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Patients admitted via interhospital transfer (IHT) experience increased risk-adjusted mortality, adverse events, length of stay, and discharge to facility; however, the etiology is not well understood. We hypothesize that IHTs are more likely to experience in-hospital delirium as compared with admissions to the hospital via the emergency department (ED) and clinic. This is a cross-sectional study of all adult admissions to medical, surgical, neurological, and obstetrics and gynecology services at an academic medical center who were screened for delirium between August 2018 and January 2020. Unit of analysis was admission source (IHT vs ED vs clinic) as the independent variable and the primary outcome was in-hospital delirium, assessed with initial brief confusion assessment method (bCAM) screening. 30,100 hospitalizations were included in this study with 3925 admissions (13.0%) screening positive for delirium at the initial bCAM assessment. The prevalence of delirium was much higher in IHTs at 22.3% (1334/5971) when compared with clinic at 5.8% (244/4214) and ED at 11.8% (2347/19,915) admissions. Multivariable logistic regression adjusting for demographics and comorbidities showed that IHT admissions had higher odds (OR 1.91, 95% CI 1.74 to 2.10) and clinic admissions had lower odds (OR 0.56, 95% CI 0.48 to 0.64) of in-hospital delirium compared with ED admissions. Increased odds of delirium in IHT admissions may contribute to the observed increased length of stay, discharge to facility, and mortality. These results emphasize the importance of routine screening and possible intervention prior to patient transfer.

Dyspnea is a common presenting complaint seen by hospitalists. The differential is broad, including life-threatening and less urgent etiologies. We report a 43-year-old male presenting to an inpatient medicine service with dyspnea in the setting of asthma, tobacco and occupational exposures, and no prior cardiac history. Use of point-of-care ultrasound (POCUS) immediately confirmed diagnosis of acute decompensated heart failure, allowing prompt decision making and care. Use of POCUS is widespread among emergency physicians and intensivists; however, use among medical students, internal medicine residents, and hospitalists remains variable. Increased use of POCUS by hospitalists may increase speed and accuracy of diagnosis., Competing Interests: Please check the following as appropriate: All authors have participated in (a) conception and design, or analysis and interpretation of the data; (b) drafting the article or revising it critically for important intellectual content; and (c) approval of the final version. This manuscript has not been submitted to, nor is under review at, another journal or other publishing venue. The authors have no affiliation with any organization with a direct or indirect financial interest in the subject matter discussed in the manuscript. The following authors have affiliations with organizations with direct or indirect financial interest in the subject matter discussed in the manuscript:, (© 2022 The Authors.)

Background: Treating hyperglycaemia and obesity in individuals with type 2 diabetes using multi-receptor agonists can improve short-term and long-term outcomes. LY3437943 is a single peptide with agonist activity for glucagon, glucose-dependent insulinotropic polypeptide (GIP), and glucagon-like peptide 1 (GLP-1) receptors that is currently in development for the treatment of type 2 diabetes and for the treatment of obesity and associated comorbidities. We investigated the safety, pharmacokinetics, and pharmacodynamics of multiple weekly doses of LY3437943 in people with type 2 diabetes in a 12-week study., Methods: In this phase 1b, proof-of-concept, double-blind, placebo-controlled, randomised, multiple-ascending dose trial, adults (aged 20-70 years) with type 2 diabetes for at least 3 months, a glycated haemoglobin A 1c (HbA 1c ) value of 7·0-10·5%, body-mass index of 23-50 kg/m 2 , and stable bodyweight (<5% change in previous 3 months) were recruited at four centres in the USA. Using an interactive web-response system, participants were randomly assigned to receive once-weekly subcutaneous injections of LY3437943, placebo, or dulaglutide 1·5 mg over a 12-week period. Five ascending dose cohorts were studied, with randomisation in each cohort such that a minimum of nine participants received LY3437943, three received placebo, and one received dulaglutide 1·5 mg within each cohort. The top doses in the two highest dose cohorts were attained via stepwise dose escalations. The primary outcome was to investigate the safety and tolerability of LY3437943, and characterising the pharmacodynamics and pharmacokinetics were secondary outcomes. Safety was analysed in all participants who received at least one dose of study drug, and pharmacodynamics and pharmacokinetics in all participants who received at least one dose of study drug and had evaluable data. This trial is registered at ClinicalTrials.gov, NCT04143802., Findings: Between Dec 18, 2019, and Dec 28, 2020, 210 people were screened, of whom 72 were enrolled, received at least one dose of study drug, and were included in safety analyses. 15 participants had placebo, five had dulaglutide 1·5 mg and, for LY3437943, nine had 0·5 mg, nine had 1·5 mg, 11 had 3 mg, 11 had 3/6 mg, and 12 had 3/6/9/12 mg. 29 participants discontinued the study prematurely. Treatment-emergent adverse events were reported by 33 (63%), three (60%), and eight (54%) participants who received LY3437943, dulaglutide 1·5 mg, and placebo, respectively, with gastrointestinal disorders being the most frequently reported treatment-emergent adverse events. The pharmacokinetics of LY3437943 were dose proportional and its half-life was approximately 6 days. At week 12, placebo-adjusted mean daily plasma glucose significantly decreased from baseline at the three highest dose LY3437943 groups (least-squares mean difference -2·8 mmol/L [90% CI -4·63 to -0·94] for 3 mg; -3·1 mmol/L [-4·91 to -1·22] for 3/6 mg; and -2·9 mmol/L [-4·70 to -1·01] for 3/6/9/12 mg). Placebo-adjusted sHbA 1c also decreased significantly in the three highest dose groups (-1·4% [90% CI -2·17 to -0·56] for 3 mg; -1·6% [-2·37 to -0·75] for 3/6 mg; and -1·2% [-2·05 to -0·45] for 3/6/9/12 mg). Placebo-adjusted bodyweight reduction with LY3437943 appeared to be dose dependent (up to -8·96 kg [90% CI -11·16 to -6·75] in the 3/6/9/12 mg group)., Interpretation: In this early phase study, LY3437943 showed an acceptable safety profile, and its pharmacokinetics suggest suitability for once-weekly dosing. This finding, together with the pharmacodynamic findings of robust reductions in glucose and bodyweight, provides support for phase 2 development., Funding: Eli Lilly and Company., Competing Interests: Declaration of interests SU, TC, MTL, YD, SG, AH, CTB, and ZM are employees and shareholders of Eli Lilly and Company. MKT is an employee and shareholder of Eli Lilly and Company, and reports being industry chair of a steering committee on Accelerating Medicines Partnership-Type 2 Diabetes, and a steering committee member on Accelerating Medicines Partnership-Common Metabolic Diseases. DAD reports research grants and advisory fees from Eli Lilly and Company; research grants from Merck; consulting fees from Intarcia and Sun Pharmaceuticals; and editorial fees from American Diabetes Association journals. MH-I is an employee of QPS and was the principal investigator of this study. We declare no other competing interests., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Nontyphoidal Salmonella (NTS) is a leading cause of acute gastrointestinal illness in Canada, and reported cases have been on the rise since the early 2000s. To address this trend, agri-food industry partners and government have worked to identify and implement interventions, guided by the enhanced information provided by whole-genome sequencing, to reduce the incidence of NTS. A substantial reduction in the number of NTS cases reported occurred in 2019. Due to underreporting and underdiagnosis factors, the observed decrease in the number of reported cases represents a fraction of the true number of illnesses averted in the community. The objective of this study was to: (1) use burden of illness estimation methodologies to estimate the true number of NTS illnesses, hospitalizations, and deaths prevented, and (2) estimate the economic savings associated with the prevention of these cases. Compared with the previous 5 years, there were an estimated 25,821 fewer illnesses, 213 fewer hospitalizations, and 2 fewer deaths attributable to NTS in 2019. This corresponds to an estimated reduction of 26.9 million Canadian dollars in the economic burden of NTS. Although causality cannot be proven by this study, the findings are suggestive that the strategically implemented suite of public health actions, including genomic-based surveillance, policy changes, and interventions by the government and industry, were successful in reducing the economic and health burden of NTS infections in Canada.

