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We evaluated the added value of infection control-guided, on demand, and locally performed severe acute respiratory coronavirus virus 2 (SARS-CoV-2) genomic sequencing to support outbreak investigation and control in acute-care settings.
Design and setting:
This 18-month prospective molecular epidemiology study was conducted at a tertiary-care hospital in Montreal, Canada. When nosocomial transmission was suspected by local infection control, viral genomic sequencing was performed locally for all putative outbreak cases. Molecular and conventional epidemiology data were correlated on a just-in-time basis to improve understanding of coronavirus disease 2019 (COVID-19) transmission and reinforce or adapt control measures.
Results:
Between April 2020 and October 2021, 6 outbreaks including 59 nosocomial infections (per the epidemiological definition) were investigated. Genomic data supported 7 distinct transmission clusters involving 6 patients and 26 healthcare workers. We identified multiple distinct modes of transmission, which led to reinforcement and adaptation of infection control measures. Molecular epidemiology data also refuted (n = 14) suspected transmission events in favor of community acquired but institutionally clustered cases.
Conclusion:
SARS-CoV-2 genomic sequencing can refute or strengthen transmission hypotheses from conventional nosocomial epidemiological investigations, and guide implementation of setting-specific control strategies. Our study represents a template for prospective, on site, outbreak-focused SARS-CoV-2 sequencing. This approach may become increasingly relevant in a COVID-19 endemic state where systematic sequencing within centralized surveillance programs is not available.
Current psychiatric diagnoses, although heritable, have not been clearly mapped onto distinct underlying pathogenic processes. The same symptoms often occur in multiple disorders, and a substantial proportion of both genetic and environmental risk factors are shared across disorders. However, the relationship between shared symptoms and shared genetic liability is still poorly understood.
Aims
Well-characterised, cross-disorder samples are needed to investigate this matter, but few currently exist. Our aim is to develop procedures to purposely curate and aggregate genotypic and phenotypic data in psychiatric research.
Method
As part of the Cardiff MRC Mental Health Data Pathfinder initiative, we have curated and harmonised phenotypic and genetic information from 15 studies to create a new data repository, DRAGON-Data. To date, DRAGON-Data includes over 45 000 individuals: adults and children with neurodevelopmental or psychiatric diagnoses, affected probands within collected families and individuals who carry a known neurodevelopmental risk copy number variant.
Results
We have processed the available phenotype information to derive core variables that can be reliably analysed across groups. In addition, all data-sets with genotype information have undergone rigorous quality control, imputation, copy number variant calling and polygenic score generation.
Conclusions
DRAGON-Data combines genetic and non-genetic information, and is available as a resource for research across traditional psychiatric diagnostic categories. Algorithms and pipelines used for data harmonisation are currently publicly available for the scientific community, and an appropriate data-sharing protocol will be developed as part of ongoing projects (DATAMIND) in partnership with Health Data Research UK.
The herbicides that inhibit 4-hydroxyphenylpyruvate dioxygenase (HPPD) are primarily used for weed control in corn, barley, oat, rice, sorghum, sugarcane, and wheat production fields in the United States. The objectives of this review were to summarize 1) the history of HPPD-inhibitor herbicides and their use in the United States; 2) HPPD-inhibitor resistant weeds, their mechanism of resistance, and management; 3) interaction of HPPD-inhibitor herbicides with other herbicides; and 4) the future of HPPD-inhibitor-resistant crops. As of 2022, three broadleaf weeds (Palmer amaranth, waterhemp, and wild radish) have evolved resistance to the HPPD inhibitor. The predominance of metabolic resistance to HPPD inhibitor was found in aforementioned three weed species. Management of HPPD-inhibitor-resistant weeds can be accomplished using alternate herbicides such as glyphosate, glufosinate, 2,4-D, or dicamba; however, metabolic resistance poses a serious challenge, because the weeds may be cross-resistant to other herbicide sites of action, leading to limited herbicide options. An HPPD-inhibitor herbicide is commonly applied with a photosystem II (PS II) inhibitor to increase efficacy and weed control spectrum. The synergism with an HPPD inhibitor arises from depletion of plastoquinones, which allows increased binding of a PS II inhibitor to the D1 protein. New HPPD inhibitors from the azole carboxamides class are in development and expected to be available in the near future. HPPD-inhibitor-resistant crops have been developed through overexpression of a resistant bacterial HPPD enzyme in plants and the overexpression of transgenes for HPPD and a microbial gene that enhances the production of the HPPD substrate. Isoxaflutole-resistant soybean is commercially available, and it is expected that soybean resistant to other HPPD inhibitor herbicides such as mesotrione, stacked with resistance to other herbicides, will be available in the near future.
