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The evolution of multicellularity paved the way for significant increases in biological complexity. Although multicellularity has evolved many times independently, we know relatively little about its origins. Directed evolution is a promising approach to studying early steps in this major transition, but current experimental systems have examined only a subset of the possible evolutionary routes to multicellularity. Here we consider egalitarian routes to multicellularity, in which unrelated unicellular organisms evolve to become a multicellular organism. Inspired by microbial syntrophies and lichens, we outline three such routes from a system of different species to an interdependent relationship that replicates. We compare these routes to contemporary experimental systems and consider how physical structure, the threat of invasion, division of labour and co-transmission affect their evolution.
Health utility instruments are increasingly being used to measure impairment in health-related quality of life (HRQoL) after stroke. Population-based studies of HRQoL after stroke and assessment of differences by age and functional domain are needed.
We used the Canadian Community Health Survey linked with administrative databases to determine HRQoL using the Health Utilities Index Mark 3 (HUI3) among those with prior hospitalization or emergency department visit for stroke and compared to controls without stroke. We used multivariable linear regression to determine the difference in HUI3 between those with stroke and controls for the global index and individual attributes, with assessment for modification by age (<60, 60–74, and 75+ years) and sex, and we combined estimates across survey years using random effects meta-analysis.
Our cohort contained 1240 stroke survivors and 123,765 controls and was weighted to be representative of the Canadian household population. Mean health utility was 0.63 (95% confidence interval [CI] 0.58, 0.68) for those with stroke and 0.83 (95% CI 0.82, 0.84) for controls. There was significant modification by age, but not sex, with the greatest adjusted reduction in HUI3 among stroke respondents aged 60–74 years. Individual HUI3 attributes with the largest reductions in utility among stroke survivors compared to controls were mobility, cognition, emotion, and pain.
In this population-based study, the reduction in HUI3 among stroke survivors compared to controls was greatest among respondents aged 60–74, and in attributes of mobility, cognition, emotion, and pain. These results highlight the persistent impairment of HRQoL in the chronic phase of stroke and potential targets for community support.
To assess extent of a healthcare-associated outbreak of severe acute respiratory coronavirus virus 2 (SARS-CoV-2) and to evaluate the effectiveness of infection control measures, including universal masking.
Outbreak investigation including 4 large-scale point-prevalence surveys.
Integrated VA healthcare system with 2 facilities and 330 beds.
Index patient and 250 exposed patients and staff.
We identified exposed patients and staff and classified them as probable and confirmed cases based on symptoms and testing. We performed a field investigation and an assessment of patient and staff interactions to develop probable transmission routes. Infection prevention interventions included droplet and contact precautions, employee quarantine, and universal masking with medical and cloth face masks. We conducted 4 point-prevalence surveys of patient and staff subsets using real-time reverse-transcriptase polymerase chain reaction for SARS-CoV-2.
Among 250 potentially exposed patients and staff, 14 confirmed cases of coronavirus disease 2019 (COVID-19) were identified. Patient roommates and staff with prolonged patient contact were most likely to be infected. The last potential date of transmission from staff to patient was day 22, the day universal masking was implemented. Subsequent point-prevalence surveys in 126 patients and 234 staff identified 0 patient cases and 5 staff cases of COVID-19, without evidence of healthcare-associated transmission.
Universal masking with medical face masks was effective in preventing further spread of SARS-CoV-2 in our facility in conjunction with other traditional infection prevention measures.
During the Randomized Assessment of Rapid Endovascular Treatment (EVT) of Ischemic Stroke (ESCAPE) trial, patient-level micro-costing data were collected. We report a cost-effectiveness analysis of EVT, using ESCAPE trial data and Markov simulation, from a universal, single-payer system using a societal perspective over a patient’s lifetime.
Primary data collection alongside the ESCAPE trial provided a 3-month trial-specific, non-model, based cost per quality-adjusted life year (QALY). A Markov model utilizing ongoing lifetime costs and life expectancy from the literature was built to simulate the cost per QALY adopting a lifetime horizon. Health states were defined using the modified Rankin Scale (mRS) scores. Uncertainty was explored using scenario analysis and probabilistic sensitivity analysis.
