Specific Neural Expression and Potential Nootropic Drug Targets’ (Lam et al., Cell Reports, Vol. 21, 2017, 2597–2613). Specifically, Hill offered several interrelated comments suggesting potential problems with our use of a new analytic method called Multi-Trait Analysis of GWAS (MTAG) (Turley et al., Nature Genetics, Vol. 50, 2018, 229–237). In this brief article, we respond to each of these concerns. Using empirical data, we conclude that our MTAG results do not suffer from ‘inflation in the FDR [false discovery rate]’, as suggested by Hill (Twin Research and Human Genetics, Vol. 21, 2018, 84–88), and are not ‘more relevant to the genetic contributions to education than they are to the genetic contributions to intelligence’.
Prior research has documented shared heritable contributions to non-suicidal self-injury (NSSI) and suicidal ideation (SI) as well as NSSI and suicide attempt (SA). In addition, trauma exposure has been implicated in risk for NSSI and suicide. Genetically informative studies are needed to determine common sources of liability to all three self-injurious thoughts and behaviors, and to clarify the nature of their associations with traumatic experiences.
Methods
Multivariate biometric modeling was conducted using data from 9526 twins [59% female, mean age = 31.7 years (range 24–42)] from two cohorts of the Australian Twin Registry, some of whom also participated in the Childhood Trauma Study and the Nicotine Addiction Genetics Project.
Results
The prevalences of high-risk trauma exposure (HRT), NSSI, SI, and SA were 24.4, 5.6, 27.1, and 4.6%, respectively. All phenotypes were moderately to highly correlated. Genetic influences on self-injurious thoughts and behaviors and HRT were significant and highly correlated among men [rG = 0.59, 95% confidence interval (CI) (0.37–0.81)] and women [rG = 0.56 (0.49–0.63)]. Unique environmental influences were modestly correlated in women [rE = 0.23 (0.01–0.45)], suggesting that high-risk trauma may confer some direct risk for self-injurious thoughts and behaviors among females.
Conclusions
Individuals engaging in NSSI are at increased risk for suicide, and common heritable factors contribute to these associations. Preventing trauma exposure may help to mitigate risk for self-harm and suicide, either directly or indirectly via reductions in liability to psychopathology more broadly. In addition, targeting pre-existing vulnerability factors could significantly reduce risk for life-threatening behaviors among those who have experienced trauma.
While our fascination with understanding the past is sufficient to warrant an increased focus on synthesis, solutions to important problems facing modern society require understandings based on data that only archaeology can provide. Yet, even as we use public monies to collect ever-greater amounts of data, modes of research that can stimulate emergent understandings of human behavior have lagged behind. Consequently, a substantial amount of archaeological inference remains at the level of the individual project. We can more effectively leverage these data and advance our understandings of the past in ways that contribute to solutions to contemporary problems if we adapt the model pioneered by the National Center for Ecological Analysis and Synthesis to foster synthetic collaborative research in archaeology. We propose the creation of the Coalition for Archaeological Synthesis coordinated through a U.S.-based National Center for Archaeological Synthesis. The coalition will be composed of established public and private organizations that provide essential scholarly, cultural heritage, computational, educational, and public engagement infrastructure. The center would seek and administer funding to support collaborative analysis and synthesis projects executed through coalition partners. This innovative structure will enable the discipline to address key challenges facing society through evidentially based, collaborative synthetic research.
To assess antimicrobial prescriber knowledge, attitudes, and practices (KAP) regarding antimicrobial stewardship (AS) and associated barriers to optimal prescribing.
DESIGN
Cross-sectional survey.
SETTING
Online survey.
PARTICIPANTS
A convenience sample of 2,900 US antimicrobial prescribers at 5 acute-care hospitals within a hospital network.
INTERVENTION
The following characteristics were assessed with an anonymous, online survey in February 2015: attitudes and practices related to antimicrobial resistance, AS programs, and institutional AS resources; antimicrobial prescribing and AS knowledge; and practices and confidence related to antimicrobial prescribing.
RESULTS
In total, 402 respondents completed the survey. Knowledge gaps were identified through case-based questions. Some respondents sometimes selected overly broad therapy for the susceptibilities given (29%) and some “usually” or “always” preferred using the most broad-spectrum empiric antimicrobials possible (32%). Nearly all (99%) reported reviewing antimicrobial appropriateness at 48–72 hours, but only 55% reported “always” doing so. Furthermore, 45% of respondents felt that they had not received adequate training regarding antimicrobial prescribing. Some respondents lacked confidence selecting empiric therapy using antibiograms (30%), interpreting susceptibility results (24%), de-escalating therapy (18%), and determining duration of therapy (31%). Postprescription review and feedback (PPRF) was the most commonly cited AS intervention (79%) with potential to improve patient care.
CONCLUSIONS
Barriers to appropriate antimicrobial selection and de-escalation of antimicrobial therapy were identified among front-line prescribers in acute-care hospitals. Prescribers desired more AS-related education and identified PPRF as the most helpful AS intervention to improve patient care. Educational interventions should be preceded by and tailored to local assessment of educational needs.
Measurements made by an underwater glider deployed near the Ross Ice Shelf were used to identify the presence of Ice Shelf Water (ISW), which is defined as seawater with its potential temperature lower than its surface freezing point temperature. Properties logged by the glider included in situ temperature, electrical conductivity, pressure, GPS location at surfacings and time. For most of the first 30 recorded dives of its deployment, evidence suggests the glider was prevented from surfacing due to being under the ice shelf. For dives under the ice shelf, farthest from the ice shelf front, ISW layers of varying thicknesses and depth locations were observed; between 2 m thick (centred at 231 m depth) to >93 m thick (centred at >360 m). For dives under the ice shelf, close to the ice shelf front, either no ISW was observed or ISW layers were centred at shallower depths (116–127 m). Thicker ISW layers (e.g. up to 250 m thickness centred at 421 m) were observed for some glider dives in open water in front of the Ross Ice Shelf. No in situ supercooling (water colder than the pressure-dependent freezing point temperature) was observed.