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Many patients with mental health disorders become increasingly isolated at home due to anxiety about going outside. A cognitive perspective on this difficulty is that threat cognitions lead to the safety-seeking behavioural response of agoraphobic avoidance.
We sought to develop a brief questionnaire, suitable for research and clinical practice, to assess a wide range of cognitions likely to lead to agoraphobic avoidance. We also included two additional subscales assessing two types of safety-seeking defensive responses: anxious avoidance and within-situation safety behaviours.
198 patients with psychosis and agoraphobic avoidance and 1947 non-clinical individuals completed the item pool and measures of agoraphobic avoidance, generalised anxiety, social anxiety, depression and paranoia. Factor analyses were used to derive the Oxford Cognitions and Defences Questionnaire (O-CDQ).
The O-CDQ consists of three subscales: threat cognitions (14 items), anxious avoidance (11 items), and within-situation safety behaviours (8 items). Separate confirmatory factor analyses demonstrated a good model fit for all subscales. The cognitions subscale was significantly associated with agoraphobic avoidance (r = .672, p < .001), social anxiety (r = .617, p < .001), generalized anxiety (r = .746, p < .001), depression (r = .619, p < .001) and paranoia (r = .655, p < .001). Additionally, both the O-CDQ avoidance (r = .867, p < .001) and within-situation safety behaviours (r = .757, p < .001) subscales were highly correlated with agoraphobic avoidance. The O-CDQ demonstrated excellent internal consistency (cognitions Cronbach’s alpha = .93, avoidance Cronbach’s alpha = .94, within-situation Cronbach’s alpha = .93) and test–re-test reliability (cognitions ICC = 0.88, avoidance ICC = 0.92, within-situation ICC = 0.89).
The O-CDQ, consisting of three separate scales, has excellent psychometric properties and may prove a helpful tool for understanding agoraphobic avoidance across mental health disorders.
Early in the COVID-19 pandemic, the World Health Organization stressed the importance of daily clinical assessments of infected patients, yet current approaches frequently consider cross-sectional timepoints, cumulative summary measures, or time-to-event analyses. Statistical methods are available that make use of the rich information content of longitudinal assessments. We demonstrate the use of a multistate transition model to assess the dynamic nature of COVID-19-associated critical illness using daily evaluations of COVID-19 patients from 9 academic hospitals. We describe the accessibility and utility of methods that consider the clinical trajectory of critically ill COVID-19 patients.
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.
To examine the genetic architecture of AAO and PAO and their association with bipolar disorder disease characteristics.
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.
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.
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.
Advanced imaging techniques are enhancing research capacity focussed on the developmental origins of adult health and disease (DOHaD) hypothesis, and consequently increasing awareness of future health risks across various subareas of DOHaD research themes. Understanding how these advanced imaging techniques in animal models and human population studies can be both additively and synergistically used alongside traditional techniques in DOHaD-focussed laboratories is therefore of great interest. Global experts in advanced imaging techniques congregated at the advanced imaging workshop at the 2019 DOHaD World Congress in Melbourne, Australia. This review summarizes the presentations of new imaging modalities and novel applications to DOHaD research and discussions had by DOHaD researchers that are currently utilizing advanced imaging techniques including MRI, hyperpolarized MRI, ultrasound, and synchrotron-based techniques to aid their DOHaD research focus.
Studies suggest that alcohol consumption and alcohol use disorders have distinct genetic backgrounds.
We examined whether polygenic risk scores (PRS) for consumption and problem subscales of the Alcohol Use Disorders Identification Test (AUDIT-C, AUDIT-P) in the UK Biobank (UKB; N = 121 630) correlate with alcohol outcomes in four independent samples: an ascertained cohort, the Collaborative Study on the Genetics of Alcoholism (COGA; N = 6850), and population-based cohorts: Avon Longitudinal Study of Parents and Children (ALSPAC; N = 5911), Generation Scotland (GS; N = 17 461), and an independent subset of UKB (N = 245 947). Regression models and survival analyses tested whether the PRS were associated with the alcohol-related outcomes.
In COGA, AUDIT-P PRS was associated with alcohol dependence, AUD symptom count, maximum drinks (R2 = 0.47–0.68%, p = 2.0 × 10−8–1.0 × 10−10), and increased likelihood of onset of alcohol dependence (hazard ratio = 1.15, p = 4.7 × 10−8); AUDIT-C PRS was not an independent predictor of any phenotype. In ALSPAC, the AUDIT-C PRS was associated with alcohol dependence (R2 = 0.96%, p = 4.8 × 10−6). In GS, AUDIT-C PRS was a better predictor of weekly alcohol use (R2 = 0.27%, p = 5.5 × 10−11), while AUDIT-P PRS was more associated with problem drinking (R2 = 0.40%, p = 9.0 × 10−7). Lastly, AUDIT-P PRS was associated with ICD-based alcohol-related disorders in the UKB subset (R2 = 0.18%, p < 2.0 × 10−16).
AUDIT-P PRS was associated with a range of alcohol-related phenotypes across population-based and ascertained cohorts, while AUDIT-C PRS showed less utility in the ascertained cohort. We show that AUDIT-P is genetically correlated with both use and misuse and demonstrate the influence of ascertainment schemes on PRS analyses.
