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The present study explored relationships among personality, Alzheimer’s disease (AD) biomarkers, and dementia by addressing the following questions: (1) Does personality discriminate healthy aging and earliest detectable stage of AD? (2) Does personality predict conversion from healthy aging to early-stage AD? (3) Do AD biomarkers mediate any observed relationships between personality and dementia status/conversion?
Both self- and informant ratings of personality were obtained in a large well-characterized longitudinal sample of cognitively normal older adults (N = 436) and individuals with early-stage dementia (N = 74). Biomarkers included amyloid imaging, hippocampal volume, cerebral spinal fluid (CSF) Aβ42, and CSF tau.
Higher neuroticism, lower conscientiousness, along with all four biomarkers strongly discriminated cognitively normal controls from early-stage AD individuals. The direct effects of neuroticism and conscientiousness were only mediated by hippocampal volume. Conscientiousness along with all biomarkers predicted conversion from healthy aging to early-stage AD; however, none of the biomarkers mediated the relationship between conscientiousness and conversion. Conscientiousness predicted conversion as strongly as the biomarkers, with the exception of hippocampal volume.
Conscientiousness and to a lesser extent neuroticism serve as important independent behavioral markers for AD risk.
Electron microscopy is uniquely suited for atomic-resolution imaging of heterogeneous and complex materials, where composition, physical, and electronic structure need to be analyzed simultaneously. Historically, the technique has demonstrated optimal performance at room temperature, since practical aspects such as vibration, drift, and contamination limit exploration at extreme temperature regimes. Conversely, quantum materials that exhibit exotic physical properties directly tied to the quantum mechanical nature of electrons are best studied (and often only exist) at extremely low temperatures. As a result, emergent phenomena, such as superconductivity, are typically studied using scanning probe-based techniques that can provide exquisite structural and electronic characterization, but are necessarily limited to surfaces. In this article, we focus not on the various methods that have been used to examine quantum materials at extremely low temperatures, but on what could be accomplished in the field of quantum materials if the power of electron microscopy to provide structural analysis at the atomic scale was extended to extremely low temperatures.
Brette argues that coding as a concept is inappropriate for explanations of neurocognitive phenomena. Here, we argue that Brette's conceptual analysis mischaracterizes the structure of causal claims in coding and other forms of analysis-by-decomposition. We argue that analyses of this form are permissible and conceptually coherent and offer essential tools for building and developing models of neurocognitive systems like the brain.
The Green et al., Paranoid Thoughts Scale (GPTS) – comprising two 16-item scales assessing ideas of reference (Part A) and ideas of persecution (Part B) – was developed over a decade ago. Our aim was to conduct the first large-scale psychometric evaluation.
In total, 10 551 individuals provided GPTS data. Four hundred and twenty-two patients with psychosis and 805 non-clinical individuals completed GPTS Parts A and B. An additional 1743 patients with psychosis and 7581 non-clinical individuals completed GPTS Part B. Factor analysis, item response theory, and receiver operating characteristic analyses were conducted.
The original two-factor structure of the GPTS had an inadequate model fit: Part A did not form a unidimensional scale and multiple items were locally dependant. A Revised-GPTS (R-GPTS) was formed, comprising eight-item ideas of reference and 10-item ideas of persecution subscales, which had an excellent model fit. All items in the new Reference (a = 2.09–3.67) and Persecution (a = 2.37–4.38) scales were strongly discriminative of shifts in paranoia and had high reliability across the spectrum of severity (a > 0.90). The R-GPTS score ranges are: average (Reference: 0–9; Persecution: 0–4); elevated (Reference: 10–15; Persecution: 5–10); moderately severe (Reference: 16–20; Persecution:11–17); severe (Reference: 21–24; Persecution: 18–27); and very severe (Reference: 25+; Persecution: 28+). Recommended cut-offs on the persecution scale are 11 to discriminate clinical levels of persecutory ideation and 18 for a likely persecutory delusion.
