Comparative transcriptomics can be used to translate an understanding of gene regulatory networks from model systems to less studied species. Here, we use RNA-Seq to determine and compare gene expression dynamics through the floral transition in the model species Arabidopsis thaliana and the closely related crop Brassica rapa. We find that different curve registration functions are required for different genes, indicating that there is no single common ‘developmental time’ between Arabidopsis and B. rapa. A detailed comparison between Arabidopsis and B. rapa and between two B. rapa accessions reveals different modes of regulation of the key floral integrator SOC1, and that the floral transition in the B. rapa accessions is triggered by different pathways. Our study adds to the mechanistic understanding of the regulatory network of flowering time in rapid cycling B. rapa and highlights the importance of registration methods for the comparison of developmental gene expression data.

ABSTRACT IMPACT: The pathophysiologic features of a metabolomic endotype that predicts patient outcomes due to sepsis have the potential to direct new therapies that target immune dysregulation and bioenergetic insufficiency. OBJECTIVES/GOALS: Acute respiratory failure (ARF) requiring mechanical ventilation is a frequent complication of sepsis and other disorders. It is associated with high morbidity and mortality. Despite its severity and prevalence, little is known about metabolic and bioenergetic changes that accompanying ARF. METHODS/STUDY POPULATION: In this study, semiquantitative and quantitative ultrahigh performance liquid chromatography mass spectrometry (UHPLC MS) analysis was performed on patient serum collected from the Trial with Acute Respiratory failure patients: evaluation of Global Exercise Therapies (TARGET). Serum from survivors (n=15) and nonsurvivors (n=15) was collected at day 1 and day 3 after admission to the medical intensive care unit as well as at discharge in survivors. Pathway analysis of the biochemical changes was performed to determine whether the disruption in specific metabolic pathways can identify the bioenergetic and metabolomic profile of these patients. RESULTS/ANTICIPATED RESULTS: Significant metabolomic differences were related to biosynthetic intermediates of redox cofactors nicotinamide adenine dinucleotide (NAD) and NAD phosphate (NADP), increased acyl-carnitines, and decreased acyl-glycerophosphocholines in nonsurvivors compared to survivors. The metabolites associated with poor outcomes are substrates of enzymatic processes dependent on NAD(P), while the abundance of NAD cofactors rely on the bioavailability of dietary vitamins B1, B2 and B6. Changes in the efficiency of the nicotinamide-derived cofactors’ biosynthetic pathways also associate with an alteration of the glutathione-dependent drug metabolism as characterized by the substantial differences observed in the acetaminophen metabolome. DISCUSSION/SIGNIFICANCE OF FINDINGS: This metabolomic endotype represents a previously unappreciated association between severity of outcomes and micronutrient deficiency, thus pointing to new pharmacologic targets and highlighting the need for nutritional remediation upon hospitalization to improve patient outcomes due to ARF.

The vacuum-exhausted isolation locker (VEIL) provides a safety barrier during the care of COVID-19 patients. The VEIL is a 175-L enclosure with exhaust ports to continuously extract air through viral particle filters connected to hospital suction. Our experiments show that the VEIL contains and exhausts exhaled aerosols and droplets.

Conservation measures providing food-rich habitats through agri-environment schemes (AES) have the potential to affect the demography and local abundance of species limited by food availability. The European Turtle Dove Streptopelia turtur is one of Europe’s fastest declining birds, with breeding season dietary changes coincident with a reduction in reproductive output suggesting food limitation during breeding. In this study we provided seed-rich habitats at six intervention sites over a 4-year period and tested for impacts of the intervention on breeding success, ranging behaviour and the local abundance of territorial turtle doves. Nesting success and chick biometrics were unrelated to the local availability of seed-rich habitat or to the proximity of intervention plots. Nestling weight was higher close to human habitation consistent with an influence of anthropogenic supplementary food provision. Small home ranges were associated with a high proportion of non-farmed habitats, while large home ranges were more likely to contain seed-rich habitat suggesting that breeding doves were willing to travel further to utilize such habitat where available. Extensively managed grassland and intervention plot fields were selected by foraging turtle doves. A slower temporal decline in the abundance of breeding males on intervention sites probably reflects enhanced habitat suitability during territory settlement. Refining techniques to deliver sources of sown, natural, and supplementary seed that are plentiful, accessible, and parasite-free is likely to be crucial for the conservation of turtle doves.

