Combination GLP-1 and Insulin Treatment Fails to Alter Myocardial Fuel Selection Versus Insulin Alone in Type 2 Diabetes

Context Glucagon-like peptide-1 (GLP-1) and the clinically available GLP-1 agonists have been shown to exert effects on the heart. It is unclear whether these effects occur at clinically used doses in vivo in humans, possibly contributing to CVD risk reduction. Objective To determine whether liraglutide at clinical dosing augments myocardial glucose uptake alone or in combination with insulin compared to insulin alone in metformin-treated Type 2 diabetes mellitus. Design Comparison of myocardial fuel utilization after 3 months of treatment with insulin detemir, liraglutide, or combination detemir+liraglutide. Setting Academic hospital Participants Type 2 diabetes treated with metformin plus oral agents or basal insulin. Interventions Insulin detemir, liraglutide, or combination added to background metformin Main Outcome Measures Myocardial blood flow, fuel selection and rates of fuel utilization evaluated using positron emission tomography, powered to demonstrate large effects. Results We observed greater myocardial blood flow in the insulin-treated groups (median[25th, 75th percentile]: detemir 0.64[0.50, 0.69], liraglutide 0.52[0.46, 0.58] and detemir+liraglutide 0.75[0.55, 0.77] mL/g/min, p=0.035 comparing 3 groups and p=0.01 comparing detemir groups to liraglutide alone). There were no evident differences between groups in myocardial glucose uptake (detemir 0.040[0.013, 0.049], liraglutide 0.055[0.019, 0.105], detemir+liraglutide 0.037[0.009, 0.046] µmol/g/min, p=0.68 comparing 3 groups). Similarly there were no treatment group differences in measures of myocardial fatty acid uptake or handling, and no differences in total oxidation rate. Conclusions These observations argue against large effects of GLP-1 agonists on myocardial fuel metabolism as mediators of beneficial treatment effects on myocardial function and ischemia protection

Equivalence of arterial and venous blood for [11C]CO2-metabolite analysis following intravenous administration of 1-[11C]acetate and 1-[11C]palmitate

PURPOSE: Sampling of arterial blood for metabolite correction is often required to define a true radiotracer input function in quantitative modeling of PET data. However, arterial puncture for blood sampling is often undesirable. To establish whether venous blood could substitute for arterial blood in metabolite analysis for quantitative PET studies with 1-[(11)C]acetate and 1-[(11)C]palmitate, we compared the results of [(11)C]CO2-metabolite analyses performed on simultaneously collected arterial and venous blood samples. METHODS: Paired arterial and venous blood samples were drawn from anesthetized pigs at 1, 3, 6, 8, 10, 15, 20, 25 and 30min after i.v. administration of 1-[(11)C]acetate and 1-[(11)C]palmitate. Blood radioactivity present as [(11)C]CO2 was determined employing a validated 10-min gas-purge method. Briefly, total blood (11)C radioactivity was counted in base-treated [(11)C]-blood samples, and non-[(11)C]CO2 radioactivity was counted after the [(11)C]-blood was acidified using 6N HCl and bubbled with air for 10min to quantitatively remove [(11)C]CO2. RESULTS: An excellent correlation was found between concurrent arterial and venous [(11)C]CO2 levels. For the [(11)C]acetate study, the regression equation derived to estimate the venous [(11)C]CO2 from the arterial values was: y=0.994x+0.004 (r(2)=0.97), and for the [(11)C]palmitate: y=0.964x-0.001 (r(2)=0.9). Over the 1-30min period, the fraction of total blood (11)C present as [(11)C]CO2 rose from 4% to 64% for acetate, and 0% to 24% for palmitate. The rate of [(11)C]CO2 appearance in venous blood appears similar for the pig model and humans following i.v. [(11)C]-acetate administration. CONCLUSION: Venous blood [(11)C]CO2 values appear suitable as substitutes for arterial blood samples in [(11)C]CO2 metabolite analysis after administration of [(11)C]acetate or [(11)C]palmitate ADVANCES IN KNOWLEDGE AND IMPLICATIONS FOR PATIENT CARE: Quantitative PET studies employing 1-[(11)C]acetate and 1-[(11)C]palmitate can employ venous blood samples for metabolite correction of an image-derived tracer arterial input function, thereby avoiding the risks of direct arterial blood sampling