Chytrids are important drivers of aquatic ecosystems as phytoplankton parasites. The interaction between these parasites and their hosts are shaped by abiotic factors such as temperature and light. Here, we performed a full-factorial experiment to study how temperature and light interact to affect the dynamics of the bloom-forming toxic cyanobacterium Planktothrix rubescens and its chytrid parasite. We used a dynamic host-parasite model to explore how temperature and light affect long term dynamics. At low temperatures, chytrids do not survive. Higher light and temperature levels stimulated both phytoplankton and chytrid growth, with complex effects on their dynamics. Model exploration indicates that increasing temperature and light shifts equilibrium outcomes from P. rubescens persisting alone to stable coexistence and then to limit cycles. This provides an alternative biological explanation for why P. rubescens is mainly found in the relatively cold and dark lake metalimnion - it may enable avoidance of its parasite. Our study emphasizes the importance of investigating how abiotic factors interact with biotic interactions to drive complex outcomes., (© 2022. The Author(s).)

With an increasing prevalence of obesity, there is a need for new therapies to improve body weight management and metabolic health. Multireceptor agonists in development may provide approaches to fulfill this unmet medical need. LY3437943 is a novel triple agonist peptide at the glucagon receptor (GCGR), glucose-dependent insulinotropic polypeptide receptor (GIPR), and glucagon-like peptide-1 receptor (GLP-1R). In vitro, LY3437943 shows balanced GCGR and GLP-1R activity but more GIPR activity. In obese mice, administration of LY3437943 decreased body weight and improved glycemic control. Body weight loss was augmented by the addition of GCGR-mediated increases in energy expenditure to GIPR- and GLP-1R-driven calorie intake reduction. In a phase 1 single ascending dose study, LY3437943 showed a safety and tolerability profile similar to other incretins. Its pharmacokinetic profile supported once-weekly dosing, and a reduction in body weight persisted up to day 43 after a single dose. These findings warrant further clinical assessment of LY3437943., Competing Interests: Declaration of interests All authors are employees and stockholders of Eli Lilly and Company and have no other conflicts of interest to declare. C.L. is a former employee of Eli Lilly and Company., (Copyright © 2022 The Author(s). Published by Elsevier Inc. All rights reserved.)

Climate change is an existential threat, and our ability to conduct experiments on how organisms will respond to it is limited by logistics and resources, making it vital that experiments be maximally useful. The majority of experiments on phytoplankton responses to warming and CO 2 use only two levels of each driver. However, to project the characters of future populations, we need a mechanistic and generalisable explanation for how phytoplankton respond to concurrent changes in temperature and CO 2 . This requires experiments with more driver levels, to produce response surfaces that can aid in the development of predictive models. We recommend prioritising experiments or programmes that produce such response surfaces on multiple scales for phytoplankton., (Copyright © 2022 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: Tirzepatide, a dual glucose-dependent insulinotropic polypeptide (GIP)/GLP-1 receptor agonist, shows a remarkable ability to lower blood glucose, enabling many patients with long-standing type 2 diabetes to achieve normoglycaemia. We aimed to understand the physiological mechanisms underlying the action of tirzepatide in type 2 diabetes., Methods: This multicentre, randomised, double-blind, parallel-arm, phase 1 study was done at two centres in Germany. Eligible patients were aged 20-74 years, had type 2 diabetes for at least 6 months, and were being treated with lifestyle advice and stable doses of metformin, with or without one additional stable dose of another oral antihyperglycaemic medicine, 3 months before study entry. Via a randomisation table, patients were randomly assigned (3:3:2) to subcutaneously receive either tirzepatide 15 mg, semaglutide 1 mg, or placebo once per week. Endpoint measurements were done at baseline and the last week of therapy (week 28). The primary endpoint was the effect of tirzepatide versus placebo on the change in clamp disposition index (combining measures of insulin secretion and sensitivity) from baseline to week 28 of treatment and was analysed in the pharmacodynamic analysis set, which comprised all randomly assigned participants who received at least one dose of a study drug and had evaluable pharmacodynamic data. Safety was analysed in the safety population, which comprised all randomly assigned participants who received at least one dose of a study drug. Secondary endpoints included the effect of tirzepatide versus semaglutide on the change in clamp disposition index from baseline to week 28 of treatment, glucose control, total insulin secretion rate, M value (insulin sensitivity), and fasting and postprandial glucagon concentrations. Exploratory endpoints included the change in fasting and postprandial insulin concentrations. This study is registered with ClinicalTrials.gov, NCT03951753, and is complete., Findings: Between June 28, 2019, and April 8, 2021, we screened 184 individuals and enrolled 117 participants, all of whom were included in the safety population (45 in the tirzepatide 15 mg group, 44 in the semaglutide 1 mg group, and 28 in the placebo group). Because of discontinuations and exclusions due to missing or unevaluable data, 39 patients in each treatment group and 24 patients in the placebo group comprised the pharmacodynamic analysis set. With tirzepatide, the clamp disposition index increased from a least squares mean of 0·3 pmol m -2 L min -2 kg -1 (SE 0·03) at baseline by 1·9 pmol m -2 L min -2 kg -1 (0·16) to total 2·3 pmol m -2 L min -2 kg -1 (SE 0·16) at week 28 and, with placebo, the clamp disposition index did not change much from baseline (least squares mean at baseline 0·4 pmol m -2 L min -2 kg -1 [SE 0·04]; change from baseline 0·0 pmol m -2 L min -2 kg -1 [0·03]; least squares mean at week 28 0·3 [SE 0·03]; estimated treatment difference [ETD] tirzepatide vs placebo 1·92 [95% CI 1·59-2·24]; p<0·0001). The improvement with tirzepatide in clamp disposition index was significantly greater than with semaglutide (ETD 0·84 pmol m -2 L min -2 kg -1 [95% CI 0·46-1·21]). This result reflected significant improvements in total insulin secretion rate (ETD 102·09 pmol min -1 m -2 [51·84-152·33]) and insulin sensitivity (ETD 1·52 mg min -1 kg -1 [0·53-2·52]) for tirzepatide versus semaglutide. On meal tolerance testing, tirzepatide significantly reduced glucose excursions (lower insulin and glucagon concentrations) compared with placebo, with effects on these variables being greater than with semaglutide. The safety profiles of tirzepatide and semaglutide were similar, with gastrointestinal adverse events being the most common (11 [24%], 13 [30%], and seven [25%] with nausea; nine [20%], 13 [30%], and six [21%] with diarrhoea; and three [7%], five [11%], and one [4%] with vomiting, for tirzepatide, semaglutide, and placebo, respectively). There were no deaths., Interpretation: The glycaemic efficacy of GIP/GLP-1 receptor agonist tirzepatide in type 2 diabetes results from concurrent improvements in key components of diabetes pathophysiology, namely β-cell function, insulin sensitivity, and glucagon secretion. These effects were large and help to explain the remarkable glucose-lowering ability of tirzepatide seen in phase 3 studies., Funding: Eli Lilly., Competing Interests: Declaration of interests TH is shareholder of the private research institute Profil, which received research funds from Adocia, Afon Technology, AstraZeneca, Biocon, Boehringer Ingelheim, Eli Lilly, Gan Lee Pharmaceuticals, Johnson & Johnson, Julphar, Mylan, Nestlé, Neuraly, Nordic Bioscience, Novo Nordisk, Sanofi, and Zealand Pharma; has received speaker honoraria and travel grants from Eli Lilly and Novo Nordisk; and is a member of advisory panels for Novo Nordisk and Valbiotis. AM has received financial support from Eli Lilly and is a consultant for Eli Lilly. JHD was on advisory boards for Adocia, Novo Nordisk, and Zealand, and is now at the European Medicines Agency, where he will not be involved in matters relating to tirzepatide; the clinical studies presented here preceded his secondment to the European Medicines Agency. SU, JL, EJP, TC, MKT, KJM, AH, and ZM, are employees and shareholders of Eli Lilly., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Purpose: To examine outcomes of eyes with neovascular age-related macular degeneration that were switched to brolucizumab because of an unsatisfactory response to bevacizumab, ranibizumab, and/or aflibercept and then switched back because of the presence or risk of intraocular inflammation., Methods: Retrospective case series of 51 eyes. Visual acuity and retinal anatomy on optical coherence tomography were recorded at the first brolucizumab injection (T1), the final brolucizumab injection (T2), and 6 months following the final brolucizumab injection (T3)., Results: At T2, 41 eyes (41/51%, 80%) had decreased subretinal fluid (31 eyes), intraretinal fluid (12 eyes), or pigment epithelial detachment height (12 eyes). At T3, decreased subretinal fluid was sustained in 17 eyes (17/31%, 55%), decreased intraretinal fluid was sustained in eight eyes (8/12%, 67%), and decreased pigment epithelial detachment height was sustained in eight eyes (8/12%, 67%). Mean logarithm of the minimum angle of resolution visual acuity at T1, T2, and T3 was 0.396 (∼20/50), 0.441 (∼20/55), and 0.468 (∼20/59), respectively. During the brolucizumab treatment period, 11 eyes (11/51%, 22%) developed intraocular inflammation, including one case of retinal vasculitis., Conclusion: Interim treatment with brolucizumab resulted in anatomical improvements in 41 eyes (41/51%, 80%) that were maintained in 22 of these eyes (22/41%, 54%) for at least 6 months after switching back to the original anti-vascular endothelial growth factor therapeutic. There were no corresponding significant changes in visual acuity.

