Switching from premixed insulin to glargine-based insulin regimen improves glycaemic control in patients with type 1 or type 2 diabetes: a retrospective primary care-based analysis

Background: Insulin glargine (glargine) and premixed insulins (premix) are alternative insulin treatments. This analysis evaluated glycaemic control in 528 patients with type 1 (n = 183) or type 2 (n = 345) diabetes, after switching from premix to a glargine-based regimen, using unselected general practice (GP) data. Methods: Data for this retrospective observational analysis were extracted from a UK GP database (The Health Improvement Network). Patients were required to have at least 12 months of available data, before and after, switching from premix to a glargine-based regimen. The principal analysis was the change in HbA1c after 12 months of treatment with glargine; secondary analyses included change in weight, bolus usage and total daily insulin dose. Inconsistent reporting of hypoglycemic episodes precludes reliable assessment of this outcome. Multivariate analyses were used to adjust for baseline characteristics and confounding variables. Results: Both cohorts showed significant reduction in mean HbA1c 12 months after the switch: by -0.67% (p < 0.001) in the type 1 cohort and by -0.53% (p < 0.001) in the type 2 cohort (adjusted data). The size of HbA1c improvement was positively correlated with baseline HbA1c; patients with a baseline HbA1c ≥ 10% had the greatest mean reduction in HbA1c, by -1.7% (p < 0.001) and -1.2% (p < 0.001), respectively. The proportion of patients receiving co-bolus prescriptions increased in the type 1 (mean 24.6% to 95.1%, p < 0.001) and type 2 (mean 16.2% to 73.9%, p < 0.001) cohorts. There was no significant change in weight in either cohort. Total mean insulin use increased in type 2 diabetes patients (from 0.67 ± 1.35 U/Kg to 0.88 ± 1.33 U/Kg, p < 0.001) with a slight decrease in type 1 diabetes patients (from 1.04 ± 2.51 U/Kg to 0.98 ± 2.58 U/Kg, p < 0.001). Conclusion: In everyday practice, patients with type 1 or type 2 diabetes inadequately controlled by premix insulins experienced significant improvement in glycaemic control over 12 months after switching to a glargine-based insulin regimen. These findings support the use of a basal-bolus glargine-based regimen in patients poorly controlled on premix.Peter Sharplin, Jason Gordon, John R Peters, Anthony P Tetlow, Andrea J Longman and Philip McEwa

4-Phenyl­sulfon­yl-2-(p-tolyl­sulfon­yl)-1H,8H-pyrrolo­[2,3-b]indole

The title compound, C23H18N2O4S2, contains a pyrrolo group fused onto the plane of an indole ring with phenyl­sulfonyl and p-toluene­sulfonyl groups bonded to the indole and pyrrolo rings. The angles between the mean planes of the pyrrolo-indole ring and the phenyl­sulfonyl and p-toluene­sulfonyl rings are 73.7 (6) and 80.6 (0)°, respectively. The dihedral angle between the mean planes of the two benzene rings is 78.7 (4)°. In the crystal, both classical N—H⋯O and non-classical C—H⋯O inter­molecular hydrogen-bonding inter­actions are observed, as well as weak π–π inter­actions [centroid–centroid distances = 3.6258 (8) and 3.9298 (8) Å], which contribute to the stability of the packing

Modeling payback from research into the efficacy of left-ventricular assist devices as destination therapy

Objectives: Ongoing developments in design have improved the outlook for left-ventricular assist device (LVAD) implantation as a therapy in end-stage heart failure. Nevertheless, early cost-effectiveness assessments, based on first-generation devices, have not been encouraging. Against this background, we set out (i) to examine the survival benefit that LVADs would need to generate before they could be deemed cost-effective; (ii) to provide insight into the likelihood that this benefit will be achieved; and (iii) from the perspective of a healthcare provider, to assess the value of discovering the actual size of this benefit by means of a Bayesian value of information analysis. Methods: Cost-effectiveness assessments are made from the perspective of the healthcare provider, using current UK norms for the value of a quality-adjusted life-year (QALY). The treatment model is grounded in published analyses of the Randomized Evaluation of Mechanical Assistance for the Treatment of Congestive Heart Failure (REMATCH) trial of first-generation LVADs, translated into a UK cost setting. The prospects for patient survival with second-generation devices is assessed using Bayesian prior distributions, elicited from a group of leading clinicians in the field. Results: Using established thresholds, cost-effectiveness probabilities under these priors are found to be low (.2 percent) for devices costing as much as £60,000. Sensitivity of the conclusions to both device cost and QALY valuation is examined. Conclusions: In the event that the price of the device in use would reduce to £40,000, the value of the survival information can readily justify investment in further trials