Complex impedance measurements of calorimeters and bolometers: correction for stray impedances

Impedance measurements provide a useful probe of the physics of bolometers and calorimeters. We describe a method for measuring the complex impedance of these devices. In previous work, stray impedances and readout electronics of the measurement apparatus have resulted in artifacts in the impedance data. The new technique allows experimenters to find an independent Thevenin or Norton equivalent circuit for each frequency. This method allows experimenters to easily isolate the device impedance from the effects of parasitic impedances and frequency dependent gains in amplifiers.Comment: 5 pages, 6 figure

Are We Preparing the Next Generation of Fisheries Professionals to Succeed in their Careers?: A Survey of AFS Members

Natural resource professionals have frequently criticized universities for poorly preparing graduates to succeed in their jobs. We surveyed members of the American Fisheries Society to determine which job skills and knowledge of academic topics employers, students, and university faculty members deemed most important to early-career success of fisheries professionals. Respondents also rated proficiency of recently hired, entry-level professionals (employers) on how well their programs prepared them for career success (students and faculty) in those same job skills and academic topics. Critical thinking and written and oral communication skills topped the list of important skills and academic topics. Employers perceived recent entry-level hires to be less well-prepared to succeed in their careers than either university faculty or students. Entry-level hires with post-graduate degrees rated higher in proficiency for highly important skills and knowledge than those with bachelor’s degrees. We conclude that although universities have the primary responsibility for developing critical thinking and basic communication skills of students, employers have equal or greater responsibility for enhancing skills of employees in teamwork, field techniques, and communicating with stakeholders. The American Fisheries Society can significantly contribute to the preparation of young fisheries professionals by providing opportunities for continuing education and networking with peers at professional conferences. ¿Estamos preparando a la siguiente generación de profesionales en pesquerías para que tengan éxito en sus carreras?: una encuesta a miembros de la AFS Los profesionales de los recursos naturales, con frecuencia, han criticado a las universidades por la preparación deficiente de los graduados para tener éxito en sus trabajos. En este trabajo se encuestaron a miembros de la Sociedad Americana de Pesquerías para determinar qué conocimiento de tópicos académicos y habilidades laborales consideran los empleados, estudiantes y miembros de facultades universitarias como las más importantes en los profesionales de las pesquerías para tener éxito al inicio de sus carreras. Los encuestados también reconocieron las habilidades de los profesionistas regresados y contratados (empleados) o qué tan bien sus programas académicos los preparaban para tener éxito en sus carreras (estudiantes y facultad) en las mismas habilidades laborales y tópicos académicos. El pensamiento crítico y las habilidades de comunicación oral y escrita encabezaron la lista de habilidades y tópicos académicos importantes. Los empleadores percibieron a las contrataciones recientes como menos preparadas para tener éxito en sus carreras que los miembros de la facultad o los propios estudiantes. Los individuos recién contratados con posgrado fueron mejor calificados en cuanto a poseer el conocimiento y las habilidades más importantes que los titulados de licenciatura. Concluimos que si bien las universidades tienen la responsabilidad primordial de desarrollar el pensamiento crítico y las habilidades de comunicación en los estudiantes, los empleadores tienen la misma o mayor responsabilidad para fomentar las habilidades de sus trabajadores en lo referente a trabajo en equipo, técnicas de trabajo en campo, y comunicación con los involucrados en las pesquerías. La Sociedad Americana de Pesquerías puede contribuir significativamente a preparar a los jóvenes profesionistas de las pesquerías mediante el otorgamiento de oportunidades para continuar con su educación y el establecimiento de redes de contactos, durante conferencias, con pares y profesionales. Préparons-nous la prochaine génération de professionnels de la pêche à réussir leur carrière?: Un sondage auprès des membres AFS Les professionnels des ressources naturelles ont fréquemment critiqué les universités, car elles préparent mal les diplômés à réussir leur carrière. Nous avons interrogé les membres de l’American Fisheries Society pour déterminer quelles compétences professionnelles et quelles connaissances académiques les employeurs, étudiants et membres du corps professoral des universités jugent les plus importantes pour le succès des professionnels de la pêche au début de leur carrière. Les répondants ont également évalué l’aptitude des professionnels récemment entrés sur le marché du travail (employeurs) ou dans quelle mesure les programmes les ont préparés à réussir leur carrière (étudiants et professeurs) dans ces mêmes compétences professionnelles et sujets académiques. La pensée critique, les compétences en communication écrite et orale étaient en tête de la liste des compétences et des sujets académiques importants. Les employeurs ont perçu les professionnels récemment entrés sur le marché du travail moins bien préparés pour réussir dans leur carrière que les professeurs d’université ou les étudiants. Les employés au niveau d’entrée possédant des diplômes postuniversitaires étaient mieux notés dans la maîtrise des compétences et des connaissances très importantes que ceux ne possédant que des diplômes de baccalauréat. Nous concluons que, bien que les universités aient la responsabilité principale de développer la pensée critique et les compétences en communication de base des étudiants, les employeurs ont la responsabilité égale ou supérieure d’améliorer ces compétences dans le travail d’équipe, les techniques de terrain et la communication avec les parties prenantes. L’American Fisheries Society peut contribuer de manière significative à la préparation des jeunes professionnels de la pêche en offrant des possibilités de formation continue et de réseautage avec des pairs lors de conférences professionnelles