Although well documented, constrictive pericarditis is a rare entity and an uncommon cause of heart failure. A stiff and noncompliant pericardium creates the disease's unique hemodynamics and leads to elevated venous pressures, hepatic sinusoidal congestion, and draining of protein-rich fluid into the peritoneal cavity presenting as ascites. The low incidence in addition to its varied and subtle clinical presentations can often lead to a delay in diagnosis. Here, we present 2 clinical cases of constrictive pericarditis in which ascitic fluid analysis was important-one patient who presented with new-onset ascites with concern for cirrhosis and another patient who presented with symptoms concerning for heart failure with ascites. Through their hospital course and workup, we highlight the importance of diagnostic sampling of ascitic fluid to prompt the consideration of constrictive pericarditis followed by utilizing advanced diagnostics, such as echocardiogram and cardiac catheterization to reach the correct diagnosis in an otherwise often overlooked pathology.

Abstract: Many foods have the potential to cause foodborne illness; however, some pose a higher risk. Data were collected through the Foodbook study, a population-based telephone survey conducted between 2014 and 2015 that assessed 10,942 Canadians' food exposures using a 7-day recall period. The 19 foods included in the survey were identified as high risk for common foodborne pathogens in Canada. Results were analyzed by age group, gender, region of residence, income, and education. Consumption proportions of high-risk foods ranged from 0.4% (raw oysters) to 49.3% (deli meats). Roughly 94% of the population reported consuming one or more high-risk food in the past week. Certain high-risk food behaviors were associated with demographic characteristics. High-risk adults such as those 65 years or older still report consuming high-risk foods of concern, including deli meats (41.8%), soft cheeses (13.7%), and smoked fish (6.3%). Consumption of certain foods differed between genders, with males consuming significantly more deli meats, hot dogs, and raw or undercooked eggs and females consuming significantly more prebagged mixed salad greens. The overall number of high-risk foods consumed was similar, with both genders most frequently consuming three to five high-risk foods. High-risk food consumption was seen to increase with increasing household income, with 14.2% of the highest income level consuming six-plus high-risk foods in the past week, compared with 7.1% of the lowest income level. If a respondent had heard of a risk of foodborne illness associated with a food, it did not affect whether it was consumed. Additional consumer food safety efforts put in place alongside current messaging may improve high-risk food consumption behaviors. Enhancing current messaging by using multifaceted communications (e.g., social media and information pamphlets) and highlighting the large incidence and severity of foodborne illnesses in Canada are important strategies to improve behavior change., (Published 2021 by the International Association for Food Protection Copyright ©, Her Majesty the Queen in Right of Canada, as represented by the Public Health Agency of Canada.)

Background: Greater visceral fat area (VFA) is associated with cardiometabolic outcomes. We sought to identify cross-sectional and longitudinal associations between amino acid (AA) levels and VFA in Japanese-Americans., Methods: From the cohort of 342 Japanese-American participants (51% men) in a study of diabetes risk factors who were free from diabetes, we measured levels of 20 AA by mass spectrometry, height, weight, waist circumference (WC), VFA, subcutaneous fat area by single-slice CT at the umbilicus. Using AA significantly associated with VFA in univariate analyses, we created a VFA prediction index, termed the 4A index. We compared area under receiver-operating characteristic curve (AUROC) of the 4A index to WC and an existing AA index (Yamakado et al. Clin Obes 2012) in classifying VFA at different cutoff values. We fit age-adjusted linear regression models to evaluate associations between AA levels and change in VFA over 5 years., Results: All 20 AA levels significantly detected VFA excess, but WC was better. The 4A index performed better than Yamakado index at classifying VFA ≥ 100 cm 2 (0.798, 0.807 vs. 0.677, 0.671 for men and women, p < 0.0033) and VFA ≥ sex-specific median values (0.797, 0.786 vs. 0.676, 0.629 for men and women, p < 0.0017). AA significantly associated with change in VFA over 5 years were asparagine, glutamate, glutamine, glycine, methionine, proline, threonine in men; and histidine, isoleucine, tyrosine in women (p < 0.05)., Conclusions: The 4A index can serve as a biomarker for VFA in Japanese-Americans and be considered for this purpose when WC is not available., (Copyright © 2021 Asia Oceania Association for the Study of Obesity. All rights reserved.)

The mycobacteriophages JeTaime (E cluster) and Luna22 (Q cluster) were isolated from soil in Providence, Rhode Island, and Charleston, South Carolina, respectively, using a Mycobacterium smegmatis mc 2 155 host. The genome of JeTaime is 75,099 bp (142 predicted genes), and that of Luna22 is 53,730 bp (87 predicted genes). Both phages exhibit Siphoviridae morphology.

Context: Novel dual glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) receptor agonist (RA) tirzepatide demonstrated substantially greater glucose control and weight loss (WL) compared with selective GLP-1RA dulaglutide., Objective: Explore mechanisms of glucose control by tirzepatide., Design: Post hoc analyses of fasting biomarkers and multiple linear regression analysis., Setting: Forty-seven sites in 4 countries., Patients or Other Participants: Three hundred and sixteen subjects with type 2 diabetes., Interventions: Tirzepatide (1, 5, 10, 15 mg), dulaglutide (1.5 mg), placebo., Main Outcome Measures: Analyze biomarkers of beta-cell function and insulin resistance (IR) and evaluate WL contributions to IR improvements at 26 weeks., Results: Homeostatic model assessment (HOMA) 2-B significantly increased with dulaglutide and tirzepatide 5, 10, and 15 mg compared with placebo (P ≤ .02). Proinsulin/insulin and proinsulin/C-peptide ratios significantly decreased with tirzepatide 10 and 15 mg compared with placebo and dulaglutide (P ≤ .007). Tirzepatide 10 and 15 mg significantly decreased fasting insulin (P ≤ .033) and tirzepatide 10 mg significantly decreased HOMA2-IR (P = .004) compared with placebo and dulaglutide. Markers of improved insulin sensitivity (IS) adiponectin, IGFBP-1, and IGFBP-2 significantly increased by 1 or more doses of tirzepatide (P < .05). To determine whether improvements in IR were directly attributable to WL, multiple linear regression analysis with potential confounding variables age, sex, metformin, triglycerides, and glycated hemoglobin A1c was conducted. WL significantly (P ≤ .028) explained only 13% and 21% of improvement in HOMA2-IR with tirzepatide 10 and 15 mg, respectively., Conclusions: Tirzepatide improved markers of IS and beta-cell function to a greater extent than dulaglutide. IS effects of tirzepatide were only partly attributable to WL, suggesting dual receptor agonism confers distinct mechanisms of glycemic control., (© The Author(s) 2020. Published by Oxford University Press on behalf of the Endocrine Society.)

Purpose of Review: Food insecurity (FI) is a serious public health issue affecting 2 billion people worldwide. FI is associated with increased risk for multiple chronic diseases, including obesity, type 2 diabetes, cardiovascular disease, and mental health. We selected these four chronic diseases given their global prevalence and comorbid associations with each other. We evaluated the most recent literature published over the past 5 years and offer strategies for the screening of FI., Recent Findings: Recent systematic reviews and meta-analyses report an association between FI and obesity in adult women as well as adult men and women living in low- and middle-income countries. Gender differences also were observed between FI and type 2 diabetes, such that adult women showed an increased risk for type 2 diabetes. This association was influenced by social determinants of health. Very low food security (i.e., high FI) was associated with increased risk for cardiovascular disease and a higher risk for cardiovascular disease mortality. Finally, several studies showed an association between FI and adverse mental health outcomes, including increased risk for stress, depression, anxiety, sleep disorders, and suicidal ideation., Summary: FI and its negative association with body weight, type 2 diabetes, cardiovascular disease, and mental health provide a compelling rationale for identification of FI in clinical settings. Brief, well-validated screening measures are available in multiple languages. Despite the need for FI screening, many guidelines do not address its implementation. For this reason, more research and targeted interventions are needed to increase FI screening rates and close the loop in the coordination of resources., Competing Interests: Conflict of InterestThe authors declare no competing interests., (© The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature 2021.)