The 3-month trial-based analysis resulted in a cost per QALY of $201,243 of EVT compared to the best standard of care. In the model-based analysis, using a societal perspective and a lifetime horizon, EVT dominated the standard of care; EVT was both more effective and less costly than the standard of care (−$91). When the time horizon was shortened to 1 year, EVT remains cost savings compared to standard of care (∼$15,376 per QALY gained with EVT). However, if the estimate of clinical effectiveness is 4% less than that demonstrated in ESCAPE, EVT is no longer cost savings compared to standard of care.
Results support the adoption of EVT as a treatment option for acute ischemic stroke, as the increase in costs associated with caring for EVT patients was recouped within the first year of stroke, and continued to provide cost savings over a patient’s lifetime.
Cardiopulmonary exercise testing performance has been shown to be a predictor of morbidity, mortality, and quality of life in patients with Fontan physiology; however, the role of exercise performance along with other diagnostics is not fully understood. We evaluated the hypothesis that reduced exercise performance correlates with poorer quality of life in Fontan patients as they continue to age.
Chart review was performed on patients 12 years and older with Fontan who had completed cardiopulmonary exercise testing and age-appropriate quality of life surveys. Quality of life outcomes were analysed against exercise performance and other descriptive data.
For the younger cohort (n = 22), exercise performance predicted quality of life with different measures across domains and had a stronger correlation than echocardiographic parameters. For the older cohort (n = 34), exercise performance did not predict quality of life.
Objective exercise performance was a useful marker for general, physical, emotional, social, and school quality of life in a younger cohort but less helpful in older adults. This is perhaps due to older patients accommodating to their conditions over time. The role of exercise performance and objective data in predicting quality of life in patients with Fontan physiology is incompletely understood and additional prospective evaluation should be undertaken.
Reward Deficiency Syndrome (RDS) is an umbrella term for all drug and nondrug addictive behaviors, due to a dopamine deficiency, “hypodopaminergia.” There is an opioid-overdose epidemic in the USA, which may result in or worsen RDS. A paradigm shift is needed to combat a system that is not working. This shift involves the recognition of dopamine homeostasis as the ultimate treatment of RDS via precision, genetically guided KB220 variants, called Precision Behavioral Management (PBM). Recognition of RDS as an endophenotype and an umbrella term in the future DSM 6, following the Research Domain Criteria (RDoC), would assist in shifting this paradigm.
Sports medicine clinicians face conflicts of interest in providing medical care to athletes. Using a survey of college football players, this study evaluates whether athletes are aware of these conflicts of interest, whether these conflicts affect athlete trust in their health care providers, or whether conflicts or athletes' trust in stakeholders are associated with athletes' injury reporting behaviors.
Emergency Medical Services (EMS) systems have developed protocols for prehospital activation of the cardiac catheterization laboratory for patients with suspected ST-elevation myocardial infarction (STEMI) to decrease first-medical-contact-to-balloon time (FMC2B). The rate of “false positive” prehospital activations is high. In order to decrease this rate and expedite care for patients with true STEMI, the American Heart Association (AHA; Dallas, Texas USA) developed the Mission Lifeline PreAct STEMI algorithm, which was implemented in Los Angeles County (LAC; California USA) in 2015. The hypothesis of this study was that implementation of the PreAct algorithm would increase the positive predictive value (PPV) of prehospital activation.
This is an observational pre-/post-study of the effect of the implementation of the PreAct algorithm for patients with suspected STEMI transported to one of five STEMI Receiving Centers (SRCs) within the LAC Regional System. The primary outcome was the PPV of cardiac catheterization laboratory activation for percutaneous coronary intervention (PCI) or coronary artery bypass graft (CABG). The secondary outcome was FMC2B.
A total of 1,877 patients were analyzed for the primary outcome in the pre-intervention period and 405 patients in the post-intervention period. There was an overall decrease in cardiac catheterization laboratory activations, from 67% in the pre-intervention period to 49% in the post-intervention period (95% CI for the difference, -14% to -22%). The overall rate of cardiac catheterization declined in post-intervention period as compared the pre-intervention period, from 34% to 30% (95% CI, for the difference -7.6% to 0.4%), but actually increased for subjects who had activation (48% versus 58%; 95% CI, 4.6%-15.0%). Implementation of the PreAct algorithm was associated with an increase in the PPV of activation for PCI or CABG from 37.9% to 48.6%. The overall odds ratio (OR) associated with the intervention was 1.4 (95% CI, 1.1-1.8). The effect of the intervention was to decrease variability between medical centers. There was no associated change in average FMC2B.