Antibiotics are among the most common medications prescribed in nursing homes. The annual prevalence of antibiotic use in residents of nursing homes ranges from 47% to 79%, and more than half of antibiotic courses initiated in nursing-home settings are unnecessary or prescribed inappropriately (wrong drug, dose, or duration). Inappropriate antibiotic use is associated with a variety of negative consequences including Clostridioides difficile infection (CDI), adverse drug effects, drug–drug interactions, and antimicrobial resistance. In response to this problem, public health authorities have called for efforts to improve the quality of antibiotic prescribing in nursing homes.

Through diversity of composition, sequence, and interfacial structure, hybrid materials greatly expand the palette of materials available to access novel functionality. The NSF Division of Materials Research recently supported a workshop (October 17–18, 2019) aiming to (1) identify fundamental questions and potential solutions common to multiple disciplines within the hybrid materials community; (2) initiate interfield collaborations between hybrid materials researchers; and (3) raise awareness in the wider community about experimental toolsets, simulation capabilities, and shared facilities that can accelerate this research. This article reports on the outcomes of the workshop as a basis for cross-community discussion. The interdisciplinary challenges and opportunities are presented, and followed with a discussion of current areas of progress in subdisciplines including hybrid synthesis, functional surfaces, and functional interfaces.

Postprandial glycaemia and insulinaemia are important risk factors for type 2 diabetes. The prevalence of insulin resistance in adolescents is increasing, but it is unknown how adolescent participant characteristics such as BMI, waist circumference, fitness and maturity offset may explain responses to a standard meal. The aim of the present study was to examine how such participant characteristics affect the postprandial glycaemic and insulinaemic responses to an ecologically valid mixed meal. Data from the control trials of three separate randomised, crossover experiments were pooled, resulting in a total of 108 participants (fifty-two boys, fifty-six girls; aged 12·5 (SD 0·6) years; BMI 19·05 (SD 2·66) kg/m2). A fasting blood sample was taken for the calculation of fasting insulin resistance, using the homoeostatic model assessment of insulin resistance (HOMA-IR). Further capillary blood samples were taken before and 30, 60 and 120 min after a standardised lunch, providing 1·5 g/kg body mass of carbohydrate, for the quantification of blood glucose and plasma insulin total AUC (tAUC). Hierarchical multiple linear regression demonstrated significant predictors for plasma insulin tAUC were waist circumference, physical fitness and HOMA-IR (F (3,98) = 36·78, P < 0·001, adjusted R 2 = 0·515). The variance in blood glucose tAUC was not significantly explained by the predictors used (F (7,94) = 1·44, P = 0·198). Significant predictors for HOMA-IR were BMI and maturity offset (F (2,102) = 14·06, P < 0·001, adjusted R 2 = 0·021). In summary, the key findings of the study are that waist circumference, followed by physical fitness, best explained the insulinaemic response to an ecologically valid standardised meal in adolescents. This has important behavioural consequences because these variables can be modified.