Gleaners and exploiters (opportunists) are organisms adapted to feeding in nutritionally poor and rich environments, respectively. A trade-off between these two strategies-a negative relationship between the rate at which organisms can acquire food and ingest it-is a critical assumption in many ecological models. Here, we evaluate evidence for this trade-off across a wide range of heterotrophic eukaryotes from unicellular nanoflagellates to large mammals belonging to both aquatic and terrestrial realms. Using data on the resource acquisition and ingestion rates in >500 species, we find no evidence of a trade-off across species. Instead, there is a positive relationship between maximum clearance rate and maximum ingestion rate. The positive relationship is not a result of lumping together diverse taxa; it holds within all subgroups of organisms we examined as well. Correcting for differences in body mass weakens but does not reverse the positive relationship, so this is not an artifact of size scaling either. Instead, this positive relationship represents a slow-fast gradient in the "pace of life" that overrides the expected gleaner-exploiter trade-off. Other trade-offs must therefore shape ecological processes, and investigating them may provide deeper insights into coexistence, competitive dynamics, and biodiversity patterns in nature. A plausible target for study is the well-documented trade-off between growth rate and predation avoidance, which can also drive the slow-fast gradient we observe here., Competing Interests: The authors declare no competing interest.

Competition for limiting resources is among the most fundamental ecological interactions and has long been considered a key driver of species coexistence and biodiversity. Species' minimum resource requirements, their R *s, are key traits that link individual physiological demands to the outcome of competition. However, a major question remains unanswered-to what extent are species' competitive traits able to evolve in response to resource limitation? To address this knowledge gap, we performed an evolution experiment in which we exposed Chlamydomonas reinhardtii for approximately 285 generations to seven environments in chemostats that differed in resource supply ratios (including nitrogen, phosphorus and light limitation) and salt stress. We then grew the ancestors and descendants in a common garden and quantified their competitive abilities for essential resources. We investigated constraints on trait evolution by testing whether changes in resource requirements for different resources were correlated. Competitive abilities for phosphorus improved in all populations, while competitive abilities for nitrogen and light increased in some populations and decreased in others. In contrast to the common assumption that there are trade-offs between competitive abilities for different resources, we found that improvements in competitive ability for a resource came at no detectable cost. Instead, improvements in competitive ability for multiple resources were either positively correlated or not significantly correlated. Using resource competition theory, we then demonstrated that rapid adaptation in competitive traits altered the predicted outcomes of competition. These results highlight the need to incorporate contemporary evolutionary change into predictions of competitive community dynamics over environmental gradients. This article is part of the theme issue 'Conceptual challenges in microbial community ecology'.

The discovery and optimization of a novel series of GPR142 agonists are described. These led to the identification of compound 21 (LY3325656), which demonstrated anti-diabetic benefits in pre-clinical studies and ADME/PK properties suitable for human dosing. Compound 21 is the first GPR142 agonist molecule advancing to phase 1 clinic trials for the treatment of Type 2 diabetes., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Background and Aims: Supraglottic airway devices have several roles including maintenance of a clear upper airway during general anesthesia. We primarily compared the efficacy of Baska mask (BM) and laryngeal mask airway supreme (LMAS) for the rate of first time successful placement and the seal pressure. The secondary outcome measures included laryngopharyngeal morbidity and the correct positioning of the gastric port., Material and Methods: A sample size of 30 was calculated in each study group. A total of 70 study participants were included in the statistical analysis of which 36 patients were in the BM group and 34 patients were in the LMAS group., Results: The BM was successfully inserted in 28 patients (77.8%), whereas LMAS was successfully inserted in 33 patients (97.1%) in the first attempt ( P = 0.028). The mean oropharyngeal seal pressure in the BM group was higher (33.28 ± 6.80 cm H 2 O) than compared to the LMAS group (27.47 ± 2.34 cm H 2 O) with a P value <0.001. There was no significant difference between the two groups in the incidence of postoperative laryngopharyngeal morbidity both in the immediate postoperative period ( P = 0.479) and that seen 24 hours post operatively ( P = 0.660). The nasogastric tube could easily be inserted in the entire study population., Conclusion: From the present study, it is concluded that the BM creates a higher oropharyngeal seal pressure than the LMAS. However, the BM is more difficult to insert. The incidence of postoperative laryngopharyngeal morbidity is similar in both groups., Competing Interests: There are no conflicts of interest., (Copyright: © 2020 Journal of Anaesthesiology Clinical Pharmacology.)

Background: Uncorrected maternal hypotension occurring during obstetric emergencies may result in maternal and fetal morbidity. Fluid status of the pregnant mother is a major variable which affects the maternal hemodynamics during patient management, and there is no objective assessment tool for the same. A relatively new sonographic parameter, the inferior vena cava aorta (IVC/Ao) diameter index or caval aortic index, showed promise in this regard, and its application was studied in obstetric patients., Methodology: A prospective analytical study was conducted involving 50 pregnant and 50 nonpregnant women of reproductive age group. Using both subxiphoid and transhepatic views, their normal fasting caval aortic indices were determined from the ratio of mean IVC diameter to the mean aortic diameter. Descriptive and inferential statistical analyses were carried out accordingly., Results: Normal IVC/Ao diameter index for nonpregnant healthy women of reproductive age was 1.11 ± 0.29 in the subxiphoid view and 1.21 ± 0.33 in the transhepatic view. The difference between the two views was not statistically significant. IVC/Ao diameter index for a normal term pregnant woman was 1.03 ± 0.26, and term pregnancy does not significantly cause variation in the index., Conclusions: Caval aortic index is a useful noninvasive tool to assess volume status and guide fluid management in pregnant women presenting to the emergency department, and the transhepatic view is comparable to the traditional subxiphoid view for the measurement of the same., Competing Interests: There are no conflicts of interest., (Copyright: © 2020 Journal of Emergencies, Trauma, and Shock.)

Purpose: To understand the relationship between baseline ischemic index (IsI) values on ultra-widefield fluorescein angiography and classification as ischemic central retinal vein occlusion (CRVO)., Methods: Single-center retrospective cohort study of CRVO patients imaged using ultra-widefield fluorescein angiography from which IsI values were calculated. An ischemic CRVO was defined as those eyes with an afferent pupillary defect and counting fingers acuity or worse or neovascularization during the first year of follow-up. Logistic regression was performed to characterize the relation between the IsI and clinical outcomes., Results: Sixty eyes of 60 treatment-naive CRVO patients with baseline ultra-widefield fluorescein angiography and ≥1 year of follow-up were identified. Those with an IsI ≥35% were significantly more likely to have an ischemic CRVO during the first year of follow-up than those with an IsI <35% (83.3 vs. 13.9%, odds ratio 111, P < 0.0001). Baseline and final logarithm of the minimum angle of resolution acuity were worse in eyes with an IsI ≥35% (1.18 vs. 0.46, P < 0.001 and 1.26 vs. 0.45, P < 0.001, respectively) despite similar baseline and final central subfield thickness (P = 0.1-0.23)., Conclusion: A baseline IsI of ≥35% on ultra-widefield fluorescein angiography in eyes with treatment-naive CRVO was sensitive (90%) and specific (92.5%) for classification as an ischemic CRVO during the first year of follow-up.

