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Toxoplasma gondii non-archetypal strains have distinct virulence profiles and immunological activation in the host when compared with archetypal strains. The present work aims to perform an analysis of the inflammatory profile during acute and early chronic infection by T. gondii atypical strain in an experimental murine model. After euthanasia, blood was collected for the quantification of specific IgG antibodies and their subtypes (IgG1/IgG3) by ELISA; bronchoalveolar lavage (BAL) was realized and immunophenotyping of lymphocytes population was performed at 12- and 30-days post infection (dpi); the levels of IFN-γ, IL-12, IL-10, TNF-α, IL-6, IL-17, nitric oxide and total proteins were determined in the BAL supernatant. Tissue cyst burden was determined in the brain homogenate, and the parasite load in the lungs was assessed by quantitative reverse transcription polymerase chain reaction (qRT-PCR). Infection with the CK4 strain induced a lower brain cyst load similar parasite burden in the lungs, and higher levels of IgG1 and IgG3, when compared to ME49. The group infected with the CK4 strain presented higher levels of systemic IFN-γ, and both infected groups displayed similarly elevated levels of systemic TNF-α, IL-6 and IL-17 at 30 dpi, as well as higher numbers of CD4+ and CD8+ T lymphocytes in the acute stage of infection, followed by higher numbers of central and effector CD4+ T cells. IFN-γ levels in the BAL fluid were significantly higher in animals infected with the CK4 strain in both the acute and early chronic stage of infection, highlighting the involvement of the lung environment.
Urinary tract infections (UTI) are common and women with typical symptoms may be treated empirically without culture. We evaluated the utility of urine culture in men presenting with typical symptoms of uncomplicated UTI. Most pathogens isolated retained susceptibility to first-line antimicrobials suggesting urine cultures may be unnecessary in this population.
Ambulatory antibiotic stewardship has traditionally focused on acute respiratory infections with few studies evaluating metrics for other commonly encountered ambulatory conditions, including urinary tract infections (UTI). We describe the development and validation of an electronically captured appropriate antibiotic use metric for ambulatory UTIs using coding data.
Conventional understanding and research regarding prognostic understanding too often focuses on transmission of information. However, merely overcoming barriers to patient understanding may not be sufficient. In this article the authors provide a more nuanced understanding of prognostic awareness, using oncological care as an overarching example, and discuss factors that may lead to prognostic discordance between physicians and patients. We summarize the current literature and research and present a model developed by the authors to characterize barriers to prognostic awareness. Ultimately, multiple influences on prognostic understanding may impede acceptance by patients even when adequate transfer of information takes place. Physicians should improve how they transmit prognostic information, as this information may be processed in different ways. A model of misunderstandings in awareness, ranging from patient understanding to patient belief, may be useful to guide future discussions. Future decision-making studies should consider these many variables so that interventions may be created to address all aspects of the prognostic disclosure process.
Data compilations expand the scope of research; however, data citation practice lags behind advances in data use. It remains uncommon for data users to credit data producers in professionally meaningful ways. In paleontology, databases like the Paleobiology Database (PBDB) enable assessment of patterns and processes spanning millions of years, up to global scale. The status quo for data citation creates an imbalance wherein publications drawing data from the PBDB receive significantly more citations (median: 4.3 ± 3.5 citations/year) than the publications producing the data (1.4 ± 1.3 citations/year). By accounting for data reuse where citations were neglected, the projected citation rate for data-provisioning publications approached parity (4.2 ± 2.2 citations/year) and the impact factor of paleontological journals (n = 55) increased by an average of 13.4% (maximum increase = 57.8%) in 2019. Without rebalancing the distribution of scientific credit, emerging “big data” research in paleontology—and science in general—is at risk of undercutting itself through a systematic devaluation of the work that is foundational to the discipline.
Social isolation in childhood can be detrimental to physical and mental health. Children with neurodevelopmental disorders, such as attention deficit hyperactivity disorder (ADHD), may be particularly at risk for becoming socially isolated. Similarly, isolated children have limited opportunities to observe, model, and learn age-appropriate interpersonal interactions with other children which could increase ADHD behaviours.
Objectives
This study examined longitudinal associations between ADHD symptoms and social isolation across childhood. We tested the direction of this association across time, while accounting for pre-existing characteristics, and assessed whether this association varied by ADHD presentation, informant, sex, and socioeconomic status.