Genomic characterization of Pseudomonas spp. on food: Implications for spoilage, antimicrobial resistance and human infection

Background: Pseudomonas species are common on food, but their contribution to the antimicrobial resistance gene (ARG) burden within food or as a source of clinical infection is unknown. Pseudomonas aeruginosa is an opportunistic pathogen responsible for a wide range of infections and is often hard to treat due to intrinsic and acquired ARGs commonly carried by this species. This study aimed to understand the potential role of Pseudomonas on food as a reservoir of ARGs and to assess the presence of potentially clinically significant Pseudomonas aeruginosa strains on food. To achieve this, we assessed the genetic relatedness (using whole genome sequencing) and virulence of food-derived isolates to those collected from humans. Results: A non-specific culturing approach for Pseudomonas recovered the bacterial genus from 28 of 32 (87.5%) retail food samples, although no P. aeruginosa was identified. The Pseudomonas species recovered were not clinically relevant, contained no ARGs and are likely associated with food spoilage. A specific culture method for P. aeruginosa resulted in the recovery of P. aeruginosa from 14 of 128 (11%) retail food samples; isolates contained between four and seven ARGs each and belonged to 16 sequence types (STs), four of which have been isolated from human infections. Food P. aeruginosa isolates from these STs demonstrated high similarity to human-derived isolates, differing by 41–312 single nucleotide polymorphisms (SNPs). There were diverse P. aeruginosa collected from the same food sample with distinct STs present on some samples and isolates belonging to the same ST differing by 19–67 SNPs. The Galleria mellonella infection model showed that 15 of 16 STs isolated from food displayed virulence between a low-virulence (PAO1) and a high virulence (PA14) control. Conclusion: The most frequent Pseudomonas recovered from food examined in this study carried no ARGs and are more likely to play a role in food spoilage rather than infection. P. aeruginosa isolates likely to be able to cause human infections and with multidrug resistant genotypes are present on a relatively small but still substantial proportions of retail foods examined. Given the frequency of exposure, the potential contribution of food to the burden of P. aeruginosa infections in humans should be evaluated more closely

Effect of angiotensin receptor blockade on insulin sensitivity and endothelial function in abdominally obese hypertensive patients with impaired fasting glucose

