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The schizophrenia polygenic risk score (SCZ-PRS) is an emerging tool in psychiatry.
We aimed to evaluate the utility of SCZ-PRS in a young, transdiagnostic, clinical cohort.
SCZ-PRSs were calculated for young people who presented to early-intervention youth mental health clinics, including 158 patients of European ancestry, 113 of whom had longitudinal outcome data. We examined associations between SCZ-PRS and diagnosis, clinical stage and functioning at initial assessment, and new-onset psychotic disorder, clinical stage transition and functional course over time in contact with services.
Compared with a control group, patients had elevated PRSs for schizophrenia, bipolar disorder and depression, but not for any non-psychiatric phenotype (for example cardiovascular disease). Higher SCZ-PRSs were elevated in participants with psychotic, bipolar, depressive, anxiety and other disorders. At initial assessment, overall SCZ-PRSs were associated with psychotic disorder (odds ratio (OR) per s.d. increase in SCZ-PRS was 1.68, 95% CI 1.08–2.59, P = 0.020), but not assignment as clinical stage 2+ (i.e. discrete, persistent or recurrent disorder) (OR = 0.90, 95% CI 0.64–1.26, P = 0.53) or functioning (R = 0.03, P = 0.76). Longitudinally, overall SCZ-PRSs were not significantly associated with new-onset psychotic disorder (OR = 0.84, 95% CI 0.34–2.03, P = 0.69), clinical stage transition (OR = 1.02, 95% CI 0.70–1.48, P = 0.92) or persistent functional impairment (OR = 0.84, 95% CI 0.52–1.38, P = 0.50).
In this preliminary study, SCZ-PRSs were associated with psychotic disorder at initial assessment in a young, transdiagnostic, clinical cohort accessing early-intervention services. Larger clinical studies are needed to further evaluate the clinical utility of SCZ-PRSs, especially among individuals with high SCZ-PRS burden.
Finding the ways that work to deliver the innovation needed should be given parity of esteem with getting the prices right as a focus of the economics profession and policy systems. Learn from experience as regards carbon pricing and carbon-reducing innovation; insights from the latter coming mainly from the US, China and Europe; demographically relatively small countries – Denmark (wind) and Australia (solar PV) – can make outsize contributions. A carbon price ceiling is too low to drive innovation; generating carbon-reducing innovation requires that it be explicitly recognized as a priority, and nurtured accordingly: identify the priority area(s) where innovation at scale will be necessary to make progress; baseline the elements of the innovation ecosystem which are already in place, and the gaps that need to be filled. Key elements include institutions and incentives that promote innovation, a research and enterprise community that make it happen, and a supportive public.
A recent genome-wide association study (GWAS) identified 12 independent loci significantly associated with attention-deficit/hyperactivity disorder (ADHD). Polygenic risk scores (PRS), derived from the GWAS, can be used to assess genetic overlap between ADHD and other traits. Using ADHD samples from several international sites, we derived PRS for ADHD from the recent GWAS to test whether genetic variants that contribute to ADHD also influence two cognitive functions that show strong association with ADHD: attention regulation and response inhibition, captured by reaction time variability (RTV) and commission errors (CE).
The discovery GWAS included 19 099 ADHD cases and 34 194 control participants. The combined target sample included 845 people with ADHD (age: 8–40 years). RTV and CE were available from reaction time and response inhibition tasks. ADHD PRS were calculated from the GWAS using a leave-one-study-out approach. Regression analyses were run to investigate whether ADHD PRS were associated with CE and RTV. Results across sites were combined via random effect meta-analyses.
When combining the studies in meta-analyses, results were significant for RTV (R2 = 0.011, β = 0.088, p = 0.02) but not for CE (R2 = 0.011, β = 0.013, p = 0.732). No significant association was found between ADHD PRS and RTV or CE in any sample individually (p > 0.10).
We detected a significant association between PRS for ADHD and RTV (but not CE) in individuals with ADHD, suggesting that common genetic risk variants for ADHD influence attention regulation.
The novel SARS-CoV-2 virus was first reported in Wuhan, China in December 2019 and is notable for being highly contagious and potentially lethal and is mainly spread by droplet transmission. The US healthcare system’s response to the COVID-19 pandemic has been challenged by a shortage of personal protective equipment (PPE), especially N95 respirators. Restricted use, re-use, and sanitation of PPE have been widely adopted to provide protection for frontline healthcare workers caring for often critically ill and highly contagious patients. This objective of this manuscript is to describe our validated process for N95 respirator sanitation.