Methods
Participants included 2,232 children from the Environmental Risk (E-Risk) Longitudinal Twin Study. ADHD symptoms and social isolation were measured at ages 5, 7, 10, and 12. We used random-intercept cross-lagged panel models to assess the directionality of the association across childhood.
Results
Children with increased ADHD symptoms were consistently at increased risk of becoming socially isolated later in childhood, over and above stable characteristics (β=0.05-0.08). These longitudinal associations were not bidirectional; isolated children were not at risk of worsening ADHD symptoms later on. Children with a hyperactive ADHD presentation were more likely to become isolated, compared to an inattentive presentation. This was evident in the school setting, as observed by teachers, but not by mothers at home.
Conclusions
Our findings highlight the importance of enhancing peer social support and inclusion for children with ADHD, particularly in school settings. We add explanatory value over and above traditional longitudinal methods as our results represent how individual children change over time, relative to their own pre-existing characteristics.
No established guidelines exist regarding the role of oral antibiotic therapy (OAT) to treat bloodstream infections (BSIs), and practices may vary depending on clinician specialty and experience.
Objective:
To assess practice patterns regarding oral antibiotic use for treatment of bacteremia in infectious diseases clinicians (IDCs, including physicians and pharmacists and trainees in these groups) and non–infectious diseases clinicians (NIDCs).
Design:
Open-access survey.
Participants:
Clinicians caring for hospitalized patients receiving antibiotics.
Methods:
An open-access, web-based survey was distributed to clinicians at a Midwestern academic medical center using e-mail and to clinicians outside the medical center using social media. Respondents answered questions regarding confidence prescribing OAT for BSI in different scenarios. We used χ2 analysis for categorical data evaluated association between responses and demographic groups.
Results:
Of 282 survey responses, 82.6% of respondents were physicians, 17.4% pharmacists, and IDCs represented 69.2% of all respondents. IDCs were more likely to select routine use of OAT for BSI due to gram-negative anaerobes (84.6% vs 59.8%; P < .0001), Klebsiella spp (84.5% vs 69.0%; P < .009), Proteus spp (83.6% vs 71.3%; P < .027), and other Enterobacterales (79.5% vs 60.9%; P < .004). Our survey results revealed significant differences in selected treatment of Staphylococcus aureus syndromes. Fewer IDCs than NIDCs selected OAT to complete treatment for methicillin-resistant S. aureus (MRSA) BSI due to gluteal abscess (11.9% vs 25.6%; P = .012) and methicillin-susceptible S. aureus (MSSA) BSI due to septic arthritis (13.9% vs 20.9%; P = .219).
Conclusions:
Practice variation and discordance with evidence for the use of OAT for BSIs exists among IDCs versus NIDCs, highlighting opportunities for education in both clinician groups.
David Gibson’s (2008) examination of research on conversational interaction highlighted methodological and theoretical gaps in current understanding – particularly around the localized construction of interaction and the reproduction of social structures. This paper extends extant formal models used by group process researchers to explain how exogenous status structures shape local interaction by incorporating insights from qualitative work examining the local production of conversational interaction. Relational events serve as a bridge between conversation analytic understandings of the deep structure of conversation and expectation states formal models of permeation. We propose a theoretical integration of the status organizing process (permeation) and local turn-taking rules (deep structure) as a more complete model of conversational behavior in task groups. We test a formalized construction of this preliminary theory by examining turn-taking using data from 55 task groups whose members vary in gender, authority, and legitimacy of that authority. This integrated model offers substantial improvements in prediction accuracy over using status information alone. We then propose ways to expand the integrated theoretical framework to advance current understandings of action and events in conversation. Finally, we offer suggestions for insights from group processes theories that could be incorporated into network models of interaction outside of this theoretical framework.
