(13) C magnetic resonance spectroscopy measurements with hyperpolarized [1-(13) C] pyruvate can be used to detect the expression of transgenic pyruvate decarboxylase activity in vivo.

PURPOSE: Dissolution dynamic nuclear polarization can increase the sensitivity of the (13) C magnetic resonance spectroscopy experiment by at least four orders of magnitude and offers a novel approach to the development of MRI gene reporters based on enzymes that metabolize (13) C-labeled tracers. We describe here a gene reporter based on the enzyme pyruvate decarboxylase (EC 4.1.1.1), which catalyzes the decarboxylation of pyruvate to produce acetaldehyde and carbon dioxide. METHODS: Pyruvate decarboxylase from Zymomonas mobilis (zmPDC) and a mutant that lacked enzyme activity were expressed using an inducible promoter in human embryonic kidney (HEK293T) cells. Enzyme activity was measured in the cells and in xenografts derived from the cells using (13) C MRS measurements of the conversion of hyperpolarized [1-(13) C] pyruvate to H(13) CO3-. RESULTS: Induction of zmPDC expression in the cells and in the xenografts derived from them resulted in an approximately two-fold increase in the H(13) CO3-/[1-(13) C] pyruvate signal ratio following intravenous injection of hyperpolarized [1-(13) C] pyruvate. CONCLUSION: We have demonstrated the feasibility of using zmPDC as an in vivo reporter gene for use with hyperpolarized (13) C MRS. Magn Reson Med 76:391-401, 2016. © 2015 The Authors. Magnetic Resonance in Medicine published by Wiley Periodicals, Inc. on behalf of International Society for Magnetic Resonance in Medicine. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.PD was in receipt of a studentship funded by CRUK and S.-S.T. a Yousef Jameel studentship. TBR was in receipt of an Intra-European Marie Curie (FP7-PEOPLE- 2009-IEF, Imaging Lymphoma) and Long-term EMBO (EMBO-ALT-1145-2009) fellowships and E.M.S. and I.M.R were recipients of fellowships from the European Union Seventh Framework Programme (FP7/2007-2013) under the Marie Curie Initial Training Network METAFLUX (project number 264780). E.M.S. also acknowledges the educational support of Programme for Advanced Medical Education from Calouste Gulbenkian Foundation, Champalimaud Foundation, Ministerio de Saude and Fundacao para a Ciencia e Tecnologia, Portugal. The work was supported by a CRUK Programme Grant (17242) to KMB. The polarizer and related materials were provided by GE-Healthcare.This is the final version of the article. It first appeared from Wiley via http://dx.doi.org/10.1002/mrm.2587

Global sea-surface iodide observations, 1967-2018

The marine iodine cycle has significant impacts on air quality and atmospheric chemistry. Specifically, the reaction of iodide with ozone in the top few micrometres of the surface ocean is an important sink for tropospheric ozone (a pollutant gas) and the dominant source of reactive iodine to the atmosphere. Sea surface iodide parameterisations are now being implemented in air quality models, but these are currently a major source of uncertainty. Relatively little observational data is available to estimate the global surface iodide concentrations, and this data has not hitherto been openly available in a collated, digital form. Here we present all available sea surface (<20 m depth) iodide observations. The dataset includes values digitised from published manuscripts, published and unpublished data supplied directly by the originators, and data obtained from repositories. It contains 1342 data points, and spans latitudes from 70°S to 68°N, representing all major basins. The data may be used to model sea surface iodide concentrations or as a reference for future observations

Route and duration of antibiotic therapy in acute cellulitis: a systematic review and meta-analysis of the effectiveness and harms of antibiotic treatment

Objectives Compared with guideline recommendations, antibiotic overuse is common in treating cellulitis. We conducted a systematic review and meta-analyses on antibiotic route and duration of treatment for cellulitis in adults and children. Methods We searched MEDLINE, EMBASE and trial registries from inception to Dec 11, 2019 for interventional and observational studies of antibiotic treatment for cellulitis. Exclusions included case series/reports, pre-septal/orbital cellulitis and non-English language articles. Random-effects meta-analyses were used to produce summary relative risk (RR) estimates for our primary outcome of clinical response. PROSPERO CRD42018100602. Results We included 47/8423 articles, incorporating data from eleven trials (1855 patients) in two meta-analyses. The overall risk of bias was moderate. Only two trials compared the same antibiotic agent in each group. We found no evidence of difference in clinical response rates for antibiotic route or duration (RR(oral:IV)=1.12, 95%CI 0.98–1.27, I 2=32% and RR(shorter:longer)=0.99, 95%CI 0•96–1.03, I 2 = 0%, respectively). Findings were consistent in observational studies. Follow-up data beyond 30 days were sparse. Conclusions The evidence base for antibiotic treatment decisions in cellulitis is flawed by biased comparisons, short follow-up and lack of data around harms of antibiotic overuse. Future research should focus on developing patient-tailored antibiotic prescribing for cellulitis to reduce unnecessary antibiotic use

Abstracts from the NIHR INVOLVE Conference 2017

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The Influence of External Loads on Movement Precision During Active Shoulder Internal Rotation Movements as Measured by 3 Indices of Accuracy