Process development, validation, and implementation
Level-I urban academic medical center
A multidisciplinary team developed a novel evidence-based process for N95 respirator re-processing and sanitation using ultraviolet (UV) light. Dose measurement, structural integrity, moisture content, particle filtration, fit testing, and environmental testing were performed for both quality control and validation of the process.
The process achieved UV light dosing for sanitation while maintaining the functional and structural integrity of the N95 respirators, with a daily potential throughput capacity of ˜12,000 masks. This process has supported our health system to provide respiratory PPE to all frontline team members.
This novel method of N95 respirator sanitation can safely enable re-use of the N95 respirator essential for healthcare workers caring for patients with COVID-19. Our high-throughput process can extend local supplies of this critical PPE until the national supply is replenished.
The long-term inflammatory impact of diet could potentially elevate the risk of periodontal disease through modification of systemic inflammation. The aim of the present study was to prospectively investigate the associations between a food based, reduced rank regression (RRR) derived, empirical dietary inflammatory pattern (EDIP) and incidence of periodontitis. The study population was composed of 34,940 men from the Health Professionals Follow-Up Study, who were free of periodontal disease and major illnesses at baseline (1986). Participants provided medical and dental history through mailed questionnaires every 2 years, and dietary data through validated semi-quantitative food frequency questionnaires every 4 years. We used Cox proportional hazard models to examine the associations between EDIP scores and validated self-reported incidence of periodontal disease over a 24-year follow-up period. No overall association between EDIP and the risk of periodontitis was observed; the hazard ratio comparing the highest EDIP quintile (most proinflammatory diet) to the lowest quintile was 0.99 (95% confidence interval: 0.89 -1.10, p-value for trend = 0.97). A secondary analysis showed that among obese non-smokers (i.e. never and former smokers at baseline), the hazard ratio for periodontitis comparing the highest EDIP quintile to the lowest was 1.39 (95% confidence interval: 0.98 -1.96, p-value for trend = 0.03). In conclusion, no overall association was detected between EDIP and incidence of self-reported periodontitis in the study population. From the subgroups evaluated EDIP was significantly associated with increased risk of periodontitis only among nonsmokers who were obese. Hence, this association must be interpreted with caution.
In most of the world Toxoplasma gondii is comprised of archetypal types (types I, II and III); however, South America displays several non-archetypal strains. This study used an experimental mouse model to characterize the immune response and parasite kinetics following infection with different parasite genotypes. An oral inoculation of 50 oocysts per mouse from T. gondii M4 type II (archetypal, avirulent), BrI or BrIII (non-archetypal, virulent and intermediate virulent, respectively) for groups (G)2, G3 and G4, respectively was used. The levels of mRNA expression of cytokines, immune compounds, cell surface markers and receptor adapters [interferon gamma (IFNγ), interleukin (IL)-12, CD8, CD4, CD25, CXCR3 and MyD88] were quantified by SYBR green reverse transcription-quantitative polymerase chain reaction. Lesions were characterized by histology and detection by immunohistochemistry established distribution of parasites. Infection in G2 mice was mild and characterized by an early MyD88-dependent pathway. In G3, there were high levels of expression of pro-inflammatory cytokines IFNγ and IL-12 in the mice showing severe clinical symptoms at 8–11 days post infection (dpi), combined with the upregulation of CD25, abundant tachyzoites and tissue lesions in livers, lungs and intestines. Significant longer expression of IFNγ and IL-12 genes, with other Th1-balanced immune responses, such as increased levels of CXCR3 and MyD88 in G4, resulted in survival of mice and chronic toxoplasmosis, with the occurrence of tissue cysts in brain and lungs, at 14 and 21 dpi. Different immune responses and kinetics of gene expression appear to be elicited by the different strains and non-archetypal parasites demonstrated higher virulence.
