Systematic Review of the Cost Effectiveness of Insulin Analogues in Type 1 and Type 2 Diabetes Mellitus.

PubMed

Shafie, Asrul Akmal; Ng, Chin Hui; Tan, Yui Ping; Chaiyakunapruk, Nathorn

2017-02-01

Insulin analogues have a pharmacokinetic advantage over human insulin and are increasingly used to treat diabetes mellitus. A summary of their cost effectiveness versus other available treatments was required. Our objective was to systematically review the published cost-effectiveness studies of insulin analogues for the treatment of patients with type 1 diabetes mellitus (T1DM) and type 2 diabetes mellitus (T2DM). We searched major databases and health technology assessment agency reports for economic evaluation studies published up until 30 September 2015. Two reviewers performed data extraction and assessed the quality of the data using the CHEERS (Consolidated Health Economic Evaluation Reporting Standards) guidelines. Seven of the included studies assessed short-acting insulin analogues, 12 assessed biphasic insulin analogues, 30 assessed long-acting insulin analogues and one assessed a combination of short- and long-acting insulin analogues. Only 17 studies involved patients with T1DM, all were modelling studies and 12 were conducted in Canada. The incremental cost-effectiveness ratios (ICERs) for short-acting insulin analogues ranged from dominant to $US435,913 per quality-adjusted life-year (QALY) gained, the ICERs for biphasic insulin analogues ranged from dominant to $US57,636 per QALY gained and the ICERs for long-acting insulin analogues ranged from dominant to $US599,863 per QALY gained. A total of 15 studies met all the CHEERS guidelines reporting quality criteria. Only 26 % of the studies assessed heterogeneity in their analyses. Current evidence indicates that insulin analogues are cost effective for T1DM; however, evidence for their use in T2DM is not convincing. Additional evidence regarding compliance and efficacy is required to support the broader use of long-acting and biphasic insulin analogues in T2DM. The value of insulin analogues depends strongly on reductions in hypoglycaemia event rates and its efficacy in lowering glycated haemoglobin

Iontophoresis of monomeric insulin analogues in vitro: effects of insulin charge and skin pretreatment.

PubMed

Langkjaer, L; Brange, J; Grodsky, G M; Guy, R H

1998-01-23

The aim of this study was to investigate the influence of association state and net charge of human insulin analogues on the rate of iontophoretic transport across hairless mouse skin, and the effect of different skin pretreatments on said transport. No insulin flux was observed with anodal delivery probably because of degradation at the Ag/AgCl anode. The flux during cathodal iontophoresis through intact skin was insignificant for human hexameric insulin, and only low and variable fluxes were observed for monomeric insulins. Using stripped skin on the other hand, the fluxes of monomeric insulins with two extra negative charges were 50-100 times higher than that of hexameric human insulin. Introducing three additional charges led to a further 2-3-fold increase in flux. Wiping the skin gently with absolute alcohol prior to iontophoresis resulted in a 1000-fold increase in transdermal transport of insulin relative to that across untreated skin, i.e. to almost the same level as stripping the skin. The alcohol pretreatment reduced the electrical resistance of the skin, presumably by lipid extraction. In conclusion, monomeric insulin analogues with at least two extra negative charges can be iontophoretically delivered across hairless mouse skin, whereas insignificant flux is observed with human, hexameric insulin. Wiping the skin with absolute alcohol prior to iontophoresis gave substantially improved transdermal transport of monomeric insulins resulting in clinically relevant delivery rates for basal treatment.

Trends in the use and cost of human and analogue insulins in a Colombian population, 2011-2015.

PubMed

Torres, D R; Portilla, A; Machado-Duque, M E; Machado-Alba, J E

2017-12-01

Diabetes mellitus is a common disease among the general population and imposes considerable costs on health care systems. Insulin is used to treat type 1 diabetes mellitus and as an adjuvant to oral agents in advanced stages of type 2 diabetes mellitus. The objective was to describe the trends in use and cost of human and analogue insulins for Colombian patients. Descriptive retrospective analysis of prescriptions of human and analogue insulins on a monthly basis for the period from July 1, 2011 to February 2, 2015. Information was collected for the database population of two insurance companies. Frequencies and proportions were calculated; estimated economic impact was expressed as net cost and cost per thousand inhabitants per day. During the observation period, there was continuous growth in use of insulin, mainly in analogue forms (34.0% growth). At the start of the study, 10.4% of subjects were using an analogue insulin; this figure was 62.6% at the end of the study. In 2012, the average cost per 1000 inhabitants/day was US$1.7 for analogue and US$0.8 for human insulins. At the end of the observation period these costs had risen to US$9.2 for analogue (441.1% increase) and fallen to US$0.5 for human insulin (58.3% decrease). There has been an increase in the unit cost and frequency of use of insulin analogues for anti-diabetic therapy in Colombian patients. Moreover, there is controversy over whether insulin analogues are a more cost-effective treatment than human insulins for the general diabetic population. Copyright © 2017 The Royal Society for Public Health. Published by Elsevier Ltd. All rights reserved.

Current european regulatory perspectives on insulin analogues.

PubMed

Enzmann, Harald G; Weise, Martina

2011-07-07

Insulin analogues are increasingly considered as an alternative to human insulin in the therapy of diabetes mellitus. Insulin analogues (IAs) are chemically different from human insulin and may have different pharmacokinetic or pharmacodynamic properties. The significance of the modifications of the insulin molecule for the safety profile of IAs must be considered. This review describes the regulatory procedure and the expectations for the scientific content of European marketing authorization applications for innovative IAs submitted to the European Medicines Agency. Particular consideration is given to a potential cancer hazard. Specific regulatory guidance on how to address a possible carcinogenic or tumor promoting effect of innovative IAs in non-clinical studies is available. After marketing authorization, the factual access of patients to the new product will be determined to great extent by health technology assessment bodies, reimbursement decisions and the price. Whereas the marketing authorization is a European decision, pricing and reimbursement are national or regional responsibilities. The assessment of benefit and risk by the European Medicines Agency is expected to influence future decisions on price and reimbursement on a national or regional level. Collaborations between regulatory agencies and health technology assessment bodies have been initiated on European and national level to facilitate the use of the European Medicines Agency's benefit risk assessment as basis on which to build the subsequent health technology assessment. The option for combined or joint scientific advice procedures with regulators and health technology assessment bodies on European level or on a national level in several European Member States may help applicants to optimize their development program and dossier preparation in regard of both European marketing authorization application and reimbursement decisions.

Flexibility of rapid-acting insulin analogues in children and adolescents with diabetes mellitus.

PubMed

Danne, Thomas

2007-01-01

Every year, approximately 70,000 children aged<15 years develop type 1 diabetes mellitus (DM) worldwide. Achieving glycosylated hemoglobin control is a very important aim, but quality-of-life concerns for the child and the family should also have high priority in the management of pediatric DM. This review outlines some of the issues involved in treating type 1 DM in children and adolescents, as well as the use of rapid-acting insulin analogues in basal-bolus therapy and continuous subcutaneous insulin infusion pumps. This review article was based on a presentation at a satellite symposium entitled "Realising the Value of Modern Insulins: Reaching Further with Rapid-Acting Insulin Analogues "that was convened during the XIXth World Diabetes Congress, December 3, 2006, in Cape Town, South Africa. Treating children and adolescents with DM is a challenge that should not be ignored. Furthermore, DM in children is quite different from that in adults. Numerous factors have to be taken into account when evaluating treatment for children with DM in comparison with treatment for adult DM: sleep patterns; unpredictable activities, especially eating behaviors; limited size of injection sites, making it difficult to rotate injections; higher insulin sensitivity; and frequent infectious diseases. In addition, achieving normal psychosocial development may be just as important as achieving strict metabolic control in this population. Rapid-acting insulin analogues can be used effectively in these individuals with type 1 DM. The pharmacokinetic profile of insulin aspart suggests that it is suitable for flexible mealtime administration in children and adolescents. Indeed, clinical studies in children and adolescents have shown the efficacy and tolerability of postprandial administration of insulin aspart, particularly in comparison with soluble human insulin. Postprandial administration of insulin aspart, compared with preprandial soluble human insulin, has also been studied in

Clinical use of the co-formulation of insulin degludec and insulin aspart.

PubMed

Kumar, A; Awata, T; Bain, S C; Ceriello, A; Fulcher, G R; Unnikrishnan, A G; Arechavaleta, R; Gonzalez-Gálvez, G; Hirose, T; Home, P D; Kaku, K; Litwak, L; Madsbad, S; Pinget, M; Mehta, R; Mithal, A; Tambascia, M; Tibaldi, J; Christiansen, J S

2016-08-01

To provide a review of the available data and practical use of insulin degludec with insulin aspart (IDegAsp). Premixed insulins provide basal and prandial glucose control; however, they have an intermediate-acting prandial insulin component and do not provide as effective basal coverage as true long-acting insulins, owing to the physicochemical incompatibility of their individual components, coupled with the inflexibility of adjustment. The molecular structure of the co-formulation of IDegAsp, a novel insulin preparation, allows these two molecules to coexist without affecting their individual pharmacodynamic profiles. Clinical evidence in phase 2/3 trials of IDegAsp efficacy and safety in type 1 and type 2 diabetes mellitus (T1DM and T2DM) have been assessed and summarised. In people with T2DM, once- and twice-daily dosing provides similar overall glycaemic control (HbA1c ) to current modern insulins, but with lower risk of nocturnal hypoglycaemia. In prior insulin users, glycaemic control was achieved with lower or equal insulin doses vs. other basal+meal-time or premix insulin regimens. In insulin-naïve patients with T2DM, IDegAsp can be started once or twice-daily, based on individual need. People switching from more than once-daily basal or premix insulin therapy can be converted unit-to-unit to once-daily IDegAsp, although this strategy should be assessed by the physician on an individual basis. IDegAsp offers physicians and people with T2DM a simpler insulin regimen than other available basal-bolus or premix-based insulin regimens, with stable daytime basal coverage, a lower rate of hypoglycaemia and some flexibility in injection timing compared with premix insulins. © 2016 John Wiley & Sons Ltd.

Comparison of subcutaneous soluble human insulin and insulin analogues (AspB9, GluB27; AspB10; AspB28) on meal-related plasma glucose excursions in type I diabetic subjects.

PubMed

Kang, S; Creagh, F M; Peters, J R; Brange, J; Vølund, A; Owens, D R

1991-07-01

To compare postprandial glucose excursions and plasma free insulin-analogue levels after subcutaneous injection of three novel human insulin analogues (AspB10; AspB9, GluB27; and AspB28) with those after injection of soluble human insulin (Actrapid HM U-100). Six male subjects with insulin-dependent diabetes, at least 1 wk apart and after an overnight fast and basal insulin infusion, received 72 nmol (approximately 12 U) s.c. of soluble human insulin 30 min before, or 72 nmol of each of the three analogues immediately before, a standard 500-kcal meal. Mean basal glucoses were similar on the 4 study days. Compared to human insulin (6.3 +/- 0.8 mM), mean +/- SE peak incremental glucose rises were similar after analogues AspB10 (5.4 +/- 0.8 mM) and AspB9, GluB27 (5.4 +/- 0.7 mM) and significantly lower after analogue AspB28 (3.6 +/- 1.2 mM, P less than 0.02). Relative to soluble human insulin (100% +/- SE21), incremental areas under the glucose curve between 0 and 240 min were 79% +/- 34 (AspB10, NS), 70% +/- 29 (AspB9, GluB27, NS), and 43% +/- 23 (AspB28, P less than 0.02). Basal plasma free insulin levels were similar on the 4 study days. Plasma free insulin-analogue levels rose rapidly to peak 30 min after injection at 308 +/- 44 pM (AspB10); 1231 +/- 190 pM (AspB9, GluB27) and 414 +/- 42 pM (AspB28) and were significantly higher than corresponding (i.e., 30 min postmeal) plasma free insulin levels of 157 +/- 15 pM (P less than 0.02 in each case). Plasma profiles of the insulin analogues were more physiological than that of human insulin after subcutaneous injection. All three analogues given immediately before the meal are at least as effective as soluble human insulin given 30 min earlier. These analogues are promising potential candidates for short-acting insulins of the future.

Systematic review and meta-analysis of short-acting insulin analogues in patients with diabetes mellitus.

PubMed

Plank, Johannes; Siebenhofer, Andrea; Berghold, Andrea; Jeitler, Klaus; Horvath, Karl; Mrak, Peter; Pieber, Thomas R

2005-06-27

This article compares the effect of treatment with short-acting insulin (SAI) analogues vs regular insulin on glycemic control, hypoglycemic episodes, quality of life, and diabetes-specific complications. Electronic searches (Cochrane Library, MEDLINE, and EMBASE) and additional searching (pharmaceutical companies, experts, approval agencies, abstracts of diabetology meetings) were performed. Two reviewers independently screened randomized controlled trials to determine inclusion. Forty-two randomized controlled trials that assessed the effect of SAI analogues vs regular insulin in 7933 patients with type 1 diabetes mellitus, type 2 diabetes mellitus, and gestational diabetes mellitus were identified. The weighted mean difference between hemoglobin A(1c) values obtained using SAI analogues and regular insulin was -0.12% (95% confidence interval [CI], -0.17% to -0.07%) for adult patients with type 1 diabetes mellitus and -0.02% (95% CI, -0.10% to 0.07%) for patients with type 2 diabetes mellitus. The standardized mean difference for overall hypoglycemia (episodes per patient per month) was -0.05 (95% CI, -0.22 to 0.11) and -0.04 (95% CI, -0.12 to 0.04) comparing SAI analogues with regular insulin in adult patients with type 1 and type 2 diabetes mellitus, respectively. No differences between treatments were observed in children with type 1 diabetes, pregnant women with type 1 diabetes mellitus, and women with gestational diabetes. Concerning quality of life, improvement was observed only in open-label studies in patients with type 1 diabetes mellitus. No differences were seen in a double-blinded study of patients with type 1 or in the studies of patients with type 2 diabetes mellitus. Our analysis suggests only a minor benefit to hemoglobin A(1c) values in adult patients with type 1 diabetes mellitus but no benefit in the remaining population with type 2 or gestational diabetes from SAI analogue treatment.

Evaluation of the quality of life of patients with diabetes mellitus treated with conventional or analogue insulins.

PubMed

Machado-Alba, Jorge Enrique; Medina-Morales, Diego Alejandro; Echeverri-Cataño, Luis Felipe

2016-06-01

The results of two scales that measure quality of life of patients with diabetes mellitus treated with conventional or analogue insulin were evaluated and compared. Descriptive, observational, cross-sectional study, conducted in the cities of Pereira and Manizales, Colombia, in a care facility between 1 August 2013 and 30 March 2014. A total of 238 patients diagnosed with diabetes mellitus type 1 or type 2 who had been undergoing treatment with conventional or analogue insulin for at least 6months. Comparison of the results of the Diabetes 39 (specific) and European Quality of Life-5 Dimensions (EQ-5D) (generic) tools it was performed. Comparisons between the results of the two instruments were performed. Tests for parametric and non-parametric distribution (Pearson's correlation coefficient, Mann-Whitney U test, Student's t-test and Wilcoxon test) were used. The mean age was 57.7±16.6years. Conventional insulin was prescribed to 69.6% of patients, and analogue insulin was prescribed to 30.4% of patients. Diabetes-39 (D-39) showed 24.7% of subjects with a high quality of life. No statistically significant differences were found when comparing patients prescribed conventional or analogue insulin (p=0.35; 95% confidence interval [CI]: 0.375-1.419). In the EQ-5D survey, 45.7% claimed to have a high quality of life, without statistically significant differences between groups (p=0.56; 95%CI: 0.676-2.047). No differences between patients receiving conventional insulin versus analogue insulin were detected in terms of quality of life. The group aged over 60years requires special attention to improve their quality of life, and programs should focus on those individuals. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Insulin prices, availability and affordability: a cross-sectional survey of pharmacies in Hubei Province, China.

PubMed

Liu, Chenxi; Zhang, Xinping; Liu, Chaojie; Ewen, Margaret; Zhang, Zinan; Liu, Guoqin

2017-08-24

Poor access to affordable insulin results in serious and needless complications and premature deaths for those with diabetes who need this essential medicine. To help address this issue, we assessed insulin availability, prices, affordability and price components in Hubei Province as China has the heaviest burden of diabetes globally. In 2016, insulin availability and price data was collected in the capital and five other cities. A total of 30 public sector outlets (hospitals and primary care institutions) and 30 private pharmacies were sampled, using an adaptation of the World Health Organization/Health Action International methodology, Data was collected for all human and analogue insulins in stock, then analyzed by type (prandial, basal or pre-mixed) and duration of action. Prices were expressed as Median Price Ratios (MPRs) to Australian PBS prices. Price components were tracked for five insulin products in two cities.. Affordability was assessed as the number of days' wages of the lowest paid unskilled government worker needed to purchase 10 ml 100 IU/ml (approximately 30 days' supply). Mean availability was highest in public hospitals for prandial (70%), basal (80%) and pre-mixed insulin (90%). In primary care institutions and private pharmacies mean availability ranged from 10% to 33%. Median prices of all insulin types were higher that Australian PBS prices in all three sectors for human and analogue insulins (ranging from1.36-2.59 times). Patients have to pay 4 to 16 days' wages to purchase a month's treatment depending on the insulin type and sector. The largest component of the patient price was the manufacturers' selling price (60%). Taxes in the form of import duties and VAT are applied in some sectors. The availability of insulin in primary care institutions and private retail pharmacies was very low in Hubei. Only public hospitals had good insulin availability. Insulin prices were high in all sectors making this life-saving medicine unaffordable

Glycaemic control and prevalence of hypoglycaemic events in children and adolescents with type 1 diabetes mellitus treated with insulin analogues.

PubMed

Plavšić, Ljiljana; Mitrović, Katarina; Todorović, Sladjana; Vuković, Rade; Milenković, Tatjana; Zdravković, Dragan

2014-09-01

An ideal insulin regimen for children and adolescents with type 1 diabetes mellitus (T1DM) should be physiological, flexibile and predictable, protecting against hypoglycaemia. The aim of this study was to evaluate the influence of insulin analogues on glycaemic control and the occurance of hypoglycaemic episodes in children and adolescents with T1DM. The study group consisted of 151 children and adolescents (90 boys, 61 girls) treated with human insulins for at least 12 months before introducing insulin analogues. All the patients were divided into two groups: the group I consisted of 72 (47.7%) patients treated with three injections of regular human insulin before meals and long-acting analogue (RHI/LA), and the group II of 79 (52.30%) patients treated with a combination of rapid-acting and long-acting analogue (RA/LA). The levels of glycated hemoglobin (HbA1c) and the number of hypoglycaemic episodes were assessed at the beginning of therapy with insulin analogues, and after 6 and 12 months. The mean HbA1c was significantly lower in the group I (RHI/LA) after 6 months (9.15% vs 8.20%, p < 0.001) and after 12 months (9.15% vs 8.13%, p < 0.001) as well as in the group II (RA/LA) after 6 months (9.40% vs 8.240%, p < 0.001) and after 12 months of insulin analogues treatment (9.40% vs 8.38%, p < 0.001). The frequency of severe hypoglycaemia was significantly lower in both groups after 6 months (in the group I from 61.1% to 4.2% and in the group II from 54.4% to 1.3%, p < 0.001), and after 12 months (in the group I from 61.1% to 1.4% and in the group II from 54.4% to 1.3%, p < 0.001). Significantly better HbA1c values and lower risk of severe hypoglycaemia were established in children and adolescents with T1DM treated with insulin analogues.

Absorption kinetics and action profiles of subcutaneously administered insulin analogues (AspB9GluB27, AspB10, AspB28) in healthy subjects.

PubMed

Kang, S; Brange, J; Burch, A; Vølund, A; Owens, D R

1991-11-01

The subcutaneous absorption and resulting changes in plasma insulin or analogue, glucose, C-peptide, and blood intermediary metabolite concentrations after subcutaneous bolus injection of three soluble human insulin analogues (AspB9GluB27, monomeric; AspB28, mixture of monomers and dimers; and AspB10, dimeric) and soluble human insulin were evaluated. Fasting healthy male volunteers (n = 7) were studied on five occasions 1 wk apart randomly receiving 0.6 nmol.kg-1 s.c. 125I-labeled AspB10 or soluble human insulin (Novolin R, Novo, Copenhagen); 1st study and 0.6 nmol.kg-1 s.c. 125I-labeled AspB28, AspB9GluB27 or soluble human insulin (2nd study). Residual radioactivity at the injection site was measured over 8 h with frequent venous sampling for plasma immunoreactive insulin or analogue, glucose, C-peptide, and blood intermediary metabolite concentrations. The three analogues were absorbed 2-3 times faster than human insulin. The mean +/- SE time to 50% residual radioactivity was 94 +/- 6 min for AspB10 compared with 184 +/- 10 min for human insulin (P less than 0.001), 83 +/- 8 min for AspB28 (P less than 0.005), and 63 +/- 9 min for AspB9GluB27 (P less than 0.001) compared with 182 +/- 21 min for human insulin. delta Peak plasma insulin analogue levels were significantly higher after each analogue than after human insulin (P less than 0.005). With all three analogues, the mean hypoglycemic nadir occurred earlier at 61-65 min postinjection compared with 201-210 min for the reference human insulins (P less than 0.005). The magnitude of the hypoglycemic nadir was greater after AspB9GluB27 (P less than 0.05) and AspB28 (P less than 0.001) compared with human insulin. There was a significantly faster onset and offset of responses in C-peptide and intermediary metabolite levels after the analogues than after human insulin (P less than 0.05). The rapid absorption and biological actions of these analogues offer potential therapeutic advantages over the current short

Insulin lispro: a pharmacoeconomic review of its use in diabetes mellitus.

PubMed

Dunn, Christopher J; Plosker, Greg L

2002-01-01

Insulin lispro is a recombinant insulin analogue with transposed amino acids (proline and lysine) at positions 28 and 29 near the C-terminus of the B-chain. The most prominent practical advantage of insulin lispro over human soluble insulin lies in its very rapid onset of action. This property allows it to be injected immediately before meals and minimises the demands made on patients with type 1 diabetes mellitus, and those with type 2 disease who require insulin, by the ongoing need for careful meal planning and timing. Numerous clinical studies have shown significant improvements in postprandial glycaemic control, with some evidence of reduced rates of severe or nocturnal hypoglycaemia, relative to conventional human insulin in patients receiving lispro-based insulins. Quality-of-life studies show consistent preferences by patients for and increased treatment satisfaction with insulin lispro over human soluble insulin, particularly with variations of the Diabetes Treatment Satisfaction Questionnaire. Willingness of patients and taxpayers to pay additional costs for insulin lispro or a premixed lispro-based formulation over conventional human insulins, and cost benefits favouring formulary inclusion, have been shown in well designed studies carried out in Australia and Canada. Spanish data suggest cost effectiveness in terms of episodes of severe hypoglycaemia avoided, and preliminary German resource utilisation data indicate cost savings related to reduced hospitalisation and general practice costs, with insulin lispro relative to human soluble insulin. Insulin lispro and premixed formulations of lispro-based insulins offer quality-of-life improvements relative to conventional human insulins in patients with diabetes mellitus. Participants in well designed studies have expressed a preference for lispro-based insulins and have been shown to be willing to pay for the advantages they offer, and current cost-benefit data favour the inclusion of these insulins in

Effects of switching from prandial premixed insulin therapy to basal plus two times bolus insulin therapy on glycemic control and quality of life in patients with type 2 diabetes mellitus

PubMed Central

Ito, Hiroyuki; Abe, Mariko; Antoku, Shinichi; Omoto, Takashi; Shinozaki, Masahiro; Nishio, Shinya; Mifune, Mizuo; Togane, Michiko

2014-01-01

Background The effects of switching from prandial premixed insulin therapy (PPT) injected three times a day to basal plus two times bolus insulin therapy (B2B) on glycemic control and quality of life were investigated in patients with type 2 diabetes mellitus. Methods The clinical course was prospectively observed during the first 16 weeks after switching to B2B (insulin glargine plus insulin glulisine before breakfast and dinner) in 27 subjects previously treated with PPT using 50/50 premixed insulin. The Diabetes Treatment Satisfaction Questionnaire (DTSQ) was administered at the start and end of the study. Results The glycated hemoglobin (HbA1c) level (8.3%±1.8% to 8.2%±1.1%) and the DTSQ score did not change between the start and end of the study. An improvement in HbA1c level was found in nine (33%) subjects. The change in HbA1c showed a significant negative correlation with baseline HbA1c, and was significantly better in patients with a baseline HbA1c >8.0% than in those with an HbA1c ≤8.0% (−0.9±2.0 versus 0.3±0.6, respectively, P=0.02). The change in DTSQ score representing treatment satisfaction was significantly greater in patients whose HbA1c level was improved than in those in whom it was not (2.7±3.6 versus −0.8±3.5, P=0.04). Conclusion B2B was noninferior to PPT with regard to HbA1c levels in patients with type 2 diabetes mellitus. B2B should be considered particularly for subjects whose glycemic control is poor despite PPT. PMID:24790413

Effects of switching from prandial premixed insulin therapy to basal plus two times bolus insulin therapy on glycemic control and quality of life in patients with type 2 diabetes mellitus.

PubMed

Ito, Hiroyuki; Abe, Mariko; Antoku, Shinichi; Omoto, Takashi; Shinozaki, Masahiro; Nishio, Shinya; Mifune, Mizuo; Togane, Michiko

2014-01-01

The effects of switching from prandial premixed insulin therapy (PPT) injected three times a day to basal plus two times bolus insulin therapy (B2B) on glycemic control and quality of life were investigated in patients with type 2 diabetes mellitus. The clinical course was prospectively observed during the first 16 weeks after switching to B2B (insulin glargine plus insulin glulisine before breakfast and dinner) in 27 subjects previously treated with PPT using 50/50 premixed insulin. The Diabetes Treatment Satisfaction Questionnaire (DTSQ) was administered at the start and end of the study. The glycated hemoglobin (HbA1c) level (8.3% ± 1.8% to 8.2% ± 1.1%) and the DTSQ score did not change between the start and end of the study. An improvement in HbA1c level was found in nine (33%) subjects. The change in HbA1c showed a significant negative correlation with baseline HbA1c, and was significantly better in patients with a baseline HbA1c >8.0% than in those with an HbA1c ≤ 8.0% (-0.9 ± 2.0 versus 0.3 ± 0.6, respectively, P = 0.02). The change in DTSQ score representing treatment satisfaction was significantly greater in patients whose HbA1c level was improved than in those in whom it was not (2.7 ± 3.6 versus -0.8 ± 3.5, P = 0.04). B2B was noninferior to PPT with regard to HbA1c levels in patients with type 2 diabetes mellitus. B2B should be considered particularly for subjects whose glycemic control is poor despite PPT.

Comparison of the impact of human vs analogue insulins on glycosylated haemoglobin in a population with diabetes mellitus.

PubMed

Machado-Alba, Jorge Enrique; Medina-Morales, Diego Alejandro

2016-12-01

To compare the effect on metabolic control of treatment with conventional and analogue insulins for patients with diabetes mellitus. Retrospective cohort study held in cities of Colombia (Pereira and Manizales). People insured by the paid healthcare system, who were diagnosed with diabetes mellitus type 1 and 2, and treated with conventional and analogue insulin for at least 6 months prior to the start of the study were sampled and followed up for 18 months. Data were collected from clinical records for each patient. Treatment groups were compared according to the type of insulin received. A total of 313 patients were included; overall, 56.9% were women and the mean age was 57.3 years. No statistically significant difference was found in glycosylated haemoglobin reduction at 3, 6 and 18 months when comparing patients receiving glargine vs NPH insulin (P=.403) and NPH plus zinc crystalline insulin vs glargine plus glulisine (P=.514). The percentage of patients with metabolic control increased from 27.8% to 34.2% during follow-up with all types of insulin. Insulin analogues were not superior to human insulin for glycaemic control. A significant proportion of patients did not attain the treatment goals; therefore, it is necessary to implement measures to improve the monitoring and control of diabetes mellitus. © 2016 John Wiley & Sons Ltd.

Factors associated with reaching or not reaching target HbA1c after initiation of basal or premixed insulin in patients with type 2 diabetes.

PubMed

Scheen, A J; Schmitt, H; Jiang, H H; Ivanyi, T

2017-02-01

To evaluate factors associated with reaching or not reaching target glycated haemoglobin (HbA 1c ) levels by analysing the respective contributions of fasting hyperglycaemia (FHG), also referred to as basal hyperglycaemia, vs postprandial hyperglycaemia (PHG) before and after initiation of a basal or premixed insulin regimen in patients with type 2 diabetes. This post-hoc analysis of insulin-naïve patients in the DURABLE study randomised to receive either insulin glargine or insulin lispro mix 25 evaluated the percentages of patients achieving a target HbA 1c of <7.0% (<53mmol/mol) per baseline HbA 1c quartiles, and the effect of each insulin regimen on the relative contributions of PHG and FHG to overall hyperglycaemia. Patients had comparable demographic characteristics and similar HbA 1c and FHG values at baseline in each HbA 1c quartile regardless of whether they reached the target HbA 1c . The higher the HbA 1c quartile, the greater was the decrease in HbA 1c , but also the smaller the percentage of patients achieving the target HbA 1c . HbA 1c and FHG decreased more in patients reaching the target, resulting in significantly lower values at endpoint in all baseline HbA 1c quartiles with either insulin treatment. Patients not achieving the target HbA 1c had slightly higher insulin doses, but lower total hypoglycaemia rates. Smaller decreases in FHG were associated with not reaching the target HbA 1c , suggesting a need to increase basal or premixed insulin doses to achieve targeted fasting plasma glucose and improve patient response before introducing more intensive prandial insulin regimens. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

Computational study of the activity, dynamics, energetics and conformations of insulin analogues using molecular dynamics simulations: Application to hyperinsulinemia and the critical residue B26.

PubMed

Papaioannou, Anastasios; Kuyucak, Serdar; Kuncic, Zdenka

2017-09-01

Due to the increasing prevalence of diabetes, finding therapeutic analogues for insulin has become an urgent issue. While many experimental studies have been performed towards this end, they have limited scope to examine all aspects of the effect of a mutation. Computational studies can help to overcome these limitations, however, relatively few studies that focus on insulin analogues have been performed to date. Here, we present a comprehensive computational study of insulin analogues-three mutant insulins that have been identified with hyperinsulinemia and three mutations on the critical B26 residue that exhibit similar binding affinity to the insulin receptor-using molecular dynamics simulations with the aim of predicting how mutations of insulin affect its activity, dynamics, energetics and conformations. The time evolution of the conformers is studied in long simulations. The probability density function and potential of mean force calculations are performed on each insulin analogue to unravel the effect of mutations on the dynamics and energetics of insulin activation. Our conformational study can decrypt the key features and molecular mechanisms that are responsible for an enhanced or reduced activity of an insulin analogue. We find two key results: 1) hyperinsulinemia may be due to the drastically reduced activity (and binding affinity) of the mutant insulins. 2) Y26 B S and Y26 B E are promising therapeutic candidates for insulin as they are more active than WT-insulin. The analysis in this work can be readily applied to any set of mutations on insulin to guide development of more effective therapeutic analogues.

Fields of application of continuous subcutaneous insulin infusion in the treatment of diabetes and implications in the use of rapid-acting insulin analogues.

PubMed

Pitocco, D; Rizzi, A; Scavone, G; Tanese, L; Zaccardi, F; Manto, A; Ghirlanda, G

2013-09-01

In western countries, diabetes mellitus, because of macrovascular and microvascular complications related to it, is still an important cause of death. Patients with type 1 diabetes mellitus (T1DM) have a six-time higher risk of mortality than healthy patients. Since the Diabetes Control and Complications Trial (DCCT) established how an intensive therapy is necessary to prevent diabetes mellitus complications, many studies have been conducted to understand which method is able to reach an optimal metabolic control. In the past 30 years continuous subcutaneous insulin infusion established/introduced as a validate alternative to multiple daily injections. Several trials demonstrated that, when compared to MDI, CSII brings to a better metabolic control, in terms of a reduction of glycated hemoglobin and blood glucose variability, hypoglycemic episodes and improvement in quality of life. Because of their pharmacokinetic and pharmacodynamic characteristics, rapid-action insulin analogues are imposed as best insulin to be used in CSII. The rapid onset and the fast reached peak make them better mimic the way how pancreas secretes insulin. CSII by pump is not free from issues. Catheter occlusions, blockages, clogs can arrest insulin administration. The consequent higher levels of glycemic values, can easily bring to the onset of ketoacidosis, with an high risk for patients' life. Aspart is a rapid analogue obtained by aminoacidic substitution. It is as effective as lispro and glulisine in gaining a good metabolic control and even better in reducing glucose variability. Some studies tried to compare rapid analogues in terms of stability. Obtained data are controversial. An in vivo study evidenced higher stability or glulisine, while studies in vitro highlighted a higher safety of aspart. Nowadays it is not possible to assess which analogues is safer. When the infusion set is changed every 48 hours equivalent rates of occlusions have been observed.

EADSG Guidelines: Insulin Therapy in Diabetes.

PubMed

Silver, Bahendeka; Ramaiya, Kaushik; Andrew, Swai Babu; Fredrick, Otieno; Bajaj, Sarita; Kalra, Sanjay; Charlotte, Bavuma M; Claudine, Karigire; Makhoba, Anthony

2018-04-01

A diagnosis of diabetes or hyperglycemia should be confirmed prior to ordering, dispensing, or administering insulin (A). Insulin is the primary treatment in all patients with type 1 diabetes mellitus (T1DM) (A). Typically, patients with T1DM will require initiation with multiple daily injections at the time of diagnosis. This is usually short-acting insulin or rapid-acting insulin analogue given 0 to 15 min before meals together with one or more daily separate injections of intermediate or long-acting insulin. Two or three premixed insulin injections per day may be used (A). The target glycated hemoglobin A1c (HbA1c) for all children with T1DM, including preschool children, is recommended to be < 7.5% (< 58 mmol/mol). The target is chosen aiming at minimizing hyperglycemia, severe hypoglycemia, hypoglycemic unawareness, and reducing the likelihood of development of long-term complications (B). For patients prone to glycemic variability, glycemic control is best evaluated by a combination of results with self-monitoring of blood glucose (SMBG) (B). Indications for exogenous insulin therapy in patients with type 2 diabetes mellitus (T2DM) include acute illness or surgery, pregnancy, glucose toxicity, contraindications to or failure to achieve goals with oral antidiabetic medications, and a need for flexible therapy (B). In T2DM patients, with regards to achieving glycemic goals, insulin is considered alone or in combination with oral agents when HbA1c is ≥ 7.5% (≥ 58 mmol/mol); and is essential for treatment in those with HbA1c ≥ 10% (≥ 86 mmol/mol), when diet, physical activity, and other antihyperglycemic agents have been optimally used (B). The preferred method of insulin initiation in T2DM is to begin by adding a long-acting (basal) insulin or once-daily premixed/co-formulation insulin or twice-daily premixed insulin, alone or in combination with glucagon-like peptide-1 receptor agonist (GLP-1 RA) or in combination with other oral antidiabetic

Personalized intensification of insulin therapy in type 2 diabetes - does a basal-bolus regimen suit all patients?

PubMed

Giugliano, D; Sieradzki, J; Stefanski, A; Gentilella, R

2016-08-01

Many patients with type 2 diabetes mellitus (T2DM) require insulin therapy. If basal insulin fails to achieve glycemic control, insulin intensification is one possible treatment intensification strategy. We summarized clinical data from randomized clinical trials designed to compare the efficacy and safety of basal-bolus and premixed insulin intensification regimens. We defined a between-group difference of ≥0.3% in end-of-study glycated hemoglobin (HbA1c) as clinically meaningful. A PubMed database search supplemented by author-identified papers yielded 15 trials which met selection criteria: randomized design, patients with T2DM receiving basal-bolus (bolus injection ≤3 times/day) vs. premixed (≤3 injections/day) insulin regimens, primary/major endpoint(s) HbA1c- and/or hypoglycemia-related, and trial duration ≥12 weeks. Glycemic control improved with both basal-bolus and premixed insulin regimens with - in most cases - acceptable levels of weight gain and hypoglycemia. A clinically meaningful difference between regimens in glycemic control was recorded in only four comparisons, all of which favored basal-bolus therapy. The incidence of hypoglycemia was significantly different between regimens in only three comparisons, one of which favored premixed insulin and two basal-bolus therapy. Of the four trials that reported a significant difference between regimens in bodyweight change, two favored basal-bolus therapy and two favored premixed insulin. Thus, on a population level, neither basal-bolus therapy nor premixed insulin showed a consistent advantage in terms of glycemic control, hypoglycemic risk, or bodyweight gain. It is therefore recommended that clinicians should adopt an individualized approach to insulin intensification - taking into account the benefits and risks of each treatment approach and the attitude and preferences of each patient - in the knowledge that both basal-bolus and premixed regimens may be successful.

Effect of insulin analogues on frequency of non-severe hypoglycaemia in patients with type 1 diabetes prone to severe hypoglycaemia: The HypoAna trial.

PubMed

Agesen, R M; Kristensen, P L; Beck-Nielsen, H; Nørgaard, K; Perrild, H; Christiansen, J S; Jensen, T; Hougaard, P; Parving, H H; Thorsteinsson, B; Tarnow, L; Pedersen-Bjergaard, U

2016-09-01

Insulin analogues reduce the risk of hypoglycaemia compared with human insulin in patients with type 1 diabetes (T1D) and minor hypoglycaemia problems. The HypoAna trial showed that, in patients with recurrent severe hypoglycaemia, treatment based on insulin analogues reduces the risk of severe hypoglycaemia. The present study aims to assess whether this also applies to non-severe hypoglycaemia events during the day and at night. This 2-year investigator-initiated multicentre, prospective, randomized, open, blinded endpoint (PROBE) trial involved patients with T1D and at least two episodes of severe hypoglycaemia during the previous year. Using a balanced crossover design, patients were randomized to basal-bolus therapy based on analogue (detemir/aspart) or human (NPH/regular) insulins. A total of 114 participants were included. Endpoints were the number of severe hypoglycaemic events and non-severe events, including documented symptomatic and asymptomatic episodes occurring during the day and at night (ClinicalTrials.gov number: NCT00346996). Analogue-based treatment resulted in a 6% (2-10%; P=0.0025) overall relative risk reduction of non-severe hypoglycaemia. This was due to a 39% (32-46%; P<0.0001) reduction of non-severe nocturnal hypoglycaemia, seen for both symptomatic (48% [36-57%]; P<0.0001) and asymptomatic (28% [14-39%]; P=0.0004) nocturnal hypoglycaemia episodes. No clinically significant differences in hypoglycaemia occurrence were observed between the insulin regimens during the day. The time needed to treat one patient with insulin analogues to avoid one episode (TNT1) of non-severe nocturnal hypoglycaemia was approximately 3 months. In T1D patients prone to severe hypoglycaemia, treatment with analogue insulin reduced the risk of non-severe nocturnal hypoglycaemia compared with human insulin. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

Human insulin analogues modified at the B26 site reveal a hormone conformation that is undetected in the receptor complex

DOE Office of Scientific and Technical Information (OSTI.GOV)

Žáková, Lenka; Kletvíková, Emília; Lepšík, Martin

[AsnB26]- and [GlyB26]-insulin mutants attain a B26-turn like fold without assistance of chemical modifications. Their structures match the insulin receptor interface and expand the spectrum of insulin conformations. The structural characterization of the insulin–insulin receptor (IR) interaction still lacks the conformation of the crucial B21–B30 insulin region, which must be different from that in its storage forms to ensure effective receptor binding. Here, it is shown that insulin analogues modified by natural amino acids at the TyrB26 site can represent an active form of this hormone. In particular, [AsnB26]-insulin and [GlyB26]-insulin attain a B26-turn-like conformation that differs from that inmore » all known structures of the native hormone. It also matches the receptor interface, avoiding substantial steric clashes. This indicates that insulin may attain a B26-turn-like conformation upon IR binding. Moreover, there is an unexpected, but significant, binding specificity of the AsnB26 mutant for predominantly the metabolic B isoform of the receptor. As it is correlated with the B26 bend of the B-chain of the hormone, the structures of AsnB26 analogues may provide the first structural insight into the structural origins of differential insulin signalling through insulin receptor A and B isoforms.« less

High-mix insulins

PubMed Central

Kalra, Sanjay; Farooqi, Mohammad Hamed; El-Houni, Ali E.

2015-01-01

Premix insulins are commonly used insulin preparations, which are available in varying ratios of different molecules. These drugs contain one short- or rapid-acting, and one intermediate- or long-acting insulin. High-mix insulins are mixtures of insulins that contain 50% or more than 50% of short-acting insulin. This review describes the clinical pharmacology of high-mix insulins, including data from randomized controlled trials. It suggests various ways, in which high-mix insulin can be used, including once daily, twice daily, thrice daily, hetero-mix, and reverse regimes. The authors provide a rational framework to help diabetes care professionals, identify indications for pragmatic high-mix use. PMID:26425485

A prospective randomised cross-over study of the effect of insulin analogues and human insulin on the frequency of severe hypoglycaemia in patients with type 1 diabetes and recurrent hypoglycaemia (the HypoAna trial): study rationale and design

PubMed Central

2012-01-01

Background Severe hypoglycaemia still represents a significant problem in insulin-treated diabetes. Most patients do not experience severe hypoglycaemia often. However, 20% of patients with type 1 diabetes experience recurrent severe hypoglycaemia corresponding to at least two episodes per year. The effect of insulin analogues on glycaemic control has been documented in large trials, while their effect on the frequency of severe hypoglycaemia is less clear, especially in patients with recurrent severe hypoglycaemia. The HypoAna Trial is designed to investigate whether short-acting and long-acting insulin analogues in comparison with human insulin are superior in reducing the occurrence of severe hypoglycaemic episodes in patients with recurrent hypoglycaemia. This paper reports the study design of the HypoAna Trial. Methods/design The study is a Danish two-year investigator-initiated, prospective, randomised, open, blinded endpoint (PROBE), multicentre, cross-over trial investigating the effect of insulin analogues versus human insulin on the frequency of severe hypoglycaemia in subjects with type 1 diabetes. Patients are randomised to treatment with basal-bolus therapy with insulin detemir / insulin aspart or human NPH insulin / human regular insulin in random order. The major inclusion criterion is history of two or more episodes of severe hypoglycaemia in the preceding year. Discussion In contrast to almost all other studies in this field the HypoAna Trial includes only patients with major problems with hypoglycaemia. The HypoAna Trial will elucidate whether basal-bolus regimen with short-acting and long-acting insulin analogues in comparison with human insulin are superior in reducing occurrence of severe hypoglycaemic episodes in hypoglycaemia prone patients with type 1 diabetes. http://www.clinicaltrials.gov: NCT00346996. PMID:22727048

Comparative assessment of the efficacy and safety of acarbose and metformin combined with premixed insulin in patients with type 2 diabetes mellitus.

PubMed

Wu, Honghua; Liu, Jie; Lou, Qingqing; Liu, Jing; Shen, Li; Zhang, Mingxia; Lv, Xiaofeng; Gu, Mingjun; Guo, Xiaohui

2017-09-01

This study, a subgroup analysis of the data from the Organization Program of DiabEtes INsulIN ManaGement study, aimed to compare the efficacy and safety profiles of acarbose and metformin used in combination with premixed insulin.This analysis included 80 and 192 patients taking only 1 oral antidiabetic drug, classified into acarbose (treated with acarbose + insulin) and metformin groups (treated with metformin + insulin), respectively. The efficacy and safety data were analyzed for within- and between-group differences. The clinical trial registry number was NCT01338376.The percentage of patients who achieved target hemoglobin A1c (HbA1c) <7% in the acarbose and metformin groups were 38.75% and 30.73%, respectively, after a 16-week treatment. The average HbA1c levels in the acarbose and metformin groups were comparable at baseline and decreased significantly in both groups at the end of the study. All 7 blood glucose decreased significantly in both groups at endpoint compared with that at baseline. Insulin consumption was higher in the metformin group in terms of total daily amount and units/kg body weight. Incidences of hypoglycemia were similar in both groups. Body weight changed significantly in both groups from baseline to endpoint, but with no significant difference between the groups. Mean scores of Morisky Medication Adherence Scale improved in both groups at endpoint.Combination of insulin with acarbose or metformin could improve glycemic control in patients with type 2 diabetes mellitus. Acarbose and metformin were found to be comparable in terms of efficacy, weight gain, and incidence of hypoglycemia.

Multinational Consensus: Insulin Initiation with Insulin Degludec/Aspart (IDegAsp).

PubMed

Kalra, Sanjay; Atkin, Stephen; Cervera, Antonio; Das, Ashok Kumar; Demir, Ozgur; Demir, Tevfik; Fariduddin, Md; Vo, Khoa Tuan; Ku, Bon Jeong; Kumar, Ajay; Latif, Zafar A; Malek, Rachid; Matawaran, Bien J; Mehta, Roopa; Tran, Nam Quang; Panelo, Araceli; Ruder, Sundeep; Saldana, Joel Rodriquez; Shaikh, Khalid A; Shakya, Amit; Shrestha, Dina; Unnikrishnan, A G

2018-05-23

Insulin degludec/aspart (IDegAsp) is the first soluble insulin co-formulation, combining a long-acting insulin degludec (IDeg) and rapid-acting insulin aspart (IAsp). In type 2 diabetes patients with oral antidiabetes agent (OAD) inadequacy, insulin initiation with IDegAsp once daily provides superior long-term glycemic control compared to insulin glargine, with similar fasting plasma glucose (FPG) and insulin doses, and numerically lower rates of overall and nocturnal hypoglycemia. Furthermore, in patients with uncontrolled type 2 diabetes previously treated with insulins, IDegAsp twice daily effectively improves glycated hemoglobin and FPG, with fewer hypoglycemic episodes versus premix insulins and basal bolus therapy. In patients with type 1 diabetes mellitus, IDegAsp once daily with two doses of IAsp is a convenient, yet effective, regimen as compared to the conventional 4-5 injection-based basal bolus therapy. IDegAsp is an appropriate and reasonable option for initiation of insulin therapy in both type 1 and type 2 diabetes.

Comparative assessment of the efficacy and safety of acarbose and metformin combined with premixed insulin in patients with type 2 diabetes mellitus

PubMed Central

Wu, Honghua; Liu, Jie; Lou, Qingqing; Liu, Jing; Shen, Li; Zhang, Mingxia; Lv, Xiaofeng; Gu, Mingjun; Guo, Xiaohui

2017-01-01

Abstract This study, a subgroup analysis of the data from the Organization Program of DiabEtes INsulIN ManaGement study, aimed to compare the efficacy and safety profiles of acarbose and metformin used in combination with premixed insulin. This analysis included 80 and 192 patients taking only 1 oral antidiabetic drug, classified into acarbose (treated with acarbose + insulin) and metformin groups (treated with metformin + insulin), respectively. The efficacy and safety data were analyzed for within- and between-group differences. The clinical trial registry number was NCT01338376. The percentage of patients who achieved target hemoglobin A1c (HbA1c) <7% in the acarbose and metformin groups were 38.75% and 30.73%, respectively, after a 16-week treatment. The average HbA1c levels in the acarbose and metformin groups were comparable at baseline and decreased significantly in both groups at the end of the study. All 7 blood glucose decreased significantly in both groups at endpoint compared with that at baseline. Insulin consumption was higher in the metformin group in terms of total daily amount and units/kg body weight. Incidences of hypoglycemia were similar in both groups. Body weight changed significantly in both groups from baseline to endpoint, but with no significant difference between the groups. Mean scores of Morisky Medication Adherence Scale improved in both groups at endpoint. Combination of insulin with acarbose or metformin could improve glycemic control in patients with type 2 diabetes mellitus. Acarbose and metformin were found to be comparable in terms of efficacy, weight gain, and incidence of hypoglycemia. PMID:28858080

Insulin degludec and insulin aspart: novel insulins for the management of diabetes mellitus

PubMed Central

Atkin, Stephen; Javed, Zeeshan; Fulcher, Gregory

2015-01-01

Patients with type 2 diabetes mellitus require insulin as disease progresses to attain or maintain glycaemic targets. Basal insulin is commonly prescribed initially, alone or with one or more rapid-acting prandial insulin doses, to limit mealtime glucose excursions (a basal–bolus regimen). Both patients and physicians must balance the advantages of improved glycaemic control with the risk of hypoglycaemia and increasing regimen complexity. The rapid-acting insulin analogues (insulin aspart, insulin lispro and insulin glulisine) all have similar pharmacokinetic and pharmacodynamic characteristics and clinical efficacy/safety profiles. However, there are important differences in the pharmacokinetic and pharmacodynamic profiles of basal insulins (insulin glargine, insulin detemir and insulin degludec). Insulin degludec is an ultra-long-acting insulin analogue with a flat and stable glucose-lowering profile, a duration of action exceeding 30 h and less inter-patient variation in glucose-lowering effect than insulin glargine. In particular, the chemical properties of insulin degludec have allowed the development of a soluble co-formulation with prandial insulin aspart (insulin degludec/insulin aspart) that provides basal insulin coverage for at least 24 h with additional mealtime insulin for one or two meals depending on dose frequency. Pharmacokinetic and pharmacodynamic studies have shown that the distinct, long basal glucose-lowering action of insulin degludec and the prandial glucose-lowering effect of insulin aspart are maintained in the co-formulation. Evidence from pivotal phase III clinical trials indicates that insulin degludec/insulin aspart translate into sustained glycaemic control with less hypoglycaemia and the potential for a simpler insulin regimen with fewer daily injections. PMID:26568812

Remission in models of type 1 diabetes by gene therapy using a single-chain insulin analogue

NASA Astrophysics Data System (ADS)

Lee, Hyun Chul; Kim, Su-Jin; Kim, Kyung-Sup; Shin, Hang-Cheol; Yoon, Ji-Won

2000-11-01

A cure for diabetes has long been sought using several different approaches, including islet transplantation, regeneration of β cells and insulin gene therapy. However, permanent remission of type 1 diabetes has not yet been satisfactorily achieved. The development of type 1 diabetes results from the almost total destruction of insulin-producing pancreatic β cells by autoimmune responses specific to β cells. Standard insulin therapy may not maintain blood glucose concentrations within the relatively narrow range that occurs in the presence of normal pancreatic β cells. We used a recombinant adeno-associated virus (rAAV) that expresses a single-chain insulin analogue (SIA), which possesses biologically active insulin activity without enzymatic conversion, under the control of hepatocyte-specific L-type pyruvate kinase (LPK) promoter, which regulates SIA expression in response to blood glucose levels. Here we show that SIA produced from the gene construct rAAV-LPK-SIA caused remission of diabetes in streptozotocin-induced diabetic rats and autoimmune diabetic mice for a prolonged time without any apparent side effects. This new SIA gene therapy may have potential therapeutic value for the cure of autoimmune diabetes in humans.

Identification of residues in the insulin molecule important for binding to insulin-degrading enzyme.

PubMed

Affholter, J A; Cascieri, M A; Bayne, M L; Brange, J; Casaretto, M; Roth, R A

1990-08-21

Insulin-degrading enzyme (IDE) hydrolyzes insulin at a limited number of sites. Although the positions of these cleavages are known, the residues of insulin important in its binding to IDE have not been defined. To this end, we have studied the binding of a variety of insulin analogues to the protease in a solid-phase binding assay using immunoimmobilized IDE. Since IDE binds insulin with 600-fold greater affinity than it does insulin-like growth factor I (25 nM and approximately 16,000 nM, respectively), the first set of analogues studied were hybrid molecules of insulin and IGF I. IGF I mutants [insB1-17,17-70]IGF I, [Tyr55,Gln56]IGF I, and [Phe23,Phe24,Tyr25]IGF I have been synthesized and share the property of having insulin-like amino acids at positions corresponding to primary sites of cleavage of insulin by IDE. Whereas the first two exhibit affinities for IDE similar to that of wild type IGF I, the [Phe23,Phe24,Tyr25]IGF I analogue has a 32-fold greater affinity for the immobilized enzyme. Replacement of Phe-23 by Ser eliminates this increase. Removal of the eight amino acid D-chain region of IGF I (which has been predicted to interfere with binding to the 23-25 region) results in a 25-fold increase in affinity for IDE, confirming the importance of residues 23-25 in the high-affinity recognition of IDE. A similar role for the corresponding (B24-26) residues of insulin is supported by the use of site-directed mutant and semisynthetic insulin analogues. Insulin mutants [B25-Asp]insulin and [B25-His]insulin display 16- and 20-fold decreases in IDE affinity versus wild-type insulin.(ABSTRACT TRUNCATED AT 250 WORDS)

Flashback resistant pre-mixer assembly

DOEpatents

Laster, Walter R [Oviedo, FL; Gambacorta, Domenico [Oviedo, FL

2012-02-14

A pre-mixer assembly associated with a fuel supply system for mixing of air and fuel upstream from a main combustion zone in a gas turbine engine. The pre-mixer assembly includes a swirler assembly disposed about a fuel injector of the fuel supply system and a pre-mixer transition member. The swirler assembly includes a forward end defining an air inlet and an opposed aft end. The pre-mixer transition member has a forward end affixed to the aft end of the swirler assembly and an opposed aft end defining an outlet of the pre-mixer assembly. The aft end of the pre-mixer transition member is spaced from a base plate such that a gap is formed between the aft end of the pre-mixer transition member and the base plate for permitting a flow of purge air therethrough to increase a velocity of the air/fuel mixture exiting the pre-mixer assembly.

Original paper: Efficacy and safety analysis of insulin degludec/insulin aspart compared with biphasic insulin aspart 30: A phase 3, multicentre, international, open-label, randomised, treat-to-target trial in patients with type 2 diabetes fasting during Ramadan.

PubMed

Hassanein, Mohamed; Echtay, Akram Salim; Malek, Rachid; Omar, Mahomed; Shaikh, Shehla Sajid; Ekelund, Magnus; Kaplan, Kadriye; Kamaruddin, Nor Azmi

2018-01-01

To compare the efficacy and safety of insulin degludec/insulin aspart (IDegAsp) and biphasic insulin aspart 30 (BIAsp 30) before, during and after Ramadan in patients with type 2 diabetes mellitus (T2DM) who fasted during Ramadan. In this multinational, randomised, treat-to-target trial, patients with T2DM who intended to fast and were on basal, pre- or self-mixed insulin ± oral antidiabetic drugs for ≥90 days were randomised (1:1) to IDegAsp twice daily (BID) or BIAsp 30 BID. Treatment period included pre-Ramadan treatment initiation (with insulin titration for 8-20 weeks), Ramadan (4 weeks) and post-Ramadan (4 weeks). Insulin doses were reduced by 30-50% for the pre-dawn meal (suhur) on the first day of Ramadan, and readjusted to the pre-Ramadan levels at the end of Ramadan. Hypoglycaemia was analysed as overall (severe or plasma glucose <3.1 mmol/L [56 mg/dL]), nocturnal (00:01-05:59) or severe (requiring assistance of another person). During the treatment period, IDegAsp (n = 131) had significantly lower overall and nocturnal hypoglycaemia rates with similar glycaemic efficacy, versus BIAsp 30 (n = 132). During Ramadan, despite achieving significantly lower pre-iftar (meal at sunset) self-measured plasma glucose (estimated treatment difference: -0.54 mmol/L [-1.02; -0.07] 95% CI , p = .0247; post hoc) with similar overall glycaemic efficacy, IDegAsp showed significantly lower overall and nocturnal hypoglycaemia rates versus BIAsp 30. IDegAsp is a suitable therapeutic agent for patients who need insulin for sustained glucose control before, during and after Ramadan fasting, with a significantly lower risk of hypoglycaemia, versus BIAsp 30, an existing premixed insulin analogue. Copyright © 2017. Published by Elsevier B.V.

Combining insulins for optimal blood glucose control in type 1 and 2 diabetes: Focus on insulin glulisine

PubMed Central

Ulrich, Heather; Snyder, Benjamin; K Garg, Satish

2007-01-01

Normalization of blood glucose is essential for the prevention of diabetes mellitus (DM)-related microvascular and macrovascular complications. Despite substantial literature to support the benefits of glucose lowering and clear treatment targets, glycemic control remains suboptimal for most people with DM in the United States. Pharmacokinetic limitations of conventional insulins have been a barrier to achieving treatment targets secondary to adverse effects such as hypoglycemia and weight gain. Recombinant DNA technology has allowed modification of the insulin molecule to produce insulin analogues that overcome these pharmacokinetic limitations. With time action profiles that more closely mimic physiologic insulin secretion, rapid acting insulin analogues (RAAs) reduce post-prandial glucose excursions and hypoglycemia when compared to regular human insulin (RHI). Insulin glulisine (Apidra®) is a rapid-acting insulin analogue created by substituting lysine for asparagine at position B3 and glutamic acid for lysine at position B29 on the B chain of human insulin. The quick absorption of insulin glulisine more closely reproduces physiologic first-phase insulin secretion and its rapid acting profile is maintained across patient subtypes. Clinical trials have demonstrated comparable or greater efficacy of insulin glulisine versus insulin lispro or RHI, respectively. Efficacy is maintained even when insulin glulisine is administered post-meal. In addition, glulisine appears to have a more rapid time action profile compared with insulin lispro across various body mass indexes (BMIs). The safety and tolerability profile of insulin glulisine is also comparable to that of insulin lispro or RHI in type 1 or 2 DM and it has been shown to be as safe and effective when used in a continuous subcutaneous insulin infusion (CSII). In summary, insulin glulisine is a safe, effective, and well tolerated rapid-acting insulin analogue across all BMIs and a worthy option for prandial

Monomeric insulins and their experimental and clinical implications.

PubMed

Brange, J; Owens, D R; Kang, S; Vølund, A

1990-09-01

Due to the inherent pharmacokinetic properties of available insulins, normoglycemia is rarely, if ever, achieved in insulin-dependent diabetic patients without compromising their quality of life. Subcutaneous insulin absorption is influenced by many factors, among which the associated state of insulin (hexameric) in pharmaceutical formulation may be of importance. This review describes the development of a series of human insulin analogues with reduced tendency to self-association that, because of more rapid absorption, are better suited to meal-related therapy. DNA technology has made it possible to prepare insulins that remain dimeric or even monomeric at high concentration by introducing one or a few amino acid substitutions into human insulin. These analogues were characterized and used for elucidating the mechanisms involved in subcutaneous absorption and were investigated in preliminary clinical studies. Their relative receptor binding and in vitro potency (free-fat cell assay), ranging from 0.05 to 600% relative to human insulin, were strongly correlated (r = 0.97). In vivo, most of the analogues exhibited approximately 100% activity, explainable by a dominating receptor-mediated clearance. This was confirmed by clamp studies in which correlation between receptor binding and clearance was observed. Thus, an analogue with reduced binding and clearance gives higher circulating concentrations, counterbalancing the reduced potency at the cellular level. Absorption studies in pigs revealed a strong inverse correlation (r = 0.96) between the rate of subcutaneous absorption and the mean association state of the insulin analogues. These studies also demonstrated that monomeric insulins were absorbed three times faster than human insulin. In healthy subjects, rates of disappearance from subcutis were two to three times faster for dimeric and monomeric analogues than for human insulin. Concomitantly, a more rapid rise in plasma insulin concentration and an earlier

Safety and efficacy of insulin glargine 300 u/mL compared with other basal insulin therapies in patients with type 2 diabetes mellitus: a network meta-analysis.

PubMed

Freemantle, Nick; Chou, Engels; Frois, Christian; Zhuo, Daisy; Lehmacher, Walter; Vlajnic, Aleksandra; Wang, Hongwei; Chung, Hsing-Wen; Zhang, Quanwu; Wu, Eric; Gerrits, Charles

2016-02-15

To compare the efficacy and safety of a concentrated formulation of insulin glargine (Gla-300) with other basal insulin therapies in patients with type 2 diabetes mellitus (T2DM). This was a network meta-analysis (NMA) of randomised clinical trials of basal insulin therapy in T2DM identified via a systematic literature review of Cochrane library databases, MEDLINE and MEDLINE In-Process, EMBASE and PsycINFO. Changes in HbA1c (%) and body weight, and rates of nocturnal and documented symptomatic hypoglycaemia were assessed. 41 studies were included; 25 studies comprised the main analysis population: patients on basal insulin-supported oral therapy (BOT). Change in glycated haemoglobin (HbA1c) was comparable between Gla-300 and detemir (difference: -0.08; 95% credible interval (CrI): -0.40 to 0.24), neutral protamine Hagedorn (NPH; 0.01; -0.28 to 0.32), degludec (-0.12; -0.42 to 0.20) and premixed insulin (0.26; -0.04 to 0.58). Change in body weight was comparable between Gla-300 and detemir (0.69; -0.31 to 1.71), NPH (-0.76; -1.75 to 0.21) and degludec (-0.63; -1.63 to 0.35), but significantly lower compared with premixed insulin (-1.83; -2.85 to -0.75). Gla-300 was associated with a significantly lower nocturnal hypoglycaemia rate versus NPH (risk ratio: 0.18; 95% CrI: 0.05 to 0.55) and premixed insulin (0.36; 0.14 to 0.94); no significant differences were noted in Gla-300 versus detemir (0.52; 0.19 to 1.36) and degludec (0.66; 0.28 to 1.50). Differences in documented symptomatic hypoglycaemia rates of Gla-300 versus detemir (0.63; 0.19 to 2.00), NPH (0.66; 0.27 to 1.49) and degludec (0.55; 0.23 to 1.34) were not significant. Extensive sensitivity analyses supported the robustness of these findings. NMA comparisons are useful in the absence of direct randomised controlled data. This NMA suggests that Gla-300 is also associated with a significantly lower risk of nocturnal hypoglycaemia compared with NPH and premixed insulin, with glycaemic control comparable to

GAIN Premix Facility: an innovative approach for improving access to quality vitamin and mineral premix in fortification initiatives.

PubMed

Guinot, Philippe; Jallier, Vincent; Blasi, Alessandro; Guyondet, Christophe; Van Ameringen, Marc

2012-12-01

Vitamin and mineral premix is one of the most significant recurring input costs for large-scale food fortification programs. A number of barriers exist to procuring adequate quality premix, including accessing suppliers, volatile prices for premix, lack of quality assurance and monitoring of delivered products, and lack of funds to purchase premix. To develop and test a model to procure premix through a transparent and efficient process in which an adequate level of quality is guaranteed and a financial mechanism is in place to support countries or specific target groups when there are insufficient resources to cover the cost of premix. Efforts focused on premixes used to fortify flour, such as wheat or maize (iron, zinc, B vitamins, and vitamin A), edible oils (vitamins A and D), and other food vehicles, such as fortified complementary foods, complementary food supplements, and condiments. A premix procurement model was set up with three distinct components: a certification process that establishes industry-wide standards and guidelines for premix, a procurement facility that makes premix more accessible to countries and private industry engaged in fortification, and a credit facility mechanism that helps projects finance premix purchases. After three years of operation, 15 premix suppliers and 29 micronutrient manufacturers have been certified, and more than US$23 million worth of premix that met quality standards has been supplied in 34 countries in Africa, Central and Southern Asia, and Eastern Europe, reaching an estimated 242 million consumers. The Premix Facility demonstrated its effectiveness in ensuring access to high-quality premixes, therefore enabling the success of various fortification programs.

Utilization patterns of insulin therapy and healthcare services among Japanese insulin initiators during their first year: a descriptive analysis of administrative hospital data.