The present study examined patterns of stability and change in loneliness across adolescence. Data were drawn from the Environmental Risk (E-Risk) Longitudinal Twin Study, a UK population-representative cohort of 2,232 individuals born in 1994 and 1995. Loneliness was assessed when participants were aged 12 and 18. Loneliness showed modest stability across these ages (r = .25). Behavioral genetic modeling indicated that stability in loneliness was explained largely by genetic influences (66%), while change was explained by nonshared environmental effects (58%). Individuals who reported loneliness at both ages were broadly similar to individuals who only reported it at age 18, with both groups at elevated risk of mental health problems, physical health risk behaviors, and education and employment difficulties. Individuals who were lonely only at age 12 generally fared better; however, they were still more likely to finish school with lower qualifications. Positive family influences in childhood predicted reduced risk of loneliness at age 12, while negative peer experiences increased the risk. Together, the findings show that while early adolescent loneliness does not appear to exert a cumulative burden when it persists, it is nonetheless a risk for a range of concomitant impairments, some of which can endure.
Multicentre research databases can provide insights into healthcare processes to improve outcomes and make practice recommendations for novel approaches. Effective audits can establish a framework for reporting research efforts, ensuring accurate reporting, and spearheading quality improvement. Although a variety of data auditing models and standards exist, barriers to effective auditing including costs, regulatory requirements, travel, and design complexity must be considered.
Materials and methods:
The Congenital Cardiac Research Collaborative conducted a virtual data training initiative and remote source data verification audit on a retrospective multicentre dataset. CCRC investigators across nine institutions were trained to extract and enter data into a robust dataset on patients with tetralogy of Fallot who required neonatal intervention. Centres provided de-identified source files for a randomised 10% patient sample audit. Key auditing variables, discrepancy types, and severity levels were analysed across two study groups, primary repair and staged repair.
Results:
Of the total 572 study patients, data from 58 patients (31 staged repairs and 27 primary repairs) were source data verified. Amongst the 1790 variables audited, 45 discrepancies were discovered, resulting in an overall accuracy rate of 97.5%. High accuracy rates were consistent across all CCRC institutions ranging from 94.6% to 99.4% and were reported for both minor (1.5%) and major discrepancies type classifications (1.1%).
Conclusion:
Findings indicate that implementing a virtual multicentre training initiative and remote source data verification audit can identify data quality concerns and produce a reliable, high-quality dataset. Remote auditing capacity is especially important during the current COVID-19 pandemic.
Operators are mindful of the balloon-to-aortic annulus ratio when performing balloon aortic valvuloplasty. The method of measurement of the aortic valve annulus has not been standardised.
Methods and results:
Patients who underwent aortic valvuloplasty at two paediatric centres between 2007 and 2014 were included. The valve annulus measured by echocardiography and angiography was used to calculate the balloon-to-aortic annulus ratio and measurements were compared. The primary endpoint was an increase in aortic insufficiency by ≥2 degrees. Ninety-eight patients with a median age at valvuloplasty of 2.1 months (Interquartile range (IQR): 0.2–105.5) were included. The angiographic-based annulus was 8.2 mm (IQR: 6.8–16.0), which was greater than echocardiogram-based annulus of 7.5 mm (IQR: 6.1–14.8) (p < 0.001). This corresponded to a significantly lower angiographic balloon-to-aortic annulus ratio of 0.9 (IQR: 0.9–1.0), compared to an echocardiographic ratio of 1.1 (IQR: 1.0–1.1) (p < 0.001). The degree of discrepancy in measured diameter increased with smaller valve diameters (p = 0.041) and in neonates (p = 0.044). There was significant disagreement between angiographic and echocardiographic balloon-to-aortic annulus ratio measures regarding “High” ratio of >1.2, with angiographic ratio flagging only 2/12 (16.7%) of patients flagged by echocardiographic ratio as “High” (p = 0.012). Patients who had an increase in the degree of aortic insufficiency post valvuloplasty, only 3 (5.5%) had angiographic ratio > 1.1, while 21 (38%) had echocardiographic ratio >1.1 (p < 0.001). Patients with resultant ≥ moderate insufficiency more often had an echocardiographic ratio of >1.1 than angiographic ratio of >1.1 There was no association between increase in balloon-to-aortic annulus ratio and gradient reduction.
Conclusions:
Angiographic measurement is associated with a greater measured aortic valve annulus and the development of aortic insufficiency. Operators should use caution when relying solely on angiographic measurement when performing balloon aortic valvuloplasty.