The implementation of the PreAct algorithm in the LAC EMS system was associated with an overall increase in the PPV of cardiac catheterization laboratory activation.
The occurrence of code-switching in online communication, when a writer switches among multiple languages, presents a challenge for natural language processing tools, since they are designed for texts written in a single language. To answer the challenge, this paper presents detailed research on ways to detect code-switching in Arabic text automatically. We compare the prediction by partial matching (PPM) compression-based classifier, implemented in Tawa, and a traditional machine learning classifier sequential minimal optimization (SMO), implemented in Waikato Environment for Knowledge Analysis, working specifically on Arabic text taken from Facebook. Three experiments were conducted in order to: (1) detect code-switching among the Egyptian dialect and English; (2) detect code-switching among the Egyptian dialect, the Saudi dialect, and English; and (3) detect code-switching among the Egyptian dialect, the Saudi dialect, Modern Standard Arabic (MSA), and English. Our experiments showed that PPM achieved a higher accuracy rate than SMO with 99.8% versus 97.5% in the first experiment and 97.8% versus 80.7% in the second. In the third experiment, PPM achieved a lower accuracy rate than SMO with 53.2% versus 60.2%. Code-switching between Egyptian Arabic and English text is easiest to detect because Arabic and English are generally written in different character sets. It is more difficult to distinguish between Arabic dialects and MSA as these use the same character set, and most users of Arabic, especially Saudis and Egyptians, frequently mix MSA with their dialects. We also note that the MSA corpus used for training the MSA model may not represent MSA Facebook text well, being built from news websites. This paper also describes in detail the new Arabic corpora created for this research and our experiments.
Nuclear rings are excellent laboratories to study star formation (SF) under extreme conditions. We compiled a sample of 9 galaxies that exhibit bright nuclear rings at 3-33 GHz radio continuum observed with the Jansky Very Large Array, of which 5 are normal star-forming galaxies and 4 are Luminous Infrared Galaxies (LIRGs). Using high frequency radio continuum as an extinction-free tracer of SF, we estimated the size and star formation rate of each nuclear ring and a total of 37 individual circumnuclear star-forming regions. Our results show that majority of the SF in the sample LIRGs take place in their nuclear rings, and circumnuclear SF in local LIRGs are much more spatially concentrated compared to those in the local normal galaxies and previously studied nuclear and extra-nuclear SF in normal galaxies at both low and high redshifts.
The purpose of the present review is to describe how human physiology at very low carbohydrate intakes relates to the criteria for nutritional essentiality. Although we did not limit ourselves to one particular type or function of carbohydrates, we did primarily focus on glucose utilisation as that function was used to determine the recommended daily allowance. In the general population, the human body is able to endogenously synthesise carbohydrates, and does not show signs of deficiency in the absence of dietary carbohydrates. However, in certain genetic defects, such as glycogen storage disease type I, absence of dietary carbohydrates causes abnormalities that are resolved with dietary supplementation of carbohydrates. Therefore, dietary carbohydrates may be defined as conditionally essential nutrients because they are nutrients that are not required in the diet for the general population but are required for specific subpopulations. Ketosis may be considered a physiological normal state due to its occurrence in infants in addition to at very low carbohydrate intakes. Although sources of dietary carbohydrates can provide beneficial micronutrients, no signs of micronutrient deficiencies have been reported in clinical trials of low-carbohydrate ketogenic diets. Nonetheless, more research is needed on how micronutrient requirements can change depending on the dietary and metabolic context. More research is also needed on the role of dietary fibre during a low-carbohydrate ketogenic diet as the beneficial effects of dietary fibre were determined on a standard diet and several studies have shown beneficial effects of decreasing non-digestible carbohydrates.