PubMed

Ikeda, Shunya; Crawford, Bruce; Sato, Masayo

2016-01-12

Type 2 diabetes poses an increasing healthcare burden in Japan. Although insulin treatment has diversified in recent years, the literature on the utilization of healthcare services among patients with type 2 diabetes undergoing different insulin therapy regimens is scarce. The current study aimed to characterize the real-world insulin treatment patterns and associated utilization of healthcare services among patients with type 2 diabetes who initiated insulin therapy during the study period. We examined data from a hospital-based database consisting of administrative and laboratory data from 121 acute-phase hospitals throughout Japan from April 2008 to August 2012. Patients diagnosed with type 2 diabetes and receiving continuous insulin therapy, defined by three insulin claims or more, were included in the analysis. Of the 2,145 insulin initiators, at initiation 46.5% received rapid-acting insulin alone, 36.6% received an intensive regimen, 11.4% received long-acting insulin alone, and 5.5% received pre-mixed insulin alone. Patients treated with rapid-acting insulin alone were older, experienced more comorbid conditions, had lower HbA1c, and more often had initiated their insulin treatment at inpatient admission, compared to patients treated with other types of insulin. Inpatient admission was more common and longer for patients taking rapid-acting insulin and an intensive regimen than those taking long-acting or pre-mixed insulin, and most were readmitted within 1 year. Utilization of outpatient clinics was approximately once per month, and emergency department visits were observed to be rare. This retrospective observational descriptive study found varied treatment and healthcare service utilization patterns, as well as disparities in patient characteristics across insulin regimens. Future research should assess the basis for these various utilization patterns associated with insulin to conduct robust analyses of clinical and economic outcomes.

Acylated apelin-13 amide analogues exhibit enzyme resistance and prolonged insulin releasing, glucose lowering and anorexic properties.

PubMed

O'Harte, Finbarr P M; Parthsarathy, Vadivel; Hogg, Christopher; Flatt, Peter R

2017-12-15

The adipokine, apelin has many biological functions but its activity is curtailed by rapid plasma degradation. Fatty acid derived apelin analogues represent a new and exciting avenue for the treatment of obesity-diabetes. This study explores four novel fatty acid modified apelin-13 analogues, namely, (Lys 8 GluPAL)apelin-13 amide, pGlu(Lys 8 GluPAL)apelin-13 amide, Lys 8 GluPAL(Tyr 13 )apelin-13 and Lys 8 GluPAL(Val 13 )apelin-13. Fatty acid modification extended the half-life of native apelin-13 to >24 h in vitro. pGlu(Lys 8 GluPAL)apelin-13 amide was the most potent insulinotropic analogue in BRIN-BD11 cells and isolated islets with maximal stimulatory effects of up to 2.7-fold (p < .001). (Lys 8 GluPAL)apelin-13 amide (1.9-fold) and Lys 8 GluPAL(Tyr 13 )apelin-13 (1.7-fold) were less effective, whereas Lys 8 GluPAL(Val 13 )apelin-13 had an inhibitory effect on insulin secretion. Similarly, pGlu(Lys 8 GluPAL)apelin-13 amide was most potent in increasing beta-cell intracellular Ca 2+ concentrations (1.8-fold, p < .001) and increasing glucose uptake in 3T3-L1 adipocytes (2.3-fold, p < .01). Persistent biological action was observed with both pGlu(Lys 8 GluPAL)apelin-13 amide and (Lys 8 GluPAL)apelin-13 amide significantly reducing blood glucose (39-43%, p < .01) and enhancing insulin secretion (43-56%, p < .001) during glucose tolerance tests in diet-induced obese mice. pGlu(Lys 8 GluPAL)apelin-13 amide and (Lys 8 GluPAL)apelin-13 amide also inhibited feeding (28-40%, p < .001), whereas Lys 8 GluPAL(Val 13 )apelin-13 increased food intake (8%, p < .05) in mice. These data indicate that novel enzymatically stable analogues of apelin-13 may be suitable for future development as therapeutic agents for obesity-diabetes. Copyright © 2017 Elsevier Inc. All rights reserved.

Mealtime 50/50 basal + prandial insulin analogue mixture with a basal insulin analogue, both plus metformin, in the achievement of target HbA1c and pre- and postprandial blood glucose levels in patients with type 2 diabetes: a multinational, 24-week, randomized, open-label, parallel-group comparison.

PubMed

Robbins, David C; Beisswenger, Paul J; Ceriello, Antonio; Goldberg, Ronald B; Moses, Robert G; Pagkalos, Emmanuil M; Milicevic, Zvonko; Jones, Cate A; Sarwat, Samiha; Tan, Meng H

2007-11-01

In people without diabetes, approximately 50% of daily insulin secretion is basal and the remainder is postprandial. Hence, it would be expected that insulin replacement therapy in a 50/50 ratio with each meal would mimic physiologic insulin secretion better than treatment with once-daily basal insulin in patients with diabetes mellitus. Using lispro mix (LM) 50/50 before meals may be a logical approach to achieving glycemic targets (glycosylated hemoglobin [HbA(lc)] and pre- and postprandial blood glucose [BG] concentrations) in these patients. The aim of this study was to test the hypothesis that treatment with a premixed insulin analogue containing 50/50 basal + prandial insulins administered before each meal would achieve lower overall and mealtime glycemic control than once-daily basal insulin analogue, both plus metformin (Met), in patients with type 2 diabetes mellitus. This 24-week, randomized, open-label, parallel-group trial was conducted at 38 sites across Australia, Greece, India, The Netherlands, Poland, Puerto Rico, and the United States. Male and female patients aged 35 to 75 years with type 2 diabetes mellitus and an HbA(1c) level of 6.5% to 11.0%, who were receiving metformin and/or a sulfonylurea with a stable dose of 0 to 2 daily insulin injections over the previous 3 months were eligible. Patients were randomly assigned to receive LM50/50 (50% insulin lispro protamine suspension [ILPS] and 50% lispro) TID plus metformin (to a maximally tolerated daily dosage of 500-1000 mg BID) (LM50/50 + Met) or insulin glargine QD at bedtime plus metformin (500-1000 mg BID) (G + Met) for 24 weeks. With LM50/50 + Met, the insulin dose was titrated to target a fasting BG (FBG) level of <6.7 mmol/L (<120 mg/dL) and a 2-hour post-prandial BG (PPBG) level of <8.0 mmol/L (<144 mg/dL); those who did not reach the FBG target would be switched from presupper LM50/50 to LM75/25 (75% ILPS, 25% lispro). A total of 315 patients were randomized and received treatment (158

Fuel premixing module for gas turbine engine combustor

NASA Technical Reports Server (NTRS)

Chin, Jushan (Inventor); Rizk, Nader K. (Inventor); Razdan, Mohan K. (Inventor); Marshall, Andre W. (Inventor)

2005-01-01

A fuel-air premixing module is designed to reduce emissions from a gas turbine engine. In one form, the premixing module includes a central pilot premixer module with a main premixer module positioned thereround. Each of the portions of the fuel-air premixing module include an axial inflow swirler with a plurality of fixed swirler vanes. Fuel is injected into the main premixer module between the swirler vanes of the axial inflow swirler and at an acute angle relative to the centerline of the premixing module.

Premixed Turbulent Flame Propagation in Microgravity

NASA Technical Reports Server (NTRS)

Menon, S.; Disseau, M.; Chakravarthy, V. K.; Jagoda, J.

1997-01-01

Papers included address the following topics: (1) Turbulent premixed flame propagation in microgravity; (2) The effect of gravity on turbulent premixed flame propagation - a preliminary cold flow study; and (3) Characteristics of a subgrid model for turbulent premixed combustion.

Challenges constraining insulin access in Nepal-a country with no local insulin production.

PubMed

Sharma, Abhishek; Bhandari, Parash Mani; Neupane, Dipika; Kaplan, Warren A; Mishra, Shiva Raj

2018-05-01

Nepal is facing an increasing burden of diabetes and relies almost entirely on insulin imported through India. We employed a modified version of the WHO/Health Action International standard survey to assess insulin availability and prices, along with qualitative interviews with insulin retailers (pharmacists) and wholesalers in the Kathmandu Valley, Nepal. The mean availability of the two human insulins listed on the 2011 Nepal Essential Medicine List were 14.3% and 42.85% in the surveyed private- and public-sector pharmacies, respectively, compared with the WHO target of 80% availability. The median consumer price of human insulin cartridges, analogue insulin cartridges and pens was, respectively, 2.1, 4.6 and 5.3 times that of human insulin vials (US$5.54). The insulin cartridges made in India were less expensive (p<0.001) than those made elsewhere. The lowest-paid worker would need to spend between 3 and 17 days' wages to purchase a monthly insulin supply out of pocket. Insulin access is limited in Kathmandu owing to low availability and the highly unaffordable price. Insulin access could improve with the government exploring additional suppliers, pooling insulin tenders, auditing insulin utilization and developing independent prescribing guidelines. Furthermore, there is a need to educate physicians and develop a consensus statement on insulin initiation to curb the growing analogue use and promote rational use.

Multiple tube premixing device

DOEpatents

Uhm, Jong Ho; Naidu, Balachandar; Ziminksy, Willy Steve; Kraemer, Gilbert Otto; Yilmaz, Ertan; Lacy, Benjamin; Stevenson, Christian; Felling, David

2013-08-13

The present application provides a premixer for a combustor. The premixer may include a fuel plenum with a number of fuel tubes and a burner tube with a number of air tubes. The fuel tubes extend about the air tubes.

Multiple tube premixing device

DOEpatents

Uhm, Jong Ho; Varatharajan, Balachandar; Ziminsky, Willy Steve; Kraemer, Gilbert Otto; Yilmaz, Ertan; Lacy, Benjamin; Stevenson, Christian; Felling, David

2012-12-11

The present application provides a premixer for a combustor. The premixer may include a fuel plenum with a number of fuel tubes and a burner tube with a number of air tubes. The fuel tubes extend about the air tubes.

Influence of Unweighting on Insulin Signal Transduction in Muscle

NASA Technical Reports Server (NTRS)

Tischler, Marc E.

2002-01-01

Unweighting of the juvenile soleus muscle is characterized by an increased binding capacity for insulin relative to muscle mass due to sparing of the receptors during atrophy. Although carbohydrate metabolism and protein degradation in the unweighted muscle develop increased sensitivity to insulin in vivo, protein synthesis in vivo and system A amino acid transport in vitro do not appear to develop such an enhanced response. The long-term goal is to identify the precise nature of this apparent resistance in the insulin signal transduction pathway and to consider how reduced weight-bearing may elicit this effect, by evaluating specific components of the insulin signalling pathway. Because the insulin-signalling pathway has components in common with the signal transduction pathway for insulin-like growth factor (IGF-1) and potentially other growth factors, the study could have important implications in the role of weight-bearing function on muscle growth and development. Since the insulin signalling pathway diverges following activation of insulin receptor tyrosine kinase, the immediate specific aims will be to study the receptor tyrosine kinase (IRTK) and those branches, which lead to phosphorylation of insulin receptor substrate-1 (IRS-1) and of Shc protein. To achieve these broader objectives, we will test in situ, by intramuscular injection, the responses of glucose transport, system A amino acid transport and protein synthesis to insulin analogues for which the receptor has either a weaker or much stronger binding affinity compared to insulin. Studies will include: (1) estimation of the ED(sub 50) for each analogue for these three processes; (2) the effect of duration (one to four days) of unweighting on the response of each process to all analogues tested; (3) the effect of unweighting and the analogues on IRTK activity; and (4) the comparative effects of unweighting and analogue binding on the tyrosine phosphorylation of IRTK, IRS-1, and Shc protein.

Rational steering of insulin binding specificity by intra-chain chemical crosslinking

NASA Astrophysics Data System (ADS)

Viková, Jitka; Collinsová, Michaela; Kletvíková, Emília; Buděšínský, Miloš; Kaplan, Vojtěch; Žáková, Lenka; Veverka, Václav; Hexnerová, Rozálie; Aviñó, Roberto J. Tarazona; Straková, Jana; Selicharová, Irena; Vaněk, Václav; Wright, Daniel W.; Watson, Christopher J.; Turkenburg, Johan P.; Brzozowski, Andrzej M.; Jiráček, Jiří

2016-01-01

Insulin is a key hormone of human metabolism with major therapeutic importance for both types of diabetes. New insulin analogues with more physiological profiles and better glycemic control are needed, especially analogues that preferentially bind to the metabolic B-isoform of insulin receptor (IR-B). Here, we aimed to stabilize and modulate the receptor-compatible conformation of insulin by covalent intra-chain crosslinking within its B22-B30 segment, using the CuI-catalyzed Huisgen 1,3-dipolar cycloaddition reaction of azides and alkynes. This approach resulted in 14 new, systematically crosslinked insulin analogues whose structures and functions were extensively characterized and correlated. One of the analogues, containing a B26-B29 triazole bridge, was highly active in binding to both IR isoforms, with a significant preference for IR-B. Our results demonstrate the potential of chemistry-driven modulation of insulin function, also shedding new light on the functional importance of hormone’s B-chain C-terminus for its IR-B specificity.

The new era of biotech insulin analogues.

PubMed

Brange, J

1997-07-01

Many of the structural properties of insulin have evolved in response to the requirements of biosynthesis, processing, transport and storage in the pancreatic beta cells, properties that are not necessary for the biological action of the hormone. It is therefore not surprising that wild-type insulin has far from optimal characteristics for replacement therapy. For example, native human insulin self-associates to hexameric units, which limits the possibilities for the absorption of the molecule by various routes. During the last decade new techniques of molecular design have emerged and recombinant DNA technology offers new and exciting opportunities for rational protein drug design. This review describes examples of recent advances in insulin engineering aimed at optimizing the hormone for therapy. Such approaches focus on improvements in the pharmacokinetic properties, storage stability, and feasibility for less intrusive routes of administration.

The role of GLP-1 mimetics and basal insulin analogues in type 2 diabetes mellitus: guidance from studies of liraglutide

PubMed Central

Barnett, A H

2012-01-01

In people with type 2 diabetes mellitus (T2DM), the incretin effect is reduced, but the recent advent of dipeptidyl peptidase-4 inhibitors and glucagon-like peptide (GLP)-1 agonists/analogues has enabled restoration of at least some of the function of the incretin system, with accompanying improvements in glycaemic control. Two GLP-1 receptor agonists/analogues are currently approved for the treatment of T2DM—exenatide (Byetta®, Eli Lilly & Co., Indianapolis, IN, US) and liraglutide (Victoza®, Novo Nordisk, Bagsvaerd, Denmark); a once-weekly formulation of exenatide (Bydureon®, Eli Lilly & Co.) has also been approved by the European Medicines Agency. The National Institute for Health and Clinical Excellence (NICE) has recently published guidance on the use of liraglutide in T2DM, based on evidence from the Liraglutide Effect and Action in Diabetes (LEAD) Phase III trial programme, which compared liraglutide with existing glucose-lowering therapies, such as exenatide and insulin glargine. The LEAD programme reported HbA1c reductions from 0.8 to 1.5% with liraglutide (1.2 and 1.8 mg), accompanied by low rates of hypoglycaemia and some weight loss; side effects were primarily gastrointestinal in nature (e.g. nausea and diarrhoea). Based on the findings of the LEAD studies and the NICE recommendation, liraglutide now represents an important therapy widely available in the UK for certain patient groups, including those with a body mass index (BMI) ≥35.0 kg/m2, and patients with a BMI <35 kg/m2 who are considered unsuitable for insulin and are failing to meet targets for glycaemic control with oral agents. NICE guidelines still suggest that most patients without considerable obesity (BMI <35 kg/m2) are probably best managed using insulin therapy. Evidence also suggests a future role for GLP-1 mimetics in combination with basal insulin. PMID:22051096

Therapeutically interchangeable? A study of real-world outcomes associated with switching basal insulin analogues among US patients with type 2 diabetes mellitus using electronic medical records data.

PubMed

Levin, P; Wei, W; Miao, R; Ye, F; Xie, L; Baser, O; Gill, J

2015-03-01

To evaluate real-world clinical outcomes for switching basal insulin analogues [insulin glargine (GLA) and insulin detemir (DET)] among US patients with type 2 diabetes mellitus (T2DM). Using the GE Centricity Electronic Medical Records database, this retrospective study examined two cohorts: cohort 1, comprising patients previously on GLA and then either switching to DET (DET-S) or continuing with GLA (GLA-C); and cohort 2, comprising patients previously on DET and then either switching to GLA (GLA-S) or continuing with DET (DET-C). Within each cohort, treatment groups were propensity-score-matched on baseline characteristics. At 1-year follow-up, insulin treatment patterns, glycated haemoglobin (HbA1c) levels, hypoglycaemic events, weight and body mass index (BMI) were evaluated. The analysis included 13 942 patients: cohort 1: n = 10 657 (DET-S, n = 1797 matched to GLA-C, n = 8860) and cohort 2: n = 3285 (GLA-S, n = 858 matched to DET-C, n = 2427). Baseline characteristics were similar between the treatment groups in each cohort. At 1-year follow-up, in cohort 1, patients in the DET-S subgroup were significantly less persistent with treatment, more likely to use a rapid-acting insulin analogue, had higher HbA1c values, lower HbA1c reductions and lower proportions of patients achieving HbA1c <7.0 or <8.0% compared with patients in the GLA-C subgroup, while hypoglycaemia rates and BMI/weight values and change from baseline were similar in the two subgroups. In cohort 2, overall, there were contrasting findings between patients in the GLA-S and those in the DET-C subgroup. This study showed contrasting results when patients with T2DM switched between basal insulin analogues, although these preliminary results may be subject to limitations in the analysis. Nevertheless, this study calls into question the therapeutic interchangeability of GLA and DET, and this merits further investigation. © 2014 The Authors. Diabetes, Obesity and

Clinical experience with insulin detemir, biphasic insulin aspart and insulin aspart in people with type 2 diabetes: Results from the Mumbai cohort of the A1chieve study.

PubMed

Talwalkar, P G; Gupta, Vishal; Kovil, Rajiv

2013-11-01

The A1chieve, a multicentric (28 countries), 24-week, non-interventional study evaluated the safety and effectiveness of insulin detemir, biphasic insulin aspart and insulin aspart in people with T2DM (n = 66,726) in routine clinical care across four continents. Data was collected at baseline, at 12 weeks and at 24 weeks. This short communication presents the results for patients enrolled from Mumbai, India. A total of 2112 patients were enrolled in the study. Four different insulin analogue regimens were used in the study. Patients had started on or were switched to biphasic insulin aspart (n = 1561), insulin detemir (n = 313), insulin aspart (n = 144), basal insulin plus insulin aspart (n = 53) and other insulin combinations (n = 41). At baseline glycaemic control was poor for both insulin naïve (mean HbA1c: 8.7%) and insulin user (mean HbA1c: 9.2%) groups. After 24 weeks of treatment, both the groups showed improvement in HbA1c (insulin naïve: -1.4%, insulin users: -1.8%). SADRs including major hypoglycaemic events or episodes did not occur in any of the study patients. Starting or switching to insulin analogues was associated with improvement in glycaemic control with a low rate of hypoglycaemia.

Optimization of Premix Powders for Tableting Use.

PubMed

Todo, Hiroaki; Sato, Kazuki; Takayama, Kozo; Sugibayashi, Kenji

2018-05-08

Direct compression is a popular choice as it provides the simplest way to prepare the tablet. It can be easily adopted when the active pharmaceutical ingredient (API) is unstable in water or to thermal drying. An optimal formulation of preliminary mixed powders (premix powders) is beneficial if prepared in advance for tableting use. The aim of this study was to find the optimal formulation of the premix powders composed of lactose (LAC), cornstarch (CS), and microcrystalline cellulose (MCC) by using statistical techniques. Based on the "Quality by Design" concept, a (3,3)-simplex lattice design consisting of three components, LAC, CS, and MCC was employed to prepare the model premix powders. Response surface method incorporating a thin-plate spline interpolation (RSM-S) was applied for estimation of the optimum premix powders for tableting use. The effect of tablet shape identified by the surface curvature on the optimization was investigated. The optimum premix powder was effective when the premix was applied to a small quantity of API, although the function of premix was limited in the case of the formulation of large amount of API. Statistical techniques are valuable to exploit new functions of well-known materials such as LAC, CS, and MCC.

Gas turbine premixing systems

DOEpatents

Kraemer, Gilbert Otto; Varatharajan, Balachandar; Evulet, Andrei Tristan; Yilmaz, Ertan; Lacy, Benjamin Paul

2013-12-31

Methods and systems are provided for premixing combustion fuel and air within gas turbines. In one embodiment, a combustor includes an upstream mixing panel configured to direct compressed air and combustion fuel through premixing zone to form a fuel-air mixture. The combustor includes a downstream mixing panel configured to mix additional combustion fuel with the fule-air mixture to form a combustion mixture.

Lean premixed/prevaporized combustion

NASA Technical Reports Server (NTRS)

Lefebvre, A. H. (Editor)

1977-01-01

Recommendations were formulated on the status and application of lean premixed/prevaporized combustion to the aircraft gas turbine for the reduction of pollutant emissions. The approach taken by the NASA Stratospheric Cruise Emission Reduction Program (SCERP) in pursuing the lean premixed/prevaporized combustion technique was also discussed. The proceedings contains an overview of the SCERP program, the discussions and recommendations of the participants, and an overall summary.

The role of GLP-1 mimetics and basal insulin analogues in type 2 diabetes mellitus: guidance from studies of liraglutide.

PubMed

Barnett, A H

2012-04-01

In people with type 2 diabetes mellitus (T2DM), the incretin effect is reduced, but the recent advent of dipeptidyl peptidase-4 inhibitors and glucagon-like peptide (GLP)-1 agonists/analogues has enabled restoration of at least some of the function of the incretin system, with accompanying improvements in glycaemic control. Two GLP-1 receptor agonists/analogues are currently approved for the treatment of T2DM-exenatide (Byetta®, Eli Lilly & Co., Indianapolis, IN, US) and liraglutide (Victoza®, Novo Nordisk, Bagsvaerd, Denmark); a once-weekly formulation of exenatide (Bydureon®, Eli Lilly & Co.) has also been approved by the European Medicines Agency. The National Institute for Health and Clinical Excellence (NICE) has recently published guidance on the use of liraglutide in T2DM, based on evidence from the Liraglutide Effect and Action in Diabetes (LEAD) Phase III trial programme, which compared liraglutide with existing glucose-lowering therapies, such as exenatide and insulin glargine. The LEAD programme reported HbA1c reductions from 0.8 to 1.5% with liraglutide (1.2 and 1.8 mg), accompanied by low rates of hypoglycaemia and some weight loss; side effects were primarily gastrointestinal in nature (e.g. nausea and diarrhoea). Based on the findings of the LEAD studies and the NICE recommendation, liraglutide now represents an important therapy widely available in the UK for certain patient groups, including those with a body mass index (BMI) ≥35.0 kg/m(2) , and patients with a BMI <35 kg/m(2) who are considered unsuitable for insulin and are failing to meet targets for glycaemic control with oral agents. NICE guidelines still suggest that most patients without considerable obesity (BMI <35 kg/m(2) ) are probably best managed using insulin therapy. Evidence also suggests a future role for GLP-1 mimetics in combination with basal insulin. © 2011 Blackwell Publishing Ltd.

Addition of rapid-acting insulin to basal insulin therapy in type 2 diabetes: indications and modalities.

PubMed

Monnier, L; Colette, C

2006-02-01

There are many reasons to believe that in the near future, the treatment of patients with Type 2 diabetes will be characterised by an increased use of insulin therapy. To ensure that insulin regimens are acceptable to patients, and implemented by physicians, they should be as simple and efficient as possible. Simplicity is synonymous with the regimen of once-daily basal insulin glargine given at any time of the day (at the same time each day). With such a strategy, the dose is adjusted by titrating to target fasting blood glucose values of 5.0 - 7.2 mmol/L (90 - 130 mg/dL). When these targets can no longer be achieved with reasonable doses of long-acting insulin, a rapid-acting insulin analogue should be added at meal times. A step-by-step strategy can be used; it is recommended that initially, a single daily prandial bolus of a rapid-acting insulin analogue is administered before the meal that leads to the highest post-meal blood glucose excursions. Further boluses can be added at other meal times as necessary, i.e, when post-meal blood glucose values remain above 10.0 mmol/L (180 mg/dL) and 7.8 mmol/L (140 mg/dL) at mid-morning and 2h-post-lunch or post-dinner times, respectively. This stepwise strategy may eventually lead to a standard basal-bolus regimen with 3 pre-meal injections of rapid-acting insulin analogues, a potentially small trade-off for achieving fairly-well controlled diabetes.

Clinical experience with insulin detemir, biphasic insulin aspart and insulin aspart in people with type 2 diabetes: Results from the Northern Tunisia cohort of the A1chieve study

PubMed Central

Blouza, Samira; Jamoussi, Henda

2013-01-01

Background: The A1chieve, a multicentric (28 countries), 24-week, non-interventional study evaluated the safety and effectiveness of insulin detemir, biphasic insulin aspart and insulin aspart in people with T2DM (n = 66,726) in routine clinical care across four continents. Materials and Methods: Data was collected at baseline, at 12 weeks and at 24 weeks. This short communication presents the results for patients enrolled from Northern Tunisia. Results: A total of 443 patients were enrolled in the study. Four different insulin analogue regimens were used in the study. Study patients had started on or were switched to biphasic insulin aspart (n = 137), insulin detemir (n = 243), insulin aspart (n = 11), basal insulin plus insulin aspart (n = 39) and other insulin combinations (n = 13). At baseline glycaemic control was poor for both insulin naïve (mean HbA1c: 10.2%) and insulin user (mean HbA1c: 9.8%) groups. After 24 weeks of treatment, both the study groups showed improvement in HbA1c (insulin naïve: −2.1%, insulin users: −0.9%). SADRs including major hypoglycaemic events or episodes did not occur in any of the study patients. Conclusion: Starting or switching to insulin analogues was associated with improvement in glycaemic control with a low rate of hypoglycaemia. PMID:24404473

[New insulin types in type 1 diabetes mellitus].

PubMed

Mesa, Jordi

2015-07-20

Since its discovery almost a century ago, insulin remains the mainstay of treatment of patients with type 1 diabetes mellitus. Although progress in the synthesis of new formulations has been remarkable, the physiological profile of insulin is still different from that observed with preparations available nowadays. In the last decade, the introduction into clinical practice of insulin analogues has allowed significantly improvement in glycemic control and has facilitated the spread of basal/bolus patterns, the most physiological ones until now. Despite the benefits of basal analogues, glycemia often varies considerably when used as a single daily injection and this is why new molecules have been further investigated. Improvement has been achieved especially in terms of duration and rate of hypoglycemia, the main limiting factor of intensive therapy. This article reviews the available data concerning the new basal insulin analogues, degludec, pegylated lispro and glargine U300, and new formulations currently under development. Copyright © 2014 Elsevier España, S.L.U. All rights reserved.

Insulin during pregnancy, labour and delivery.

PubMed

de Valk, Harold W; Visser, Gerard H A

2011-02-01

Optimal glycaemic control is of the utmost importance to achieve the best possible outcome of a pregnancy complicated by diabetes. This holds for pregnancies in women with preconceptional type 1 or type 2 diabetes as well as for pregnancies complicated by gestational diabetes. Glycaemic control is conventionally expressed in the HbA1c value but the HbA1c value does not completely capture the complexity of glycaemic control. The daily glucose profile measured by the patients themselves through measurements performed in capillary blood obtained by finger stick provides valuable information needed to adjust insulin therapy. Hypoglycaemia is the major threat to the pregnant woman or the woman with tight glycaemic control in the run-up to pregnancy. Repetitive hypoglycaemia can lead to hypoglycaemia unawareness, which is reversible with prevention of hypoglycaemia. A delicate balance should be struck between preventing hyperglycaemia and hypoglycaemia. Insulin requirements are not uniform across the day: it is low during the night with a more or less pronounced rise at dawn, followed by a gradual decrease during the remainder of the day. A basal amount of insulin is needed to regulate the endogenous glucose production, short-acting insulin shots are needed to handle exogenous glucose loads. Insulin therapy means two choices: the type of insulin used and the method of insulin administration. Regarding the type of insulin, the choice is between human and analogue insulins. The analogue short-acting insulin aspart has been shown to be safe during pregnancy in a randomised trial and has received registration for this indication; the short-acting analogue insulin lispro has been shown to be safe in observational studies. No such information is available on the long-acting insulin analogues detemir and glargine and both are prescribed off-label with human long-acting insulin as obvious alternatives. Randomised trials have not been able to show superiority of continuous

Trends in Medicaid Reimbursements for Insulin From 1991 Through 2014.

PubMed

Luo, Jing; Avorn, Jerry; Kesselheim, Aaron S

2015-10-01

Insulin is a vital medicine for patients with diabetes mellitus. Newer, more expensive insulin products and the lack of generic insulins in the United States have increased costs for patients and insurers. To examine Medicaid payment trends for insulin products. Cost information is available for all 50 states and has been recorded since the 1990s. A time-series analysis comparing reimbursements and prices. Using state- and national-level Medicaid data from 1991 to 2014, we identified all patients who used 1 or more of the 16 insulin products that were continuously available in the United States between 2006 and 2014. Insulin products were classified into rapid-acting and long-acting analogs, short-acting, intermediate, and premixed insulins based on American Diabetes Association Guidelines. Inflation-adjusted payments made to pharmacies by Medicaid per 1 mL (100 IU) of insulin in 2014 US dollars. Since 1991, Medicaid reimbursement per unit (1 mL) of insulin dispensed has risen steadily. In the 1990s, Medicaid reimbursed pharmacies between $2.36 and $4.43 per unit. By 2014, reimbursement for short-acting insulins increased to $9.64 per unit; intermediate, $9.22; premixed, $14.79; and long-acting, $19.78. Medicaid reimbursement for rapid-acting insulin analogs rose to $19.81 per unit. The rate of increase in reimbursement was higher for insulins with patent protection ($0.20 per quarter) than without ($0.05 per quarter) (P<.001).Total Medicaid reimbursements peaked at $407.4 million dollars in quarter 2 of 2014. Total volume peaked at 29.9 million units in quarter 4 of 2005 and was 21.2 million units in quarter 2 of 2014. Between 1991 and 2014, there was a near-exponential upward trend in Medicaid payments on a per-unit basis for a wide variety of insulin products regardless of formulation, duration of action, and whether the product was patented. Although reimbursements for newer, patent-protected insulin analogs increased at a faster rate than reimbursements for

Multidimensional flamelet-generated manifolds for partially premixed combustion

DOE Office of Scientific and Technical Information (OSTI.GOV)

Nguyen, Phuc-Danh; Vervisch, Luc; Subramanian, Vallinayagam

2010-01-15

Flamelet-generated manifolds have been restricted so far to premixed or diffusion flame archetypes, even though the resulting tables have been applied to nonpremixed and partially premixed flame simulations. By using a projection of the full set of mass conservation species balance equations into a restricted subset of the composition space, unsteady multidimensional flamelet governing equations are derived from first principles, under given hypotheses. During the projection, as in usual one-dimensional flamelets, the tangential strain rate of scalar isosurfaces is expressed in the form of the scalar dissipation rates of the control parameters of the multidimensional flamelet-generated manifold (MFM), which ismore » tested in its five-dimensional form for partially premixed combustion, with two composition space directions and three scalar dissipation rates. It is shown that strain-rate-induced effects can hardly be fully neglected in chemistry tabulation of partially premixed combustion, because of fluxes across iso-equivalence-ratio and iso-progress-of-reaction surfaces. This is illustrated by comparing the 5D flamelet-generated manifold with one-dimensional premixed flame and unsteady strained diffusion flame composition space trajectories. The formal links between the asymptotic behavior of MFM and stratified flame, weakly varying partially premixed front, triple-flame, premixed and nonpremixed edge flames are also evidenced. (author)« less

[Cloning, expressing of exendin-4 analogue and bioactivity analysis in vivo].

PubMed

Li, Taiming; Gu, Chunjiao; Ge, Xiaoyu; Li, Zhezhe; Wang, Dan; Ma, Yanhong; Liu, Tao; Zhang, Meiyou; Li, Li; Liu, Jingjing

2012-07-01

To construct, express and purify Exendin-4 analogue and detect its biological activity in vivo. Insert gene sequence into fusion partner ofpED plasmid which is helped to purification, entitled the new recombinant plasmid 5 Exendin-4 analogue polypeptide gene and fusion partner gene was linked by acid hydrolysisgene, transformed to E. coli BL21 and the fusion protein was induced by lactose. After acid hydrolysis, the Exendin-4 analogue polypeptide separated from fusion chaperon. Anion charge chromatography were used to further purification. 6 to 8 week-old ICR mice were injected (s.c) with Exendin-4 analogue, blood glucose and plasma insulin level was detected in different period after oral glucose tolerance test. The results show that high expression of inclusion body was induced by lactose, which accounted for 40% of germ proteins, the Exendin-4 analogue was obtained with the purity of 91.8% after being purified by anion charge chromatography. Bioactivity assay showed that the level of blood glucose of mouse which treated with exendin-4 analogue was obviously decreased to normal (P < 0.01), and the level of plasma insulin was increased obviously (P < 0.01).

Frequency of blood glucose testing among insulin-treated diabetes mellitus patients in the United Kingdom.

PubMed

Lee, Won Chan; Smith, Elise; Chubb, Barrie; Wolden, Michael Lyng

2014-03-01

Through a retrospective database analysis, this study seeks to provide an understanding of the utilization of SMBG by insulin therapy and diabetes type and to estimate healthcare costs of blood glucose monitoring in the UK diabetes population. Data were obtained from the IMS LifeLink Electronic Medical Record-Europe (EMR-EU) Database, a longitudinal database containing anonymized patient records from physician-practice data systems of office-based physicians in the UK. Depending on the insulin types used for type 1 and type 2 diabetes, patients were sub-categorized into one of four insulin regimen groups (basal, bolus, pre-mixed, or basal-bolus). Frequency of blood glucose testing was assessed descriptively throughout the 12-month post-index period, and generalized linear models were used to evaluate the effect of baseline characteristics, including insulin type, on the likelihood of blood glucose test utilization. Healthcare resource utilization and costs for all-cause services were assessed by insulin type. This study identified 8322 type 1 and type 2 diabetes patients with two insulin pharmacy records between January 1, 2009 and December 31, 2010. After applying study inclusion and exclusion criteria, a total of 2676 (32.2%) insulin-treated diabetes mellitus patients in the UK were identified, with the number of pharmacy blood glucose test strips averaging 771.1 (median 600). The glucose testing frequency was lowest among basal-only insulin patients and pre-mixed insulin patients (mean=576.2 [median=450] and mean=599.5 [median=500], respectively; non-significantly different) compared to other insulin types. Although the data did not capture the glucose frequency comprehensively, it varied significantly by insulin types, and was higher than what is recommended in the guidelines for patients with type 2 diabetes.

Clinical experience with insulin detemir type 2 diabetes mellitus, biphasic insulin aspart and insulin aspart in people with type 2 diabetes: Results from the Rabat-Sale-Zemmour-Zaer Region cohort of the A1chieve study.

PubMed

Chraibi, Abdelmjid; Belmejdoub, Ghizlane

2013-11-01

The A1chieve, a multicentric (28 countries), 24-week, non-interventional study evaluated the safety and effectiveness of insulin detemir, biphasic insulin aspart and insulin aspart in people with T2DM (n = 66 726) in routine clinical care across four continents. Data was collected at baseline, at 12 weeks and at 24 weeks. This short communication presents the results for patients enrolled from Rabat-Sale-Zemmour-Zaer region, Morocco. A total of 424 patients were enrolled in the study. Four different insulin analogue regimens were used in the study. Study patients had started on or were switched to biphasic insulin aspart (n = 177), insulin detemir (n = 150), insulin aspart (n = 11), basal insulin plus insulin aspart (n = 45) and other insulin combinations (n = 41). At baseline glycaemic control was poor for both insulin naïve (mean HbA1c: 10.1%) and insulin user (mean HbA1c: 9.4%) groups. After 24 weeks of treatment, all the study groups showed improvement in HbA1c (insulin naïve: -2.5%, insulin users: -1.8%). Major hypoglycaemia was observed in the insulin user group after 24 weeks (0.1 events/patient-year). SADRs were reported in 0.5% of insulin users. Starting or switching to insulin analogues was associated with improvement in glycaemic control with a low rate of hypoglycaemia.

Fully Premixed Low Emission, High Pressure Multi-Fuel Burner

NASA Technical Reports Server (NTRS)

Nguyen, Quang-Viet (Inventor)

2012-01-01

A low-emissions high-pressure multi-fuel burner includes a fuel inlet, for receiving a fuel, an oxidizer inlet, for receiving an oxidizer gas, an injector plate, having a plurality of nozzles that are aligned with premix face of the injector plate, the plurality of nozzles in communication with the fuel and oxidizer inlets and each nozzle providing flow for one of the fuel and the oxidizer gas and an impingement-cooled face, parallel to the premix face of the injector plate and forming a micro-premix chamber between the impingement-cooled face and the in injector face. The fuel and the oxidizer gas are mixed in the micro-premix chamber through impingement-enhanced mixing of flows of the fuel and the oxidizer gas. The burner can be used for low-emissions fuel-lean fully-premixed, or fuel-rich fully-premixed hydrogen-air combustion, or for combustion with other gases such as methane or other hydrocarbons, or even liquid fuels.

Toxicological Effects during and following Persistent Insulin-Induced Hypoglycaemia in Healthy Euglycaemic Rats.

PubMed

Jensen, Vivi F H; Mølck, Anne-Marie; Berthelsen, Line O; Alifrangis, Lene; Andersen, Lene; Chapman, Melissa; Lykkesfeldt, Jens; Bøgh, Ingrid B

2017-07-01

New insulin analogues with a longer duration of action and a 'peakless' pharmacokinetic profile have been developed to improve efficacy, safety and convenience for patients with diabetes. During non-clinical development, according to regulatory guidelines, these analogues are tested in healthy euglycaemic rats rendering them persistently hypoglycaemic. Little is known about the effect of persistent (24 hr/day) insulin-induced hypoglycaemia (IIH) in rats, complicating interpretation of results in pre-clinical studies with new longer-acting insulin analogues. In this study, we investigated the effects of persistent IIH and their reversibility in euglycaemic rats. Histopathological changes in insulin-infused animals included partly reversible axonal and reversible myofibre degeneration in peripheral nerve and skeletal muscle tissue, respectively, as well as reversible pancreatic islet atrophy and partly reversible increase in unilocular adipocytes in brown adipose tissue. Additionally, results suggested increased gluconeogenesis. The observed hyperphagia, the pancreatic, peripheral nerve and skeletal muscle changes were considered related to the hypoglycaemia. Cessation of insulin infusion resulted in transient hyperglycaemia, decreased food consumption and body-weight loss before returning to control levels. The implications for the interpretation of non-clinical studies with long-acting insulin analogues are discussed. © 2017 Nordic Association for the Publication of BCPT (former Nordic Pharmacological Society).

LEM-CF Premixed Tool Kit

DOE Office of Scientific and Technical Information (OSTI.GOV)

2015-01-19

The purpose of LEM-CF Premixed Tool Kit is to process premixed flame simulation data from the LEM-CF solver (https://fileshare.craft-tech.com/clusters/view/lem-cf) into a large-eddy simulation (LES) subgrid model database. These databases may be used with a user-defined-function (UDF) that is included in the Tool Kit. The subgrid model UDF may be used with the ANSYS FLUENT flow solver or other commercial flow solvers.

Choice of Insulin in Type 2 Diabetes: A Southeast Asian Perspective.

PubMed

Kalra, Sanjay; Thai, Hong Quang; Deerochanawong, Chaicharn; Su-Yen, Goh; Mohamed, Mafauzy; Latt, Tint Swe; Aye, Than Than; Latif, Zafar Ahmed; Katulanda, Prasad; Khun, Touch; Satha, Sum; Vongvandy, Vadsana

2017-01-01

Southeast Asia faces a diabetes epidemic, which has created significant challenges for health care. The unique Asian diabetes phenotype, coupled with peculiar lifestyle, diet, and healthcare-seeking behavior, makes it imperative to develop clinical pathways and guidelines which address local needs and requirements. From an insulin-centric viewpoint, the preparations prescribed in such pathways should be effective, safe, well tolerated, nonintrusive, and suitable for the use in multiple clinical situations including initiation and intensification. This brief communication describes the utility of premixed or dual action insulin in such clinical pathways and guidelines.

Choice of Insulin in Type 2 Diabetes: A Southeast Asian Perspective

PubMed Central

Kalra, Sanjay; Thai, Hong Quang; Deerochanawong, Chaicharn; Su-Yen, Goh; Mohamed, Mafauzy; Latt, Tint Swe; Aye, Than Than; Latif, Zafar Ahmed; Katulanda, Prasad; Khun, Touch; Satha, Sum; Vongvandy, Vadsana

2017-01-01

Southeast Asia faces a diabetes epidemic, which has created significant challenges for health care. The unique Asian diabetes phenotype, coupled with peculiar lifestyle, diet, and healthcare-seeking behavior, makes it imperative to develop clinical pathways and guidelines which address local needs and requirements. From an insulin-centric viewpoint, the preparations prescribed in such pathways should be effective, safe, well tolerated, nonintrusive, and suitable for the use in multiple clinical situations including initiation and intensification. This brief communication describes the utility of premixed or dual action insulin in such clinical pathways and guidelines. PMID:28553609

Gas turbine premixer with internal cooling

DOEpatents

York, William David; Johnson, Thomas Edward; Lacy, Benjamin Paul; Stevenson, Christian Xavier

2012-12-18

A system that includes a turbine fuel nozzle comprising an air-fuel premixer. The air-fuel premixed includes a swirl vane configured to swirl fuel and air in a downstream direction, wherein the swirl vane comprises an internal coolant path from a downstream end portion in an upstream direction through a substantial length of the swirl vane.

Studies of Premixed Laminar and Turbulent Flames at Microgravity

NASA Technical Reports Server (NTRS)

Abid, M.; Aung, K.; Ronney, P. D.; Sharif, J. A.; Wu, M.-S.

1999-01-01

Several topics relating to combustion limits in premixed flames at reduced gravity have been studied. These topics include: (1) flame balls; (2) numerical simulation of flame ball and planar flame structure and stability; (3) experimental simulation of buoyancy effects in premixed flames using aqueous autocatalytic reactions; and (4) premixed flame propagation in Hele-Shaw cells.

Posology of insulins: A review of standard textbooks and product inserts.

PubMed

Bhutani, Garima; Kalra, Sanjay

2015-01-01

The study is aimed to assess whether the information contained in standard pharmacology, endocrinology, and diabetology textbooks regarding timings of administration, frequency and dose of various insulins is adequate and also to see whether the information contained in these texts is concordant with product inserts. Four standard textbooks of pharmacology, two of diabetology and three of endocrinology were assessed for the published information regarding dose, timing, and frequency of insulin administration. The product inserts of commonly available insulins in India were also studied for the same. Various omissions and disparities could be seen in the coverage of insulins in standard textbooks. Posology information about premixed insulins and basal insulins have been omitted by the majority of the textbooks. Details about dose, frequency and timings of ultra-short acting insulins have also not been covered by all textbooks. Some discrepancies regarding prescribing information was also noted in product inserts, especially in case of newer insulins. Thus, this article stresses upon the need of a uniform source of information for providing adequate and standardized knowledge regarding timing, frequency, and dose of insulins.

Clinical experience with insulin detemir type 2 diabetes mellitus, biphasic insulin aspart and insulin aspart in people with type 2 diabetes: Results from the Rabat-Sale-Zemmour-Zaer Region cohort of the A1chieve study

PubMed Central

Chraibi, Abdelmjid; Belmejdoub, Ghizlane

2013-01-01

Background: The A1chieve, a multicentric (28 countries), 24-week, non-interventional study evaluated the safety and effectiveness of insulin detemir, biphasic insulin aspart and insulin aspart in people with T2DM (n = 66 726) in routine clinical care across four continents. Materials and Methods: Data was collected at baseline, at 12 weeks and at 24 weeks. This short communication presents the results for patients enrolled from Rabat-Sale-Zemmour-Zaer region, Morocco. Results: A total of 424 patients were enrolled in the study. Four different insulin analogue regimens were used in the study. Study patients had started on or were switched to biphasic insulin aspart (n = 177), insulin detemir (n = 150), insulin aspart (n = 11), basal insulin plus insulin aspart (n = 45) and other insulin combinations (n = 41). At baseline glycaemic control was poor for both insulin naïve (mean HbA1c: 10.1%) and insulin user (mean HbA1c: 9.4%) groups. After 24 weeks of treatment, all the study groups showed improvement in HbA1c (insulin naïve: −2.5%, insulin users: −1.8%). Major hypoglycaemia was observed in the insulin user group after 24 weeks (0.1 events/patient-year). SADRs were reported in 0.5% of insulin users. Conclusion: Starting or switching to insulin analogues was associated with improvement in glycaemic control with a low rate of hypoglycaemia. PMID:24404470

Colorimetric determination of selenium in mineral premixes .

PubMed

Hurlbut, J A; Burkepile, R G; Geisler, C A; Kijak, P J; Rummel, N G

1997-01-01

A method is described for determination of sodium selenite or sodium selenate in mineral-based premixes. It is based on the formation of intense-yellow piazselenol by Se(IV) and 3,3'-diaminobenzidine. Mineral premixes typically contain calcium carbonate as a base material and magnesium carbonate, silicon dioxide, and iron(III) oxide as minor components or additives. In this method, the premix is digested briefly in nitric acid, diluted with water, and filtered to remove any Iron(III) oxide. Ethylenediaminetetraacetic acid and HCl are added to the filtrate, which is heated to near boiling for 1 h to convert any selenate to selenite. After heating, the solution is buffered between pH 2 and 3 with NaOH and formic acid and treated with NH2OH and EDTA; any Se present forms a complex with 3,3'-diaminobenzidine at 60 degrees C. The solution is made basic with NH4OH, and the piazselenol is extracted into toluene. The absorbance of the complex in dried toluene is measured at 420 nm. The method was validated independently by 2 laboratories. Samples analyzed included calcium carbonate fortified with 100, 200, and 300 micrograms Se in the form of sodium selenite or sodium selenate, a calcium carbonate premix containing sodium selenite, a calcium carbonate premix containing sodium selenate, and a commercial premix; 5 replicates of each sample type were analyzed by each laboratory. Average recoveries ranged from 89 to 109% with coefficients of variation from 1.2 to 13.6%.

The Biosulin equivalence in standard therapy (BEST) study - a multicentre, open-label, non-randomised, interventional, observational study in subjects using Biosulin 30/70 for the treatment of insulin-dependent type 1 and type 2 diabetes mellitus.

PubMed

Segal, D; Tupy, D; Distiller, L

2013-04-02

The need for more cost-effective insulin therapy is critical in reducing the burden on patients and health systems. Biosimilar insulins have the potential to dramatically lower healthcare costs by delivering insulin with a similar anti-glycaemic effect and adverse reaction profile. The purpose of this study was to confirm equivalence in glycaemic outcomes and side-effect profiles between Biosulin 30/70 and other human premixed insulin preparations on the South African market in a clinical practice setting. Subjects in this interventional, observational, multicentre, open-label, prospective study were switched from their existing human premix insulin (Actraphane, Humulin 30/70 or Insuman) to the study insulin Biosulin 30/70. The primary endpoint was the change in HbA1c from baseline to 6 months. Seventy-seven adult patients with type 1(n=18) or type 2 (n=59) diabetes were enrolled. The baseline HbA1c in the overall cohort was 7.9%, 8.0% at 3 months (p=0.50) and 7.6% at 6 months (p=0.14).There was a small increase in the total daily dose of insulin used in both the type 1 and type 2 cohort, from 0.62 to 0.65 units/kg/day (p=0.0004). There was no significant difference in weight in the study subjects during the 6-month period on Biosulin 30/70 (p=0.67). Biosulin 30/70 achieved at least equivalent glycaemic control to existing human premix insulins, with no reported new or severe adverse events. Increased use of biosimilar insulins has the potential for significant cost savings.

[Adherence of type 2 diabetes patients on insulin analogues application: missed dose, time imprecision and dose reduction. The results of GAPP2TM(Global Attitudes of Physicians and Patient) survey in the Czech Republic].

PubMed

Prázný, Martin

2014-11-01

Irregular insulin dose is one of the main problems associated with insulin therapy in patients with type 2 diabetes; its extent is not known precisely. The aim of survey conducted in the Czech Republic in the international project GAPP2 - Global Attitudes of Patients and Physicians was to determine the incidence and the impact of irregular use of basal insulin analogues in patients with type 2 diabetes, to point out the reasons for these irregularities and to focus on how physicians discuss irregular application of insulin with patients. The project GAPP2 is an international cross-sectional study performed on-line via the Internet using a questionnaire filled by diabetic patients treated with insulin analogues and physicians who treat these patients. The survey was conducted in two steps in 17 countries; the first step included 6 countries and was completed in the beginning of 2012, the second step involved 11 other countries including the Czech Republic with termination in 2014. The survey was designed to obtain the views of patients and physicians on certain aspects of insulin treatment and persistent issues in this field in the real daily practice. Special focus was on the incidence and management of hypoglycaemia as well as on irregularities of insulin application. In the part dedicated to adherence to basal insulin application were observed three types of irregular insulin therapy: missed dose, time imprecision of dose (± 2 hours vs. the prescribed time) and dose reduction in all cases in the past 30 days before completing the questionnaire. In addition, it was investigated the attitude and relation of patients to these issues. The results have shown that irregular insulin dose in the Czech Republic is less frequent than in other countries involved in the GAPP2 research. Nevertheless, approximately one fifth of diabetic patients using insulin analogues in basal-bolus or only basal therapy regimen is related to this problem. The last irregular insulin

Incorporating a Generic Model of Subcutaneous Insulin Absorption into the AIDA v4 Diabetes Simulator 3. Early Plasma Insulin Determinations

PubMed Central

Lehmann, Eldon D.; Tarín, Cristina; Bondia, Jorge; Teufel, Edgar; Deutsch, Tibor

2009-01-01

Introduction AIDA is an interactive educational diabetes simulator that has been available without charge via the Internet for over 12 years. Recent articles have described the incorporation of a novel generic model of insulin absorption into AIDA as a way of enhancing its capabilities. The basic model components to be integrated have been overviewed, with the aim being to provide simulations of regimens utilizing insulin analogues, as well as insulin doses greater than 40 IU (the current upper limit within the latest release of AIDA [v4.3a]). Some preliminary calculated insulin absorption results have also recently been described. Methods This article presents the first simulated plasma insulin profiles from the integration of the generic subcutaneous insulin absorption model, and the currently implemented model in AIDA for insulin disposition. Insulin absorption has been described by the physiologically based model of Tarín and colleagues. A single compartment modeling approach has been used to specify how absorbed insulin is distributed in, and eliminated from, the human body. To enable a numerical solution of the absorption model, a spherical subcutaneous depot for the injected insulin dose has been assumed and spatially discretized into shell compartments with homogeneous concentrations, having as its center the injection site. The number of these compartments will depend on the dose and type of insulin. Insulin inflow arises as the sum of contributions to the different shells. For this report the first bench testing of plasma insulin determinations has been done. Results Simulated plasma insulin profiles are provided for currently available insulin preparations, including a rapidly acting insulin analogue (e.g., lispro/Humalog or aspart/Novolog), a short-acting (regular) insulin preparation (e.g., Actrapid), intermediate-acting insulins (both Semilente and neutral protamine Hagedorn types), and a very long-acting insulin analogue (e.g., glargine/Lantus), as

[News and perspectives in insulin treatment].

PubMed

Haluzík, Martin

2014-09-01

Insulin therapy is a therapeutic cornerstone in patients with type 1 diabetes and also in numerous patients with type 2 diabetes especially with longer history of diabetes. The initiation of insulin therapy in type 2 diabetes patients is often delayed which is at least partially due to suboptimal pharmacokinetic characteristics of available insulins. The development of novel insulins with more favorable characteristics than those of current insulins is therefore still ongoing. The aim of this paper is to review current knowledge of novel insulins that have been recently introduced to the market or are getting close to routine clinical use. We will also focus on the perspectives of insulin therapy in the long-term run including the alternative routes of insulin administration beyond its classical subcutaneous injection treatment.Key words: alternative routes of insulin administration - diabetes mellitus - hypoglycemia - insulin - insulin analogues.

Continuous subcutaneous insulin infusion in diabetes: patient populations, safety, efficacy, and pharmacoeconomics.

PubMed

Pozzilli, Paolo; Battelino, Tadej; Danne, Thomas; Hovorka, Roman; Jarosz-Chobot, Przemyslawa; Renard, Eric

2016-01-01

The level of glycaemic control necessary to achieve optimal short-term and long-term outcomes in subjects with type 1 diabetes mellitus (T1DM) typically requires intensified insulin therapy using multiple daily injections or continuous subcutaneous insulin infusion. For continuous subcutaneous insulin infusion, the insulins of choice are the rapid-acting insulin analogues, insulin aspart, insulin lispro and insulin glulisine. The advantages of continuous subcutaneous insulin infusion over multiple daily injections in adult and paediatric populations with T1DM include superior glycaemic control, lower insulin requirements and better health-related quality of life/patient satisfaction. An association between continuous subcutaneous insulin infusion and reduced hypoglycaemic risk is more consistent in children/adolescents than in adults. The use of continuous subcutaneous insulin infusion is widely recommended in both adult and paediatric T1DM populations but is limited in pregnant patients and those with type 2 diabetes mellitus. All available rapid-acting insulin analogues are approved for use in adult, paediatric and pregnant populations. However, minimum patient age varies (insulin lispro: no minimum; insulin aspart: ≥2 years; insulin glulisine: ≥6 years) and experience in pregnancy ranges from extensive (insulin aspart, insulin lispro) to limited (insulin glulisine). Although more expensive than multiple daily injections, continuous subcutaneous insulin infusion is cost-effective in selected patient groups. This comprehensive review focuses on the European situation and summarises evidence for the efficacy and safety of continuous subcutaneous insulin infusion, particularly when used with rapid-acting insulin analogues, in adult, paediatric and pregnant populations. The review also discusses relevant European guidelines; reviews issues that surround use of this technology; summarises the effects of continuous subcutaneous insulin infusion on patients

Continuous subcutaneous insulin infusion in diabetes: patient populations, safety, efficacy, and pharmacoeconomics

PubMed Central

Battelino, Tadej; Danne, Thomas; Hovorka, Roman; Jarosz‐Chobot, Przemyslawa; Renard, Eric

2015-01-01

Summary The level of glycaemic control necessary to achieve optimal short‐term and long‐term outcomes in subjects with type 1 diabetes mellitus (T1DM) typically requires intensified insulin therapy using multiple daily injections or continuous subcutaneous insulin infusion. For continuous subcutaneous insulin infusion, the insulins of choice are the rapid‐acting insulin analogues, insulin aspart, insulin lispro and insulin glulisine. The advantages of continuous subcutaneous insulin infusion over multiple daily injections in adult and paediatric populations with T1DM include superior glycaemic control, lower insulin requirements and better health‐related quality of life/patient satisfaction. An association between continuous subcutaneous insulin infusion and reduced hypoglycaemic risk is more consistent in children/adolescents than in adults. The use of continuous subcutaneous insulin infusion is widely recommended in both adult and paediatric T1DM populations but is limited in pregnant patients and those with type 2 diabetes mellitus. All available rapid‐acting insulin analogues are approved for use in adult, paediatric and pregnant populations. However, minimum patient age varies (insulin lispro: no minimum; insulin aspart: ≥2 years; insulin glulisine: ≥6 years) and experience in pregnancy ranges from extensive (insulin aspart, insulin lispro) to limited (insulin glulisine). Although more expensive than multiple daily injections, continuous subcutaneous insulin infusion is cost‐effective in selected patient groups. This comprehensive review focuses on the European situation and summarises evidence for the efficacy and safety of continuous subcutaneous insulin infusion, particularly when used with rapid‐acting insulin analogues, in adult, paediatric and pregnant populations. The review also discusses relevant European guidelines; reviews issues that surround use of this technology; summarises the effects of continuous subcutaneous insulin

Consensus on Insulin Dose and Titration Algorithms in Ambulatory Care of Type 2 Diabetes in India.

PubMed

Kovil, Rajiv; Chawla, Manoj; Rajput, Rajesh; Singh, A K; Sinha, Binayak; Ghosal, Samit; Ballani, Piya; Gupta, Sunil; Tanna, Snehal; Bandukwala, S M; Shah, Tejas; Negalur, Vijay; Bhoraskar, Anil; Aravind, S R; Zargar, Abdul H; Kesavadev, Jothydev; Das, Ashok Kumar

2017-02-01

Insulin is the oldest of the currently available treatment options in Type 2 diabetes mellitus (T2DM) and is considered as the most effective glucose lowering agent. Despite this, decision on starting insulin therapy is often delayed in India as well as worldwide due to various barriers at both patient and physician levels. Appropriate insulin dosing and titration is also critical to the successful achievement of tight glycaemic control. To provide simple and easily implementable guidelines to primary care physicians on appropriate insulin dosing and titration of various insulin regimens for both initiation and intensification. Each insulin regimen (once daily [OD] basal, OD, twice daily and thrice daily premixed, basal-plus and basal-bolus) was presented and evaluated for dosing and titration based on established guidelines, data from approved pack inserts, and published scientific literature. These evaluations were then factored into the national context based on the expert committee representatives patient-physician experience in their clinical practice and common therapeutic practices followed in India. Recommendations for dosing and titration of basal, basal-plus, premixed and basal-bolus insulins were developed. The key recommendations are that insulin doses can be adjusted once or twice weekly; adjustment can be based on lowest/mean of three recent self-monitoring of plasma glucose pre-meal/fasting plasma glucose (FPG) values. The titration should be based on FPG or pre-meal value of 80-130 mg/dL and the dose should be reduced by 10-20% for patients reporting hypoglycaemia(<70mg/dL). The consensus based recommendations mentioned in this paper will be a useful reference tool for health care practitioners, to initiate, optimise and intensify insulin therapy and to successfully achieve optimal glucose control.

New Basal Insulins: a Clinical Perspective of Their Use in the Treatment of Type 2 Diabetes and Novel Treatment Options Beyond Basal Insulin.

PubMed

Frias, Patrick F; Frias, Juan Pablo

2017-08-18

The purpose of this review was to review advances in basal insulin formulations and new treatment options for patients with type 2 diabetes not achieving glycemic targets despite optimized basal insulin therapy. Advances in basal insulin formulations have resulted in products with increasingly favorable pharmacokinetic and pharmacodynamic properties, including flatter, peakless action profiles, less inter- and intra-patient variability, and longer duration of activity. These properties have translated to significantly reduced risk of hypoglycemia (particularly during the night) compared with previous generation basal insulins. When optimized basal insulin therapy is not sufficient to obtain or maintain glycemic goals, various options exist to improve glycemic control, including intensification of insulin therapy with the addition of prandial insulin or changing to pre-mixed insulin and, more recently, the addition of a GLP-1 receptor agonist, either as a separate injection or as a component of one of the new fixed-ratio combinations of a basal insulin and GLP-1 RA. New safer and often more convenient basal insulins and fixed ratio combinations containing basal insulin (and GLP-1 receptor agonist) are available today for patients with type 2 diabetes not achieving glycemic goals. Head-to-head studies comparing the latest generation basal insulins are underway, and future studies assessing the fixed-ratio combinations will be important to better understand their differentiating features.

Non-metabolisable insulin glargine does not promote breast cancer growth in a mouse model of type 2 diabetes

PubMed Central

Gallagher, Emily J.; Zelenko, Zara; Tobin-Hess, Aviva; Werner, Ulrich; Tennagels, Norbert; LeRoith, Derek

2016-01-01

Aims/hypothesis Previous epidemiological studies have reported a potential link between insulin analogues and breast cancer; however, a prospective randomised controlled trial showed neutral effects of insulin glargine on cancer risk. Insulin glargine is metabolised in vivo to an M1 metabolite. A question remains whether a subset of individuals with slower rates of glargine metabolism or who are on high doses could, theoretically, have an increased risk of cancer progression if a tumour is already present. In this study, we aimed to determine whether a non-metabolisable form of insulin glargine induced murine breast cancer growth. Methods A mouse model of type 2 diabetes (MKR) was used for these studies. MKR mice were injected with two murine mammary cancer cell lines: Mvt-1 cells (derived from MMTV-c-Myc/Vegf tumours) and Met1 cells (derived from MMTV-polyoma virus middle T antigen tumours). Mice were treated with 25 U/kg per day of the long-acting insulin analogues, insulin glargine, insulin detemir, insulin degludec or non-metabolisable glargine, or vehicle. Results No difference in tumour growth was seen in terms of tumour size after insulin glargine, detemir, degludec or vehicle injections. Non-metabolisable glargine did not increase tumour growth compared with insulin glargine or vehicle. Insulin glargine and non-metabolisable glargine led to insulin receptor phosphorylation in vivo rather than IGF-1 receptor phosphorylation. Conclusions/interpretation These results demonstrate that in a mouse model of type 2 diabetes, at high concentrations, basal insulin analogues and a non-metabolisable glargine analogue do not promote the progression of breast tumours. PMID:27241182

Annular fuel and air co-flow premixer

DOEpatents

Stevenson, Christian Xavier; Melton, Patrick Benedict; York, William David

2013-10-15

Disclosed is a premixer for a combustor including an annular outer shell and an annular inner shell. The inner shell defines an inner flow channel inside of the inner shell and is located to define an outer flow channel between the outer shell and the inner shell. A fuel discharge annulus is located between the outer flow channel and the inner flow channel and is configured to inject a fuel flow into a mixing area in a direction substantially parallel to an outer airflow through the outer flow channel and an inner flow through the inner flow channel. Further disclosed are a combustor including a plurality of premixers and a method of premixing air and fuel in a combustor.

Recombinant Human Insulin in Global Diabetes Management – Focus on Clinical Efficacy

PubMed Central

Mbanya, Jean Claude; Sandow, Juergen; Landgraf, Wolfgang

2017-01-01

Abstract Biosynthetic human insulin and insulin analogues are the mainstay of insulin therapy for both type 1 and type 2 diabetes although access to human insulin at affordable prices remains a global issue. The world is experiencing an exponential rise in the prevalence of diabetes presenting an urgent need to establish effective diabetes therapy in countries burdened by inadequate health care budgets, malnutrition and infectious diseases. Recombinant human insulin has replaced animal insulins and animal-based semisynthetic human insulin thereby available in sufficient quantities and at affordable prices able to provide global access to insulin therapy. In many patients, analog insulins can offer additional clinical benefit, although at a considerably higher price thus severely restricting availability in low income countries. The approval process for recombinant human insulins (i.e. biosimilars) and analogue insulins is highly variable in the developing countries in contrast to Europe and in North America, where it is well established within a strict regulatory framework. This review aims to discuss the future access to human insulin therapy in a global context with an ever increasing burden of diabetes and significant economic implications. PMID:29632602

Safety, cost, and clinical considerations for the use of premixed parenteral nutrition.

PubMed

Hall, Jacob W

2015-06-01

Premixed parenteral nutrition (PN) can be used for PN therapy in place of traditional compounded or customized PN. Premixed PN may have a number of advantages over compounded PN such as decreased costs, decreased compounding time, reduced chance for error, and reduced incidence of bloodstream infections. However, premixed PN may not be appropriate for all patients and may have other additional costs associated with its use. This article discusses the data available with regard to the use of premixed PN, focusing on the potential advantages and disadvantages of using premixed PN, and also discusses the implementation of premixed PN in a large tertiary cancer center. © 2015 American Society for Parenteral and Enteral Nutrition.

Studies of Premixed Laminar and Turbulent Flames at Microgravity

NASA Technical Reports Server (NTRS)

Kwon, O. C.; Abid, M.; Porres, J.; Liu, J. B.; Ronney, P. D.; Struk, P. M.; Weiland, K. J.

2003-01-01

Several topics relating to premixed flame behavior at reduced gravity have been studied. These topics include: (1) flame balls; (2) flame structure and stability at low Lewis number; (3) experimental simulation of buoyancy effects in premixed flames using aqueous autocatalytic reactions; and (4) premixed flame propagation in Hele-Shaw cells. Because of space limitations, only topic (1) is discussed here, emphasizing results from experiments on the recent STS-107 Space Shuttle mission, along with numerical modeling efforts.

