The Effect of a Liberal Approach to Glucose Control in Critically Ill Patients with Type 2 Diabetes: A Multicenter, Parallel-Group, Open-Label Randomized Clinical Trial.

Rationale: Blood glucose concentrations affect outcomes in critically ill patients, but the optimal target blood glucose range in those with type 2 diabetes is unknown. Objectives: To evaluate the effects of a "liberal" approach to targeted blood glucose range during ICU admission. Methods: This mutlicenter, parallel-group, open-label randomized clinical trial included 419 adult patients with type 2 diabetes expected to be in the ICU on at least three consecutive days. In the intervention group intravenous insulin was commenced at a blood glucose >252 mg/dl and titrated to a target range of 180-252 mg/dl. In the comparator group insulin was commenced at a blood glucose >180 mg/dl and titrated to a target range of 108-180 mg/dl. The primary outcome was incident hypoglycemia (<72 mg/dl). Secondary outcomes included glucose metrics and clinical outcomes. Measurements and Main Results: By Day 28, at least one episode of hypoglycemia occurred in 10 of 210 (5%) patients assigned the intervention and 38 of 209 (18%) patients assigned the comparator (incident rate ratio, 0.21 [95% confidence interval (CI), 0.09 to 0.49]; P < 0.001). Those assigned the intervention had greater blood glucose concentrations (daily mean, minimum, maximum), less glucose variability, and less relative hypoglycemia (P < 0.001 for all comparisons). By Day 90, 62 of 210 (29.5%) in the intervention and 52 of 209 (24.9%) in the comparator group had died (absolute difference, 4.6 percentage points [95% CI, -3.9% to 13.2%]; P = 0.29). Conclusions: A liberal approach to blood glucose targets reduced incident hypoglycemia but did not improve patient-centered outcomes. Clinical trial registered with Australian New Zealand Clinical Trials Registry (ACTRN 12616001135404).

Near-term climate risks and solar radiation modification: a roadmap approach for physical sciences research.

Current impacts and escalating risks of climate change require strong and decisive action to reduce greenhouse gas (GHG) emissions. They also highlight the urgency of research to enhance safety for human and natural systems, especially for those most vulnerable. This is reflected in two recent US National Academies of Science, Engineering, and Medicine studies that recommended a national focus on advancing our understanding of how to manage urgent current and future climate risks, and the study of approaches for increasing the reflection of sunlight from the atmosphere to reduce global warming, a process referred to as sunlight reflection modification (SRM). Here, we build on these recommendations by proposing a roadmap approach for the planning, coordination, and delivery of research to support a robust scientific assessment of SRM to reduce near-term climate risks in a defined timeframe. This approach is designed to support the evaluation of SRM as a possible rapid, temporary, additive measure to reduce catastrophic impacts from anthropogenic climate change, not as a substitute for aggressive GHG mitigation. Assessing SRM is proposed to be undertaken in the context of climate hazard risks through 2050, weighing the impacts associated with likely climate change trajectories against scenarios of possible SRM implementations. Provided that research is undertaken openly and that scientific resources are made widely available, the transparency of the process and the evidence generated would contribute to the democratization of information, participation by diverse stakeholders, more informed decision-making, and better opportunities for all people to weigh SRM options against climate change risks.

Light absorption from particulate impurities in snow and ice determined by spectrophotometric analysis of filters.

Light absorption by particulate impurities in snow and ice can affect the surface albedo and is important for the climate. The absorption properties of these particles can be determined by collecting and melting snow samples and extracting the particulate material by filtration of the meltwater. This paper describes the optical design and testing of a new instrument to measure the absorption spectrum from 400 to 750 nm wavelength of the particles collected on filters using an "integrating-sandwich" configuration. The measured absorption is shown to be unaffected by scattering of light from the deposited particulates. A set of calibration standards is used to derive an upper limit for the concentration of black carbon (BC) in the snow. The wavelength dependence of the absorption spectra from 450 to 600 nm is used to calculate an absorption Ångstrom exponent for the aerosol. This exponent is used to estimate the actual BC concentration in the snow samples as well as the relative contributions of BC and non-BC constituents to the absorption of solar radiation integrated over the wavelength band 300 to 750 nm.

