Extravehicular activity at geosynchronous earth orbit

The basic contract to define the system requirements to support the Advanced Extravehicular Activity (EVA) has three phases: EVA in geosynchronous Earth orbit; EVA in lunar base operations; and EVA in manned Mars surface exploration. The three key areas to be addressed in each phase are: environmental/biomedical requirements; crew and mission requirements; and hardware requirements. The structure of the technical tasks closely follows the structure of the Advanced EVA studies for the Space Station completed in 1986

Advanced extravehicular activity systems requirements definition study. Phase 2: Extravehicular activity at a lunar base

The focus is on Extravehicular Activity (EVA) systems requirements definition for an advanced space mission: remote-from-main base EVA on the Moon. The lunar environment, biomedical considerations, appropriate hardware design criteria, hardware and interface requirements, and key technical issues for advanced lunar EVA were examined. Six remote EVA scenarios (three nominal operations and three contingency situations) were developed in considerable detail

Metallointercalators: structure of rac-bis(ethylenediamine)(9,10-phenanthrenequinone diimine)rhodium(III) tribromide trihydrate

Bis(ethylenediamine)(phenanthrenequinone diimine)rhodium(III) tribromide trihydrate has a nearly planar phenanthrenequinone diimine ligand and two ordered ethylenediamine ligands, giving a distorted octahedral coordination to the compound. The N-Rh-N angles range from 77.1 (6) to 96.5°, with the largest deviations from 90° associated with the N atoms of the phenanthrenequinone diimine ligand. The two Rh-N distances involving these N atoms are 0.05 Å shorter than Rh-N distances to ethylenediamine ligands; other distances and angles are within normal ranges

Aquilegia, Vol. 23 No. 5, September-October 1999: Newsletter of the Colorado Native Plant Society

https://epublications.regis.edu/aquilegia/1176/thumbnail.jp

Time trends in prescribing of type 2 diabetes drugs, glycaemic response and risk factors:a retrospective analysis of primary care data, 2010-2017

This is the author accepted manuscript. The final version is available on open access from Wiley via the DOI in this recordAim: Prescribing in type 2 diabetes has changed markedly in recent years, with increasing use of newer, more expensive glucose-lowering drugs. We aimed to describe population-level time trends in both prescribing patterns and short-term patient outcomes (HbA1c, weight, blood pressure, hypoglycemia and treatment discontinuation) after initiating new therapy. Materials and methods: We studied 81,532 UK patients with type 2 diabetes initiating a first to fourth line drug in primary care between 2010-2017 inclusive (Clinical Practice Research Datalink). Trends in new prescriptions and subsequent six and twelve-month adjusted changes in glycemic response (reduction in HbA1c), weight, blood pressure, and rates of hypoglycemia and treatment discontinuation were examined. Results: DPP4-inhibitor use second-line near doubled (41% of new prescriptions in 2017 vs. 22% 2010), replacing sulfonylureas as the most common second-line drug (29% 2017 vs. 53% 2010). SGLT2-inhibitors, introduced in 2013, comprised 17% of new first-fourth line prescriptions by 2017. First-line use of metformin remained stable (91% of new prescriptions in 2017 vs. 91% 2010). Over the study period there was little change in average glycemic response and treatment discontinuation. There was a modest reduction in weight second and third-line (second line 2017 vs. 2010: -1.5 kg (95%CI -1.9;-1.1), p<0.001), and a slight reduction in systolic blood pressure first to third-line (2017 vs. 2010 difference range -1.7 to -2.1 mmHg, all p<0.001). Hypoglycemia rates decreased second-line (incidence rate ratio 0.94 per-year (95%CI 0.88;1.00, p=0.04)), mirroring the decline in use of sulfonylureas. 4 Conclusions: Recent changes in prescribing of therapy in type 2 diabetes have not led to a change in glycemic response and have resulted in modest improvements in other population-level short-term patient outcomes.Medical Research Council (MRC)National Institute for Health Research (NIHR)Wellcome Trus

Design and Performance of the Hotrod Melt-Tip Ice-Drilling System

We introduce the design and performance of a melt-tip ice-drilling system designed to insert a temperature sensor cable into ice. The melt tip is relatively simple and low cost, designed for a one-way trip to the ice-bed interface. The drilling system consists of a melt tip, umbilical cable, winch, interface, power supply, and support items. The melt tip and the winch are the most novel elements of the drilling system, and we make the hardware and electrical designs of these components available open access. Tests conducted in a laboratory ice well indicate that the melt tip has an electrical energy to forward melting heat transfer efficiency of ~35 % with a theoretical maximum penetration rate of ~12 m/hr at maximum 6.0 kW power. In contrast, ice-sheet testing suggests the melt tip has an analogous heat transfer efficiency of ~15 % with a theoretical maximum penetration rate of ~6 m/hr. We expect the efficiency gap between laboratory and field performance to decrease with increasing operator experience. Umbilical freeze-in due to borehole refreezing is the primary depth-limiting factor of the drilling system. Enthalpy-based borehole refreezing assessments predict refreezing below critical umbilical diameter in ~4 hours at -20 ˚C ice temperatures and ~20 hours at -2 ˚C. This corresponds to a theoretical depth limit of up to ~200 m, depending on firn thickness, ice temperature and operator experience.</p