Large eddy simulation of bluff body stabilized premixed and partially premixed combustion

NASA Astrophysics Data System (ADS)

Porumbel, Ionut

Large Eddy Simulation (LES) of bluff body stabilized premixed and partially premixed combustion close to the flammability limit is carried out in this thesis. The main goal of the thesis is the study of the equivalence ratio effect on flame stability and dynamics in premixed and partially premixed flames. An LES numerical algorithm able to handle the entire range of combustion regimes and equivalence ratios is developed for this purpose. The algorithm has no ad-hoc adjustable model parameters and is able to respond automatically to variations in the inflow conditions, without user intervention. Algorithm validation is achieved by conducting LES of reactive and non-reactive flow. Comparison with experimental data shows good agreement for both mean and unsteady flow properties. In the reactive flow, two scalar closure models, Eddy Break-Up (EBULES) and Linear Eddy Mixing (LEMLES), are used and compared. Over important regions, the flame lies in the Broken Reaction Zone regime. Here, the EBU model assumptions fail. In LEMLES, the reaction-diffusion equation is not filtered, but resolved on a linear domain and the model maintains validity. The flame thickness predicted by LEMLES is smaller and the flame is faster to respond to turbulent fluctuations, resulting in a more significant wrinkling of the flame surface when compared to EBULES. As a result, LEMLES captures better the subtle effects of the flame-turbulence interaction, the flame structure shows higher complexity, and the far field spreading of the wake is closer to the experimental observations. Three premixed (φ = 0.6, 0.65, and 0.75) cases are simulated. As expected, for the leaner case (φ = 0.6) the flame temperature is lower, the heat release is reduced and vorticity is stronger. As a result, the flame in this case is found to be unstable. In the rich case (φ = 0.75), the flame temperature is higher, and the spreading rate of the wake is increased due to the higher amount of heat release. The ignition

[Mild hypoglycaemia is common in type 2 diabetic patients treated with insulin analogues in the Czech Republic and the patients are concerned about it: results of a GAPP2TM survey (Global Attitudes of Physicians and Patient)].

PubMed

Prázný, Martin

2015-03-01

Mild hypoglycaemia affects diabetes management, productivity and quality of life of patients. Data are scarce about the incidence of mild hypoglycaemia in daily life of type 2 diabetic patients treated with insulin analogues. The aim was to focus on the incidence of mild hypoglycaemia and its consequences in the international GAPP2 survey (Global Attitudes of Patient and Physicians) conducted also in the Czech Republic. The GAPP2 project - Global Attitudes of Patients and Physicians is an international cross-sectional study conducted online via Internet in a questionnaire form dedicated to type 2 diabetic patients treated with insulin analogues and physicians who treat these patients. The survey was realized in two steps including 17 countries. The first step was completed by six countries in 2012. The second step was terminated by additional eleven countries including the Czech Republic in 2014. The survey was designed to obtain data on some aspects of insulin therapy and persistent issues in daily practice from the views of patients and physicians. One part of survey was dedicated to mild hypoglycaemia occurring in treatment with insulin analogues. The incidence of mild hypoglycaemia and the reaction of patients and physicians on hypoglycaemia (including modification of therapy, self-monitoring) were investigated. Moreover, there was investigated the impact of mild hypoglycaemia on quality of life from the view of patients and physicians. The results of the survey have shown that mild hypoglycaemia is common in patients with insulin analogues in the Czech Republic. In addition, patients in the Czech Republic are more afraid from hypoglycaemia and feel more limited in daily life in comparison to other countries in GAPP2 survey. Patients try to avoid nocturnal hypoglycaemia through reduction or omission of prescribed dose of insulin. Furthermore, research has observed that physicians are poorly informed by patients about incidence and severity of hypoglycaemia. The

Challenges constraining access to insulin in the private-sector market of Delhi, India

PubMed Central

Kaplan, Warren A

2016-01-01

Objective India's majority of patients—including those living with diabetes—seek healthcare in the private sector through out-of-pocket (OOP) payments. We studied access to insulin in the private-sector market of Delhi state, India. Methods A modified World Health Organization/Health Action International (WHO/HAI) standard survey to assess insulin availability and prices, and qualitative interviews with insulin retailers (pharmacists) and wholesalers to understand insulin market dynamics. Results In 40 pharmacy outlets analysed, mean availability of the human and analogue insulins on the 2013 Delhi essential medicine list was 44.4% and 13.1%, respectively. 82% of pharmacies had domestically manufactured human insulin phials, primarily was made in India under licence to overseas pharmaceutical companies. Analogue insulin was only in cartridge and pen forms that were 4.42 and 5.81 times, respectively, the price of human insulin phials. Domestically manufactured human phial and cartridge insulin (produced for foreign and Indian companies) was less expensive than their imported counterparts. The lowest paid unskilled government worker in Delhi would work about 1.5 and 8.6 days, respectively, to be able to pay OOP for a monthly supply of human phial and analogue cartridge insulin. Interviews suggest that the Delhi insulin market is dominated by a few multinational companies that import and/or license in-country production. Several factors influence insulin uptake by patients, including doctor's prescribing preference. Wholesalers have negative perceptions about domestic insulin manufacturing. Conclusions The Delhi insulin market is an oligopoly with limited market competition. Increasing competition from Indian companies is going to require some additional policies, not presently in place. As more Indian companies produce biosimilars, brand substitution policies are needed to be able to benefit from market competition. PMID:28588966

Challenges constraining access to insulin in the private-sector market of Delhi, India.

PubMed

Sharma, Abhishek; Kaplan, Warren A

2016-01-01

India's majority of patients-including those living with diabetes-seek healthcare in the private sector through out-of-pocket (OOP) payments. We studied access to insulin in the private-sector market of Delhi state, India. A modified World Health Organization/Health Action International (WHO/HAI) standard survey to assess insulin availability and prices, and qualitative interviews with insulin retailers (pharmacists) and wholesalers to understand insulin market dynamics. In 40 pharmacy outlets analysed, mean availability of the human and analogue insulins on the 2013 Delhi essential medicine list was 44.4% and 13.1%, respectively. 82% of pharmacies had domestically manufactured human insulin phials, primarily was made in India under licence to overseas pharmaceutical companies. Analogue insulin was only in cartridge and pen forms that were 4.42 and 5.81 times, respectively, the price of human insulin phials. Domestically manufactured human phial and cartridge insulin (produced for foreign and Indian companies) was less expensive than their imported counterparts. The lowest paid unskilled government worker in Delhi would work about 1.5 and 8.6 days, respectively, to be able to pay OOP for a monthly supply of human phial and analogue cartridge insulin. Interviews suggest that the Delhi insulin market is dominated by a few multinational companies that import and/or license in-country production. Several factors influence insulin uptake by patients, including doctor's prescribing preference. Wholesalers have negative perceptions about domestic insulin manufacturing. The Delhi insulin market is an oligopoly with limited market competition. Increasing competition from Indian companies is going to require some additional policies, not presently in place. As more Indian companies produce biosimilars, brand substitution policies are needed to be able to benefit from market competition.

Large eddy simulation of premixed and non-premixed combustion in a Stagnation Point Reverse Flow combustor

NASA Astrophysics Data System (ADS)

Undapalli, Satish

A new combustor referred to as Stagnation Point Reverse Flow (SPRF) combustor has been developed at Georgia Tech to meet the increasingly stringent emission regulations. The combustor incorporates a novel design to meet the conflicting requirements of low pollution and high stability in both premixed and non-premixed modes. The objective of this thesis work is to perform Large Eddy Simulations (LES) on this lab-scale combustor and elucidate the underlying physics that has resulted in its excellent performance. To achieve this, numerical simulations have been performed in both the premixed and non-premixed combustion modes, and velocity field, species field, entrainment characteristics, flame structure, emissions, and mixing characteristics have been analyzed. Simulations have been carried out first for a non-reactive case to resolve relevant fluid mechanics without heat release by the computational grid. The computed mean and RMS quantities in the non-reacting case compared well with the experimental data. Next, the simulations were extended for the premixed reactive case by employing different sub-grid scale combustion chemistry closures: Eddy Break Up (EBU), Artificially Thickened Flame (TF) and Linear Eddy Mixing (LEM) models. Results from the EBU and TF models exhibit reasonable agreement with the experimental velocity field. However, the computed thermal and species fields have noticeable discrepancies. Only LEM with LES (LEMLES), which is an advanced scalar approach, has been able to accurately predict both the velocity and species fields. Scalar mixing plays an important role in combustion, and this is solved directly at the sub-grid scales in LEM. As a result, LEM accurately predicts the scalar fields. Due to the two way coupling between the super-grid and sub-grid quantities, the velocity predictions also compare very well with the experiments. In other approaches, the sub-grid effects have been either modeled using conventional approaches (EBU) or need

LIF measurements and chemical kinetic analysis of methylidyne formation in high-pressure counter-flow partially premixed and non-premixed flames

NASA Astrophysics Data System (ADS)

Naik, S. V.; Laurendeau, N. M.

2004-11-01

We report quantitative, spatially resolved, linear laser-induced fluorescence (LIF) measurements of methylidyne concentration ([CH]) in laminar, methane air, counter-flow partially premixed and non-premixed flames using excitation near 431.5 nm in the A X (0,0) band. For partially premixed flames, fuel-side equivalence ratios (ϕB) of 1.45, 1.6 and 2.0 are studied at pressures of 1, 3, 6, 9 and 12 atm. For non-premixed flames, the fuel-side mixture consists of 25% CH4 and 75% N2; measurements are obtained at pressures of 1, 2, 3, 4, 5, 6, 9 and 12 atm. The quantitative CH measurements are compared with predictions from an opposed-flow flame code utilizing two GRI chemical kinetic mechanisms (versions 2.11 and 3.0). LIF measurements of [CH] are corrected for variations in the quenching rate coefficient by using major species concentrations and temperatures generated by the code along with suitable quenching cross sections for CH available from the literature. A pathway analysis provides relative contributions from important elementary reactions to the total amount of CH produced at various pressures. Key reactions controlling peak CH concentrations are also identified by using a sensitivity analysis. For the partially premixed flames, measured CH profiles are reproduced reasonably well by GRI 3.0, although some quantitative disagreement exists at all pressures. Two CH radical peaks are observed for ϕB=1.45 and ϕB=1.6 at pressures above 3 atm. Peak CH concentrations for the non-premixed flames are significantly underpredicted by GRI 3.0. The latter agrees with previously reported NO concentrations, which are also underpredicted in these same high-pressure counter-flow diffusion flames.

Therapeutics in pediatric diabetes: insulin and non-insulin approaches. Part of a series on Pediatric Pharmacology, guest edited by Gianvincenzo Zuccotti, Emilio Clementi, and Massimo Molteni.

PubMed

Kim, Jongoh; Kim, Se Min; Nguyen, Ha Cam Thuy; Redondo, Maria Jose

2012-01-01

Treatment of pediatric diabetes can be challenging. Strict glucose control can be accompanied by hypoglycemia and weight gain. Recently, there have been many developments in insulin preparations and delivery methods which make insulin levels more close to a physiologic pattern. Newly developed rapid/long acting analogues and delivery devices such as continuous subcutaneous insulin infusion (CSII, insulin pump) may reduce hypoglycemia and improve glycemic control. CSII combined with continuous glucose monitoring can achieve even better glycemic control. The closed-loop system is rapidly evolving and an artificial pancreas will be available in the near future. It is now recognized that several hormones other than insulin such as glucagon, amylin, and incretins contribute to glucose homeostasis. The role of co-adjuncts such as metformin, amylin analogues, and incretin based therapy is now emerging. Immunotherapy in a high risk population or patients in the early phase of type 1 diabetes may prevent further destruction of pancreatic β cells. Copyright © 2011 Elsevier Ltd. All rights reserved.

The structure of partially-premixed methane/air flames under varying premixing

NASA Astrophysics Data System (ADS)

Kluzek, Celine; Karpetis, Adonios

2008-11-01

The present work examines the spatial and scalar structure of laminar, partially premixed methane/air flames with the objective of developing flamelet mappings that capture the effect of varying premixture strength (air addition in fuel.) Experimental databases containing full thermochemistry measurements within laminar axisymmetric flames were obtained at Sandia National Laboratories, and the measurements of all major species and temperature are compared to opposed-jet one-dimensional flow simulation using Cantera and the full chemical kinetic mechanism of GRI 3.0. Particular emphasis is placed on the scalar structure of the laminar flames, and the formation of flamelet mappings that capture all of the salient features of thermochemistry in a conserved scalar representation. Three different premixture strengths were examined in detail: equivalence ratios of 1.8, 2.2, and 3.17 resulted in clear differences in the flame scalar structure, particularly in the position of the rich premixed flame zone and the attendant levels of major and intermediate species (carbon monoxide and hydrogen).

Incorporating a Generic Model of Subcutaneous Insulin Absorption into the AIDA v4 Diabetes Simulator: 1. A Prospective Collaborative Development Plan

PubMed Central

Lehmann, Eldon D.; Tarín, Cristina; Bondia, Jorge; Teufel, Edgar; Deutsch, Tibor

2007-01-01

Introduction AIDA v4 is an interactive educational diabetes simulator that has been made available, for over a decade, without charge via the Internet. The software is currently freely accessible at http://www.2aida.org. This report sets out a collaborative development plan to enhance the program with a new model of subcutaneous insulin absorption, which permits the simulation of rapidly acting and very long-acting insulin analogues, as well as insulin injection doses larger than 40 units. Methods A novel, generic, physiological subcutaneous insulin absorption model is overviewed and a methodology is proposed by which this can be substituted in place of the previously adopted insulin absorption model utilized within AIDA v4.3a. Apart from this substitution it is proposed to retain the existing model of the glucoregulatory system currently used in AIDA v4.3a. Results Initial simulation results based on bench testing of this approach using MATLAB are presented for the exogenous insulin flow profile (Iex) following subcutaneous injections of a rapidly acting insulin analogue, a short-acting (regular) insulin preparation, intermediate-acting insulins (both Semilente and neutral protamine Hagedorn types), and a very long-acting insulin analogue. Discussion It is proposed to implement this collaborative development plan—first by bench testing the approach in MATLAB and then by integrating the generic subcutaneous insulin absorption Iex model into the AIDA simulator in Pascal. The aim is to provide enhanced functionality and educational simulations of regimens utilizing novel insulin analogues, as well as injections larger than 40 units of insulin. PMID:19885100

Long-acting insulin analogues for type 1 diabetes: An overview of systematic reviews and meta-analysis of randomized controlled trials.

PubMed

Laranjeira, Fernanda O; de Andrade, Keitty R C; Figueiredo, Ana C M G; Silva, Everton N; Pereira, Mauricio G

2018-01-01

The comparison between long acting insulin analogues (LAIA) and human insulin (NPH) has been investigated for decades, with many randomized controlled trials (RCTs) and systematic reviews giving mixed results. This overlapping and contradictory evidence has increased uncertainty on coverage decisions at health systems level. To conduct an overview of systematic reviews and update existing reviews, preparing new meta-analysis to determine whether LAIA are effective for T1D patients compared to NPH. We identified systematic reviews of RCTs that evaluated the efficacy of LAIA glargine or detemir, compared to NPH insulin for T1D, assessing glycated hemoglobin (A1C) and hypoglycemia. Data sources included Pubmed, Cochrane Library, EMBASE and hand-searching. The methodological quality of studies was independently assessed by two reviewers, using AMSTAR and Jadad scale. We found 11 eligible systematic reviews that contained a total of 25 relevant clinical trials. Two reviewers independently abstracted data. We found evidence that LAIA are efficacious compared to NPH, with estimates showing a reduction in nocturnal hypoglycemia episodes (RR 0.66; 95% CI 0.57; 0.76) and A1C (95% CI 0.23; 0.12). No significance was found related to severe hypoglycemia (RR 0.94; 95% CI 0.71; 1.24). This study design has allowed us to carry out the most comprehensive assessment of RCTs on this subject, filling a gap in diabetes research. Our paper addresses a question that is important not only for decision makers but also for clinicians.

Soot Formation in Freely-Propagating Laminar Premixed Flames

NASA Technical Reports Server (NTRS)

Lin, K.-C.; Hassan, M. I.; Faeth, G. M.

1997-01-01

Soot formation within hydrocarbon-fueled flames is an important unresolved problem of combustion science. Thus, the present study is considering soot formation in freely-propagating laminar premixed flames, exploiting the microgravity environment to simplify measurements at the high-pressure conditions of interest for many practical applications. The findings of the investigation are relevant to reducing emissions of soot and continuum radiation from combustion processes, to improving terrestrial and spacecraft fire safety, and to developing methods of computational combustion, among others. Laminar premixed flames are attractive for studying soot formation because they are simple one-dimensional flows that are computationally tractable for detailed numerical simulations. Nevertheless, studying soot-containing burner-stabilized laminar premixed flames is problematical: spatial resolution and residence times are limited at the pressures of interest for practical applications, flame structure is sensitive to minor burner construction details so that experimental reproducibility is not very good, consistent burner behavior over the lengthy test programs needed to measure soot formation properties is hard to achieve, and burners have poor durability. Fortunately, many of these problems are mitigated for soot-containing, freely-propagating laminar premixed flames. The present investigation seeks to extend work in this laboratory for various soot processes in flames by observing soot formation in freely-propagating laminar premixed flames. Measurements are being made at both Normal Gravity (NG) and MicroGravity (MG), using a short-drop free-fall facility to provide MG conditions.

Dynamics and structure of turbulent premixed flames

NASA Technical Reports Server (NTRS)

Bilger, R. W.; Swaminathan, N.; Ruetsch, G. R.; Smith, N. S. A.

1995-01-01

In earlier work (Mantel & Bilger, 1994) the structure of the turbulent premixed flame was investigated using statistics based on conditional averaging with the reaction progress variable as the conditioning variable. The DNS data base of Trouve and Poinsot (1994) was used in this investigation. Attention was focused on the conditional dissipation and conditional axial velocity in the flame with a view to modeling these quantities for use in the conditional moment closure (CMC) approach to analysis of kinetics in premixed flames (Bilger, 1993). Two remarkable findings were made: there was almost no acceleration of the axial velocity in the flame front itself; and the conditional scalar dissipation remained as high, or higher, than that found in laminar premixed flames. The first finding was surprising since in laminar flames all the fluid acceleration occurs through the flame front, and this could be expected also for turbulent premixed flames at the flamelet limit. The finding gave hope of inventing a new approach to the dynamics of turbulent premixed flames through use of rapid distortion theory or an unsteady Bernoulli equation. This could lead to a new second order closure for turbulent premixed flames. The second finding was contrary to our measurements with laser diagnostics in lean hydrocarbon flames where it is found that conditional scalar dissipation drops dramatically below that for laminar flamelets when the turbulence intensity becomes high. Such behavior was not explainable with a one-step kinetic model, even at non-unity Lewis number. It could be due to depletion of H2 from the reaction zone by preferential diffusion. The capacity of the flame to generate radicals is critically dependent on the levels of H2 present (Bilger, et al., 1991). It seemed that a DNS computation with a multistep reduced mechanism would be worthwhile if a way could be found to make this feasible. Truly innovative approaches to complex problems often come only when there is the

Lean, premixed, prevaporized combustion for aircraft gas turbine engines

NASA Technical Reports Server (NTRS)

Mularz, E. J.

1979-01-01

The application of lean, premixed, prevaporized combustion to aircraft turbine engine systems can result in benefits in terms of superior combustion performance, improved combustor and turbine durability, and environmentally acceptable pollutant emissions. Lean, premixed prevaporized combustion is particularly attractive for reducing the oxides of nitrogen emissions during high altitude cruise. The NASA stratospheric cruise emission reduction program will evolve and demonstrate lean, premixed, prevaporized combustion technology for aircraft engines. This multiphased program is described. In addition, the various elements of the fundamental studies phase of the program are reviewed, and results to date of many of these studies are summarized.

Turbulent flame propagation in partially premixed flames

NASA Technical Reports Server (NTRS)

Poinsot, T.; Veynante, D.; Trouve, A.; Ruetsch, G.

1996-01-01

Turbulent premixed flame propagation is essential in many practical devices. In the past, fundamental and modeling studies of propagating flames have generally focused on turbulent flame propagation in mixtures of homogeneous composition, i.e. a mixture where the fuel-oxidizer mass ratio, or equivalence ratio, is uniform. This situation corresponds to the ideal case of perfect premixing between fuel and oxidizer. In practical situations, however, deviations from this ideal case occur frequently. In stratified reciprocating engines, fuel injection and large-scale flow motions are fine-tuned to create a mean gradient of equivalence ratio in the combustion chamber which provides additional control on combustion performance. In aircraft engines, combustion occurs with fuel and secondary air injected at various locations resulting in a nonuniform equivalence ratio. In both examples, mean values of the equivalence ratio can exhibit strong spatial and temporal variations. These variations in mixture composition are particularly significant in engines that use direct fuel injection into the combustion chamber. In this case, the liquid fuel does not always completely vaporize and mix before combustion occurs, resulting in persistent rich and lean pockets into which the turbulent flame propagates. From a practical point of view, there are several basic and important issues regarding partially premixed combustion that need to be resolved. Two such issues are how reactant composition inhomogeneities affect the laminar and turbulent flame speeds, and how the burnt gas temperature varies as a function of these inhomogeneities. Knowledge of the flame speed is critical in optimizing combustion performance, and the minimization of pollutant emissions relies heavily on the temperature in the burnt gases. Another application of partially premixed combustion is found in the field of active control of turbulent combustion. One possible technique of active control consists of pulsating

Insulin lispro 25/75 and insulin lispro 50/50 as starter insulin in Japanese patients with type 2 diabetes: subanalysis of the CLASSIFY randomized trial.

PubMed

Watada, Hirotaka; Imori, Makoto; Li, Pengfei; Iwamoto, Noriyuki

2017-07-28

In Japan, premixed insulins are commonly used as starter insulin for type 2 diabetes. This subpopulation analysis assessed the efficacy and safety of twice-daily LM25 (25% insulin lispro/75% insulin lispro protamine) and LM50 (50% insulin lispro/50% insulin lispro protamine) as starter insulin in Japanese subjects, and compared these results with the whole-trial populations of East Asian subjects. In this subpopulation analysis of an open-label, phase 4, randomized trial (CLASSIFY), Japanese subjects received LM25 (n = 88) or LM50 (n = 84) twice-daily for 26 weeks. The primary outcome was change from baseline at Week 26 in glycated hemoglobin (HbA1c). Results for Japanese subjects were generally similar to those for the whole-trial population. Similar changes from baseline in HbA1c were observed for LM25 and LM50 groups (least squares [LS] mean difference [95% confidence interval] of LM25 - LM50 = 0.13 [-0.16, 0.41]%, 1.42 [-1.75, 4.48] mmol/mol, p = 0.388). More LM50-treated subjects than LM25-treated subjects achieved HbA1c targets of <7.0% (59.5% versus 43.2%; p = 0.034) or ≤6.5% (45.2% versus 28.4%; p = 0.027). The reduction in postprandial blood glucose concentrations after morning and evening meals was statistically significantly greater for LM50 than for LM25. The incidence of both hypoglycemia and treatment-emergent adverse events were similar between treatment groups. Both LM25 and LM50 twice daily appear to be effective and well tolerated as starter insulin, although LM50 might be more effective for Japanese type 2 diabetes patients.

Premixed polymer concrete overlays.

DOT National Transportation Integrated Search

1990-01-01

The results of a study undertaken to evaluate premixed polymer concrete overlays (PMPCO) over a 3-year period are presented. The PMPCO evaluated were constructed with polyester amide para resin and silica sand 1;. polyester styrene resin 1 and silica...

Premixed direct injection nozzle

DOEpatents

Zuo, Baifang [Simpsonville, SC; Johnson, Thomas Edward [Greer, SC; Lacy, Benjamin Paul [Greer, SC; Ziminsky, Willy Steve [Simpsonville, SC

2011-02-15

An injection nozzle having a main body portion with an outer peripheral wall is disclosed. The nozzle includes a plurality of fuel/air mixing tubes disposed within the main body portion and a fuel flow passage fluidly connected to the plurality of fuel/air mixing tubes. Fuel and air are partially premixed inside the plurality of the tubes. A second body portion, having an outer peripheral wall extending between a first end and an opposite second end, is connected to the main body portion. The partially premixed fuel and air mixture from the first body portion gets further mixed inside the second body portion. The second body portion converges from the first end toward said second end. The second body portion also includes cooling passages that extend along all the walls around the second body to provide thermal damage resistance for occasional flame flash back into the second body.

Assessment of implantable infusion pumps for continuous infusion of human insulin in rats: potential for group housing.

PubMed

Jensen, Vivi Flou Hjorth; Mølck, Anne-Marie; Mårtensson, Martin; Strid, Mette Aagaard; Chapman, Melissa; Lykkesfeldt, Jens; Bøgh, Ingrid Brück

2017-06-01

Group housing is considered to be important for rats, which are highly sociable animals. Single housing may impact behaviour and levels of circulating stress hormones. Rats are typically used in the toxicological evaluation of insulin analogues. Human insulin (HI) is frequently used as a reference compound in these studies, and a comparator model of persistent exposure by HI infusion from external pumps has recently been developed to support toxicological evaluation of long-acting insulin analogues. However, this model requires single housing of the animals. Developing an insulin-infusion model which allows group housing would therefore greatly improve animal welfare. The aim of the present study was to investigate the suitability of implantable infusion pumps for HI infusion in group-housed rats. Group housing of rats implanted with a battery-driven pump proved to be possible. Intravenous infusion of HI lowered blood glucose levels persistently for two weeks, providing a comparator model for use in two-week repeated-dose toxicity studies with new long-acting insulin analogues, which allows group housing, and thereby increasing animal welfare compared with an external infusion model.

A Review of the Clinical Efficacy and Safety of Insulin Degludec and Glargine 300 U/mL in the Treatment of Diabetes Mellitus.

PubMed

Woo, Vincent C

2017-08-01

The treatment of type 1 diabetes mellitus (T1DM) and type 2 diabetes mellitus (T2DM) using insulin is not ideal at this time. Despite advances made with basal insulin analogues, many individuals achieve less than optimal glycemic control or are at risk for hypoglycemia. Currently available basal insulin analogues do not deliver steady, peakless, continuous insulin for >24 hours and are associated with adverse events, including hypoglycemia. The objective of this paper was to review the clinical efficacy and safety of upcoming long-acting insulin analogues such as insulin degludec and insulin glargine 300 U/mL (Gla-300). A comprehensive literature search of PubMed and Google Scholar was conducted from 1966 to 2015. The search included randomized controlled trials that specifically assessed the efficacy and safety of insulin degludec and Gla-300 in patients with T1DM and T2DM. The efficacy of insulin degludec and Gla-300 in achieving glycemic control has been reported in clinical trials in adults with T1DM and T2DM. Not only did a large number of patients succeed in meeting glycosylated hemoglobin targets, but they also experienced reductions in hypoglycemic events. These 2 therapies are associated with a reduced risk of nocturnal hypoglycemia and are generally well tolerated. The long-acting insulin analogues insulin degludec and Gla-300 are promising therapies in the treatment of T1DM and T2DM. Their improved insulin delivery for >24 hours offers glycemic control with a good safety profile. Copyright © 2017 Elsevier HS Journals, Inc. All rights reserved.

Numerical evaluation of equivalence ratio measurement using OH{sup *} and CH{sup *} chemiluminescence in premixed and non-premixed methane-air flames

DOE Office of Scientific and Technical Information (OSTI.GOV)

Panoutsos, C.S.; Hardalupas, Y.; Taylor, A.M.K.P.

This work presents results from detailed chemical kinetics calculations of electronically excited OH (A{sup 2}{sigma}, denoted as OH{sup *}) and CH (A{sup 2}{delta}, denoted as CH{sup *}) chemiluminescent species in laminar premixed and non-premixed counterflow methane-air flames, at atmospheric pressure. Eight different detailed chemistry mechanisms, with added elementary reactions that account for the formation and destruction of the chemiluminescent species OH{sup *} and CH{sup *}, are studied. The effects of flow strain rate and equivalence ratio on the chemiluminescent intensities of OH{sup *}, CH{sup *} and their ratio are studied and the results are compared to chemiluminescent intensity ratio measurementsmore » from premixed laminar counterflow natural gas-air flames. This is done in order to numerically evaluate the measurement of equivalence ratio using OH{sup *} and CH{sup *} chemiluminescence, an experimental practise that is used in the literature. The calculations reproduced the experimental observation that there is no effect of strain rate on the chemiluminescent intensity ratio of OH{sup *} to CH{sup *}, and that the ratio is a monotonic function of equivalence ratio. In contrast, the strain rate was found to have an effect on both the OH{sup *} and CH{sup *} intensities, in agreement with experiment. The calculated OH{sup *}/CH{sup *} values showed that only five out of the eight mechanisms studied were within the same order of magnitude with the experimental data. A new mechanism, proposed in this work, gave results that agreed with experiment within 30%. It was found that the location of maximum emitted intensity from the excited species OH{sup *} and CH{sup *} was displaced by less than 65 and 115 {mu}m, respectively, away from the maximum of the heat release rate, in agreement with experiments, which is small relative to the spatial resolution of experimental methods applied to combustion applications, and, therefore, it is expected that

Blood glucose and serum insulin responses to breakfast including guar gum and cooked or uncooked milk in type 2 (non-insulin-dependent) diabetic patients.

PubMed

Uusitupa, M; Aro, A; Korhonen, T; Tuunainen, A; Sarlund, H; Penttilä, I

1984-06-01

The post-prandial blood glucose and serum insulin responses to test meals, each including 300 ml fat-free milk taken separately with the meal or premixed before cooking into the meal consisting of oatmeal porridge, were studied in 10 diet-treated Type 2 (non-insulin-dependent) diabetic subjects. The modifying effect of guar gum on the responses was also studied by supplementing both types of test meals with 5 g granulated guar gum taken at the beginning of the meal. The blood glucose response was higher after the meal which contained cooked milk than after the respective meal with milk taken separately. The guar gum supplementation attenuated the blood glucose response after the meals, but the effect was more pronounced after the meal containing cooked milk. Post-prandial serum insulin responses were similar after all test meals. The results suggest that cooking may facilitate the absorption of lactose from milk-containing foods, and that supplementation with guar gum may counteract this response.

Cellular Cations Control Conformational Switching of Inositol Pyrophosphate Analogues

PubMed Central

Hager, Anastasia; Wu, Mingxuan; Wang, Huanchen; Brown, Nathaniel W.; Shears, Stephen B.

2016-01-01

The inositol pyrophosphate messengers (PP-InsPs) are emerging as an important class of cellular regulators. These molecules have been linked to numerous biological processes, including insulin secretion and cancer cell migration, but how they trigger such a wide range of cellular responses has remained unanswered in many cases. Here, we show that the PP-InsPs exhibit complex speciation behaviour and propose that a unique conformational switching mechanism could contribute to their multifunctional effects. We synthesised non-hydrolysable bisphosphonate analogues and crystallised the analogues in complex with mammalian PPIP5K2 kinase. Subsequently, the bisphosphonate analogues were used to investigate the protonation sequence, metal-coordination properties, and conformation in solution. Remarkably, the presence of potassium and magnesium ions enabled the analogues to adopt two different conformations near physiological pH. Understanding how the intrinsic chemical properties of the PP-InsPs can contribute to their complex signalling outputs will be essential to elucidate their regulatory functions. PMID:27460418

Chaos in an imperfectly premixed model combustor.

PubMed

Kabiraj, Lipika; Saurabh, Aditya; Karimi, Nader; Sailor, Anna; Mastorakos, Epaminondas; Dowling, Ann P; Paschereit, Christian O

2015-02-01

This article reports nonlinear bifurcations observed in a laboratory scale, turbulent combustor operating under imperfectly premixed mode with global equivalence ratio as the control parameter. The results indicate that the dynamics of thermoacoustic instability correspond to quasi-periodic bifurcation to low-dimensional, deterministic chaos, a route that is common to a variety of dissipative nonlinear systems. The results support the recent identification of bifurcation scenarios in a laminar premixed flame combustor (Kabiraj et al., Chaos: Interdiscip. J. Nonlinear Sci. 22, 023129 (2012)) and extend the observation to a practically relevant combustor configuration.

Analgesic efficacy of equimolar 50% nitrous oxide/oxygen gas premix (Kalinox®) as compared with a 5% eutectic mixture of lidocaine/prilocaine (EMLA®) in chronic leg ulcer debridement.

PubMed

Traber, Juerg; Held, Ulrike; Signer, Maria; Huebner, Tobias; Arndt, Stefan; Neff, Thomas A

2017-08-01

Chronic foot and leg ulcers are a common health problem worldwide. A mainstay of chronic ulcer therapy is sharp mechanical wound debridement requiring potent analgesia. In this prospective, controlled, single-centre, crossover design study, patients were assigned to either the administration of topical analgesia with 5% lidocaine/prilocaine cream or the inhalation of an analgesic 50% N 2 O/O 2 gas premix. Primary outcome parameter was level of pain at maximum wound depth during debridement as measured by a visual analogue scale. Secondary outcomes included level of pain after debridement, overall duration of treatment session, duration and completeness of debridement, and the patient's subjective perception of analgesic quality during debridement. Pain level increased from 0·60/0·94 (first/second debridement; baseline) to 1·76/2·50 (debridement) with 5% lidocaine/prilocaine and from 1·00/1·35 (baseline) to 3·95/3·29 (debridement) with 50% N 2 O/O 2 gas premix. Patient satisfaction was 90·48%/94·44% (first/second debridement) with topical 5% lidocaine/prilocaine analgesia and 90·48%/76·47% with the inhalation of 50% N 2 O/O 2 gas premix. Debridement was completed in a significantly higher percentage of 85·71%/88·89% (first/second debridement) with 5% lidocaine/prilocaine than with 50% N 2 O/O 2 gas premix (42·86%/58·82%) (odds ratio 6·7; P = 0·001). This study provides sound evidence that analgesia with topically administered 5% lidocaine/prilocaine cream is superior to the use of inhaled 50% N 2 O/O 2 gas premix in chronic leg ulcer debridement. © 2016 Medicalhelplines.com Inc and John Wiley & Sons Ltd.

Study on Combustion Oscillation of Premixed Flame with Pilot Fuel at Elevated Pressures

NASA Astrophysics Data System (ADS)

Ohtsuka, Masaya; Yoshida, Shohei; Hirata, Yoshitaka; Kobayashi, Nariyoshi

Acoustically-coupled combustion oscillation is studied for premixed flame with pilot fuel to be used in gas turbine combustors. Premixed gas is passed through swirl vanes and burnt with the centrally injected pilot fuel. The dependencies of pressure, fuel to air ratio, premixed fuel rate, inlet velocity and air temperature on the combustion oscillation are investigated. Two kinds of oscillation modes of ˜100Hz and ˜350Hz are activated according to inlet velocities. Fluctuating pressures are amplified when the premixed fuel rate is over ˜80% at elevated pressures. The fluctuating pressure peak moves to a higher premixed fuel ratio region with increased pressure or fuel to air ratio for the Helmholz type mode. Combustion oscillation occurs when the pilot fuel velocity is changed proportionally with the flame length.

Four-year evolution of insulin regimens, glycaemic control, hypoglycaemia and body weight after starting insulin therapy in type 2 diabetes across three continents.

PubMed

Home, Philip D; Dain, Marie-Paule; Freemantle, Nick; Kawamori, Ryuzo; Pfohl, Martin; Brette, Sandrine; Pilorget, Valérie; Scherbaum, Werner A; Vespasiani, Giacomo; Vincent, Maya; Balkau, Beverley

2015-05-01

It is of interest to understand how insulin therapy currently evolves in clinical practice, in the years after starting insulin in people with type 2 diabetes. We aimed to describe this evolution prospectively over 4 years, to assist health care planning. People who had started any insulin were identified from 12 countries on three continents. Baseline, then yearly follow-up, data were extracted from clinical records over 4 years. Of the 2999 eligible people, 2272 were followed over 4 years. When starting insulin, mean (SD) duration of diabetes was 10.6 (7.8) years, HbA1c 9.5 (2.0)% (80 [22]mmol/mol) and BMI 29.3 (6.3)kg/m(2). Initial insulin therapy was basal 52%, premix 23%, mealtime+basal 14%, mealtime 8% and other 3%; at 4 years, 30%, 25%, 33%, 2% and 5%, respectively, with 5% not on insulin. Insulin dose was 20.2U/day at the start and 45.8U/day at year 4. There were 1258 people (55%) on their original regimen at 4 years, and this percentage differed according to baseline insulin regimen. HbA1c change was -2.0 (2.2)% (-22 [24]mmol/mol) and was similar by final insulin regimen. Hypoglycaemia prevalence was <20% in years 1-4. Body weight change was mostly in year 1, and was very variable, mean +2.7 (7.5)kg at year 4. Different insulin regimens were started in people with differing characteristics, and they evolved differently; insulin dose, hypoglycaemia and body weight change were diverse and largely independent of regimen. Copyright © 2015 The Authors. Published by Elsevier Ireland Ltd.. All rights reserved.

Laminar Premixed and Diffusion Flames (Ground-Based Study)

NASA Technical Reports Server (NTRS)

Dai, Z.; El-Leathy, A. M.; Lin, K.-C.; Sunderland, P. B.; Xu, F.; Faeth, G. M.; Urban, D. L. (Technical Monitor); Yuan, Z.-G. (Technical Monitor)

2000-01-01

Ground-based studies of soot processes in laminar flames proceeded in two phases, considering laminar premixed flames and laminar diffusion flames, in turn. The test arrangement for laminar premixed flames involved round flat flame burners directed vertically upward at atmospheric pressure. The test arrangement for laminar jet diffusion flames involved a round fuel port directed vertically upward with various hydrocarbon fuels burning at atmospheric pressure in air. In both cases, coflow was used to prevent flame oscillations and measurements were limited to the flame axes. The measurements were sufficient to resolve soot nucleation, growth and oxidation rates, as well as the properties of the environment needed to evaluate mechanisms of these processes. The experimental methods used were also designed to maintain capabilities for experimental methods used in corresponding space-based experiments. This section of the report will be limited to consideration of flame structure for both premixed and diffusion flames.

Decision analysis applied to the purchase of frozen premixed intravenous admixtures.

PubMed

Witte, K W; Eck, T A; Vogel, D P

1985-04-01

A structured decision-analysis model was used to evaluate frozen premixed cefazolin admixtures. Decision analysis is a process of stating the desired outcome, establishing and weighting evaluation criteria, identifying options for reaching the outcome, evaluating and numerically ranking each option for each criterion, multiplying the ranking by the weight for each criterion, and calculating total points for each option. It was used to compare objectively frozen premixed cefazolin admixtures with batch reconstitution from vials and reconstitution of lyophilized, ready-to-mix containers. In this institution the model numerically demonstrated a distinct preference for the premixed frozen admixture over these other alternatives. A comparison of these results with the total cost impact of each option resulted in a decision to purchase the frozen premixed solution. The advantages of the frozen premixed solution that contributed most to this decision were decreased waste and personnel time. The latter was especially important since it allowed for the reallocation of personnel resources to other potentially cost-reducing clinical functions. Decision analysis proved to be an effective tool for formalizing the process of selecting among various alternatives to reach a desired outcome in this hospital pharmacy.

Turbulent transport in premixed flames

NASA Technical Reports Server (NTRS)

Rutland, C. J.; Cant, R. S.

1994-01-01

Simulations of planar, premixed turbulent flames with heat release were used to study turbulent transport. Reynolds stress and Reynolds flux budgets were obtained and used to guide the investigation of important physical effects. Essentially all pressure terms in the transport equations were found to be significant. In the Reynolds flux equations, these terms are the major source of counter-gradient transport. Viscous and molecular terms were also found to be significant, with both dilatational and solenoidal terms contributing to the Reynolds stress dissipation. The BML theory of premixed turbulent combustion was critically examined in detail. The BML bimodal pdf was found to agree well with the DNS data. All BML decompositions, through the third moments, show very good agreement with the DNS results. Several BML models for conditional terms were checked using the DNS data and were found to require more extensive development.

PREMIX: PRivacy-preserving EstiMation of Individual admiXture.

PubMed

Chen, Feng; Dow, Michelle; Ding, Sijie; Lu, Yao; Jiang, Xiaoqian; Tang, Hua; Wang, Shuang

2016-01-01

In this paper we proposed a framework: PRivacy-preserving EstiMation of Individual admiXture (PREMIX) using Intel software guard extensions (SGX). SGX is a suite of software and hardware architectures to enable efficient and secure computation over confidential data. PREMIX enables multiple sites to securely collaborate on estimating individual admixture within a secure enclave inside Intel SGX. We implemented a feature selection module to identify most discriminative Single Nucleotide Polymorphism (SNP) based on informativeness and an Expectation Maximization (EM)-based Maximum Likelihood estimator to identify the individual admixture. Experimental results based on both simulation and 1000 genome data demonstrated the efficiency and accuracy of the proposed framework. PREMIX ensures a high level of security as all operations on sensitive genomic data are conducted within a secure enclave using SGX.

Effect of chloroquine on insulin and glucose homoeostasis in normal subjects and patients with non-insulin-dependent diabetes mellitus.

PubMed Central

Smith, G D; Amos, T A; Mahler, R; Peters, T J

1987-01-01

Plasma glucose, insulin, and C peptide concentrations were determined after an oral glucose load in normal subjects and in a group of patients with non-insulin-dependent diabetes mellitus before and during a short course of treatment with chloroquine. In the control group there was a small but significant reduction in fasting blood glucose concentration but overall glucose tolerance and hormone concentrations were unaffected. In contrast, the patients with non-insulin-dependent diabetes mellitus showed a significant improvement in their glucose tolerance, which paralleled the severity of their diabetes. This response seems to reflect decreased degradation of insulin rather than increased pancreatic output. These observations suggest that treatment with chloroquine or suitable analogues may be a new approach to the management of diabetes. PMID:3103729

Premix formulation for making the Indonesian otak-otak

NASA Astrophysics Data System (ADS)

Tawali, A. B.; Wakiah, N.; Ramli, A. R.; Mahendradatta, M.; Tawali, S.; Made, S.

2018-05-01

Otak-otak is one indigenous foods from Indonesia which made from fish paste, tapioca flour and spices. The aim of this research was to produce premix flour for making otak-otak using mackerel surimi, tapioca flour and spices and to evaluate their chemical properties and sensory acceptability of the product. Mackerel surimi was first dried, miled into powder form then mixed with tapioca flour and spices. The result showed that, otak-otak which made from Premix-B formula (40% mackerel surimi powder and 60% tapioca flour) was the best result for all sensory attributes. It presented “like moderately” for hedonic score. Protein, ash, moisture, carbohydrate, and fat contents of the premix-B formula were 23.51%, 2.44%, 7.31%, 71.02%, 4.28%, respectively, which met the SNI requirements. Overall, this study clearly showed that it was possible to make otak-otak with less complicated process and the product did not have any negative results on sensory perception.

Use of Piggyback Electrolytes for Patients Receiving Individually Prescribed vs Premixed Parenteral Nutrition.

PubMed

Busch, Rebecca A; Curtis, Caitlin S; Leverson, Glen E; Kudsk, Kenneth A

2015-07-01

Parenteral nutrition (PN) is available as individualized prescriptions frequently prepared with an automated compounding device or as commercially prepared premixed solutions. Our institution exclusively used individualized PN until an amino acid shortage forced a temporary switch to premixed solutions. In general, premixed solutions contain lower electrolyte levels than individualized formulations prescribed for patients with normal organ function. We aimed to quantify supplemental intravenous piggyback (IVPB) electrolyte use in adult patients receiving individualized and premixed PN and to quantify any effect on difference in the cost of therapy. We compared use of supplemental IVPB electrolytes administered to patients receiving PN during consecutive periods prior to and during the amino acid shortage. Electrolyte IVPBs tabulated were potassium chloride, 10 and 20 mEq; magnesium sulfate, 2 g and 4 g; potassium phosphate, 7.5 and 15 mmol; and sodium phosphate, 7.5 and 15 mmol IVPB. There was no statistical difference in the number of PN formulations administered per day during each period (14.7 ± 3.9 vs 14.0 ± 2.6, individualized vs premixed, respectively). Total IVPB electrolytes prescribed per day increased significantly from the individualized PN period to the premixed PN period (7.03 ± 3.8 vs 13.8 ± 6.8; P < .0001). The additional IVPB electrolyte supplementation required in patients receiving premixed PN was associated with an additional $11,855.74 cost per 30 days of therapy compared with those who received individualized PN. Inpatient use of premixed PN results in a significant increase in IVPB electrolyte supplementation and cost compared with individualized PN use. © 2014 American Society for Parenteral and Enteral Nutrition.

Studies of Premixed Laminar and Turbulent Flames at Microgravity

NASA Technical Reports Server (NTRS)

Ronney, Paul D.

1993-01-01

The work of the Principal Investigator (PI) has encompassed four topics related to the experimental and theoretical study of combustion limits in premixed flames at microgravity, as discussed in the following sections. These topics include: (1) radiation effects on premixed gas flames; (2) flame structure and stability at low Lewis number; (3) flame propagation and extinction is cylindrical tubes; and (4) experimental simulation of combustion processes using autocatalytic chemical reactions.

Agonism and Antagonism at the Insulin Receptor

PubMed Central

Knudsen, Louise; Hansen, Bo Falck; Jensen, Pia; Pedersen, Thomas Åskov; Vestergaard, Kirsten; Schäffer, Lauge; Blagoev, Blagoy; Oleksiewicz, Martin B.; Kiselyov, Vladislav V.; De Meyts, Pierre

2012-01-01

Insulin can trigger metabolic as well as mitogenic effects, the latter being pharmaceutically undesirable. An understanding of the structure/function relationships between insulin receptor (IR) binding and mitogenic/metabolic signalling would greatly facilitate the preclinical development of new insulin analogues. The occurrence of ligand agonism and antagonism is well described for G protein-coupled receptors (GPCRs) and other receptors but in general, with the exception of antibodies, not for receptor tyrosine kinases (RTKs). In the case of the IR, no natural ligand or insulin analogue has been shown to exhibit antagonistic properties, with the exception of a crosslinked insulin dimer (B29-B’29). However, synthetic monomeric or dimeric peptides targeting sites 1 or 2 of the IR were shown to be either agonists or antagonists. We found here that the S961 peptide, previously described to be an IR antagonist, exhibited partial agonistic effects in the 1–10 nM range, showing altogether a bell-shaped dose-response curve. Intriguingly, the agonistic effects of S961 were seen only on mitogenic endpoints (3H-thymidine incorporation), and not on metabolic endpoints (14C-glucose incorporation in adipocytes and muscle cells). The agonistic effects of S961 were observed in 3 independent cell lines, with complete concordance between mitogenicity (3H-thymidine incorporation) and phosphorylation of the IR and Akt. Together with the B29-B’29 crosslinked dimer, S961 is a rare example of a mixed agonist/antagonist for the human IR. A plausible mechanistic explanation based on the bivalent crosslinking model of IR activation is proposed. PMID:23300584

Gravity Effects Observed In Partially Premixed Flames

NASA Technical Reports Server (NTRS)

Puri, Ishwar K.; Aggarwal, Suresh K.; Lock, Andrew J.; Gauguly, Ranjan; Hegde, Uday

2003-01-01

Partially premixed flames (PPFs) contain a rich premixed fuel air mixture in a pocket or stream, and, for complete combustion to occur, they require the transport of oxidizer from an appropriately oxidizer-rich (or fuel-lean) mixture that is present in another pocket or stream. Partial oxidation reactions occur in fuel-rich portions of the mixture and any remaining unburned fuel and/or intermediate species are consumed in the oxidizer-rich portions. Partial premixing, therefore, represents that condition when the equivalence ratio (phi) in one portion of the flowfield is greater than unity, and in another section its value is less than unity. In general, for combustion to occur efficiently, the global equivalence ratio is in the range fuel-lean to stoichiometric. These flames can be established by design by placing a fuel-rich mixture in contact with a fuel-lean mixture, but they also occur otherwise in many practical systems, which include nonpremixed lifted flames, turbulent nonpremixed combustion, spray flames, and unwanted fires. Other practical applications of PPFs are reported elsewhere. Although extensive experimental studies have been conducted on premixed and nonpremixed flames under microgravity, there is a absence of previous experimental work on burner stabilized PPFs in this regard. Previous numerical studies by our group employing a detailed numerical model showed gravity effects to be significant on the PPF structure. We report on the results of microgravity experiments conducted on two-dimensional (established on a Wolfhard-Parker slot burner) and axisymmetric flames (on a coannular burner) that were investigated in a self-contained multipurpose rig. Thermocouple and radiometer data were also used to characterize the thermal transport in the flame.

Flow-combustion interactions in ducted flameholder-stabilized premixed flames

NASA Astrophysics Data System (ADS)

Soteriou, Marios; Arienti, Marco; Erickson, Robert

2006-11-01

Turbulent premixed combustion is present in many power generation and propulsion systems due to its large energy conversion rate (as compared to non-premixed combustion) and its potential for reduced emissions (at the lean limit). As a result, the study of turbulent premixed flames has received substantial attention in the past through experiment, analysis and simulation. In the recent past, unsteady Computational Fluid Dynamics (CFD) based models have been increasingly leveraged towards the in depth study of the physics of turbulent premixed flames. The bulk of this effort focuses on the response of the flame to turbulence. In contrast, we focus on the opposite problem, i.e. the modification of the turbulent flowfield by the flame. This topic has also received some attention but with a strong emphasis on planar (in the mean), flames propagating normal to the flow. Instead, we focus on flameholder-stabilized ducted flames, i.e. ones in which the flame is confined and substantially inclined to the incoming flow. The fundamental mechanisms by which the flame impacts the flow, i.e. dilatation, baroclinic vorticity generation and molecular diffusion enhancement are discussed in detail and their relative impact quantified. Limitations of modeling these mechanisms in current state of the art CFD models are also addressed.

Closed loop insulin delivery in diabetes.

PubMed

Battelino, Tadej; Omladič, Jasna Šuput; Phillip, Moshe

2015-06-01

The primary goal of type 1 diabetes treatment is attaining near-normal glucose values. This currently remains out of reach for most people with type 1 diabetes despite intensified insulin treatment in the form of insulin analogues, educational interventions, continuous glucose monitoring, and sensor augmented insulin pump. The main remaining problem is risk of hypoglycaemia, which cannot be sufficiently reduced in all patient groups. Additionally, patients' burn-out often develops with years of tedious day-to-day diabetes management, rendering available diabetes-related technology less efficient. Over the past 40 years, several attempts have been made towards computer-programmed insulin delivery in the form of closed loop, with faster developments especially in the past decade. Automated insulin delivery has reduced human error in glycaemic control and considerably lessened the burden of routine self-management. In this chapter, data from randomized controlled trials with closed-loop insulin delivery that included type 1 diabetes population are summarized, and an evidence-based vision for possible routine utilization of closed loop is provided. Copyright © 2015 Elsevier Ltd. All rights reserved.

Projections for insulin treatment for diabetics.

PubMed

Cao, Ying; Lam, Laura

2002-06-01

The evolution of insulin treatment of diabetes has dramatically changed the natural course of this disease. Modern recombinant DNA technology has brought about many new insulin analogues with improved pharmacokinetics, resulting in better glycemic control. In addition, improved insulin delivery systems, such as insulin pumps and pens, have been introduced to provide convenience and to enhance patient compliance. Efforts are currently being devoted to developing noninvasive insulin formulations, such as oral and pulmonary insulin. A number of products are at different stages of clinical trials. Meanwhile, the quest for a permanent cure for diabetes continues. The frontier of diabetes research has gone through a period of substantial expansion, with the emergence of new areas that include gene therapy, islet cell transplantation and diabetic vaccine. Technological breakthroughs, such as recombinant DNA, nanotechnology, microarray-aided genomics and proteomics, will provide more profound insights into the pathogenesis, and the immunological and biological basis of diabetes. Our growing knowledge in these areas will ultimately contribute to the discovery of preventive methods against or a cure for this disease.

Importance of Insulin Immunoassays in the Diagnosis of Factitious Hypoglycemia

PubMed Central

Nalbantoğlu Elmas, Özlem; Demir, Korcan; Soylu, Nusret; Çelik, Nilüfer; Özkan, Behzat

2014-01-01

We report two cases emphasizing the importance of insulin assays for evaluation of hypoglycemia in diabetic patients. Case 1 was a 96/12-year-old female patient with type 1 diabetes mellitus and case 2 was a 1010/12-year-old male patient with DIDMOAD. Both patients were on a basal-bolus insulin regimen. Both were admitted because of persistent hypoglycemia. Analyses of serum samples obtained at the time of hypoglycemia initially showed low insulin and C-peptide levels. Recurrent episodes of unexplained hypoglycemia necessitated measurement of insulin levels by using different insulin assays, which revealed hyperinsulinemic hypoglycemia with low C-peptide levels, findings which confirmed a diagnosis of factitious hypoglycemia. Surreptitious administration of insulin should not be excluded in diabetic patients with hypoglycemia without taking into account the rate of cross-reactivity of insulin analogues with the insulin assay used. PMID:25541899

Treating Diabetes Mellitus: Pharmacophore Based Designing of Potential Drugs from Gymnema sylvestre against Insulin Receptor Protein

PubMed Central

Hossain, Mohammad Uzzal; Khan, Md. Arif; Rakib-Uz-Zaman, S. M.; Ali, Mohammad Tuhin; Islam, Md. Saidul; Keya, Chaman Ara; Salimullah, Md.

2016-01-01

Diabetes mellitus (DM) is one of the most prevalent metabolic disorders which can affect the quality of life severely. Injectable insulin is currently being used to treat DM which is mainly associated with patient inconvenience. Small molecules that can act as insulin receptor (IR) agonist would be better alternatives to insulin injection. Herein, ten bioactive small compounds derived from Gymnema sylvestre (G. sylvestre) were chosen to determine their IR binding affinity and ADMET properties using a combined approach of molecular docking study and computational pharmacokinetic elucidation. Designing structural analogues were also performed for the compounds associated with toxicity and less IR affinity. Among the ten parent compounds, six were found to have significant pharmacokinetic properties with considerable binding affinity towards IR while four compounds were associated with toxicity and less IR affinity. Among the forty structural analogues, four compounds demonstrated considerably increased binding affinity towards IR and less toxicity compared with parent compounds. Finally, molecular interaction analysis revealed that six parent compounds and four analogues interact with the active site amino acids of IR. So this study would be a way to identify new therapeutics and alternatives to insulin for diabetic patients. PMID:27034931

Treating Diabetes Mellitus: Pharmacophore Based Designing of Potential Drugs from Gymnema sylvestre against Insulin Receptor Protein.

PubMed

Hossain, Mohammad Uzzal; Khan, Md Arif; Rakib-Uz-Zaman, S M; Ali, Mohammad Tuhin; Islam, Md Saidul; Keya, Chaman Ara; Salimullah, Md

2016-01-01

Diabetes mellitus (DM) is one of the most prevalent metabolic disorders which can affect the quality of life severely. Injectable insulin is currently being used to treat DM which is mainly associated with patient inconvenience. Small molecules that can act as insulin receptor (IR) agonist would be better alternatives to insulin injection. Herein, ten bioactive small compounds derived from Gymnema sylvestre (G. sylvestre) were chosen to determine their IR binding affinity and ADMET properties using a combined approach of molecular docking study and computational pharmacokinetic elucidation. Designing structural analogues were also performed for the compounds associated with toxicity and less IR affinity. Among the ten parent compounds, six were found to have significant pharmacokinetic properties with considerable binding affinity towards IR while four compounds were associated with toxicity and less IR affinity. Among the forty structural analogues, four compounds demonstrated considerably increased binding affinity towards IR and less toxicity compared with parent compounds. Finally, molecular interaction analysis revealed that six parent compounds and four analogues interact with the active site amino acids of IR. So this study would be a way to identify new therapeutics and alternatives to insulin for diabetic patients.

Preparation of lipid nanoemulsions by premix membrane emulsification with disposable materials.

PubMed

Gehrmann, Sandra; Bunjes, Heike

2016-09-25

The possibility to prepare nanoemulsions as drug carrier systems on small scale was investigated with disposable materials. For this purpose premix membrane emulsification (premix ME) as a preparation method for nanoemulsions with narrow particle size distributions on small scale was used. The basic principle of premix ME is that the droplets of a coarse pre-emulsion get disrupted by the extrusion through a porous membrane. In order to implement the common preparation setup for premix ME with disposable materials, the suitability of different syringe filters (made from polyethersulfone, cellulose acetate, cellulose ester and nylon) and different pharmaceutically relevant emulsifiers (phospholipids, polysorbate 80 and sucrose laurate) for the preparation of nanoemulsions was investigated. Already the preparation of the premix could be realized by emulsification with the help of two disposable syringes. As shown for a phospholipid-stabilized emulsion, the polyethersulfone filter was the most appropriate one and was used for the study with different emulsifiers. With this syringe filter, the median particle size of all investigated emulsions was below 500nm after 21 extrusion cycles through a 200nm filter and a subsequent extrusion cycle through a 100nm filter. Furthermore, the particle size distribution of the polysorbate 80- and sucrose laurate-stabilized emulsions prepared this way was very narrow (span value of 0.7). Copyright © 2016 Elsevier B.V. All rights reserved.

21 CFR 170.60 - Nitrites and/or nitrates in curing premixes.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 21 Food and Drugs 3 2011-04-01 2011-04-01 false Nitrites and/or nitrates in curing premixes. 170... and Decisions § 170.60 Nitrites and/or nitrates in curing premixes. (a) Nitrites and/or nitrates are.... (b) Nitrites and/or nitrates, when packaged separately from flavoring and seasoning in curing...

21 CFR 170.60 - Nitrites and/or nitrates in curing premixes.

Code of Federal Regulations, 2013 CFR

2013-04-01

... 21 Food and Drugs 3 2013-04-01 2013-04-01 false Nitrites and/or nitrates in curing premixes. 170... and Decisions § 170.60 Nitrites and/or nitrates in curing premixes. (a) Nitrites and/or nitrates are.... (b) Nitrites and/or nitrates, when packaged separately from flavoring and seasoning in curing...

21 CFR 170.60 - Nitrites and/or nitrates in curing premixes.

Code of Federal Regulations, 2012 CFR

2012-04-01

... 21 Food and Drugs 3 2012-04-01 2012-04-01 false Nitrites and/or nitrates in curing premixes. 170... and Decisions § 170.60 Nitrites and/or nitrates in curing premixes. (a) Nitrites and/or nitrates are.... (b) Nitrites and/or nitrates, when packaged separately from flavoring and seasoning in curing...

Effect of combined application insulin and insulin detemir on continous glucose monitor in children with type 1 diabetes mellitus.

PubMed

Chen, Xiao-Yun; Dong, Qing; Li, Gui-Mei

2015-01-01

Insulin detemir is a soluble long-acting human insulin analogue at neutral pH with a unique mechanism of action, which could strengthen the effects of insulin. This study aims to explore the effects of insulin combined with insulin detemir on the continous glucose in children with type 1 diabetes mellitus. In this study, 150 patients with type 1 diabetes enrolled were included and randomly divided into 3 groups: insulin group (group A), insulin detemir group (group B) and insulin combined with insulin detemir group (group C). Each subject underwent 72 h of continuous glucose monitoring (CGM). MAGE, HbA1c and Noctumal Hypoglycemia levels were examined by using the ELISA kits. The body weight changes were also detected in this study. The results indicated that the information including age, body weight, disease duration and glucose level and HbA1c percentage on the start time point among three groups indicated no statistical differences. Insulin combined with insulin detemir decrease MAGE and HbA1c level in Group C compared to Group A and Group A (P < 0.05). Insulin combined with insulin detemir decreas noctumal hypoglycemia levels and body weight changes (P < 0.05). In conclusion, this study confirmed efficacy of insulin detemir by demonstrating non-inferiority of insulin detemir compared with insulin with respect to HbA1c, with an improved safety profile including significantly fewer hypoglycaemic episodes and less undesirable weight gain in children.

Premixed Turbulent Flame Propagation in Microgravity

NASA Technical Reports Server (NTRS)

Menon, Suresh

1999-01-01

A combined numerical-experimental study has been carried out to investigate the structure and propagation characteristics of turbulent premixed flames with and without the influence of buoyancy. Experimentally, the premixed flame characteristics are studied in the wrinkled regime using a Couette flow facility and an isotropic flow facility in order to resolve the scale of flame wrinkling. Both facilities were chosen for their ability to achieve sustained turbulence at low Reynolds number. This implies that conventional diagnostics can be employed to resolve the smallest scales of wrinkling. The Couette facility was also built keeping in mind the constraints imposed by the drop tower requirements. Results showed that the flow in this Couette flow facility achieves full-developed turbulence at low Re and all turbulence statistics are in good agreement with past measurements on large-scale facilities. Premixed flame propagation studies were then carried out both using the isotropic box and the Couette facility. Flame imaging showed that fine scales of wrinkling occurs during flame propagation. Both cases in Ig showed significant buoyancy effect. To demonstrate that micro-g can remove this buoyancy effect, a small drop tower was built and drop experiments were conducted using the isotropic box. Results using the Couette facility confirmed the ability to carry out these unique reacting flow experiments at least in 1g. Drop experiments at NASA GRC were planned but were not completed due to termination of this project.

Experimental Investigation of Premixed Turbulent Hydrocarbon/Air Bunsen Flames

NASA Astrophysics Data System (ADS)

Tamadonfar, Parsa

Through the influence of turbulence, the front of a premixed turbulent flame is subjected to the motions of eddies that leads to an increase in the flame surface area, and the term flame wrinkling is commonly used to describe it. If it is assumed that the flame front would continue to burn locally unaffected by the stretch, then the total turbulent burning velocity is expected to increase proportionally to the increase in the flame surface area caused by wrinkling. When the turbulence intensity is high enough such that the stretch due to hydrodynamics and flame curvature would influence the local premixed laminar burning velocity, then the actual laminar burning velocity (that is, flamelet consumption velocity) should reflect the influence of stretch. To address this issue, obtaining the knowledge of instantaneous flame front structures, flame brush characteristics, and burning velocities of premixed turbulent flames is necessary. Two axisymmetric Bunsen-type burners were used to produce premixed turbulent flames, and three optical measurement techniques were utilized: Particle image velocimetry to measure the turbulence statistics; Rayleigh scattering method to measure the temperature fields of premixed turbulent flames, and Mie scattering method to visualize the flame front contours of premixed turbulent flames. Three hydrocarbons (methane, ethane, and propane) were used as the fuel in the experiments. The turbulence was generated using different perforated plates mounted upstream of the burner exit. A series of comprehensive parameters including the thermal flame front thickness, characteristic flame height, mean flame brush thickness, mean volume of the turbulent flame region, two-dimensional flame front curvature, local flame front angle, two-dimensional flame surface density, wrinkled flame surface area, turbulent burning velocity, mean flamelet consumption velocity, mean turbulent flame stretch factor, mean turbulent Markstein length and number, and mean

Physicochemical basis for the rapid time-action of LysB28ProB29-insulin: dissociation of a protein-ligand complex.

PubMed Central

Bakaysa, D. L.; Radziuk, J.; Havel, H. A.; Brader, M. L.; Li, S.; Dodd, S. W.; Beals, J. M.; Pekar, A. H.; Brems, D. N.