Context: Using constant, variable, and absolute error to measure movement accuracy might provide a more complete description of joint position sense than any of these values alone. Objective: To determine the effect of loaded movements and type of feedback on shoulder joint position sense and movement velocity. Design: Applied study with repeated measures comparing type of feedback and the presence of a load. Setting: Laboratory. Patients or Other Participants: Twenty healthy subjects (age = 27.2 ± 3.3 years, height = 173.2 ± 18.1 cm, mass = 70.8 ± 14.5 kg) were seated with their arms in a custom shoulder wheel. Intervention(s): Subjects internally rotated 27° in the plane of the scapula, with either visual feedback provided by a video monitor or proprioceptive feedback provided by prior passive positioning, to a target at 48° of external rotation. Subjects performed the internal rotation movements with video feedback and proprioceptive feedback and with and without load (5% of body weight). Main Outcome Measure(s): High-speed motion analysis recorded peak rotational velocity and accuracy. Constant, variable, and absolute error for joint position sense was calculated from the final position. Results: Unloaded movements demonstrated significantly greater variable error than for loaded movements (2.0 ± 0.7° and 1.5 ± 0.4°, respectively) (P < .05), but there were no differences in constant or absolute error. Peak velocity was greater for movements with proprioceptive feedback (45.6 ± 2.9°/s) than visual feedback (39.1 ± 2.1°/s) and for unloaded (47.8 ± 3.6°/s) than loaded (36.9 ± 1.0°/s) movements (P < .05). Conclusions: Shoulder joint position sense demonstrated greater variable error unloaded versus loaded movements. Both visual feedback and additional loads decreased peak rotational velocity

The Influence of External Loads on Movement Precision During Active Shoulder Internal Rotation Movements as Measured by 3 Indices of Accuracy

CONTEXT: Using constant, variable, and absolute error to measure movement accuracy might provide a more complete description of joint position sense than any of these values alone. OBJECTIVE: To determine the effect of loaded movements and type of feedback on shoulder joint position sense and movement velocity. DESIGN: Applied study with repeated measures comparing type of feedback and the presence of a load. SETTING: Laboratory. PATIENTS OR OTHER PARTICIPANTS: Twenty healthy subjects (age = 27.2 +/- 3.3 years, height = 173.2 +/- 18.1 cm, mass = 70.8 +/- 14.5 kg) were seated with their arms in a custom shoulder wheel. INTERVENTION(S): Subjects internally rotated 27 degrees in the plane of the scapula, with either visual feedback provided by a video monitor or proprioceptive feedback provided by prior passive positioning, to a target at 48 degrees of external rotation. Subjects performed the internal rotation movements with video feedback and proprioceptive feedback and with and without load (5% of body weight). MAIN OUTCOME MEASURE(S): High-speed motion analysis recorded peak rotational velocity and accuracy. Constant, variable, and absolute error for joint position sense was calculated from the final position. RESULTS: Unloaded movements demonstrated significantly greater variable error than for loaded movements (2.0 +/- 0.7 degrees and 1.5 +/- 0.4 degrees, respectively) (P \u3c .05), but there were no differences in constant or absolute error. Peak velocity was greater for movements with proprioceptive feedback (45.6 +/- 2.9 degrees/s) than visual feedback (39.1 +/- 2.1 degrees/s) and for unloaded (47.8 +/- 3.6 degrees/s) than loaded (36.9 +/- 1.0 degrees/s) movements (P \u3c .05). CONCLUSIONS: Shoulder joint position sense demonstrated greater variable error unloaded versus loaded movements. Both visual feedback and additional loads decreased peak rotational velocity

Measures of Accuracy for Active Shoulder Movements at 3 Different Speeds With Kinesthetic and Visual Feedback

Study Design Repeated-measures experiment. Objective To compare measures of end point accuracy (EPA) for 2 feedback conditions: (1) visual and kinesthetic feedback and (2) kinesthetic feedback alone, during shoulder movements, at 3 different speeds. Background Shoulder joint kinesthesia is typically reported with EPA measures, such as constant error. Reporting multiple measures of EPA, such as variable error and absolute error, could provide a more detailed description of performance. Methods and Measures Subjects were seated with the shoulder abducted 90° in the scapular plane and externally rotated 75°, with the forearm placed in a custom shoulder wheel. Subjects internally rotated the shoulder 27° to a target position at 48° of shoulder external rotation for both conditions. Motion analysis was used to determine peak angular velocity and 3 EPA measures for shoulder movements. Each EPA measure was compared between the 2 feedback conditions and among the 3 speeds with a separate 2-way analysis of variance. Results Movements performed with kinesthetic feedback alone, measured by constant error (P\u3c.01), variable error (P\u3c.01), and absolute error (P\u3c.01), were less accurate than movements performed with visual and kinesthetic feedback. Faster movements were less accurate when measured by constant error (P = .01) and absolute error (P\u3c.01) than slower movements. Subjects tended to overshoot the target in the absence of visual feedback; however, movement speed played minimal role in the overshooting. Conclusions Multiple measures of EPA, such as constant, variable, and absolute error during simple restricted shoulder movements may provide additional information regarding the evaluation of a motor performance or identify different central nervous system control mechanisms for joint kinesthesia