Individual-level variation arising from responses to environmental gradients influences population and community dynamics. How such responses empirically relate to the mechanisms that govern species coexistence is, however, poorly understood. Previous results from l ake phytoplankton communities suggested that the evenness of organismal traits in multiple dimensions increases with resource limitation, possibly due to resource partitioning at the individual level. Here we experimentally tested the emergence of this pattern by growing two phytoplankton species (Pseudokirchneriella subcapitata and Microcystis aeruginosa) under a gradient of light intensity, in monoculture and jointly. Under low light (resource) conditions, the populations diversified into a wide range of phenotypes, which were evenly distributed in multidimensional trait space (defined by four pigment-related trait dimensions), consistent with the observed field pattern. Our interpretation is that under conditions of light limitation, individual phytoplankton cells alter photosynthetic traits to reduce overlap in light acquisition, acquiring unexploited resources and thereby likely maximising individual success. Our results provide prime experimental evidence that resource limitation increases the evenness of conspecific and heterospecific microbial phenotypes along trait axes, advancing our understanding of trait-based coexistence.

Investigations into an outbreak of foodborne disease attempt to identify the source of illness as quickly as possible. Population-based reference values for food consumption can assist in investigation by providing comparison data for hypothesis generation and also strengthening the evidence associated with a food product through hypothesis testing. In 2014-2015 a national phone survey was conducted in Canada to collect data on food consumption patterns using a 3- or 7-day recall period. The resulting food consumption values over the two recall periods were compared. The majority of food products did not show a significant difference in the consumption over 3 days and 7 days. However, comparison of reference values from the 3-day recall period to data from an investigation into a Salmonella Infantis outbreak was shown to support the conclusion that chicken was the source of the outbreak whereas the reference values from a 7-day recall did not support this finding. Reference values from multiple recall periods can assist in the hypothesis generation and hypothesis testing phase of foodborne outbreak investigations.

The mechanisms that restrict regeneration and maintain cell identity following injury are poorly characterized in higher vertebrates. Following β-cell loss, 1-2% of the glucagon-producing α-cells spontaneously engage in insulin production in mice. Here we explore the mechanisms inhibiting α-cell plasticity. We show that adaptive α-cell identity changes are constrained by intra-islet insulin- and Smoothened-mediated signalling, among others. The combination of β-cell loss or insulin-signalling inhibition, with Smoothened inactivation in α- or δ-cells, stimulates insulin production in more α-cells. These findings suggest that the removal of constitutive 'brake signals' is crucial to neutralize the refractoriness to adaptive cell-fate changes. It appears that the maintenance of cell identity is an active process mediated by repressive signals, which are released by neighbouring cells and curb an intrinsic trend of differentiated cells to change.

Animal companionship can have many physical and psychological benefits; however, animals can also be a source of zoonotic infection, including enteric illnesses; it has been estimated that in Canada, nearly 85,000 enteric illnesses due to eight pathogens occur each year related to animal contact. There is a lack of baseline data on animal-related exposures in Canada and around the world. This information is critical to inform quantitative and qualitative risk assessments to prioritize intervention efforts in public health and reduce the associated burden of enteric illness. To help address this issue and assist evaluation of the risks associated with animal contact, the Foodbook study, conducted in 2014-2015, assessed exposure to animals, animal food and animal-related venues within the last 7 days among Canadians. Data were analysed by province and territory, age group and urban/rural residency. Overall, dogs and cats were the most commonly reported animal exposures (43.3% and 31.9%, respectively). The data suggest farm animal exposure occurs primarily at a farm/barn, and to a lesser extent at other animal-related venues (e.g., petting zoos or agricultural fairs). Approximately one in 25 respondents handled raw pet food within the last 7 days; the majority of which had also been exposed to a dog (86.4%). Children aged 0-9 years reported relatively high exposure to four types of high-risk animals: rodents (5.6%), poultry (4.0%), reptiles (2.1%) and amphibians (1.8%); with the most vulnerable children aged <5 years also reporting exposure to many of these high-risk animals. These results highlight potential areas for targeted intervention that can focus on high-risk populations (e.g., young children) exhibiting potentially risky behaviour such as being exposed to certain high-risk animals, or handling pet food, treats and raw pet food diets. Additionally, these results support the need to better understand the burden of enteric illness associated with animals and their environments., (© 2018 The Authors. Journal of Oral Rehabilitation Published by John Wiley & Sons Ltd.)

Background: Phosphatidylcholine and deoxycholate (PC-DC) injections have been used as nonsurgical alternatives to liposuction. DC as a constituent for lipolysis has recently been approved by the US Food and Drug Administration., Aim: PC and DC have independently been used in lipolysis. We hereby present a systematic review of literature on injection lipolysis and share our experience of using DC in combination with PC for injection lipolysis. We have retrospectively evaluated the effects of PC-DC treatments in varied age groups, both sexes, and over different target areas., Materials and Methods: This study spans over 14 years wherein 1269 patients of different age groups and sex were treated with injection lipolysis with PC-DC combination. The PC-DC cocktail injection was given to all patients for an average four sessions every 4 weeks, and the results were assessed after 8 weeks from the last session., Results: The effects were best appreciated over the face (malar, jawline, and submental areas) and upper arm, whereas average effect was observed on the thighs and around the knees. We have also used lipolysis as a primary modality as well as a touch-up modality following liposuction. The results are better appreciated in primary lipolysis. The need for follow-up sessions (1-2 sessions) of lipolysis and the quantification of results in subsequent sessions reveal that maximal improvement is achieved in the first session., Conclusion: PC-DC cocktail used for lipolysis as a local administration is effective for reducing unwanted fat. It shows great efficacy in treating localized fat, especially over the face and bra roll in the women of younger age group (20-30 years)., Competing Interests: There are no conflicts of interest.

Scanning flow cytometry (SFCM) is characterized by the measurement of time-resolved pulses of fluorescence and scattering, enabling the high-throughput quantification of phytoplankton morphology and pigmentation. Quantifying variation at the single cell and colony level improves our ability to understand dynamics in natural communities. Automated high-frequency monitoring of these communities is presently limited by the absence of repeatable, rapid protocols to analyse SFCM datasets, where images of individual particles are not available. Here we demonstrate a repeatable, semi-automated method to (1) rapidly clean SFCM data from a phytoplankton community by removing signals that do not belong to live phytoplankton cells, (2) classify individual cells into trait clusters that correspond to functional groups, and (3) quantify the biovolumes of individual cells, the total biovolume of the whole community and the total biovolumes of the major functional groups. Our method involves the development of training datasets using lab cultures, the use of an unsupervised clustering algorithm to identify trait clusters, and machine learning tools (random forests) to (1) evaluate variable importance, (2) classify data points, and (3) estimate biovolumes of individual cells. We provide example datasets and R code for our analytical approach that can be adapted for analysis of datasets from other flow cytometers or scanning flow cytometers.

Recent studies have reported significant advances in the differentiation of human pluripotent stem cells to clinically relevant cell types such as the insulin producing beta-like cells and motor neurons. However, many of the current differentiation protocols lead to heterogeneous cell cultures containing cell types other than the targeted cell fate. Genetically modified human pluripotent stem cells reporting the expression of specific genes are of great value for differentiation protocol optimization and for the purification of relevant cell populations from heterogeneous cell cultures. Here we present the generation of human induced pluripotent stem cell (iPSC) lines with a GFP reporter inserted in the endogenous NKX6.1 locus. Characterization of the reporter lines demonstrated faithful GFP labelling of NKX6.1 expression during pancreas and motor neuron differentiation. Cell sorting and gene expression profiling by RNA sequencing revealed that NKX6.1-positive cells from pancreatic differentiations closely resemble human beta cells. Furthermore, functional characterization of the isolated cells demonstrated that glucose-stimulated insulin secretion is mainly confined to the NKX6.1-positive cells. We expect that the NKX6.1-GFP iPSC lines and the results presented here will contribute to the further refinement of differentiation protocols and characterization of hPSC-derived beta cells and motor neurons for disease modelling and cell replacement therapies., (Copyright © 2018 The Authors. Published by Elsevier B.V. All rights reserved.)

Forecasting changes to ecological communities is one of the central challenges in ecology. However, nonlinear dependencies, biotic interactions and data limitations have limited our ability to assess how predictable communities are. Here, we used a machine learning approach and environmental monitoring data (biological, physical and chemical) to assess the predictability of phytoplankton cell density in one lake across an unprecedented range of time-scales. Communities were highly predictable over hours to months: model R 2 decreased from 0.89 at 4 hours to 0.74 at 1 month, and in a long-term dataset lacking fine spatial resolution, from 0.46 at 1 month to 0.32 at 10 years. When cyanobacterial and eukaryotic algal cell densities were examined separately, model-inferred environmental growth dependencies matched laboratory studies, and suggested novel trade-offs governing their competition. High-frequency monitoring and machine learning can set prediction targets for process-based models and help elucidate the mechanisms underlying ecological dynamics., (© 2018 John Wiley & Sons Ltd/CNRS.)