In Québec, Canada, we evaluated the risk of severe acute respiratory coronavirus virus 2 (SARS-CoV-2) infection associated with (1) the demographic and employment characteristics among healthcare workers (HCWs) and (2) the workplace and household exposures and the infection prevention and control (IPC) measures among patient-facing HCWs.
Design:
Test-negative case-control study.
Setting:
Provincial health system.
Participants:
HCWs with PCR-confirmed coronavirus disease 2019 (COVID-19) diagnosed between November 15, 2020, and May 29, 2021 (ie, cases), were compared to HCWs with compatible symptoms who tested negative during the same period (ie, controls).
Methods:
Adjusted odds ratios (aORs) of infection were estimated using regression logistic models evaluating demographic and employment characteristics (all 4,919 cases and 4,803 controls) or household and workplace exposures and IPC measures (2,046 patient-facing cases and 1,362 controls).
Results:
COVID-19 risk was associated with working as housekeeping staff (aOR, 3.6), as a patient-support assistant (aOR, 1.9), and as nursing staff (aOR, 1.4), compared to administrative staff. Other risk factors included being unexperienced (aOR, 1.5) and working in private seniors’ homes (aOR, 2.1) or long-term care facilities (aOR, 1.5), compared to acute-care hospitals. Among patient-facing HCWs, exposure to a household contact was reported by 9% of cases and was associated with the highest risk of infection (aOR, 7.8). Most infections were likely attributable to more frequent exposure to infected patients (aOR, 2.7) and coworkers (aOR, 2.2). Wearing an N95 respirator during contacts with COVID-19 patients (aOR, 0.7) and vaccination (aOR, 0.2) were the measures associated with risk reduction.
Conclusion:
In the context of the everchanging SARS-CoV-2 virus with increasing transmissibility, measures to ensure HCW protection, including vaccination and respiratory protection, and patient safety will require ongoing evaluation.
We examine diseconomies of scale for two different investment approaches: quantitative and fundamental. Using separate account (SA) data where the investment approach is self-identified, we find that fundamental SAs exhibit greater diseconomies of scale than quantitative SAs. Looking at liquidity costs, we find that quantitative SAs hold more diversified portfolios of higher liquidity stocks than fundamental SAs, thereby reducing their expected liquidity costs. We also find that consistent with lower information processing/hierarchy costs, the speed of information diffusion is higher for quant SAs. Accounting for these differences helps to explain the differences in diseconomies of scale.
Subthreshold/attenuated syndromes are established precursors of full-threshold mood and psychotic disorders. Less is known about the individual symptoms that may precede the development of subthreshold syndromes and associated social/functional outcomes among emerging adults.
Methods
We modeled two dynamic Bayesian networks (DBN) to investigate associations among self-rated phenomenology and personal/lifestyle factors (role impairment, low social support, and alcohol and substance use) across the 19Up and 25Up waves of the Brisbane Longitudinal Twin Study. We examined whether symptoms and personal/lifestyle factors at 19Up were associated with (a) themselves or different items at 25Up, and (b) onset of a depression-like, hypo-manic-like, or psychotic-like subthreshold syndrome (STS) at 25Up.