In-situ resonant band engineering of solution-processed semiconductors generates high performance n-type thermoelectric nano-inks.

Thermoelectric devices possess enormous potential to reshape the global energy landscape by converting waste heat into electricity, yet their commercial implementation has been limited by their high cost to output power ratio. No single "champion" thermoelectric material exists due to a broad range of material-dependent thermal and electrical property optimization challenges. While the advent of nanostructuring provided a general design paradigm for reducing material thermal conductivities, there exists no analogous strategy for homogeneous, precise doping of materials. Here, we demonstrate a nanoscale interface-engineering approach that harnesses the large chemically accessible surface areas of nanomaterials to yield massive, finely-controlled, and stable changes in the Seebeck coefficient, switching a poor nonconventional p-type thermoelectric material, tellurium, into a robust n-type material exhibiting stable properties over months of testing. These remodeled,&nbsp;n-type nanowires display extremely high power factors (~500 µW m-1K-2) that are orders of magnitude higher than their bulk&nbsp;p-type counterparts

Physical and economic performance of dairy cows managed within contrasting grassland based milk production systems over three successive lactation

Publication history: Accepted - 11 December 2021; Published online - 3 February 2022.A diverse range of grassland-based milk produc- tion systems are practiced on dairy farms in temper- ate regions, with systems differing in relation to the proportion of grazed grass, conserved forages and concentrates in diet, calving season, duration of hous- ing, cow genotype, and performance levels. The current study was conducted to examine performance within diverse grassland-based systems of milk production under experimental conditions. This study examined 4 milk production systems over 3 successive lactations (20 cows per system during each lactation). With win- ter calving-fully housed (WC-FH), Holstein cows were housed for the entire lactation and offered a complete diet consisting of grass silage, maize silage, and con- centrates [approximately 50% forage on a dry matter (DM) basis]. With winter calving-conventional (WC- Con), Holstein cows were housed and offered the same diet from calving until turnout (late March) as offered with WC-FH, and thereafter cows were given access to grazing and supplemented with 5.0 kg of concentrate/ cow daily. Two spring-calving systems were examined, the former involving Holstein cows (SC-H) and the lat- ter Jersey × Holstein crossbred cows (SC-J×H). Cows on these systems were offered a grass silage-concentrate mix (70% forage on a DM basis) until turnout (late February), and thereafter cows were given access to grazing supplemented with 1.0 kg of concentrate/ cow per day. The contributions of concentrates (3,080, 2,175, 722, and 760 kg of DM/cow per lactation), conserved forages (3,199, 1,556, 1,053, and 1,066 kg of DM/cow per lactation), and grazed grass (0, 2,041, 2,788, and 2,692 kg of DM/cow per lactation) to total DMI (6,362, 5,763, 4,563, and 4,473 kg of DM/cow per lactation) with WC-FH, WC-Con, SC-H, and SC-J×H, respectively, varied considerably. Similarly, milk yield (9,333, 8,443, 6,464, and 6,049 kg/cow per lactation), milk fat content (44.9, 43.3, 42.8, and 49.0 g/kg), and milk protein content (34.6, 34.9, 33.6, and 36.3 g/kg) differed between systems (WC-FH, WC-Con, SC-H, and SC-J×H, respectively). The higher milk yields with the WC systems reflect the greater concentrate inputs with these systems, whereas the greater milk fat and protein content with SC-J×H reflect the use of Jersey crossbred cows. Crossbred cows on SC-J×H produced a similar yield of milk solids as Holstein cows on SC-H. Cows on WC-FH ended the lactation with a greater body weight (BW) and body condition score than cows on any other treatment. While Jersey crossbred cows on SC-J×H had a lower BW than Holstein cows on SC-H, cows on these 2 systems were not different for any of the other BW, body condition score, or blood metabolite parameters examined. Cows on WC-FH had a greater interval from calving to conception, a greater mastitis incidence, and a greater locomotion score than cows on the spring calving systems. Whole-system stocking rates and annual milk outputs were calcu- lated as 2.99, 2.62, 2.48, and 2.50 cows/ha, and 25,706, 20,822, 15,289, and 14,564 kg of milk/ha, with each of WC-FH, WC-Con, SC-H, and SC-J×H, respectively. Gross margin per cow was highest with WC-Con, gross margin per hectare was highest with WC-FH, and gross margin per kilogram of milk was highest with SC-J×H. This study demonstrated that diverse grassland-based milk production systems are associated with very dif- ferent levels of performance when examined per cow and per hectare.This work was funded by the Department of Agriculture and Rural Development in Northern Ireland (DAERA), and by AgriSearch (farmer levy)