Positive symptoms are a useful predictor of aggression in schizophrenia. Although a similar pattern of abnormal brain structures related to both positive symptoms and aggression has been reported, this observation has not yet been confirmed in a single sample.
To study the association between positive symptoms and aggression in schizophrenia on a neurobiological level, a prospective meta-analytic approach was employed to analyze harmonized structural neuroimaging data from 10 research centers worldwide. We analyzed brain MRI scans from 902 individuals with a primary diagnosis of schizophrenia and 952 healthy controls.
The result identified a widespread cortical thickness reduction in schizophrenia compared to their controls. Two separate meta-regression analyses revealed that a common pattern of reduced cortical gray matter thickness within the left lateral temporal lobe and right midcingulate cortex was significantly associated with both positive symptoms and aggression.
These findings suggested that positive symptoms such as formal thought disorder and auditory misperception, combined with cognitive impairments reflecting difficulties in deploying an adaptive control toward perceived threats, could escalate the likelihood of aggression in schizophrenia.
The cognitive process of worry, which keeps negative thoughts in mind and elaborates the content, contributes to the occurrence of many mental health disorders. Our principal aim was to develop a straightforward measure of general problematic worry suitable for research and clinical treatment. Our secondary aim was to develop a measure of problematic worry specifically concerning paranoid fears.
An item pool concerning worry in the past month was evaluated in 250 non-clinical individuals and 50 patients with psychosis in a worry treatment trial. Exploratory factor analysis and item response theory (IRT) informed the selection of scale items. IRT analyses were repeated with the scales administered to 273 non-clinical individuals, 79 patients with psychosis and 93 patients with social anxiety disorder. Other clinical measures were administered to assess concurrent validity. Test-retest reliability was assessed with 75 participants. Sensitivity to change was assessed with 43 patients with psychosis.
A 10-item general worry scale (Dunn Worry Questionnaire; DWQ) and a five-item paranoia worry scale (Paranoia Worries Questionnaire; PWQ) were developed. All items were highly discriminative (DWQ a = 1.98–5.03; PWQ a = 4.10–10.7), indicating small increases in latent worry lead to a high probability of item endorsement. The DWQ was highly informative across a wide range of the worry distribution, whilst the PWQ had greatest precision at clinical levels of paranoia worry. The scales demonstrated excellent internal reliability, test-retest reliability, concurrent validity and sensitivity to change.
The new measures of general problematic worry and worry about paranoid fears have excellent psychometric properties.
Impact craters are the dominant landform on Mercury and range from the largest basins to the smallest young craters. Peak-ring basins are especially prevalent on Mercury, although basins of all forms are far undersaturated, probably the result of the extensive volcanic emplacement of intercrater plains and younger smooth plains between about 4.1 and 3.5 Ga. This chapter describes the geology of the two largest well-preserved basins, Caloris and Rembrandt, and the three smaller Raditladi, Rachmaninoff, and Mozart basins. We describe analyses of crater size–frequency distributions and relate them to populations of asteroid impactors (Late Heavy Bombardment in early epochs and the near-Earth asteroid population observable today during most of Mercury’s history), to secondary cratering, and to exogenic and endogenic processes that degrade and erase craters. Secondary cratering is more important on Mercury than on other solar system bodies and shaped much of the surface on kilometer and smaller scales, compromising our ability to use craters for relative and absolute age-dating of smaller geological units. Failure to find “vulcanoids” and satellites of Mercury suggests that such bodies played a negligible role in cratering Mercury. We describe an absolute cratering chronology for Mercury’s geological evolution as well as its uncertainties.
Movement disorders associated with exposure to antipsychotic drugs are common and stigmatising but underdiagnosed.
To develop and evaluate a new clinical procedure, the ScanMove instrument, for the screening of antipsychotic-associated movement disorders for use by mental health nurses.
Item selection and content validity assessment for the ScanMove instrument were conducted by a panel of neurologists, psychiatrists and a mental health nurse, who operationalised a 31-item screening procedure. Interrater reliability was measured on ratings for 30 patients with psychosis from ten mental health nurses evaluating video recordings of the procedure. Criterion and concurrent validity were tested comparing the ScanMove instrument-based rating of 13 mental health nurses for 635 community patients from mental health services with diagnostic judgement of a movement disorder neurologist based on the ScanMove instrument and a reference procedure comprising a selection of commonly used rating scales.
Interreliability analysis showed no systematic difference between raters in their prediction of any antipsychotic-associated movement disorders category. On criterion validity testing, the ScanMove instrument showed good sensitivity for parkinsonism (90%) and hyperkinesia (89%), but not for akathisia (38%), whereas specificity was low for parkinsonism and hyperkinesia, and moderate for akathisia.
The ScanMove instrument demonstrated good feasibility and interrater reliability, and acceptable sensitivity as a mental health nurse-administered screening tool for parkinsonism and hyperkinesia.