Objective: GPR142 agonists are being pursued as novel diabetes therapies by virtue of their insulin secretagogue effects. But it is undetermined whether GPR142's functions in pancreatic islets are limited to regulating insulin secretion. The current study expands research on its action., Methods and Results: We demonstrated by in situ hybridization and immunostaining that GPR142 is expressed not only in β cells but also in a subset of α cells. Stimulation of GPR142 by a selective agonist increased glucagon secretion in both human and mouse islets. More importantly, the GPR142 agonist also potentiated glucagon-like peptide-1 (GLP-1) production and its release from islets through a mechanism that involves upregulation of prohormone convertase 1/3 expression. Strikingly, stimulation of insulin secretion and increase in insulin content via GPR142 engagement requires intact GLP-1 receptor signaling. Furthermore, GPR142 agonist increased β cell proliferation and protected both mouse and human islets against stress-induced apoptosis., Conclusions: Collectively, we provide here evidence that local GLP-1 release from α cells defines GPR142's beneficial effects on improving β cell function and mass, and we propose that GPR142 agonism may have translatable and durable efficacy for the treatment of type 2 diabetes., (Copyright © 2018 The Authors. Published by Elsevier GmbH.. All rights reserved.)

Objective: The rs7903146 T allele in transcription factor 7 like 2 ( TCF7L2 ) is strongly associated with type 2 diabetes (T2D), but the mechanisms for increased risk remain unclear. We evaluated the physiologic and hormonal effects of TCF7L2 genotype before and after interventions that influence glucose physiology., Research Design and Methods: We genotyped rs7903146 in 608 individuals without diabetes and recorded biochemical data before and after 1 ) one dose of glipizide (5 mg) on visit 1 and 2 ) a 75-g oral glucose tolerance test (OGTT) performed after administration of metformin 500 mg twice daily over 2 days. Incretin levels were measured in 150 of the 608 participants., Results: TT risk-allele homozygotes had 1.6 mg/dL higher baseline fasting glucose levels and 2.5 pg/mL lower glucagon levels per T allele than carriers of other genotypes at baseline. In a subset of participants, the T allele was associated with higher basal glucagon-like peptide 1 (GLP-1) levels at visit 1 (β = 1.52, P = 0.02 and β = 0.96, P = 0.002 for total and active GLP-1, respectively), and across all points of the OGTT after metformin administration. Regarding drug response, the T allele was associated with a shorter time (β = -7.00, P = 0.03) and a steeper slope (β = 0.23, P = 0.04) to trough glucose levels after glipizide administration, and lower visit 2 fasting glucose level adjusted for visit 1 fasting glucose level (β = -1.02, P = 0.04) and a greater decline in glucose level between visits (β = -1.61, P = 0.047) after metformin administration., Conclusions: Our findings demonstrate that common variation at TCF7L2 influences acute responses to both glipizide and metformin in people without diabetes and highlight altered incretin signaling as a potential mechanism by which TCF7L2 variation increases T2D risk., (© 2018 by the American Diabetes Association.)

Understanding how microbial diversity influences ecosystem properties is of paramount importance. Cellular traits-which determine responses to the abiotic and biotic environment-may help us rigorously link them. However, our capacity to measure traits in natural communities has thus far been limited. Here we compared the predictive power of trait richness (trait space coverage), evenness (regularity in trait distribution) and divergence (prevalence of extreme phenotypes) derived from individual-based measurements with two species-level metrics (taxonomic richness and evenness) when modelling the productivity of natural phytoplankton communities. Using phytoplankton data obtained from 28 lakes sampled at different spatial and temporal scales, we found that the diversity in individual-level morphophysiological traits strongly improved our ability to predict community resource-use and biomass yield. Trait evenness-the regularity in distribution of individual cells/colonies within the trait space-was the strongest predictor, exhibiting a robust negative relationship across scales. Our study suggests that quantifying individual microbial phenotypes in trait space may help us understand how to link physiology to ecosystem-scale processes. Elucidating the mechanisms scaling individual-level trait variation to microbial community dynamics could there improve our ability to forecast changes in ecosystem properties across environmental gradients.

Intramuscular triglyceride (IMTG) concentration is elevated in insulin-resistant individuals and was once thought to promote insulin resistance. However, endurance-trained athletes have equivalent concentration of IMTG compared with individuals with type 2 diabetes, and have very low risk of diabetes, termed the "athlete's paradox." We now know that IMTG synthesis is positively related to insulin sensitivity, but the exact mechanisms for this are unclear. To understand the relationship between IMTG synthesis and insulin sensitivity, we measured IMTG synthesis in obese control subjects, endurance-trained athletes, and individuals with type 2 diabetes during rest, exercise, and recovery. IMTG synthesis rates were positively related to insulin sensitivity, cytosolic accumulation of DAG, and decreased accumulation of C18:0 ceramide and glucosylceramide. Greater rates of IMTG synthesis in athletes were not explained by alterations in FFA concentration, DGAT1 mRNA expression, or protein content. IMTG synthesis during exercise in Ob and T2D indicate utilization as a fuel despite unchanged content, whereas IMTG concentration decreased during exercise in athletes. mRNA expression for genes involved in lipid desaturation and IMTG synthesis were increased after exercise and recovery. Further, in a subset of individuals, exercise decreased cytosolic and membrane di-saturated DAG content, which may help explain insulin sensitization after acute exercise. These data suggest IMTG synthesis rates may influence insulin sensitivity by altering intracellular lipid localization, and decreasing specific ceramide species that promote insulin resistance.

Enteric pathogens are commonly known to be transmitted through food or water; however, contact with animals is another important transmission route. This study estimated the annual burden of illness attributable to animal contact for eight enteric pathogens in Canada. Using data from a Canadian expert elicitation on transmission routes, the proportion of enteric illnesses attributable to animal contact was estimated for each pathogen to estimate the annual number of illnesses, hospitalizations and deaths in Canada. For each estimate, a mean and probability intervals were generated. Of all illnesses caused by these eight pathogens, 16% were estimated attributable to animal contact. This estimate translates to 86 000 (31 000-166 000) illnesses, 488 (186-890) hospitalizations and 12 (2-28) deaths annually for the eight pathogens combined. Campylobacter spp. is the leading cause of illnesses annually, with an estimated 38 000 (14 000-71 000) illnesses occurring each year, followed by non-typhoidal Salmonella spp. (17 000, 6000-32 000). The majority of hospitalizations were attributable to non-typhoidal Salmonella spp. (36%) and Campylobacter spp. (31%). Non-typhoidal Salmonella spp. (28%) and Listeria monocytogenes (31%) were responsible for the majority of the estimated deaths. These results identify farm animal and pet/pet food exposure as key pathways of transmission for several pathogens. The estimated burden of illness associated with animal contact is substantial.

Understanding consumers' food safety practices and knowledge supports food safety education for the prevention of foodborne illness. The objective of this study was to describe Canadian consumer food safety practices and knowledge. This study identifies demographic groups for targeted food safety education messaging and establishes a baseline measurement to assess the effectiveness of food safety interventions over time. Questions regarding consumer food safety practices and knowledge were included in a population-based telephone survey, Foodbook, conducted from November 2014 to March 2015. The results were analyzed nationally by age group and by gender. The results showed that approximately 90% of Canadians reported taking the recommended cleaning and separating precautions when handling raw meat to prevent foodborne illness. Only 29% of respondents reported using a food thermometer when cooking any meat, and even fewer (12%) reported using a food thermometer for small cuts of meat such as chicken pieces. The majority (>80%) of Canadians were aware of the foodborne illness risks related to chicken and hamburger, but fewer (<40%) were aware of the risks related to frozen chicken nuggets, alfalfa sprouts, soft unpasteurized cheese, and unpasteurized juices. Generally, men were less likely to follow cooking instructions on packaging and took fewer steps to prevent cross-contamination than women. The youngest (18 to 29 years) age group was less likely to take steps to avoid cross-contamination and was less aware of the risks associated with eating an undercooked hamburger. The oldest (60+ years) respondents were less likely to be aware of the risks associated with raw eggs, alfalfa sprouts, and unpasteurized juice than the middle (30 to 59 years) age group. As a priority, food safety education in Canada should focus on increasing people's awareness of high-risk foods, specifically foods for which the awareness of risk found in this study was low; targeting messaging to demographic groups as appropriate; and promoting the use of food thermometers when cooking meat and poultry.