Development of a treatment selection algorithm for SGLT2 and DPP-4 inhibitor therapies in people with type 2 diabetes:a retrospective cohort study

Background: Current treatment guidelines do not provide recommendations to support the selection of treatment for most people with type 2 diabetes. We aimed to develop and validate an algorithm to allow selection of optimal treatment based on glycaemic response, weight change, and tolerability outcomes when choosing between SGLT2 inhibitor or DPP-4 inhibitor therapies. Methods: In this retrospective cohort study, we identified patients initiating SGLT2 and DPP-4 inhibitor therapies after Jan 1, 2013, from the UK Clinical Practice Research Datalink (CPRD). We excluded those who received SGLT2 or DPP-4 inhibitors as first-line treatment or insulin at the same time, had estimated glomerular filtration rate (eGFR) of less than 45 mL/min per 1·73 m2, or did not have a valid baseline glycated haemoglobin (HbA1c) measure (&lt;53 or ≥120 mmol/mol). The primary efficacy outcome was the HbA1c value reached 6 months after drug initiation, adjusted for baseline HbA1c. Clinical features associated with differential HbA1c outcome on the two therapies were identified in CPRD (n=26 877), and replicated in reanalysis of 14 clinical trials (n=10 414). An algorithm to predict individual-level differential HbA1c outcome on the two therapies was developed in CPRD (derivation; n=14 069) and validated in head-to-head trials (n=2499) and CPRD (independent validation; n=9376). In CPRD, we further explored heterogeneity in 6-month weight change and treatment discontinuation. Findings: Among 10 253 patients initiating SGLT2 inhibitors and 16 624 patients initiating DPP-4 inhibitors in CPRD, baseline HbA1c, age, BMI, eGFR, and alanine aminotransferase were associated with differential HbA1c outcome with SGLT2 inhibitor and DPP-4 inhibitor therapies. The median age of participants was 62·0 years (IQR 55·0–70·0). 10 016 (37·3%) were women and 16 861 (62·7%) were men. An algorithm based on these five features identified a subgroup, representing around four in ten CPRD patients, with a 5 mmol/mol or greater observed benefit with SGLT2 inhibitors in all validation cohorts (CPRD 8·8 mmol/mol [95% CI 7·8–9·8]; CANTATA-D and CANTATA-D2 trials 5·8 mmol/mol [3·9–7·7]; BI1245.20 trial 6·6 mmol/mol [2·2–11·0]). In CPRD, predicted differential HbA1c response with SGLT2 inhibitor and DPP-4 inhibitor therapies was not associated with weight change. Overall treatment discontinuation within 6 months was similar in patients predicted to have an HbA1c benefit with SGLT2 inhibitors over DPP-4 inhibitors (median 15·2% [13·2–20·3] vs 14·4% [12·9–16·7]). A smaller subgroup predicted to have greater HbA1c reduction with DPP-4 inhibitors were twice as likely to discontinue SGLT2 inhibitors than DPP-4 inhibitors (median 26·8% [23·4–31·0] vs 14·8% [12·9–16·8]). Interpretation: A validated treatment selection algorithm for SGLT2 inhibitor and DPP-4 inhibitor therapies can support decisions on optimal treatment for people with type 2 diabetes. Funding: BHF-Turing Cardiovascular Data Science Award and the UK Medical Research Council

Risk factors for genital infections in people initiating SGLT2 inhibitors and their impact on discontinuation

Introduction: To identify risk factors, absolute risk, and impact on treatment discontinuation of genital infections with sodium-glucose co-transporter-2 inhibitors (SGLT2i). Research design and methods: We assessed the relationship between baseline characteristics and genital infection in 21 004 people with type 2 diabetes initiating SGLT2i and 55 471 controls initiating dipeptidyl peptidase-4 inhibitors (DPP4i) in a UK primary care database. We assessed absolute risk of infection in those with key risk factors and the association between early genital infection and treatment discontinuation. Results: Genital infection was substantially more common in those treated with SGLT2i (8.1% within 1 year) than DPP4i (1.8%). Key predictors of infection with SGLT2i were female sex (HR 3.64; 95% CI 3.23 to 4.11) and history of genital infection; &lt;1 year before initiation (HR 4.38; 3.73 to 5.13), 1–5 years (HR 3.04; 2.64 to 3.51), and &gt;5 years (HR 1.79; 1.55 to 2.07). Baseline HbA1c was not associated with infection risk for SGLT2i, in contrast to DPP4i where risk increased with higher HbA1c. One-year absolute risk of genital infection with SGLT2i was highest for those with a history of prior infection (females 23.7%, males 12.1%), compared with those without (females 10.8%, males 2.7%). Early genital infection was associated with a similar discontinuation risk for SGLT2i (HR 1.48; 1.21–1.80) and DPP4i (HR 1.58; 1.21–2.07). Conclusions: Female sex and history of prior infection are simple features that can identify subgroups at greatly increased risk of genital infections with SGLT2i therapy. These data can be used to risk-stratify patients. High HbA1c is not a risk factor for genital infections with SGLT2i