Results
The first DBN identified 11 items that when endorsed at 19Up were more likely to be reendorsed at 25Up (e.g., hypersomnia, impaired concentration, impaired sleep quality) and seven items that when endorsed at 19Up were associated with different items being endorsed at 25Up (e.g., earlier fatigue and later role impairment; earlier anergia and later somatic pain). In the second DBN, no arcs met our a priori threshold for inclusion. In an exploratory model with no threshold, >20 items at 19Up were associated with progression to an STS at 25Up (with lower statistical confidence); the top five arcs were: feeling threatened by others and a later psychotic-like STS; increased activity and a later hypo-manic-like STS; and anergia, impaired sleep quality, and/or hypersomnia and a later depression-like STS.
Conclusions
These probabilistic models identify symptoms and personal/lifestyle factors that might prove useful targets for indicated preventative strategies.
Background: RSV is underrecognized in hospitalized adults. A better understanding of RSV in this population could help prioritize targeted viral-testing resources. Hospitalization and in-hospital outcomes are widely accepted as markers of clinical severity with respect to acute respiratory illness (ARI). We compared characteristics and clinical outcomes between adults hospitalized with ARI from October 2016 through May 2019. Methods: All hospitalized adults (≥ 18 years) who met a standardized case definition of ARI were prospectively enrolled across 3 respiratory seasons from 9 hospitals participating in the US Hospitalized Adult Influenza Vaccine Effectiveness Network (HAIVEN). Demographic data were collected during enrollment interviews, and electronic medical records (EMRs) were reviewed to extract comorbidity data. Throat and nasal swabs collected at enrollment were tested for ARI pathogens using real-time PCR assays at respective HAIVEN research laboratory sites. Characteristics and clinical outcomes of participants were compared using χ2 or nonparametric tests where appropriate. Multivariable logistic regression models were used to test associations between infection status, characteristics, and clinical outcomes, adjusting for age, sex, race, Charlson comorbidity index (CCI), body mass index (BMI), site, season, and days to admission. Results: In total, 10,311 adults were included, 22.3% (n = 2,300) were aged 18–49 years, 33.2% (n = 3,423) were aged 50–64 years, and 44.5% (n = 4,588) were aged ≥65 years. Moreover, 6% of adults tested positive for RSV (n = 622), 18.8% positive for influenza (n = 1,940), and 75.1% negative for both (n = 7,749). Obesity and age ≥65 years were significantly associated with RSV detection when compared with participants negative for both RSV and influenza. Patients aged 18–49 years and ≥65 years with RSV had significantly higher median CCI scores compared to patients with influenza (Fig. 1.). The proportion of adults with CHF or COPD was significantly (p-value Conclusions: Severe RSV illness may differ from severe influenza illness, and those infected with RSV may have different characteristics than those infected with influenza. Hospitalized adults with RSV infection were more likely to have underlying cardiopulmonary comorbidities and higher CCI scores as well as experience an extended length of hospital stay and need for mechanical ventilation. These data highlight the importance of retaining testing for RSV in older adults hospitalized with ARI.
The remarkable archaeological record of Neolithic Orkney has ensured that these islands play a prominent role in narratives of European late prehistory, yet knowledge of the subsequent Bronze Age is comparatively poor. The Bronze Age settlement and cemetery at the Links of Noltland, on the island of Westray, offers new evidence, including aDNA, that points to a substantial population replacement between the Late Neolithic and Bronze Age. Focusing on funerary practice, the authors argue for interconnecting identities centred on household and community, patrilocality and inheritance. The findings prompt a reconsideration of the Orcadian Bronze Age, with wider implications for population movement and the uptake of cultural innovations more widely across prehistoric north-western Europe.