The psychometric evaluation indicated a need to improve the GPTS. The R-GPTS is a more precise measure, has excellent psychometric properties, and is recommended for future studies of paranoia.
You are anaesthetizing for a list of total knee replacements and wonder whether there is evidence as to whether femoral nerve block makes any difference to post-operative pain. You conduct a literature review and turn up some studies.
Englacial layers in Antarctica and Greenland are indicators of the dynamic, rheological and subglacial configuration of the ice sheets. Airborne radar sounder data is the primary remote sensing solution for directly observing englacial layers and structures at the glacier-catchment to ice-sheet scale. However, when traditional along-track synthetic aperture radar (SAR) processing is applied, steep layers can disappear, limiting the detectability and interpretability of englacial layer geometry. This study provides a reconstruction algorithm to address the problem of destructive phase interference during the radargram formation. We develop and apply a novel SAR processor optimized for layer detection that enhances the Signal-to-Noise ratio (SNR) of specular reflectors. The algorithm also enables the automatic estimation of layer slope. We demonstrate the algorithm using data acquired at the Institute Ice Stream, West Antarctica.
On September 1, 2019, Hurricane Dorian made landfall as a category 5 hurricane on Great Abaco Island, Bahamas. Hurricane Dorian matched the “Labor Day” hurricane of 1935 as the strongest recorded Atlantic hurricane to make landfall with maximum sustained winds of 185 miles/h.1 At the request of the Government of the Bahamas, Team Rubicon activated a World Health Organization Type 1 Mobile Emergency Medical Team and responded to Great Abaco Island. The team provided medical care and reconnaissance of medical clinics on the island and surrounding cays…
A multi-disciplinary research project has been begun in the fields next to the site of Tel Shalem (fig. 1), the locus of important discoveries since the 1970s (primarily the bronze statue of Hadrian). Recent geophysical prospections have detected the clear layout of a Roman fort and possibly even two successive forts. Two short excavation seasons carried out in 2017 and 2019, with a focus on the principia, resulted in finds that shed new light on the nature, history and identity of the site.
Field studies were conducted from 2009 through 2011 at the Sustainable Agriculture Research and Extension Center near Lingle, Wyoming, to evaluate great northern bean response to PRE flumioxazin mixed with either trifluralin, pendimethalin, or ethalfluralin. Seven treatments were arranged in a randomized complete block with three or four replicates y−1. The soil texture of the study site was loam in 2009 and 2011, and sandy loam in 2010. Soil organic matter ranged from 1.4% to 1.8%. Treatments included flumioxazin plus trifluralin, flumioxazin plus pendimethalin, flumioxazin plus ethalfluralin, ethalfluralin plus EPTC, imazamox plus bentazon (POST), hand-weeded control, and nontreated control. Dry bean density 4 wk after planting differed among herbicide treatments (P < 0.001). Treatments that included flumioxazin reduced dry bean density 54% compared with treatments without flumioxazin. Dry bean yield was influenced by dry bean density; on average, yield in flumioxazin-containing herbicide treatments was 30% less than treatments not containing flumioxazin, even though weed control was generally greater in flumioxazin treatments.
Major depressive disorder and neuroticism (Neu) share a large genetic basis. We sought to determine whether this shared basis could be decomposed to identify genetic factors that are specific to depression.
We analysed summary statistics from genome-wide association studies (GWAS) of depression (from the Psychiatric Genomics Consortium, 23andMe and UK Biobank) and compared them with GWAS of Neu (from UK Biobank). First, we used a pairwise GWAS analysis to classify variants as associated with only depression, with only Neu or with both. Second, we estimated partial genetic correlations to test whether the depression's genetic link with other phenotypes was explained by shared overlap with Neu.
