18F-Labelled exendin to image GLP-1 receptor-expressing tissues: from niche to blockbuster?

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Ability of Archival Tags to Provide Estimates of Geographical Position Based on Light Intensity

Key words: archival tags, ambient light level, geoposition algorithm, light attenuation, positional errors, crepuscular, Equinox, pelagic fishes Abstract: We tested the ability of archival tags and their associated algorithms to esti-mate geographical position based on ambient light intensity by attaching six tags (three tags each from Northwest Marine Technologies [NMT] and Wild-life Computers [WC]) at different depths to a stationary mooring line in the Pacific Ocean (approx. 166º42'W, 24º00'N), for approximately one year (29-Aug-98 to 16-Aug-99). Upon retrieval, one tag each from the two vendors had malfunctioned: from these no data (NMT) or only partial data (WC) could be downloaded. An algorithm onboard the NMT tag automatically calculated geographical positions. For the WC tags, three different algorithms were used to estimate geographical positions from the recorded light intensity data. Es-timates of longitude from all tags were significantly less variable than those for latitude. The mean absolute error for longitude estimates from the NMT tags ranged from 0.29 to 0.35º, and for the WC tags from 0.13 to 0.25º. Th

A multicentre phase II study of cisplatin and gemcitabine for malignant mesothelioma

Our previous phase II study of cisplatin and gemcitabine in malignant mesothelioma showed a 47.6% (95% CI 26.2–69.0%) response rate with symptom improvement in responding patients. Here we confirm these findings in a multicentre setting, and assess the effect of this treatment on quality of life and pulmonary function. Fifty-three patients with pleural malignant mesothelioma received cisplatin 100 mg m−2 i.v. day 1 and gemcitabine 1000 mg m−2 i.v. days 1, 8, and 15 of a 28 day cycle for a maximum of six cycles. Quality of life and pulmonary function were assessed at each cycle. The best response achieved in 52 assessable patients was: partial response, 17 (33%, 95% CI 20–46%); stable disease, 31 (60%); and progressive disease, four (8%). The median time to disease progression was 6.4 months, median survival from start of treatment 11.2 months, and median survival from diagnosis 17.3 months. Vital capacity and global quality of life remained stable in all patients and improved significantly in responding patients. Major toxicities were haematological, limiting the mean relative dose intensity of gemcitabine to 75%. This schedule of cisplatin and gemcitabine is active in malignant mesothelioma in a multicentre setting. Investigation of alternative scheduling is needed to decrease haematological toxicity and increase the relative dose intensity of gemcitabine whilst maintaining response rate and quality of life

Pacific origin of the abrupt increase in Indian Ocean heat content during the warming hiatus

Global mean surface warming has stalled since the end of the twentieth century1, 2, but the net radiation imbalance at the top of the atmosphere continues to suggest an increasingly warming planet. This apparent contradiction has been reconciled by an anomalous heat flux into the ocean3, 4, 5, 6, 7, 8, induced by a shift towards a La Niña-like state with cold sea surface temperatures in the eastern tropical Pacific over the past decade or so. A significant portion of the heat missing from the atmosphere is therefore expected to be stored in the Pacific Ocean. However, in situ hydrographic records indicate that Pacific Ocean heat content has been decreasing9. Here, we analyse observations along with simulations from a global ocean–sea ice model to track the pathway of heat. We find that the enhanced heat uptake by the Pacific Ocean has been compensated by an increased heat transport from the Pacific Ocean to the Indian Ocean, carried by the Indonesian throughflow. As a result, Indian Ocean heat content has increased abruptly, which accounts for more than 70% of the global ocean heat gain in the upper 700 m during the past decade. We conclude that the Indian Ocean has become increasingly important in modulating global climate variability

Lifestyle variables and the risk of myocardial infarction in the General Practice Research Database

<p>Abstract</p> <p>Background</p> <p>The primary objective of this study is to estimate the association between body mass index (BMI) and the risk of first acute myocardial infarction (AMI). As a secondary objective, we considered the association between other lifestyle variables, smoking and heavy alcohol use, and AMI risk.</p> <p>Methods</p> <p>This study was conducted in the general practice research database (GPRD) which is a database based on general practitioner records and is a representative sample of the United Kingdom population. We matched cases of first AMI as identified by diagnostic codes with up to 10 controls between January 1^st, 2001 and December 31^st, 2005 using incidence density sampling. We used multiple imputation to account for missing data.</p> <p>Results</p> <p>We identified 19,353 cases of first AMI which were matched on index date, GPRD practice and age to 192,821 controls. There was a modest amount of missing data in the database, and the patients with missing data had different risks than those with recorded values. We adjusted our analysis for each lifestyle variable jointly and also for age, sex, and number of hospitalizations in the past year. Although a record of underweight (BMI <18.0 kg/m²) did not alter the risk for AMI (adjusted odds ratio (OR): 1.00; 95% confidence interval (CI): 0.87–1.11) when compared with normal BMI (18.0–24.9 kg/m²), obesity (BMI ≥30 kg/m²) predicted an increased risk (adjusted OR: 1.41; 95% CI: 1.35–1.47). A history of smoking also predicted an increased risk of AMI (adjusted OR: 1.81; 95% CI: 1.75–1.87) as did heavy alcohol use (adjusted OR: 1.15; 95% CI: 1.06–1.26).</p> <p>Conclusion</p> <p>This study illustrates that obesity, smoking and heavy alcohol use, as recorded during routine care by a general practitioner, are important predictors of an increased risk of a first AMI. In contrast, low BMI does not increase the risk of a first AMI.</p