The Yellow Sea region is of high global importance for waterbird populations, but recent systematic bird count data enabling identification of the most important sites are relatively sparse for some areas. Surveys of waterbirds at three sites on the coast of southern Jiangsu Province, China, in 2014 and 2015 produced peak counts of international importance for 24 species, including seven globally threatened and six Near Threatened species. The area is of particular global importance for the ‘Critically Endangered’ Spoon-billed Sandpiper Calidris pygmaea (peak count across all three study sites: 62 in spring  and 225 in autumn  and ‘Endangered’ Spotted Greenshank Tringa guttifer (peak count across all three study sites: 210 in spring  and 1,110 in autumn ). The southern Jiangsu coast is therefore currently the most important migratory stopover area in the world, in both spring and autumn, for both species. Several serious and acute threats to waterbirds were recorded at these study sites. Paramount is the threat of large-scale land claim which would completely destroy intertidal mudflats of critical importance to waterbirds. Degradation of intertidal mudflat habitats through the spread of invasive Spartina, and mortality of waterbirds by entrapment in nets or deliberate poisoning are also real and present serious threats here. Collisions with, and displacement by, wind turbines and other structures, and industrial chemical pollution may represent additional potential threats. We recommend the rapid establishment of effective protected areas for waterbirds in the study area, maintaining large areas of open intertidal mudflat, and the urgent removal of all serious threats currently faced by waterbirds here.
The StratEx program used a self-contained space suit and balloon system to loft pilot Alan Eustace to a record-breaking altitude and skydive from 135,897 feet (41,422 m). After releasing from the balloon and a stabilized freefall, the pilot safely landed using a parachute system based on a modified tandem parachute rig. A custom spacesuit provided life support using a similar system to NASA’s (National Aeronautics and Space Administration; Washington, DC USA) Extravehicular Mobility Unit. It also provided tracking, communications, and connection to the parachute system. A recovery support team, including at least two medical personnel and two spacesuit technicians, was charged with reaching the pilot within five minutes of touchdown to extract him from the suit and provide treatment for any injuries. The team had to track the flight at all times, be prepared to respond in case of premature release, and to operate in any terrain. Crew recovery operations were planned and tailored to anticipate outcomes during this novel event in a systematic fashion, through scenario and risk analysis, in order to minimize the probability and impact of injury. This analysis, detailed here, helped the team configure recovery assets, refine navigation and tracking systems, develop procedures, and conduct training. An extensive period of testing and practice culminated in three manned flights leading to a successful mission and setting the record for exit altitude, distance of fall with stabilizing device, and vertical speed with a stabilizing device. During this mission, recovery teams reached the landing spot within one minute, extracted the pilot, and confirmed that he was not injured. This strategy is presented as an approach to prehospital planning and care for improved safety during crew recovery in novel, extreme events.
AntonsenEL. Crew Recovery and Contingency Planning for a Manned Stratospheric Balloon Flight – the StratEx Program. Prehosp Disaster Med.2016;31(5):524–531.
Archaeologists working in the Salish Sea (Strait of Georgia and Puget Sound)
region of the Pacific Northwest have unearthed human burials and
non-mortuary features dated to 4000–3500 cal B.P. containing tens and even
hundreds of thousands of stone and shell disc beads. Several sites are
reported here, including burials recently excavated from site DjRw–14
located in the territory of the shíshálh Nation. We argue that the disc
beads constituted an important form of material wealth at this time, based
on the amount of labor that would have been required to produce them and the
capacity for beads to accrue in value after their production. A model of
material wealth-based inequality is developed for a period much older than
many archaeologists working in the region have previously thought.
Levels of pollution, including contamination by toxic metals, in the Thames estuary reduced over the last four decades of the 20th century. This 2014 study investigates whether the declines in the bioavailabilities of trace metals (Ag, Cd, Co, Cr, Cu, Fe, Mn, Ni, Pb, V, Zn) have continued in the 21st century, using a suite of littoral biomonitors also employed in 2001 – the brown seaweed Fucus vesiculosus, the strandline, talitrid amphipod Orchestia gammarellus and the estuarine barnacle Amphibalanus improvisus. Bioaccumulated concentrations represent relative measures of the total bioavailabilities of each metal to the biomonitor over a previous time period, and can be compared over space and over time. Trace metal bioavailabilities varied along the estuary, and, in general, fell between 2001 and 2014, a reflection of the continuing remediation of the Thames estuary from its severely polluted state in the middle of the 20th century.
Reducing the delay of backend interconnects is critical in delivering improved performance in next generation computer chips. One option is to implement interlayer dielectric (ILD) materials with increasingly lower dielectric constant (k) values. Despite industry need, there has been a recent decrease in study and production of these materials in academia and business communities. We have generated a backbone and porogen system that allows us to control porosity from 0 to 60% volume, achieve k-values from 3.4 to 1.6, maintain high chemical stability to various wet cleans, and deliver uniquely high mechanical strength at a given porosity. Finite element modeling and experimental results demonstrate that further improvements can be achieved through control of the pore volume into an ordered network. With hopes to spur more materials development, this paper discusses some molecular design and nanoscale hierarchical principles relevant to making next generation low-k ILD materials.