We found evidence that most genomic regions (25/37) associated with depression are likely to be shared with Neu. The overlapping common genetic variance of depression and Neu was genetically correlated primarily with psychiatric disorders. We found that the genetic contributions to depression, that were not shared with Neu, were positively correlated with metabolic phenotypes and cardiovascular disease, and negatively correlated with the personality trait conscientiousness. After removing shared genetic overlap with Neu, depression still had a specific association with schizophrenia, bipolar disorder, coronary artery disease and age of first birth. Independent of depression, Neu had specific genetic correlates in ulcerative colitis, pubertal growth, anorexia and education.
Our findings demonstrate that, while genetic risk factors for depression are largely shared with Neu, there are also non-Neu-related features of depression that may be useful for further patient or phenotypic stratification.
Simulation plays an integral role in the Canadian healthcare system with applications in quality improvement, systems development, and medical education. High-quality, simulation-based research will ensure its effective use. This study sought to summarize simulation-based research activity and its facilitators and barriers, as well as establish priorities for simulation-based research in Canadian emergency medicine (EM).
Simulation-leads from Canadian departments or divisions of EM associated with a general FRCP-EM training program surveyed and documented active EM simulation-based research at their institutions and identified the perceived facilitators and barriers. Priorities for simulation-based research were generated by simulation-leads via a second survey; these were grouped into themes and finally endorsed by consensus during an in-person meeting of simulation leads. Priority themes were also reviewed by senior simulation educators.
Twenty simulation-leads representing all 14 invited institutions participated in the study between February and May, 2018. Sixty-two active, simulation-based research projects were identified (median per institution = 4.5, IQR 4), as well as six common facilitators and five barriers. Forty-nine priorities for simulation-based research were reported and summarized into eight themes: simulation in competency-based medical education, simulation for inter-professional learning, simulation for summative assessment, simulation for continuing professional development, national curricular development, best practices in simulation-based education, simulation-based education outcomes, and simulation as an investigative methodology.
This study summarized simulation-based research activity in EM in Canada, identified its perceived facilitators and barriers, and built national consensus on priority research themes. This represents the first step in the development of a simulation-based research agenda specific to Canadian EM.
The National Institute of Health has mandated good clinical practice (GCP) training for all clinical research investigators and professionals. We developed a GCP game using the Kaizen-Education platform. The GCP Kaizen game was designed to help clinical research professionals immerse themselves into applying International Conference on Harmonization GCP (R2) guidelines in the clinical research setting through case-based questions.
Students were invited to participate in the GCP Kaizen game as part of their 100% online academic Masters during the Spring 2019 semester. The structure of the game consisted of 75 original multiple choice and 25 repeated questions stemming from fictitious vignettes that were distributed across 10 weeks. Each question presented a teachable rationale after the answers were submitted. At the end of the game, a satisfaction survey was issued to collect player satisfaction data on the game platform, content, experience as well as perceptions of GCP learning and future GCP concept application.
There were 71 total players who participated and answered at least one question. Of those, 53 (75%) answered all 100 questions. The game had a high Cronbach’s alpha, and item analyses provided information on question quality, thus assisting us in future quality edits before re-testing and wider dissemination.
The GCP Kaizen game provides an alternative method for mandated GCP training using principles of gamification. It proved to be a reliable and an effective educational method with high player satisfaction.
Although efficacious treatments for major depression are available, efficacy is suboptimal and recurrence is common. Effective preventive strategies could reduce disability associated with the disorder, but current options are limited. Cognitive bias modification (CBM) is a novel and safe intervention that attenuates biases associated with depression. This study investigated whether the delivery of a CBM programme designed to attenuate negative cognitive biases over a period of 1 year would decrease the incidence of major depression among adults with subthreshold symptoms of depression.
Randomised double-blind controlled trial delivered an active CBM intervention or a control intervention over 52 weeks. Two hundred and two community-dwelling adults who reported subthreshold levels of depression were randomised (100 intervention, 102 control). The primary outcome of interest was the incidence of major depressive episode assessed at 11, 27 and 52 weeks. Secondary outcomes included onset of clinically significant symptoms of depression, change in severity of depression symptoms and change in cognitive biases.