1996-01-01

The rate-limiting step for the absorption of insulin solutions after subcutaneous injection is considered to be the dissociation of self-associated hexamers to monomers. To accelerate this absorption process, insulin analogues have been designed that possess full biological activity and yet have greatly diminished tendencies to self-associate. Sedimentation velocity and static light scattering results show that the presence of zinc and phenolic ligands (m-cresol and/or phenol) cause one such insulin analogue, LysB28ProB29-human insulin (LysPro), to associate into a hexameric complex. Most importantly, this ligand-bound hexamer retains its rapid-acting pharmacokinetics and pharmacodynamics. The dissociation of the stabilized hexameric analogue has been studied in vitro using static light scattering as well as in vivo using a female pig pharmacodynamic model. Retention of rapid time-action is hypothesized to be due to altered subunit packing within the hexamer. Evidence for modified monomer-monomer interactions has been observed in the X-ray crystal structure of a zinc LysPro hexamer (Ciszak E et al., 1995, Structure 3:615-622). The solution state behavior of LysPro, reported here, has been interpreted with respect to the crystal structure results. In addition, the phenolic ligand binding differences between LysPro and insulin have been compared using isothermal titrating calorimetry and visible absorption spectroscopy of cobalt-containing hexamers. These studies establish that rapid-acting insulin analogues of this type can be stabilized in solution via the formation of hexamer complexes with altered dissociation properties. PMID:8976561

Fucosterol activates the insulin signaling pathway in insulin resistant HepG2 cells via inhibiting PTP1B.

PubMed

Jung, Hyun Ah; Bhakta, Himanshu Kumar; Min, Byung-Sun; Choi, Jae Sue

2016-10-01

Insulin resistance is a characteristic feature of type 2 diabetes mellitus (T2DM) and is characterized by defects in insulin signaling. This study investigated the modulatory effects of fucosterol on the insulin signaling pathway in insulin-resistant HepG2 cells by inhibiting protein tyrosine phosphatase 1B (PTP1B). In addition, molecular docking simulation studies were performed to predict binding energies, the specific binding site of fucosterol to PTP1B, and to identify interacting residues using Autodock 4.2 software. Glucose uptake was determined using a fluorescent D-glucose analogue and the glucose tracer 2-[N-(7-nitrobenz-2-oxa-1,3-diazol-4-yl) amino]-2-deoxyglucose, and the signaling pathway was detected by Western blot analysis. We found that fucosterol enhanced insulin-provoked glucose uptake and conjointly decreased PTP1B expression level in insulin-resistant HepG2 cells. Moreover, fucosterol significantly reduced insulin-stimulated serine (Ser307) phosphorylation of insulin receptor substrate 1 (IRS1) and increased phosphorylation of Akt, phosphatidylinositol-3-kinase, and extracellular signal- regulated kinase 1 at concentrations of 12.5, 25, and 50 µM in insulin-resistant HepG2 cells. Fucosterol inhibited caspase-3 activation and nuclear factor kappa B in insulin-resistant hepatocytes. These results suggest that fucosterol stimulates glucose uptake and improves insulin resistance by downregulating expression of PTP1B and activating the insulin signaling pathway. Thus, fucosterol has potential for development as an anti-diabetic agent.

Insulin therapy at onset of type 2 diabetes mellitus--a new concept.

PubMed

Sahay, B K

2011-04-01

In this study, insulin therapy was initiated at onset of disease in patients whose fasting blood glucose was more than 250 mg/dl. All enrolled subjects were treated with human premixed insulin (30/70) administered subcutaneously twice daily before breakfast and before dinner. A total of 113 subjects entered the study fulfilling the inclusion criteria. Good glycaemic control was achieved in a few days. The dosage requirement of insulin came down gradually after control was achieved as manifest by hypoglycaemia--leading to withdrawal of insulin. Some of them were managed with diet and exercise alone. Others required small doses of oral antidiabetic agents (OAD). There were no cases of secondary failure to OADs. Ten cases are on average duration of follow-up of 10 years. Two cases are under good control with diet and exercise alone, seven on treatment with oral hypoglycemic agents and one of them requiring insulin to maintain HbAlc below 7%. Thus insulin therapy at onset provides an opportunity to correct all the underlying pathogenic mechanisms, i.e., glucotoxicity, lipotoxicity and prevents beta cell apoptosis and suppresses inflammation, leading to beta cell protection. Such timely intervention provides long term benefits, laying the foundation for the concept of beta cell preservation rather that only replacing beta cell function. Hence we propose that all patients with type 2 diabetes should be offered insulin therapy at the onset of their diabetes for a period of 2-4 weeks.

Premixed calcium silicate cement for endodontic applications

PubMed Central

Persson, Cecilia; Engqvist, Håkan

2011-01-01

Calcium silicate-based materials (also called MTA) are increasingly being used in endodontic applications. However, the handling properties of MTA are not optimal when it comes to injectability and cohesion. Premixing the cements using glycerol avoids these issues. However, there is a lack of data on the effect of common cement variables on important properties of premixed cements for endodontic applications. In this study, the effects of liquid-to-powder ratio, amount of radiopacifier and amount of calcium sulfate (added to control the setting time) were screened using a statistical model. In the second part of the study, the liquid-to-powder ratio was optimized for cements containing three different amounts of radiopacifier. Finally, the effect of using glycerol rather than water was evaluated in terms of radiopacity. The setting time was found to increase with the amount of radiopacifier when the liquid-to-powder ratio was fixed. This was likely due to the higher density of the radiopacifier in comparison to the calcium silicate, which gave a higher liquid-to-powder ratio in terms of volume. Using glycerol rather than water to mix the cements led to a decrease in radiopacity of the cement. In conclusion, we were able to produce premixed calcium silicate cements with acceptable properties for use in endodontic applications. PMID:23507729

Premixed calcium phosphate cements: synthesis, physical properties, and cell cytotoxicity.

PubMed

Xu, Hockin H K; Carey, Lisa E; Simon, Carl G; Takagi, Shozo; Chow, Laurence C

2007-04-01

Calcium phosphate cement (CPC) is a promising material for dental, periodontal, and craniofacial repairs. However, its use requires on-site powder-liquid mixing that increases the surgical placement time and raises concerns of insufficient and inhomogeneous mixing. The objective of this study was to determine a formulation of premixed CPC (PCPC) with rapid setting, high strength, and good in vitro cell viability. PCPCs were formulated from CPC powder+non-aqueous liquid+gelling agent+hardening accelerator. Five PCPCs were thus developed: PCPC-Tartaric, PCPC-Malonic, PCPC-Citric, PCPC-Glycolic, and PCPC-Malic. Formulations and controls were compared for setting time, diametral tensile strength, and osteoblast cell compatibility. Setting time (mean+/-S.D.; n=4) for PCPC-Tartaric was 8.2+/-0.8 min, significantly less than the 61.7+/-1.5 min for the Premixed Control developed previously (p<0.001). On 7th day immersion, the diametral tensile strength of PCPC-Tartaric reached 6.5+/-0.8 MPa, higher than 4.5+/-0.8 MPa of Premixed Control (p=0.036). Osteoblast cells displayed a polygonal morphology and attached to the nano-hydroxyapatite crystals in the PCPCs. All cements had similar live cell density values (p=0.126), indicating that the new PCPCs were as cell compatible as a non-premixed CPC control known to be biocompatible. Each of the new PCPCs had a cell viability that was not significantly different (p>0.1) from that of the non-premixed CPC control. PCPCs will eliminate the powder-liquid mixing during surgery and may also improve the cement performance. The new PCPCs supported cell attachment and yielded a high cell density and viability. Their mechanical strengths approached the reported strengths of sintered porous hydroxyapatite implants and cancellous bone. These nano-crystalline hydroxyapatite cements may be useful in dental, periodontal, and craniofacial repairs.

Association of hypoglycaemia severity with clinical, patient‐reported and economic outcomes in US patients with type 2 diabetes using basal insulin

PubMed Central

Lee, Lulu K.; Gupta, Shaloo; Preblick, Ron

2018-01-01

Aims To evaluate the clinical and patient‐reported outcomes and healthcare utilization and costs associated with patient‐reported hypoglycaemia in US adults with type 2 diabetes (T2D) treated with basal insulin. Materials and methods This was an observational, cross‐sectional, survey‐based study of adults with T2D on basal insulin ± oral antidiabetes drugs (OADs) or rapid‐acting/premixed insulin, who had in the past ever experienced hypoglycaemia, using US data from the National Health and Wellness Survey. Eligible patients were categorized as having no hypoglycaemia (38.7%), non‐severe hypoglycaemia (55.1%), or severe hypoglycaemia (6.2%) in the preceding 3 months. Outcomes included health‐related quality of life (HRQoL), work productivity and activity impairment, healthcare resource utilization, and estimated direct and indirect costs. Multivariable regression models were performed to control for patient characteristics. Results Patients who experienced severe hypoglycaemia had significantly (P < .05) lower HRQoL scores, greater overall impairment of work productivity and activity, greater healthcare resource utilization, and higher costs compared with those who experienced non‐severe or no hypoglycaemia. Patients with non‐severe hypoglycaemia also reported an impact on the number of provider visits, indirect costs, and HRQoL. Conclusions Patients with T2D using basal insulin ± OADs or rapid‐acting/premixed insulin in the United States who experienced severe hypoglycaemia had greater impairment of activity and work productivity, utilized more healthcare resources, and incurred higher associated costs than those with non‐severe or no hypoglycaemia. The study also demonstrated the impact that non‐severe hypoglycaemic events have on economic and HRQoL outcomes. Reducing the incidence and severity of hypoglycaemia could lead to clinically meaningful improvements in HRQoL and may result in lower healthcare utilization and associated costs

Spectral kinetic energy transfer in turbulent premixed reacting flows.

PubMed

Towery, C A Z; Poludnenko, A Y; Urzay, J; O'Brien, J; Ihme, M; Hamlington, P E

2016-05-01

Spectral kinetic energy transfer by advective processes in turbulent premixed reacting flows is examined using data from a direct numerical simulation of a statistically planar turbulent premixed flame. Two-dimensional turbulence kinetic-energy spectra conditioned on the planar-averaged reactant mass fraction are computed through the flame brush and variations in the spectra are connected to terms in the spectral kinetic energy transport equation. Conditional kinetic energy spectra show that turbulent small-scale motions are suppressed in the burnt combustion products, while the energy content of the mean flow increases. An analysis of spectral kinetic energy transfer further indicates that, contrary to the net down-scale transfer of energy found in the unburnt reactants, advective processes transfer energy from small to large scales in the flame brush close to the products. Triadic interactions calculated through the flame brush show that this net up-scale transfer of energy occurs primarily at spatial scales near the laminar flame thermal width. The present results thus indicate that advective processes in premixed reacting flows contribute to energy backscatter near the scale of the flame.

Three-Dimensional Direct Numerical Simulation of Methane-Air Turbulent Premixed Flames with Reduced Kinetic Mechanism

NASA Astrophysics Data System (ADS)

Tanahashi, Mamoru; Kikuta, Satoshi; Miyauchi, Toshio

2004-11-01

Three-dimensional DNS of methane-air turbulent premixed flames have been conducted to investigate local extinction mechanism of turbulent premixed flames. A reduced kinetic mechanism (MeCH-19), which is created from GRI-Mech. 2.11 and includes 23 reactive species and 19 step reactions, are used to simulate CH_4-O_2-N2 reaction in turbulence. The effectiveness of this reduced kinetic mechanism has been conformed by preliminary two-dimensional DNS with the reduced kinetic mechanism and two detailed kinetic mechanisms; GRI-Mech. 2.11 and Miller & Bowman. Flame structures of methane-air turbulent premixed flames are compared with those of hydrogen-air turbulent premixed flames which have been obtained by 3D-DNS with a detailed kinetic mechanism in our previous study. Local extinctions occur in methane-air turbulent premixed flames, whereas no extinction is observed for hydrogen-air flames in nearly same turbulence condition. The local extinction mechanism is discussed based on eddy/flame interaction in small scales.

Titration of basal insulin or immediate addition of rapid acting insulin in patients not at target using basal insulin supported oral antidiabetic treatment - A prospective observational study in 2202 patients.

PubMed

Siegmund, Thorsten; Pfohl, Martin; Forst, Thomas; Pscherer, Stefan; Bramlage, Peter; Foersch, Johannes; Borck, Anja; Seufert, Jochen

Optimal treatment intensification strategies in patients with type-2 diabetes mellitus (T2DM) receiving basal insulin supported oral antidiabetic therapy (BOT) remain controversial. The objective of the present study was to compare outcomes of BOT-intensification by either the uptitration of long-acting insulin glargine or by the immediate addition of a rapid acting insulin analogue (RAIA). This was a prospective, observational, 24-week study in T2DM patients with BOT using insulin glargine and baseline glycated hemoglobin (HbA1c) between 7.0 and 8.5%. Patients were stratified by their physicians to one of the following treatment intensification strategies: Basal insulin titration to target with discretionary subsequent addition of RAIA at weeks 12 or 24 (GLAR), or immediate addition of RAIA at baseline (GLARplus). A total of 3266 patients were prescreened of whom 2202 fulfilled the selection criteria. Of these, 1684 patients were documented in the GLAR group and 518 in the GLARplus group. In the GLAR group, in 91 (5.5%) and 21 patients (1.3%) RAIA was added at weeks 12 and 24, respectively. The groups displayed similar baseline characteristics; except, mean diabetes duration was slightly shorter in the GLAR group (8.7 vs. 9.4 years). During the study, insulin glargine dose was increased from 18.7 to 26.4U (plus 7.7U) in GLAR and from 24.9 to 27.3U (plus 2.4U) in GLARplus patients. Mean RAIA dose was 9.6±4.7U at the final visit. After 24 weeks, HbA1c was reduced by 0.8 and 0.9% in the GLAR and GLARplus groups, respectively (both p<0.001). An HbA1c of ≤7.0% was achieved in 49.2% of GLAR and 48.5% of GLARplus patients. In both groups, we observed improvements in cardiovascular risk factors such as lipids and blood pressure. The rates of symptomatic (1.6 vs. 1.7%) and severe (0.18 vs. 0.19%) hypoglycemic episodes were low and comparable in both groups. These findings provide evidence that treatment intensification in patients with type 2 diabetes not at glycemic

Insulin regimens and glycemic control in different parts of Europe over 4years after starting insulin in people with type 2 diabetes: Data from the CREDIT non-interventional study.

PubMed

Blonde, Lawrence; Marre, Michel; Vincent, Maya; Brette, Sandrine; Pilorget, Valerie; Danchin, Nicholas; Vespasiani, Giacomo; Home, Philip

2017-11-01

A number of insulin regimens are used in type 2 diabetes. This analysis aims to better understand the evolution of insulin therapy in different regions of Europe. Data from people starting any insulin were collected in eastern Europe (EEur: Croatia, Russia, Ukraine), northern Europe (NEur: Finland, Germany, UK) and southern Europe (SEur: France, Italy, Portugal, Spain). Retrospective data on starting insulin and prospective follow-up data were extracted from clinical records. At 4years, 1699 (76.0%) of 2236 eligible people had data. EEur participants were mostly female, younger and had shorter diabetes duration on starting insulin, yet had highest baseline HbA1c and more micro-/macrovascular disease. A majority (60%-64%) in all regions started on basal insulin alone, declining to 30%-38% at 4years, with most switching to basal+mealtime insulin regimen (24%-40%). Higher baseline (28%) and 4-year use (34%) of premix insulin was observed in NEur. Change in HbA1c (SD) ranged from -1.2 (2.1)% (-13 [23]mmol/mol) in NEur to -2.4 (2.0)% (-26 [22]mmol/mol) in EEur. Weight change ranged from +1.9 (8.3) kg in NEur to +3.2 (7.0) kg in SEur. Overall documented hypoglycemia ranged from 0.3 (1.3) to 1.3 (4.4) events/person/6-months (NEur vs. EEur, respectively) and was stable with time. Severe hypoglycemia rates remained low. When starting insulin, HbA1c and prevalence of complications were higher in EEur. Regional differences exist in choice of insulin regimens in Europe. However, people starting insulin improved and sustained their glycemic control regardless of regional differences or insulin regimens used. Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.

Statistics of premixed flame cells

NASA Technical Reports Server (NTRS)

Noever, David A.

1991-01-01

The statistics of random cellular patterns in premixed flames are analyzed. Agreement is found with a variety of topological relations previously found for other networks, namely, Lewis's law and Aboav's law. Despite the diverse underlying physics, flame cells are shown to share a broad class of geometric properties with other random networks-metal grains, soap foams, bioconvection, and Langmuir monolayers.

Combustion-acoustic stability analysis for premixed gas turbine combustors

NASA Technical Reports Server (NTRS)

Darling, Douglas; Radhakrishnan, Krishnan; Oyediran, Ayo; Cowan, Lizabeth

1995-01-01

Lean, prevaporized, premixed combustors are susceptible to combustion-acoustic instabilities. A model was developed to predict eigenvalues of axial modes for combustion-acoustic interactions in a premixed combustor. This work extends previous work by including variable area and detailed chemical kinetics mechanisms, using the code LSENS. Thus the acoustic equations could be integrated through the flame zone. Linear perturbations were made of the continuity, momentum, energy, chemical species, and state equations. The qualitative accuracy of our approach was checked by examining its predictions for various unsteady heat release rate models. Perturbations in fuel flow rate are currently being added to the model.

Bioavailability of insulin detemir and human insulin at the level of peripheral interstitial fluid in humans, assessed by open-flow microperfusion.

PubMed

Bodenlenz, M; Ellmerer, M; Schaupp, L; Jacobsen, L V; Plank, J; Brunner, G A; Wutte, A; Aigner, B; Mautner, S I; Pieber, T R

2015-12-01

To find an explanation for the lower potency of insulin detemir observed in humans compared with unmodified human insulin by investigating insulin detemir and human insulin concentrations directly at the level of peripheral insulin-sensitive tissues in humans in vivo. Euglycaemic-hyperinsulinaemic clamp experiments were performed in healthy volunteers. Human insulin was administered i.v. at 6 pmol/kg/min and insulin detemir at 60 pmol/kg/min, achieving a comparable steady-state pharmacodynamic action. In addition, insulin detemir was doubled to 120 pmol/kg/min. Minimally invasive open-flow microperfusion (OFM) sampling methodology was combined with inulin calibration to quantify human insulin and insulin detemir in the interstitial fluid (ISF) of subcutaneous adipose and skeletal muscle tissue. The human insulin concentration in the ISF was ∼115 pmol/l or ∼30% of the serum concentration, whereas the insulin detemir concentration in the ISF was ∼680 pmol/l or ∼2% of the serum concentration. The molar insulin detemir interstitial concentration was five to six times higher than the human insulin interstitial concentration and metabolic clearance of insulin detemir from serum was substantially reduced compared with human insulin. OFM proved useful for target tissue measurements of human insulin and the analogue insulin detemir. Our tissue data confirm a highly effective retention of insulin detemir in the vascular compartment. The higher insulin detemir relative to human insulin tissue concentrations at comparable pharmacodynamics, however, indicate that the lower potency of insulin detemir in humans is attributable to a reduced effect in peripheral insulin-sensitive tissues and is consistent with the reduced in vitro receptor affinity. © 2015 John Wiley & Sons Ltd.

Theoretical and experimental investigation of turbulent premixed flames

NASA Astrophysics Data System (ADS)

Azzazy, M. T. F.

1982-11-01

A model is proposed to describe the propagation of a plane oblique flame into a turbulent flow of premixed reactants. The model incorporates a transport equation for the single or joint PDF's of passive scalers, in addition to the conservation equations of mass, momentum, energy and K.E. of turbulence. In the first phase of developing the model, the reaction mechanism was treated as a single step irreversible exothermic reaction. In this case, the PDF of the progress variable was parameterized and solved with the conservation equations. The second phase considered a two step reaction mechanism in an attempt to explore the role played by the radicals in the propagation of turbulent premixed flames. For both the two phases, the flame speed and angle are eigenvalues of the solution. Laser induced fluorescence spectroscopy (LIFS) was used to measure the PDF of OH concentration in a laboratory scale burner simulating the flame studied by the model. The premixed methane-air flame is stabilized on a rod flame holder downstream of a turbulence producing grid. The experimentally observed PDF's of the hydroxil radical concentration, and the statistical moments, used to describe and compare the PDF's and moments of the two reaction model.

Comparison Between Premixed and Compounded Parenteral Nutrition Solutions in Hospitalized Patients Requiring Parenteral Nutrition.

PubMed

Beattie, Colleen; Allard, Johane; Raman, Maitreyi

2016-04-01

Parenteral nutrition (PN) may be provided through compounded or premixed solutions. To determine the proportion of stable custom-compounded PN prescriptions that would fit within a 20% deviance of an existing premixed PN solution. A retrospective study design was used. Inpatients who received PN in non-critical care units in the preceding year were screened for eligibility. Results are reported descriptively as means (95% confidence intervals) and proportions. We reviewed 97 PN prescriptions that met inclusion criteria. Stable hospital PN prescriptions compared with the reference premixed prescription provided 1838 (1777-1898) vs 1843 (1781-1905) kcal/d, P = .43; dextrose, 266 (254-277) vs 225 (216-234) g/d, P < .001; amino acids, 100 (95.9-104) vs 95.2 (91.7-98.7) g/d, P < .001; and lipids, 53.2 (51.3-55.1) vs 76.5 (73.8-79.2) g/d, P < .001. Fifty-eight of 97 (59.8%) matched for 2 of 3 macronutrients. Hospital compared with premixed lipid was lower 53.6 (43-64.2) g/d vs 75.5 (60.5-90.5) g/d, P < .001. Electrolytes differed between hospital and premixed solutions: sodium, 98.6 (95.0-102) vs 66.9 (64.6-69.9) mmol/L, P < .001; potassium, 93.7 (89.0-98.3) vs 57.4 (55.4-59.4) mmol/L, P < .001; and magnesium, 5.4 (4.8-5.4) vs 7.6 (7.4-7.9) mmol/L. Calories and protein were remarkably similar, but dextrose, lipid, and electrolytes differed between hospital PN and the reference premixed prescription. We believe that there may be a role for premixed solutions in quaternary centers in stable non-critically ill patients. © 2016 American Society for Parenteral and Enteral Nutrition.

Verification of Bioanalytical Method for Quantification of Exogenous Insulin (Insulin Aspart) by the Analyser Advia Centaur® XP.

PubMed

Mihailov, Rossen; Stoeva, Dilyana; Pencheva, Blagovesta; Pentchev, Eugeni

2018-03-01

In a number of cases the monitoring of patients with type I diabetes mellitus requires measurement of the exogenous insulin levels. For the purpose of a clinical investigation of the efficacy of a medical device for application of exogenous insulin aspart, a verification of the method for measurement of this synthetic analogue of the hormone was needed. The information in the available medical literature for the measurement of the different exogenous insulin analogs is insufficient. Thus, verification was required to be in compliance with the active standards in Republic of Bulgaria. A manufactured method developed for ADVIA Centaur XP Immunoassay, Siemens Healthcare, was used which we verified using standard solutions and a patient serum pool by adding the appropriate quantity exogenous insulin aspart. The method was verified in accordance with the bioanalytical method verification criteria and regulatory requirements for using a standard method: CLIA chemiluminescence immunoassay ADVIA Centaur® XP. The following parameters are determined and monitored: intra-day precision and accuracy, inter-day precision and accuracy, limit of detection and lower limit of quantification, linearity, analytical recovery. The routine application of the method for measurement of immunoreactive insulin using the analyzer ADVIA Centaur® XP is directed to the measurement of endogenous insulin. The method is applicable for measuring different types of exogenous insulin, including insulin aspart.

Diabetes and Ramadan: An Update On Use of Glycemic Therapies During Fasting

PubMed Central

Ahmed, Mohamed H.; Abdu, Tarig A. M.

2011-01-01

The fasting of Ramadan is observed by a large proportion of Muslims with diabetes. Recommendations for the management of diabetes during Ramadan were last published in 2005 by the American Diabetes Association. Several studies in this field have since been published, some addressing the use of new pharmacological agents in managing diabetes during Ramadan. The incritin memetics are potentially safe during Ramadan; the DPP4 inhibitors vildagliptin and sitagliptin provide an effective and safe therapeutic option, administered either alone or in combination with metformin or sulfonylureas. There are no published studies on the use of GLP-1 receptor agonists during Ramadan. Among the sulfonylureas, gliclazide MR (modified release) and glimepride can be safely used during Ramadan, but glibenclamide should be avoided due to the associated risk of hypoglycemia. In selected patients with type 1 and type 2 diabetes, the long-acting insulin analogues glargine and detemir, as well as the premixed insulin analogues, can be used with minimal risk of metabolic derangement or hypoglycemia; the risk is higher in type 1 diabetes. Insulin pumps can potentially empower patients with diabetes and enable safe fasting during the month of Ramadan. Further clinical trials are needed to evaluate the safety and efficacy of new antidiabetic agents and new diabetes-related technologies during Ramadan. PMID:21727749

Diabetes and Ramadan: an update on use of glycemic therapies during fasting.

PubMed

Ahmed, Mohamed H; Abdu, Tarig A M

2011-01-01

The fasting of Ramadan is observed by a large proportion of Muslims with diabetes. Recommendations for the management of diabetes during Ramadan were last published in 2005 by the American Diabetes Association. Several studies in this field have since been published, some addressing the use of new pharmacological agents in managing diabetes during Ramadan. The incritin memetics are potentially safe during Ramadan; the DPP4 inhibitors vildagliptin and sitagliptin provide an effective and safe therapeutic option, administered either alone or in combination with metformin or sulfonylureas. There are no published studies on the use of GLP-1 receptor agonists during Ramadan. Among the sulfonylureas, gliclazide MR (modified release) and glimepride can be safely used during Ramadan, but glibenclamide should be avoided due to the associated risk of hypoglycemia. In selected patients with type 1 and type 2 diabetes, the long-acting insulin analogues glargine and detemir, as well as the premixed insulin analogues, can be used with minimal risk of metabolic derangement or hypoglycemia; the risk is higher in type 1 diabetes. Insulin pumps can potentially empower patients with diabetes and enable safe fasting during the month of Ramadan. Further clinical trials are needed to evaluate the safety and efficacy of new antidiabetic agents and new diabetes-related technologies during Ramadan.

An Investigation of a Hybrid Mixing Model for PDF Simulations of Turbulent Premixed Flames

NASA Astrophysics Data System (ADS)

Zhou, Hua; Li, Shan; Wang, Hu; Ren, Zhuyin

2015-11-01

Predictive simulations of turbulent premixed flames over a wide range of Damköhler numbers in the framework of Probability Density Function (PDF) method still remain challenging due to the deficiency in current micro-mixing models. In this work, a hybrid micro-mixing model, valid in both the flamelet regime and broken reaction zone regime, is proposed. A priori testing of this model is first performed by examining the conditional scalar dissipation rate and conditional scalar diffusion in a 3-D direct numerical simulation dataset of a temporally evolving turbulent slot jet flame of lean premixed H2-air in the thin reaction zone regime. Then, this new model is applied to PDF simulations of the Piloted Premixed Jet Burner (PPJB) flames, which are a set of highly shear turbulent premixed flames and feature strong turbulence-chemistry interaction at high Reynolds and Karlovitz numbers. Supported by NSFC 51476087 and NSFC 91441202.

Premixed calcium phosphate cements: Synthesis, physical properties, and cell cytotoxicity

PubMed Central

Xu, Hockin H.K.; Carey, Lisa E.; Simon, Carl G.; Takagi, Shozo; Chow, Laurence C.

2009-01-01

Objectives Calcium phosphate cement (CPC) is a promising material for dental, periodontal, and craniofacial repairs. However, its use requires on-site powder–liquid mixing that increases the surgical placement time and raises concerns of insufficient and inhomogeneous mixing. The objective of this study was to determine a formulation of premixed CPC (PCPC) with rapid setting, high strength, and good in vitro cell viability. Methods PCPCs were formulated from CPC powder + non-aqueous liquid + gelling agent + hardening accelerator. Five PCPCs were thus developed: PCPC-Tartaric, PCPC-Malonic, PCPC-Citric, PCPC-Glycolic, and PCPC-Malic. Formulations and controls were compared for setting time, diametral tensile strength, and osteoblast cell compatibility. Results Setting time (mean ± S.D.; n = 4) for PCPC-Tartaric was 8.2 ± 0.8 min, significantly less than the 61.7 ± 1.5 min for the Premixed Control developed previously (p < 0.001). On 7th day immersion, the diametral tensile strength of PCPC-Tartaric reached 6.5 ± 0.8 MPa, higher than 4.5 ± 0.8 MPa of Premixed Control (p = 0.036). Osteoblast cells displayed a polygonal morphology and attached to the nano-hydroxyapatite crystals in the PCPCs. All cements had similar live cell density values (p = 0.126), indicating that the new PCPCs were as cell compatible as a non-premixed CPC control known to be biocompatible. Each of the new PCPCs had a cell viability that was not significantly different (p > 0.1) from that of the non-premixed CPC control. Significance PCPCs will eliminate the powder–liquid mixing during surgery and may also improve the cement performance. The new PCPCs supported cell attachment and yielded a high cell density and viability. Their mechanical strengths approached the reported strengths of sintered porous hydroxyapatite implants and cancellous bone. These nano-crystalline hydroxyapatite cements may be useful in dental, periodontal, and craniofacial repairs. PMID:16678895

Design of a Premixed Gaseous Rocket Engine Injector for Ethylene and Oxygen

DTIC Science & Technology

2006-12-01

and uniform combustion zone. An engine will benefit by having a greater characteristic exhaust velocity efficiency (ηc*), less soot production and...the challenges of designing a premixed injector. The design requirements for the engine are to provide a wide range of combustion pressure... Engineering Original Premixed Injector1 Downstream of the three inch combustion chamber a bolt-on conical nozzle was attached. This nozzle had a

Subject-driven titration of biphasic insulin aspart 30 twice daily is non-inferior to investigator-driven titration in Chinese patients with type 2 diabetes inadequately controlled with premixed human insulin: A randomized, open-label, parallel-group, multicenter trial.

PubMed

Yang, Wenying; Zhu, Lvyun; Meng, Bangzhu; Liu, Yu; Wang, Wenhui; Ye, Shandong; Sun, Li; Miao, Heng; Guo, Lian; Wang, Zhanjian; Lv, Xiaofeng; Li, Quanmin; Ji, Qiuhe; Zhao, Weigang; Yang, Gangyi

2016-01-01

The present study was to compare the efficacy and safety of subject-driven and investigator-driven titration of biphasic insulin aspart 30 (BIAsp 30) twice daily (BID). In this 20-week, randomized, open-label, two-group parallel, multicenter trial, Chinese patients with type 2 diabetes inadequately controlled by premixed/self-mixed human insulin were randomized 1:1 to subject-driven or investigator-driven titration of BIAsp 30 BID, in combination with metformin and/or α-glucosidase inhibitors. Dose adjustment was decided by patients in the subject-driven group after training, and by investigators in the investigator-driven group. Eligible adults (n = 344) were randomized in the study. The estimated glycated hemoglobin (HbA1c) reduction was 14.5 mmol/mol (1.33%) in the subject-driven group and 14.3 mmol/mol (1.31%) in the investigator-driven group. Non-inferiority of subject-titration vs investigator-titration in reducing HbA1c was confirmed, with estimated treatment difference -0.26 mmol/mol (95% confidence interval -2.05, 1.53) (-0.02%, 95% confidence interval -0.19, 0.14). Fasting plasma glucose, postprandial glucose increment and self-measured plasma glucose were improved in both groups without statistically significant differences. One severe hypoglycemic event was experienced by one subject in each group. A similar rate of nocturnal hypoglycemia (events/patient-year) was reported in the subject-driven (1.10) and investigator-driven (1.32) groups. There were 64.5 and 58.1% patients achieving HbA1c <53.0 mmol/mol (7.0%), and 51.2 and 45.9% patients achieving the HbA1c target without confirmed hypoglycemia throughout the trial in the subject-driven and investigator-driven groups, respectively. Subject-titration of BIAsp 30 BID was as efficacious and well-tolerated as investigator-titration. The present study supported patients to self-titrate BIAsp 30 BID under physicians' supervision.

Adding prandial GLP-1 receptor agonists to basal insulin: a promising option for type 2 diabetes therapy.

PubMed

Goldenberg, Ronald M; Berard, Lori

2018-01-01

Diabetes mellitus is a serious and increasingly prevalent condition in Canada and around the world. Treatment strategies have become increasingly complex, with a widening array of pharmacological agents available for glycemic management in type 2 diabetes mellitus (T2DM). New therapies that act in concert with available basal insulins may represent alternatives to basal insulin intensification with prandial or pre-mixed insulin. Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) have recently shown promise as useful additions to basal insulin, with significant reductions in glycated hemoglobin and potentially beneficial effects on body weight. This review will focus on pivotal clinical trials to assess the potential benefits of adding prandial GLP-1 RAs to basal insulin in patients with T2DM. Clinical studies combining prandial GLP-1 RAs and basal insulin (published between 2011 and July 2017) were identified and reviewed in PubMed, the Cochrane Central Register of Clinical Trials (Issue 6, June 2017), and clinicaltrials.gov. Most of the studies presented in this review show that the addition of a prandial GLP-1 RA to basal insulin results in equal or slightly superior efficacy compared to the addition of prandial insulin, together with weight loss and less hypoglycemia. The results of the studies suggest that a prandial GLP-1 RA as an add-on to basal insulin may be a safe and effective treatment intensification option (vs basal-plus or basal-bolus insulin).

Theoretical and experimental investigation of turbulent premixed flames

DOE Office of Scientific and Technical Information (OSTI.GOV)

Azzazy, M.T.F.

1982-01-01

A model is proposed to describe the propagation of a plane oblique flame into a turbulent flow of premixed reactants. The model incorporates a transport equation for the single or joint PDF's of passive scalers, in addition to the conservation equations of mass, momentum, energy and K.E. of turbulence. In the first phase of developing the model, the reaction mechanism was treated as a single step irreversible exothermic reaction. In this case, the PDF of the progress variable was parameterized and solved with the conservation equations. The second phase considered a two step reaction mechanism in an attempt to exploremore » the role played by the radicals in the propagation of turbulent premixed flames. For both the two phases, the flame speed and angle are Eigenvalues of the solution. Laser Induced Fluoresence Spectroscopy (LIFS) was used to measure the PDF of OH concentration in a laboratory scale burner simulating the flame studied by the model. The premixed Methane-Air flame was stabilized on a rod flame holder downstream of a turbulence producing grid. Measurements in both the streamwise and transverse directions were made for a variety of flow conditions. The experimentally observed PDF's of the hydroxil radical concentration, and the statistical moments, were used to describe and compare the PDF's and moments of the two reaction model.« less

Dry low NOx combustion system with pre-mixed direct-injection secondary fuel nozzle

DOEpatents

Zuo, Baifang; Johnson, Thomas; Ziminsky, Willy; Khan, Abdul

2013-12-17

A combustion system includes a first combustion chamber and a second combustion chamber. The second combustion chamber is positioned downstream of the first combustion chamber. The combustion system also includes a pre-mixed, direct-injection secondary fuel nozzle. The pre-mixed, direct-injection secondary fuel nozzle extends through the first combustion chamber into the second combustion chamber.

Swozzle based burner tube premixer including inlet air conditioner for low emissions combustion

DOEpatents

Tuthill, Richard Sterling; Bechtel, II, William Theodore; Benoit, Jeffrey Arthur; Black, Stephen Hugh; Bland, Robert James; DeLeonardo, Guy Wayne; Meyer, Stefan Martin; Taura, Joseph Charles; Battaglioli, John Luigi

2002-01-01

A burner for use in a combustion system of a heavy-duty industrial gas turbine includes a fuel/air premixer having an air inlet, a fuel inlet, and an annular mixing passage. The fuel/air premixer mixes fuel and air into a uniform mixture for injection into a combustor reaction zone. The burner also includes an inlet flow conditioner disposed at the air inlet of the fuel/air premixer for controlling a radial and circumferential distribution of incoming air. The pattern of perforations in the inlet flow conditioner is designed such that a uniform air flow distribution is produced at the swirler inlet annulus in both the radial and circumference directions. The premixer includes a swozzle assembly having a series of preferably air foil shaped turning vanes that impart swirl to the airflow entering via the inlet flow conditioner. Each air foil contains internal fuel flow passages that introduce natural gas fuel into the air stream via fuel metering holes that pass through the walls of the air foil shaped turning vanes. By injecting fuel in this manner, an aerodynamically clean flow field is maintained throughout the premixer. By injecting fuel via two separate passages, the fuel/air mixture strength distribution can be controlled in the radial direction to obtain optimum radial concentration profiles for control of emissions, lean blow outs, and combustion driven dynamic pressure activity as machine and combustor load are varied.

[The diabetic child and the specifics of insulin therapy].

PubMed

Dirlewanger, M; Perrenoud, L; Castellsague-Perolini, M; Schwitzgebel, V M

2007-04-18

The incidence of diabetes type I has increased considerably in young children with an annual increase in Switzerland of 23,8% over the last ten years. The development of rapid acting and long acting analogues allowed a significant progress in treatment. Multiple daily insulin injections together with carbohydrate counting as well as continuous subcutaneous insulin infusion (CSII) improved the quality of life and led to an increased daily flexibility. The incidence of severe hypoglycaemic events has decreased at the same time metabolic control improved. The development of interstitial glucose measurement (online) coupled to the insulin pump represents a step further towards the artificial pancreas. The new therapeutic strategies of immunomodulation will hopefully lead to secondary and tertiary prevention of diabetes.

Partially Premixed Flame (PPF) Research for Fire Safety

NASA Technical Reports Server (NTRS)

Puri, Ishwar K.; Aggarwal, Suresh K.; Lock, Andrew J.; Hegde, Uday

2004-01-01

Incipient fires typically occur after the partial premixing of fuel and oxidizer. The mixing of product species into the fuel/oxidizer mixture influences flame stabilization and fire spread. Therefore, it is important to characterize the impact of different levels of fuel/oxidizer/product mixing on flame stabilization, liftoff and extinguishment under different gravity conditions. With regard to fire protection, the agent concentration required to achieve flame suppression is an important consideration. The initial stage of an unwanted fire in a microgravity environment will depend on the level of partial premixing and the local conditions such as air currents generated by the fire itself and any forced ventilation (that influence agent and product mixing into the fire). The motivation of our investigation is to characterize these impacts in a systematic and fundamental manner.

Lean Premixed Combustion Stabilized by Low Swirl a Promising Concept for Practical Applications

NASA Technical Reports Server (NTRS)

Cheng, R. K.

1999-01-01

Since its inception, the low-swirl burner (LSB) has shown to be a useful laboratory apparatus for fundamental studies of premixed turbulent flames. The LSB operates under wide ranges of equivalence ratios, flow rates, and turbulence intensities. Its flame is lifted and detached from the burner and allows easy access for laser diagnostics. The flame brush is axisymmetric and propagates normal to the incident reactants. Therefore, the LSB is well suited for investigating detailed flame structures and empirical coefficients such as flame speed, turbulence transport, and flame generated turbulence. Due to its capability to stabilize ultra-lean premixed turbulent flames (phi approx. = 0.55), the LSB has generated interest from the gas appliance industry for use as an economical low-NO(x) burner. Lean premixed combustion emits low levels of NO(x), due primarily to the low flame temperature. Therefore, it is a very effective NO(x) prevention method without involving selective catalytic reduction (SCR), fuel-air staging, or flue gas recirculation (FGR). En the gas turbine industry, substantial research efforts have already been undertaken and engines with lean premixed combustors are already in use. For commercial and residential applications, premixed pulsed combustors and premixed ceramic matrix burners are commercially available. These lean premixed combustion technologies, however, tend to be elaborate but have relatively limited operational flexibility, and higher capital, operating and maintenance costs. Consequently, these industries are continuing the development of lean premixed combustion technologies as well as exploring new concepts. This paper summarizes the research effects we have undertaken in the past few years to demonstrate the feasibility of applying the low-swirl flame stabilization method for a wide range of heating and power generation systems. The principle of flame stabilization by low-swirl is counter to the conventional high-swirl methods that

Computations of turbulent lean premixed combustion using conditional moment closure

NASA Astrophysics Data System (ADS)

Amzin, Shokri; Swaminathan, Nedunchezhian

2013-12-01

Conditional Moment Closure (CMC) is a suitable method for predicting scalars such as carbon monoxide with slow chemical time scales in turbulent combustion. Although this method has been successfully applied to non-premixed combustion, its application to lean premixed combustion is rare. In this study the CMC method is used to compute piloted lean premixed combustion in a distributed combustion regime. The conditional scalar dissipation rate of the conditioning scalar, the progress variable, is closed using an algebraic model and turbulence is modelled using the standard k-ɛ model. The conditional mean reaction rate is closed using a first order CMC closure with the GRI-3.0 chemical mechanism to represent the chemical kinetics of methane oxidation. The PDF of the progress variable is obtained using a presumed shape with the Beta function. The computed results are compared with the experimental measurements and earlier computations using the transported PDF approach. The results show reasonable agreement with the experimental measurements and are consistent with the transported PDF computations. When the compounded effects of shear-turbulence and flame are strong, second order closures may be required for the CMC.

Differential lipid profile and hormonal response in type 2 diabetes by exogenous insulin aspart versus the insulin secretagogue repaglinide, at the same glycemic control.

PubMed

Chisalita, Simona I; Lindström, Torbjörn; Eson Jennersjö, Pär; Paulsson, Johan F; Westermark, Gunilla T; Olsson, Anders G; Arnqvist, Hans J

2009-03-01

Our aim was to study, at the same glycemic control, how treatment with either the insulin secretagogue repaglinide or exogenous insulin aspart affects endogenous insulin secretion, plasma insulin and IAPP (islet amyloid polypeptide) levels, GH-IGF (growth hormone-insulin-like growth factor) axis and plasma lipoprotein concentrations in patients with type 2 diabetes. Five patients, age 65.0+/-4.1 years (mean+/-SE), body weight 82.5+/-5.0 kg, BMI (body mass index) 27.7+/-1.5 kg/m(2) were treated for 10 weeks with repaglinide or insulin aspart in a randomized, cross-over study. At the end of each treatment a 24-h metabolic profile was performed. Blood glucose, C-peptide, free human insulin, free total (human and analogue) insulin, proinsulin, IAPP, IGF-I, IGFBP-1 (IGF binding protein-1), GHBP (growth hormone binding protein) and plasma lipoprotein concentrations were measured. Similar 24-h blood glucose profiles were obtained with repaglinide and insulin aspart treatment. During the repaglinide treatment, the meal related peaks of C-peptide and free human insulin were about twofold higher than during treatment with insulin aspart. Proinsulin, GHBP were higher and IAPP levels tended to be higher during repaglinide compared to insulin aspart. Postprandial plasma total cholesterol, triglycerides and apolipoprotein B concentrations were higher on repaglinide than on insulin aspart treatment. Our results show that, at the same glycemic control, treatment with exogenous insulin aspart in comparison with the insulin secretagogue repaglinide result in a lower endogenous insulin secretion, and a tendency towards a less atherogenic postprandial lipid profile.

Implementation of Premixed Equilibrium Chemistry Capability in OVERFLOW

NASA Technical Reports Server (NTRS)

Olsen, M. E.; Liu, Y.; Vinokur, M.; Olsen, T.

2003-01-01

An implementation of premixed equilibrium chemistry has been completed for the OVERFLOW code, a chimera capable, complex geometry flow code widely used to predict transonic flowfields. The implementation builds on the computational efficiency and geometric generality of the solver.

Implementation of Premixed Equilibrium Chemistry Capability in OVERFLOW

NASA Technical Reports Server (NTRS)

Olsen, Mike E.; Liu, Yen; Vinokur, M.; Olsen, Tom

2004-01-01

An implementation of premixed equilibrium chemistry has been completed for the OVERFLOW code, a chimera capable, complex geometry flow code widely used to predict transonic flowfields. The implementation builds on the computational efficiency and geometric generality of the solver.

Study of premixing phase of steam explosion with JASMINE code in ALPHA program

DOE Office of Scientific and Technical Information (OSTI.GOV)

Moriyama, Kiyofumi; Yamano, Norihiro; Maruyama, Yu

Premixing phase of steam explosion has been studied in ALPHA Program at Japan Atomic Energy Research Institute (JAERI). An analytical model to simulate the premixing phase, JASMINE (JAERI Simulator for Multiphase Interaction and Explosion), has been developed based on a multi-dimensional multi-phase thermal hydraulics code MISTRAL (by Fuji Research Institute Co.). The original code was extended to simulate the physics in the premixing phenomena. The first stage of the code validation was performed by analyzing two mixing experiments with solid particles and water: the isothermal experiment by Gilbertson et al. (1992) and the hot particle experiment by Angelini et al.more » (1993) (MAGICO). The code predicted reasonably well the experiments. Effectiveness of the TVD scheme employed in the code was also demonstrated.« less

Contrasting weight changes with LY2605541, a novel long-acting insulin, and insulin glargine despite similar improved glycaemic control in T1DM and T2DM.

PubMed

Jacober, S J; Rosenstock, J; Bergenstal, R M; Prince, M J; Qu, Y; Beals, J M

2014-04-01

The basal insulin analogue LY2605541, a PEGylated insulin lispro with prolonged duration of action, was previously shown to be associated with modest weight loss in Phase 2, randomized, open-label trials in type 2 (N=288) and type 1 (N=137) diabetes mellitus (T2DM and T1DM), compared with modest weight gain with insulin glargine. Exploratory analyses were conducted to further characterize these findings. Pearson correlations between change in body weight and other variables were calculated. Continuous variables were analysed using a mixed linear model with repeated measurements. Proportions of subjects with weight loss were analysed using Fisher's exact test for T2DM and Nagelkerke's method for T1DM. Weight loss was more common in LY2605541-treated patients than in patients treated with insulin glargine (T2DM: 56.9 vs. 40.2%, p=0.011; T1DM: 66.1 vs. 40.3%, p<0.001). More LY2605541-treated patients experienced ≥5% weight loss compared to patients treated with glargine (T2DM: 4.8 vs. 0%, p=0.033; T1DM: 11.9 vs. 0.8%, p<0.001). In both the T1DM and T2DM studies, weight change did not correlate with baseline body mass index (BMI), or change in HDL-cholesterol in either treatment group. No consistent correlations were found across both studies between weight change and any of the variables assessed; however, weight change was significantly correlated with hypoglycaemia rate in glargine-treated T2DM patients. In two Phase 2 trials, improved glycaemic control with long-acting basal insulin analogue LY2605541 is associated with weight loss in previously insulin-treated patients. This weight change is independent of baseline BMI or hypoglycaemia.

Determinants of intensive insulin therapeutic regimens in patients with type 1 diabetes: data from a nationwide multicenter survey in Brazil

PubMed Central

2014-01-01

Background To evaluate the determinants of intensive insulin regimens (ITs) in patients with type 1 diabetes (T1D). Methods This multicenter study was conducted between December 2008 and December 2010 in 28 public clinics in 20 Brazilian cities. Data were obtained from 3,591 patients (56.0% female, 57.1% Caucasian). Insulin regimens were classified as follows: group 1, conventional therapy (CT) (intermediate human insulin, one to two injections daily); group 2 (three or more insulin injections of intermediate plus regular human insulin); group 3 (three or more insulin injections of intermediate human insulin plus short-acting insulin analogues); group 4, basal-bolus (one or two insulin injections of long-acting plus short-acting insulin analogues or regular insulin); and group 5, basal-bolus with continuous subcutaneous insulin infusion (CSII). Groups 2 to 5 were considered IT groups. Results We obtained complete data from 2,961 patients. Combined intermediate plus regular human insulin was the most used therapeutic regimen. CSII was used by 37 (1.2%) patients and IT by 2,669 (90.2%) patients. More patients on IT performed self-monitoring of blood glucose and were treated at the tertiary care level compared to CT patients (p < 0.001). The majority of patients from all groups had HbA1c levels above the target. Overweight or obesity was not associated with insulin regimen. Logistic regression analysis showed that economic status, age, ethnicity, and level of care were associated with IT (p < 0.001). Conclusions Given the prevalence of intensive treatment for T1D in Brazil, more effective therapeutic strategies are needed for long term-health benefits. PMID:24920963

Effect of long acting somatostatin-analogue, SMS 201 995, on gut hormone secretion in normal subjects.

PubMed

Kraenzlin, M E; Wood, S M; Neufeld, M; Adrian, T E; Bloom, S R

1985-06-15

SMS 201 995 is a new long acting analogue of somatostatin. We have investigated its effect on basal and meal stimulated secretion of gut hormones and have shown that after a single s.c. injection of 50 micrograms it lowers significantly the basal plasma levels of pancreatic polypeptide, secretin, motilin, pancreatic glucagon and insulin, it also effectively suppresses the postprandial release of pancreatic polypeptide, gastrin, secretin, gastric inhibitory peptide, pancreatic glucagon and insulin. Except for the usual brief discomfort of an injection, no symptoms or untoward effects were observed.

Gravitational Influences on Flame Propagation through Non-Uniform, Premixed Gas Systems

NASA Technical Reports Server (NTRS)

Miller, Fletcher J.; Easton, John; Ross, Howard D.; Marchese, Anthony; Perry, David; Kulis, Michael

2001-01-01

Flame propagation through non-uniformly premixed (or layered) gases has importance both in useful combustion systems and in unintentional fires. As summarized previously, non-uniform premixed gas combustion receives scant attention compared to the more usual limiting cases of diffusion or uniformly premixed flames, especially regarding the role gravity plays. This paper summarizes our progress on furthering the knowledge of layered combustion, in which a fuel concentration gradient exists normal to the direction of flame spread. We present experimental and numerical results for flame spread through propanol-air layers formed near the flash point temperature (25 C) or near the stoichiometric temperature (33 C). Both the model and experimental results show that the removal of gravity results in a faster spreading flame, by as much as 80% depending on conditions. This is exactly the opposite effect as that predicted by an earlier model reported. We also found that having a gallery lid results in faster flame spread, an effect more pronounced at normal gravity, demonstrating the importance of enclosure geometry. Also reported here is the beginning of our spectroscopic measurements of fuel vapor.

Direct numerical simulations of premixed autoignition in compressible uniformly-sheared turbulence

NASA Astrophysics Data System (ADS)

Towery, Colin; Darragh, Ryan; Poludnenko, Alexei; Hamlington, Peter

2017-11-01

High-speed combustion systems, such as scramjet engines, operate at high temperatures and pressures, extremely short combustor residence times, very high rates of shear stress, and intense turbulent mixing. As a result, the reacting flow can be premixed and have highly-compressible turbulence fluctuations. We investigate the effects of compressible turbulence on the ignition delay time, heat-release-rate (HRR) intermittency, and mode of autoignition of premixed Hydrogen-air fuel in uniformly-sheared turbulence using new three-dimensional direct numerical simulations with a multi-step chemistry mechanism. We analyze autoignition in both the Eulerian and Lagrangian reference frames at eight different turbulence Mach numbers, Mat , spanning the quasi-isentropic, linear thermodynamic, and nonlinear compressibility regimes, with eddy shocklets appearing in the nonlinear regime. Results are compared to our previous study of premixed autoignition in isotropic turbulence at the same Mat and with a single-step reaction mechanism. This previous study found large decreases in delay times and large increases in HRR intermittency between the linear and nonlinear compressibility regimes and that detonation waves could form in both regimes.

Large Eddy Simulation of High-Speed, Premixed Ethylene Combustion

NASA Technical Reports Server (NTRS)

Ramesh, Kiran; Edwards, Jack R.; Chelliah, Harsha; Goyne, Christopher; McDaniel, James; Rockwell, Robert; Kirik, Justin; Cutler, Andrew; Danehy, Paul

2015-01-01

A large-eddy simulation / Reynolds-averaged Navier-Stokes (LES/RANS) methodology is used to simulate premixed ethylene-air combustion in a model scramjet designed for dual mode operation and equipped with a cavity for flameholding. A 22-species reduced mechanism for ethylene-air combustion is employed, and the calculations are performed on a mesh containing 93 million cells. Fuel plumes injected at the isolator entrance are processed by the isolator shock train, yielding a premixed fuel-air mixture at an equivalence ratio of 0.42 at the cavity entrance plane. A premixed flame is anchored within the cavity and propagates toward the opposite wall. Near complete combustion of ethylene is obtained. The combustor is highly dynamic, exhibiting a large-scale oscillation in global heat release and mass flow rate with a period of about 2.8 ms. Maximum heat release occurs when the flame front reaches its most downstream extent, as the flame surface area is larger. Minimum heat release is associated with flame propagation toward the cavity and occurs through a reduction in core flow velocity that is correlated with an upstream movement of the shock train. Reasonable agreement between simulation results and available wall pressure, particle image velocimetry, and OH-PLIF data is obtained, but it is not yet clear whether the system-level oscillations seen in the calculations are actually present in the experiment.

A stochastic multi-scale method for turbulent premixed combustion

NASA Astrophysics Data System (ADS)

Cha, Chong M.

2002-11-01

The stochastic chemistry algorithm of Bunker et al. and Gillespie is used to perform the chemical reactions in a transported probability density function (PDF) modeling approach of turbulent combustion. Recently, Kraft & Wagner have demonstrated a 100-fold gain in computational speed (for a 100 species mechanism) using the stochastic approach over the conventional, direct integration method of solving for the chemistry. Here, the stochastic chemistry algorithm is applied to develop a new transported PDF model of turbulent premixed combustion. The methodology relies on representing the relevant spatially dependent physical processes as queuing events. The canonical problem of a one-dimensional premixed flame is used for validation. For the laminar case, molecular diffusion is described by a random walk. For the turbulent case, one of two different material transport submodels can provide the necessary closure: Taylor dispersion or Kerstein's one-dimensional turbulence approach. The former exploits ``eddy diffusivity'' and hence would be much more computationally tractable for practical applications. Various validation studies are performed. Results from the Monte Carlo simulations compare well to asymptotic solutions of laminar premixed flames, both with and without high activation temperatures. The correct scaling of the turbulent burning velocity is predicted in both Damköhler's small- and large-scale turbulence limits. The effect of applying the eddy diffusivity concept in the various regimes is discussed.

Intrauterine-like growth rates can be achieved with premixed parenteral nutrition solution in preterm infants.

PubMed

Rigo, Jacques; Senterre, Thibault

2013-12-01

Growth failure in neonatal intensive care units is a major challenge for pediatricians and neonatologists. The use of early "aggressive" parenteral nutrition (PN), with >2.5 g/(kg ·d) of amino acids and at least 40 kcal/(kg ·d) of energy from the first day of life, has been shown to provide nutritional intakes in the range recommended by international guidelines, reducing nutritional deficit and the incidence of postnatal growth restriction in preterm infants. However, nutritional practices and adherence to recommendations may vary in different hospitals. Two ready-to-use (RTU), premixed parenteral solutions (PSs) designed for preterm infants have been prospectively evaluated: a binary RTU premixed PS from our hospital pharmacy and a commercially premixed 3-chamber bag (Baxter Healthcare). These premixed PSs provide nitrogen and energy intakes in the range of the most recent recommendations, reducing or eliminating the early cumulative nutritional deficit in very-low-birth-weight infants, and avoiding the development of postnatal growth restriction. A further rationale for RTU premixed PSs is that preterm infants require balanced PN that contains not only amino acids and energy but also minerals and electrolytes from the first day of life in order to reduce the incidence of metabolic disorders frequently reported in extremely-low-birth-weight infants during the early weeks of life.

Comparison of insulin lispro mix 25 with insulin lispro mix 50 as insulin starter in Chinese patients with type 2 diabetes mellitus (CLASSIFY study): Subgroup analysis of a Phase 4 open-label randomized trial.

PubMed

Su, Qing; Liu, Chao; Zheng, Hongting; Zhu, Jun; Li, Peng Fei; Qian, Lei; Yang, Wen Ying

2017-06-01

Premixed insulins are recommended starter insulins in Chinese patients after oral antihyperglycemic medication (OAM) failure. In the present study, we compared the efficacy and safety of insulin lispro mix 25 (LM25) twice daily (b.i.d.) and insulin lispro mix 50 (LM50) b.i.d. as a starter insulin regimen in Chinese patients with type 2 diabetes mellitus (T2DM) who had inadequate glycemic control with OAMs. The primary efficacy outcome in the present open-label parallel randomized clinical trial was change in HbA1c from baseline to 26 weeks. Patients were randomized in a ratio of 1:  1 to LM25 (n = 80) or LM50 (n = 76). A mixed-effects model with repeated measures was used to analyze continuous variables. The Cochran-Mantel-Haenszel test with stratification factor was used to analyze categorical variables. At the end of the study, LM50 was more efficacious than LM25 in reducing mean HbA1c levels (least-squares [LS] mean difference 0.48; 95 % confidence interval [CI] 0.22, 0.74; P < 0.001). More subjects in the LM50 than LM25 group achieved HbA1c targets of <7.0 % (72.4 % vs 45.0 %; P = 0.001) or ≤6.5 % (52.6 % vs 20.0 %; P < 0.001). Furthermore, LM50 was more effective than LM25 at reducing HbA1c in patients with baseline HbA1c, blood glucose excursion, and postprandial glucose greater than or equal to median levels (P ≤ 0.001). The rate and incidence of hypoglycemic episodes and increase in weight at the end of the study were similar between treatment groups. In Chinese patients with T2DM, LM50 was more efficacious than LM25 as a starter insulin. © 2016 The Authors. Journal of Diabetes published by John Wiley & Sons Australia, Ltd and Ruijin Hospital, Shanghai Jiaotong University School of Medicine.

Varic acid analogues from fungus as PTP1B inhibitors: Biological evaluation and structure-activity relationships.

PubMed

Sun, Wenlong; Zhuang, Chunlin; Li, Xia; Zhang, Bowei; Lu, Xinhua; Zheng, Zhihui; Dong, Yuesheng

2017-08-01

Protein tyrosine phosphatase 1B (PTP1B) inhibitors as potential therapies for diabetes and obesity have attracted much attention in recent years. Six varic acid analogues were isolated from two strains of fungi and evaluated for PTP1B inhibition activities. The structure-activity relationships were also characterized and predicted by molecular modeling. Further kinetic studies indicated the reversible and competitive inhibition manner of varic acid analogues. Trivaric acid showed insulin-sensitizing effect not only in vitro but also in vivo, representing a promising lead compound for further optimization. Copyright © 2017 Elsevier Ltd. All rights reserved.

Partially premixed prevalorized kerosene spray combustion in turbulent flow

DOE Office of Scientific and Technical Information (OSTI.GOV)

Chrigui, M.; Ahmadi, W.; Sadiki, A.

2010-04-15

A detailed numerical simulation of kerosene spray combustion was carried out on a partially premixed, prevaporized, three-dimensional configuration. The focus was on the flame temperature profile dependency on the length of the pre-vaporization zone. The results were analyzed and compared to experimental data. A fundamental study was performed to observe the temperature variation and flame flashback. Changes were made to the droplet diameter, kerosene flammability limits, a combustion model parameter and the location of the combustion initialization. Investigations were performed for atmospheric pressure, inlet air temperature of 90 C and a global equivalence ratio of 0.7. The simulations were carriedmore » out using the Eulerian Lagrangian procedure under a fully two-way coupling. The Bray-Moss-Libby model was adjusted to account for the partially premixed combustion. (author)« less

Measurements and Modeling of Nitric Oxide Formation in Counterflow, Premixed CH4/O2/N2 Flames

NASA Technical Reports Server (NTRS)

Thomsen, D. Douglas; Laurendeau, Normand M.

2000-01-01

Laser-induced fluorescence (LIF) measurements of NO concentration in a variety of CH4/O2/N2 flames are used to evaluate the chemical kinetics of NO formation. The analysis begins with previous measurements in flat, laminar, premixed CH4/O2/N2 flames stabilized on a water-cooled McKenna burner at pressures ranging from 1 to 14.6 atm, equivalence ratios from 0.5 to 1.6, and volumetric nitrogen/oxygen dilution ratios of 2.2, 3.1 and 3.76. These measured results are compared to predictions to determine the capabilities and limitations of the comprehensive kinetic mechanism developed by the Gas Research Institute (GRI), version 2.11. The model is shown to predict well the qualitative trends of NO formation in lean-premixed flames, while quantitatively underpredicting NO concentration by 30-50%. For rich flames, the model is unable to even qualitatively match the experimental results. These flames were found to be limited by low temperatures and an inability to separate the flame from the burner surface. In response to these limitations, a counterflow burner was designed for use in opposed premixed flame studies. A new LIF calibration technique was developed and applied to obtain quantitative measurements of NO concentration in laminar, counterflow premixed, CH4/O2/N2 flames at pressures ranging from 1 to 5.1 atm, equivalence ratios of 0.6 to 1.5, and an N2/O2 dilution ratio of 3.76. The counterflow premixed flame measurements are combined with measurements in burner-stabilized premixed flames and counterflow diffusion flames to build a comprehensive database for analysis of the GRI kinetic mechanism. Pathways, quantitative reaction path and sensitivity analyses are applied to the GRI mechanism for these flame conditions. The prompt NO mechanism is found to severely underpredict the amount of NO formed in rich premixed and nitrogen-diluted diffusion flames. This underprediction is traced to uncertainties in the CH kinetics as well as in the nitrogen oxidation chemistry

Intravenous glucagon in a deliberate insulin overdose in an adolescent with type 1 diabetes mellitus.

PubMed

White, Mary; Zacharin, Margaret R; Werther, George A; Cameron, Fergus J

2016-02-01

Massive insulin overdose may be associated with unpredictable and prolonged hypoglycemia. Concerns surrounding the potential provocation of insulin release from beta cells have previously prevented the use of intravenous glucagon as an adjunct to infusion of dextrose in this situation. We describe the case of a 15-yr-old boy with type 1 diabetes mellitus (T1DM) who presented with profound hypoglycemia following an overdose of an unknown quantity of premixed insulin. Owing to an increasing dextrose requirement and a dependence on hourly intramuscular glucagon injections, a continuous intravenous infusion of glucagon was commenced which successfully avoided the requirement for central venous access or concentrated dextrose infusion. Nausea was managed with anti-emetics. Intramuscular and subcutaneous glucagon is effective in the management of refractory and severe hypoglycemia in youth with both T1DM and hyperinsulinism. Concerns regarding the precipitation of rebound hypoglycemia with the use of intravenous glucagon do not relate to those with T1DM. This treatment option may be a useful adjunct in the management of insulin overdose in youth with T1DM and may avoid the requirement for invasive central venous access placement. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Insulin glulisine: a review of its use in the management of diabetes mellitus.

PubMed

Garnock-Jones, Karly P; Plosker, Greg L

2009-05-29

Insulin glulisine (Apidra) is a human insulin analogue approved for the improvement of glycaemic control in adults, adolescents and children with diabetes mellitus. It has similar binding properties, and is associated with a faster onset but similar level of glucose disposal, to regular human insulin (RHI). Insulin glulisine and insulin lispro have similar effects on glucose levels. Insulin glulisine is effective when compared to other short- and rapid-acting insulins, demonstrating either noninferiority, no significant difference, or superiority in primary endpoints in studies involving patients with type 1 and type 2 diabetes. It is more effective and has a faster onset and shorter duration of activity than RHI. Insulin glulisine is as effective as insulin lispro in patients with type 1 diabetes; however, there is a need for further, well designed head-to-head comparisons with insulin lispro in patients with type 2 diabetes and with insulin aspart in patients with type 1 or type 2 diabetes to fully establish the place of insulin glulisine in the management of diabetes. Insulin glulisine has a flexible administration period, as it can be administered immediately before or after meals. Hypoglycaemia, a common risk with insulins, occurs at a similar rate among recipients of insulin glulisine to that seen with other insulins. Thus, insulin glulisine is an effective and well tolerated option for the treatment of patients with type 1 and type 2 diabetes.