We report on the mobility and orientation of finite-size, neutrally buoyant, prolate ellipsoids (of aspect ratio $\varLambda =4$) in Taylor–Couette flow, using interface-resolved numerical simulations. The set-up consists of a particle-laden flow between a rotating inner and a stationary outer cylinder. The flow regimes explored are the well-known Taylor vortex, wavy vortex and turbulent Taylor vortex flow regimes. We simulate two particle sizes $\ell /d=0.1$ and $\ell /d=0.2$, $\ell$ denoting the particle major axis and $d$ the gap width between the cylinders. The volume fractions are $0.01\,\%$ and $0.07\,\%$, respectively. The particles, which are initially randomly positioned, ultimately display characteristic spatial distributions which can be categorised into four modes. Modes (i) to (iii) are observed in the Taylor vortex flow regime, while mode (iv) encompasses both the wavy vortex and turbulent Taylor vortex flow regimes. Mode (i) corresponds to stable orbits away from the vortex cores. Remarkably, in a narrow $\textit {Ta}$ range, particles get trapped in the Taylor vortex cores (mode (ii)). Mode (iii) is the transition when both modes (i) and (ii) are observed. For mode (iv), particles distribute throughout the domain due to flow instabilities. All four modes show characteristic orientational statistics. The focus of the present study is on mode (ii). We find the particle clustering for this mode to be size-dependent, with two main observations. Firstly, particle agglomeration at the core is much higher for $\ell /d=0.2$ compared with $\ell /d=0.1$. Secondly, the $\textit {Ta}$ range for which clustering is observed depends on the particle size. For this mode (ii) we observe particles to align strongly with the local cylinder tangent. The most pronounced particle alignment is observed for $\ell /d=0.2$ at around $\textit {Ta}=4.2\times 10^5$. This observation is found to closely correspond to a minimum of axial vorticity at the Taylor vortex core ($\textit {Ta}=6\times 10^5$) and we explain why.
Little is known about the raising number of specialized units for patients with dementia and very severe challenging behavior in the Netherlands. This study describes organizational and treatment characteristics of a sample of these units.
Methods:
The organizational and treatment characteristics were studied with digital questionnaires completed by the unit managers, interviews with the main physician(s) and observation of the physical environment. The questionnaire consisted of questions about general patient characteristics, unit characteristics and staff characteristics. Furthermore, an interview was held with the main/treating physician often together with another physician or psychologist. The interview guide consisted of questions about admission criteria, the role of staff involved and the treatment process.
Results:
Thirteen units participated. Five units were part of a mental health (MH) institution, seven units were part of a nursing home (NH) organization and one unit was a cooperation of MH and NH. Unit sizes ranged from 10 to 28 places. Ten of thirteen units started in 2010 or later. The age of patients admitted was estimated at 75 years. The percentage of involuntary admitted patients was 53% at MH-units and 18% at NH-units. Unit managers mentioned that due to a difference in reimbursement between MH and NH units had difficulty providing the specialized care. Another problem managers faced was recruiting nursing staff. Units strived for expertise in general staffing from both MH and NH. The education level of the nursing staff was comparable between MH and NH. At every unit a physician with background in elderly care medicine or geriatrics and a psychiatrist was involved. Interviewees stressed the role of the nursing staff in the treatment. They were key in providing the care and treatment that, since the main goal of interventions is treatment of and coping with challenging behavior.
Conclusion:
The main finding of this study is that units caring for patients with dementia and challenging behavior, despite barriers in regulations and staffing shortage, search for combining expertise from nursing home care and psychiatry in their treatment.
Seeman, Morris, and Summers misrepresent or misunderstand the arguments we have made, as well as their own previous work. Here, we correct these inaccuracies. We also reiterate our support for hypothesis-driven and evidence-based research.
Cardiac surgery for CHD was pioneered in Washington, DC by Charles Hufnagel and Edgar Davis working at Georgetown University and Children’s Hospital of the District of Columbia. Children’s Hospital, now Children’s National Hospital, had been established just 5 years after the end of the Civil War. In the 1950s, Davis and Hufnagel undertook many open-heart operations using the technique of surface cooling, hypothermia, and circulatory arrest. Hufnagel and Lewis Scott, who founded the cardiology department at Children’s, were trained in Boston by Gross and Nadas. Judson Randolph, also a trainee of Gross, introduced cardiac surgery using cardiopulmonary bypass and established the General Pediatric Surgery department at Children’s in the 1960s. The transition of hospital staffing from community-based private physicians to full-time hospital employees was often controversial but was complete by the turn of the millennium. The 21st century has seen continuing growth of the new Children’s National Heart Institute and consolidation of several congenital cardiac programmes in Washington, DC.