New Strategies for Exploring RNA's 2′-OH Expose the Importance of Solvent during Group II Intron Catalysis

AbstractThe 2′-hydroxyl group contributes inextricably to the functional behavior of many RNA molecules, fulfilling numerous essential chemical roles. To assess how hydroxyl groups impart functional behavior to RNA, we developed a series of experimental strategies using an array of nucleoside analogs. These strategies provide the means to investigate whether a hydroxyl group influences function directly (via hydrogen bonding or metal ion coordination), indirectly (via space-filling capacity, inductive effects, and sugar conformation), or through interactions with solvent. The nucleoside analogs span a broad range of chemical diversity, such that quantitative structure activity relationships (QSAR) now become possible in the exploration of RNA biology. We employed these strategies to investigate the spliced exons reopening (SER) reaction of the group II intron. Our results suggest that the cleavage site 2′-hydroxyl may mediate an interaction with a water molecule

The Spectroscopic Orbit of the Evolved Binary HD 197770

We have used spectra taken between 1992 and 1997 to derive the spectroscopic orbit of the eclipsing double-lined spectroscopic binary HD 197770. This binary has a period of 99.69 +/- 0.02 days and K amplitudes of 31.2 +/- 0.8 and 47.1 +/- 0.4 km s^{-1} for components A & B, respectively. The msin^{3}i values for A & B are 2.9 and 1.9, respectively, and are close to the actual masses due to the eclipsing nature of this binary. Both components of HD 197770 have spectral types near B2 III. This means both components are undermassive by about a factor of five and, thus, evolved stars. Additional evidence of the evolved nature of HD 197770 is found in 25, 60, and 100 micron IRAS images of HD 197770. These images show 2 apparent shells centered on HD 197770; a bright 60 micron shell with a 14' diameter and a larger (1.2 degeree diameter) bubble-like feature. At least one of the components of HD 197770 is likely to be a post-AGB star.Comment: will be published in the AJ (1998 June), also availible at http://snake.phys.lsu.edu/~gordon/papers/hd197770.htm

Incretin treatment and risk of pancreatitis in patients with type 2 diabetes mellitus : systematic review and meta-analysis of randomised and non-randomised studies