Two phases of archaeological investigation were performed in the Novi Sad City Museum at Petrovaradin Fortress. In this study, we summarize the results of geo-archaeological investigations of the second period of excavation inside the Novi Sad City Museum building. The fortress is situated on a Danube terrace with the top of the bedrock at ca.123 m asl. The investigated section consists of undisturbed fine-sandy silt. The grain-size distribution of the sediments indicates clearly its alluvial reworking but shows also a general similarity with typical primary loess in the region. All analyzed proxies indicate slightly stronger weathering in the upper part of the profile. Luminescence ages suggest that the investigated sequence covers the last glacial period and the terrace presumably formed during MIS 4. Subsequently, the Danube started its incision at the start of the next warmer period (MIS 3) onward. This terrace age and elevation enable us to derive an uplift rate of the terrace of ca. 0.73 mm/a for the last 60 ka, which seems to increase towards the present. Basal loessic material, in which artifacts occur, likely in the reworked position, indicate that the area close to today's Petrovaradin Fortress was already inhabited in MIS 5.
Predictors of new-onset bipolar disorder (BD) or psychotic disorder (PD) have been proposed on the basis of retrospective or prospective studies of ‘at-risk’ cohorts. Few studies have compared concurrently or longitudinally factors associated with the onset of BD or PDs in youth presenting to early intervention services. We aimed to identify clinical predictors of the onset of full-threshold (FT) BD or PD in this population.
Multi-state Markov modelling was used to assess the relationships between baseline characteristics and the likelihood of the onset of FT BD or PD in youth (aged 12–30) presenting to mental health services.
Of 2330 individuals assessed longitudinally, 4.3% (n = 100) met criteria for new-onset FT BD and 2.2% (n = 51) met criteria for a new-onset FT PD. The emergence of FT BD was associated with older age, lower social and occupational functioning, mania-like experiences (MLE), suicide attempts, reduced incidence of physical illness, childhood-onset depression, and childhood-onset anxiety. The emergence of a PD was associated with older age, male sex, psychosis-like experiences (PLE), suicide attempts, stimulant use, and childhood-onset depression.
Identifying risk factors for the onset of either BD or PDs in young people presenting to early intervention services is assisted not only by the increased focus on MLE and PLE, but also by recognising the predictive significance of poorer social function, childhood-onset anxiety and mood disorders, and suicide attempts prior to the time of entry to services. Secondary prevention may be enhanced by greater attention to those risk factors that are modifiable or shared by both illness trajectories.
Since the beginning of 2020, the COVID-19 pandemic has dramatically influenced almost every aspect of human life. Activities requiring human gatherings have either been postponed, cancelled, or held completely virtually. To supplement lack of in-person contact, people have increasingly turned to virtual settings on-line, advantages of which include increased inclusivity and accessibility and reduction of carbon footprint. However, emerging online technologies cannot fully replace, in-person scientific events. In-person meetings are not susceptible to poor internet connectivity problems, and they provide novel opportunities for socialization, creating new collaborations, and sharing ideas. To continue such activities, a hybrid model for scientific events could be a solution offering both in-person and virtual components. While participants can freely choose the mode of their participation, virtual meetings would most benefit those who cannot attend in-person due to the limitations. In-person portions of meetings should be organized with full consideration of prevention and safety strategies including risk assessment and mitigation, venue and environmental sanitation, participant protection and disease prevention, and promoting the hybrid model. This new way of interaction between scholars can be considered as a part of a resilience system which was neglected previously and should become a part of routine practice in scientific community.
Antarctica's ice shelves modulate the grounded ice flow, and weakening of ice shelves due to climate forcing will decrease their ‘buttressing’ effect, causing a response in the grounded ice. While the processes governing ice-shelf weakening are complex, uncertainties in the response of the grounded ice sheet are also difficult to assess. The Antarctic BUttressing Model Intercomparison Project (ABUMIP) compares ice-sheet model responses to decrease in buttressing by investigating the ‘end-member’ scenario of total and sustained loss of ice shelves. Although unrealistic, this scenario enables gauging the sensitivity of an ensemble of 15 ice-sheet models to a total loss of buttressing, hence exhibiting the full potential of marine ice-sheet instability. All models predict that this scenario leads to multi-metre (1–12 m) sea-level rise over 500 years from present day. West Antarctic ice sheet collapse alone leads to a 1.91–5.08 m sea-level rise due to the marine ice-sheet instability. Mass loss rates are a strong function of the sliding/friction law, with plastic laws cause a further destabilization of the Aurora and Wilkes Subglacial Basins, East Antarctica. Improvements to marine ice-sheet models have greatly reduced variability between modelled ice-sheet responses to extreme ice-shelf loss, e.g. compared to the SeaRISE assessments.