Vortex combustor for low NOX emissions when burning lean premixed high hydrogen content fuel

DOEpatents

Steele, Robert C; Edmonds, Ryan G; Williams, Joseph T; Baldwin, Stephen P

2012-11-20

A trapped vortex combustor. The trapped vortex combustor is configured for receiving a lean premixed gaseous fuel and oxidant stream, where the fuel includes hydrogen gas. The trapped vortex combustor is configured to receive the lean premixed fuel and oxidant stream at a velocity which significantly exceeds combustion flame speed in a selected lean premixed fuel and oxidant mixture. The combustor is configured to operate at relatively high bulk fluid velocities while maintaining stable combustion, and low NOx emissions. The combustor is useful in gas turbines in a process of burning synfuels, as it offers the opportunity to avoid use of diluent gas to reduce combustion temperatures. The combustor also offers the possibility of avoiding the use of selected catalytic reaction units for removal of oxides of nitrogen from combustion gases exiting a gas turbine.

Vortex combustor for low NOx emissions when burning lean premixed high hydrogen content fuel

DOEpatents

Steele, Robert C [Woodinville, WA; Edmonds, Ryan G [Renton, WA; Williams, Joseph T [Kirkland, WA; Baldwin, Stephen P [Winchester, MA

2009-10-20

A trapped vortex combustor. The trapped vortex combustor is configured for receiving a lean premixed gaseous fuel and oxidant stream, where the fuel includes hydrogen gas. The trapped vortex combustor is configured to receive the lean premixed fuel and oxidant stream at a velocity which significantly exceeds combustion flame speed in a selected lean premixed fuel and oxidant mixture. The combustor is configured to operate at relatively high bulk fluid velocities while maintaining stable combustion, and low NOx emissions. The combustor is useful in gas turbines in a process of burning synfuels, as it offers the opportunity to avoid use of diluent gas to reduce combustion temperatures. The combustor also offers the possibility of avoiding the use of selected catalytic reaction units for removal of oxides of nitrogen from combustion gases exiting a gas turbine.

Insulin Glargine 300 U/mL: A Review in Diabetes Mellitus.

PubMed

Blair, Hannah A; Keating, Gillian M

2016-03-01

Insulin glargine 300 U/mL (Toujeo(®)) is a long-acting basal insulin analogue approved for the treatment of diabetes mellitus. Insulin glargine 300 U/mL has a more stable and prolonged pharmacokinetic/pharmacodynamic profile than insulin glargine 100 U/mL (Lantus(®)), with a duration of glucose-lowering activity exceeding 24 h. In several 6-month phase III trials, insulin glargine 300 U/mL achieved comparable glycaemic control to that seen with insulin glargine 100 U/mL in patients with type 1 or type 2 diabetes, albeit with consistently higher daily basal insulin requirements. These improvements in glycaemic control were maintained during longer-term (12 months) treatment. Insulin glargine 300 U/mL was generally associated with a lower risk of nocturnal hypoglycaemia than insulin glargine 100 U/mL in insulin-experienced patients with type 2 diabetes, while the risk of nocturnal hypoglycaemia did not significantly differ between treatment groups in insulin-naïve patients with type 2 diabetes or in patients with type 1 diabetes. To conclude, once-daily subcutaneous insulin glargine 300 U/mL is an effective and generally well tolerated basal insulin therapy option for patients with type 1 or type 2 diabetes.

Changes in metformin use and other antihyperglycemic therapies after insulin initiation in patients with type 2 diabetes.

PubMed

Pilla, Scott J; Dotimas, James R; Maruthur, Nisa M; Clark, Jeanne M; Yeh, Hsin-Chieh

2018-05-01

When patients with type 2 diabetes initiate insulin, metformin should be continued while continuation of other antihyperglycemics has unclear benefit. We aimed to identify practice patterns in antihyperglycemic therapy during the insulin transition, and determine factors associated with metformin continuation. We performed a retrospective analysis of the Look AHEAD (Action for Health in Diabetes) trial which randomized overweight/obese adults under ambulatory care for type 2 diabetes to an intensive lifestyle intervention or diabetes support and education. Among the 931 participants who initiated insulin over ten years, we described longitudinal changes in antihyperglycemic medications during the insulin transition, and performed multivariable logistic regression to estimate the association between patient characteristics and metformin continuation. Before insulin initiation, 81.0% of patients used multiple antihyperglycemics, the most common being metformin, sulfonylureas, and thiazolidinediones. After insulin initiation, metformin was continued in 80.3% of patients; other antihyperglycemics were continued less often, yet 58.0% of patients were treated with multiple non-insulin antihyperglycemics. Metformin continuation was inversely associated with age (fully adjusted (a) OR 0.60 per 10 years [0.42-0.86]), serum creatinine above safety thresholds (aOR 0.09 [0.02-0.36]), lower income (P = 0.025 for trend), taking more medications (aOR 0.92 per medication [0.86-0.98]), and initiating rapid, short, or premixed insulin (aOR 0.59 [0.39-0.89]). The vast majority of patients with type 2 diabetes continue metformin after insulin initiation, consistent with guidelines. Other antihyperglycemics are frequently continued along with insulin, and further research is needed to determine which, if any, patients may benefit from this. Copyright © 2018 Elsevier B.V. All rights reserved.

The conditional moment closure method for modeling lean premixed turbulent combustion

NASA Astrophysics Data System (ADS)

Martin, Scott Montgomery

Natural gas fired lean premixed gas turbines have become the method of choice for new power generation systems due to their high efficiency and low pollutant emissions. As emission regulations for these combustion systems become more stringent, the use of numerical modeling has become an important a priori tool in designing clean and efficient combustors. Here a new turbulent combustion model is developed in an attempt to improve the state of the art. The Conditional Moment Closure (CMC) method is a new theory that has been applied to non-premixed combustion with good success. The application of the CMC method to premixed systems has been proposed, but has not yet been done. The premixed CMC method replaces the species mass fractions as independent variables with the species mass fractions that are conditioned on a reaction progress variable (RPV). Conservation equations for these new variables are then derived and solved. The general idea behind the CMC method is that the behavior of the chemical species is closely coupled to the reaction progress variable. Thus, species conservation equations that are conditioned on the RPV will have terms involving the fluctuating quantities that are much more likely to be negligible. The CMC method accounts for the interaction between scalar dissipation (micromixing) and chemistry, while de-coupling the kinetics from the bulk flow (macromixing). Here the CMC method is combined with a commercial computational fluid dynamics program, which calculates the large-scale fluid motions. The CMC model is validated by comparison to 2-D reacting backward facing step data. Predicted species, temperature and velocity fields are compared to experimental data with good success. The CMC model is also validated against the University of Washington's 3-D jet stirred reactor (JSR) data, which is an idealized lean premixed combustor. The JSR results are encouraging, but not as good as the backward facing step. The largest source of error is from

New ways of insulin delivery.

PubMed

Heinemann, L

2011-02-01

The predominant number of papers published from the middle of 2009 to the middle of 2010 about alternative routes of insulin administration (ARIA) were still about inhaled insulin. Long-term experience with Exubera was the topic of a number of publications that are also of relevance for inhaled insulin in general. The clinical trials performed with AIR insulin by Eli Lilly were published in a supplement issue of one diabetes technology journal and most of these will be presented. A number of other publications (also one in a high ranked journal) about their inhaled insulin were from another company: MannKind. The driving force behind Technosphere insulin (TI) - which is the only one still in clinical development - is Al Mann; he has put a lot of his personal fortune in this development. We will know the opinion of the regulatory authorities about TI in the near future; however, I am personally relatively confident that the Food and Drug Administration will provide TI with market approval. The more critical question for me is: will diabetologists and patients jump on this product once it becomes commercially available? Will it become a commercial success? In view of many negative feelings in the scientific community about inhaled insulin, it might be of help that MannKind publish their studies with TI systematically. Acknowledging being a believer in this route of insulin administration myself, one has to state that Exubera and AIR insulin had not offered profound advantages in terms of pharmacokinetic (PK) and pharmacodynamic (PD) properties in comparison with subcutaneously (SC) applied regular human insulin (RHI) and rapid-acting insulin analogues. The time-action profiles of these inhaled insulins were more or less comparable with that of rapid-acting insulin analogues. This is clearly different with TI which exhibits a strong metabolic effect shortly after application and a rapid decline in the metabolic effect thereafter; probably the duration of action is

The role of basal insulin and GLP-1 receptor agonist combination products in the management of type 2 diabetes

PubMed Central

Inman, Taylor R.; Plyushko, Erika; Austin, Nicholas P.; Johnson, Jeremy L.

2018-01-01

The prevalence of type 2 diabetes necessitates the development of new treatment options to individualize therapy. Basal insulin has been a standard treatment option for years, while glucagon-like peptide-1 receptor agonists (GLP-1 RAs) have grown in use over the past decade due to glucose-lowering efficacy and weight loss potential. There are two new combination injectable products that have recently been approved combining basal insulins with GLP-1 RAs in single pen-injector devices. United States guidelines recently emphasize the option to use combination injectable therapy with GLP-1 RAs and basal insulin once the basal insulin has been optimally titrated as a second- or third-line agent in addition to metformin without reaching the goal A1c. Insulin glargine/lixisenatide 100/33 (IGlarLixi) can be dosed between 15 and 60 units once daily from a single pen-injector device. Insulin degludec/liraglutide 100/3.6 (IDegLira) can be dosed between 10 and 50 units once daily, also from a single pen-injector device. Maximum doses, while measured in units, correspond to limits defined by each individual GLP-1 RA. The dual use of basal insulin plus GLP-1 RA is non-inferior compared with basal insulin plus a single injection of prandial insulin at the largest meal and compared with twice daily-dosed premixed insulins; and this combination is associated with weight loss and less hypoglycemia. These new combination products could help providers effectively and efficiently follow clinical practice guidelines while enhancing patient adherence with injectable medications. PMID:29796245

The role of basal insulin and GLP-1 receptor agonist combination products in the management of type 2 diabetes.

PubMed

Inman, Taylor R; Plyushko, Erika; Austin, Nicholas P; Johnson, Jeremy L

2018-05-01

The prevalence of type 2 diabetes necessitates the development of new treatment options to individualize therapy. Basal insulin has been a standard treatment option for years, while glucagon-like peptide-1 receptor agonists (GLP-1 RAs) have grown in use over the past decade due to glucose-lowering efficacy and weight loss potential. There are two new combination injectable products that have recently been approved combining basal insulins with GLP-1 RAs in single pen-injector devices. United States guidelines recently emphasize the option to use combination injectable therapy with GLP-1 RAs and basal insulin once the basal insulin has been optimally titrated as a second- or third-line agent in addition to metformin without reaching the goal A1c. Insulin glargine/lixisenatide 100/33 (IGlarLixi) can be dosed between 15 and 60 units once daily from a single pen-injector device. Insulin degludec/liraglutide 100/3.6 (IDegLira) can be dosed between 10 and 50 units once daily, also from a single pen-injector device. Maximum doses, while measured in units, correspond to limits defined by each individual GLP-1 RA. The dual use of basal insulin plus GLP-1 RA is non-inferior compared with basal insulin plus a single injection of prandial insulin at the largest meal and compared with twice daily-dosed premixed insulins; and this combination is associated with weight loss and less hypoglycemia. These new combination products could help providers effectively and efficiently follow clinical practice guidelines while enhancing patient adherence with injectable medications.

Gravitational Influences on Flame Propagation Through Non-Uniform, Premixed Gas Systems

NASA Technical Reports Server (NTRS)

Miller, Fletcher J.; Easton, John; Marchese, Anthony; Hovermann, Fred

2003-01-01

Flame propagation through non-uniformly premixed (or layered) gases has importance both in useful combustion systems and in unintentional fires. As summarized recently and in previous Microgravity Workshop papers, non-uniform premixed gas combustion receives scant attention compared to the more usual limiting cases of diffusion or uniformly premixed flames, especially regarding the role gravity plays. This paper summarizes our recent findings on gravitational effects on layered combustion along a floor, in which the fuel concentration gradient exists normal to the direction of flame spread. In an effort to understand the mechanism by which the flames spread faster in microgravity (and much faster, in laboratory coordinates, than the laminar burning velocity for uniform mixtures), we have begun making pressure measurements across the spreading flame front that are described here. Earlier researchers, testing in 1g, claimed that hydrostatic pressure differences could account for the rapid spread rates. Additionally, we present the development of a new apparatus to study flame spread in free (i.e., far from walls), non-homogeneous fuel layers formed in a flow tunnel behind an airfoil that has been tested in normal gravity.

Studies of premixed laminar and turbulent flames at microgravity

NASA Technical Reports Server (NTRS)

Ronney, Paul D.

1993-01-01

A two and one-half year experimental and theoretical research program on the properties of laminar and turbulent premixed gas flames at microgravity was conducted. Progress during this program is identified and avenues for future studies are discussed.

Implementation of subcutaneous insulin protocol for non-critically ill hospitalized patients in andalusian tertiary care hospitals.

PubMed

Martínez-Brocca, María Asunción; Morales, Cristóbal; Rodríguez-Ortega, Pilar; González-Aguilera, Beatriz; Montes, Cristina; Colomo, Natalia; Piédrola, Gonzalo; Méndez-Muros, Mariola; Serrano, Isabel; Ruiz de Adana, Maria Soledad; Moreno, Alberto; Fernández, Ignacio; Aguilar, Manuel; Acosta, Domingo; Palomares, Rafael

2015-02-01

In 2009, the Andalusian Society of Endocrinology and Nutrition designed a protocol for subcutaneous insulin treatment in hospitalized non-critically ill patients (HIP). To analyze implementation of HIP at tertiary care hospitals from the Andalusian Public Health System. A descriptive, multicenter study conducted in 8 tertiary care hospitals on a random sample of non-critically ill patients with diabetes/hyperglycemia (n=306) hospitalized for ≥48 hours in 5 non-surgical (SM) and 2 surgical (SQ) departments. Type 1 and other specific types of diabetes, pregnancy and nutritional support were exclusion criteria. 288 patients were included for analysis (62.5% males; 70.3±10.3 years; 71.5% SM, 28.5% SQ). A scheduled subcutaneous insulin regimen based on basal-bolus-correction protocol was started in 55.9% (95%CI: 50.5-61.2%) of patients, 63.1% SM vs. 37.8% SQ (P<.05). Alternatives to insulin regimen based on basal-bolus-correction included sliding scale insulin (43.7%), diet (31.3%), oral antidiabetic drugs (17.2%), premixed insulin (1.6%), and others (6.2%). For patients previously on oral antidiabetic drugs, in-hospital insulin dose was 0.32±0.1 IU/kg/day. In patients previously on insulin, in-hospital insulin dose was increased by 17% [-13-53], and in those on insulin plus oral antidiabetic drugs, in-hospital insulin dose was increased by 26.4% [-6-100]. Supplemental insulin doses used for<40 IU/day and 40-80 IU/day were 72.2% and 56.7% respectively. HbA1c was measured in 23.6% of patients (95CI%: 18.8-28.8); 27.7% SM vs. 13.3% SQ (P<.05). Strategies are needed to improve implementation of the inpatient subcutaneous insulin protocol, particularly in surgical departments. Sliding scale insulin is still the most common alternative to insulin regimen based on basal-bolus-correction scheduled insulin. Metabolic control assessment during hospitalization should be encouraged. Copyright © 2014 SEEN. Published by Elsevier España, S.L.U. All rights reserved.

Observational 6-month open-label study of Japanese type 2 diabetes patients switching from NPH insulin to insulin detemir in basal-bolus regimen: 23rd article of the Japan Diabetes Clinical Data Management Study Group (JDDM23).

PubMed

Oishi, M; Abe, N; Yokoyama, H; Kuribayashi, N; Tomonaga, O; Matoba, K; Kobayashi, M

2012-01-01

Glycaemic control is critical to prevent diabetic complications and mortality. This 6-month, open-label, observational study assessed the efficacy and safety of switching Japanese patients with type 2 diabetes from neutral protamine Hagedorn (NPH) insulin to insulin detemir. Patients with type 2 diabetes (n = 126) receiving basal-bolus insulin therapy with NPH insulin plus rapid-acting insulin analogues were recruited. NPH insulin was replaced with insulin detemir for 6 months. Glycosylated haemoglobin (HbA(1c)), fasting plasma glucose (FPG), daily glucose levels and hypoglycaemia were monitored. Nocturnal quality of life was assessed by insulin therapy related quality of life at night questionnaire. HbA(1c), FPG and body weight were all significantly reduced after treatment with insulin detemir for 6 months, without increasing severe hypoglycaemia. Insulin dose increased significantly over the same time. There were significant improvements in overall nocturnal quality of life, as well as well-being. Treatment with insulin detemir for 6 months resulted in substantial benefits, including reduced HbA(1c), FPG and body weight, and improvements in nocturnal quality of life, without increasing hypoglycaemia.

Experimental Investigation of Turbulence-Chemistry Interaction in High-Reynolds-Number Turbulent Partially Premixed Flames

DTIC Science & Technology

2016-06-23

4 . TITLE AND SUBTITLE [U] Experimental investigation of turbulence-chemistry interaction in high-Reynolds-number 5a. CONTRACT NUMBER turbulent...nonpremixed/partially premixed flames and turbulence-chemistry interaction. Turbulent mixing of mixture fraction has been studied extensively [ 4 , 14]. In a...two-feed non-premixed flame, the mixture fraction is defined as: ξ = Y − Yo YF − Yo (1) where Y is a conserved quantity such as the mass fraction of any

Experimental study on flame propagation characteristics of Hydrogen premixed gas in gas pipeline

NASA Astrophysics Data System (ADS)

Ma, Danzhu; Li, Zhuang; Jia, Fengrui; Li, Zhou

2018-06-01

Hydrogen is the cleanest high-energy gas fuel, and also is the main industrial material. However, hydrogen is more explosive and more powerful than conventional gas fuels, which restricts its application. In particular, the expansion of premixed combustion under a strong constraint is more complicated, the reaction spreads faster. The flame propagation characteristics of premixed hydrogen/air were investigated by experiment. The mechanism of reaction acceleration is discussed, and then the speed of the flame propagation and the reaction pressure were tested and analysed.

Mechanisms of combustion limits in premixed gas flames at microgravity

NASA Technical Reports Server (NTRS)

Ronney, Paul D.

1991-01-01

A three-year experimental and theoretical research program on the mechanisms of combustion limits of premixed gasflames at microgravity was conducted. Progress during this program is identified and avenues for future studies are discussed.

Study of Turbulent Premixed Flame Propagation using a Laminar Flamelet Model

NASA Technical Reports Server (NTRS)

Im, H. G.

1995-01-01

The laminar flamelet concept in turbulent reacting flows is considered applicable to many practical combustion systems (Linan & Williams 1993). For turbulent premixed combustion, the laminar flamelet regime is valid when turbulent Karlovitz number is less than unity, which is equivalent to stating that the characteristic thickness of the flame is less than that of a Kolmogorov eddy; this is known as the Klimov-Williams criterion (Williams 1985). In such a case, the flame maintains its laminar structure, and the effect of turbulent flow is merely to wrinkle and strain the flame front. The propagating wrinkled premixed flame can then be described as an infinitesimally thin surface dividing the unburnt fresh mixture and the burnt product.

Direct Numerical Simulation of a Cavity-Stabilized Ethylene/Air Premixed Flame

NASA Astrophysics Data System (ADS)

Chen, Jacqueline; Konduri, Aditya; Kolla, Hemanth; Rauch, Andreas; Chelliah, Harsha

2016-11-01

Cavity flame holders have been shown to be important for flame stabilization in scramjet combustors. In the present study the stabilization of a lean premixed ethylene/air flame in a rectangular cavity at thermo-chemical conditions relevant to scramjet combustors is simulated using a compressible reacting multi-block direct numerical simulation solver, S3D, incorporating a 22 species ethylene-air reduced chemical model. The fuel is premixed with air to an equivalence ratio of 0.4 and enters the computational domain at Mach numbers between 0.3 and 0.6. An auxiliary inert channel flow simulation is used to provide the turbulent velocity profile at the inlet for the reacting flow simulation. The detailed interaction between intense turbulence, nonequilibrium concentrations of radical species formed in the cavity and mixing with the premixed main stream under density variations due to heat release rate and compressibility effects is quantified. The mechanism for flame stabilization is quantified in terms of relevant non-dimensional parameters, and detailed analysis of the flame and turbulence structure will be presented. We acknowledge the sponsorship of the AFOSR-NSF Joint Effort on Turbulent Combustion Model Assumptions and the DOE Office of Basic Energy Sciences, Division of Chemical Sciences, Geosciences, and Biosciences.

Modeling of Dissipation Element Statistics in Turbulent Non-Premixed Jet Flames

NASA Astrophysics Data System (ADS)

Denker, Dominik; Attili, Antonio; Boschung, Jonas; Hennig, Fabian; Pitsch, Heinz

2017-11-01

The dissipation element (DE) analysis is a method for analyzing and compartmentalizing turbulent scalar fields. DEs can be described by two parameters, namely the Euclidean distance l between their extremal points and the scalar difference in the respective points Δϕ . The joint probability density function (jPDF) of these two parameters P(Δϕ , l) is expected to suffice for a statistical reconstruction of the scalar field. In addition, reacting scalars show a strong correlation with these DE parameters in both premixed and non-premixed flames. Normalized DE statistics show a remarkable invariance towards changes in Reynolds numbers. This feature of DE statistics was exploited in a Boltzmann-type evolution equation based model for the probability density function (PDF) of the distance between the extremal points P(l) in isotropic turbulence. Later, this model was extended for the jPDF P(Δϕ , l) and then adapted for the use in free shear flows. The effect of heat release on the scalar scales and DE statistics is investigated and an extended model for non-premixed jet flames is introduced, which accounts for the presence of chemical reactions. This new model is validated against a series of DNS of temporally evolving jet flames. European Research Council Project ``Milestone''.

The Effect of Premixed Al-Cu Powder on the Stir Zone in Friction Stir Welding of AA3003-H18

NASA Astrophysics Data System (ADS)

Abnar, B.; Kazeminezhad, M.; Kokabi, A. H.

2015-02-01

In this research, 3-mm-thick AA3003-H18 non-heat-treatable aluminum alloy plates were joined by friction stir welding (FSW). It was performed by adding pure Cu and premixed Cu-Al powders at various rotational speeds of 800, 1000, and 1200 rpm and constant traveling speeds of 100 mm/min. At first, the powder was filled into the gap (0.2 or 0.4 mm) between two aluminum alloy plates, and then the FSW process was performed in two passes. The microstructure, mechanical properties, and formation of intermetallic compounds were investigated in both cases of using pure Cu and premixed Al-Cu powders. The results of using pure Cu and premixed Al-Cu powders were compared in the stir zone at various rotational speeds. The copper particle distribution and formation of Al-Cu intermetallic compounds (Al2Cu and AlCu) in the stir zone were desirable using premixed Al-Cu powder into the gap. The hardness values were significantly increased by formation of Al-Cu intermetallic compounds in the stir zone and it was uniform throughout the stir zone when premixed Al-Cu powder was used. Also, longitudinal tensile strength from the stir zone was higher when premixed Al-Cu powder was used instead of pure Cu powder.

Insulin therapy in neonatal diabetes mellitus: a review of the literature.

PubMed

Rabbone, Ivana; Barbetti, Fabrizio; Gentilella, Raffaella; Mossetto, Gilberto; Bonfanti, Riccardo; Maffeis, Claudio; Iafusco, Dario; Piccinno, Elvira

2017-07-01

Neonatal diabetes mellitus (NDM) is a rare disorder, and guidance is limited regarding its optimal management. We reviewed insulin usage in NDM, with a focus on continuous subcutaneous insulin infusion (CSII). A PubMed search identified 40 reports of patients with NDM treated with insulin published between 1994 and 2016. Data concerning treatment of NDM are limited. CSII resolves some of the issues associated with insulin therapy in neonates. No clinical trials of CSII in NDM have been reported. Case reports suggest that CSII is a safe and effective means of treating NDM. CSII was initiated to improve glycaemic control, for practicality and convenience, and to overcome difficulties associated with the maintenance of long-term intravenous catheters. CSII can provide better glycaemic control than multiple daily injections, with few hypoglycaemic events. Continuous glucose monitoring integrated with the pump helps provide more precise control of blood glucose levels. CSII generally uses short-acting insulin or rapid-acting insulin analogues, and those that are approved for use in neonates appear to be appropriate for the treatment of NDM using an insulin pump. Information from case reports indicates that CSII is safe and effective for the management of NDM. Copyright © 2017 Elsevier B.V. All rights reserved.

Inhibition of Insulin Amyloid Fibrillation by a Novel Amphipathic Heptapeptide

PubMed Central

Ratha, Bhisma N.; Ghosh, Anirban; Brender, Jeffrey R.; Gayen, Nilanjan; Ilyas, Humaira; Neeraja, Chilukoti; Das, Kali P.; Mandal, Atin K.; Bhunia, Anirban

2016-01-01

The aggregation of insulin into amyloid fibers has been a limiting factor in the development of fast acting insulin analogues, creating a demand for excipients that limit aggregation. Despite the potential demand, inhibitors specifically targeting insulin have been few in number. Here we report a non-toxic and serum stable-designed heptapeptide, KR7 (KPWWPRR-NH2), that differs significantly from the primarily hydrophobic sequences that have been previously used to interfere with insulin amyloid fibrillation. Thioflavin T fluorescence assays, circular dichroism spectroscopy, and one-dimensional proton NMR experiments suggest KR7 primarily targets the fiber elongation step with little effect on the early oligomerization steps in the lag time period. From confocal fluorescence and atomic force microscopy experiments, the net result appears to be the arrest of aggregation in an early, non-fibrillar aggregation stage. This mechanism is noticeably different from previous peptide-based inhibitors, which have primarily shifted the lag time with little effect on later stages of aggregation. As insulin is an important model system for understanding protein aggregation, the new peptide may be an important tool for understanding peptide-based inhibition of amyloid formation. PMID:27679488

Dynamic properties of combustion instability in a lean premixed gas-turbine combustor.

PubMed

Gotoda, Hiroshi; Nikimoto, Hiroyuki; Miyano, Takaya; Tachibana, Shigeru

2011-03-01

We experimentally investigate the dynamic behavior of the combustion instability in a lean premixed gas-turbine combustor from the viewpoint of nonlinear dynamics. A nonlinear time series analysis in combination with a surrogate data method clearly reveals that as the equivalence ratio increases, the dynamic behavior of the combustion instability undergoes a significant transition from stochastic fluctuation to periodic oscillation through low-dimensional chaotic oscillation. We also show that a nonlinear forecasting method is useful for predicting the short-term dynamic behavior of the combustion instability in a lean premixed gas-turbine combustor, which has not been addressed in the fields of combustion science and physics.

Establishing bioequivalence of veterinary premixes (Type A medicated articles).

PubMed

Hunter, R P; Lees, P; Concordet, D; Toutain, P-L

2012-04-01

a) Key issues concerning Premix (Type A medicated articles) Bioequivalence evaluations: 1) This is a complex issue concerning both route of administration and formulation. 2) If the animal is not at the bunk/trough, the animal is not self-administering (eating medicated feed), thus there can be no drug absorption. b) Differing opinions among scientists and regulatory authorities/expert bodies regarding: 1) No harmonization on how to design, conduct, and interpret in vivo studies. 2) Applicability of biowaivers to Type A (premix) products. 3) Why are topdress and complete feed considered differently? Are they different formulations or different routes of administration? 4) Single dose vs. multi-dose studies. 5) What is the final formulation? c) What are the next steps: 1) Harmonize current bioequivalence guidelines through the VICH process. 2) Determine the applicability/non-applicability of the Biopharmaceutical Classification System (BCS). 3) Establish the Total Mixed Ration (i.e. formulation) effects. 4) Define the test subject (individual, pen, etc.). © 2012 Blackwell Publishing Ltd.

Molecular Dynamics Simulations of Insulin: Elucidating the Conformational Changes that Enable Its Binding.

PubMed

Papaioannou, Anastasios; Kuyucak, Serdar; Kuncic, Zdenka

2015-01-01

A sequence of complex conformational changes is required for insulin to bind to the insulin receptor. Recent experimental evidence points to the B chain C-terminal (BC-CT) as the location of these changes in insulin. Here, we present molecular dynamics simulations of insulin that reveal new insights into the structural changes occurring in the BC-CT. We find three key results: 1) The opening of the BC-CT is inherently stochastic and progresses through an open and then a "wide-open" conformation--the wide-open conformation is essential for receptor binding, but occurs only rarely. 2) The BC-CT opens with a zipper-like mechanism, with a hinge at the Phe24 residue, and is maintained in the dominant closed/inactive state by hydrophobic interactions of the neighboring Tyr26, the critical residue where opening of the BC-CT (activation of insulin) is initiated. 3) The mutation Y26N is a potential candidate as a therapeutic insulin analogue. Overall, our results suggest that the binding of insulin to its receptor is a highly dynamic and stochastic process, where initial docking occurs in an open conformation and full binding is facilitated through interactions of insulin receptor residues with insulin in its wide-open conformation.

Optimization of instant dalia dessert pre-mix production by using response surface methodology.

PubMed

Jha, Alok; Shalini, B N; Patel, Ashok Ambalal; Singh, Mithilesh; Rasane, Prasad

2015-02-01

Dalia, a wheat-based, particulate containing dairy dessert is popularly consumed as a breakfast food and is also considered as a health food. Though popular throughout Northern parts of the country, its limited shelf-life even under refrigeration imposes severe restrictions on its organized manufacture and marketing. In order to promote dalia dessert as a marketable product, in the present study, a process was developed for manufacture of instant dalia pre-mix, as a dry product with long shelf-life, which could be attractively packaged and easily reconstituted for consumption. During the investigation, the effect of different levels of milk solids and wheat solids was studied on dalia pre-mix quality by employing a central composite rotatable design (CCRD). The suggested formulation had 17.82 % milk solids and 2.87 % wheat solids. This formulation was found to be most appropriate for manufacture of instant dalia pre-mix with predicted sensory scores (Max. 100) of 85.35, 41.98 and 67.27 for mouthfeel, consistency and flavor, respectively; the viscosity of the product was 941.0 cp.

21 CFR 170.60 - Nitrites and/or nitrates in curing premixes.

Code of Federal Regulations, 2010 CFR

2010-04-01

... additives when combined in curing premixes with spices and/or other flavoring or seasoning ingredients that... hydrolyzed vegetable protein), oleoresins of spices, soy products, and spice extractives. Such food additives...

[Contribution of the laboratory in hypoglycemia diagnosis induced by insulin administration in a 2-year-old girl].

PubMed

Dejoie, T; Ramos, E; Baron, S; Bach-Ngohou, K; Masson, D

2008-01-01

We report the case of a 2 year-old child presented to the emergency department following a seizure. The child was hypotonic and examination was unremarkable but laboratory tests confirmed a severe hypoglycaemia. The insulin level, inappropriately high for the glycemia and the peptide C undetectable suggested exogenous hyperinsulinism. We conclude that the hypoglycaemia was likely the result of Munchhausen syndrome by proxy. The specificity of two immunoassays used (Elecsys Roche and IRMA CisBio) for the synthetic analogues of insulin explains the discrepancy between the insulin levels obtained but was crucially useful to the approach of the cause of the hypoglycaemia.

An Investigation of a Hybrid Mixing Timescale Model for PDF Simulations of Turbulent Premixed Flames

NASA Astrophysics Data System (ADS)

Zhou, Hua; Kuron, Mike; Ren, Zhuyin; Lu, Tianfeng; Chen, Jacqueline H.

2016-11-01

Transported probability density function (TPDF) method features the generality for all combustion regimes, which is attractive for turbulent combustion simulations. However, the modeling of micromixing due to molecular diffusion is still considered to be a primary challenge for TPDF method, especially in turbulent premixed flames. Recently, a hybrid mixing rate model for TPDF simulations of turbulent premixed flames has been proposed, which recovers the correct mixing rates in the limits of flamelet regime and broken reaction zone regime while at the same time aims to properly account for the transition in between. In this work, this model is employed in TPDF simulations of turbulent premixed methane-air slot burner flames. The model performance is assessed by comparing the results from both direct numerical simulation (DNS) and conventional constant mechanical-to-scalar mixing rate model. This work is Granted by NSFC 51476087 and 91441202.

The hybrid RANS/LES of partially premixed supersonic combustion using G/Z flamelet model

NASA Astrophysics Data System (ADS)

Wu, Jinshui; Wang, Zhenguo; Bai, Xuesong; Sun, Mingbo; Wang, Hongbo

2016-10-01

In order to describe partially premixed supersonic combustion numerically, G/Z flamelet model is developed and compared with finite rate model in hybrid RANS/LES simulation to study the strut-injection supersonic combustion flow field designed by the German Aerospace Center. A new temperature calculation method based on time-splitting method of total energy is introduced in G/Z flamelet model. Simulation results show that temperature predictions in partially premixed zone by G/Z flamelet model are more consistent with experiment than finite rate model. It is worth mentioning that low temperature reaction zone behind the strut is well reproduced. Other quantities such as average velocity and average velocity fluctuation obtained by developed G/Z flamelet model are also in good agreement with experiment. Besides, simulation results by G/Z flamelet also reveal the mechanism of partially premixed supersonic combustion by the analyses of the interaction between turbulent burning velocity and flow field.

Premixing quality and flame stability: A theoretical and experimental study

NASA Technical Reports Server (NTRS)

Radhakrishnan, K.; Heywood, J. B.; Tabaczynski, R. J.

1979-01-01

Models for predicting flame ignition and blowout in a combustor primary zone are presented. A correlation for the blowoff velocity of premixed turbulent flames is developed using the basic quantities of turbulent flow, and the laminar flame speed. A statistical model employing a Monte Carlo calculation procedure is developed to account for nonuniformities in a combustor primary zone. An overall kinetic rate equation is used to describe the fuel oxidation process. The model is used to predict the lean ignition and blow out limits of premixed turbulent flames; the effects of mixture nonuniformity on the lean ignition limit are explored using an assumed distribution of fuel-air ratios. Data on the effects of variations in inlet temperature, reference velocity and mixture uniformity on the lean ignition and blowout limits of gaseous propane-air flames are presented.

Laser-saturated fluorescence of nitric oxide and chemiluminescence measurements in premixed ethanol flames

DOE Office of Scientific and Technical Information (OSTI.GOV)

Marques, Carla S.T.; Barreta, Luiz G.; Sbampato, Maria E.

In this study, nitric oxide laser-saturated fluorescence (LSF) measurements were acquired from premixed ethanol flames at atmospheric pressure in a burner. NO-LSF experimental profiles for fuel-rich premixed ethanol flames ({phi} = 1.34 and {phi} = 1.66) were determined through the excitation/detection scheme of the Q{sub 2}(26.5) rotational line in the A{sup 2}{sigma}{sup +} - X{sup 2}{pi} (0,0) vibronic band and {gamma}(0,1) emission band. A calibration procedure by NO doping into the flame was applied to establish the NO concentration profiles in these flames. Chemiluminescent emission measurements in the (0, 0) vibronic emission bands of the OH{sup *} (A{sup 2}{sigma}{sup +}more » - X{sup 2}{pi}) and CH{sup *}(A{sup 2}{delta} - X{sup 2}{pi}) radicals were also obtained with high spatial and spectral resolution for fuel-rich premixed ethanol flames to correlate them with NO concentrations. Experimental chemiluminescence profiles and the ratios of the integrated areas under emission spectra (A{sub CH*}/A{sub CH*}(max.) and A{sub CH*}/A{sub OH*}) were determined. The relationships between chemiluminescence and NO concentrations were established along the premixed ethanol flames. There was a strong connection between CH{sup *} radical chemiluminescence and NO formation and the prompt-NO was identified as the governing mechanism for NO production. The results suggest the optimum ratio of the chemiluminescence of two radicals (A{sub CH*}/A{sub OH*}) for NO diagnostic purposes. (author)« less

Soot Formation in Laminar Premixed Methane/Oxygen Flames at Atmospheric Pressure

NASA Technical Reports Server (NTRS)

Xu, F.; Lin, K.-C.; Faeth, G. M.

1998-01-01

Flame structure and soot formation were studied within soot-containing laminar premixed mc1hane/oxygen flames at atmospheric pressure. The following measurements were made: soot volume fractions by laser extinction, soot temperatures by multiline emission, gas temperatures (where soot was absent) by corrected fine-wire thermocouples, soot structure by thermophoretic sampling and transmission electron microscope (TEM), major gas species concentrations by sampling and gas chromatography, and gas velocities by laser velocimetry. Present measurements of gas species concentrations were in reasonably good agreement with earlier measurements due to Ramer et al. as well as predictions based on the detailed mechanisms of Frenklach and co-workers and Leung and Lindstedt: the predictions also suggest that H atom concentrations are in local thermodynamic equilibrium throughout the soot formation region. Using this information, it was found that measured soot surface growth rates could be correlated successfully by predictions based on the hydrogen-abstraction/carbon-addition (HACA) mechanisms of both Frenklach and co-workers and Colket and Hall, extending an earlier assessment of these mechanisms for premixed ethylene/air flames to conditions having larger H/C ratios and acetylene concentrations. Measured primary soot particle nucleation rates were somewhat lower than the earlier observations for laminar premixed ethylene/air flames and were significantly lower than corresponding rates in laminar diffusion flames. for reasons that still must be explained.

Understanding and predicting soot generation in turbulent non-premixed jet flames.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wang, Hai; Kook, Sanghoon; Doom, Jeffrey

2010-10-01

This report documents the results of a project funded by DoD's Strategic Environmental Research and Development Program (SERDP) on the science behind development of predictive models for soot emission from gas turbine engines. Measurements of soot formation were performed in laminar flat premixed flames and turbulent non-premixed jet flames at 1 atm pressure and in turbulent liquid spray flames under representative conditions for takeoff in a gas turbine engine. The laminar flames and open jet flames used both ethylene and a prevaporized JP-8 surrogate fuel composed of n-dodecane and m-xylene. The pressurized turbulent jet flame measurements used the JP-8 surrogatemore » fuel and compared its combustion and sooting characteristics to a world-average JP-8 fuel sample. The pressurized jet flame measurements demonstrated that the surrogate was representative of JP-8, with a somewhat higher tendency to soot formation. The premixed flame measurements revealed that flame temperature has a strong impact on the rate of soot nucleation and particle coagulation, but little sensitivity in the overall trends was found with different fuels. An extensive array of non-intrusive optical and laser-based measurements was performed in turbulent non-premixed jet flames established on specially designed piloted burners. Soot concentration data was collected throughout the flames, together with instantaneous images showing the relationship between soot and the OH radical and soot and PAH. A detailed chemical kinetic mechanism for ethylene combustion, including fuel-rich chemistry and benzene formation steps, was compiled, validated, and reduced. The reduced ethylene mechanism was incorporated into a high-fidelity LES code, together with a moment-based soot model and models for thermal radiation, to evaluate the ability of the chemistry and soot models to predict soot formation in the jet diffusion flame. The LES results highlight the importance of including an optically

The insulin dilemma in resource-limited countries. A way forward?

PubMed

Gill, G V; Yudkin, J S; Keen, H; Beran, D

2011-01-01

The International Insulin Foundation (IIF) has developed and validated a needs-assessment instrument called the Rapid Assessment Protocol for Insulin Access (RAPIA) which has been used in seven countries in four continents to analyse the constraints to delivering effective continuing care for people with diabetes. One major contributor to the difficulties in availability of insulin is a failure to use the least costly sources and types of insulin and other effective drugs for diabetes. The purchase of insulins can consume as much as 10% of government expenditure on drugs, this being highly sensitive to the selection of newer analogue insulins as first-choice options, which cost between three and 13 times more than biosynthetic human insulin. Insulin cartridges for use with injection pens further add to costs. Similar considerations apply to most of the newer treatments for people with type 2 diabetes, which may cost up to 40 times more than metformin and sulfonylureas, still considered first-line drugs by European and US guidelines. Both biosynthetic human insulin and the first-line oral hypoglycaemic drugs are available from generic manufacturers. With the present price differentials, there is thus a growing need for countries involved in tendering for sourcing insulin to be provided with the guarantees of Good Manufacturing Practice, quality and bioequivalence, which would come from a WHO Pre-Qualification Scheme as currently exists for a variety of drugs for chronic diseases, both communicable and non-communicable. The IIF has developed a position statement on the provision and choice of diabetes treatments in resource-limited settings which should be applicable wherever consideration of resources is a component of therapeutic decision making.

Direct numerical simulation of a high Ka CH 4/air stratified premixed jet flame

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wang, Haiou; Hawkes, Evatt R.; Savard, Bruno

Here, direct numerical simulation (DNS) of a high Karlovitz number (Ka) CH 4/air stratified premixed jet flame was performed and used to provide insights into fundamentals of turbulent stratified premixed flames and their modelling implications. The flame exhibits significant stratification where the central jet has an equivalence ratio of 0.4, which is surrounded by a pilot flame with an equivalence ratio of 0.9. A reduced chemical mechanism for CH 4/air combustion based on GRI-Mech3.0 was used, including 268 elementary reactions and 28 transported species.

Direct numerical simulation of a high Ka CH 4/air stratified premixed jet flame

DOE PAGES

Wang, Haiou; Hawkes, Evatt R.; Savard, Bruno; ...

2018-04-24

Here, direct numerical simulation (DNS) of a high Karlovitz number (Ka) CH 4/air stratified premixed jet flame was performed and used to provide insights into fundamentals of turbulent stratified premixed flames and their modelling implications. The flame exhibits significant stratification where the central jet has an equivalence ratio of 0.4, which is surrounded by a pilot flame with an equivalence ratio of 0.9. A reduced chemical mechanism for CH 4/air combustion based on GRI-Mech3.0 was used, including 268 elementary reactions and 28 transported species.

Commercial premixed parenteral nutrition: Is it right for your institution?

PubMed

Miller, Sarah J

2009-01-01

Two-compartment premixed parenteral nutrition (PN) products are heavily promoted in the United States. These products may present safety advantages over PN solutions mixed by a local pharmacy, although clinical data to support this assertion are scarce. Multicompartment products can be labor-saving for pharmacy and therefore may be cost-effective for some institutions. Before adopting such products for use, an institution must determine that standardized PN solutions are acceptable for many or most of their patients compared with customized PN compounded specifically for individual patients. A larger selection of premixed products is available in Europe and some other parts of the world compared with the United States. Availability of a broader selection of products in the United States, including 3-compartment bags and a wider range of macronutrient concentrations and volumes, may make the use of such products more desirable in the future.

Premixed calcium silicate cement for endodontic applications: injectability, setting time and radiopacity.

PubMed

Persson, Cecilia; Engqvist, Håkan

2011-01-01

Calcium silicate-based materials (also called MTA) are increasingly being used in endodontic applications. However, the handling properties of MTA are not optimal when it comes to injectability and cohesion. Premixing the cements using glycerol avoids these issues. However, there is a lack of data on the effect of common cement variables on important properties of premixed cements for endodontic applications. In this study, the effects of liquid-to-powder ratio, amount of radiopacifier and amount of calcium sulfate (added to control the setting time) were screened using a statistical model. In the second part of the study, the liquid-to-powder ratio was optimized for cements containing three different amounts of radiopacifier. Finally, the effect of using glycerol rather than water was evaluated in terms of radiopacity. The setting time was found to increase with the amount of radiopacifier when the liquid-to-powder ratio was fixed. This was likely due to the higher density of the radiopacifier in comparison to the calcium silicate, which gave a higher liquid-to-powder ratio in terms of volume. Using glycerol rather than water to mix the cements led to a decrease in radiopacity of the cement. In conclusion, we were able to produce premixed calcium silicate cements with acceptable properties for use in endodontic applications.

On the Structure and Stabilization Mechanisms of Planar and Cylindrical Premixed Flames

NASA Technical Reports Server (NTRS)

Eng, James A.; Zhu, Delin; Law, Chung K.

1993-01-01

The configurational simplicity of the stationary one-dimensional flames renders them intrinsically attractive for fundamental flame structure studies. The possibility and fidelity of studies of such flames on earth, however, have been severely restricted by the unidirectional nature of the gravity vector. To demonstrate these complications, let us first consider the premixed flame. Here a stationary, one-dimensional flame can be established by using the flat-flame burner. We next consider nonpremixed flames. First it may be noted that in an unbounded gravity-free environment, the only stationary one-dimensional flame is the spherical flame. Indeed, this is a major motivation for the study of microgravity droplet combustion, in which the gas-phase processes can be approximated to be quasi-steady because of the significant disparity between the gas and liquid densities for subcritical combustion. In view of the above considerations, an experimental and theoretical program on cylindrical and spherical premixed and nonpremixed flames in microgravity has been initiated. For premixed flames, we are interested in: (1) assessing the heat loss versus flow divergence as the dominant stabilization mechanism; (2) determining the laminar flame speed by using this configuration; and (3) understanding the development of flamefront instability and the effects of the flame curvature on the burning intensity.

Development of Criteria for Flameholding Tendencies within Premixer Passages for High Hydrogen Content Fuels

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lewis, Elliot Sullivan-; McDonell, Vincent G.

Due to increasingly stringent air quality requirements stationary power gas turbines have moved to lean-premixed operation, which reduces pollutant emissions but can result in flashback. Flashback can cause serious damage to the premixer hardware. Curtailing flashback can be difficult with hydrocarbon fuels and becomes even more challenging when hydrogen is used as the fuel. The two main approaches for coping with flashback are either to design a combustor that is resistant to flashback, or to design a premixer that will not anchor a flame if flashback occurs. Even with a well-designed combustor flashback can occur under certain circumstances, thus itmore » is necessary to determine how to avoid flameholding within the premixer passageways of a gas turbine. To this end, an experiment was designed that would determine the flameholding propensities at elevated pressures and temperatures of three different classes of geometric features commonly found in gas turbine premixers, with both natural gas and hydrogen fuel. Experiments to find the equivalence ratio at blow off were conducted within an optically accessible test apparatus with four flameholders: 0.25 and 0.50 inch diameter cylinders, a reverse facing step with a height of 0.25 inches, and a symmetric airfoil with a thickness of 0.25 inches and a chord length of one inch. Tests were carried out at temperatures between 300 K and 750 K, at pressures up to 9 atmospheres. Typical bulk velocities were between 40 and 100 m/s. The effect of airfoil’s angle of rotation was also investigated. Blow off for hydrogen flames was found to occur at much lower adiabatic flame temperatures than natural gas flames. Additionally it was observed that at high pressures and high turbulence intensities, reactant velocity does not have a noticeable effect on the point of blow off due in large part to corresponding increases in turbulent flame speed. Finally a semi empirical correlation was developed that predicts flame extinction

Quantification of trace metals in infant formula premixes using laser-induced breakdown spectroscopy

NASA Astrophysics Data System (ADS)

Cama-Moncunill, Raquel; Casado-Gavalda, Maria P.; Cama-Moncunill, Xavier; Markiewicz-Keszycka, Maria; Dixit, Yash; Cullen, Patrick J.; Sullivan, Carl

2017-09-01

Infant formula is a human milk substitute generally based upon fortified cow milk components. In order to mimic the composition of breast milk, trace elements such as copper, iron and zinc are usually added in a single operation using a premix. The correct addition of premixes must be verified to ensure that the target levels in infant formulae are achieved. In this study, a laser-induced breakdown spectroscopy (LIBS) system was assessed as a fast validation tool for trace element premixes. LIBS is a promising emission spectroscopic technique for elemental analysis, which offers real-time analyses, little to no sample preparation and ease of use. LIBS was employed for copper and iron determinations of premix samples ranging approximately from 0 to 120 mg/kg Cu/1640 mg/kg Fe. LIBS spectra are affected by several parameters, hindering subsequent quantitative analyses. This work aimed at testing three matrix-matched calibration approaches (simple-linear regression, multi-linear regression and partial least squares regression (PLS)) as means for precision and accuracy enhancement of LIBS quantitative analysis. All calibration models were first developed using a training set and then validated with an independent test set. PLS yielded the best results. For instance, the PLS model for copper provided a coefficient of determination (R2) of 0.995 and a root mean square error of prediction (RMSEP) of 14 mg/kg. Furthermore, LIBS was employed to penetrate through the samples by repetitively measuring the same spot. Consequently, LIBS spectra can be obtained as a function of sample layers. This information was used to explore whether measuring deeper into the sample could reduce possible surface-contaminant effects and provide better quantifications.

The route of liquid precursor to ZnO nanoparticles in premixed combustion spray pyrolysis

NASA Astrophysics Data System (ADS)

Widiyastuti, W.; Machmudah, Siti; Nurtono, Tantular; Winardi, Sugeng

2018-04-01

Zinc oxide nanoparticles had been successfully synthesized by premixed combustion spray pyrolysis. Zinc acetate was dissolved in distilled water was selected as a liquid precursor. Zinc nitrate was also used for comparison the effect of precursor type on the generated particles morphology and the crystallinity. The premixed combustion reaction used liquefied petroleum gas (LPG) mainly consisting of butane and propane as a fuel and compressed air used as an oxidizer. The liquid precursor was atomized using a custom two fluid nozzle to generate droplets. Then, the droplets were sprayed by the flow of air as a carrier gas into the premixed combustion reactor. The zinc precursor was decomposed to zinc oxide due to the high temperature as a result of combustion reaction inside the reactor resulting in nanoparticles formation. The particle size decreased with the increase of the fuel flow rate. In addition, it can be found that at the same flow rate of fuel, the particle size of zinc oxide synthesized using zinc nitrate is larger than that of the use of zinc acetate as a precursor.

Insulin and the polycystic ovary syndrome.

PubMed

Macut, Djuro; Bjekić-Macut, Jelica; Rahelić, Dario; Doknić, Mirjana

2017-08-01

Polycystic ovary syndrome (PCOS) is the most prevalent endocrinopathy among women during reproductive age. PCOS is characterised by hyperandrogenaemia, hyperinsulinaemia, and deranged adipokines secretion from the adipose tissue. In addition to the reduced insulin sensitivity, PCOS women exhibit β-cell dysfunction as well. Low birth weight and foetal exposure to androgens may contribute to the development of the PCOS phenotype during life. Further metabolic complications lead to dyslipidaemia, worsening obesity and glucose tolerance, high prevalence of metabolic syndrome, and greater susceptibility to diabetes. PCOS women show age-related existence of hypertension, and subtle endothelial and vascular changes. Adverse reproductive outcomes include anovulatory infertility, and unrecognised potentiation of the hormone-dependent endometrial cancer. The main therapeutic approach is lifestyle modification. Metformin is the primary insulin-sensitising drug to be used as an adjuvant therapy to lifestyle modification in patients with insulin resistance and impaired glucose tolerance, as well as in those referred to infertility treatment. Thiazolidinediones should be reserved for women intolerant of or refractory to metformin, while glucagon-like peptide 1 analogues has a potential therapeutic use in obese PCOS women. Randomised clinical trials and repetitive studies on different PCOS phenotypes for the preventive actions and therapeutic options are still lacking, though. Copyright © 2017 Elsevier B.V. All rights reserved.

Effects of Non-Equilibrium Plasmas on Low-Pressure, Premixed Flames. Part 1: CH* Chemiluminescence, Temperature, and OH

DTIC Science & Technology

2018-01-16

1    Effects of Non -Equilibrium Plasmas on Low-Pressure, Premixed Flames. Part 1: CH* Chemiluminescence, Temperature, and OH Ting Li, Igor V...investigate the effects of nanosecond, repetitively-pulsed, non -equilibrium plasma discharges on laminar, low-pressure, premixed burner-stabilized hydrogen/O2...sources, both of which generate uniform, low-temperature, volumetric, non -equilibrium plasma discharges, are used to study changes in

Large Eddy Simulation of Flame Flashback in Swirling Premixed Flames

NASA Astrophysics Data System (ADS)

Lietz, Christopher; Raman, Venkatramanan

2014-11-01

In the design of high-hydrogen content gas turbines for power generation, flashback of the turbulent flame by propagation through the low velocity boundary layers in the premixing region is an operationally dangerous event. Predictive models that could accurately capture the onset and subsequent behavior of flashback would be indispensable in gas turbine design. The large eddy simulation (LES) approach is used here to model this process. The goal is to examine the validity of a probability distribution function (PDF) based model in the context of a lean premixed flame in a confined geometry. A turbulent swirling flow geometry and corresponding experimental data is used for validation. A suite of LES calculations are performed on a large unstructured mesh for varying fuel compositions operating at several equivalence ratios. It is shown that the PDF based method can predict some statistical properties of the flame front, with improvement over other models in the same application.

Evaluation of fuel preparation systems for lean premixing-prevaporizing combustors

NASA Technical Reports Server (NTRS)

Dodds, W. J.; Ekstedt, E. E.

1985-01-01

A series of experiments was carried out in order to produce design data for a premixing prevaporizing fuel-air mixture preparation system for aircraft gas turbine engine combustors. The fuel-air mixture uniformity of four different system design concepts was evaluated over a range of conditions representing the cruise operation of a modern commercial turbofan engine. Operating conditions including pressure, temperature, fuel-to-air ratio, and velocity, exhibited no clear effect on mixture uniformity of systems using pressure-atomizing fuel nozzles and large-scale mixing devices. However, the performance of systems using atomizing fuel nozzles and large-scale mixing devices was found to be sensitive to operating conditions. Variations in system design variables were also evaluated and correlated. Mixing uniformity was found to improve with system length, pressure drop, and the number of fuel injection points per unit area. A premixing system capable of providing mixing uniformity to within 15 percent over a typical range of cruise operating conditions is demonstrated.

Lowest Glucose Variability and Hypoglycemia Are Observed With the Combination of a GLP-1 Receptor Agonist and Basal Insulin (VARIATION Study).

PubMed

Bajaj, Harpreet S; Venn, Karri; Ye, Chenglin; Patrick, Avril; Kalra, Shivani; Khandwala, Hasnain; Aslam, Nadeem; Twum-Barima, David; Aronson, Ronnie

2017-02-01

There is a dearth of published literature comparing glucose variability (GV) between different insulin regimens in type 2 diabetes. This cohort study compares GV using continuous glucose monitoring (CGM) in patients with well-controlled type 2 diabetes using four common insulin regimens: basal insulin + oral drugs (BO), basal insulin + glucagon-like peptide 1 receptor agonist (GLP-1 RA) (BGLP), premixed insulin (PM), and basal-bolus insulin (BB). Consecutive patients from three endocrinology clinics who met study criteria-type 2 diabetes, age 18 to 80 years, BMI ≤ 45 kg/m 2 , stable insulin regimen for a minimum of 6 months, and stable A1C value ≤7.5% (58 mmol/mol) before study enrollment-underwent 6-day masked CGM. Hypoglycemia was defined as a sensor glucose concentration <70 mg/dL on CGM. A total of 160 patients with comparable baseline characteristics formed four equal insulin regimen cohorts. The daily glucose SD (the primary outcome) was significantly lower in the BGLP cohort versus the BO, PM, and BB cohorts (P = 0.03, P = 0.01, and P < 0.01, respectively), and remained so after adjusting for age, BMI, type 2 diabetes duration, and A1C. Similarly, daily hypoglycemia outcomes on CGM were least for the BGLP cohort. The lowest GV and lowest hypoglycemia were observed in patients using the combination of basal insulin with a GLP-1 RA, supporting the complementary glycemic action of these agents in type 2 diabetes. These observed benefits in GV and hypoglycemia may contribute to the cardiovascular outcome reduction seen with GLP-1 RA therapy and should be investigated further. © 2017 by the American Diabetes Association.

Amino group of salicylic acid exhibits enhanced inhibitory potential against insulin amyloid fibrillation with protective aptitude toward amyloid induced cytotoxicity.

PubMed

Zaman, Masihuz; Khan, Mohsin Vahid; Zakariya, Syed Mohammad; Nusrat, Saima; Meeran, Syed Mustapha; Alam, Parvez; Ajmal, Mohammad Rehan; Wahiduzzaman, Wahiduzzaman; Shahein, Yasser E; Abouelella, Amira M; Khan, Rizwan Hasan

2018-05-01

Protein misfolding and aggregation lead to amyloid generation that in turn may induce cell membrane disruption and leads to cell apoptosis. In an effort to prevent or treat amyloidogenesis, large number of studies has been paying attention on breakthrough of amyloid inhibitors. In the present work, we aim to access the effect of two drugs, that is, acetylsalicylic acid and 5-amino salicylic acid on insulin amyloids by using various biophysical, imaging, cell viability assay, and computational approaches. We established that both drugs reduce the turbidity, light scattering and fluorescence intensity of amyloid indicator dye thioflavin T. Premixing of drugs with insulin inhibited the nucleation phase and inhibitory potential was boosted by increasing the concentration of the drug. Moreover, addition of drugs at the studied concentrations attenuated the insulin fibril induced cytotoxicity in breast cancer cell line MDA-MB-231. Our results highlight the amino group of salicylic acid exhibited enhanced inhibitory effects on insulin fibrillation in comparison to acetyl group. It may be due to presence of amino group that helps it to prolong the nucleation phase with strong binding as well as disruption of aromatic and hydrophobic stacking that plays a key role in amyloid progression. © 2017 Wiley Periodicals, Inc.

Central nervous insulin resistance: a promising target in the treatment of metabolic and cognitive disorders?

PubMed

Hallschmid, M; Schultes, B

2009-11-01

Research on functions and signalling pathways of insulin has traditionally focused on peripheral tissues such as muscle, fat and liver, while the brain was commonly believed to be insensitive to the effects of this hormone secreted by pancreatic beta cells. However, since the discovery some 30 years ago that insulin receptors are ubiquitously found in the central nervous system, an ever-growing research effort has conclusively shown that circulating insulin accesses the brain, which itself does not synthesise insulin, and exerts pivotal functions in central nervous networks. As an adiposity signal reflecting the amount of body fat, insulin provides direct negative feedback to hypothalamic nuclei that control whole-body energy and glucose homeostasis. Moreover, insulin affects distinct cognitive processes, e.g. by triggering the formation of psychological memory contents. Accordingly, metabolic and cognitive disorders such as obesity, type 2 diabetes mellitus and Alzheimer's disease are associated with resistance of central nervous structures to the effects of insulin, which may derive from genetic polymorphisms as well as from long-term exposure to excess amounts of circulating insulin due to peripheral insulin resistance. Thus, overcoming central nervous insulin resistance, e.g. by pharmacological interventions, appears to be an attractive strategy in the treatment and prevention of these disorders. Enhancement of central nervous insulin signalling by administration of intranasal insulin, insulin analogues and insulin sensitisers in basic research approaches has yielded encouraging results that bode well for the successful translation of these effects into future clinical practice.

Effects of Insulin and Octreotide on Memory and Growth Hormone in Alzheimer's Disease

PubMed Central

Watson, G. Stennis; Baker, Laura D.; Cholerton, Brenna A.; Rhoads, Kristoffer W.; Merriam, George R.; Schellenberg, Gerard D.; Asthana, PhD;Sanjay; Cherrier, Monique; Craft, Suzanne

2009-01-01

Both insulin alone and the somatostatin analogue octreotide alone facilitate memory in patients with Alzheimer's disease (AD). Since octreotide inhibits endogenous insulin secretion, the cognitive effects of insulin and octreotide may not be independent. This study tested the individual and interactive effects of insulin and octreotide on memory and plasma growth hormone (GH) levels in older adults. Participants were 16 memory-impaired (AD=7, amnestic mild cognitive impairment=9; apolipoprotein E [APOE] ε4- [no ε4 alleles]=9, ε4+ [1-2 ε4 alleles]=7) and 19 cognitively-intact older adults (APOE ε4-=17, ε4+=1). On separate days, fasting participants received counterbalanced infusions of (1) insulin (1 mU·kg-1·min-1) and dextrose to maintain euglycemia, (2) octreotide (150 μg/h), (3) insulin, dextrose, and octreotide, or (4) saline. Story recall was the principal endpoint. Insulin alone facilitated delayed recall for ε4-patients, relative to ε4+ patients (P=0.0012). Furthermore, ε4- patients with higher Mattis Dementia Rating Scale (DRS) scores had greater octreotide-induced memory facilitation (P=0.0298). For healthy adults, octreotide facilitated memory (P=0.0122). Unexpectedly, hyperinsulinemia with euglycemia increased GH levels in healthy controls (P=0.0299). Thus, insulin and octreotide appear to regulate memory in older adults. APOE ε4 genotype modulates responses to insulin and octreotide. Finally, insulin may regulate GH levels during euglycemia. PMID:19625744

Characteristics Predictive for a Successful Switch from Insulin Analogue Therapy to Oral Hypoglycemic Agents in Patients with Type 2 Diabetes

PubMed Central

Kim, Gyuri; Lee, Yong-ho; Kang, Eun Seok; Cha, Bong-Soo; Lee, Hyun Chul

2016-01-01

Purpose The objective of this study was to investigate clinical and laboratory parameters that could predict which patients could maintain adequate glycemic control after switching from initial insulin therapy to oral hypoglycemic agents (OHAs) among patients with type 2 diabetes (T2D). Materials and Methods We recruited 275 patients with T2D who had been registered in 3 cohorts of initiated insulin therapy and followed up for 33 months. The participants were divided into 2 groups according to whether they switched from insulin to OHAs (Group I) or not (Group II), and Group I was further classified into 2 sub-groups: maintenance on OHAs (Group IA) or resumption of insulin (Group IB). Results Of 275 patients with insulin initiation, 63% switched to OHAs (Group I) and 37% continued insulin (Group II). Of these, 44% were in Group IA and 19% in Group IB. The lowest tertile of baseline postprandial C-peptide-to-glucose ratio (PCGR), higher insulin dose at switching to OHAs, and higher HbA1c level at 6 months after switching to OHAs were all associated with OHA failure (Group IB; p=0.001, 0.046, and 0.014, respectively). The lowest tertile of PCGR was associated with ultimate use of insulin (Group IB and Group II; p=0.029). Conclusion Higher baseline level of PCGR and lower HbA1c levels at 6 months after switching to OHAs may be strong predictors for the successful maintenance of OHAs after switching from insulin therapy in Korean patients with T2D. PMID:27593867

NASA/ESMD Analogue Mission Plans

NASA Technical Reports Server (NTRS)

Hoffman, Stephen J.

2007-01-01

A viewgraph presentation exploring Earth and its analogues is shown. The topics include: 1) ESMD Goals for the Use of Earth Analogues; 2) Stakeholders Summary; 3) Issues with Current Analogue Situation; 4) Current state of Analogues; 5) External Implementation Plan (Second Step); 6) Recent Progress in Utilizing Analogues; 7) Website Layout Example-Home Page; 8) Website Layout Example-Analogue Site; 9) Website Layout Example-Analogue Mission; 10) Objectives of ARDIG Analog Initiatives; 11) Future Plans; 12) Example: Cold-Trap Sample Return; 13) Example: Site Characterization Matrix; 14) Integrated Analogue Studies-Prerequisites for Human Exploration; and 15) Rating Scale Definitions.

Structure of the Soot Growth Region of Laminar Premixer Methane/Oxygen Flames

NASA Technical Reports Server (NTRS)

Xu, F.; Faeth, G. M.

1999-01-01

Soot is a dominant feature of hydrocarbon/air flames, affecting their reaction mechanisms and structure. As a result, soot processes affect capabilities for computational combustion as well as predictions of flame radiation and pollution emissions. Motivated by these observations, the present investigation extended past work on soot growth in laminar premixed flames, seeking to evaluate model predictions of flame structure. Xu et al. report direct measurements of soot residence times, soot concentrations, soot structure, gas temperatures and gas compositions for premixed flames similar to those studied by Harris and Weiner and Ramer et al. respectively. It was found that predictions of major stable gas species concentrations based on mechanisms of Leung and Lindstedt and Frenklach and coworkers, were in good agreement with the measurements. The results were also used to evaluate the hydrogen-abstraction/carbon-addition (HACA) soot growth mechanisms of Frenklach and coworkers and Colket and Hall. It was found that these mechanisms were effective using quite reasonable correlations for the steric factors appearing in the theories. The successful evaluation of the HACA mechanism of soot growth in Refs. 1 and 2 is encouraging but one aspect of this evaluation is a concern. In particular, H-atom concentrations play a crucial role in the HACA mechanism and it was necessary to estimate these concentrations because they were not measured directly. These estimates were made assuming local thermodynamic equilibrium between H, and H based on measured temperatures and H2 concentrations and the equilibrium constant data of Kee et al.. This approach was justified by the flame structure predictions; nevertheless, direct evaluation of equilibrium estimates of H-atom concentrations in the soot growth regions of laminar premixed flames is needed to provide more convincing proof of this behavior. Thus, the objective of the present investigation was to complete new measurements of the

Diabetic management in high risk patients (pregnancy, insulin pumps).