Study protocol and statistical analysis plan for the Liberal Glucose Control in Critically Ill Patients with Pre-existing Type 2 Diabetes (LUCID) trial.

BACKGROUND: Contemporary glucose management of intensive care unit (ICU) patients with type 2 diabetes is based on trial data derived predominantly from patients without type 2 diabetes. This is despite the recognition that patients with type 2 diabetes may be relatively more tolerant of hyperglycaemia and more susceptible to hypoglycaemia. It is uncertain whether glucose targets should be more liberal in patients with type 2 diabetes. OBJECTIVE: To detail the protocol, analysis and reporting plans for a randomised clinical trial - the Liberal Glucose Control in Critically Ill Patients with Pre-existing Type 2 Diabetes (LUCID) trial - which will evaluate the risks and benefits of targeting a higher blood glucose range in patients with type 2 diabetes. DESIGN, SETTING, PARTICIPANTS AND INTERVENTION: A multicentre, parallel group, open label phase 2B randomised controlled clinical trial of 450 critically ill patients with type 2 diabetes. Patients will be randomised 1:1 to liberal blood glucose (target 10.0-14.0 mmol/L) or usual care (target 6.0-10.0 mmol/L). MAIN OUTCOME MEASURES: The primary endpoint is incident hypoglycaemia (< 4.0 mmol/L) during the study intervention. Secondary endpoints include biochemical and feasibility outcomes. RESULTS AND CONCLUSION: The study protocol and statistical analysis plan described will delineate conduct and analysis of the trial, such that analytical and reporting bias are minimised. TRIAL REGISTRATION: This trial has been registered on the Australian New Zealand Clinical Trials Registry (ACTRN No. 12616001135404) and has been endorsed by the Australian and New Zealand Intensive Care Society Clinical Trials Group.

Pharmacokinetic data support 6-hourly dosing of intravenous vitamin C to critically ill patients with septic shock.

OBJECTIVES: To study vitamin C pharmacokinetics in septic shock. DESIGN: Prospective pharmacokinetic study. SETTING: Two intensive care units. PARTICIPANTS: Twenty-one patients with septic shock enrolled in a randomised trial of high dose vitamin C therapy in septic shock. INTERVENTION: Patients received 1.5 g intravenous vitamin C every 6 hours. Plasma samples were obtained before and at 1, 4 and 6 hours after drug administration, and vitamin C concentrations were measured by high performance liquid chromatography. MAIN OUTCOME MEASURES: Clearance, volume of distribution, and half-life were calculated using noncompartmental analysis. Data are presented as median (interquartile range [IQR]). RESULTS: Of the 11 participants who had plasma collected before any intravenous vitamin C administration, two (18%) were deficient (concentrations < 11 µmol/L) and three (27%) had hypovitaminosis C (concentrations between 11 and 23 µmol/L), with a median concentration 28 µmol/L (IQR, 11-44 µmol/L). Volume of distribution was 23.3 L (IQR, 21.9-27.8 L), clearance 5.2 L/h (IQR, 3.3-5.4 L/h), and half-life 4.3 h (IQR, 2.6-7.5 h). For the participants who had received at least one dose of intravenous vitamin C before sampling, T0 concentration was 258 µmol/L (IQR, 162- 301 µmol/L). Pharmacokinetic parameters for subsequent doses were a median volume of distribution 39.9 L (IQR, 31.4-44.4 L), clearance 3.6 L/h (IQR, 2.6-6.5 L/h), and half-life 6.9 h (IQR, 5.7-8.5 h). CONCLUSION: Intravenous vitamin C (1.5 g every 6 hours) corrects vitamin C deficiency and hypovitaminosis C and provides an appropriate dosing schedule to achieve and maintain normal or elevated vitamin C levels in septic shock.

Black carbon and other light-absorbing impurities in snow in the Chilean Andes.