Little is known about how the Royal College of Emergency Medicine (RCEM) residency programs are selecting their residents. This creates uncertainty regarding alignment between current selection processes and known best practices. We seek to describe the current selection processes of Canadian RCEM programs.
An online survey was distributed to all RCEM program directors and assistant directors. The survey instrument included 22 questions and sought both qualitative and quantitative data from the following six domains: application file, letters of reference, elective selection, interview, rank order, and selection process evaluation.
We received responses from 13 of 14 programs for an aggregate response rate of 92.9%. A candidate's letters of reference were identified as the most important criterion from the paper application (38.5%). Having a high level of familiarity with the applicant was the most important characteristic of a reference letter author (46.2%). In determining rank order, 53.8% of programs weighed the interview more heavily than the paper application. Once final candidate scores are established following the interview stage, all program respondents indicated that further adjustment is made to the final rank order list. Only 1 of 13 program respondents reported ever having completed a formal evaluation of their selection process.
We have identified elements of the selection process that will inform recommendations for programs, students, and referees. We encourage programs to conduct regular reviews of their selection process going forward to be in alignment with best practices.
Brain imaging studies have shown altered amygdala activity during emotion processing in children and adolescents with oppositional defiant disorder (ODD) and conduct disorder (CD) compared to typically developing children and adolescents (TD). Here we aimed to assess whether aggression-related subtypes (reactive and proactive aggression) and callous-unemotional (CU) traits predicted variation in amygdala activity and skin conductance (SC) response during emotion processing.
We included 177 participants (n = 108 cases with disruptive behaviour and/or ODD/CD and n = 69 TD), aged 8–18 years, across nine sites in Europe, as part of the EU Aggressotype and MATRICS projects. All participants performed an emotional face-matching functional magnetic resonance imaging task.
Differences between cases and TD in affective processing, as well as specificity of activation patterns for aggression subtypes and CU traits, were assessed. Simultaneous SC recordings were acquired in a subsample (n = 63). Cases compared to TDs showed higher amygdala activity in response to negative faces (fearful and angry) v. shapes. Subtyping cases according to aggression-related subtypes did not significantly influence on amygdala activity; while stratification based on CU traits was more sensitive and revealed decreased amygdala activity in the high CU group. SC responses were significantly lower in cases and negatively correlated with CU traits, reactive and proactive aggression.
Our results showed differences in amygdala activity and SC responses to emotional faces between cases with ODD/CD and TD, while CU traits moderate both central (amygdala) and peripheral (SC) responses. Our insights regarding subtypes and trait-specific aggression could be used for improved diagnostics and personalized treatment.
This chapter analyzes the fragmentation of architectures of earth system governance. We start with a conceptualization of governance fragmentation and its relation to concepts such as polycentricity and institutional complexity. We then review the origins of governance fragmentation and its problematization, methodological approaches to studying fragmentation and the impacts and consequences of fragmentation. We conclude by identifying future research directions in this domain. Our research shows that fragmentation is ubiquitous, that it varies among policy areas and governance areas and that it is a variable that can be assessed in comparative research across policy areas and over time. The review is based on a comprehensive study of the literature on governance fragmentation over the last decade. We draw on a Scopus search on all articles published in the subject area of social sciences from 2009 to 2018, supplemented by additional studies, such as books, book chapters and a few policy briefs and working papers.
Hierarchization is a deliberate process to create a vertically nested governance architecture where actors and institutions in a lower rank are bound or otherwise compelled to obey, respond to or contribute to higher-order norms and objectives. Drawing on this definition, we review recent research on hierarchization in earth system governance and the political and legal processes that establish, maintain and legitimize it. Here we present three mutually non-exclusive forms of hierarchization – systematization, centralization and prioritization. Each involves different actors and rationales, mechanisms and strategies, while achieving different purposes with varying governance outcomes. We illustrate our argument with empirical examples including the proposed Global Pact for the Environment, the proposal to establish a world environment organization and the Sustainable Development Goals. We conclude with an assessment of the benefits and drawbacks of hierarchization as an approach to some of the challenges inherent in earth system governance, and offer suggestions for future research.