Temperature and nutrients are fundamental, highly nonlinear drivers of biological processes, but we know little about how they interact to influence growth. This has hampered attempts to model population growth and competition in dynamic environments, which is critical in forecasting species distributions, as well as the diversity and productivity of communities. To address this, we propose a model of population growth that includes a new formulation of the temperature-nutrient interaction and test a novel prediction: that a species' optimum temperature for growth, T opt , is a saturating function of nutrient concentration. We find strong support for this prediction in experiments with a marine diatom, Thalassiosira pseudonana: T opt decreases by 3-6 °C at low nitrogen and phosphorus concentrations. This interaction implies that species are more vulnerable to hot, low-nutrient conditions than previous models accounted for. Consequently the interaction dramatically alters species' range limits in the ocean, projected based on current temperature and nitrate levels as well as those forecast for the future. Ranges are smaller not only than projections based on the individual variables, but also than those using a simpler model of temperature-nutrient interactions. Nutrient deprivation is therefore likely to exacerbate environmental warming's effects on communities., (© 2017 John Wiley & Sons Ltd.)

Chemical micropollutants occur worldwide in the environment at low concentrations and in complex mixtures, and how they affect the ecology of natural systems is still uncertain. Dynamics of natural communities are driven by the interaction between individual organisms and their growth environment, which is mediated by the organisms' expressed phenotypic traits. We tested whether exposure to a mixture of 12 pharmaceuticals and personal care products (PPCP) influences phenotypic trait diversity in lake phytoplankton communities and their ability to regulate biomass production to fit environmental changes (response capacity). We exposed natural phytoplankton assemblages to three mixture levels in permeable microcosms maintained at three depths in a eutrophic lake for one week, during which the environmental conditions were fluctuating. We studied individual-level traits, phenotypic diversity and community biomass. PPCP reduced individual-level trait variance and overall community phenotypic diversity, but maintained higher standing phytoplankton biomass compared to untreated controls. Estimated effect sizes of PPCP on traits and community properties were very large (partial Eta-squared > 0.15). The PPCP mixture antagonistically interacted with the natural environmental gradient in habitats offered by different depths and, at concentrations comparable to those in waste-water effluents, prevented communities from converging to the same phenotypic structure and total biomass of unexposed controls. We show that micropollutants can alter individual-level trait diversity of lake phytoplankton communities and therefore their capacity to respond to natural environmental gradients, potentially affecting aquatic ecosystem processes.

Acute gastrointestinal illness (AGI) is an important public health issue, with many pathogen sources and modes of transmission. A one-year telephone survey was conducted in Canada (2014-2015) to estimate the incidence of self-reported AGI in the previous 28 days and to describe health care seeking behaviour, using a symptom-based case definition. Excluding cases with respiratory symptoms, it is estimated that there are 0.57 self-reported AGI episodes per person-year, almost 19.5 million episodes in Canada each year. The proportion of cases seeking medical care was nearly 9%, of which 17% reported being requested to submit a sample for laboratory testing, and 49% of those requested complied and provided a sample. Results can be used to inform burden of illness and source attribution studies and indicate that AGI continues to be an important public health issue in Canada.

Campylobacteriosis is the leading bacterial gastrointestinal disease internationally, contributing significantly to the enteric illness burden. Cases have been associated with the consumption of raw milk, a behavior that has garnered attention recently. Estimates of the prevalence and levels of Campylobacter spp. in raw milk are lacking, which hinders risk assessment attempts. This article is a systematic review and meta-analysis of reported prevalence and levels of zoonotic Campylobacter spp. in the raw milk of cows, goats, and sheep in Canada, the United States, Europe, Australia, and New Zealand. The relevant literature was reviewed, and trained reviewers examined the results for inclusion of articles in the meta-analysis. Relevant data (prevalence and/or level of Campylobacter in raw milk, country of origin, animal species, sample source, Campylobacter species identified, etc.) were extracted, and a meta-analysis was performed in Stata v. 12 (Metaprop command). The weighted mean prevalence of Campylobacter spp. in raw milk samples was 1.18%. Subgroup analyses were conducted to examine how prevalence varied by study characteristics, with the highest prevalence values in studies from the United Kingdom (by country, 6.4%), about cows (by animal species, 1.3%), and including samples taken from inline filters (by sample source, 1.75%) and in studies that included species that are not pathogenic to humans (by Campylobacter species, 1.14%). Two articles each included a single Campylobacter level, 0.16 ± 0.3 and approximately 0.047 most probable number per ml. Despite a relatively low prevalence, consumption of raw milk is inherently risky because no treatment has been used to inactivate pathogens. This potential risk further supports maintaining regulations to limit the sales of raw milk.

Waterborne illness related to the consumption of contaminated or inadequately treated water is a global public health concern. Although the magnitude of drinking water-related illnesses in developed countries is lower than that observed in developing regions of the world, drinking water is still responsible for a proportion of all cases of acute gastrointestinal illness (AGI) in Canada. The estimated burden of endemic AGI in Canada is 20·5 million cases annually - this estimate accounts for under-reporting and under-diagnosis. About 4 million of these cases are domestically acquired and foodborne, yet the proportion of waterborne cases is unknown. There is evidence that individuals served by private systems and small community systems may be more at risk of waterborne illness than those served by municipal drinking water systems in Canada. However, little is known regarding the contribution of these systems to the overall drinking water-related AGI burden in Canada. Private water supplies serve an estimated 12% of the Canadian population, or ~4·1 million people. An estimated 1·4 million (4·1%) people in Canada are served by small groundwater (2·6%) and surface water (1·5%) supplies. The objective of this research is to estimate the number of AGI cases attributable to water consumption from these supplies in Canada using a quantitative microbial risk assessment (QMRA) approach. This provides a framework for others to develop burden of waterborne illness estimates for small water supplies. A multi-pathogen QMRA of Giardia, Cryptosporidium, Campylobacter, E. coli O157 and norovirus, chosen as index waterborne pathogens, for various source water and treatment combinations was performed. It is estimated that 103 230 AGI cases per year are due to the presence of these five pathogens in drinking water from private and small community water systems in Canada. In addition to providing a mechanism to assess the potential burden of AGI attributed to small systems and private well water in Canada, this research supports the use of QMRA as an effective source attribution tool when there is a lack of randomized controlled trial data to evaluate the public health risk of an exposure source. QMRA is also a powerful tool for identifying existing knowledge gaps on the national scale to inform future surveillance and research efforts.

The estimated burden of endemic acute gastrointestinal illness (AGI) annually in Canada is 20·5 million cases. Approximately 4 million of these cases are domestically acquired and foodborne, yet the proportion of waterborne cases is unknown. A number of randomized controlled trials have been completed to estimate the influence of tap water from municipal drinking water plants on the burden of AGI. In Canada, 83% of the population (28 521 761 people) consumes tap water from municipal drinking water plants serving >1000 people. The drinking water-related AGI burden associated with the consumption of water from these systems in Canada is unknown. The objective of this research was to estimate the number of AGI cases attributable to consumption of drinking water from large municipal water supplies in Canada, using data from four household drinking water intervention trials. Canadian municipal water treatment systems were ranked into four categories based on source water type and quality, population size served, and treatment capability and barriers. The water treatment plants studied in the four household drinking water intervention trials were also ranked according to the aforementioned criteria, and the Canadian treatment plants were then scored against these criteria to develop four AGI risk groups. The proportion of illnesses attributed to distribution system events vs. source water quality/treatment failures was also estimated, to inform the focus of future intervention efforts. It is estimated that 334 966 cases (90% probability interval 183 006-501 026) of AGI per year are associated with the consumption of tap water from municipal systems that serve >1000 people in Canada. This study provides a framework for estimating the burden of waterborne illness at a national level and identifying existing knowledge gaps for future research and surveillance efforts, in Canada and abroad.