Adherence to the interventions was modest though did not differ between conditions. Incidence of major depressive episodes was low. Conditions did not differ in the incidence of major depressive episodes. Likewise, conditions did not differ in the incidence of clinically significant levels of depression, change in the severity of depression symptoms or change in cognitive biases.
Active CBM intervention did not decrease the incidence of major depressive episodes as compared to a control intervention. However, adherence to the intervention programme was modest and the programme failed to modify the expected mechanism of action.
Apolipoprotein E (APOE) E4 is the main genetic risk factor for Alzheimer’s disease (AD). Due to the consistent association, there is interest as to whether E4 influences the risk of other neurodegenerative diseases. Further, there is a constant search for other genetic biomarkers contributing to these phenotypes, such as microtubule-associated protein tau (MAPT) haplotypes. Here, participants from the Ontario Neurodegenerative Disease Research Initiative were genotyped to investigate whether the APOE E4 allele or MAPT H1 haplotype are associated with five neurodegenerative diseases: (1) AD and mild cognitive impairment (MCI), (2) amyotrophic lateral sclerosis, (3) frontotemporal dementia (FTD), (4) Parkinson’s disease, and (5) vascular cognitive impairment.
Genotypes were defined for their respective APOE allele and MAPT haplotype calls for each participant, and logistic regression analyses were performed to identify the associations with the presentations of neurodegenerative diseases.
Our work confirmed the association of the E4 allele with a dose-dependent increased presentation of AD, and an association between the E4 allele alone and MCI; however, the other four diseases were not associated with E4. Further, the APOE E2 allele was associated with decreased presentation of both AD and MCI. No associations were identified between MAPT haplotype and the neurodegenerative disease cohorts; but following subtyping of the FTD cohort, the H1 haplotype was significantly associated with progressive supranuclear palsy.
This is the first study to concurrently analyze the association of APOE isoforms and MAPT haplotypes with five neurodegenerative diseases using consistent enrollment criteria and broad phenotypic analysis.
Sleep disturbance is a symptom of and a well-known risk factor for depression. Further, atypical functioning of the HPA axis has been linked to the pathogenesis of depression. The purpose of this study was to examine the role of adolescent HPA axis functioning in the link between adolescent sleep problems and later depressive symptoms. Methods: A sample of 157 17–18 year old adolescents (61.8% female) completed the Pittsburgh Sleep Quality Inventory (PSQI) and provided salivary cortisol samples throughout the day for three consecutive days. Two years later, adolescents reported their depressive symptoms via the Center for Epidemiological Studies Depression Scale (CES-D). Results: Individuals (age 17–18) with greater sleep disturbance reported greater depressive symptoms two years later (age 19–20). This association occurred through the indirect effect of sleep disturbance on the cortisol awakening response (CAR) (indirect effect = 0.14, 95%CI [.02 -.39]). Conclusions: One pathway through which sleep problems may lead to depressive symptoms is by up-regulating components of the body’s physiological stress response system that can be measured through the cortisol awakening response. Behavioral interventions that target sleep disturbance in adolescents may mitigate this neurobiological pathway to depression during this high-risk developmental phase.
This paper assesses how Westerners depicted Chinese entrepreneurship in the late Qing period. The paper, which is based on a range of primary sources in English, Portuguese, and French, shows that Western views of Chinese entrepreneurs were highly diverse and that while some contemporary authors viewed Chinese entrepreneurship through an Orientalist lens, others rejected this paradigm by stressing that Chinese people, or at least some subsets of the Han Chinese population, were extremely entrepreneurial. Another group of authors modified the Orientalist stereotype of Chinese stagnation by suggesting that Chinese businesspeople were capable of the lower entrepreneurial functions (e.g., simple arbitrage) but not the higher branches of entrepreneurship, which involved innovation and creative destruction. These entrepreneurial functions were, ethnocentrically, regarded as the domain of Westerners. The paper may extend our understanding about how the past still affects our current perception of Chinese entrepreneurship. It also develops our understanding of the cultural histories of entrepreneurship and Sino-Western business.