PubMed

Vanhaverbeke, G; Mertens, A; Mathieu, C

2004-01-01

During the past decades our understanding about the clinical impact of diabetes has changed. We now know for certain that a good (read : near normal) glycemic control is necessary to prevent chronic complications of this disease in women regardless of the type of diabetes. Pregnancy is a specific situation whereby a "near normal" control is wanted not only for the patient but also for the fetus. Several studies have shown a correlation beween glycemic control and complications of pregnancy. Reaching optimal glycemic control is mandatory even before the pregnancy starts, considering the time window of occurance of the severe foetal congenital malformations (first weeks of pregnancy). The role of pre-conception care is emphasized. Optimal control in type 1 and type 2 diabetic patients can best be reached through intensive insulin therapy, but reaching normoglycemia is mainly limited by the occurence of hypoglycemia. The introduction of the new insulin analogues is an important step in our arsenal to achieve control using multiple daily insulin injections, but Novorapid and Lantus have not yet been approved for use in pregnancy. Insulin pumps are often used in pregnant patients, allowing an even better glycemic control with less hypoglycemia. An absolute requirement for CSII therapy to be successful is patient education and motivation by an experienced team.

Clinical inertia with regard to intensifying therapy in people with type 2 diabetes treated with basal insulin.

PubMed

Khunti, K; Nikolajsen, A; Thorsted, B L; Andersen, M; Davies, M J; Paul, S K

2016-04-01

To investigate whether clinical inertia, the failure to intensify treatment regimens when required, exists in people with type 2 diabetes treated with basal insulin. This was a retrospective cohort study involving patients with type 2 diabetes in the UK Clinical Practice Research Datalink database between January 2004 and December 2011, with follow-up until December 2013. A total of 11 696 patients were included in the analysis. Among all patients, 36.5% had their treatment intensified during the study period; of these, the treatment of 50.0, 42.5 and 7.4% was intensified with bolus or premix insulin or glucagon-like peptide-1 receptor agonists, respectively. The median time from initiation of basal insulin to treatment intensification was 4.3 years [95% confidence interval (CI) 4.1, 4.6]. Among patients clinically eligible for treatment intensification [glycated haemoglobin (HbA1c) ≥7.5% (58 mmol/mol)], 30.9% had their treatment regimen intensified. The median time to intensification in this group was 3.7 years (95% CI 3.4, 4.0). Increasing age, duration of diabetes, oral antihyperglycaemic agent usage and Charlson comorbidity index score were associated with a significant delay in the time to intensification (p < 0.05). Among patients with HbA1c ≥7.5% (58 mmol/mol), 32.1% stopped basal insulin therapy. Strategies should be developed to increase the number of patients undergoing therapy intensification and to reduce the delay in intensifying therapy for suitable patients on basal insulin. Initiatives to support patients continuing on insulin are also required. © 2016 The Authors. Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd.

Interaction of turbulent premixed flames with combustion products: Role of stoichiometry

DOE Office of Scientific and Technical Information (OSTI.GOV)

Coriton, Bruno Rene Leon; Frank, Jonathan H.; Gomez, Alessandro

Stabilization methods of turbulent flames often involve mixing of reactants with hot products of combustion. The stabilizing effect of combustion product enthalpy has been long recognized, but the role played by the chemical composition of the product gases is typically overlooked. We employ a counterflow system to pinpoint the effects of the combustion product stoichiometry on the structure of turbulent premixed flames under conditions of both stable burning and local extinction. To that end, a turbulent jet of lean-to-rich, CH 4/O 2/N 2-premixed reactants at a turbulent Reynolds number of 1050 was opposed to a stream of hot products ofmore » combustion that were generated in a preburner. While the combustion product stream temperature was kept constant, its stoichiometry was varied independently from that of the reactant stream, leading to reactant-to-product stratification of relevance to practical combustion systems. The detailed structure of the turbulent flame front was analyzed in two series of experiments using laser-induced fluorescence (LIF): joint CH 2O LIF and OH LIF measurements and joint CO LIF and OH LIF measurements. Results revealed that a decrease in local CH 2O+OH and CO+OH reaction rates coincide with the depletion of OH radicals in the vicinity of the combustion product stream. These critical combustion reaction rates were more readily quenched in the presence of products of combustion from a stoichiometric flame, whereas they were favored by lean combustion products. As a result, stoichiometric combustion products contributed to a greater occurrence of local extinction. Furthermore, they limited the capacity of premixed reactants to ignite and of the turbulent premixed flames to stabilize. In contrast, lean and rich combustion products facilitated flame ignition and stability and reduced the rate of local extinction. The influence of the combustion product stream on the turbulent flame front was limited to a zone of approximately two

Interaction of turbulent premixed flames with combustion products: Role of stoichiometry

DOE PAGES

Coriton, Bruno Rene Leon; Frank, Jonathan H.; Gomez, Alessandro

2016-05-30

Stabilization methods of turbulent flames often involve mixing of reactants with hot products of combustion. The stabilizing effect of combustion product enthalpy has been long recognized, but the role played by the chemical composition of the product gases is typically overlooked. We employ a counterflow system to pinpoint the effects of the combustion product stoichiometry on the structure of turbulent premixed flames under conditions of both stable burning and local extinction. To that end, a turbulent jet of lean-to-rich, CH 4/O 2/N 2-premixed reactants at a turbulent Reynolds number of 1050 was opposed to a stream of hot products ofmore » combustion that were generated in a preburner. While the combustion product stream temperature was kept constant, its stoichiometry was varied independently from that of the reactant stream, leading to reactant-to-product stratification of relevance to practical combustion systems. The detailed structure of the turbulent flame front was analyzed in two series of experiments using laser-induced fluorescence (LIF): joint CH 2O LIF and OH LIF measurements and joint CO LIF and OH LIF measurements. Results revealed that a decrease in local CH 2O+OH and CO+OH reaction rates coincide with the depletion of OH radicals in the vicinity of the combustion product stream. These critical combustion reaction rates were more readily quenched in the presence of products of combustion from a stoichiometric flame, whereas they were favored by lean combustion products. As a result, stoichiometric combustion products contributed to a greater occurrence of local extinction. Furthermore, they limited the capacity of premixed reactants to ignite and of the turbulent premixed flames to stabilize. In contrast, lean and rich combustion products facilitated flame ignition and stability and reduced the rate of local extinction. The influence of the combustion product stream on the turbulent flame front was limited to a zone of approximately two

Insulin therapy for adult patients with type 2 diabetes mellitus: a position statement of the Korean Diabetes Association, 2017.

PubMed

Lee, Byung-Wan; Kim, Jin Hwa; Ko, Seung-Hyun; Hur, Kyu Yeon; Kim, Nan-Hee; Rhee, Sang Youl; Kim, Hyun Jin; Moon, Min Kyong; Park, Seok-O; Choi, Kyung Mook

2017-11-01

The Korean Diabetes Association (KDA) has regularly updated its Clinical Practice Guidelines. In 2017, the KDA published a position statement on the use of antihyperglycemic agents for patients with type 2 diabetes mellitus (T2DM). Growing evidence from new multinational clinical trials using novel and traditional insulin analogues has also been accumulated. Following global trends, many results of clinical trials, especially concerning the clinical efficacy and safety of insulin therapy, have been published about Korean patients with T2DM. After a systematic search of recent evidence, the KDA updated and modified its clinical practice recommendations regarding the initiation, choice, and intensification of insulin and created an insulin treatment algorithm for the first time to guide physicians caring for adult Korean patients with T2DM.

Lean, Premixed-Prevaporized (LPP) combustor conceptual design study

NASA Technical Reports Server (NTRS)

Dickman, R. A.; Dodds, W. J.; Ekstedt, E. E.

1979-01-01

Four combustion systems were designed and sized for the energy efficient engine. A fifth combustor was designed for the cycle and envelope of the twin-spool, high bypass ratio, high pressure ratio turbofan engine. Emission levels, combustion performance, life, and reliability assessments were made for these five combustion systems. Results of these design studies indicate that cruise NOx emission can be reduced by the use of lean, premixed-prevaporaized combustion and airflow modulation.

Studying the Hurdles of Insulin Prescription (SHIP©): development, scoring and initial validation of a new self-administered questionnaire

PubMed Central

Martinez, Luc; Consoli, Silla M; Monnier, Louis; Simon, Dominique; Wong, Olivier; Yomtov, Bernard; Guéron, Béatrice; Benmedjahed, Khadra; Guillemin, Isabelle; Arnould, Benoit

2007-01-01

Background Although insulin therapy is well-accepted by symptomatic diabetic patients, it is still often delayed in less severe patients, in whom injectable insulin remains under-used. A better understanding of patients' perception of insulin would eventually help physicians to adopt the most appropriate dialogue when having to motivate patients to initiate or to intensify insulin injection. Methods The 'Studying the Hurdles of Insulin Prescription' (SHIP) questionnaire was developed based on a list of concepts derived from three diabetic patients' focus groups, and was included into two cross-sectional studies with similar design: SHIP Oral study and SHIP Premix study. Diabetic patients treated with oral hypoglycaemic agents (OHA; n = 1,494) and patients already treated with insulin (n = 1,150) completed the questionnaire at baseline, 6- and 12 months. Psychometric properties were assessed: 1) structure analysis by Principal Component Analysis (PCA) with Varimax rotation, 2) internal consistency reliability (Cronbach's alpha), and 3) concurrent validity (Spearman correlation coefficients with the Fear of Self-Injecting (FSI) score of the Diabetes Fear of Injecting and Self-testing Questionnaire. Reluctance/motivation towards insulin was assessed. Scores' ability to predict patients' insulin injection reluctance/motivation and initiation/intensification was evaluated with the Area Under the Receiver Operating Characteristic (ROC) Curve (AUC). Results PCA analysis confirmed the structure of the 14 items grouped into 3 dimensions: 'acceptance and motivation', 'fear and constraints', and 'restraints and barriers' towards insulin injection. Internal consistency reliability was excellent (Cronbach's alpha > 0.70); concurrent validity was good. The three scores were significantly predictive of patients' reluctance/motivation towards insulin injection initiation, as they were of patients' actual switch, except for the 'restraints and barriers' dimension. 'Acceptance and

The effect of stratification on premixed swirl-flame flashback by using porous center-body injection

NASA Astrophysics Data System (ADS)

McCaslin, Andrew; Ranjan, Rakesh; Clemens, Noel

2016-11-01

Boundary layer flashback must be prevented in order to stably operate stationary gas turbines. One strategy to avoid flashback is to create equivalence-ratio stratification, such as by reducing the fuel/air ratio in the boundary layer below the flammability limit. Typically, stratification is achieved by using radially non-uniform fuel injection. The goal of the current study is to reduce the propensity of flashback in a premixed annular swirl combustor that uses a premix section with center-body. A porous metal center-body (10 micron pore size) is used to bleed air directly into the boundary layer and thus locally reduce the equivalence ratio. Planar laser-induced fluorescence imaging of anisole-seeded flow is carried out to assess the stratification in the flow. Time-resolved PIV and chemiluminescence imaging are used to investigate flashback at atmospheric pressure conditions. A comparative study between fully premixed and stratified flame flashback is conducted to determine how stratification influences flashback physics. This work was sponsored by the DOE NETL under Grant DEFC2611-FE0007107. This source of funding is gratefully acknowledged.

Pdf modeling for premixed turbulent combustion based on the properties of iso-concentration surfaces

NASA Technical Reports Server (NTRS)

Vervisch, L.; Kollmann, W.; Bray, K. N. C.; Mantel, T.

1994-01-01

In premixed turbulent flames the presence of intense mixing zones located in front of and behind the flame surface leads to a requirement to study the behavior of iso-concentration surfaces defined for all values of the progress variable (equal to unity in burnt gases and to zero in fresh mixtures). To support this study, some theoretical and mathematical tools devoted to level surfaces are first developed. Then a database of direct numerical simulations of turbulent premixed flames is generated and used to investigate the internal structure of the flame brush, and a new pdf model based on the properties of iso-surfaces is proposed.

Effects of Buoyancy on Laminar and Turbulent Premixed V-Flame

NASA Technical Reports Server (NTRS)

Cheng, Robert K.; Bedat, Benoit

1997-01-01

Turbulent combustion occurs naturally in almost all combustion systems and involves complex dynamic coupling of chemical and fluid mechanical processes. It is considered as one of the most challenging combustion research problems today. Though buoyancy has little effect on power generating systems operating under high pressures (e.g., IC engines and turbines), flames in atmospheric burners and the operation of small to medium furnaces and boilers are profoundly affected by buoyancy. Changes in burner orientation impacts on their blow-off, flash-back and extinction limits, and their range of operation, burning rate, heat transfer, and emissions. Theoretically, buoyancy is often neglected in turbulent combustion models. Yet the modeling results are routinely compared with experiments of open laboratory flames that are obviously affected by buoyancy. This inconsistency is an obstacle to reconciling experiments and theories. Consequently, a fundamental understanding of the coupling between turbulent flames and buoyancy is significant to both turbulent combustion science and applications. The overall effect of buoyancy relates to the dynamic interaction between the flame and its surrounding, i.e., the so-called elliptical problem. The overall flame shape, its flowfield, stability, and mean and local burning rates are dictated by both upstream and downstream boundary conditions. In steady propagating premixed flames, buoyancy affects the products region downstream of the flame zone. These effects are manifested upstream through the mean and fluctuating pressure fields to influence flame stretch and flame wrinkling. Intuitively, the effects buoyancy should diminish with increasing flow momentum. This is the justification for excluding buoyancy in turbulent combustion models that treats high Reynolds number flows. The objectives of our experimental research program is to elucidate flame-buoyancy coupling processes in laminar and turbulent premixed flames, and to

Premixed direct injection disk

DOEpatents

York, William David; Ziminsky, Willy Steve; Johnson, Thomas Edward; Lacy, Benjamin; Zuo, Baifang; Uhm, Jong Ho

2013-04-23

A fuel/air mixing disk for use in a fuel/air mixing combustor assembly is provided. The disk includes a first face, a second face, and at least one fuel plenum disposed therebetween. A plurality of fuel/air mixing tubes extend through the pre-mixing disk, each mixing tube including an outer tube wall extending axially along a tube axis and in fluid communication with the at least one fuel plenum. At least a portion of the plurality of fuel/air mixing tubes further includes at least one fuel injection hole have a fuel injection hole diameter extending through said outer tube wall, the fuel injection hole having an injection angle relative to the tube axis. The invention provides good fuel air mixing with low combustion generated NOx and low flow pressure loss translating to a high gas turbine efficiency, that is durable, and resistant to flame holding and flash back.

Coupling between premixed flame propagation and swirl flow during boundary layer flashback

NASA Astrophysics Data System (ADS)

Ebi, Dominik; Ranjan, Rakesh; Clemens, Noel T.

2018-07-01

Flashback of premixed methane-air flames in the turbulent boundary layer of swirling flows is investigated experimentally. The premix section of the atmospheric model swirl combustor features an axial swirler with an attached center-body. Our previous work with this same configuration investigated the flame propagation during flashback using particle image velocimetry (PIV) with liquid droplets as seed particles that precluded making measurements in the burnt gases. The present study investigates the transient velocity field in the unburnt and burnt gas region by means of solid-particle seeding and high-speed stereoscopic PIV. The global axial and circumferential lab-frame flame propagation speed is obtained simultaneously based on high-speed chemiluminescence movies. By combining the PIV data with the global flame propagation speed, the quasi-instantaneous swirling motion of the velocity field is constructed on annular shells, which provides a more intuitive view on the complex three-dimensional flow-flame interaction. Previous works showed that flashback is led by flame tongues. We find that the important flow-flame interaction occurs on the far side of these flame tongues relative to the approach flow, which we henceforth refer to as the leading side. The leading side is found to propagate as a classical premixed flame front relative to the strongly modified approach flow field. The blockage imposed by flame tongues is not limited to the immediate vicinity of the flame base, but occurs along the entire leading side.

Field Effects of Buoyancy on Lean Premixed Turbulent Flames

NASA Technical Reports Server (NTRS)

Cheng, R. K.; Johnson, M. R.; Greenberg, P. S.; Wernet, M. P.

2003-01-01

The study of field effects of buoyancy on premixed turbulent flames is directed towards the advancement of turbulent combustion theory and the development of cleaner combustion technologies. Turbulent combustion is considered the most important unsolved problem in combustion science and laboratory studies of turbulence flame processes are vital to theoretical development. Although buoyancy is dominant in laboratory flames, most combustion models are not yet capable to consider buoyancy effects. This inconsistency has impeded the validation of theories and numerical simulations with experiments. Conversely, the understanding of buoyancy effects is far too limited to help develop buoyant flame models. Our research is also relevant to combustion technology because lean premixed combustion is a proven method to reduce the formation of oxides of nitrogen (NOx). In industrial lean premixed combustion systems, their operating conditions make them susceptible to buoyancy thus affecting heat distribution, emissions, stability, flashback and blowoff. But little knowledge is available to guide combustion engineers as to how to avoid or overcome these problems. Our hypothesis is that through its influence on the mean pressure field, buoyancy has direct and indirect effects on local flame/turbulence interactions. Although buoyancy acts on the hot products in the farfield the effect is also felt in the nearfield region upstream of the flame. These changes also influence the generation and dissipation of turbulent kinetic energy inside the flame brush and throughout the flowfield. Moreover, the plume of an open flame is unstable and the periodic fluctuations make additional contributions to flame front dynamics in the farfield. Therefore, processes such as flame wrinkling, flow acceleration due to heat release and flame- generated vorticity are all affected. Other global flame properties (e.g. flame stabilization limits and flame speed) may all be coupled to buoyancy. This

PREMIXED FLAME PROPAGATION AND MORPHOLOGY IN A CONSTANT VOLUME COMBUSTION CHAMBER

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hariharan, A; Wichman, IS

2014-06-04

This work presents an experimental and numerical investigation of premixed flame propagation in a constant volume rectangular channel with an aspect ratio of six (6) that serves as a combustion chamber. Ignition is followed by an accelerating cusped finger-shaped flame-front. A deceleration of the flame is followed by the formation of a "tulip"-shaped flame-front. Eventually, the flame is extinguished when it collides with the cold wall on the opposite channel end. Numerical computations are performed to understand the influence of pressure waves, instabilities, and flow field effects causing changes to the flame structure and morphology. The transient 2D numerical simulationmore » results are compared with transient 3D experimental results. Issues discussed are the appearance of oscillatory motions along the flame front and the influences of gravity on flame structure. An explanation is provided for the formation of the "tulip" shape of the premixed flame front.« less

Insulin Glulisine in Pregnancy - Experience from Clinical Trials and Post-marketing Surveillance.

PubMed

Doder, Zoran; Vanechanos, Demi; Oster, Manfred; Landgraf, Wolfgang; Lin, Stephen

2015-04-01

Pregnancies complicated by gestational diabetes or pre-existing type 1 or type 2 diabetes mellitus are associated with a higher rate of adverse outcomes compared with pregnancies in the background population. These outcomes include miscarriage, pre-term delivery, pre-eclampsia, perinatal mortality and congenital malformations. Insulin glulisine (Apidra ® , Sanofi) is a rapid-acting insulin analogue indicated for the treatment of adults, adolescents and children 6 years or older with diabetes mellitus where treatment with insulin is required. Here, all post-marketing and clinical trials safety data with insulin glulisine in pregnancy available to Sanofi up to June 2014 are summarised together with the findings of a comprehensive literature search. Cumulatively, a total of 303 pregnancy exposures to insulin glulisine were received. Of these 303 pregnancy exposures, there were 116 live births, 12 spontaneous abortions, two late foetal intra-uterine deaths (>28 weeks), three elective abortions and 170 cases without a known pregnancy outcome. There were six cases of congenital malformations; of these, there were five live births; in the other case a live birth was not confirmed. The congenital malformations reported to date do not reveal a pattern of defects. In conclusion, the evidence to date does not suggest a causal association between insulin glulisine and an increased risk of pregnancy complications or congenital malformations.

Criteria Development for Gas Turbine Premixer Flameholding Tendencies of Natural Gas and High Hydrogen Content Fuels

NASA Astrophysics Data System (ADS)

Sullivan-Lewis, Elliot Gregory

Due to increasingly stringent air quality requirements, stationary power gas turbines have moved to lean-premixed operation, which reduces pollutant emissions but can result in flashback. Flashback can cause serious damage to the premixer hardware. Curtailing flashback can be difficult with hydrocarbon fuels and becomes even more challenging when the fuel contains hydrogen. The two main approaches for coping with flashback are either to design a combustor that is resistant to flashback, or to design a premixer that will not anchor a flame if flashback occurs. Even with a well-designed combustor, flashback can occur under certain circumstances. Thus it is necessary to determine how to avoid flameholding within the premixer passageways of a gas turbine. To this end, an experiment was designed that would determine the flameholding propensities at elevated pressures and temperatures of three different classes of geometric features commonly found in gas turbine premixers, with both natural gas and hydrogen containing fuel. Experiments to find the equivalence ratio at blow off were conducted within an optically accessible test apparatus with four flameholders: 0.25 and 0.50 inch diameter cylinders, a reverse facing step with a height of 0.25 inches, and a symmetric airfoil with a thickness of 0.25 inches and a chord length of one inch. Tests were carried out at temperatures between 300 K and 750 K, at pressures up to 9 atmospheres. Typical bulk velocities were between 40 and 100 m/s. The effect of the airfoil's angle of rotation was also investigated. Blow off for hydrogen reactions was found to occur at much lower adiabatic flame temperatures than natural gas reactions. Additionally it was observed that at high pressures and high turbulence intensities, reactant velocity does not have a noticeable effect on the point of blow off due in large part to corresponding increases in turbulent flame speed. Finally a semi empirical correlation was developed that predicts flame

Soot Formation in Laminar Premixed Methane/Oxygen Flames at Atmospheric Pressure. Appendix H

NASA Technical Reports Server (NTRS)

Xu, F.; Lin, K.-C.; Faeth, G. M.; Urban, D. L. (Technical Monitor); Yuan, Z.-G. (Technical Monitor)

2001-01-01

Flame structure and soot formation were studied within soot-containing laminar premixed methanefoxygen flames at atmospheric pressure. The following measurements were made: soot volume fractions by laser extinction, soot temperatures by multiline emission, gas temperatures (where soot was absent) by corrected fine-wire thermocouples, soot structure by thermophoretic sampling and transmission electron microscope (TEM), major gas species concentrations by sampling and gas chromatography, and gas velocities by laser velocimetry. Present measurements of gas species concentrations were in reasonably good agreement with earlier measurements due to Ramer et al. as well as predictions based on the detailed mechanisms of Frenklach and co-workers and Leung and Lindstedt; the predictions also suggest that H atom concentrations are in local thermodynamic equilibrium throughout the soot formation region. Using this information, it was found that measured soot surface growth rates could be correlated successfully by predictions based on the hydrogenabstraction/carbon-addition (HACA) mechanisms of both Frenklach and co-workers and Colket and Hall, extending an earlier assessment of these mechanisms for premixed ethylene/air flames to conditions having larger H/C ratios and acetylene concentrations. Measured primary soot particle nucleation rates were somewhat lower than the earlier observations for laminar premixed ethylene/air flames and were significantly lower than corresponding rates in laminar diffusion flames, for reasons that still must be explained.

Insulin Therapy for Adult Patients with Type 2 Diabetes Mellitus: A Position Statement of the Korean Diabetes Association, 2017.

PubMed

Lee, Byung Wan; Kim, Jin Hwa; Ko, Seung Hyun; Hur, Kyu Yeon; Kim, Nan Hee; Rhee, Sang Youl; Kim, Hyun Jin; Moon, Min Kyong; Park, Seok O; Choi, Kyung Mook

2017-10-01

The Korean Diabetes Association (KDA) has regularly updated its Clinical Practice Guidelines. In 2017, the KDA published a position statement on the use of antihyperglycemic agents for patients with type 2 diabetes mellitus (T2DM). Growing evidence from new multinational clinical trials using novel and traditional insulin analogues has also been accumulated. Following global trends, many results of clinical trials, especially concerning the clinical efficacy and safety of insulin therapy, have been published about Korean patients with T2DM. After a systematic search of recent evidence, the KDA updated and modified its clinical practice recommendations regarding the initiation, choice, and intensification of insulin and created an insulin treatment algorithm for the first time to guide physicians caring for adult Korean patients with T2DM. Copyright © 2017 Korean Diabetes Association.

Management of type-1 and type-2 diabetes by insulin injections in diabetology clinics - a scientific research review.

PubMed

Aziz, Kamran M A

2012-05-01

Better control of the diabetic metabolic state will prevent the diabetes complications. However in current clinical practice, it is sometimes difficult to achieve this goal. Additionally, physicians find themselves in an equivocal position to initiate insulin therapy, its selection, combining with Oral agents and further management. The current article was written to focus on diabetes pathogenesis at molecular level, its classification and management by insulin injections. Knowledge of basic biochemistry, pharmacology with kinetics of Insulin is essential for diabetes management. Nonetheless, it should be a priority to search for evidence based clinical methodologies for selecting the patients for initiating, modifying or combining the insulin therapy. Type-1 diabetic patients are best controlled on basal bolus insulin regimens. However in type-2 diabetes, metformin with lifestyle modifications should be the first line therapy, thereafter combined with oral hypoglycemic agents or shifting to insulin gradually if diabetes remains uncontrolled. Metformin is recommended to be prescribed with insulin as compared to oral hypoglycemic agents which should be discontinued while starting insulin. Monitoring the insulin therapy on regular visits to diabetologist and diabetes multidisciplinary team remains the integral part of diabetes management. The review also outlines relevant and recent insulin analogue patents for the management of Diabetes.

Response mechanisms of attached premixed flames subjected to harmonic forcing

NASA Astrophysics Data System (ADS)

Shreekrishna

The persistent thrust for a cleaner, greener environment has prompted air pollution regulations to be enforced with increased stringency by environmental protection bodies all over the world. This has prompted gas turbine manufacturers to move from nonpremixed combustion to lean, premixed combustion. These lean premixed combustors operate quite fuel-lean compared to the stochiometric, in order to minimize CO and NOx productions, and are very susceptible to oscillations in any of the upstream flow variables. These oscillations cause the heat release rate of the flame to oscillate, which can engage one or more acoustic modes of the combustor or gas turbine components, and under certain conditions, lead to limit cycle oscillations. This phenomenon, called thermoacoustic instabilities, is characterized by very high pressure oscillations and increased heat fluxes at system walls, and can cause significant problems in the routine operability of these combustors, not to mention the occasional hardware damages that could occur, all of which cumulatively cost several millions of dollars. In a bid towards understanding this flow-flame interaction, this research works studies the heat release response of premixed flames to oscillations in reactant equivalence ratio, reactant velocity and pressure, under conditions where the flame preheat zone is convectively compact to these disturbances, using the G-equation. The heat release response is quantified by means of the flame transfer function and together with combustor acoustics, forms a critical component of the analytical models that can predict combustor dynamics. To this end, low excitation amplitude (linear) and high excitation amplitude (nonlinear) responses of the flame are studied in this work. The linear heat release response of lean, premixed flames are seen to be dominated by responses to velocity and equivalence ratio fluctuations at low frequencies, and to pressure fluctuations at high frequencies which are in the

DNS of turbulent premixed slot flames with mixture inhomogeneity: a study of NOx formation

NASA Astrophysics Data System (ADS)

Luca, Stefano; Attili, Antonio; Bisetti, Fabrizio

2016-11-01

A set of Direct Numerical Simulations of three-dimensional methane/air lean flames in a spatially developing turbulent slot burner are performed. The flames are in the thin-reaction zone regimes and the jet Reynolds number is 5600. This configuration is of interest since it displays turbulent production by mean shear as in real devices. The gas phase hydrodynamics are modeled with the reactive, unsteady Navier-Stokes equations in the low Mach number limit. Combustion is treated with finite-rate chemistry. The jet is characterized by a non-uniform equivalence ratio at the inlet and varying levels of incomplete premixing for the methane/air mixture are considered. The global equivalence ratio is 0.7 and temperature is 800 K. All simulations are performed at 4 atm. The instantaneous profiles of the mass fractions of methane and air at the inlet are sampled from a set of turbulent channel simulations that provide realistic, fully turbulent fields. The data are analyzed to study the influence of partial premixing on the flame structure. Particular focus is devoted to the assessment of heat release rate fluctuations and NOx formation. In particular, the effects of partial premixing on the production rates for the various pathways to NOx formation are investigated.

21 CFR 170.60 - Nitrites and/or nitrates in curing premixes.

Code of Federal Regulations, 2014 CFR

2014-04-01

... 21 Food and Drugs 3 2014-04-01 2014-04-01 false Nitrites and/or nitrates in curing premixes. 170... guanylate, hydrolysates of animal or plant origin (such as hydrolyzed vegetable protein), oleoresins of... of an authorizing food additive regulation. A food additive petition submitted pursuant to §§ 171.1...

Insulin Glulisine in Pregnancy – Experience from Clinical Trials and Post-marketing Surveillance

PubMed Central

Vanechanos, Demi; Oster, Manfred; Landgraf, Wolfgang; Lin, Stephen

2015-01-01

Abstract Pregnancies complicated by gestational diabetes or pre-existing type 1 or type 2 diabetes mellitus are associated with a higher rate of adverse outcomes compared with pregnancies in the background population. These outcomes include miscarriage, pre-term delivery, pre-eclampsia, perinatal mortality and congenital malformations. Insulin glulisine (Apidra®, Sanofi) is a rapid-acting insulin analogue indicated for the treatment of adults, adolescents and children 6 years or older with diabetes mellitus where treatment with insulin is required. Here, all post-marketing and clinical trials safety data with insulin glulisine in pregnancy available to Sanofi up to June 2014 are summarised together with the findings of a comprehensive literature search. Cumulatively, a total of 303 pregnancy exposures to insulin glulisine were received. Of these 303 pregnancy exposures, there were 116 live births, 12 spontaneous abortions, two late foetal intra-uterine deaths (>28 weeks), three elective abortions and 170 cases without a known pregnancy outcome. There were six cases of congenital malformations; of these, there were five live births; in the other case a live birth was not confirmed. The congenital malformations reported to date do not reveal a pattern of defects. In conclusion, the evidence to date does not suggest a causal association between insulin glulisine and an increased risk of pregnancy complications or congenital malformations. PMID:29632561

Humanin: A Novel Central Regulator of Peripheral Insulin Action

PubMed Central

Muzumdar, Radhika H.; Huffman, Derek M.; Atzmon, Gil; Buettner, Christoph; Cobb, Laura J.; Fishman, Sigal; Budagov, Temuri; Cui, Lingguang; Einstein, Francine H.; Poduval, Aruna; Hwang, David; Barzilai, Nir; Cohen, Pinchas

2009-01-01

Background Decline in insulin action is a metabolic feature of aging and is involved in the development of age-related diseases including Type 2 Diabetes Mellitus (T2DM) and Alzheimer's disease (AD). A novel mitochondria-associated peptide, Humanin (HN), has a neuroprotective role against AD-related neurotoxicity. Considering the association between insulin resistance and AD, we investigated if HN influences insulin sensitivity. Methods and Findings Using state of the art clamp technology, we examined the role of central and peripheral HN on insulin action. Continuous infusion of HN intra-cerebro-ventricularly significantly improved overall insulin sensitivity. The central effects of HN on insulin action were associated with activation of hypothalamic STAT-3 signaling; effects that were negated by co-inhibition of hypothalamic STAT-3. Peripheral intravenous infusions of novel and potent HN derivatives reproduced the insulin-sensitizing effects of central HN. Inhibition of hypothalamic STAT-3 completely negated the effects of IV HN analog on liver, suggesting that the hepatic actions of HN are centrally mediated. This is consistent with the lack of a direct effect of HN on primary hepatocytes. Furthermore, single treatment with a highly-potent HN analog significantly lowered blood glucose in Zucker diabetic fatty rats. Based upon the link of HN with two age-related diseases, we examined if there were age associated changes in HN levels. Indeed, the amount of detectable HN in hypothalamus, skeletal muscle, and cortex was decreased with age in rodents, and circulating levels of HN were decreased with age in humans and mice. Conclusions We conclude that the decline in HN with age could play a role in the pathogenesis of age-related diseases including AD and T2DM. HN represents a novel link between T2DM and neurodegeneration and along with its analogues offers a potential therapeutic tool to improve insulin action and treat T2DM. PMID:19623253

A high-pressure premixed flat-flame burner for chemical process studies. [of pollutant formation in hydrocarbon flames

NASA Technical Reports Server (NTRS)

Miller, I. M.

1978-01-01

A premixed flat-flame burner was designed and tested with methane-air mixtures at pressures from 1.1 to 20 atm and equivalence ratios from 0.7 to 1.1. Reactant velocity in the burner mixing chamber was used to characterize the range of stable flames at each pressure-equivalence-ratio condition. Color photographs of the flames were used to determine flame zone thickness and flame height. The results show that this burner can be used for chemical process studies in premixed high pressure methane-air flames up to 20 atm.

Velocity and Reactive Scalar Dissipation Spectra in Turbulent Premixed Flames

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kolla, Hemanth; Zhao, Xin-Yu; Chen, Jacqueline H.

Dissipation spectra of velocity and reactive scalars—temperature and fuel mass fraction—in turbulent premixed flames are studied using direct numerical simulation data of a temporally evolving lean hydrogen-air premixed planar jet (PTJ) flame and a statistically stationary planar lean methane-air (SP) flame. Furthermore, the equivalence ratio in both cases was 0.7, the pressure 1 atm while the unburned temperature was 700 K for the hydrogen-air PTJ case and 300 K for methane-air SP case, that resulted in data sets with a density ratio of 3 and 5, respectively. The turbulent Reynolds numbers for the cases ranged from 200 to 428.4, themore » Damköhler number from 3.1 to 29.1, and the Karlovitz number from 0.1 to 4.5. The dissipation spectra collapse when normalized by the respective Favre-averaged dissipation rates. But, the normalized dissipation spectra in all the cases deviate noticeably from those predicted by classical scaling laws for constant-density turbulent flows and bear a clear influence of the chemical reactions on the dissipative range of the energy cascade.« less

Velocity and Reactive Scalar Dissipation Spectra in Turbulent Premixed Flames

DOE PAGES

Kolla, Hemanth; Zhao, Xin-Yu; Chen, Jacqueline H.; ...

2016-06-09

Dissipation spectra of velocity and reactive scalars—temperature and fuel mass fraction—in turbulent premixed flames are studied using direct numerical simulation data of a temporally evolving lean hydrogen-air premixed planar jet (PTJ) flame and a statistically stationary planar lean methane-air (SP) flame. Furthermore, the equivalence ratio in both cases was 0.7, the pressure 1 atm while the unburned temperature was 700 K for the hydrogen-air PTJ case and 300 K for methane-air SP case, that resulted in data sets with a density ratio of 3 and 5, respectively. The turbulent Reynolds numbers for the cases ranged from 200 to 428.4, themore » Damköhler number from 3.1 to 29.1, and the Karlovitz number from 0.1 to 4.5. The dissipation spectra collapse when normalized by the respective Favre-averaged dissipation rates. But, the normalized dissipation spectra in all the cases deviate noticeably from those predicted by classical scaling laws for constant-density turbulent flows and bear a clear influence of the chemical reactions on the dissipative range of the energy cascade.« less

[Dmt(1)]DALDA analogues modified with tyrosine analogues at position 1.

PubMed

Cai, Yunxin; Lu, Dandan; Chen, Zhen; Ding, Yi; Chung, Nga N; Li, Tingyou; Schiller, Peter W

2016-08-01

Analogues of [Dmt(1)]DALDA (H-Dmt-d-Arg-Phe-Lys-NH2; Dmt=2',6'-dimethyltyrosine), a potent μ opioid agonist peptide with mitochondria-targeted antioxidant activity were prepared by replacing Dmt with various 2',6'-dialkylated Tyr analogues, including 2',4',6'-trimethyltyrosine (Tmt), 2'-ethyl-6'-methyltyrosine (Emt), 2'-isopropyl-6'-methyltyrosine (Imt) and 2',6'-diethyltyrosine (Det). All compounds were selective μ opioid agonists and the Tmt(1)-, Emt(1) and Det(1)-analogues showed subnanomolar μ opioid receptor binding affinities. The Tmt(1)- and Emt(1)-analogues showed improved antioxidant activity compared to the Dmt(1)-parent peptide in the DPPH radical-scavenging capacity assay, and thus are of interest as drug candidates for neuropathic pain treatment. Copyright © 2016 Elsevier Ltd. All rights reserved.

The somatostatin analogue octreotide confers sensitivity to rapamycin treatment on pituitary tumor cells.

PubMed

Cerovac, Vesna; Monteserin-Garcia, Jose; Rubinfeld, Hadara; Buchfelder, Michael; Losa, Marco; Florio, Tullio; Paez-Pereda, Marcelo; Stalla, Günter K; Theodoropoulou, Marily

2010-01-15

Rapamycin and its analogues have significant antiproliferative action against a variety of tumors. However, sensitivity to rapamycin is reduced by Akt activation that results from the ablative effects of rapamycin on a p70 S6K-induced negative feedback loop that blunts phosphoinositide 3-kinase (PI3K)-mediated support for Akt activity. Thus, sensitivity to rapamycin might be increased by imposing an upstream blockade to the PI3K/Akt pathway. Here, we investigated this model using the somatostatin analogue octreotide as a tool to decrease levels of activated Ser(473)-phosphorylated Akt (pAkt-Ser(473)) in pituitary tumor cells that express somatostatin receptors. Octreotide increased levels of phosphorylated insulin receptor substrate-1 that were suppressed by rapamycin, subsequently decreasing levels of pAkt-Ser(473) through effects on phosphotyrosine phosphatase SHP-1. Octreotide potentiated the antiproliferative effects of rapamycin in immortalized pituitary tumor cells or human nonfunctioning pituitary adenoma cells in primary cell culture, sensitizing tumor cells even to low rapamycin concentrations. Combined treatment of octreotide and rapamycin triggered G(1) cell cycle arrest, decreasing E2F transcriptional activity and cyclin E levels by increasing levels of p27/Kip1. These findings show that adjuvant treatment with a somatostatin analogue can sensitize pituitary tumor cells to the antiproliferative effects of rapamycin.

DNS and modeling of the interaction between turbulent premixed flames and walls

NASA Technical Reports Server (NTRS)

Poinsot, T. J.; Haworth, D. C.

1992-01-01

The interaction between turbulent premixed flames and walls is studied using a two-dimensional full Navier-Stokes solver with simple chemistry. The effects of wall distance on the local and global flame structure are investigated. Quenching distances and maximum wall heat fluxes during quenching are computed in laminar cases and are found to be comparable to experimental and analytical results. For turbulent cases, it is shown that quenching distances and maximum heat fluxes remain of the same order as for laminar flames. Based on simulation results, a 'law-of-the-wall' model is derived to describe the interaction between a turbulent premixed flame and a wall. This model is constructed to provide reasonable behavior of flame surface density near a wall under the assumption that flame-wall interaction takes place at scales smaller than the computational mesh. It can be implemented in conjunction with any of several recent flamelet models based on a modeled surface density equation, with no additional constraints on mesh size or time step.

Inadequacy representation of flamelet-based RANS model for turbulent non-premixed flame

NASA Astrophysics Data System (ADS)

Lee, Myoungkyu; Oliver, Todd; Moser, Robert

2017-11-01

Stochastic representations for model inadequacy in RANS-based models of non-premixed jet flames are developed and explored. Flamelet-based RANS models are attractive for engineering applications relative to higher-fidelity methods because of their low computational costs. However, the various assumptions inherent in such models introduce errors that can significantly affect the accuracy of computed quantities of interest. In this work, we develop an approach to represent the model inadequacy of the flamelet-based RANS model. In particular, we pose a physics-based, stochastic PDE for the triple correlation of the mixture fraction. This additional uncertain state variable is then used to construct perturbations of the PDF for the instantaneous mixture fraction, which is used to obtain an uncertain perturbation of the flame temperature. A hydrogen-air non-premixed jet flame is used to demonstrate the representation of the inadequacy of the flamelet-based RANS model. This work was supported by DARPA-EQUiPS(Enabling Quantification of Uncertainty in Physical Systems) program.

Flame Structure and Dynamics for an Array of Premixed Methane-Air Jets

NASA Astrophysics Data System (ADS)

Nigam, Siddharth P.; Lapointe, Caelan; Christopher, Jason D.; Wimer, Nicholas T.; Hayden, Torrey R. S.; Rieker, Gregory B.; Hamlington, Peter E.

2017-11-01

Premixed flames have been studied extensively, both experimentally and computationally, and their properties are reasonably well characterized for a range of conditions and configurations. However, the premixed combustion process is potentially much more difficult to predict when many such flames are arranged in a closely spaced array. These arrays must be better understood, in particular, for the design of industrial burners used in chemical and heat treatment processes. Here, the effects of geometric array parameters (e.g., angle and diameter of jet inlets, number of inlets and their respective orientation) and operating conditions (e.g., jet velocities, fuel-air ratio) on flame structure and dynamics are studied using large eddy simulations (LES). The simulations are performed in OpenFOAM using multi-step chemistry for a methane-air mixture, and temperature and chemical composition fields are characterized for a variety of configurations as functions of height above the array. Implications of these results for the design and operation of industrial burners are outlined.

Embedded computer controlled premixing inline injection system for air-assisted variable-rate sprayers

USDA-ARS?s Scientific Manuscript database

Improvements to reduce chemical waste and environmental pollution for variable-rate sprayers used in orchards and ornamental nurseries require inline injection techniques. A microprocessor controlled premixing inline injection system implementing a ceramic piston chemical metering pump and two small...

Is the current standard of care leading to cost-effective outcomes for patients with type 2 diabetes requiring insulin? A long-term health economic analysis for the UK.

PubMed

Valentine, W J; Curtis, B H; Pollock, R F; Van Brunt, K; Paczkowski, R; Brändle, M; Boye, K S; Kendall, D M

2015-07-01

The aim of the analysis was to investigate whether insulin intensification, based on the use of intensive insulin regimens as recommended by the current standard of care in routine clinical practice, would be cost-effective for patients with type 2 diabetes in the UK. Clinical data were derived from a retrospective analysis of 3185 patients with type 2 diabetes on basal insulin in The Health Improvement Network (THIN) general practice database. In total, 48% (614 patients) intensified insulin therapy, defined by adding bolus or premix insulin to a basal regimen, which was associated with a reduction in HbA1c and an increase in body mass index. Projections of clinical outcomes and costs (2011 GBP) over patients' lifetimes were made using a recently validated type 2 diabetes model. Immediate insulin intensification was associated with improvements in life expectancy, quality-adjusted life expectancy and time to onset of complications versus no intensification or delaying intensification by 2, 4, 6, or 8 years. Direct costs were higher with the insulin intensification strategy (due to the acquisition costs of insulin). Incremental cost-effectiveness ratios for insulin intensification were GBP 32,560, GBP 35,187, GBP 40,006, GBP 48,187 and GBP 55,431 per QALY gained versus delaying intensification 2, 4, 6 and 8 years, and no intensification, respectively. Although associated with improved clinical outcomes, insulin intensification as practiced in the UK has a relatively high cost per QALY and may not lead to cost-effective outcomes for patients with type 2 diabetes as currently defined by UK cost-effectiveness thresholds. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Growth hormone, IGF-I and insulin and their abuse in sport

PubMed Central

Holt, R I G; Sönksen, P H

2008-01-01

There is widespread anecdotal evidence that growth hormone (GH) is used by athletes for its anabolic and lipolytic properties. Although there is little evidence that GH improves performance in young healthy adults, randomized controlled studies carried out so far are inadequately designed to demonstrate this, not least because GH is often abused in combination with anabolic steroids and insulin. Some of the anabolic actions of GH are mediated through the generation of insulin-like growth factor-I (IGF-I), and it is believed that this is also being abused. Athletes are exposing themselves to potential harm by self-administering large doses of GH, IGF-I and insulin. The effects of excess GH are exemplified by acromegaly. IGF-I may mediate and cause some of these changes, but in addition, IGF-I may lead to profound hypoglycaemia, as indeed can insulin. Although GH is on the World Anti-doping Agency list of banned substances, the detection of abuse with GH is challenging. Two approaches have been developed to detect GH abuse. The first is based on an assessment of the effect of exogenous recombinant human GH on pituitary GH isoforms and the second is based on the measurement of markers of GH action. As a result, GH abuse can be detected with reasonable sensitivity and specificity. Testing for IGF-I and insulin is in its infancy, but the measurement of markers of GH action may also detect IGF-I usage, while urine mass spectroscopy has begun to identify the use of insulin analogues. PMID:18376417

Application of near-infrared spectroscopy in the detection of fat-soluble vitamins in premix feed

NASA Astrophysics Data System (ADS)

Jia, Lian Ping; Tian, Shu Li; Zheng, Xue Cong; Jiao, Peng; Jiang, Xun Peng

2018-02-01

Vitamin is the organic compound and necessary for animal physiological maintenance. The rapid determination of the content of different vitamins in premix feed can help to achieve accurate diets and efficient feeding. Compared with high-performance liquid chromatography and other wet chemical methods, near-infrared spectroscopy is a fast, non-destructive, non-polluting method. 168 samples of premix feed were collected and the contents of vitamin A, vitamin E and vitamin D3 were detected by the standard method. The near-infrared spectra of samples ranging from 10 000 to 4 000 cm-1 were obtained. Partial least squares regression (PLSR) and support vector machine regression (SVMR) were used to construct the quantitative model. The results showed that the RMSEP of PLSR model of vitamin A, vitamin E and vitamin D3 were 0.43×107 IU/kg, 0.09×105 IU/kg and 0.17×107 IU/kg, respectively. The RMSEP of SVMR model was 0.45×107 IU/kg, 0.11×105 IU/kg and 0.18×107 IU/kg. Compared with nonlinear regression method (SVMR), linear regression method (PLSR) is more suitable for the quantitative analysis of vitamins in premix feed.

Novel recombinant insulin analogue with flexible C-terminus in B chain. NMR structure of biosynthetic engineered A22G-B31K-B32R human insulin monomer in water/acetonitrile solution.

PubMed

Borowicz, Piotr; Bocian, Wojciech; Sitkowski, Jerzy; Bednarek, Elżbieta; Mikiewicz-Syguła, Diana; Błażej-Sosnowska, Sylwia; Bogiel, Monika; Rusek, Dorota; Kurzynoga, Dariusz; Kozerski, Lech

2011-11-01

A tertiary structure of recombinant A22(G)-B31(K)-B32(R)-human insulin monomer (insulin GKR) has been characterized by (1)H, (13)C NMR at natural isotopic abundance using NOESY, TOCSY, (1)H/(13)C-GHSQC, and (1)H/(13)C-GHSQC-TOCSY spectra. Translational diffusion studies indicate the monomer structure in water/acetonitrile (65/35vol.%). CSI analysis confirms existence of secondary structure motifs present in human insulin standard (HIS). Both techniques allow to establish that in this solvent recombinant insulin GKR exists as a monomer. Starting from structures calculated by the program CYANA, two different refinement protocols used molecular dynamics simulated annealing with the program AMBER; in vacuum (AMBER_VC), and including a generalized Born solvent model (AMBER_GB). From these calculations an ensemble of 20 structures of lowest energy was chosen which represents the tertiary structure of studied insulin. Here we present novel insulin with added A22(G) amino acid which interacts with β-turn environment resulting in high flexibility of B chain C-terminus. Copyright © 2011 Elsevier B.V. All rights reserved.

Fenofibrate Decreases Insulin Clearance and Insulin Secretion to Maintain Insulin Sensitivity*

PubMed Central

Ramakrishnan, Sadeesh K.; Russo, Lucia; Ghanem, Simona S.; Patel, Payal R.; Oyarce, Ana Maria; Heinrich, Garrett; Najjar, Sonia M.

2016-01-01

High fat diet reduces the expression of CEACAM1 (carcinoembryonic antigen-related cell adhesion molecule 1), a transmembrane glycoprotein that promotes insulin clearance and down-regulates fatty acid synthase activity in the liver upon its phosphorylation by the insulin receptor. Because peroxisome proliferator-activated receptor α (PPARα) transcriptionally suppresses CEACAM1 expression, we herein examined whether high fat down-regulates CEACAM1 expression in a PPARα-dependent mechanism. By activating PPARα, the lipid-lowering drug fenofibrate reverses dyslipidemia and improves insulin sensitivity in type 2 diabetes in part by promoting fatty acid oxidation. Despite reducing glucose-stimulated insulin secretion, fenofibrate treatment does not result in insulin insufficiency. To examine whether this is mediated by a parallel decrease in CEACAM1-dependent hepatic insulin clearance pathways, we fed wild-type and Pparα−/− null mice a high fat diet supplemented with either fenofibrate or Wy14643, a selective PPARα agonist, and examined their effect on insulin metabolism and action. We demonstrated that the decrease in insulin secretion by fenofibrate and Wy14643 is accompanied by reduction in insulin clearance in wild-type but not Pparα−/− mice, thereby maintaining normoinsulinemia and insulin sensitivity despite continuous high fat intake. Intact insulin secretion in L-CC1 mice with protected hepatic insulin clearance and CEACAM1 levels provides in vivo evidence that insulin secretion responds to changes in insulin clearance to maintain physiologic insulin and glucose homeostasis. These results also emphasize the relevant role of hepatic insulin extraction in regulating insulin sensitivity. PMID:27662905

Role of the glucose-sensing receptor in insulin secretion.

PubMed

Kojima, Itaru; Medina, Johan; Nakagawa, Yuko

2017-09-01

Glucose is a primary stimulator of insulin secretion. It has been thought that glucose exerts its effect by a mechanism solely dependent on glucose metabolism. We show here that glucose induces rapid Ca 2+ and cyclic AMP signals in β-cells. These rapid signals are independent of glucose-metabolism and are reproduced by non-metabolizable glucose analogues. These results led us to postulate that glucose activates a cell-surface receptor, namely the glucose-sensing receptor. Rapid signals induced by glucose are blocked by inhibition of a sweet taste receptor subunit T1R3 and a calcium-sensing receptor subunit CaSR. In accordance with these observations, T1R3 and CaSR form a heterodimer. In addition, a heterodimer of T1R3 and CaSR is activated by glucose. These results suggest that a heterodimer of T1R3 and CaSR is a major component of the glucose-sensing receptor. When the glucose-sensing receptor is blocked, glucose-induced insulin secretion is inhibited. Also, ATP production is significantly attenuated by the inhibition of the receptor. Conversely, stimulation of the glucose-sensing receptor by either artificial sweeteners or non-metabolizable glucose analogue increases ATP. Hence, the glucose-sensing receptor signals promote glucose metabolism. Collectively, glucose activates the cell-surface glucose-sensing receptor and promotes its own metabolism. Glucose then enters the cells and is metabolized through already activated metabolic pathways. The glucose-sensing receptor is a key molecule regulating the action of glucose in β-cells. © 2017 John Wiley & Sons Ltd.

Premixed flames in closed cylindrical tubes

NASA Astrophysics Data System (ADS)

Metzener, Philippe; Matalon, Moshe

2001-09-01

We consider the propagation of a premixed flame, as a two-dimensional sheet separating unburned gas from burned products, in a closed cylindrical tube. A nonlinear evolution equation, that describes the motion of the flame front as a function of its mean position, is derived. The equation contains a destabilizing term that results from the gas motion induced by thermal expansion and has a memory term associated with vorticity generation. Numerical solutions of this equation indicate that, when diffusion is stabilizing, the flame evolves into a non-planar form whose shape, and its associated symmetry properties, are determined by the Markstein parameter, and by the initial data. In particular, we observe the development of convex axisymmetric or non-axisymmetric flames, tulip flames and cellular flames.

Effect of Premixed Fuel Preparation for Partially Premixed Combustion with a Low Octane Gasoline on a Light-Duty Multi-Cylinder Compression Ignition Engine

DOE PAGES

Dempsey, Adam B.; Curran, Scott; Wagner, Robert M.; ...

2015-05-12

Gasoline compression ignition concepts with the majority of the fuel being introduced early in the cycle are known as partially premixed combustion (PPC). Previous research on single- and multi-cylinder engines has shown that PPC has the potential for high thermal efficiency with low NOx and soot emissions. A variety of fuel injection strategies has been proposed in the literature. These injection strategies aim to create a partially stratified charge to simultaneously reduce NOx and soot emissions while maintaining some level of control over the combustion process through the fuel delivery system. The impact of the direct injection strategy to createmore » a premixed charge of fuel and air has not previously been explored, and its impact on engine efficiency and emissions is not well understood. This paper explores the effect of sweeping the direct injected pilot timing from -91° to -324° ATDC, which is just after the exhaust valve closes for the engine used in this study. During the sweep, the pilot injection consistently contained 65% of the total fuel (based on command duration ratio), and the main injection timing was adjusted slightly to maintain combustion phasing near top dead center. A modern four cylinder, 1.9 L diesel engine with a variable geometry turbocharger, high pressure common rail injection system, wide included angle injectors, and variable swirl actuation was used in this study. The pistons were modified to an open bowl configuration suitable for highly premixed combustion modes. The stock diesel injection system was unmodified, and the gasoline fuel was doped with a lubricity additive to protect the high pressure fuel pump and the injectors. The study was conducted at a fixed speed/load condition of 2000 rpm and 4.0 bar brake mean effective pressure (BMEP). The pilot injection timing sweep was conducted at different intake manifold pressures, swirl levels, and fuel injection GTP-15-1067, Dempsey 2 pressures. The gasoline used in this study

Modeling and simulation of combustion dynamics in lean-premixed swirl-stabilized gas-turbine engines

NASA Astrophysics Data System (ADS)

Huang, Ying

This research focuses on the modeling and simulation of combustion dynamics in lean-premixed gas-turbines engines. The primary objectives are: (1) to establish an efficient and accurate numerical framework for the treatment of unsteady flame dynamics; and (2) to investigate the parameters and mechanisms responsible for driving flow oscillations in a lean-premixed gas-turbine combustor. The energy transfer mechanisms among mean flow motions, periodic motions and background turbulent motions in turbulent reacting flow are first explored using a triple decomposition technique. Then a comprehensive numerical study of the combustion dynamics in a lean-premixed swirl-stabilized combustor is performed. The analysis treats the conservation equations in three dimensions and takes into account finite-rate chemical reactions and variable thermophysical properties. Turbulence closure is achieved using a large-eddy-simulation (LES) technique. The compressible-flow version of the Smagorinsky model is employed to describe subgrid-scale turbulent motions and their effect on large-scale structures. A level-set flamelet library approach is used to simulate premixed turbulent combustion. In this approach, the mean flame location is modeled using a level-set G-equation, where G is defined as a distance function. Thermophysical properties are obtained using a presumed probability density function (PDF) along with a laminar flamelet library. The governing equations and the associated boundary conditions are solved by means of a four-step Runge-Kutta scheme along with the implementation of the message passing interface (MPI) parallel computing architecture. The analysis allows for a detailed investigation into the interaction between turbulent flow motions and oscillatory combustion of a swirl-stabilized injector. Results show good agreement with an analytical solution and experimental data in terms of acoustic properties and flame evolution. A study of flame bifurcation from a stable

The global, centralized approach of the GAIN Premix Facility has made oil fortification in Indonesia more affordable.

PubMed

Jallier, Vincent; Guyondet, Christophe; Provent, Adeline; Laillou, Arnaud; Soekirman; Moench-Pfanner, Regina

2013-06-01

Access to high-grade micronutrients is a recurring challenge that often threatens the long-term sustainability of food fortification programs. To assess the efficiency of the Global Alliance for Improved Nutrition (GAIN) Premix Facility in procuring quality, affordable vitamin A for fortification of edible oil in Indonesia. A global approach to procurement of standard items was used by combining volumes across various demand streams in order to reduce the total cost of acquisition through economies of scale. The GAIN Premix Facility undertook a detailed analysis of vitamin A requirements across its existing customer base, which served as a basis for developing a reliable demand forecast. A consolidated, competitive tender was launched that resulted in the setting up of a long-term commercial agreement with the selected supplier to lock in the most competitive price for a given period of time. The direct benefit to oil manufacturers of fortifying with vitamin A is that the cost of fortification went down significantly compared with prices they would have been offered had they ordered vitamin A individually. In Indonesia, this consolidated procurement approach has allowed a 14.5% decrease in the unit price of vitamin A. The GAIN Premix Facility demonstrated its effectiveness in acting as a global procurement platform by aggregating demand across different customers and leveraging improved prices through increased volumes. Building on the success of this effort, the GAIN Premix Facility is replicating this global approach for procurement of other standard items being procured across fortification programs worldwide.

[Increasing cost of insulin therapy in Belgium. From a critical analysis of the situation to a search for practical solutions].

PubMed

Scheen, A J

2006-09-01

Cost related to insulin therapy is markedly increasing in Belgium, as in other Eucopean countries. In the present paper, we will briefly analyze the main reasons for such aa increase, integrate such observation withIn the global context of diabetes management and suggest some solutions to provide best care to insulin-treated diabetic patients at a reasonable cost. The rise of the cost of insulin therapy has a multifactorial origin. It mainly results from an increase in the number of diabetic patients, a more intensive management, In both type 1 and type 2 diabetes, and a greater use of more expansive insulin analogues. It is important to analyze the increase of the cost of insulin therapy within the global burden of diabetes melitus. Only a better responsibility of all health care partners, patients, physicians, pharmaceutical companies, public health authorities, could provide solutions allowing diabetic people to profit from best treatments they should receive in order to prevent diabetic complications, by far the main cause of expenses.

Benchmarking Insulin Treatment Persistence Among Patients with Type 2 Diabetes Across Different U.S. Payer Segments.

PubMed

Wei, Wenhui; Jiang, Jenny; Lou, Youbei; Ganguli, Sohini; Matusik, Mark S

2017-03-01

Treatment persistence with basal insulins is crucial to achieving sustained glycemic control, which is associated with a reduced risk of microvascular disease and other complications of type 2 diabetes (T2D). However, studies suggest that persistence with basal insulin treatment is often poor. To measure and benchmark real-world basal insulin treatment persistence among patients with T2D across different payer segments in the United States. This was a retrospective observational study of data from a national pharmacy database (Walgreen Co., Deerfield, IL). The analysis included patients with T2D aged ≥ 18 years who filled ≥ 1 prescription for basal insulins between January 2013 and June 2013 (the index prescription) and who had also filled prescriptions for ≥ 1 oral antidiabetes drug in the database. Patients with claims for premixed insulin were excluded. Treatment persistence was defined as remaining on the study medication(s) during the 1-year follow-up period. Patients were stratified according to treatment history (existing basal insulin users vs. new insulin users), payer segments (commercially insured, Medicare, Medicaid, or cash-pay), type of basal insulin (insulin glargine, insulin detemir, or neutral protamine Hagedorn insulin [NPH]), and device for insulin administration (pen or vial/syringe). A total of 274,102 patients were included in this analysis, 82% of whom were existing insulin users. In terms of payer segments, 45.3% of patients were commercially insured, 47.8% had Medicare, 5.9% had Medicaid, and 1.1% were cash-pay. At the 1-year follow-up, basal insulin treatment persistence rate was 66.8% overall, 61.7% for new users, and 67.9% for existing users. In general, for both existing and new basal insulin users, higher persistence rate and duration were associated with Medicare versus cash-pay patients, use of insulin pens versus vial/syringe, and use of insulin glargine versus NPH. This large-scale study provides a benchmark of basal insulin

Pulsed jet combustion generator for non-premixed charge engines

DOEpatents

Oppenheim, A. K.; Stewart, H. E.

1990-01-01

A device for introducing fuel into the head space of cylinder of non-premixed charge (diesel) engines is disclosed, which distributes fuel in atomized form in a plume, whose fluid dynamic properties are such that the compression heated air in the cylinder head space is entrained into the interior of the plume where it is mixed with and ignites the fuel in the plume interior, to thereby control combustion, particularly by use of a multiplicity of individually controllable devices per cylinder.

Insulin degludec results in lower rates of nocturnal hypoglycaemia and fasting plasma glucose vs. insulin glargine: A meta-analysis of seven clinical trials.

PubMed

Russell-Jones, D; Gall, M-A; Niemeyer, M; Diamant, M; Del Prato, S

2015-10-01

Basal insulin analogues have a reduced risk of hypoglycaemia compared with NPH insulin, but hypoglycaemia still remains a major impediment to achieving recommended fasting plasma glucose (FPG) targets in patients with diabetes. Insulin degludec (IDeg) is a new basal insulin that forms soluble multihexamers after subcutaneous injection resulting in an ultra-long duration of action and stable glucose-lowering effect. The aim of this analysis was to compare the effect of IDeg on FPG and nocturnal confirmed hypoglycaemia as compared to insulin glargine (IGlar). Data were included from seven phase 3a, randomised, open-label, treat-to-target clinical trials in which once-daily IDeg was compared with once-daily IGlar. Two trials included a total of 957 patients with type 1 diabetes (T1D) and five trials included a total of 3360 patients with type 2 diabetes (T2D); all trials were 26 or 52 weeks in duration. Confirmed hypoglycaemia was defined as plasma glucose <3.1 mmol/L or severe episodes requiring assistance, and nocturnal hypoglycaemia occurred between 00:01 and 05:59. In all trials, the mean end-of-trial FPG was lower for IDeg than IGlar, reaching statistical significance in three trials. Similarly, IDeg was associated with a lower rate of nocturnal confirmed hypoglycaemia vs. IGlar, which was statistically significant in three trials, regardless of type of diabetes or background therapy. This analysis shows that the lower rate of nocturnal confirmed hypoglycaemia seen with IDeg relative to IGlar is accompanied by a reduced mean FPG, in particular in patients with T2D. Copyright © 2015 Elsevier B.V. All rights reserved.

Premixed-Gas Flame Propagation in Hele-Shaw Cells

NASA Technical Reports Server (NTRS)

Sharif, J.; Abid, M.; Ronney, P. D.

1999-01-01

It is well known that buoyancy and thermal expansion affect the propagation ra and shapes of premixed gas flames. The understanding of such effects is complicated by the large density ratio between the reactants and products, which induces a baroclinic production of vorticity due to misalignment of density and pressure gradients at the front, which in turn leads to a complicated multi-dimensional flame/flow interaction. The Hele-Shaw cell, i.e., the region between closely-spaced flat parallel plates, is probably the simplest system in which multi-dimensional convection is presents consequently, the behavior of fluids in this system has been studied extensively (Homsy, 1987). Probably the most important characteristic of Hele-Shaw flows is that when the Reynolds number based on gap width is sufficiently small, the Navier-Stokes equations averaged over the gap reduce to a linear relation, namely a Laplace equation for pressure (Darcy's law). In this work, flame propagation in Hele-Shaw cells is studied to obtain a better understanding of buoyancy and thermal expansion effects on premixed flames. This work is also relevant to the study of unburned hydrocarbon emissions produced by internal combustion engines since these emissions are largely a result of the partial burning or complete flame quenching in the narrow, annular gap called the "crevice volume" between the piston and cylinder walls (Heywood, 1988). A better understanding of how flames propagate in these volumes through experiments using Hele-Shaw cells could lead to identification of means to reduce these emissions.

The insulin-like growth factor I system: physiological and pathophysiological implication in cardiovascular diseases associated with metabolic syndrome.