Vertical profiles of black carbon (BC) and other light-absorbing impurities were measured in seasonal snow and permanent snowfields in the Chilean Andes during Austral winters 2015 and 2016, at 22 sites between latitudes 18°S and 41°S. The samples were analyzed for spectrally-resolved visible light absorption. For surface snow, the average mass mixing ratio of BC was 15 ng/g in northern Chile (18-33°S), 28 ng/g near Santiago (a major city near latitude 33°S, where urban pollution plays a significant role), and 13 ng/g in southern Chile (33-41°S). The regional average vertically-integrated loading of BC was 207 µg/m2 in the north, 780 µg/m2 near Santiago, and 2500 µg/m2 in the south, where the snow season was longer and the snow was deeper. For samples collected at locations where there had been no new snowfall for a week or more, the BC concentration in surface snow was high (~10-100 ng/g) and the sub-surface snow was comparatively clean, indicating the dominance of dry deposition of BC. Mean albedo reductions due to light-absorbing impurities were 0.0150, 0.0160, and 0.0077 for snow grain radii of 100 µm for northern Chile, the region near Santiago, and southern Chile; respective mean radiative forcings for the winter months were 2.8, 1.4, and 0.6 W/m2. In northern Chile, our measurements indicate that light-absorption by impurities in snow was dominated by dust rather than BC.

Comparing initial diagnostic excision biopsy of cutaneous malignant melanoma in primary versus secondary care: A study of Irish National data.

BACKGROUND: The incidence of melanoma is rising worldwide. Current Irish guidelines from the National Cancer Control Programme state suspicious pigmented lesions should not be removed in primary care. There are conflicting guidelines and research advising who should remove possible melanomas. OBJECTIVES: To determine whether initial diagnostic excision biopsy of cutaneous malignant melanoma in primary versus secondary care leads to poorer survival. METHODS: Analysis of data comprising 7116 cases of cutaneous malignant melanoma from the National Cancer Registry Ireland between January 2002 and December 2011. Single predictor variables were examined by the chi-square or Mann-Whitney U test. The effects of single predictor variables on survival were examined by Cox proportionate hazards modelling and a multivariate Cox model of survival based on excision in a non-hospital setting versus hospital setting was derived with adjusted and unadjusted hazard ratios. RESULTS: Over a 10-year period 8.5% of melanomas in Ireland were removed in a non-hospital setting. When comparing melanoma death between the hospital and non-hospital groups, the adjusted hazard ratio was 1.56 (95%CI: 1.08-2.26); (P = .02), indicating a non-inferior outcome for the melanoma cases initially treated in the non-hospital group, after adjustment for significant covariates. CONCLUSION: This study suggests that initial excision biopsy carried out in general practice does not lead to a poorer outcome. [Box: see text].

Feasibility of intercity and trans-Atlantic telerobotic remote ultrasound: assessment facilitated by a nondedicated bandwidth connection.

We discuss the concept of ultrasound imaging at a distance by presenting the evaluation of a customized, lightweight, human-safe robotic arm for low-force, long-distance, telerobotic ultrasonography. We undertook intercity and trans-Atlantic telerobotic ultrasound simulation from master stations located in New York, New York and Munich, Germany, and imaged a phantom and a human volunteer located at a slave station in Burlington, Massachusetts, using standard Internet bandwidth <100 Mbps and <50 Mbps, respectively. The data from the robotic arm were tracked for understanding the time efficiency of the human interactions at the master stations. Comparison of a beginner in ultrasound operation with a professional sonographer revealed that although proficiency in using ultrasound was not a prerequisite for operating the robotic arm, previous experience in using clinical ultrasound was associated with progressively lower probe maneuvering time and speed due to an enhanced ability of the veteran operator in adjusting the finer angular motions of the probe. These results suggest that long-distance telerobotic echocardiography over a local nondedicated Internet bandwidth is feasible and can be rapidly learned by sonographers for cost-effective resource utilization.

Source attribution of black carbon in Arctic snow.

Snow samples obtained at 36 sites in Alaska, Canada, Greenland, Russia, and the Arctic Ocean in early 2007 were analyzed for light-absorbing aerosol concentration together with a suite of associated chemical species. The light absorption data, interpreted as black carbon concentrations, and other chemical data were input into the EPA PMF 1.1 receptor model to explore the sources for black carbon in the snow. The analysis found four factors or sources: two distinct biomass burning sources, a pollution source, and a marine source. The first three of these were responsible for essentially all of the black carbon, with the two biomass sources (encompassing both open and closed combustion) together accounting for >90% of the black carbon.