Glyphosate-resistant (GR) canola is a widely grown crop across western Canada and has quickly become a prolific volunteer weed. Glyphosate-resistant soybean is rapidly gaining acreage in western Canada. Thus, there is a need to evaluate herbicide options to manage volunteer GR canola in GR soybean crops. We conducted an experiment to evaluate the efficacy of various PRE and POST herbicides applied sequentially to volunteer GR canola and to evaluate soybean injury caused by these herbicides. Trials were conducted across Saskatchewan and Manitoba in 2014 and 2015. All treatments provided a range of suppression (>70%) to control (>80%) of volunteer canola. All treatments with the exception of the glyphosate-treated control reduced aboveground canola biomass by an average of 96%. As well, canola seed contamination was reduced from 36% to less than 5% when a PRE and POST herbicide were both used. Moreover, all combinations of herbicides used had excellent crop safety (<10%). All PRE and POST herbicide combinations provided better control of volunteer canola compared with the glyphosate-only control, but tribenuron followed by bentazon and tribenuron followed by imazamox plus bentazon provided solutions that were low cost, currently available (registered in western Canada), and had the potential to minimize development of herbicide resistance in other weeds.
Cigarette smoking is highly prevalent among young people experiencing homelessness, and many of these smokers are motivated to quit. However, there is a lack of readily available cessation services for this population, which is highly mobile and can be challenging to engage in services.
We describe the development of a smoking cessation text messaging intervention (TMI) for homeless youth who are interested in quitting smoking.
Participants were 18–25 years old and recruited from drop-in centers serving homeless youth. Three focus groups (N = 18) were conducted with smokers to refine the TMI content, and a separate sample of smokers (N = 8) provided feedback on the TMI after using it for 1 week. Survey data assessed the TMI's acceptability and feasibility.
Participants generally rated the TMI as helpful and relevant, and nearly all had cell phone plans that included unlimited texting and were able to view TMI content with few difficulties. Qualitative feedback on strengths/limitations of the TMI in terms of content, tone, and delivery parameters was used to finalize the TMI for a future evaluation.
Results suggest that a TMI is a feasible and acceptable option for young people experiencing homelessness who are interested in quitting smoking.
In recent years, soybean acreage has increased significantly in western Canada. One of the challenges associated with growing soybean in western Canada is the control of volunteer glyphosate-resistant (GR) canola, because most soybean cultivars are also glyphosate resistant. The objective of this research was to determine the impact of soybean seeding rate and planting date on competition with volunteer canola. We also attempted to determine how high seeding rate could be raised while still being economically feasible for producers. Soybean was seeded at five different seeding rates (targeted 10, 20, 40, 80, and 160 plants m−2) and three planting dates (targeted mid-May, late May, and early June) at four sites across western Canada in 2014 and 2015. Soybean yield consistently increased with higher seeding rates, whereas volunteer canola biomass decreased. Planting date generally produced variable results across site-years. An economic analysis determined that the optimal rate was 40 to 60 plants m−2, depending on market price, and the optimal planting date range was from May 20 to June 1.
OBJECTIVES/SPECIFIC AIMS: Early life stress is known to greatly impact neurodevelopment during critical periods, conferring risk for various psychopathologies, including the onset and exacerbation of schizophrenia and anxiety disorders. The endocannabinoid system is highly integrated into the stress response and may be one means by which early life stress produces such deleterious effects. Using a naturalistic, ecologically valid animal model, this study explored interactions between the stress response and endocannabinoid systems within the cerebellum, a region dense with the CB1 endocannabinoid receptors and shown to be susceptible to stress. METHODS/STUDY POPULATION: This study explored behavioral and neural impacts of early life stress in Long-Evans rats reared with or without limited access to bedding material during postnatal day (PND) 2-9. Corticosterone (CORT) levels were measured at PND8 and 70. During PND50-70, rats were assessed on Novel Object Recognition to test memory, Rotarod to evaluate cerebellar integrity, Elevated Plus Maze to assay anxiety, Social Preference, and Eyeblink Conditioning, a cerebellar-dependent and endocannabinoid-mediated task. Lipid analysis was performed on PND70 tissue samples of cerebellar interpositus (IP) nucleus via high-performance liquid chromatography and tandem mass spectrometry. RESULTS/ANTICIPATED RESULTS: Both male and female rats experiencing early life stress exhibited significantly impaired recognition memory (N = 16-20/group). Female rats having undergone stress exhibited decreased social preference compared to normally reared females (N = 11/group). Stressed