PubMed

Ren, Jun; Anversa, Piero

2015-02-15

Metabolic syndrome is a cluster of risk factors including obesity, dyslipidemia, hypertension, and insulin resistance. A number of theories have been speculated for the pathogenesis of metabolic syndrome including impaired glucose and lipid metabolism, lipotoxicity, oxidative stress, interrupted neurohormonal regulation and compromised intracellular Ca(2+) handling. Recent evidence has revealed that adults with severe growth hormone (GH) and insulin-like growth factor I (IGF-1) deficiency such as Laron syndrome display increased risk of stroke and cardiovascular diseases. IGF-1 signaling may regulate contractility, metabolism, hypertrophy, apoptosis, autophagy, stem cell regeneration and senescence in the heart to maintain cardiac homeostasis. An inverse relationship between plasma IGF-1 levels and prevalence of metabolic syndrome as well as associated cardiovascular complications has been identified, suggesting the clinical promises of IGF-1 analogues or IGF-1 receptor activation in the management of metabolic and cardiovascular diseases. However, the underlying pathophysiological mechanisms between IGF-1 and metabolic syndrome are still poorly understood. This mini-review will discuss the role of IGF-1 signaling cascade in the prevalence of metabolic syndrome in particular the susceptibility to overnutrition and sedentary life style-induced obesity, dyslipidemia, insulin resistance and other features of metabolic syndrome. Special attention will be dedicated in IGF-1-associated changes in cardiac responses in various metabolic syndrome components such as insulin resistance, obesity, hypertension and dyslipidemia. The potential risk of IGF-1 and IGF-1R stimulation such as tumorigenesis is discussed. Therapeutic promises of IGF-1 and IGF-1 analogues including mecasermin, mecasermin rinfabate and PEGylated IGF-1 will be discussed. Copyright © 2014 Elsevier Inc. All rights reserved.

The premixed flame in uniform straining flow

NASA Technical Reports Server (NTRS)

Durbin, P. A.

1982-01-01

Characteristics of the premixed flame in uniform straining flow are investigated by the technique of activation-energy asymptotics. An inverse method is used, which avoids some of the restrictions of previous analyses. It is shown that this method recovers known results for adiabatic flames. New results for flames with heat loss are obtained, and it is shown that, in the presence of finite heat loss, straining can extinguish flames. A stability analysis shows that straining can suppress the cellular instability of flames with Lewis number less than unity. Strain can produce instability of flames with Lewis number greater than unity. A comparison shows quite good agreement between theoretical deductions and experimental observations of Ishizuka, Miyasaka & Law (1981).

Effects of pressure fluctuations on the combustion process in turbulent premixed flames

NASA Astrophysics Data System (ADS)

Beardsell, Guillaume; Lapointe, Simon; Blanquart, Guillaume

2016-11-01

The need for a thorough understanding of turbulence-combustion interactions in compressible flows is driven by recent technological developments in propulsion as well as renewed interest in the development of next generation supersonic and hypersonic vehicles. In such flows, pressure fluctuations displaying a wide range of length and timescales are present. These fluctuations are expected to impact the combustion process to varying degrees, depending amongst other things on the amplitude of the pressure variations and the timescales of the chemical reactions taking place in the flame. In this context, numerical simulations of these flows can provide insight into the impact of pressure fluctuations on the combustion process. In the present work, we analyze data from simulations of statistically-flat premixed n-heptane/air flames at high Karlovitz numbers. The compressible Navier-Stokes equations are solved exactly (DNS) and results obtained with both detailed kinetic modeling and one-step chemistry are considered. The effects of pressure fluctuations on the fuel burning rate are investigated. The findings are compared with results obtained from simulations of one-dimensional premixed flames subjected to various pressure waves.

Direct numerical simulations of flow-chemistry interactions in statistically turbulent premixed flames

NASA Astrophysics Data System (ADS)

Arias, Paul; Uranakar, Harshavardhana; Chaudhuri, Swetaprovo; Im, Hong

2015-11-01

The effects of Damköhler number and Karlovitz number on the flame dynamics of three-dimensional statistically planar turbulent premixed flames are investigated by direct numerical simulation incorporating detailed chemistry and transport for a hydrogen-air mixture. The mean inlet velocity was dynamically adjusted to ensure a stable flame within the computational domain, allowing the investigation of time-averaged quantities of interest. A particular interest was on understanding the effects of turbulence on the displacement speed of the flame relative to the local fluid flow. Results show a linear dependence on the displacement speed as a function of total strain, consistent with earlier work on premixed-laminar flames. Additional analysis on the local flame thickness reveals that the effect of turbulence is twofold: (1) the increase in mixing results in flame thinning due to the enhancement of combustion at early onset of the flame, and (2) for large Reynolds number flows, the penetration of the turbulence far into the preheat zone and into the reaction zone results in localized flame broadening.

Evaluation of resistant starch, glycemic index and fortificants content of premix rice coated with various concentrations and types of edible coating materials

NASA Astrophysics Data System (ADS)

Yulianto, W. A.; Susiati, A. M.; Adhini, H. A. N.

2018-01-01

The incidence of diabetes in Indonesia has been increasing year by year. Diets with a low glycemic index and high resistant starch foods can assist diabetics in controlling their blood glucose levels. Diabetics are known to have micro-nutrient deficiencies of chromium, magnesium and vitamin D that can be overcome by consuming parboiled rice fortified by use of a coating method. The fortification of parboiled rice (premix rice) can be achieved by coating with HPMC (hydroxypropyl methyl cellulose), MC (methyl cellulose), CMC (carboxyl methyl cellulose), gum arabic and rice starch. This research aimed to evaluate the levels of resistant starch, glycemic index and fortificants of premix rice coated with different concentrations and types of edible coating materials. This research used completely randomized design, with treatments to the concentrations and the types of edible coating (HPMC, CMC, MC, gum arabic and rice starch). The concentrations of edible coating were 0.15%, 0.2% and 0.25% for cellulose derivative coatings; 25%, 30%, 35% for gum arabic and 2%, 3.5% and 5% for rice starch. This research shows that fortified premix rice coated with various concentrations and types of edible coating materials is high in resistant starch and has a low glycemic index. The coating treatment affects the levels of magnesium and vitamin D, but does not affect the levels of chromium in parboiled rice. The premix rice with a low glycemic index and high nutrient content (chromium, magnesium and vitamin D) was premix rice coated by CMC 0.25% and HPMC 0.25% with glycemic indeces of 39.34 and 38.50, respectively.

Premixed autoignition in compressible turbulence

NASA Astrophysics Data System (ADS)

Konduri, Aditya; Kolla, Hemanth; Krisman, Alexander; Chen, Jacqueline

2016-11-01

Prediction of chemical ignition delay in an autoignition process is critical in combustion systems like compression ignition engines and gas turbines. Often, ignition delay times measured in simple homogeneous experiments or homogeneous calculations are not representative of actual autoignition processes in complex turbulent flows. This is due the presence of turbulent mixing which results in fluctuations in thermodynamic properties as well as chemical composition. In the present study the effect of fluctuations of thermodynamic variables on the ignition delay is quantified with direct numerical simulations of compressible isotropic turbulence. A premixed syngas-air mixture is used to remove the effects of inhomogeneity in the chemical composition. Preliminary results show a significant spatial variation in the ignition delay time. We analyze the topology of autoignition kernels and identify the influence of extreme events resulting from compressibility and intermittency. The dependence of ignition delay time on Reynolds and turbulent Mach numbers is also quantified. Supported by Basic Energy Sciences, Dept of Energy, United States.

Multivariate Prediction Equations for HbA1c Lowering, Weight Change, and Hypoglycemic Events Associated with Insulin Rescue Medication in Type 2 Diabetes Mellitus: Informing Economic Modeling.

PubMed

Willis, Michael; Asseburg, Christian; Nilsson, Andreas; Johnsson, Kristina; Kartman, Bernt

2017-03-01

Type 2 diabetes mellitus (T2DM) is chronic and progressive and the cost-effectiveness of new treatment interventions must be established over long time horizons. Given the limited durability of drugs, assumptions regarding downstream rescue medication can drive results. Especially for insulin, for which treatment effects and adverse events are known to depend on patient characteristics, this can be problematic for health economic evaluation involving modeling. To estimate parsimonious multivariate equations of treatment effects and hypoglycemic event risks for use in parameterizing insulin rescue therapy in model-based cost-effectiveness analysis. Clinical evidence for insulin use in T2DM was identified in PubMed and from published reviews and meta-analyses. Study and patient characteristics and treatment effects and adverse event rates were extracted and the data used to estimate parsimonious treatment effect and hypoglycemic event risk equations using multivariate regression analysis. Data from 91 studies featuring 171 usable study arms were identified, mostly for premix and basal insulin types. Multivariate prediction equations for glycated hemoglobin A 1c lowering and weight change were estimated separately for insulin-naive and insulin-experienced patients. Goodness of fit (R 2 ) for both outcomes were generally good, ranging from 0.44 to 0.84. Multivariate prediction equations for symptomatic, nocturnal, and severe hypoglycemic events were also estimated, though considerable heterogeneity in definitions limits their usefulness. Parsimonious and robust multivariate prediction equations were estimated for glycated hemoglobin A 1c and weight change, separately for insulin-naive and insulin-experienced patients. Using these in economic simulation modeling in T2DM can improve realism and flexibility in modeling insulin rescue medication. Copyright © 2017 International Society for Pharmacoeconomics and Outcomes Research (ISPOR). Published by Elsevier Inc. All

Premixed Digestion Salts for Kjeldahl Determination of Total Nitrogen in Selected Forest Soils

Treesearch

B. G. Blackmon

1971-01-01

Estimates of total soil nitrogen by a standard Kjeldahl procedure and a modified procedure employing packets of premixed digestion salts were closely correlated. (r2 = 0.983). The modified procedure appears to be as reliable all the standard method for determining total nitrogen in southern alluvial forest soils.

Dipeptidyl peptidase-4 inhibitors or sodium glucose co-transporter-2 inhibitors as an add-on to insulin therapy: A comparative review

PubMed Central

Singh, Awadhesh Kumar; Singh, Ritu

2016-01-01

The gradual decline in β-cell function is inevitable in type 2 diabetes mellitus and therefore, substantial proportions of patients require insulin subsequently, in order to achieve optimal glucose control. While weight gain, hypoglycemia, and fluid retention especially during dose intensification is a known limitation to insulin therapy, these adverse effects also reduce patient satisfaction and treatment adherence. It is also possible that the benefits of intensive control achieved by insulin therapy, perhaps get nullified by the weight gain and hypoglycemia. In addition, improvement in plasma glucose or glycated hemoglobin (HbA1c) itself is associated with weight gain. Notably, studies have already suggested that reduction in body weight by ~3–5%, may allow a significantly better glycemic control. Thus, a class of drugs, which can reduce HbA1c effectively, yet are weight neutral or preferably reduce body weight, could be the most sought out strategy as an add-on therapy to insulin. While sulfonylureas (SUs) are associated with weight gain and hypoglycemia, pioglitazone increases body weight and fluid retention. Moreover, SUs are not recommended once premix or prandial insulin is commenced. The addition of newer agents, such as glucagon-like peptide-1 receptor agonist to insulin certainly appears to be an effective tool in reducing both HbA1c and body weight as is evident across the studies; however, this approach incurs an additional injection as well as cost. Dipeptidyl peptidase-4 inhibitors (DPP-4I) and sodium-glucose co-transporter-2 inhibitors (SGLT-2I) are other exciting options, as an add-on to insulin therapy primarily because these are oral drugs and do not possess any intrinsic potential of hypoglycemia. Furthermore, these are either weight neutral or induce significant weight loss. This review article aims to comparatively analyze the safety and efficacy of DPP-4I and SGLT-2I, as an add-on therapy to insulin. PMID:26904466

Premixer assembly for mixing air and fuel for combustion

DOEpatents

York, William David; Johnson, Thomas Edward; Keener, Christopher Paul

2016-12-13

A premixer assembly for mixing air and fuel for combustion includes a plurality of tubes disposed at a head end of a combustor assembly. Also included is a tube of the plurality of tubes, the tube including an inlet end and an outlet end. Further included is at least one non-circular portion of the tube extending along a length of the tube, the at least one non-circular portion having a non-circular cross-section, and the tube having a substantially constant cross-sectional area along its length

Optimal parameters for laser tissue soldering: II. Premixed versus separate dye-solder techniques.

PubMed

McNally, K M; Sorg, B S; Chan, E K; Welch, A J; Dawes, J M; Owen, E R

2000-01-01

Laser tissue soldering by using an indocyanine green (ICG)-doped protein solder applied topically to the tissue surface and denatured with a diode laser was investigated in Part I of this study. The depth of light absorption was predominantly determined by the concentration of the ICG dye added to the solder. This study builds on that work with an in vitro investigation of the effects of limiting the zone of heat generation to the solder-tissue interface to determine whether more stable solder-tissue fusion can be achieved. An alternative laser tissue soldering technique was investigated, which increased light absorption at the vital solder-tissue interface. A thin layer of ICG dye was smeared over the surface to be treated, the protein solder was then placed directly on top of the dye, and the solder was denatured with an 808-nm diode laser. Because laser light at approximately 800 nm is absorbed primarily by the ICG dye, this thin layer of ICG solution restricted the heat source to the space between the solder and the tissue surfaces. A tensile strength analysis was conducted to compare the separate dye-solder technique with conventional techniques of laser tissue soldering for which a premixed dye-solder is applied directly to the tissue surface. The effect of hydration on bond stability of repairs formed by using both techniques was also investigated using tensile strength and scanning electron microscopy analysis. Equivalent results in terms of tensile strength were obtained for the premixed dye-solder technique using protein solders containing 0.25 mg/ml ICG (liquid solder, 220 +/- 35 N/cm(2); solid solder, 602 +/- 32 N/cm(2)) and for the separate dye-solder technique (liquid solder, 228 +/- 41 N/cm(2); solid solder, 578 +/- 29 N/cm(2)). The tensile strength of native bovine thoracic aorta was 596 +/- 31 N/cm(2). Repairs created by using the separate dye-solder technique were more stable during hydration than their premixed dye-solder counterparts. The

Insulin and adenosine regulate the phosphatidylcholine concentration in isolated rat adipocyte plasma membranes.

PubMed

Kiechle, F L; Sykes, E; Artiss, J D

1995-01-01

Blockade of adenosine receptors by 3-isobutyl-1-methylxanthine or degradation of endogenous adenosine with adenosine deaminase increased the phosphatidylcholine concentration in isolated rat adipocyte plasma membranes, an effect which was suppressed by the phosphatidylethanolamine methyltransferase inhibitor, S-adenosyl-L-homocysteine, and reversed by the adenosine analogue, N6-(L-phenylisopropyl)-adenosine. For example, the addition of N6-(L-phenylisopropyl)-adenosine to adenosine deaminase pretreated plasma membranes rapidly lowered the concentration of phosphatidylcholine by 171 nmol/mg at 30 seconds compared to control. Insulin-induced stimulation of phospholipid methylation in membranes treated with 3-isobutyl-1-methylxanthine or adenosine deaminase was achieved only after the addition of N6-(L-phenylisopropyl)-adenosine. These results suggest that adenosine receptor occupancy inhibits phospholipid methylation, is required for insulin stimulation of phospholipid methylation, and may perhaps activate a phosphatidylcholine-specific phospholipase C or phospholipase D.

Turbulent piloted partially-premixed flames with varying levels of O2/N2: stability limits and PDF calculations

NASA Astrophysics Data System (ADS)

Juddoo, Mrinal; Masri, Assaad R.; Pope, Stephen B.

2011-12-01

This paper reports measured stability limits and PDF calculations of piloted, turbulent flames of compressed natural gas (CNG) partially-premixed with either pure oxygen, or with varying levels of O2/N2. Stability limits are presented for flames of CNG fuel premixed with up to 20% oxygen as well as CNG-O2-N2 fuel where the O2 content is varied from 8 to 22% by volume. Calculations are presented for (i) Sydney flame B [Masri et al. 1988] which uses pure CNG as well as flames B15 to B25 where the CNG is partially-premixed with 15-25% oxygen by volume, respectively and (ii) Sandia methane-air (1:3 by volume) flame E [Barlow et al. 2005] as well as new flames E15 and E25 that are partially-premixed with 'reconstituted air' where the O2 content in nitrogen is 15 and 25% by volume, respectively. The calculations solve a transported PDF of composition using a particle-based Monte Carlo method and employ the EMST mixing model as well as detailed chemical kinetics. The addition of oxygen to the fuel increases stability, shortens the flames, broadens the reaction zone, and shifts the stoichiometric mixture fraction towards the inner side of the jet. It is found that for pure CNG flames where the reaction zone is narrow (∼0.1 in mixture fraction space), the PDF calculations fail to reproduce the correct level of local extinction on approach to blow-off. A broadening in the reaction zone up to about 0.25 in mixture fraction space is needed for the PDF/EMST approach to be able to capture these finite-rate chemistry effects. It is also found that for the same level of partial premixing, increasing the O2/N2 ratio increases the maximum levels of CO and NO but shifts the peak to richer mixture fractions. Over the range of oxygenation investigated here, stability limits have shown to improve almost linearly with increasing oxygen levels in the fuel and with increasing the contribution of release rate from the pilot.

A cross-sectional survey among patients and prescribers on insulin dosing irregularities and impact of mild (self-treated) hypoglycemia episodes in Spanish patients with type 2 diabetes as compared to other European patients.

PubMed

Ampudia-Blasco, Francisco J; Galán, Manuel; Brod, Meryl

2014-10-01

In Spain, data suggest that 13.8% of adults have diabetes. Two important aspects in diabetes management are mild hypoglycemic episodes and poor treatment adherence. This study assesses the impact of missed insulin doses and prevalence of mistimed and reduced insulin doses and mild hypoglycemia in patients with type 2 diabetes treated with basal insulin analogues in Spain, and compares the data collected to pooled data from 8 other European countries (OECs). GAPP2 was an international, online, cross-sectional study of diabetic patients aged ≥40 years treated with long-acting insulin analogues and their healthcare professionals. Patients and healthcare professionals were recruited from online research panels. Data reported in Spain are compared to pooled data from 8 OECs. In Spain, 1-3% of patients reported they had reduced, missed, or mistimed at least one insulin does in the previous month. Significantly more OEC patients reported dosing irregularities (15-23%; all P<0.01). In Spain, 77% of patients were worried and 59% felt guilty for missing a dose of basal insulin, while 24% reported that they were very worried about nocturnal hypoglycemia. Significantly fewer OEC patients reported worrying (47%; P<0.01) and feeling guilty (37%; P<0.01) about missing an insulin dose, or worry about nocturnal hypoglycemia (12%; P<0.01). In Spain, patients with type 2 diabetes report fewer dosing irregularities and hypoglycemic episodes as compared to patients from OECs. However, Spanish patients appear to have a reduced quality of life related to hypoglycemia as well as worry and guilt related to insulin dosing irregularities. Copyright © 2014 SEEN. Published by Elsevier Espana. All rights reserved.

The effect of a long-acting somatostatin analogue (SMS 201-995) on intermediary metabolism and gut hormones after a test meal in normal subjects.

PubMed

Fuessl, H S; Burrin, J M; Williams, G; Adrian, T E; Bloom, S R

1987-08-01

SMS 201-995 is an octapeptide analogue of somatostatin. The effect of a single subcutaneous (s.c.) injection of 50 micrograms SMS 201-995 on post-prandial intermediary metabolism was investigated in normal subjects. In spite of a long-lasting post-prandial suppression of insulin secretion, there were no significant changes in the plasma concentration of alanine, glycerol, 3-OH-butyrate or lactate. However, SMS 201-995 impairs carbohydrate tolerance, probably due to inhibition of insulin secretion. Basal and post-prandial plasma concentrations of the gut regulatory peptides pancreatic glucagon, motilin, pancreatic polypeptide, gastric inhibitory polypeptide, enteroglucagon, gastrin and peptide YY were suppressed up to 5 hours after subcutaneous administration of a single dose of SMS 201-995.

Clinical utility of insulin and insulin analogs

PubMed Central

Sanlioglu, Ahter D.; Altunbas, Hasan Ali; Balci, Mustafa Kemal; Griffith, Thomas S.; Sanlioglu, Salih

2013-01-01

Diabetes is a pandemic disease characterized by autoimmune, genetic and metabolic abnormalities. While insulin deficiency manifested as hyperglycemia is a common sequel of both Type-1 and Type-2 diabetes (T1DM and T2DM), it does not result from a single genetic defect—rather insulin deficiency results from the functional loss of pancreatic β cells due to multifactorial mechanisms. Since pancreatic β cells of patients with T1DM are destroyed by autoimmune reaction, these patients require daily insulin injections. Insulin resistance followed by β cell dysfunction and β cell loss is the characteristics of T2DM. Therefore, most patients with T2DM will require insulin treatment due to eventual loss of insulin secretion. Despite the evidence of early insulin treatment lowering macrovascular (coronary artery disease, peripheral arterial disease and stroke) and microvascular (diabetic nephropathy, neuropathy and retinopathy) complications of T2DM, controversy exists among physicians on how to initiate and intensify insulin therapy. The slow acting nature of regular human insulin makes its use ineffective in counteracting postprandial hyperglycemia. Instead, recombinant insulin analogs have been generated with a variable degree of specificity and action. Due to the metabolic variability among individuals, optimum blood glucose management is a formidable task to accomplish despite the presence of novel insulin analogs. In this article, we present a recent update on insulin analog structure and function with an overview of the evidence on the various insulin regimens clinically used to treat diabetes. PMID:23584214

Isolation and Characterization of Acetylated Derivative of Recombinant Insulin Lispro Produced in Escherichia coli.

PubMed

Szewczak, Joanna; Bierczyńska-Krzysik, Anna; Piejko, Marcin; Mak, Paweł; Stadnik, Dorota

2015-07-01

Insulin lispro is a rapid-acting insulin analogue produced by recombinant DNA technology. As a biosynthetic drug, the protein undergoes strict monitoring aiming for detection and characterization of impurities. The goal of this study was to isolate and identify a derivative of insulin lispro formed during biosynthesis. For this purpose, ion exchange chromatography in combination with endoproteinase Glu-C digestion, MALDI-TOF/TOF mass spectrometry and Edman sequencing were employed. Ion exchange chromatography analysis of related proteins in development batches of recombinant insulin lispro revealed the existence of unknown derivative in excess of the assumed limit. Its molecular mass was 42 Da higher than the theoretical mass of Lys(B31) insulin lispro--one of the expected process-related intermediates. Endoproteinase Glu-C cleavage enabled indication of the modified peptide. Tandem mass spectrometry (MS/MS) allowed to explore the location and type of the modification. The 42 amu shift was present in the mass of y-type ions, while b-type ions were in agreement with theoretical values. It suggested that the modification is present on B31 lysine. Further inquiry revealed the presence of two diagnostic ions for lysine acetylation at m/z 143.1 and 126.1. In addition, the peptide was isolated and sequenced by Edman degradation. Standards of phenylthiohydantoin derivatives of N-ε-acetyl-L-lysine and N-ε-trimethyl-L-lysine, not available commercially, were synthesized in the laboratory. The retention time of the modified residue confirmed its identity as N-ε-acetyl-L-lysine. The derivative of insulin lispro formed during biosynthesis of the drug was identified to be N-ε-acetyl-L-lysine (B31) insulin lispro.

Health economic evaluations comparing insulin glargine with NPH insulin in patients with type 1 diabetes: a systematic review

PubMed Central

2011-01-01

Background Compared to conventional human basal insulin (neutral protamine Hagedorn; NPH) the long-acting analogue insulin glargine (GLA) is associated with a number of advantages regarding metabolic control, hypoglycaemic events and convenience. However, the unit costs of GLA exceed those of NPH. This study aims to systematically review the economic evidence comparing GLA with NPH in basal-bolus treatment (intensified conventional therapy; ICT) of type 1 diabetes in order to facilitate informed decision making in clinical practice and health policy. Methods A systematic literature search was performed for the period of January 1st 2000 to December 1st 2009 via Embase, Medline, the Cochrane Library, the databases GMS (German Medical Science) and DAHTA (Deutsche Agentur für Health Technology Assessment), and the abstract books of relevant international scientific congresses. Retrieved studies were reviewed based on predefined inclusion criteria, methodological and quality aspects. In order to allow comparison between studies, currencies were converted using purchasing power parities (PPP). Results A total of 7 health economic evaluations from 4 different countries fulfilled the predefined criteria: 6 modelling studies, all of them cost-utility analyses, and one claims data analysis with a cost-minimisation design. One cost-utility analysis showed dominance of GLA over NPH. The other 5 cost-utility analyses resulted in additional costs per quality adjusted life year (QALY) gained for GLA, ranging from € 3,859 to € 57,002 (incremental cost effectiveness ratio; ICER). The cost-minimisation analysis revealed lower annual diabetes-specific costs in favour of NPH from the perspective of the German Statutory Health Insurance (SHI). Conclusions The incremental cost-utility-ratios (ICER) show favourable values for GLA with considerable variation. If a willingness-to-pay threshold of £ 30,000 (National Institute of Clinical Excellence, UK) is adopted, GLA is cost

New ways of insulin delivery.

PubMed

Heinemann, L

2010-02-01

foresee that with most new ways of insulin delivery the bioavailability/biopotency will be lower than with subcutaneous (SC) insulin administration. This in turn requires that more insulin has to be applied to induce the same metabolic (blood glucose lowering) effect in patients with diabetes. If the costs of insulin are of relevance for the price (this clearly depends on the source of insulin the individual company has to use) the price of the product will be higher relative to standard SC insulin therapy. The question is, clearly, what are the advantages of the new product? In times when SC insulin administration was painful and cumbersome it was clear that the ease of swallowing an insulin tablet was a good argument for many patients. With the invention of thin insulin needles that make the SC injection practically pain free in most cases, this argument of being 'convenient' becomes of limited relevance. However, for many patients (especially the public) the avoidance of 'injection' is an argument. The question is, how much is the patient (society) willing to pay for such a psychological 'advantage'? Most probably additional clear-cut clinical advantages must be demonstrable to convince the payers to reimburse a new product, especially when the price is higher than that of SC insulin. If, for example, postprandial glycaemic excursions are considerably better controlled because the pharmacodynamic (PD) effects are better than with SC injection of rapid-acting insulin analogues (this might be possible with inhaled Technosphere insulin), this would be a clinically relevant argument. Without such advantages, new products will have no market success. Most probably it will not be until one of the various ARIA developments (e.g. nasal insulin) makes it into a financially attractive product (sufficient return on investment) that more money will flow again in this area of research. The search for relevant articles about new ways to deliver insulin did not reveal very many

Stochastic modeling of unsteady extinction in turbulent non-premixed combustion

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lackmann, T.; Hewson, J. C.; Knaus, R. C.

Turbulent fluctuations of the scalar dissipation rate have a major impact on extinction in non-premixed combustion. Recently, an unsteady extinction criterion has been developed (Hewson, 2013) that predicts extinction dependent on the duration and the magnitude of dissipation rate fluctuations exceeding a critical quenching value; this quantity is referred to as the dissipation impulse. Furthermore, the magnitude of the dissipation impulse corresponding to unsteady extinction is related to the difficulty with which a flamelet is exintguished, based on the steady-state S-curve.

Stochastic modeling of unsteady extinction in turbulent non-premixed combustion

DOE PAGES

Lackmann, T.; Hewson, J. C.; Knaus, R. C.; ...

2016-07-19

Turbulent fluctuations of the scalar dissipation rate have a major impact on extinction in non-premixed combustion. Recently, an unsteady extinction criterion has been developed (Hewson, 2013) that predicts extinction dependent on the duration and the magnitude of dissipation rate fluctuations exceeding a critical quenching value; this quantity is referred to as the dissipation impulse. Furthermore, the magnitude of the dissipation impulse corresponding to unsteady extinction is related to the difficulty with which a flamelet is exintguished, based on the steady-state S-curve.

[New developments in the treatment and monitoring of type 1 diabetes mellitus].

PubMed

Otto-Buczkowska, Ewa; Jarosz-Chobot, Przemysława; Tucholski, Krzysztof

2008-01-01

In recent years, insulin analogues are the benefits of the use in functional intensive insulin therapy for the treatment of diabetes. Shortacting insulin (lispro, aspart and glulisine) and long-acting insulin (glargine and detemir) have been developed for the management of diabetes. Short-acting insulin analogues are an alternative to regular human insulin before meals. These new short-acting insulin analogues show more rapid onset of activity and a shorter duration of action. As a result of these pharmacokinetic differences, an improved postprandial glycemic control is achieved, without increasing the risk of hypoglycemia. In addition, these insulin analogues can be administered immediately before a meal. The long-acting insulin analogues provide basal insulin levels for 24 h when administered once (glargine) or two (detemir) daily. Compared with previous intermediate- or long-acting conventional insulin, these insulins shows a flat profile of plasma insulin levels . The use of these long-acting insulin analogues appears to be associated with a reduced incidence of hypoglycemia, especially at night. The availability of these new insulin analogues has the potential to significantly improve long-term control over blood glucose in diabetic patients. In recent years more and more frequently the method of multiple daily injections (MDI) of insulin is being replaced by the method of continuous subcutaneous insulin infusion (CSII). It is the most physiological way to administer insulin. In recent years treatment with insulin pumps has been used more frequently in the pediatric patients and in the treatment of diabetes in pregnancy. Use of continuous glucose monitoring systems enables detection of glycemia fluctuations unrevealed by selfmonitoring of blood glucose, such as night hypoglycemias and early postprandial hyperglycemias. Real-time systems allow to reduce HbA1c levels and limit number of excursions. Non-invasive glucose measurement devices are introduced. Fully

Insulin and insulin signaling play a critical role in fat induction of insulin resistance in mouse

PubMed Central

Ning, Jie; Hong, Tao; Yang, Xuefeng; Mei, Shuang; Liu, Zhenqi; Liu, Hui-Yu

2011-01-01

The primary player that induces insulin resistance has not been established. Here, we studied whether or not fat can cause insulin resistance in the presence of insulin deficiency. Our results showed that high-fat diet (HFD) induced insulin resistance in C57BL/6 (B6) mice. The HFD-induced insulin resistance was prevented largely by the streptozotocin (STZ)-induced moderate insulin deficiency. The STZ-induced insulin deficiency prevented the HFD-induced ectopic fat accumulation and oxidative stress in liver and gastrocnemius. The STZ-induced insulin deficiency prevented the HFD- or insulin-induced increase in hepatic expression of long-chain acyl-CoA synthetases (ACSL), which are necessary for fatty acid activation. HFD increased mitochondrial contents of long-chain acyl-CoAs, whereas it decreased mitochondrial ADP/ATP ratio, and these HFD-induced changes were prevented by the STZ-induced insulin deficiency. In cultured hepatocytes, we observed that expressions of ACSL1 and -5 were stimulated by insulin signaling. Results in cultured cells also showed that blunting insulin signaling by the PI3K inhibitor LY-294002 prevented fat accumulation, oxidative stress, and insulin resistance induced by the prolonged exposure to either insulin or oleate plus sera that normally contain insulin. Finally, knockdown of the insulin receptor prevented the oxidative stress and insulin resistance induced by the prolonged exposure to insulin or oleate plus sera. Together, our results show that insulin and insulin signaling are required for fat induction of insulin resistance in mice and cultured mouse hepatocytes. PMID:21586696

The evolution equation for the flame surface density in turbulent premixed combustion

NASA Technical Reports Server (NTRS)

Trouve, Arnaud

1993-01-01

The mean reaction rate in flamelet models for turbulent premixed combustion depends on two basic quantities: a mean chemical rate, called the flamelet speed, and the flame surface density. Our previous work had been primarily focused on the problem of the structure and topology of turbulent premixed flames, and it was then determined that the flamelet speed, when space-averaged, is only weakly sensitive to the turbulent flow field. Consequently, the flame surface density is the key quantity that conveys most of the effects of the turbulence on the rate of energy release. In flamelet models, this quantity is obtained via a modeled transport equation called the Sigma-equation. Past theoretical work has produced a rigorous approach that leads to an exact but unclosed formulation for the turbulent Sigma-equation. In the exact Sigma-equation, it appears that the dynamical properties of the flame surface density are determined by a single parameter, namely the turbulent flame stretch. Unfortunately, the turbulent flame stretch as well as the flame surface density is not available from experiments, and, in the absence of experimental data, little is known on the validity of the closure assumptions used in current flamelet models. Direct Numerical Simulation (DNS) is the alternative approach to get basic information on these fundamental quantities. In the present work, three-dimensional DNS of premixed flames in isotropic turbulent flow is used to estimate the different terms appearing in the Sigma-equation. A new methodology is proposed to provide the source and sink terms for the flame surface density, resolved both temporally and spatially throughout the turbulent flame brush. Using this methodology, our objective is to extract the turbulent flame stretch from the DNS data base and then perform extensive comparisons with flamelet models. Thanks to the detailed information produced by the DNS-based analysis, it is expected that this type of comparison will not only

Insulin detemir: a review of its use in the management of diabetes mellitus.

PubMed

Keating, Gillian M

2012-12-03

Insulin detemir (Levemir®) is a long-acting insulin analogue indicated for use as basal insulin therapy in patients with type 1 or 2 diabetes mellitus. The protracted action of insulin detemir is explained by increased self-association and reversible binding to albumin, which slows its systemic absorption from the injection site. In glucose-clamp studies, less within-patient variability in glucose-lowering effect was seen with insulin detemir than with neutral protamine Hagedorn (NPH) insulin or insulin glargine in patients with type 1 or 2 diabetes. The beneficial effect of insulin detemir on glycaemic control was shown in numerous randomized, open-label, multicentre trials, including when used as basal-bolus therapy in patients with type 1 or 2 diabetes and as basal therapy in addition to oral antidiabetic drugs in insulin-naive patients with type 2 diabetes. In terms of glycosylated haemoglobin (HbA(1c)).[primary endpoint in most trials], insulin detemir was generally at least as effective as NPH insulin, insulin glargine or insulin lispro protamine suspension in patients with type 1 or 2 diabetes, and at least as effective as biphasic insulin aspart in patients with type 2 diabetes. Less within-patient variability in blood glucose was also generally seen with insulin detemir than with NPH insulin in patients with type 1 or 2 diabetes. Significantly less weight gain was generally seen with insulin detemir than with NPH insulin in patients with type 1 diabetes or with insulin detemir than with NPH insulin, insulin glargine, insulin lispro protamine suspension or biphasic insulin aspart (in one study) in patients with type 2 diabetes (i.e. insulin detemir generally had a weight-sparing effect). The addition of insulin detemir to liraglutide plus metformin improved glycaemic control in insulin-naive patients with type 2 diabetes and inadequate glycaemic control, although a significantly greater reduction in bodyweight was seen in patients receiving liraglutide

Experimental study on the flame behaviors of premixed methane/air mixture in horizontal rectangular ducts

NASA Astrophysics Data System (ADS)

Chen, Dongliang; Sun, Jinhua; Chen, Sining; Liu, Yi; Chu, Guanquan

2007-01-01

In order to explore the flame propagation characteristics and tulip flame formation mechanism of premixed methane/air mixture in horizontal rectangular ducts, the techniques of Schlieren and high-speed video camera are used to study the flame behaviors of the premixed gases in a closed duct and opened one respectively, and the propagation characteristics in both cases and the formation mechanism of the tulip flame are analyzed. The results show that, the propagation flame in a closed duct is prior to form a tulip flame structure than that in an opened duct, and the tulip flame structure formation in a closed duct is related to the flame propagation velocity decrease. The sharp decrease of the flame propagation velocity is one of the reasons to the tulip flame formation, and the decrease of the flame propagation velocity is due to the decrease of the burned product flow velocity mainly.

Effects of elliptical burner geometry on partially premixed gas jet flames in quiescent surroundings

NASA Astrophysics Data System (ADS)

Baird, Benjamin

This study is the investigation of the effect of elliptical nozzle burner geometry and partial premixing, both 'passive control' methods, on a hydrogen/hydrocarbon flame. Both laminar and turbulent flames for circular, 3:1, and 4:1 aspect ratio (AR) elliptical burners are considered. The amount of air mixed with the fuel is varied from fuel-lean premixed flames to fuel-rich partially premixed flames. The work includes measurements of flame stability, global pollutant emissions, flame radiation, and flame structure for the differing burner types and fuel conditions. Special emphasis is placed on the near-burner region. Experimentally, both conventional (IR absorption, chemiluminecent, and polarographic emission analysis,) and advanced (laser induced fluorescence, planar laser induced fluorescence, Laser Doppler Velocimetry (LDV), Rayleigh scattering) diagnostic techniques are used. Numerically, simulations of 3-dimensional laminar and turbulent reacting flow are conducted. These simulations are run with reduced chemical kinetics and with a Reynolds Stress Model (RSM) for the turbulence modeling. It was found that the laminar flames were similar in appearance and overall flame length for the 3:1 AR elliptical and the circular burner. The laminar 4:1 AR elliptical burner flame split into two sub-flames along the burner major axis. This splitting had the effect of greatly shortening the 4:1 AR elliptical burner flame to have an overall flame length about half of that of the circular and 3:1 AR elliptical burner flames. The length of all three burners flames increased with increasing burner exit equivalence ratio. The blowout velocity for the three burners increased with increase in hydrogen mass fraction of the hydrogen/propane fuel mixture. For the rich premixed flames, the circular burner was the most stable, the 3:1 AR elliptical burner, was the least stable, and the 4:1 AR elliptical burner was intermediate to the two other burners. This order of stability was due

Pre-mixing apparatus for a turbine engine

DOEpatents

Lacy, Benjamin Paul [Greer, SC; Varatharajan, Balachandar [Cincinnati, OH; Ziminsky, Willy Steve [Simpsonville, SC; Kraemer, Gilbert Otto [Greer, SC; Yilmaz, Ertan [Albany, NY; Melton, Patrick Benedict [Horse Shoe, NC; Zuo, Baifang [Simpsonville, SC; Stevenson, Christian Xavier [Inman, SC; Felling, David Kenton [Greenville, SC; Uhm, Jong Ho [Simpsonville, SC

2012-04-03

A pre-mixing apparatus for a turbine engine includes a main body having an inlet portion, an outlet portion and an exterior wall that collectively establish at least one fluid delivery plenum, and a plurality of fluid delivery tubes extending through at least a portion of the at least one fluid delivery plenum. Each of the plurality of fluid delivery tubes includes at least one fluid delivery opening fluidly connected to the at least one fluid delivery plenum. With this arrangement, a first fluid is selectively delivered to the at least one fluid delivery plenum, passed through the at least one fluid delivery opening and mixed with a second fluid flowing through the plurality of fluid delivery tubes prior to being combusted in a combustion chamber of a turbine engine.

Prescription patterns of long-acting somatostatin analogues

PubMed Central

Machado-Alba, Jorge Enrique; Machado-Duque, Manuel Enrique

2017-01-01

Background: Acromegaly and endocrine tumors are uncommon morbidities that are currently treated with different drugs. Objective: To determine the prescription patterns of somatostatin analogues in patients affiliated with the Health System of Colombia. Methods: Retrospective cohort study of patients of any age and sex treated with octreotide or lanreotide between January 2011 and August 2015. Socio-demographic, clinical (indications) and pharmacological (comedications) variables were considered. Multivariate analysis was performed with SPSS 23.0. Results: We identified 289 patients, with a mean age of 56.6 ± 14.0 years and female predominance (59.5%), who underwent treatment during the 56 months of monitoring. Octreotide was used in 56.1% of cases, followed by lanreotide (43.9%), both at approved doses. We found that 4.5% of subjects changed from one drug to another over the course of therapy, which was associated with being diabetic and receiving insulin (odds ratio: 4.27; 95% confidence interval: 1.23–14.84; p = 0.014). The most common indications were acromegaly (52.2% of cases) followed by neuroendocrine tumors (15.9%). The most common comorbidities were hypertension (39.4% of cases), depression (27.3%), dyslipidemia (23.3%), diabetes mellitus (23.5%) and hypothyroidism (23.5%). Being male (odds ratio: 0.57; 95% confidence interval: 0.35–0.94; p = 0.029) and belonging to the age group between 45 and 65 years (odds ratio: 0.44; 95% confidence interval: 0.21–0.90; p = 0.024) were significantly associated with a lower risk of receiving comedications. Conclusion: Somatostatin analogues are being used at recommended doses, especially in patients with acromegaly and neuroendocrine tumors. Variables associated with change in therapy were identified. PMID:28540043

Prescription patterns of long-acting somatostatin analogues.

PubMed

Machado-Alba, Jorge Enrique; Machado-Duque, Manuel Enrique

2017-01-01

Acromegaly and endocrine tumors are uncommon morbidities that are currently treated with different drugs. To determine the prescription patterns of somatostatin analogues in patients affiliated with the Health System of Colombia. Retrospective cohort study of patients of any age and sex treated with octreotide or lanreotide between January 2011 and August 2015. Socio-demographic, clinical (indications) and pharmacological (comedications) variables were considered. Multivariate analysis was performed with SPSS 23.0. We identified 289 patients, with a mean age of 56.6 ± 14.0 years and female predominance (59.5%), who underwent treatment during the 56 months of monitoring. Octreotide was used in 56.1% of cases, followed by lanreotide (43.9%), both at approved doses. We found that 4.5% of subjects changed from one drug to another over the course of therapy, which was associated with being diabetic and receiving insulin (odds ratio: 4.27; 95% confidence interval: 1.23-14.84; p = 0.014). The most common indications were acromegaly (52.2% of cases) followed by neuroendocrine tumors (15.9%). The most common comorbidities were hypertension (39.4% of cases), depression (27.3%), dyslipidemia (23.3%), diabetes mellitus (23.5%) and hypothyroidism (23.5%). Being male (odds ratio: 0.57; 95% confidence interval: 0.35-0.94; p = 0.029) and belonging to the age group between 45 and 65 years (odds ratio: 0.44; 95% confidence interval: 0.21-0.90; p = 0.024) were significantly associated with a lower risk of receiving comedications. Somatostatin analogues are being used at recommended doses, especially in patients with acromegaly and neuroendocrine tumors. Variables associated with change in therapy were identified.

On the Structure of Premixed Flames Subjected to Extreme Levels of Turbulence

NASA Astrophysics Data System (ADS)

Skiba, Aaron William

Developing next-generation propulsion and energy production devices that are efficient, cost-effective, and generate little to no harmful emissions will require highly-accurate, robust, yet computationally tractable turbulent combustion models. Models that accurately simulate turbulent premixed combustion problems are particularly important due to the fact that burning in a premixed mode can reduce exhaust emissions. A common tool employed to identify when a particular model might be more appropriate than others is the theoretical Borghi Diagram, which possesses boundaries that are meant to separate various regimes of combustion (i.e. where a particular model is superior to others). However, the derivations of these boundaries are merely based upon intuition and dimensional reasoning, rather than experimental evidence. This thesis aims to provide such evidence; furthermore, it proposes novel approaches to delineating regimes of combustion that are consistent with experimental results. To this end, high-fidelity flame structure measurements were applied to premixed methane-air Bunsen flames subjected to extreme levels of turbulence. Specifically, 28 cases were studied with turbulence levels (u'/S L) as high as 246, longitudinal integral length scales ( Lx) as large as 43 mm, and turbulent Karlovitz ( KaT) and Reynolds (ReT) numbers up to 533 and 99,000, respectively. Two techniques were employed to measure the preheat and reaction layer thicknesses of these flames. One consisted of planar laser-induced fluorescence (PLIF) imaging of CH radicals, while the other involved taking the product of simultaneously acquired PLIF images of formaldehyde (CH2O) and hydroxyl (OH) to produce "overlap-layers." Average preheat layer thicknesses are found to increase with increasing u'/SL and with axial distance from the burner (x/D). In contrast, average reaction layer thicknesses did not vary appreciably with either u'/SL or x/D. The reaction layers are also observed to remain

Insight into the Structural and Biological Relevance of the T/R Transition of the N-Terminus of the B-Chain in Human Insulin

PubMed Central

2014-01-01

The N-terminus of the B-chain of insulin may adopt two alternative conformations designated as the T- and R-states. Despite the recent structural insight into insulin–insulin receptor (IR) complexes, the physiological relevance of the T/R transition is still unclear. Hence, this study focused on the rational design, synthesis, and characterization of human insulin analogues structurally locked in expected R- or T-states. Sites B3, B5, and B8, capable of affecting the conformation of the N-terminus of the B-chain, were subjects of rational substitutions with amino acids with specific allowed and disallowed dihedral φ and ψ main-chain angles. α-Aminoisobutyric acid was systematically incorporated into positions B3, B5, and B8 for stabilization of the R-state, and N-methylalanine and d-proline amino acids were introduced at position B8 for stabilization of the T-state. IR affinities of the analogues were compared and correlated with their T/R transition ability and analyzed against their crystal and nuclear magnetic resonance structures. Our data revealed that (i) the T-like state is indeed important for the folding efficiency of (pro)insulin, (ii) the R-state is most probably incompatible with an active form of insulin, (iii) the R-state cannot be induced or stabilized by a single substitution at a specific site, and (iv) the B1–B8 segment is capable of folding into a variety of low-affinity T-like states. Therefore, we conclude that the active conformation of the N-terminus of the B-chain must be different from the “classical” T-state and that a substantial flexibility of the B1–B8 segment, where GlyB8 plays a key role, is a crucial prerequisite for an efficient insulin–IR interaction. PMID:24819248

An experimental and numerical study of the inwardly-propagating premixed flame

NASA Astrophysics Data System (ADS)

Ibarreta, Alfonso F.

Flame stretch, described as the time rate of change of the flame surface area, can cause large changes in burning velocity of laminar premixed flames. Many experimental studies have been conducted to quantify the effects of flame stretch, but most only deal with the hydrodynamic strain component of stretch rate. In this thesis, a new experimental technique was used to study the inwardly-propagating premixed flame. This flame configuration is significant because it is subjected to the curvature component of stretch rate without the competing effects of hydrodynamic strain. Inwardly-propagating premixed flames were formed using a vortex to wrinkle a flame and create a pocket of reactants. Experiments using lean propane/air mixtures were run at both one-g and microgravity conditions to optimize the formation of large pockets of reactants. Numerical simulations of the inwardly-propagating flame (IPF) and outwardly-propagating flame (OPF) were performed for lean propane/air, methane/air and hydrogen/air mixtures. Complex chemistry as well as three different one-step reaction models were employed. Markstein numbers obtained from the experiments and computations were compared to OPF experimental data available in the literature. Researchers have used different definitions of flame location and burning velocity; the effects of these differences on the Markstein number were assessed. Experimental and numerical results indicate that the Markstein numbers obtained for the IPF are typically two to three times larger than those for the OPF. It was concluded that the observed difference in Markstein number was not caused by the IPF flame-flame interaction or the presence of intermediate species. Analysis of results obtained from the one-step reaction models identified the reasons for the difference between IPFs and OPFs: (A) the thermo-diffusive mechanism, (B) the pure curvature mechanism and (C) gas expansion. The consumption speed (Sc) was found to depend only on the thermo

[Methods quantitative for determination of water-soluble vitamins in premixes and fortified food products by micellar electrokinetic chromatography on short end of the capillary].

PubMed

Bogachuk, M N; Bessonov, V V; Perederiaev, O I

2011-01-01

It was purposed new technique by micellar electrokinetic chromatography on short end of the capillary (capillary electrophoresis system Agilent 3D CE, DAD, quartz capillary HPCE stndrd cap 56 cm, 50 microm, 50 mM borate buffer pH=9,3, 100 mM sodium dodecil sulfate) for simultaneous determination of water-soluble vitamins (B1, B2, B6, B12, PP, B5, B9, C, B8) in fortified food products and premixes. It was observed on 6 samples of vitamin premixes and 28 samples of fortified food products using this technique. Our findings are consistent with the results of research on certain vitamins, conducted by other methods. The developed technique can be used in analysis of water-soluble vitamins in premixes and fortified food products.

Once-daily basal insulin glargine versus thrice-daily prandial insulin lispro in people with type 2 diabetes on oral hypoglycaemic agents (APOLLO): an open randomised controlled trial.

PubMed

Bretzel, Reinhard G; Nuber, Ulrike; Landgraf, Wolfgang; Owens, David R; Bradley, Clare; Linn, Thomas

2008-03-29

-28] events per patient per year; p<0.0001). Respective mean weight gains were 3.01 (SD 4.33) kg and 3.54 (4.48) kg. The improvement of treatment satisfaction was greater for insulin glargine than for insulin lispro (mean difference 3.13; 95% CI 2.04-4.22). A therapeutic regimen involving the addition of either basal or prandial insulin analogue is equally effective in lowering haemoglobin A(1c). We conclude that insulin glargine provides a simple and effective option that is more satisfactory to patients than is lispro for early initiation of insulin therapy, since it was associated with a lower risk of hypoglycaemia, fewer injections, less blood glucose self monitoring, and greater patient satisfaction than was insulin lispro. Sanofi-Aventis.

Autophagy Differentially Regulates Insulin Production and Insulin Sensitivity.

PubMed

Yamamoto, Soh; Kuramoto, Kenta; Wang, Nan; Situ, Xiaolei; Priyadarshini, Medha; Zhang, Weiran; Cordoba-Chacon, Jose; Layden, Brian T; He, Congcong

2018-06-12

Autophagy, a stress-induced lysosomal degradative pathway, has been assumed to exert similar metabolic effects in different organs. Here, we establish a model where autophagy plays different roles in insulin-producing β cells versus insulin-responsive cells, utilizing knockin (Becn1 F121A ) mice manifesting constitutively active autophagy. With a high-fat-diet challenge, the autophagy-hyperactive mice unexpectedly show impaired glucose tolerance, but improved insulin sensitivity, compared to mice with normal autophagy. Autophagy hyperactivation enhances insulin signaling, via suppressing ER stress in insulin-responsive cells, but decreases insulin secretion by selectively sequestrating and degrading insulin granule vesicles in β cells, a process we term "vesicophagy." The reduction in insulin storage, insulin secretion, and glucose tolerance is reversed by transient treatment of autophagy inhibitors. Thus, β cells and insulin-responsive tissues require different autophagy levels for optimal function. To improve insulin sensitivity without hampering secretion, acute or intermittent, rather than chronic, activation of autophagy should be considered in diabetic therapy development. Copyright © 2018 The Author(s). Published by Elsevier Inc. All rights reserved.

The co-formulation of insulin degludec and insulin aspart lowers fasting plasma glucose and rates of confirmed and nocturnal hypoglycaemia, independent of baseline glycated haemoglobin levels, disease duration or body mass index: A pooled meta-analysis of phase III studies in patients with type 2 diabetes.

PubMed

Haluzík, Martin; Fulcher, Greg; Pieber, Thomas R; Bardtrum, Lars; Tutkunkardas, Deniz; Rodbard, Helena W

2018-02-16

To investigate whether the proven benefits of insulin degludec (IDeg) combined with insulin aspart (IAsp), known as IDegAsp, given twice daily, extend across a wide spectrum of patients with diabetes. This was a post hoc pooled analysis of 5 phase III randomized, 26-week, open-label, treat-to-target trials comparing IDegAsp twice daily (n = 1111) with one of two comparators: premixed insulin (biphasic insulin aspart 30 [BIAsp 30]) twice daily (n = 561) or IDeg once daily + IAsp (n = 136). Patient data were stratified according to baseline glycated haemoglobin (HbA1c) or fasting plasma glucose (FPG) categories, as well as by baseline duration of diabetes or body mass index (BMI) categories. We conducted a meta-analysis of 5 clinical trials: NCT01513590, NCT01009580, NCT01059812, NCT01680341 and NCT01713530. End-of-trial results were broadly consistent, with differences between IDegAsp and comparators observed in phase III trials. HbA1c results were similar for IDegAsp and the comparators in all baseline characteristic (HbA1c, duration of diabetes or BMI) and category groups (number ranges). Significantly lower FPG level was observed with IDegAsp vs comparators in all baseline characteristic and most category groups (excluding FPG <5.5 mmol/L). Significantly lower insulin doses were observed with IDegAsp vs comparators in all baseline characteristic and half of the category groups, and significantly lower rates of confirmed and nocturnal confirmed hypoglycaemia were observed with IDegAsp vs comparators in all baseline variable and category groups. IDegAsp retains a consistent safety and efficacy profile in patients with different baseline characteristics. © 2018 The Authors. Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd.

Effect of energetic electrons on combustion of premixed burner flame

NASA Astrophysics Data System (ADS)

Sasaki, Koichi

2011-10-01

In many studies of plasma-assisted combustion, authors superpose discharges onto flames to control combustion reactions. This work is motivated by more fundamental point of view. The standpoint of this work is that flames themselves are already plasmas. We irradiated microwave power onto premixed burner flame with the intention of heating electrons in it. The microwave power was limited below the threshold for a discharge. We obtained the enhancement of burning velocity by the irradiation of the microwave power, which was understood by the shortening of the flame length. At the same time, we observed the increases in the optical emission intensities of OH and CH radicals. Despite the increases in the optical emission intensities, the optical emission spectra of OH and CH were not affected by the microwave irradiation, indicating that the enhancement of the burning velocity was not attributed to the increase in the gas temperature. On the other hand, we observed significant increase in the optical emission intensity of the second positive system of molecular nitrogen, which is a clear evidence for electron heating in the premixed burner flame. Therefore, it is considered that the enhancement of the burning velocity is obtained by nonequilibrium combustion chemistry which is driven by energetic electrons. By irradiating pulsed microwave power, we examined the time constants for the increases and decreases in the optical emission intensities of N2, OH, CH, and continuum radiation.

AROMATIC AND POLYCYCLIC AROMATIC HYDROCARBON FORMATION IN A LAMINAR PREMIXED N-BUTANE FLAME. (R825412)

EPA Science Inventory

Abstract

Experimental and detailed chemical kinetic modeling work has been performed to investigate aromatic and polycyclic aromatic hydrocarbon (PAH) formation pathways in a premixed, rich, sooting, n-butane_¯oxygen_¯argon burner s...

Flow field and scalar measurements in a series of turbulent partially-premixed dimethyl ether/air jet flames

DOE PAGES

Coriton, Bruno; Im, Seong -Kyun; Gamba, Mirko; ...

2017-03-12

Here, we present a series of benchmark flames consisting of six partially-premixed piloted dimethyl ether (DME)/air jet flames. These flames provide an opportunity to understand turbulence-flame interactions for oxygenated fuels and to develop predictive models for these interactions using a canonical burner geometry. The development of accurate models for DME/air flames would establish a foundation for studies of more complex oxygenated fuels. The flames are stabilized on a piloted jet burner similar to that of the partially-premixed methane/air jet flames that have been studied extensively within the context of the TNF Workshop. This series of six jet flames spans jetmore » exit Reynolds numbers, ReD, from 29,300 to 73,300 and stoichiometric mixture fractions, ξ st, from 0.35 to 0.60. Flame conditions range from very low probability of localized extinction to a high probability of localized extinction and subsequent re-ignition. Measurements in the flames are compared at downstream locations from 5 to 25 diameters above the nozzle exit. Mean and fluctuating velocity components are measured using stereo particle image velocimetry (SPIV). Simultaneous laser-induced fluorescence (LIF) imaging of OH and CH 2O provides insights into the distribution of these intermediate species in partially-premixed DME/air flames. OH LIF imaging is also combined with SPIV to investigate the strain rate field across the reaction zone.« less

Flow field and scalar measurements in a series of turbulent partially-premixed dimethyl ether/air jet flames

DOE Office of Scientific and Technical Information (OSTI.GOV)

Coriton, Bruno; Im, Seong -Kyun; Gamba, Mirko

Here, we present a series of benchmark flames consisting of six partially-premixed piloted dimethyl ether (DME)/air jet flames. These flames provide an opportunity to understand turbulence-flame interactions for oxygenated fuels and to develop predictive models for these interactions using a canonical burner geometry. The development of accurate models for DME/air flames would establish a foundation for studies of more complex oxygenated fuels. The flames are stabilized on a piloted jet burner similar to that of the partially-premixed methane/air jet flames that have been studied extensively within the context of the TNF Workshop. This series of six jet flames spans jetmore » exit Reynolds numbers, ReD, from 29,300 to 73,300 and stoichiometric mixture fractions, ξ st, from 0.35 to 0.60. Flame conditions range from very low probability of localized extinction to a high probability of localized extinction and subsequent re-ignition. Measurements in the flames are compared at downstream locations from 5 to 25 diameters above the nozzle exit. Mean and fluctuating velocity components are measured using stereo particle image velocimetry (SPIV). Simultaneous laser-induced fluorescence (LIF) imaging of OH and CH 2O provides insights into the distribution of these intermediate species in partially-premixed DME/air flames. OH LIF imaging is also combined with SPIV to investigate the strain rate field across the reaction zone.« less

Errors induced by catalytic effects in premixed flame temperature measurements

NASA Astrophysics Data System (ADS)

Pita, G. P. A.; Nina, M. N. R.

The evaluation of instantaneous temperature in a premixed flame using fine-wire Pt/Pt-(13 pct)Rh thermocouples was found to be subject to significant errors due to catalytic effects. An experimental study was undertaken to assess the influence of local fuel/air ratio, thermocouple wire diameter, and gas velocity on the thermocouple reading errors induced by the catalytic surface reactions. Measurements made with both coated and uncoated thermocouples showed that the catalytic effect imposes severe limitations on the accuracy of mean and fluctuating gas temperature in the radical-rich flame zone.

Insulin Secretagogues

MedlinePlus

... the Spikes Is mealtime insulin right for you? Insulin Secretagogues September 2017 Download PDFs English Espanol Editors ... Additional Resources Affordable Insulin Project FDA What are insulin secretagogues? Insulin secretagogues are one type of medicine ...

Insulin secretion and insulin action in non-insulin-dependent diabetes mellitus: which defect is primary?

PubMed

Reaven, G M

1984-01-01

Defects in both insulin secretion and insulin action exist in patients with non-insulin-dependent diabetes mellitus (NIDDM). The loss of the acute plasma insulin response to intravenous glucose is seen in patients with relatively mild degrees of fasting hyperglycemia, but patients with severe fasting hyperglycemia also demonstrate absolute hypoinsulinemia in response to an oral glucose challenge. In contrast, day-long circulating insulin levels are within normal limits even in severely hyperglycemic patients with NIDDM. The relationship between NIDDM and insulin action in NIDDM is less complex, and is a characteristic feature of the syndrome. This metabolic defect is independent of obesity, and the severity of the resistance to insulin-stimulated glucose uptake increases with magnitude of hyperglycemia. Control of hyperglycemia with exogenous insulin ameliorates the degree of insulin resistance, and reduction of insulin resistance with weight loss in obese patients with NIDDM leads to an enhanced insulin response. Since neither therapeutic intervention is capable of restoring all metabolic abnormalities to normal, these observations do not tell us which of these two defects is primarily responsible for the development of NIDDM. Similarly, the observation that most patients with impaired glucose tolerance are hyperinsulinemic and insulin resistant does not prove that insulin resistance is the primary defect in NIDDM. In conclusion, reduction in both insulin secretion and action is seen in patients with NIDDM, and the relationship between these two metabolic abnormalities is very complex.(ABSTRACT TRUNCATED AT 250 WORDS)

Pioglitazone and exenatide enhance cognition and downregulate hippocampal beta amyloid oligomer and microglia expression in insulin-resistant rats.

PubMed

Gad, Enas S; Zaitone, Sawsan A; Moustafa, Yasser M

2016-08-01

Insulin resistance is known to be a risk factor for cognitive impairment, most likely linked to insulin signaling, microglia overactivation, and beta amyloid (Aβ) deposition in the brain. Exenatide, a long lasting glucagon-like peptide-1 (GLP-1) analogue, enhances insulin signaling and shows neuroprotective properties. Pioglitazone, a peroxisome proliferated-activated receptor-γ (PPAR-γ) agonist, was previously reported to enhance cognition through its effect on Aβ accumulation and clearance. In the present study, insulin resistance was induced in male rats by drinking fructose for 12 weeks. The effect of monotherapy with pioglitazone (10 mg·kg(-1)) and exenatide or their combination on memory dysfunction was determined and some of the probable underlying mechanisms were studied. The current results confirmed that (1) feeding male rats with fructose syrup for 12 weeks resulted in a decline of learning and memory registered in eight-arm radial maze test; (2) treatment with pioglitazone or exenatide enhanced cognition, reduced hippocampal neurodegeneration, and reduced hippocampal microglia expression and beta amyloid oligomer deposition in a manner that is equal to monotherapies. These results may give promise for the use of pioglitazone or exenatide for ameliorating the learning and memory deficits associated with insulin resistance in clinical setting.

Effect of the Glucagon-like Peptide-1 Analogue Exenatide Extended Release in Cats with Newly Diagnosed Diabetes Mellitus.

PubMed

Riederer, A; Zini, E; Salesov, E; Fracassi, F; Padrutt, I; Macha, K; Stöckle, T M; Lutz, T A; Reusch, C E

2016-01-01

Exenatide extended release (ER) is a glucagon-like peptide-1 analogue that increases insulin secretion, inhibits glucagon secretion and induces satiation in humans with type 2 diabetes mellitus. The use of exenatide ER is safe and stimulates insulin secretion in healthy cats. The objective of this study is to assess the safety of exenatide ER and its effect on body weight, remission and metabolic control in newly diagnosed diabetic cats receiving insulin and a low-carbohydrate diet. Thirty client-owned cats. Prospective placebo-controlled clinical trial. Cats were treated with exenatide ER or 0.9% saline, administered SC, once weekly. Both groups received insulin glargine and a low-carbohydrate diet. Exenatide ER was administered for 16 weeks, or in cats that achieved remission it was given for 4 weeks after discontinuing insulin treatment. Nonparametric tests were used for statistical analysis. Cats in the exenatide ER and placebo groups had transient adverse signs including decreased appetite (60% vs. 20%, respectively, P = .06) and vomiting (53% vs. 40%, respectively, P = .715). Body weight increased significantly in the placebo group (P = .002), but not in cats receiving exenatide ER. Cats on exenatide ER achieved remission or good metabolic control in 40% or 89%, respectively, whereas in control cats percentages were 20% or 58% (P = .427 and P = .178, respectively). Exenatide ER is safe in diabetic cats and does not result in weight gain. Our pilot study suggests that, should there be an additional clinically relevant beneficial effect of exenatide ER in insulin-treated cats on rate of remission and good metabolic control, it would likely approximate 20% and 30%, respectively. Copyright © 2015 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals, Inc. on behalf of the American College of Veterinary Internal Medicine.

Flame thickness and conditional scalar dissipation rate in a premixed temporal turbulent reacting jet

DOE Office of Scientific and Technical Information (OSTI.GOV)

Chaudhuri, Swetaprovo; Kolla, Hemanth; Dave, Himanshu L.

The flame structure corresponding to lean hydrogen–air premixed flames in intense sheared turbulence in the thin reaction zone regime is quantified from flame thickness and conditional scalar dissipation rate statistics, obtained from recent direct numerical simulation data of premixed temporally-evolving turbulent slot jet flames. It is found that, on average, these sheared turbulent flames are thinner than their corresponding planar laminar flames. Extensive analysis is performed to identify the reason for this counter-intuitive thinning effect. The factors controlling the flame thickness are analyzed through two different routes i.e., the kinematic route, and the transport and chemical kinetics route. The kinematicmore » route is examined by comparing the statistics of the normal strain rate due to fluid motion with the statistics of the normal strain rate due to varying flame displacement speed or self-propagation. It is found that while the fluid normal straining is positive and tends to separate iso-scalar surfaces, the dominating normal strain rate due to self-propagation is negative and tends to bring the iso-scalar surfaces closer resulting in overall thinning of the flame. The transport and chemical kinetics route is examined by studying the non-unity Lewis number effect on the premixed flames. The effects from the kinematic route are found to couple with the transport and chemical kinetics route. In addition, the intermittency of the conditional scalar dissipation rate is also examined. It is found to exhibit a unique non-monotonicity of the exponent of the stretched exponential function, conventionally used to describe probability density function tails of such variables. As a result, the non-monotonicity is attributed to the detailed chemical structure of hydrogen-air flames in which heat release occurs close to the unburnt reactants at near free-stream temperatures.« less

Flame thickness and conditional scalar dissipation rate in a premixed temporal turbulent reacting jet

DOE PAGES

Chaudhuri, Swetaprovo; Kolla, Hemanth; Dave, Himanshu L.; ...