Introduction: For rhythm control of acute atrial flutter (AAFL) in the emergency department (ED), choices include initial drug therapy or initial electrical cardioversion (ECV). We compared the strategies of pharmacological cardioversion followed by ECV if necessary (Drug-Shock), and ECV alone (Shock Only). Methods: We conducted a randomized, blinded, placebo-controlled trial (1:1 allocation) comparing two rhythm control strategies at 11 academic EDs. We included stable adult patients with AAFL, where onset of symptoms was <48 hours. Patients underwent central web-based randomization stratified by site. The Drug-Shock group received an infusion of procainamide (15mg/kg over 30 minutes) followed 30 minutes later, if necessary, by ECV at 200 joules x 3 shocks. The Shock Only group received an infusion of saline followed, if necessary, by ECV x 3 shocks. The primary outcome was conversion to sinus rhythm for ≥30 minutes at any time following onset of infusion. Patients were followed for 14 days. The primary outcome was evaluated on an intention-to-treat basis. Statistical significance was assessed using chi-squared tests and multivariable logistic regression. Results: We randomized 76 patients, and none was lost to follow-up. The Drug-Shock (N = 33) and Shock Only (N = 43) groups were similar for all characteristics including mean age (66.3 vs 63.4 yrs), duration of AAFL (30.1 vs 24.5 hrs), previous AAFL (72.7% vs 69.8%), median CHADS2 score (1 vs 1), and mean initial heart rate (128.9 vs 126.0 bpm). The Drug-Shock and Shock only groups were similar for the primary outcome of conversion (100% vs 93%; absolute difference 7.0%, 95% CI -0.6;14.6; P = 0.25). The multivariable analyses confirmed the similarity of the two strategies (P = 0.19). In the Drug-Shock group 21.2% of patients converted with the infusion. There were no statistically significant differences for time to conversion (84.2 vs 97.6 minutes), total ED length of stay (9.4 vs 7.5 hours), disposition home (100% vs 95.3%), and stroke within 14 days (0 vs 0). Premature discontinuation of infusion (usually for transient hypotension) was more common in the Drug-Shock group (9.1% vs 0.0%) but there were no serious adverse events. Conclusion: Both the Drug-Shock and Shock Only strategies were highly effective and safe in allowing AAFL patients to go home in sinus rhythm. IV procainamide alone was effective in only one fifth of patients, much less than for acute AF.

Introduction: Cases of anaphylaxis in children are often not appropriately managed by caregivers. We aimed to develop and to test the effectiveness of an education tool to help pediatric patients and their families better understand anaphylaxis and its management and to improve current knowledge and treatment guidelines adherence. Methods: The GEAR (Guidelines and Educational programs based on an Anaphylaxis Registry) is an initiative that recruits children with food-induced anaphylaxis who have visited the ED at the Montreal Children's Hospital and at The Children's Clinic located in Montreal, Quebec. The patients and parents, together, were asked to complete six questions related to the triggers, recognition and management of anaphylaxis at the time of presentation to the allergy clinic. Participants were automatically shown a 5-minute animated video addressing the main knowledge gaps related to the causes and management of anaphylaxis. At the end of the video, participants were redirected to same 6 questions to respond again. To test long-term knowledge retention, the questionnaire will be presented again in one year's time. A paired t-test was used to compare the difference between the baseline score and the follow-up score based on percentage of correct answers of the questionnaire. Results: From June to November 2019, 95 pediatric patients with diagnosed food-induced anaphylaxis were recruited. The median patient age was 4.5 years (Interquartile Range (IQR): 1.6–7.4) and half were male (51.6%). The mean questionnaire baseline score was 0.77 (77.0%, standard deviation (sd): 0.16) and the mean questionnaire follow-up score was 0.83 (83.0%, sd: 0.17). There was a significant difference between the follow-up score and baseline score (difference: 0.06, 95% CI: 0.04, 0.09). There were no associations of baseline questionnaire scores and change in scores with age and sex. Conclusion: Our video teaching method was successful in educating patients and their families to better understand anaphylaxis. The next step is to acquire long-term follow up scored to determine retention of knowledge.