Light-intensity physical activity and cardiometabolic biomarkers in US adolescents

BackgroundThe minimal physical activity intensity that would confer health benefits among adolescents is unknown. The purpose of this study was to examine the associations of accelerometer-derived light-intensity (split into low and high) physical activity, and moderate- to vigorous-intensity physical activity with cardiometabolic biomarkers in a large population-based sample.MethodsThe study is based on 1,731 adolescents, aged 12&ndash;19 years from the 2003/04 and 2005/06 National Health and Nutrition Examination Survey. Low light-intensity activity (100&ndash;799 counts/min), high light-intensity activity (800 counts/min to &lt;4 METs) and moderate- to vigorous-intensity activity (&ge;4 METs, Freedson age-specific equation) were accelerometer-derived. Cardiometabolic biomarkers, including waist circumference, systolic blood pressure, diastolic blood pressure, HDL-cholesterol, and C-reactive protein were measured. Triglycerides, LDL- cholesterol, insulin, glucose, and homeostatic model assessments of &beta;-cell function (HOMA-%B) and insulin sensitivity (HOMA-%S) were also measured in a fasting sub-sample (n=807).ResultsAdjusted for confounders, each additional hour/day of low light-intensity activity was associated with 0.59 (95% CI: 1.18&ndash;0.01) mmHG lower diastolic blood pressure. Each additional hour/day of high light-intensity activity was associated with 1.67 (2.94&ndash;0.39) mmHG lower diastolic blood pressure and 0.04 (0.001&ndash;0.07) mmol/L higher HDL-cholesterol. Each additional hour/day of moderate- to vigorous-intensity activity was associated with 3.54 (5.73&ndash;1.35) mmHG lower systolic blood pressure, 5.49 (1.11&ndash;9.77)% lower waist circumference, 25.87 (6.08&ndash;49.34)% lower insulin, and 16.18 (4.92&ndash;28.53)% higher HOMA-%S.ConclusionsTime spent in low light-intensity physical activity and high light-intensity physical activity had some favorable associations with biomarkers. Consistent with current physical activity recommendations for adolescents, moderate- to vigorous-intensity activity had favorable associations with many cardiometabolic biomarkers. While increasing MVPA should still be a public health priority, further studies are needed to identify dose-response relationships for light-intensity activity thresholds to inform future recommendations and interventions for adolescents.</div

Search for Kaluza-Klein Graviton Emission in ppˉp\bar{p} Collisions at s=1.8\sqrt{s}=1.8 TeV using the Missing Energy Signature

We report on a search for direct Kaluza-Klein graviton production in a data sample of 84 ${pb}^{-1}$ of \ppb collisions at $\sqrt{s}$ = 1.8 TeV, recorded by the Collider Detector at Fermilab. We investigate the final state of large missing transverse energy and one or two high energy jets. We compare the data with the predictions from a $3+1+n$-dimensional Kaluza-Klein scenario in which gravity becomes strong at the TeV scale. At 95% confidence level (C.L.) for $n$=2, 4, and 6 we exclude an effective Planck scale below 1.0, 0.77, and 0.71 TeV, respectively.Comment: Submitted to PRL, 7 pages 4 figures/Revision includes 5 figure

Worth the ‘EEfRT’? The Effort Expenditure for Rewards Task as an Objective Measure of Motivation and Anhedonia

Background: Of the putative psychopathological endophenotypes in major depressive disorder (MDD), the anhedonic subtype is particularly well supported. Anhedonia is generally assumed to reflect aberrant motivation and reward responsivity. However, research has been limited by a lack of objective measures of reward motivation. We present the Effort-Expenditure for Rewards Task (EEfRT or ‘‘effort’’), a novel behavioral paradigm as a means of exploring effort-based decision-making in humans. Using the EEfRT, we test the hypothesis that effort-based decision-making is related to trait anhedonia. Methods/Results: 61 undergraduate students participated in the experiment. Subjects completed self-report measures of mood and trait anhedonia, and completed the EEfRT. Across multiple analyses, we found a significant inverse relationship between anhedonia and willingness to expend effort for rewards. Conclusions: These findings suggest that anhedonia is specifically associated with decreased motivation for rewards, and provide initial validation for the EEfRT as a laboratory-based behavioral measure of reward motivation and effort-base