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.
The concept of Design for Additive Manufacturing (DfAM) is gaining popularity along with AM, despite its scopes are not well established. In particular, in the last few years, DfAM methods have been intuitively subdivided into opportunistic and restrictive. This distinction is gaining traction despite a lack of formalization. In this context, the paper investigates experts' understanding of DfAM. In particular, the authors have targeted educators, as the perception of DfAM scopes in the future will likely depend on teachers' view. A bespoke survey has been launched, which has been answer by 100 worldwide-distributed respondents. The gathered data has undergone several analyses, markedly answers to open questions asking for individual definitions of DfAM, and evaluations of the pertinence of meanings and acceptations from the literature. The results show that the main DfAM aspects focused on by first standardization attempts have been targeted, especially products, processes, opportunities and constraints. Beyond opportunistic and restrictive nuances, DfAM different understandings are characterized by different extents of cognitive endeavor, convergence vs. divergence in the design process, theoretical vs. hands on approaches.
While childhood externalizing, internalizing and comorbid problems have been associated with suicidal risk, little is known about their specific associations with suicidal ideation and attempts. We examined associations between childhood externalizing, internalizing and comorbid problems and suicidal ideation (without attempts) and attempts by early adulthood, in males and females.
Method
Participants were from the Quebec Longitudinal Study of Kindergarten Children, a population-based study of kindergarteners in Quebec from 1986 to 1988 and followed-up until 2005. We captured the co-development of teacher-rated externalizing and internalizing problems at age 6–12 using multitrajectories. Using the Diagnostic Interview Schedule administered at age 15 and 22, we identified individuals (1) who never experienced suicidal ideation/attempts, (2) experienced suicidal ideation but never attempted suicide and (3) attempted suicide.
Results
The identified profiles were no/low problems (45%), externalizing (29%), internalizing (11%) and comorbid problems (13%). After adjusting for socioeconomic and familial characteristics, children with externalizing (OR 2.00, CI 1.39–2.88), internalizing (OR 2.34, CI 1.51–3.64) and comorbid (OR 3.29, CI 2.05–5.29) problems were at higher risk of attempting suicide (v. non-suicidal) by age 22 than those with low/no problems. Females with comorbid problems were at higher risk of attempting suicide than females with one problem. Childhood problems were not associated with suicidal ideation. Externalizing (OR 2.01, CI 1.29–3.12) and comorbid problems (OR 2.28, CI 1.29–4.03) distinguished individuals who attempted suicide from those who thought about suicide without attempting.
Conclusion
Childhood externalizing problems alone or combined with internalizing problems were associated with suicide attempts, but not ideation (without attempts), suggesting that these problems confer a specific risk for suicide attempts.
Procedure induced anxiety affects the majority of children undergoing medical intervention and has been directly linked to behaviour disturbances, psychological trauma, phobias and symptoms of PTSD. Despite this, there is currently no formal training relating to the management of procedure induced anxiety for medical personnel caring for children. A distillation of more than eighty years of research, this textbook examines the nature, prevalence and consequences of anxiety in children, alongside evidence-based strategies for its effective management. Designed as a training manual, it includes a comprehensive account of positive and negative aspects of behaviour that contribute to the successful management of anxious children. Chapters cover topics such as non-verbal and verbal communication, enhanced communication management strategies, support of children with autistic spectrum disorder, ADHD, learning difficulties, the use of premedication and the role that families play. Essential reading for anaesthetists and paediatricians and a valuable resource for any practitioner working with children.
Optimum care for anxious children mandates deployment of anxiety management strategies in advance of planned interventions. For this to be achieved, we must detect children who are more likely to experience anxiety by utilising an effective screening system. The advent of pre-assessment grants the perfect opportunity to implement such a system with a view to offering specialist psychological support and intervention to those who need it.