Introduction: CAEP recently developed the acute atrial fibrillation (AF) and flutter (AFL) [AAFF] Best Practices Checklist to promote optimal care and guidance on cardioversion and rapid discharge of patients with AAFF. We sought to assess the impact of implementing the Checklist into large Canadian EDs. Methods: We conducted a pragmatic stepped-wedge cluster randomized trial in 11 large Canadian ED sites in five provinces, over 14 months. All hospitals started in the control period (usual care), and then crossed over to the intervention period in random sequence, one hospital per month. We enrolled consecutive, stable patients presenting with AAFF, where symptoms required ED management. Our intervention was informed by qualitative stakeholder interviews to identify perceived barriers and enablers for rapid discharge of AAFF patients. The many interventions included local champions, presentation of the Checklist to physicians in group sessions, an online training module, a smartphone app, and targeted audit and feedback. The primary outcome was length of stay in ED in minutes from time of arrival to time of disposition, and this was analyzed at the individual patient-level using linear mixed effects regression accounting for the stepped-wedge design. We estimated a sample size of 800 patients. Results: We enrolled 844 patients with none lost to follow-up. Those in the control (N = 316) and intervention periods (N = 528) were similar for all characteristics including mean age (61.2 vs 64.2 yrs), duration of AAFF (8.1 vs 7.7 hrs), AF (88.6% vs 82.9%), AFL (11.4% vs 17.1%), and mean initial heart rate (119.6 vs 119.9 bpm). Median lengths of stay for the control and intervention periods respectively were 413.0 vs. 354.0 minutes (P < 0.001). Comparing control to intervention, there was an increase in: use of antiarrhythmic drugs (37.4% vs 47.4%; P < 0.01), electrical cardioversion (45.1% vs 56.8%; P < 0.01), and discharge in sinus rhythm (75.3% vs. 86.7%; P < 0.001). There was a decrease in ED consultations to cardiology and medicine (49.7% vs 41.1%; P < 0.01), but a small but insignificant increase in anticoagulant prescriptions (39.6% vs 46.5%; P = 0.21). Conclusion: This multicenter implementation of the CAEP Best Practices Checklist led to a significant decrease in ED length of stay along with more ED cardioversions, fewer ED consultations, and more discharges in sinus rhythm. Widespread and rigorous adoption of the CAEP Checklist should lead to improved care of AAFF patients in all Canadian EDs.

Introduction: There are few large-scale studies assessing the true risk of epinephrine use during anaphylaxis in adults. We aimed to assess the demographics, clinical characteristics, and secondary effects of epinephrine treatment and to determine factors associated with major and minor secondary effects associated with epinephrine use among adults with anaphylaxis. Methods: From May 2012 to February 2018, adults presenting to the Hôpital du Sacré-Coeur de Montréal (HSCM) emergency department (ED) with anaphylaxis were recruited prospectively as part of the Cross-Canada Anaphylaxis Registry (C-CARE). Missed cases were identified through a previously validated algorithm. Data were collected on demographics, clinical characteristics, and management of anaphylaxis using a structured chart review. Multivariate logistic regression models were compared to estimate factors associated with side effects of epinephrine administration. Results: Over a 6-year period, 402 adult patients presented to the ED at HSCM with anaphylaxis. The median age was 38 years (Interquartile Range [IQR]: 27, 52) and 40.4% were males. The main trigger for anaphylaxis was food (53.0%). A total of 286 patients (71.1%) received epinephrine treatment, of which 23.9% were treated in the pre-hospital setting, 47.0% received treatment in the ED, and 5.0% received epinephrine in both settings. Among patients treated with epinephrine, major secondary effects were rare (1.4% of patients), including new changes to electrocardiogram, arrhythmia, and neurological symptoms. Minor secondary effects due to epinephrine were reported in 50.0% of patients, mainly inappropriate sinus tachycardia (defined as a rate over 100 beats/minute in 30.1%). Major cardiovascular secondary effects were associated with regular use of beta-blockers (aOR 1.10 [95%CI, 1.02, 1.18]), regular use of ACE-inhibitors (aOR 1.16 [95%CI, 1.07, 1.27]), and receiving more than two doses of epinephrine (aOR 1.09 [95%CI, 1.00, 1.18]). The model was adjusted for age, history of ischemic heart disease, trigger of anaphylaxis, presence of asthma, sex, and reaction severity. Inappropriate sinus tachycardia was more likely in females (aOR 1.18 [95%CI, 1.04, 1.33]) and palpitations, tremors, and psychomotor agitation were more likely in females (aOR 1.09 [95%CI, 1.00, 1.19]) and among those receiving more than two doses of epinephrine (aOR 1.49 [95%CI, 1.14, 1.96]). The models were adjusted for age, regular use of medications, history of ischemic heart disease, triggers of anaphylaxis, presence of asthma, reaction severity, and IV administration of epinephrine. Conclusion: The low rate of occurrence of major secondary effects of epinephrine in the treatment of anaphylaxis in our study demonstrates the overall safety of epinephrine use.