AngII (angiotensin II) may contribute to cardiovascular risk in obesity via adverse effects on insulin sensitivity and endothelial function. In the present study, we examined the effects of ARB (angiotensin receptor blocker) therapy (losartan, 100 mg/day) on insulin sensitivity and endothelial function in 53 subjects with stage I hypertension, abdominal obesity and impaired fasting glucose. The study design was a randomized double-blinded parallel design placebo-controlled multi-centre trial of 8 weeks duration. We used the hyperinsulinaemic-euglycaemic clamp technique to measure insulin sensitivity (expressed as the 'M/I' value) and RH-PAT (reactive hyperaemia-peripheral arterial tonometry) to measure endothelial function. Additional measures included HOMA (homoeostasis model assessment)-B, an index of pancreatic β-cell function, and markers of inflammation [e.g. CRP (C-reactive protein)] and oxidative stress (e.g. F2-isoprostanes). ARB therapy did not alter insulin sensitivity [5.2 (2.7) pre-treatment and 4.6 (1.6) post-treatment] compared with placebo therapy [6.1 (2.9) pre-treatment and 5.3 (2.7) post-treatment; P value not significant], but did improve the HOMA-B compared with placebo therapy (P=0.05). ARB therapy also did not change endothelial function [RH-PAT, 2.15 (0.7) pre-treatment and 2.11 (0.7) post-treatment] compared with placebo therapy [RH-PAT, 1.81 (0.5) pre-treatment and 1.76 (0.7) post-treatment; P value not significant]. Markers of inflammation and oxidative stress were not significantly changed by ARB therapy. In conclusion, ARB therapy did not alter peripheral insulin sensitivity or endothelial function in this cohort of patients with essential hypertension, abdominal obesity and impaired fasting glucose, but did improve pancreatic β-cell function

A randomised controlled trial of cognitive behavioural treatment for obsessive compulsive disorder in children and adolescents

Cognitive behaviour therapy (CBT) for young people with obsessive compulsive disorder (OCD) has become the treatment of first choice. However, the literature is largely based on studies emphasising exposure and response prevention. In this study, we report on a randomised controlled trial of CBT for young people carried out in typical outpatient clinic conditions which focused on cognitions. A randomised controlled trial compares 10 sessions of manualised cognitive behavioural treatment with a 12-week waiting list for adolescents and children with OCD. Assessors were blind to treatment allocation. 21 consecutive patients with OCD aged between 9 and 18 years were recruited. The group who received treatment improved more than a comparison group who waited for 3 months. The second group was treated subsequently using the same protocol and made similar gains. In conclusion, CBT can be delivered effectively to young people with OCD in typical outpatient settings

The Wide-field Infrared Survey Explorer (WISE): Mission Description and Initial On-orbit Performance

The all sky surveys done by the Palomar Observatory Schmidt, the European Southern Observatory Schmidt, and the United Kingdom Schmidt, the InfraRed Astronomical Satellite and the 2 Micron All Sky Survey have proven to be extremely useful tools for astronomy with value that lasts for decades. The Wide-field Infrared Survey Explorer is mapping the whole sky following its launch on 14 December 2009. WISE began surveying the sky on 14 Jan 2010 and completed its first full coverage of the sky on July 17. The survey will continue to cover the sky a second time until the cryogen is exhausted (anticipated in November 2010). WISE is achieving 5 sigma point source sensitivities better than 0.08, 0.11, 1 and 6 mJy in unconfused regions on the ecliptic in bands centered at wavelengths of 3.4, 4.6, 12 and 22 microns. Sensitivity improves toward the ecliptic poles due to denser coverage and lower zodiacal background. The angular resolution is 6.1, 6.4, 6.5 and 12.0 arc-seconds at 3.4, 4.6, 12 and 22 microns, and the astrometric precision for high SNR sources is better than 0.15 arc-seconds.Comment: 22 pages with 19 included figures. Updated to better match the accepted version in the A