Weed control of paraquat can be erratic and may be attributable to differing species sensitivity and/or environmental factors for which minor guidance is available on commercial labels. Therefore, the objectives of this research were to quantify selectivity of paraquat across select weed species and the influence of environmental factors. Experiments were performed under controlled conditions in the greenhouse and growth chamber. Compared with purple deadnettle (dose necessary to reduce shoot biomass by 50% = 39 g ai ha−1), waterhemp, Palmer amaranth, giant ragweed, and horseweed were 4.9, 3.3, 1.9, and 1.3 times more sensitive to paraquat, respectively. The injury progression rate over 3 d after treatment (DAT) was a more accurate predictor of final efficacy at 14 DAT than the lag phase until symptoms first appeared. For example, at the 17.5 g ha−1 dose, the injury rate of waterhemp and Palmer amaranth was, on average, 3.6 times greater than that of horseweed and purple deadnettle. The influence of various environmental factors on paraquat efficacy was weed specific. Applications made at sunrise improved control of purple deadnettle over applications at solar noon or sunset. Lower light intensities (200 or 600 μmol m−2 s−1) surrounding the time of application improved control of waterhemp and horseweed more than 1,000 μmol m−2 s−1. Day/night temperatures of 27/16 C improved horseweed and purple deadnettle control compared with day/night temperatures of 18/13 C. Though control was positively associated with injury rates in the application time of day and temperature experiments, a negative relationship was observed for waterhemp in the light-intensity experiment. Thus, although there are conditions that enhance paraquat efficacy, the specific target species must also be considered. These results advocate paraquat dose recommendations, currently based on weed height, be expanded to address sensitivity differences among weeds. Moreover, these findings contrast with paraquat labels stating temperatures of 13 C or lower do not reduce paraquat efficacy.
This article considers whether candidates strategically use emotional rhetoric in social media messages similar to the way that fear appeals are used strategically in televised campaign advertisements. We use a dataset of tweets issued by the campaign accounts of candidates for the US House of Representatives during the last two months of the 2018 midterm elections to determine whether candidate vulnerability predicts the presence of certain emotions in social media messages. Contrary to theoretical expectations, we find that vulnerability does not appear to inspire candidates to use more anxious language in their tweets. However, we do find evidence of a surprising relationship between sad rhetoric and vulnerability and that campaign context influences the use of other forms of negative rhetoric in tweets.
Being overweight is associated with reduced functional capacity in Fontan patients. Increased adiposity leads to accumulation of epicardial and intra-abdominal visceral fat, which produce proinflammatory cytokines and may affect endothelial function. This retrospective study to evaluate the association between visceral fat and Fontan haemodynamics included 23 Fontan patients >18 years old with MRI and catheterization data available. Epicardial fat volume indexed to body surface area was measured by cardiac MRI, and intra-abdominal visceral fat thickness and subcutaneous fat thickness were derived from abdominal MRI. Stepwise regression models were used to determine univariable and multivariable associations between fat measures and haemodynamics. Mean age was 28.2 ± 9.5 years and body mass index was 26 ± 4 kg/m2. Mean central venous pressure was 13 ± 3 mmHg and pulmonary vascular resistance index was 1.23WU·m2 (interquartile range: 0.95–1.56). Epicardial fat volume was associated with age (r2 = 0.37, p = 0.002), weight (r2 = 0.26, p = 0.013), body mass index (r2 = 0.27, p = 0.011), and intra-abdominal visceral fat (r2 = 0.30, p = 0.018). Subcutaneous fat thickness did not relate to these measures. There was modest correlation between epicardial fat volume and pulmonary vascular resistance (r2 = 0.27, p = 0.02) and a trend towards significant correlation between intra-abdominal fat thickness and pulmonary vascular resistance (r2 = 0.21, p = 0.06). Subcutaneous fat thickness was not associated with Fontan haemodynamics. In multivariable analysis, including age and visceral fat measures, epicardial fat was independently correlated with pulmonary vascular resistance (point estimate 0.13 ± 0.05 per 10 ml/m2 increase, p = 0.03). In conclusion, in adults with Fontan circulation, increased visceral fat is associated with higher pulmonary vascular resistance. Excess visceral fat may represent a therapeutic target to improve Fontan haemodynamics.