Introduction: Malgré les progrès au niveau des soins de réanimation lors des dernières années, le pronostic des patients souffrant d'un arrêt cardiorespiratoire (ACR) demeure abyssal et aucun médicament ne semble influencer leur devenir au long cours. Cependant, les résultats de quelques études évaluant l'impact des bêtabloqueurs chez cette population s'avèrent cependant très encourageants. L'objectif de cette revue systématique, est d’évaluer l’évidence disponible quant à l'impact des bêtabloqueurs sur le devenir des patients traités pour un ACR dont le rythme initial est défibrillable. Methods: La présente revue systématique a été préalablement enregistrée sur Prospero (CRD42018105453). Les moteurs de recherche Medline, Embase et CENTRAL ont été fouillés de leur création jusqu'au 17 octobre 2018. La recherche de littérature grise s'est faite via Web of Science et Google Scholar. Les références de tous les articles inclus ainsi que des méta-analyses existantes sur le sujet ont également été révisées. Tous les types de devis ont été considérés, sauf les études de cas et les séries de cas. Les études devaient inclure des adultes (16 ans et plus) en ACR dont le rythme initial était défibrillable, dont une partie avait reçu un médicament bêtabloquants par voie intraveineuse pendant leur ACR et l'autre un traitement standard, et présenter une mesure de résultat centrée sur le patient (retour de circulation spontanée [RCS], survie ou bon devenir neurologique). La qualité des articles a été évaluée à l'aide du ‘Newcastle Ottawa scale’. Results: Deux études observationnelles rétrospectives, menées auprès d'un total de 66 patients, ont été incluses. Il y avait une association positive entre l'administration de bêtabloquants et l'occurrence d'un RCS (rapport de cotes [RC] = 5.76 [intervalle de confiance {IC} à 95% = 1.79-18.52], p = 0.003), ainsi qu'avec la présence d'un bon devenir neurologique (RC = 4.42 [IC95% = 1.05 - 18.56], p = 0.04). Une telle association n'a cependant pas été observée par rapport à la survie au congé hospitalier. Conclusion: L'administration de bêtabloquants semble associé à un meilleur devenir chez les patients en ACR avec un rythme initial défibrillable. Étant donné la nature du devis de ces études et leur petite taille, une étude prospective de qualité serait nécessaire afin de déterminer l'efficacité de cette classe de médicament et de faire une recommandation forte à ce sujet.

Dystrobrevin binding protein 1 (DTNBP1), or dysbindin, is thought to be critical in regulating the glutamatergic system. While the dopamine pathway is known to be important in the aetiology of schizophrenia, it seems likely that glutamatergic dysfunction can lead to the development of schizophrenia. DTNBP1 is widely expressed in brain, levels are reduced in brains of schizophrenia patients and a DTNBP1 polymorphism has been associated with reduced brain expression. Despite numerous genetic studies no DTNBP1 polymorphism has been strongly implicated in schizophrenia aetiology. Using a haplotype block-based gene-tagging approach we genotyped 13 SNPs in DTNBP1 to investigate possible associations with DTNBP1 and schizophrenia. Four polymorphisms were found to be significantly associated with schizophrenia. The strongest association was found with an A/C SNP in intron 7 (rs9370822). Homozygotes for the C allele of rs9370822 were more than two and a half times as likely to have schizophrenia compared to controls. The other polymorphisms showed much weaker association and are less likely to be biologically significant. These results suggest that DTNBP1 is a good candidate for schizophrenia risk and rs9370822 is either functionally important or in disequilibrium with a functional SNP, although our observations should be viewed with caution until they are independently replicated.