Objective To investigate the risk of pancreatitis associated with the use of incretin-based treatments in patients with type 2 diabetes mellitus. Design Systematic review and meta-analysis. Data sources Medline, Embase, the Cochrane Central Register of Controlled Trials (CENTRAL), and ClinicalTrials.gov. Eligibility criteria Randomised and non-randomised controlled clinical trials, prospective or retrospective cohort studies, and case-control studies of treatment with glucagon-like peptide-1 (GLP-1) receptor agonists or dipeptidyl peptidase-4 (DPP-4) inhibitors in adults with type 2 diabetes mellitus compared with placebo, lifestyle modification, or active anti-diabetic drugs. Data collection and analysis Pairs of trained reviewers independently screened for eligible studies, assessed risk of bias, and extracted data. A modified Cochrane tool for randomised controlled trials and a modified version of the Newcastle-Ottawa scale for observational studies were used to assess bias. We pooled data from randomised controlled trials using Peto odds ratios, and conducted four prespecified subgroup analyses and a post hoc subgroup analysis. Because of variation in outcome measures and forms of data, we describe the results of observational studies without a pooled analysis. Results 60 studies (n=353 639), consisting of 55 randomised controlled trials (n=33 350) and five observational studies (three retrospective cohort studies, and two case-control studies; n=320 289) were included. Pooled estimates of 55 randomised controlled trials (at low or moderate risk of bias involving 37 pancreatitis events, raw event rate 0.11%) did not suggest an increased risk of pancreatitis with incretins versus control (odds ratio 1.11, 95% confidence interval 0.57 to 2.17). Estimates by type of incretin suggested similar results (1.05 (0.37 to 2.94) for GLP-1 agonists v control; 1.06 (0.46 to 2.45) for DPP-4 inhibitors v control). Analyses according to the type of control, mode, duration of treatment, and individual incretin agents suggested no differential effect by subgroups, and sensitivity analyses by alternative statistical modelling and effect measures did not show important differences in effect estimates. Three retrospective cohort studies (moderate to high risk of bias, involving 1466 pancreatitis events, raw event rate 0.47%) also did not suggest an increased risk of pancreatitis associated with either exenatide (adjusted odds ratios 0.93 (0.63 to 1.36) in one study and 0.9 (0.6 to 1.5) in another) or sitagliptin (adjusted hazard ratio 1.0, 0.7 to 1.3); a case-control study at moderate risk of bias (1003 cases, 4012 controls) also suggested no significant association (adjusted odds ratio 0.98, 0.69 to 1.38). Another case-control study (1269 cases, 1269 controls) at moderate risk of bias, however, suggested that the use of either exenatide or sitagliptin was associated with significantly increased odds of acute pancreatitis (use within two years v no use, adjusted odds ratio 2.07, 1.36 to 3.13). Conclusions The available evidence suggests that the incidence of pancreatitis among patients using incretins is low and that the drugs do not increase the risk of pancreatitis. Current evidence, however, is not definitive, and more carefully designed and conducted observational studies are warranted to definitively establish the extent, if any, of increased risk

Instrumental performance and results from testing of the BLAST-TNG receiver, submillimeter optics, and MKID arrays

Polarized thermal emission from interstellar dust grains can be used to map magnetic fields in star forming molecular clouds and the diffuse interstellar medium (ISM). The Balloon-borne Large Aperture Submillimeter Telescope for Polarimetry (BLASTPol) flew from Antarctica in 2010 and 2012 and produced degree-scale polarization maps of several nearby molecular clouds with arcminute resolution. The success of BLASTPol has motivated a next-generation instrument, BLAST-TNG, which will use more than 3000 linear polarization sensitive microwave kinetic inductance detectors (MKIDs) combined with a 2.5m diameter carbon fiber primary mirror to make diffraction-limited observations at 250, 350, and 500 $\mu$m. With 16 times the mapping speed of BLASTPol, sub-arcminute resolution, and a longer flight time, BLAST-TNG will be able to examine nearby molecular clouds and the diffuse galactic dust polarization spectrum in unprecedented detail. The 250 $\mu$m detector array has been integrated into the new cryogenic receiver, and is undergoing testing to establish the optical and polarization characteristics of the instrument. BLAST-TNG will demonstrate the effectiveness of kilo-pixel MKID arrays for applications in submillimeter astronomy. BLAST-TNG is scheduled to fly from Antarctica in December 2017 for 28 days and will be the first balloon-borne telescope to offer a quarter of the flight for "shared risk" observing by the community.Comment: Presented at SPIE Millimeter, Submillimeter, and Far-Infrared Detectors and Instrumentation for Astronomy VIII, June 29th, 201