Innovation Concept: Research training programs for students, especially in emergency medicine (EM), may be difficult to initiate due to lack of protected time, resources, and mentors (Chang Y, Ramnanan CJ. Academic Medicine 2015). We developed a ten-week summer program for medical students aimed at cultivating research skills through mentorship, clinical enrichment, and immersion in EM research culture through shadowing and project support. Methods: Five second year Ontario medical students were recruited to participate in the Summer Training and Research in Emergency Medicine (STAR-EM) program at University Health Network, Toronto, from June - Aug, 2019. Program design followed review of existing summer research programs and literature regarding challenges to EM research (McRae, Perry, Brehaut et al. CJEM 2018). The program had broad emergency physician (EP) engagement, with five EP research project mentors, and over ten EPs delivering academic sessions. Curriculum development was collaborative and iterative. All projects were approved by the hospital Research Ethics Board (REB). Curriculum, Tool or Material: Each weekly academic morning comprised small group teaching (topics including research methodology, manuscript preparation, health equity, quality improvement, and wellness), followed by EP-led group progress review of each student's project. Each student spent one half day per week in the emergency department (ED), shadowing an EP and identifying patients for recruitment for ongoing mentor-initiated ED research projects. Remaining time was spent on independent student project work. Presentation to faculty and program evaluation occurred in week 10. Scholarly output included one abstract submitted for publication per student. Program evaluation by students reflected a uniform impression that course material and mentorship were each excellent (100%, n = 5). Interest in pursuing academic EM as a career was identified by all students. Faculty researchers rated the program as very effective (80%, n = 4) or somewhat effective (20%, n = 1) in terms of enhancing productivity and scholarly output. Conclusion: The STAR-EM program provides a transferable model for other academic departments seeking to foster the development of future clinician investigators and enhance ED research culture. Program challenges included delays in REB approval for student projects and engaging recalcitrant staff to participate in research.
National and international research has shown the association between depression and anxiety disorders with the risk of planned and impulsive suicidal behavior. Patients with depression may have severe anxiety or agitation associated with their depression with or without comorbid additional anxiety disorder diagnoses.
Objectives
1. Evaluate differences between self rated overall suicide risk of inpatients on a treatment resistant depression unit based on presence or absence of comorbid anxiety disorder.
2. Evaluate association of pharmacogenetic testing results with self-ratings of suicide risk.
Aims
1. To determine if suicide risk of psychiatric inpatients is higher in patients with depression and comorbid anxiety disorder.
2. To determine utility of pharmacogenetic testing with suicide risk assessment and patterns of use in patients with treatment resistant depression at a large academic medical center.
Methods
This is a retrospective records review study of a sample of over 700 inpatients on a treatment resistant depression unit at the Mayo Clinic. Patients overall suicide risk self-assessments will be analyzed for differences in suicide risk assessment controlling for diagnoses, age, and sex. Pharmacogenetic testing results, including serotonin transporter and p450 2D6 testing results, will be analyzed for their association with suicide risk.
Results
Statistical analyses results are pending at time of abstract submission.
Conclusions
At a population level, the interplay between anxiety disorders and depressive symptoms is felt to be key to understanding the progression from suicidal ideation to suicidal behavior. Factors complicating this at an individual patient level along with results of research study will be discussed.
Reconstructions of prehistoric vegetation composition help establish natural baselines, variability, and trajectories of forest dynamics before and during the emergence of intensive anthropogenic land use. Pollen–vegetation models (PVMs) enable such reconstructions from fossil pollen assemblages using process-based representations of taxon-specific pollen production and dispersal. However, several PVMs and variants now exist, and the sensitivity of vegetation inferences to PVM selection, variant, and calibration domain is poorly understood. Here, we compare the reconstructions, parameter estimates, and structure of a Bayesian hierarchical PVM, STEPPS, both to observations and to REVEALS, a widely used PVM, for the pre–Euro-American settlement-era vegetation in the northeastern United States (NEUS). We also compare NEUS-based STEPPS parameter estimates to those for the upper midwestern United States (UMW). Both PVMs predict the observed macroscale patterns of vegetation composition in the NEUS; however, reconstructions of minor taxa are less accurate and predictions for some taxa differ between PVMs. These differences can be attributed to intermodel differences in structure and parameter estimates. Estimates of pollen productivity from STEPPS broadly agree with estimates produced for use in REVEALS, while comparison between pollen dispersal parameter estimates shows no significant relationship. STEPPS parameter estimates are similar between the UMW and NEUS, suggesting that STEPPS parameter estimates are transferable between floristically similar regions and scales.