Governance through goals, a relatively new global governance mechanism, has recently gained prominence, particularly since the adoption of the Sustainable Development Goals. Through this mechanism, internationally agreed policy goals orchestrate the activities of governmental and non-governmental actors. This chapter argues that governance through goals has important effects on governance architectures and their degree and type of fragmentation. To analyze these effects, we review literature around four characteristics of governance through goals: their non-legally binding nature, weak global institutional arrangements, inclusive goal-setting processes and national leeway. We argue that alternative forms of bindingness, such as reporting and accountability mechanisms, can steer actors toward a shared vision. This may result in synergistic fragmentation if broad support is obtained through inclusive processes. However, tensions and cherry-picking may arise when goals are prioritized and implemented. Further research on the effects of governance through goals is crucial given that it is likely to maintain – and gain – importance in earth system governance.
Increased fruit and vegetable (FV) intake is associated with reduced blood pressure (BP). However, it is not clear whether the effect of FV on BP depends on the type of FV consumed. Furthermore, there is limited research regarding the comparative effect of juices or whole FV on BP. Baseline data from a prospective cohort study of 10 660 men aged 50–59 years examined not only the cross-sectional association between total FV intake but also specific types of FV and BP in France and Northern Ireland. BP was measured, and dietary intake assessed using FFQ. After adjusting for confounders, both systolic BP (SBP) and diastolic BP (DBP) were significantly inversely associated with total fruit, vegetable and fruit juice intake; however, when examined according to fruit or vegetable sub-type (citrus fruit, other fruit, fruit juices, cooked vegetables and raw vegetables), only the other fruit and raw vegetable categories were consistently associated with reduced SBP and DBP. In relation to the risk of hypertension based on SBP >140 mmHg, the OR for total fruit, vegetable and fruit juice intake (per fourth) was 0·95 (95 % CI 0·91, 1·00), with the same estimates being 0·98 (95 % CI 0·94, 1·02) for citrus fruit (per fourth), 1·02 (95 % CI 0·98, 1·06) for fruit juice (per fourth), 0·93 (95 % CI 0·89, 0·98) for other fruit (per fourth), 1·05 (95 % CI 0·99, 1·10) for cooked vegetable (per fourth) and 0·86 (95 % CI 0·80, 0·91) for raw vegetable intakes (per fourth). Similar results were obtained for DBP. In conclusion, a high overall intake of fruit, vegetables and fruit juice was inversely associated with SBP, DBP and risk of hypertension, but this differed by FV sub-type, suggesting that the strength of the association between FV sub-types and BP might be related to the type consumed, or to processing or cooking-related factors.
Introduction: Workplace based assessments (WBAs) are integral to emergency medicine residency training. However many biases undermine their validity, such as an assessor's personal inclination to rate learners leniently or stringently. Outlier assessors produce assessment data that may not reflect the learner's performance. Our emergency department introduced a new Daily Encounter Card (DEC) using entrustability scales in June 2018. Entrustability scales reflect the degree of supervision required for a given task, and are shown to improve assessment reliability and discrimination. It is unclear what effect they will have on assessor stringency/leniency – we hypothesize that they will reduce the number of outlier assessors. We propose a novel, simple method to identify outlying assessors in the setting of WBAs. We also examine the effect of transitioning from a norm-based assessment to an entrustability scale on the population of outlier assessors. Methods: This was a prospective pre-/post-implementation study, including all DECs completed between July 2017 and June 2019 at The Ottawa Hospital Emergency Department. For each phase, we identified outlier assessors as follows: 1. An assessor is a potential outlier if the mean of the scores they awarded was more than two standard deviations away from the mean score of all completed assessments. 2. For each assessor identified in step 1, their learners’ assessment scores were compared to the overall mean of all learners. This ensures that the assessor was not simply awarding outlying scores due to working with outlier learners. Results: 3927 and 3860 assessments were completed by 99 and 116 assessors in the pre- and post-implementation phases respectively. We identified 9 vs 5 outlier assessors (p = 0.16) in the pre- and post-implementation phases. Of these, 6 vs 0 (p = 0.01) were stringent, while 3 vs 5 (p = 0.67) were lenient. One assessor was identified as an outlier (lenient) in both phases. Conclusion: Our proposed method successfully identified outlier assessors, and could be used to identify assessors who might benefit from targeted coaching and feedback on their assessments. The transition to an entrustability scale resulted in a non-significant trend towards fewer outlier assessors. Further work is needed to identify ways to mitigate the effects of rater cognitive biases.