males showed facilitated eyblink conditioning compared to normally reared males (N = 7-9/group). There were no group differences in rotarod or elevated plus maze performance or CORT levels at PND8 or 70 across rearing groups. At PND70, male rats experiencing early life stress exhibited a significant decrease in 2-arachidonoyl glycerol (2-AG) and arachidonic acid levels in the IP nucleus compared to normally reared males (N = 8-9/group). Compared to normally reared females, those experiencing early life stress exhibited a significant increase in prostaglandin E2 levels in the IP nucleus (N = 6-7/group). DISCUSSION/SIGNIFICANCE OF IMPACT: Early life stress, induced by limited bedding, resulted in sex-specific behavioral and lipid impairments. Results suggest that stress causes long-term alterations in endocannabinoid dynamics in males in the cerebellar IP nucleus and sex-related lipids in female cerebellum. These changes may contribute to observed long-term behavioral aberrations. Moreover, findings suggest these behavioral changes may be the result of negative-feedback dysfunction (as evidenced by decreased endocannabinoids in males) or increased neural inflammation or proliferation (as evidenced by increased prostaglandins in females). Future analysis will quantify mRNA and protein for cannabinoid receptors to better characterize aberrations to this system. Moreover, other neural regions dense with cannabinoid receptors (i.e., PFC, hippocampus) will be investigated. This work provides a basis for understanding stress impacts on the development of cognitive deficits observed in psychotic and anxiety disorders. Specifically, facilitation of eyblink conditioning complements research in humans with anxiety disorders. Broadly, understanding stress-related endocannabinoid dysregulation may provide insights into risks for, and the development of, psychopathology and uncover novel therapeutic targets with high translational power.
Although relapse in psychosis is common, a small proportion of patients will not relapse in the long term. We examined the proportion and predictors of patients who never relapsed in the 10 years following complete resolution of positive symptoms from their first psychotic episode.
Patients who previously enrolled in a 12-month randomized controlled trial on medication discontinuation and relapse following first-episode psychosis (FEP) were followed up after 10 years. Relapse of positive symptoms was operationalized as a change from a Clinical Global Impression scale positive score of <3 for at least 3 consecutive months to a score of ⩾3 (mild or more severe). Baseline predictors included basic demographics, premorbid functioning, symptoms, functioning, and neurocognitive functioning.
Out of 178 first-episode patients, 37 (21%) never relapsed during the 10-year period. Univariate predictors (p ⩽ 0.1) of patients who never relapsed included a duration of untreated psychosis (DUP) ⩽30 days, diagnosed with non-schizophrenia spectrum disorders, having less severe negative symptoms, and performing better in logical memory immediate recall and verbal fluency tests. A multivariate logistic regression analysis further suggested that the absence of any relapsing episodes was significantly related to better short-term verbal memory, shorter DUP, and non-schizophrenia spectrum disorders.
Treatment delay and neurocognitive function are potentially modifiable predictors of good long-term prognosis in FEP. These predictors are informative as they can be incorporated into an optimum risk prediction model in the future, which would help with clinical decision making regarding maintenance treatment in FEP.
Objectives: As the number of adolescents and young adults (AYAs) surviving congenital heart disease (CHD) grows, studies of long-term outcomes are needed. CHD research documents poor executive function (EF) and cerebellum (CB) abnormalities in children. We examined whether AYAs with CHD exhibit reduced EF and CB volumes. We hypothesized a double dissociation such that the posterior CB is related to EF while the anterior CB is related to motor function. We also investigated whether the CB contributes to EF above and beyond processing speed. Methods: Twenty-two AYAs with CHD and 22 matched healthy controls underwent magnetic resonance imaging and assessment of EF, processing speed, and motor function. Volumetric data were calculated using a cerebellar atlas (SUIT) developed for SPM. Group differences were compared with t tests, relationships were tested with Pearson’s correlations and Fisher’s r to z transformation, and hierarchical regression was used to test the CB’s unique contributions to EF. Results: CHD patients had reduced CB total, lobular, and white matter volume (d=.52–.99) and poorer EF (d=.79–1.01) compared to controls. Significant correlations between the posterior CB and EF (r=.29–.48) were identified but there were no relationships between the anterior CB and motor function nor EF. The posterior CB predicted EF above and beyond processing speed (ps<.001). Conclusions: This study identified a relationship between the posterior CB and EF, which appears to be particularly important for inhibitory processes and abstract reasoning. The unique CB contribution to EF above and beyond processing speed alone warrants further study. (JINS, 2018, 24, 939–948)