Aims/hypotheses: Ceramides and other sphingolipids comprise a family of lipid molecules that accumulate in skeletal muscle and promote insulin resistance. Chronic endurance exercise training decreases muscle ceramides and other sphingolipids, but less is known about the effects of a single bout of exercise., Methods: We measured basal relationships and the effect of acute exercise (1.5 h at 50% [Formula: see text]) and recovery on muscle sphingolipid content in obese volunteers, endurance trained athletes and individuals with type 2 diabetes., Results: Muscle C18:0 ceramide (p = 0.029), dihydroceramide (p = 0.06) and glucosylceramide (p = 0.03) species were inversely related to insulin sensitivity without differences in total ceramide, dihydroceramide, and glucosylceramide concentration. Muscle C18:0 dihydroceramide correlated with markers of muscle inflammation (p = 0.04). Transcription of genes encoding sphingolipid synthesis enzymes was higher in athletes, suggesting an increased capacity for sphingolipid synthesis. The total concentration of muscle ceramides and sphingolipids increased during exercise and then decreased after recovery, during which time ceramide levels reduced to significantly below basal levels., Conclusions/interpretation: These data suggest ceramide and other sphingolipids containing stearate (18:0) are uniquely related to insulin resistance in skeletal muscle. Recovery from an exercise bout decreased muscle ceramide concentration; this may represent a mechanism promoting the insulin-sensitising effects of acute exercise.

Fibroblast growth factor 21 (FGF21), a hormone implicated in the regulation of glucose homoeostasis, insulin sensitivity, lipid metabolism and body weight, is considered to be a promising therapeutic target for the treatment of metabolic disorders. Despite observations that FGF21 is rapidly proteolysed in circulation rending it potentially inactive, little is known regarding mechanisms by which FGF21 protein levels are regulated. We systematically investigated human FGF21 protein processing using mass spectrometry. In agreement with previous reports, circulating human FGF21 was found to be cleaved primarily after three proline residues at positions 2, 4 and 171. The extent of FGF21 processing was quantified in a small cohort of healthy human volunteers. Relative abundance of FGF21 proteins cleaved after Pro-2, Pro-4 and Pro-171 ranged from 16 to 30%, 10 to 25% and 10 to 34%, respectively. Dipeptidyl peptidase IV (DPP-IV) was found to be the primary protease responsible for N-terminal cleavages after residues Pro-2 and Pro-4. Importantly, fibroblast activation protein (FAP) was implicated as the protease responsible for C-terminal cleavage after Pro-171, rendering the protein inactive. The requirement of FAP for FGF21 proteolysis at the C-terminus was independently demonstrated by in vitro digestion, immunodepletion of FAP in human plasma, administration of an FAP-specific inhibitor and by human FGF21 protein processing patterns in FAP knockout mouse plasma. The discovery that FAP is responsible for FGF21 inactivation extends the FGF21 signalling pathway and may enable novel approaches to augment FGF21 actions for therapeutic applications., (© 2016 Authors.)

Temperature has a profound effect on the species composition and physiology of marine phytoplankton, a polyphyletic group of microbes responsible for half of global primary production. Here, we ask whether and how thermal reaction norms in a key calcifying species, the coccolithophore Emiliania huxleyi , change as a result of 2.5 years of experimental evolution to a temperature ≈2°C below its upper thermal limit. Replicate experimental populations derived from a single genotype isolated from Norwegian coastal waters were grown at two temperatures for 2.5 years before assessing thermal responses at 6 temperatures ranging from 15 to 26°C, with pCO 2 (400/1100/2200 μatm) as a fully factorial additional factor. The two selection temperatures (15°/26.3°C) led to a marked divergence of thermal reaction norms. Optimal growth temperatures were 0.7°C higher in experimental populations selected at 26.3°C than those selected at 15.0°C. An additional negative effect of high pCO 2 on maximal growth rate (8% decrease relative to lowest level) was observed. Finally, the maximum persistence temperature ( T max ) differed by 1-3°C between experimental treatments, as a result of an interaction between pCO 2 and the temperature selection. Taken together, we demonstrate that several attributes of thermal reaction norms in phytoplankton may change faster than the predicted progression of ocean warming.

Objective: Enteric illness represents a significant burden of illness in Canada and internationally. Building on previous research, an expert elicitation was undertaken to explore the routes of transmission for 28 pathogens involved in enteric illness in Canada. This article considers the subcategories of foodborne, waterborne, and animal contact transmission., Methods: As part of an expert elicitation, 31 experts were asked to provide estimates of source attribution for subcategories of foodborne (n = 15), waterborne (n = 10), and animal contact (n = 3) transmission. The results from an online survey were combined using triangular probability distributions, and median and 90% credible intervals were produced. The total proportion and estimated number of cases of enteric illness attributable to each type of food commodity, water source, and animal exposure route were calculated using results from the larger elicitation survey and from a recent Canadian foodborne burden of illness study (Thomas et al., 2013)., Results: Thirty experts provided foodborne subcategory estimates for 15/28 pathogens, waterborne subcategory estimates for 14/28 pathogens and animal contact subcategory estimates for 5/28. The elicitation identified raw produce, recreational water, and farm animal contact as important risk factors for enteric illness. These results also highlighted the complexity of transmission, with greater uncertainty for certain pathogens and routes of transmission., Conclusions: This study is the first of its kind to explore subcategories of foodborne, waterborne, and animal contact transmission across such a range of enteric pathogens. Despite inherent uncertainty, these estimates present an important quantitative synthesis of the roles of foodborne commodities, water sources, and pathways of animal contact in the transmission of enteric illness in Canada.

Animal contact is a potential transmission route for campylobacteriosis, and both domestic household pet and petting zoo exposures have been identified as potential sources of exposure. Research has typically focussed on the prevalence, concentration, and transmission of zoonoses from farm animals to humans, yet there are gaps in our understanding of these factors among animals in contact with the public who don't live on or visit farms. This study aims to quantify, through a systematic review and meta-analysis, the prevalence and concentration of Campylobacter carriage in household pets and petting zoo animals. Four databases were accessed for the systematic review (PubMed, CAB direct, ProQuest, and Web of Science) for papers published in English from 1992-2012, and studies were included if they examined the animal population of interest, assessed prevalence or concentration with fecal, hair coat, oral, or urine exposure routes (although only articles that examined fecal routes were found), and if the research was based in Canada, USA, Europe, Australia, and New Zealand. Studies were reviewed for qualitative synthesis and meta-analysis by two reviewers, compiled into a database, and relevant studies were used to create a weighted mean prevalence value. There were insufficient data to run a meta-analysis of concentration values, a noted study limitation. The mean prevalence of Campylobacter in petting zoo animals is 6.5% based on 7 studies, and in household pets the mean is 24.7% based on 34 studies. Our estimated concentration values were: 7.65x103cfu/g for petting zoo animals, and 2.9x105cfu/g for household pets. These results indicate that Campylobacter prevalence and concentration are lower in petting zoo animals compared with household pets and that both of these animal sources have a lower prevalence compared with farm animals that do not come into contact with the public. There is a lack of studies on Campylobacter in petting zoos and/or fair animals in Canada and abroad. Within this literature, knowledge gaps were identified, and include: a lack of concentration data reported in the literature for Campylobacter spp. in animal feces, a distinction between ill and diarrheic pets in the reported studies, noted differences in shedding and concentrations for various subtypes of Campylobacter, and consistent reporting between studies.

Background: The Foodborne Disease Burden Epidemiology Reference Group (FERG) was established in 2007 by the World Health Organization to estimate the global burden of foodborne diseases (FBDs). This paper describes the methodological framework developed by FERG's Computational Task Force to transform epidemiological information into FBD burden estimates., Methods and Findings: The global and regional burden of 31 FBDs was quantified, along with limited estimates for 5 other FBDs, using Disability-Adjusted Life Years in a hazard- and incidence-based approach. To accomplish this task, the following workflow was defined: outline of disease models and collection of epidemiological data; design and completion of a database template; development of an imputation model; identification of disability weights; probabilistic burden assessment; and estimating the proportion of the disease burden by each hazard that is attributable to exposure by food (i.e., source attribution). All computations were performed in R and the different functions were compiled in the R package 'FERG'. Traceability and transparency were ensured by sharing results and methods in an interactive way with all FERG members throughout the process., Conclusions: We developed a comprehensive framework for estimating the global burden of FBDs, in which methodological simplicity and transparency were key elements. All the tools developed have been made available and can be translated into a user-friendly national toolkit for studying and monitoring food safety at the local level.