2017-07-07

The flame structure corresponding to lean hydrogen–air premixed flames in intense sheared turbulence in the thin reaction zone regime is quantified from flame thickness and conditional scalar dissipation rate statistics, obtained from recent direct numerical simulation data of premixed temporally-evolving turbulent slot jet flames. It is found that, on average, these sheared turbulent flames are thinner than their corresponding planar laminar flames. Extensive analysis is performed to identify the reason for this counter-intuitive thinning effect. The factors controlling the flame thickness are analyzed through two different routes i.e., the kinematic route, and the transport and chemical kinetics route. The kinematicmore » route is examined by comparing the statistics of the normal strain rate due to fluid motion with the statistics of the normal strain rate due to varying flame displacement speed or self-propagation. It is found that while the fluid normal straining is positive and tends to separate iso-scalar surfaces, the dominating normal strain rate due to self-propagation is negative and tends to bring the iso-scalar surfaces closer resulting in overall thinning of the flame. The transport and chemical kinetics route is examined by studying the non-unity Lewis number effect on the premixed flames. The effects from the kinematic route are found to couple with the transport and chemical kinetics route. In addition, the intermittency of the conditional scalar dissipation rate is also examined. It is found to exhibit a unique non-monotonicity of the exponent of the stretched exponential function, conventionally used to describe probability density function tails of such variables. As a result, the non-monotonicity is attributed to the detailed chemical structure of hydrogen-air flames in which heat release occurs close to the unburnt reactants at near free-stream temperatures.« less

EXPERIMENTAL AND MODELING STUDY OF PREMIXED LAMINAR FLAMES OF ETHANOL AND METHANE

PubMed Central

Tran, Luc-Sy; Glaude, Pierre-Alexandre; Fournet, René; Battin-Leclerc, Frédérique

2013-01-01

To better understand the chemistry of the combustion of ethanol, the structure of five low pressure laminar premixed flames has been investigated: a pure methane flame (φ=1), three pure ethanol flames (φ=0.7, 1.0, and 1.3), and an ethanol/methane mixture flames (φ=1). The flames have been stabilized on a burner at a pressure of 6.7 kPa using argon as dilutant, with a gas velocity at the burner of 64.3 cm/s at 333 K. The results consist of mole fraction profiles of 20 species measured as a function of the height above the burner by probe sampling followed by online gas chromatography analyses. A mechanism for the oxidation of ethanol was proposed. The reactions of ethanol and acetaldehyde were updated and include recent theoretical calculations while that of ethenol, dimethyl ether, acetone, and propanal were added in the mechanism. This mechanism was also tested against experimental results available in the literature for laminar burning velocities and laminar premixed flame where ethenol was detected. The main reaction pathways of consumption of ethanol are analyzed. The effect of the branching ratios of reaction C2H5OH+OH→Products+H2O is also discussed. PMID:23712124

EXPERIMENTAL AND MODELING STUDY OF PREMIXED LAMINAR FLAMES OF ETHANOL AND METHANE.

PubMed

Tran, Luc-Sy; Glaude, Pierre-Alexandre; Fournet, René; Battin-Leclerc, Frédérique

2013-04-18

To better understand the chemistry of the combustion of ethanol, the structure of five low pressure laminar premixed flames has been investigated: a pure methane flame (φ=1), three pure ethanol flames (φ=0.7, 1.0, and 1.3), and an ethanol/methane mixture flames (φ=1). The flames have been stabilized on a burner at a pressure of 6.7 kPa using argon as dilutant, with a gas velocity at the burner of 64.3 cm/s at 333 K. The results consist of mole fraction profiles of 20 species measured as a function of the height above the burner by probe sampling followed by online gas chromatography analyses. A mechanism for the oxidation of ethanol was proposed. The reactions of ethanol and acetaldehyde were updated and include recent theoretical calculations while that of ethenol, dimethyl ether, acetone, and propanal were added in the mechanism. This mechanism was also tested against experimental results available in the literature for laminar burning velocities and laminar premixed flame where ethenol was detected. The main reaction pathways of consumption of ethanol are analyzed. The effect of the branching ratios of reaction C 2 H 5 OH+OH→Products+H 2 O is also discussed.

Computations of steady-state and transient premixed turbulent flames using pdf methods

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hulek, T.; Lindstedt, R.P.

1996-03-01

Premixed propagating turbulent flames are modeled using a one-point, single time, joint velocity-composition probability density function (pdf) closure. The pdf evolution equation is solved using a Monte Carlo method. The unclosed terms in the pdf equation are modeled using a modified version of the binomial Langevin model for scalar mixing of Valino and Dopazo, and the Haworth and Pope (HP) and Lagrangian Speziale-Sarkar-Gatski (LSSG) models for the viscous dissipation of velocity and the fluctuating pressure gradient. The source terms for the presumed one-step chemical reaction are extracted from the rate of fuel consumption in laminar premixed hydrocarbon flames, computed usingmore » a detailed chemical kinetic mechanism. Steady-state and transient solutions are obtained for planar turbulent methane-air and propane-air flames. The transient solution method features a coupling with a Finite Volume (FV) code to obtain the mean pressure field. The results are compared with the burning velocity measurements of Abdel-Gayed et al. and with velocity measurements obtained in freely propagating propane-air flames by Videto and Santavicca. The effects of different upstream turbulence fields, chemical source terms (different fuels and strained/unstrained laminar flames) and the influence of the velocity statistics models (HP and LSSG) are assessed.« less

Does the newer preparation of propofol, an emulsion of medium/long chain triglycerides cause less injection pain in children when premixed with lignocaine?

PubMed

Varghese, Elsa; Krishna, Handattu Mahabaleswara; Nittala, Anuradha

2010-04-01

Injection pain during propofol administration can be particularly distressing in children. The newly available emulsion of propofol in medium and long chain triglycerides (LCT) is reported to cause less injection pain because of lower concentrations of free propofol. This study compared the incidence of injection pain during administration of propofol emulsion of LCT and propofol emulsion of medium and long chain triglycerides (MCT/LCT) both premixed with lignocaine in children. This prospective, randomized, double blind study was conducted after obtaining institutional ethics committee approval, parental consent and included 84 children aged 5-15 years. Preoperatively, an intravenous cannula was inserted in all children. four children were excluded. Those included, depending on the randomization, received 3 mg x kg(-1) of either propofol LCT or propofol MCT/LCT both premixed with lignocaine (0.1%). The incidence and intensity of injection pain was assessed. Pain on injection of propofol LCT with lignocaine was observed in 16/40 children (40%), five of these children complained of severe pain. In comparison, 14/40 (35%) children complained of pain following propofol MCT/LCT premixed with lignocaine (P = 0.644), the intensity being severe in two children (P = 0.698). Propofol MCT/LCT and propofol LCT premixed with lignocaine are both associated with pain on injection in children; the incidence and intensity of the injection pain are similar.

Analysis of Lean Premixed/Prevaporized Combustion with KIVA-2

NASA Technical Reports Server (NTRS)

Deur, J. M.; Kundu, K. P.; Darling, D. D.; Cline, M. C.; Micklow, G. J.; Harper, M. R.; Simons, T. A.

1994-01-01

Requirements to reduce the emissions of pollutants from gas turbines used in aircraft propulsion and ground based power generation have led to consideration of lean premixed/prevaporized (LPP) combustion concept. This paper describes some of the LPP flame tube analyses performed at the NASA Research Center with KIVA-2, a well-known multi-dimensional CFD code for problems including sprays, turbulence, and combustion. Modifications to KIVA-2's boundary condition and chemistry treatments have been made to meet the needs of the present study. The study itself focuses on two key aspects of the LPP concept, low emissions and flame stability (including flashback and lean blowoff.

Effects of porous insert on flame dynamics in a lean premixed swirl-stabilized combustor

NASA Astrophysics Data System (ADS)

Brown, Marcus; Agrawal, Ajay; Allen, James; Kornegay, John

2016-11-01

In this study, we investigated different methods of determining the effect a porous insert has on flame dynamics during lean premixed combustion. A metallic porous insert is used to mitigate instabilities in a swirl-stabilized combustor. Thermoacoustic instabilities are seen as negative consequences of lean premixed combustion and eliminating them is the motivation for our research. Three different diagnostics techniques with high-speed Photron SA5 cameras were used to monitor flame characteristics. Particle image velocimetry (PIV) was used to observe vortical structures and recirculation zones within the combustor. Using planar laser induced fluorescence (PLIF), we were able to observe changes in the reaction zones during instabilities. Finally, utilizing a color high-speed camera, visual images depicting a flame's oscillations during the instability were captured. Using these monitoring techniques, we are able to support the claims made in previous studies stating that the porous insert in the combustor significantly reduces the thermoacoustic instability. Funding for this research was provided by the NSF REU site Grant EEC 1358991 and NASA Grant NNX13AN14A.

The cost effectiveness of rapid-acting insulin aspart compared with human insulin in type 2 diabetes patients: an analysis from the Japanese third-party payer perspective.

PubMed

Pollock, R F; Valentine, W J; Pilgaard, T; Nishimura, H

2011-01-01

The Nippon Ultra-Rapid Insulin and Diabetic Complication Evaluation Study (NICE Study) (NCT00575172) was a 5-year, open-label, randomised controlled trial which compared cardiovascular outcomes in Japanese type 2 diabetes patients intensively treated with regular human insulin or insulin aspart (NovoRapid; Novo Nordisk A/S, Bagsvaerd, Denmark), a rapid-acting insulin analogue. The aim of the present analysis was to evaluate the cost effectiveness of insulin aspart versus regular human insulin from the perspective of a Japanese third-party healthcare payer. A discrete event-simulation model was developed in Microsoft Excel to assess the within-trial cost effectiveness and make longer-term clinical projections in patients treated with regular human insulin or insulin aspart. In addition to severe hypoglycaemia, the model captured myocardial and cerebral infarction events and percutaneous coronary intervention and coronary artery bypass graft procedures. Within-trial mortality, incidence of severe hypoglycaemia and cardiovascular event probabilities were derived from the annual rates observed during the trial period, while post-trial outcomes were calculated using the event rates from the trial, adjusted for increasing patient age. Event costs were accounted from the healthcare payer perspective and expressed in 2008 Japanese yen (JPY), while health-related quality of life (HRQoL) was captured using event and state utilities. Future costs and clinical benefits were discounted at 3% annually. Life expectancy, quality-adjusted life expectancy, cardiovascular event rates and costs were evaluated over 5- and 10-year time horizons and sensitivity analyses were performed to assess variability in model outcomes. Over 5 years of treatment, insulin aspart dominated human insulin both in incremental life expectancy and in incremental quality-adjusted life-years (QALYS). Insulin aspart was associated with a small improvement in discounted life expectancy of 0.005 years (4.688 vs

Flashback detection sensor for lean premix fuel nozzles

DOEpatents

Thornton, Jimmy Dean [Morgantown, WV; Richards, George Alan [Morgantown, WV; Straub, Douglas L [Morgantown, WV; Liese, Eric Arnold [Morgantown, WV; Trader, Jr., John Lee; Fasching, George Edward [Morgantown, WV

2002-08-06

A sensor for detecting the flame occurring during a flashback condition in the fuel nozzle of a lean premix combustion system is presented. The sensor comprises an electrically isolated flashback detection electrode and a guard electrode, both of which generate electrical fields extending to the walls of the combustion chamber and to the walls of the fuel nozzle. The sensor is positioned on the fuel nozzle center body at a location proximate the entrance to the combustion chamber of the gas turbine combustion system. The sensor provides 360.degree. detection of a flashback inside the fuel nozzle, by detecting the current conducted by the flame within a time frame that will prevent damage to the gas turbine combustion system caused by the flashback condition.

Combustion efficiency of a premixed continuous flow combustor

NASA Technical Reports Server (NTRS)

Anand, M. S.; Gouldin, F. C.

1985-01-01

Exhaust gas temperature, velocity, and composition measurements at various radial locations at the combustor exit are presented for a swirling-flow continuous combustor of a confined concentric jet configuration operating on premixed propane or methane and air. The main objective of the study is to determine the effect of fuel substitution and of changes in outer flow swirl conditions on the combustor performance. It is found that there is no difference in observed properties for propane and methane firing; the use of either of the fuels results in nearly the same exit temperature and velocity profiles and the same efficiency for a given operating condition. A mechanism for combustion is proposed which explains qualitatively the changes in efficiency and pollutant emissions observed with changing swirl.

Turbulent Premixed Flame Propagation in Microgravity

NASA Technical Reports Server (NTRS)

Menon, S.; Disseau, M.; Chakravarthy, V. K.; Jagoda, J.

1997-01-01

A facility in which turbulent Couette flow could be generated in a microgravity environment was designed and built. To fit into the NASA Lewis drop tower the device had to be very compact. This means that edge effects and flow re-circulation were expected to affect the flow. The flow was thoroughly investigated using LDV and was found to be largely two dimensional away from the edges with constant turbulence intensities in the core. Slight flow asymmetries are introduced by the non symmetric re-circulation of the fluid outside the test region. Belt flutter problems were remedied by adding a pair of guide plates to the belt. In general, the flow field was found to be quite similar to previously investigated Couette flows. However, turbulence levels and associated shear stresses were higher. This is probably due to the confined re-circulation zone reintroducing turbulence into the test section. An estimate of the length scales in the flow showed that the measurements were able to resolve nearly all the length scales of interest. Using a new LES method for subgrid combustion it has been demonstrated that the new procedure is computational feasible even on workstation type environment. It is found that this model is capable of capturing the propagation of the premixed names by resolving the flame in the LES grid within 2-3 grid points. In contrast, conventional LES results in numerical smearing of the flame and completely inaccurate estimate of the turbulent propagation speed. Preliminary study suggests that there is observable effect of buoyancy in the 1g environment suggesting the need for microgravity experiments of the upcoming experimental combustion studies. With the cold flow properties characterized, an identical hot flow facility is under construction. It is assumed that the turbulence properties ahead of the flame in this new device will closely match the results obtained here. This is required since the hot facility will not enable LDV measurements. The

Nonclinical pharmacology and toxicology of the first biosimilar insulin glargine drug product (BASAGLAR®/ABASAGLAR®) approved in the European Union.

PubMed

Byrd, Richard A; Owens, Rebecca A; Blackbourne, Jamie L; Coutant, David E; Farmen, Mark W; Michael, M Dodson; Moyers, Julie S; Schultze, A Eric; Sievert, Michael K; Tripathi, Niraj K; Vahle, John L

2017-08-01

Basaglar ® /Abasaglar ® (Lilly insulin glargine [LY IGlar]) is a long-acting human insulin analogue drug product granted marketing authorisation as a biosimilar to Lantus ® (Sanofi insulin glargine [SA IGlar]) by the European Medicines Agency. We assessed the similarity of LY IGlar to the reference drug product, European Union-sourced SA IGlar (EU-SA IGlar), using nonclinical in vitro and in vivo studies. No biologically relevant differences were observed for receptor binding affinity at either the insulin or insulin-like growth factor-1 (IGF-1) receptors, or in assays of functional or de novo lipogenic activity. The mitogenic potential of LY IGlar and EU-SA IGlar was similar when tested in both insulin- and IGF-1 receptor dominant cell systems. Repeated subcutaneous daily dosing of rats for 4 weeks with 0, 0.3, 1.0, or 2.0 mg/kg LY IGlar and EU-SA IGlar produced mortalities and clinical signs consistent with severe hypoglycaemia. Glucodynamic profiles of LY IGlar and EU-SA IGlar in satellite animals showed comparable dose-related hypoglycaemia. Severe hypoglycaemia was associated with axonal degeneration of the sciatic nerve; the incidence and severity were low and did not differ between LY IGlar and EU-SA IGlar. These results demonstrated no biologically relevant differences in toxicity between LY IGlar and EU-SA IGlar. Copyright © 2017 Elsevier Inc. All rights reserved.

Exogenous thyroxine improves glucose intolerance in insulin-resistant rats.

PubMed

Vazquez-Anaya, Guillermo; Martinez, Bridget; Soñanez-Organis, José G; Nakano, Daisuke; Nishiyama, Akira; Ortiz, Rudy M

2017-03-01

Both hypothyroidism and hyperthyroidism are associated with glucose intolerance, calling into question the contribution of thyroid hormones (TH) on glucose regulation. TH analogues and derivatives may be effective treatment options for glucose intolerance and insulin resistance (IR), but their potential glucoregulatory effects during conditions of impaired metabolism are not well described. To assess the effects of thyroxine (T 4 ) on glucose intolerance in a model of insulin resistance, an oral glucose tolerance test (oGTT) was performed on three groups of rats (n = 8): (1) lean, Long Evans Tokushima Otsuka (LETO), (2) obese, Otsuka Long Evans Tokushima Fatty (OLETF) and (3) OLETF + T 4 (8.0 µg/100 g BM/day × 5 weeks). T 4 attenuated glucose intolerance by 15% and decreased IR index (IRI) by 34% in T 4 -treated OLETF compared to untreated OLETF despite a 31% decrease in muscle Glut4 mRNA expression. T 4 increased the mRNA expressions of muscle monocarboxylate transporter 10 (Mct10), deiodinase type 2 (Di2), sirtuin 1 (Sirt1) and uncoupling protein 2 (Ucp2) by 1.8-, 2.2-, 2.7- and 1.4-fold, respectively, compared to OLETF. Activation of AMP-activated protein kinase (AMPK) and insulin receptor were not significantly altered suggesting that the improvements in glucose intolerance and IR were independent of enhanced insulin-mediated signaling. The results suggest that T 4 treatment increased the influx of T 4 in skeletal muscle and, with an increase of DI2, increased the availability of the biologically active T 3 to upregulate key factors such SIRT1 and UCP2 involved in cellular metabolism and glucose homeostasis. © 2017 Society for Endocrinology.

Experimental study on a comparison of typical premixed combustible gas-air flame propagation in a horizontal rectangular closed duct.

PubMed

Jin, Kaiqiang; Duan, Qiangling; Liew, K M; Peng, Zhongjing; Gong, Liang; Sun, Jinhua

2017-04-05

Research surrounding premixed flame propagation in ducts has a history of more than one hundred years. Most previous studies focus on the tulip flame formation and flame acceleration in pure gas fuel-air flame. However, the premixed natural gas-air flame may show different behaviors and pressure dynamics due to its unique composition. Natural gas, methane and acetylene are chosen here to conduct a comparison study on different flame behaviors and pressure dynamics, and to explore the influence of different compositions on premixed flame dynamics. The characteristics of flame front and pressure dynamics are recorded using high-speed schlieren photography and a pressure transducer, respectively. The results indicate that the compositions of the gas mixture greatly influence flame behaviors and pressure. Acetylene has the fastest flame tip speed and the highest pressure, while natural gas has a faster flame tip speed and higher pressure than methane. The Bychkov theory for predicting the flame skirt motion is verified, and the results indicate that the experimental data coincide well with theory in the case of equivalence ratios close to 1.00. Moreover, the Bychkov theory is able to predict flame skirt motion for acetylene, even outside of the best suitable expansion ratio range of 6

A LES-CMC formulation for premixed flames including differential diffusion

NASA Astrophysics Data System (ADS)

Farrace, Daniele; Chung, Kyoungseoun; Bolla, Michele; Wright, Yuri M.; Boulouchos, Konstantinos; Mastorakos, Epaminondas

2018-05-01

A finite volume large eddy simulation-conditional moment closure (LES-CMC) numerical framework for premixed combustion developed in a previous studyhas been extended to account for differential diffusion. The non-unity Lewis number CMC transport equation has an additional convective term in sample space proportional to the conditional diffusion of the progress variable, that in turn accounts for diffusion normal to the flame front and curvature-induced effects. Planar laminar simulations are first performed using a spatially homogeneous non-unity Lewis number CMC formulation and validated against physical-space fully resolved reference solutions. The same CMC formulation is subsequently used to numerically investigate the effects of curvature for laminar flames having different effective Lewis numbers: a lean methane-air flame with Leeff = 0.99 and a lean hydrogen-air flame with Leeff = 0.33. Results suggest that curvature does not affect the conditional heat release if the effective Lewis number tends to unity, so that curvature-induced transport may be neglected. Finally, the effect of turbulence on the flame structure is qualitatively analysed using LES-CMC simulations with and without differential diffusion for a turbulent premixed bluff body methane-air flame exhibiting local extinction behaviour. Overall, both the unity and the non-unity computations predict the characteristic M-shaped flame observed experimentally, although some minor differences are identified. The findings suggest that for the high Karlovitz number (from 1 to 10) flame considered, turbulent mixing within the flame weakens the differential transport contribution by reducing the conditional scalar dissipation rate and accordingly the conditional diffusion of the progress variable.

Insulin for the treatment of women with gestational diabetes.

PubMed

Brown, Julie; Grzeskowiak, Luke; Williamson, Kathryn; Downie, Michelle R; Crowther, Caroline A

2017-11-05

Gestational diabetes mellitus (GDM) is associated with short- and long-term complications for the mother and her infant. Women who are unable to maintain their blood glucose concentration within pre-specified treatment targets with diet and lifestyle interventions will require anti-diabetic pharmacological therapies. This review explores the safety and effectiveness of insulin compared with oral anti-diabetic pharmacological therapies, non-pharmacological interventions and insulin regimens. To evaluate the effects of insulin in treating women with gestational diabetes. We searched Pregnancy and Childbirth's Trials Register (1 May 2017), ClinicalTrials.gov, WHO International Clinical Trials Registry Platform (ICTRP) (1 May 2017) and reference lists of retrieved studies. We included randomised controlled trials (including those published in abstract form) comparing:a) insulin with an oral anti-diabetic pharmacological therapy;b) with a non-pharmacological intervention;c) different insulin analogues;d) different insulin regimens for treating women with diagnosed with GDM.We excluded quasi-randomised and trials including women with pre-existing type 1 or type 2 diabetes. Cross-over trials were not eligible for inclusion. Two review authors independently assessed study eligibility, risk of bias, and extracted data. Data were checked for accuracy. We included 53 relevant studies (103 publications), reporting data for 7381 women. Forty-six of these studies reported data for 6435 infants but our analyses were based on fewer number of studies/participants.Overall, the risk of bias was unclear; 40 of the 53 included trials were not blinded. Overall, the quality of the evidence ranged from moderate to very low quality. The primary reasons for downgrading evidence were imprecision, risk of bias and inconsistency. We report the results for our maternal and infant GRADE outcomes for the main comparison. Insulin versus oral anti-diabetic pharmacological therapyFor the mother

Central insulin signaling is attenuated by long-term insulin exposure via insulin receptor substrate-1 serine phosphorylation, proteasomal degradation, and lysosomal insulin receptor degradation.

PubMed

Mayer, Christopher M; Belsham, Denise D

2010-01-01

Central insulin signaling is critical for the prevention of insulin resistance. Hyperinsulinemia contributes to insulin resistance, but it is not yet clear whether neurons are subject to cellular insulin resistance. We used an immortalized, hypothalamic, clonal cell line, mHypoE-46, which exemplifies neuronal function and expresses the components of the insulin signaling pathway, to determine how hyperinsulinemia modifies neuronal function. Western blot analysis indicated that prolonged insulin treatment of mHypoE-46 cells attenuated insulin signaling through phospho-Akt. To understand the mechanisms involved, time-course analysis was performed. Insulin exposure for 4 and 8 h phosphorylated Akt and p70-S6 kinase (S6K1), whereas 8 and 24 h treatment decreased insulin receptor (IR) and IR substrate 1 (IRS-1) protein levels. Insulin phosphorylation of S6K1 correlated with IRS-1 ser1101 phosphorylation and the mTOR-S6K1 pathway inhibitor rapamycin prevented IRS-1 serine phosphorylation. The proteasomal inhibitor epoxomicin and the lysosomal pathway inhibitor 3-methyladenine prevented the degradation of IRS-1 and IR by insulin, respectively, and pretreatment with rapamycin, epoxomicin, or 3-methyladenine prevented attenuation of insulin signaling by long-term insulin exposure. Thus, a sustained elevation of insulin levels diminishes neuronal insulin signaling through mTOR-S6K1-mediated IRS-1 serine phosphorylation, proteasomal degradation of IRS-1 and lysosomal degradation of the IR.

Aerodynamic features of flames in premixed gases

NASA Technical Reports Server (NTRS)

Oppenheim, A. K.

1984-01-01

A variety of experimentally established flame phenomena in premixed gases are interpreted by relating them to basic aerodynamic properties of the flow field. On this basis the essential mechanism of some well known characteristic features of flames stabilized in the wake of a bluff-body or propagating in ducts are revealed. Elementary components of the flame propagation process are shown to be: rotary motion, self-advancement, and expansion. Their consequences are analyzed under a most strict set of idealizations that permit the flow field to be treated as potential in character, while the flame is modelled as a Stefan-like interface capable of exerting a feed-back effect upon the flow field. The results provide an insight into the fundamental fluid-mechanical reasons for the experimentally observed distortions of the flame front, rationalizing in particular its ability to sustain relatively high flow velocities at amazingly low normal burning speeds.

A Numerical Study of Spray Injected in a Gas Turbine Lean Pre-Mixed Pre-Vaporized Combustor

NASA Astrophysics Data System (ADS)

Amoresano, Amedeo; Cameretti, Maria Cristina; Tuccillo, Raffaele

2015-04-01

The authors have performed a numerical study to investigate the spray evolution in a modern gas turbine combustor of the Lean Pre-Mixed Pre-vaporized type. The CFD tool is able to simulate the injection conditions, by isolating and studying some specific phenomena. The calculations have been performed by using a 3-D fluid dynamic code, the FLUENT flow solver, by choosing the injection models on the basis of a comparative analysis with some experimental data, in terms of droplet diameters, obtained by PDA technique. In a first phase of the investigation, the numerical simulation refers to non-evaporating flow conditions, in order to validate the estimation of the fundamental spray parameters. Next, the calculations employ boundary conditions close to those occurring in the actual combustor operation, in order to predict the fuel vapour distribution throughout the premixing chamber. The results obtained allow the authors to perform combustion simulation in the whole domain.

Flame-Generated Vorticity Production in Premixed Flame-Vortex Interactions

NASA Technical Reports Server (NTRS)

Patnaik, G.; Kailasanath, K.

2003-01-01

In this study, we use detailed time-dependent, multi-dimensional numerical simulations to investigate the relative importance of the processes leading to FGV in flame-vortex interactions in normal gravity and microgravity and to determine if the production of vorticity in flames in gravity is the same as that in zero gravity except for the contribution of the gravity term. The numerical simulations will be performed using the computational model developed at NRL, FLAME3D. FLAME3D is a parallel, multi-dimensional (either two- or three-dimensional) flame model based on FLIC2D, which has been used extensively to study the structure and stability of premixed hydrogen and methane flames.

A numerical investigation of premixed combustion in wave rotors

NASA Technical Reports Server (NTRS)

Nalim, M. Razi; Paxson, Daniel E.

1996-01-01

Wave rotor cycles which utilize premixed combustion processes within the passages are examined numerically using a one-dimensional CFD-based simulation. Internal-combustion wave rotors are envisioned for use as pressure-gain combustors in gas turbine engines. The simulation methodology is described, including a presentation of the assumed governing equations for the flow and reaction in the channels, the numerical integration method used, and the modeling of external components such as recirculation ducts. A number of cycle simulations are then presented which illustrate both turbulent-deflagration and detonation modes of combustion. Estimates of performance and rotor wall temperatures for the various cycles are made, and the advantages and disadvantages of each are discussed.

Chaotic dynamics in premixed hydrogen/air channel flow combustion

NASA Astrophysics Data System (ADS)

Pizza, Gianmarco; Frouzakis, Christos E.; Mantzaras, John

2012-04-01

The complex oscillatory behaviour observed in fuel-lean premixed hydrogen/air atmospheric pressure flames in an open planar channel with prescribed wall temperature is investigated by means of direct numerical simulations, employing detailed chemistry descriptions and species transport, and nonlinear dynamics analysis. As the inflow velocity is varied, the sequence of transitions includes harmonic single frequency oscillations, intermittency, mixed mode oscillations, and finally a period-doubling cascade leading to chaotic dynamics. The observed modes are described and characterised by means of phase-space portraits and next amplitude maps. It is shown that the interplay of chemistry, transport, and wall-bounded developing flow leads to considerably richer dynamics compared to fuel-lean hydrogen/air continuously stirred tank reactor studies.

Planetary habitability: lessons learned from terrestrial analogues

NASA Astrophysics Data System (ADS)

Preston, Louisa J.; Dartnell, Lewis R.

2014-01-01

Terrestrial analogue studies underpin almost all planetary missions and their use is essential in the exploration of our Solar system and in assessing the habitability of other worlds. Their value relies on the similarity of the analogue to its target, either in terms of their mineralogical or geochemical context, or current physical or chemical environmental conditions. Such analogue sites offer critical ground-truthing for astrobiological studies on the habitability of different environmental parameter sets, the biological mechanisms for survival in extreme environments and the preservation potential and detectability of biosignatures. The 33 analogue sites discussed in this review have been selected on the basis of their congruence to particular extraterrestrial locations. Terrestrial field sites that have been used most often in the literature, as well as some lesser known ones which require greater study, are incorporated to inform on the astrobiological potential of Venus, Mars, Europa, Enceladus and Titan. For example, the possibility of an aerial habitable zone on Venus has been hypothesized based on studies of life at high-altitudes in the terrestrial atmosphere. We also demonstrate why many different terrestrial analogue sites are required to satisfactorily assess the habitability of the changing environmental conditions throughout Martian history, and recommend particular sites for different epochs or potential niches. Finally, habitable zones within the aqueous environments of the icy moons of Europa and Enceladus and potentially in the hydrocarbon lakes of Titan are discussed and suitable analogue sites proposed. It is clear from this review that a number of terrestrial analogue sites can be applied to multiple planetary bodies, thereby increasing their value for astrobiological exploration. For each analogue site considered here, we summarize the pertinent physiochemical environmental features they offer and critically assess the fidelity with which

Premixed Flames Under Microgravity and Normal Gravity Conditions

NASA Astrophysics Data System (ADS)

Krikunova, Anastasia I.; Son, Eduard E.

2018-03-01

Premixed conical CH4-air flames were studied experimentally and numerically under normal straight, reversed gravity conditions and microgravity. Low-gravity experiments were performed in Drop tower. Classical Bunsen-type burner was used to find out features of gravity influence on the combustion processes. Mixture equivalence ratio was varied from 0.8 to 1.3. Wide range of flow velocity allows to study both laminar and weakly turbulized flames. High-speed flame chemoluminescence video-recording was used as diagnostic. The investigations were performed at atmospheric pressure. As results normalized flame height, laminar flame speed were measured, also features of flame instabilities were shown. Low- and high-frequency flame-instabilities (oscillations) have a various nature as velocity fluctuations, preferential diffusion instability, hydrodynamic and Rayleigh-Taylor ones etc., that was explored and demonstrated.

Highly active anticancer curcumin analogues.

PubMed

Mosley, Cara A; Liotta, Dennis C; Snyder, James P

2007-01-01

Curcumin, a compound in the human food supply, represents a near-perfect starting point for drug discovery. Consequently, a number of research groups have taken the natural product as a starting point to prepare and biologically evaluate a wide variety of curcumin analogues. One widely used structural modification truncates the central conjugated beta-diketone in curcumin to the monocarbonyl dienone. A diverse array of the latter compounds exhibit cytotoxicities against an equally diverse set of cancer-related cell lines. Importantly, these compounds still retain toxicity profiles in rodents comparable to the parent natural product, whereas some analogues (e.g., EF-24, 41) exhibit good oral bioavailability and good pharmacokinetics in mice. Thiol conjugates of EF-24 analogues have been prepared that address stability and solubility issues while demonstrating cellular activities similar to the unmodified dienones. In parallel experiments, the factor VIIa-tissue factor complex (fVIIa-TF) has been exploited to develop a targeting strategy for the analogues. In particular, the EF24-FFRck-fVIIa protein conjugate is not only somewhat more effective relative to the drug alone against breast cancer and melanocyte cells. Both simple curcumin analogues and the protein conjugate evidence antiangiogenic activity in cell culture. The implication is that the fVIIa-TF targeting process, like the dienone drugs, permits a double-pronged attack with the potential to destroy a tumor directly by apoptosis.

Review of insulin-associated hypoglycemia and its impact on the management of diabetes in Southeast Asian countries.

PubMed

Goh, Su-Yen; Hussein, Zanariah; Rudijanto, Achmad

2017-09-01

Although the incidence of diabetes is rising in Southeast Asia, there is limited information regarding the incidence and manifestation of insulin-associated hypoglycemia. The aim of the present review was to discuss what is currently known regarding insulin-associated hypoglycemia in Southeast Asia, including its known incidence and impact in the region, and how the Southeast Asian population with diabetes differs from other populations. We found a paucity of data regarding the incidence of hypoglycemia in Southeast Asia, which has contributed to the adoption of Western guidelines. This might not be appropriate, as Southeast Asians have a range of etiological, educational and cultural differences from Western populations with diabetes that might place them at greater risk of hypoglycemia if not managed optimally. For example, Southeast Asians with type 2 diabetes tend to be younger, with lower body mass indexes than their Western counterparts, and the management of type 2 diabetes with premixed insulin preparations is more common in Southeast Asia. Both of these factors might result in higher rates of hypoglycemia. In addition, Southeast Asians are often poorly educated about hypoglycemia and its management, including during Ramadan fasting. We conclude there is a need for more information about Southeast Asian populations with diabetes to assist with the construction of more appropriate national and regional guidelines for the management of hypoglycemia, more closely aligned to patient demographics, behaviors and treatment practices. Such bespoke guidelines might result in a greater degree of implementation and adherence within clinical practice in Southeast Asian nations. © 2017 The Authors. Journal of Diabetes Investigation published by Asian Association for the Study of Diabetes (AASD) and John Wiley & Sons Australia, Ltd.

EFFECTS OF EQUIVALENCE RATIO ON SPECIES AND SOOT CONCENTRATIONS IN PREMIXED N-HEPTANE FLAMES. (R828193)

EPA Science Inventory

The micro-structure of laminar premixed, atmospheric-pressure, fuel-rich flames of n-heptane/oxygen/argon has been studied at two equivalence ratios (C/O = 0.63 and C/O = 0.67). A heated quartz microprobe coupled to an online gas chromatography/mass spectrometry (HP 5890 Serie...

Biosimilar insulins.

PubMed

Heinemann, Lutz

2012-08-01

Until now most insulin used in developed countries is manufactured and distributed by a small number of multinational companies. Other pharmaceutical companies - many of these are located in countries such as India or China - are also able to manufacture insulin with modern biotechnological methods. Additionally, the patents for many insulin formulations have expired or are going to expire soon. This enables such companies to produce insulins and to apply for market approval of these as biosimilar insulins (BIs) in highly regulated markets such as the EU or the US. To understand the complexity of BIs' approval and usage, scientific and regulatory aspects have to be discussed. Differences in the manufacturing process (none of the insulin-manufacturing procedures are identical) result in the fact that all insulin that might become BIs differ from the originator insulin to some extent. The question is, have such differences in the structure of the insulin molecule and or the purity and so on clinically relevant consequences for the biological effects induced or not. The guidelines already in place in the EU for market approval require that the manufacturer demonstrates that his insulin has a safety and efficacy profile that is similar to that of the 'original' insulin formulation. Recently guidelines for biosimilars were issued in the US; however, these do not cover insulin. Although a challenging approval process for insulins to become BI might be regarded as a hurdle to keep companies out of certain markets, it is fair to say that the potential safety and efficacy issues surrounding BI are substantial and relevant, and do warrant a careful and evidence-driven approval process. Nevertheless, it is very likely that in the next years, BIs will come to the market also in highly regulated markets.

Expectations about insulin therapy, perceived insulin-delivery system social acceptability, and insulin treatment satisfaction contribute to decreases in insulin therapy self-efficacy in patients with type 2 diabetes after 36 weeks insulin therapy.

PubMed

Hayes, Risa P; Curtis, Bradley; Ilag, Liza; Nelson, David R; Wong, Mayme; Funnell, Martha

2013-09-01

Self-efficacy plays a critical role in diabetes self-care. Herein we explore factors contributing to decreased insulin therapy self-efficacy in insulin-naïve patients with type 2 diabetes mellitus (T2DM) initiating and managing insulin therapy over 36 weeks. The study was conducted within an international, randomized clinical trial comparing two insulin therapies administered by insulin pen in patients with T2DM inadequately controlled with oral antihyperglycemic medications. Patients completed the Self-Efficacy about Insulin Therapy Questionnaire (SEITQ) at baseline and endpoint. Patients also completed patient-reported measures assessing expectations about insulin therapy at baseline and perceptions about insulin therapy and insulin-delivery system (IDS) satisfaction at endpoint. Baseline and endpoint SEITQ scores were compared. Using prespecified criteria, patients were classified as having "decreased" or "no change/improved" insulin self-efficacy. Demographic, clinical, and patient-reported variables were entered into a logistic regression model with decreased insulin self-efficacy (yes or no) as the dependent variable. Baseline and endpoint SEITQ data were available for 450 insulin-naïve T2DM patients (mean age 59 years; 53% female; 57% Caucasian; mean baseline HbA1c 9.4%; 80.0 mmol/mol). Insulin therapy self-efficacy improved from baseline to endpoint (74.0 vs 77.5; P<0.001). Logistic regression analysis indicated that lower IDS satisfaction (P<0.0001), lower IDS social acceptability (P=0.004), and more positive expectations of insulin therapy (P<0.0001) were associated with decreased insulin self-efficacy. A candid discussion between clinicians and their insulin-naïve T2DM patients about the benefits and challenges of insulin therapy may prevent unrealistic expectations that could potentially undermine insulin self-efficacy. © 2013 Wiley Publishing Asia Pty Ltd and Ruijin Hospital, Shanghai Jiaotong University School of Medicine.

A Study of Strain Rate Effects for Turbulent Premixed Flames with Application to LES of a Gas Turbine Combustor Model

DOE PAGES

Kemenov, Konstantin A.; Calhoon, William H.

2015-03-24

Large-scale strain rate field, a resolved quantity which is easily computable in large-eddy simulations (LES), could have profound effects on the premixed flame properties by altering the turbulent flame speed and inducing local extinction. The role of the resolved strain rate has been investigated in a posterior LES study of GE lean premixed dry low NOx emissions LM6000 gas turbine combustor model. A novel approach which is based on the coupling of the lineareddy model with a one-dimensional counter-flow solver has been applied to obtain the parameterizations of the resolved premixed flame properties in terms of the reactive progress variable,more » the local strain rate measure, and local Reynolds and Karlovitz numbers. The strain rate effects have been analyzed by comparing LES statistics for several models of the turbulent flame speed, i.e, with and without accounting for the local strain rate effects, with available experimental data. The sensitivity of the simulation results to the inflow velocity conditions as well as the grid resolution have been also studied. Overall, the results suggest the necessity to represent the strain rate effects accurately in order to improve LES modeling of the turbulent flame speed.« less

Effects of mesh type on a non-premixed model in a flameless combustion simulation

NASA Astrophysics Data System (ADS)

Komonhirun, Seekharin; Yongyingsakthavorn, Pisit; Nontakeaw, Udomkiat

2018-01-01

Flameless combustion is a recently developed combustion system, which provides zero emission product. This phenomenon requires auto-ignition by supplying high-temperature air with low oxygen concentration. The flame is vanished and colorless. Temperature of the flameless combustion is less than that of a conventional case, where NOx reactions can be well suppressed. To design a flameless combustor, the computational fluid dynamics (CFD) is employed. The designed air-and-fuel injection method can be applied with the turbulent and non-premixed models. Due to the fact that nature of turbulent non-premixed combustion is based on molecular randomness, inappropriate mesh type can lead to significant numerical errors. Therefore, this research aims to numerically investigate the effects of mesh type on flameless combustion characteristics, which is a primary step of design process. Different meshes, i.e. tetrahedral, hexagonal are selected. Boundary conditions are 5% of oxygen and 900 K of air-inlet temperature for the flameless combustion, and 21% of oxygen and 300 K of air-inlet temperature for the conventional case. The results are finally presented and discussed in terms of velocity streamlines, and contours of turbulent kinetic energy and viscosity, temperature, and combustion products.

Plerocercoid growth factor (PGF), a human growth hormone (hGH) analogue produced by the tapeworm Spirometra mansonoides, has direct insulin-like action in adipose tissue of normal rats in vitro

DOE Office of Scientific and Technical Information (OSTI.GOV)

Salem, M.A.M.; Phares, C.K.

1986-03-01

The metabolic actions of GH can be divided into acute (insulin-like) and chronic (lipolytic/anti-insulin). The insulin-like actions of GH are most readily elicited in GH-deficient animals as GH induces resistance to its own insulin-like action. Like GH, PGF stimulates growth and cross-reacts with anti-hGH antibodies. Independent experiments were conducted comparing the direct actions of PGF to insulin or hGH in vitro. Insulin-like effects were determined by the ability of PGF, insulin or hGH to stimulate (U-/sup 14/C)glucose metabolism in epidydimal fat pads from normal rats and by inhibition of epinephrine-stimulated lipolysis. Direct stimulation of lipolysis was used as anti-insulin activity.more » To determine if PGF competes for insulin or GH receptors, adipocytes (3 x 10/sup 5/ cells/ml) were incubated with either (/sup 125/I)insulin or (/sup 125/I)hGH +/- PGF, +/- insulin or +/- hGH. PGF stimulated glucose oxidation and /sup 14/C-incorporation into lipids. Insulin, hGH and PGF inhibited lipolysis (33%, 29% and 34%, respectively). Adipose tissue was very sensitive to the lipolytic effect of hGH but PGF was neither lipolytic nor did it confer refractoriness to its insulin-like action. PGF bound to GH but not to insulin receptors. Therefore, PGF had direct insulin-like effects but did not stimulate lipolysis in tissue from normal rats in vitro.« less

Quantum analogue computing.

PubMed

Kendon, Vivien M; Nemoto, Kae; Munro, William J

2010-08-13

We briefly review what a quantum computer is, what it promises to do for us and why it is so hard to build one. Among the first applications anticipated to bear fruit is the quantum simulation of quantum systems. While most quantum computation is an extension of classical digital computation, quantum simulation differs fundamentally in how the data are encoded in the quantum computer. To perform a quantum simulation, the Hilbert space of the system to be simulated is mapped directly onto the Hilbert space of the (logical) qubits in the quantum computer. This type of direct correspondence is how data are encoded in a classical analogue computer. There is no binary encoding, and increasing precision becomes exponentially costly: an extra bit of precision doubles the size of the computer. This has important consequences for both the precision and error-correction requirements of quantum simulation, and significant open questions remain about its practicality. It also means that the quantum version of analogue computers, continuous-variable quantum computers, becomes an equally efficient architecture for quantum simulation. Lessons from past use of classical analogue computers can help us to build better quantum simulators in future.

Hyperinsulinemic hypoglycemia associated with insulin antibodies caused by exogenous insulin analog.

PubMed

Su, Chih-Ting; Lin, Yi-Chun

2016-01-01

Insulin antibodies (IA) associated with exogenous insulin administration seldom caused hypoglycemia and had different characteristics from insulin autoantibodies (IAA) found in insulin autoimmune syndrome (IAS), which was first described by Dr Hirata in 1970. The characteristic of IAS is the presence of insulin-binding autoantibodies and related fasting or late postprandial hypoglycemia. Here, we report a patient with type 1 diabetes mellitus under insulin glargine and insulin aspart treatment who developed recurrent spontaneous post-absorptive hyperinsulinemic hypoglycemia with the cause probably being insulin antibodies induced by exogenous injected insulin. Examinations of serial sera disclosed a high titre of insulin antibodies (33%, normal <5%), high insulin concentration (111.9 IU/mL) and undetectable C-peptide when hypoglycemia occurred. An oral glucose tolerance test revealed persistent high serum levels of total insulin and undetectable C-peptide. Image studies of the pancreas were unremarkable, which excluded the diagnosis of insulinoma. The patient does not take any of the medications containing sulfhydryl compounds, which had been reported to cause IAS. After administering oral prednisolone for 3 weeks, hypoglycemic episodes markedly improved, and he was discharged smoothly. Insulin autoimmune syndrome (IAS) or IAS-like situation should be one of the differential diagnosis in patients with hyperinsulinemic hypoglycemia.Although less reported, insulin antibodies (IA) caused by exogenous insulin analog should be considered as the cause of hypoglycemia.Patients with suspected insulin autoimmune syndrome (IAS) should be screened for drugs related to autoimmunity to endogenous insulin.

Numerical study of transient evolution of lifted jet flames: partially premixed flame propagation and influence of physical dimensions

NASA Astrophysics Data System (ADS)

Chen, Zhi; Ruan, Shaohong; Swaminathan, Nedunchezhian

2016-07-01

Three-dimensional (3D) unsteady Reynolds-averaged Navier-Stokes simulations of a spark-ignited turbulent methane/air jet flame evolving from ignition to stabilisation are conducted for different jet velocities. A partially premixed combustion model is used involving a correlated joint probability density function and both premixed and non-premixed combustion mode contributions. The 3D simulation results for the temporal evolution of the flame's leading edge are compared with previous two-dimensional (2D) results and experimental data. The comparison shows that the final stabilised flame lift-off height is well predicted by both 2D and 3D computations. However, the transient evolution of the flame's leading edge computed from 3D simulation agrees reasonably well with experiment, whereas evident discrepancies were found in the previous 2D study. This difference suggests that the third physical dimension plays an important role during the flame transient evolution process. The flame brush's leading edge displacement speed resulting from reaction, normal and tangential diffusion processes are studied at different typical stages after ignition in order to understand the effect of the third physical dimension further. Substantial differences are found for the reaction and normal diffusion components between 2D and 3D simulations especially in the initial propagation stage. The evolution of reaction progress variable scalar gradients and its interaction with the flow and mixing field in the 3D physical space have an important effect on the flame's leading edge propagation.

Examination of ionic wind and cathode sheath effects in a E-field premixed flame with ion density measurements

DOE Office of Scientific and Technical Information (OSTI.GOV)

Jacobs, Stewart V., E-mail: svj0001@uah.edu; Xu, Kunning G., E-mail: gabe.xu@uah.edu

2016-04-15

The effect of the ionic wind on a premixed methane-air flame under a DC electric field is studied via mapping of the ion density with Langmuir probes. Ion densities were observed to increase near the burner with increasing electrode voltage up to 6 kV. Past this electrode supply voltage, ion densities ceased increasing and began to decline in some locations within the premixed flame. The increased ion density is caused by an increase in ionic wind force and cathode sheath thickness. The plateau in density is due to the cathode sheath fully encompassing the flame front which is the ion source,more » thereby collecting all ions in the flame. The spatial density data support the ionic wind hypothesis and provide further explanation of its limits based on the plasma sheath.« less

Turbulent Premixed Flames in Microgravity

NASA Technical Reports Server (NTRS)

Menon, Suresh

1996-01-01

The experimental cold-flow facility is now full operational and is currently being used to obtain baseline turbulence data in a Couette flow. The baseline turbulence data is necessary to confirm the capability of the chosen device to generate and maintain the required turbulence intensity. Subsequent reacting flow studies will assume that a similar turbulent flow field exists ahead of the premixed flame. Some modifications and refinements had to be made to enable accurate measurements. It consists of two rollers, one (driven by a motor) which drives a continuous belt and four smaller rollers used to set the belt spacing and tension to minimize belt flutter. The entire assemble is enclosed in a structure that has the dimensions to enable future drop tower experiments of the hot facility. All critical dimensions are the same as the original plans except for the pulley ratio which has been changed to enable a wider operating regime in terms of the Reynolds number. With the current setup, Reynolds numbers as low as 100 and as high as 14,000 can be achieved. This is because the in-between belt spacing can be varied from 1 cm to 7.6 cm, and the belt speed can be accurately varied from .15 m/sec to 3.1 m/sec.

[Comparison between basal insulin glargine and NPH insulin in patients with diabetes type 1 on conventional intensive insulin therapy].

PubMed

Pesić, Milica; Zivić, Sasa; Radenković, Sasa; Velojić, Milena; Dimić, Dragan; Antić, Slobodan

2007-04-01

Insulin glargine is a long-acting insulin analog that mimics normal basal insulin secretion without pronounced peaks. The aim of this study was to compare insulin glargine with isophane insulin (NPH insulin) for basal insulin supply in patients with type 1 diabetes. A total of 48 type 1 diabetics on long term conventional intensive insulin therapy (IT) were randomized to three different regimens of basal insulin substitution: 1. continuation of NPH insulin once daily at bedtime with more intensive selfmonitoring (n = 15); 2. NPH insulin twice daily (n = 15); 3. insulin glargine once daily (n = 18). Meal time insulin aspart was continued in all groups. Fasting blood glucose (FBG) was lower in the glargine group (7.30+/-0.98 mmol/1) than in the twice daily NPH group (7.47+/-1.06 mmol/1), but without significant difference. FBG was significantly higher in the once daily NPH group (8.44+/-0.85 mmol/l; p < 0.05). HbAlc after 3 months did not change in the once daily NPH group, but decreased in the glargine group (from 7.72+/-0.86% to 6.87+/-0.50%), as well as in the twice daily NPH group (from 7.80+/-0.83% to 7.01+/-0.63%). Total daily insulin doses were similar in all groups but only in the glargine group there was an increase of basal and decrease of meal related insulin doses. The frequency of mild hypoglycemia was significantly lower in the glargine group (6.56+/-2.09) than in both NPH groups (9.0+/-1.65 in twice daily NPH group and 8.13+/-1.30 in other NPH group) (episodes/patients-month, p < 0.05). Basal insulin supplementation in type 1 diabetes mellitus with either twice daily NPH insulin or glargine can result in similar glycemic control when combined with meal time insulin aspart. However, with glargine regimen FBG, HbAlc and frequency of hypoglycemic event are lower. These facts contribute to better patients satisfaction with insulin glargine versus NPH insulin in IIT in type 1 diabetics.

[The application of artificial protein premixes for nutritive support of patients with chronic renal insufficiency, being treated by perinateal dialysis].

PubMed

Pichugina, I S; Vetchinnikova, O N; Vereshchagina, V M; Gapparov, M M; Vatazin, A V

2008-01-01

As a result of a survey of 56 patients with chronic renal insufficiency, who undergone hemodialysis, it was established, that clinical condition of patients, biochemical and hematological blood indices as well as results of anthropometric research improve upon application of artificial balanced high-protein premixes -"Nutrinil" and "Nutrien-Nefro". Irrespective of way of administration - introperitoneal ("Nutrinil" solution) or enteral ("Nutrien-Nefro" mixture) protein-energetic insufficiency diminishes or totally disappears, body weight, fat and muscle content of the body weight, as well as indices of whole protein, albumine, lymphocytes, haemoglobin, pH approache the norm. Intraperitoneal way of administration of artificial protein premixes increase patients adherence to this procedure, though enteral way of their administration is more preferable from economic point of view.

Premixed flame propagation in combustible particle cloud mixtures

NASA Technical Reports Server (NTRS)

Seshadri, K.; Yang, B.

1993-01-01

The structures of premixed flames propagating in combustible systems, containing uniformly distributed volatile fuel particles, in an oxidizing gas mixtures is analyzed. The experimental results show that steady flame propagation occurs even if the initial equivalence ratio of the combustible mixture based on the gaseous fuel available in the particles, phi(u) is substantially larger than unity. A model is developed to explain these experimental observations. In the model it is presumed that the fuel particles vaporize first to yield a gaseous fuel of known chemical composition which then reacts with oxygen in a one-step overall process. It is shown that the interplay of vaporization kinetics and oxidation process, can result in steady flame propagation in combustible mixtures where the value of phi(u) is substantially larger than unity. This prediction is in agreement with experimental observations.

Anti-insulin antibody test

MedlinePlus

Insulin antibodies - serum; Insulin Ab test; Insulin resistance - insulin antibodies; Diabetes - insulin antibodies ... You appear to have an allergic response to insulin Insulin no longer seems to control your diabetes

Resveratrol ameliorates the chemical and microbial induction of inflammation and insulin resistance in human placenta, adipose tissue and skeletal muscle.

PubMed

Tran, Ha T; Liong, Stella; Lim, Ratana; Barker, Gillian; Lappas, Martha

2017-01-01

Gestational diabetes mellitus (GDM), which complicates up to 20% of all pregnancies, is associated with low-grade maternal inflammation and peripheral insulin resistance. Sterile inflammation and infection are key mediators of this inflammation and peripheral insulin resistance. Resveratrol, a stilbene-type phytophenol, has been implicated to exert beneficial properties including potent anti-inflammatory and antidiabetic effects in non-pregnant humans and experimental animal models of GDM. However, studies showing the effects of resveratrol on inflammation and insulin resistance associated with GDM in human tissues have been limited. In this study, human placenta, adipose (omental and subcutaneous) tissue and skeletal muscle were stimulated with pro-inflammatory cytokines TNF-α and IL-1β, the bacterial product lipopolysaccharide (LPS) and the synthetic viral dsRNA analogue polyinosinic:polycytidylic acid (poly(I:C)) to induce a GDM-like model. Treatment with resveratrol significantly reduced the expression and secretion of pro-inflammatory cytokines IL-6, IL-1α, IL-1β and pro-inflammatory chemokines IL-8 and MCP-1 in human placenta and omental and subcutaneous adipose tissue. Resveratrol also significantly restored the defects in the insulin signalling pathway and glucose uptake induced by TNF-α, LPS and poly(I:C). Collectively, these findings suggest that resveratrol reduces inflammation and insulin resistance induced by chemical and microbial products. Resveratrol may be a useful preventative therapeutic for pregnancies complicated by inflammation and insulin resistance, like GDM.

Variability of Directly Measured First-Pass Hepatic Insulin Extraction and its Association With Insulin Sensitivity and Plasma Insulin.

PubMed

Asare-Bediako, Isaac; Paszkiewicz, Rebecca L; Kim, Stella P; Woolcott, Orison O; Kolka, Cathryn M; Burch, Miguel A; Kabir, Morvarid; Bergman, Richard N

2018-05-11

While the β-cells secrete insulin, it is the liver with its first-pass insulin extraction (FPE) that regulates the amount of insulin allowed into circulation for action on target tissues. The metabolic clearance rate of insulin, of which FPE is the dominant component, is reported to be a major determinant of insulin sensitivity (SI). We studied the intricate relationship between FPE, SI and fasting insulin. We used a direct method of measuring FPE, the paired portal/peripheral infusion protocol (PPII) where insulin is infused step-wise, either via the portal vein or a peripheral vein in healthy young dogs (n =12). FPE is calculated as the difference in clearance rates (slope of infusion rate vs. steady insulin plot) between the paired experiments. Significant correlations were found between FPE vs. clamp assessed SI (r s = 0.74); FPE vs. fasting insulin (r s = -0.64) and SI vs. fasting insulin (r s = - 0.67). Also, we found a wide variance in FPE (22.4 -77.2%; mean ± SD of 50.4 ± 19.1%) which is reflected in the variability of plasma insulin (48.1 ± 30.9pM) and SI (9.4 ± 5.8 x10 4 dL * kg -1 * min -1 * pM -1 ). FPE could be the nexus of regulation of both plasma insulin and SI. © 2018 by the American Diabetes Association.

Fundamental mechanisms in premixed flame propagation via vortex-flame interactions: Numerical simulations

NASA Technical Reports Server (NTRS)

Mantel, Thierry

1994-01-01

The goal of the present study is to assess numerically the ability of single-step and two-step chemical models to describe the main features encountered during the interaction between a two-dimensional vortex pair and a premixed laminar flame. In the two-step mechanism, the reaction kinetics are represented by a first chain branching reaction A + X yields 2X and a second chain termination reaction X + X yields P. This paper presents the fundamental mechanisms occurring during vortex-flame interactions and the relative impact of the major parameters encountered in turbulent premixed flames and suspected of playing a role in quenching mechanism: (1) Influence of stretch is investigated by analyzing the contribution of curvature and tangential strain on the local structure of the flame. The effect of Lewis number on the flame response to a strained field is analyzed. (2) Radiative heat losses which are suspected to be partially or totally responsible for quenching are also investigated. (3) The effect of the diffusion of the radicals is studied using a two-step mechanism in which an intermediate species is present. The parameters of the two-step mechanism are entirely determined from physical arguments. (4) Precise quantitative comparisons between the DNS and the experimental results of Samaniego et al are performed. These comparisons concern the evolution of the minimum heat release rate found along the flame front during the interaction and the distribution of the heat release rate along the flame front.

A model of insulin fibrils derived from the x-ray crystal structure of a monomeric insulin (despentapeptide insulin).

PubMed

Brange, J; Dodson, G G; Edwards, D J; Holden, P H; Whittingham, J L

1997-04-01

The crystal structure of despentapeptide insulin, a monomeric insulin, has been refined at 1.3 A spacing and subsequently used to predict and model the organization in the insulin fibril. The model makes use of the contacts in the densely packed despentapeptide insulin crystal, and takes into account other experimental evidence, including binding studies with Congo red. The dimensions of this model fibril correspond well with those measured experimentally, and the monomer-monomer contacts within the fibril are in accordance with the known physical chemistry of insulin fibrils. Using this model, it may be possible to predict mutations in insulin that might alleviate problems associated with fibril formation during insulin therapy.

Food image-induced brain activation is not diminished by insulin infusion

PubMed Central

Belfort-DeAguiar, Renata; Seo, Dongju; Naik, Sarita; Hwang, Janice; Lacadie, Cheryl; Schmidt, Christian; Constable, R. Todd; Sinha, Rajita; Sherwin, Robert

2016-01-01

Background/Objective The obesity epidemic appears to be driven in large part by our modern environment inundated by food cues, which may influence our desire to eat. While insulin decreases food intake in both animals and humans, the effect of insulin on motivation for food in the presence of food cues is not known. Therefore, the aim of this study was to evaluate the effect of an intravenous insulin infusion on the brain response to visual food cues, hunger and food craving in non-obese human subjects. Subjects/Methods Thirty-four right-handed healthy non-obese subjects (19F/15M, age: 29±8 yrs.; BMI: 23.1±2.1 kg/m2) were divided in two groups matched by age, and BMI: the Insulin Group (18 subjects) underwent a hyperinsulinemic-euglycemic-clamp, and the control group (16 subjects) received an intravenous saline infusion, while viewing high and low-calorie food and non-food pictures during a functional MRI scan. Motivation for food was determined via analogue scales for hunger, wanting and liking ratings. Results Food images induced brain responses in the hypothalamus, striatum, amygdala, insula, ventromedial prefrontal cortex (PFC), dorsolateral PFC, and occipital lobe (whole brain correction, P<0.05). Wanting (P<0.001) and liking (P<0.001) ratings were significantly higher for the food than the non-food images, but not different between insulin and saline infusion groups. Hunger ratings increased throughout the MRI scan and correlated with preference for high-calorie food pictures (r=0.70; P<0.001). However neither brain activity nor food craving were affected by hyperinsulinemia or hormonal status (leptin and ghrelin levels) (P=NS). Conclusion Our data demonstrate that visual food cues induce a strong response in motivation/reward and cognitive-executive control brain regions in non-obese subjects, but that these responses are not diminished by hyperinsulinemia per se. These findings suggest that our modern food cue saturated environment may be sufficient to

Tau hyperphosphorylation induces oligomeric insulin accumulation and insulin resistance in neurons.

PubMed

Rodriguez-Rodriguez, Patricia; Sandebring-Matton, Anna; Merino-Serrais, Paula; Parrado-Fernandez, Cristina; Rabano, Alberto; Winblad, Bengt; Ávila, Jesús; Ferrer, Isidre; Cedazo-Minguez, Angel

2017-12-01

Insulin signalling deficiencies and insulin resistance have been directly linked to the progression of neurodegenerative disorders like Alzheimer's disease. However, to date little is known about the underlying molecular mechanisms or insulin state and distribution in the brain under pathological conditions. Here, we report that insulin is accumulated and retained as oligomers in hyperphosphorylated tau-bearing neurons in Alzheimer's disease and in several of the most prevalent human tauopathies. The intraneuronal accumulation of insulin is directly dependent on tau hyperphosphorylation, and follows the tauopathy progression. Furthermore, cells accumulating insulin show signs of insulin resistance and decreased insulin receptor levels. These results suggest that insulin retention in hyperphosphorylated tau-bearing neurons is a causative factor for the insulin resistance observed in tauopathies, and describe a novel neuropathological concept with important therapeutic implications. © The Author (2017). Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Insulin Therapy

MedlinePlus

... Your Health Resources Drugs, Procedures & Devices Prescription Medicines Insulin Therapy Insulin Therapy Share Print When you digest food, your ... you eat into glucose (a form of sugar). Insulin allows this glucose to enter all the cells ...

Flame holding tolerant fuel and air premixer for a gas turbine combustor

DOEpatents

York, William David; Johnson, Thomas Edward; Ziminsky, Willy Steve

2012-11-20

A fuel nozzle with active cooling is provided. It includes an outer peripheral wall, a nozzle center body concentrically disposed within the outer wall in a fuel and air pre-mixture. The fuel and air pre-mixture includes an air inlet, a fuel inlet and a premixing passage defined between the outer wall in the center body. A gas fuel flow passage is provided. A first cooling passage is included within the center body in a second cooling passage is defined between the center body and the outer wall.

Insulin resistance in obesity can be reliably identified from fasting plasma insulin.

PubMed

ter Horst, K W; Gilijamse, P W; Koopman, K E; de Weijer, B A; Brands, M; Kootte, R S; Romijn, J A; Ackermans, M T; Nieuwdorp, M; Soeters, M R; Serlie, M J

2015-12-01

Insulin resistance is the major contributor to cardiometabolic complications of obesity. We aimed to (1) establish cutoff points for insulin resistance from euglycemic hyperinsulinemic clamps (EHCs), (2) identify insulin-resistant obese subjects and (3) predict insulin resistance from routinely measured variables. We assembled data from non-obese (n=112) and obese (n=100) men who underwent two-step EHCs using [6,6-(2)H2]glucose as tracer (insulin infusion dose 20 and 60 mU m(-2) min(-1), respectively). Reference ranges for hepatic and peripheral insulin sensitivity were calculated from healthy non-obese men. Based on these reference values, obese men with preserved insulin sensitivity or insulin resistance were identified. Cutoff points for insulin-mediated suppression of endogenous glucose production (EGP) and insulin-stimulated glucose disappearance rate (Rd) were 46.5% and 37.3 μmol kg(-)(1) min(-)(1), respectively. Most obese men (78%) had EGP suppression within the reference range, whereas only 12% of obese men had Rd within the reference range. Obese men with Rd <37.3 μmol kg(-1) min(-1) did not differ from insulin-sensitive obese men in age, body mass index (BMI), body composition, fasting glucose or cholesterol, but did have higher fasting insulin (110±49 vs 63±29 pmol l(-1), P<0.001) and homeostasis model assessment of insulin resistance (HOMA-IR) (4.5±2.2 vs 2.7±1.4, P=0.004). Insulin-resistant obese men could be identified with good sensitivity (80%) and specificity (75%) from fasting insulin >74 pmol l(-1). Most obese men have hepatic insulin sensitivity within the range of non-obese controls, but below-normal peripheral insulin sensitivity, that is, insulin resistance. Fasting insulin (>74 pmol l(-1) with current insulin immunoassay) may be used for identification of insulin-resistant (or metabolically unhealthy) obese men in research and clinical settings.

The effect of incomplete fuel-air mixing on the lean blowout limit, lean stability limit and NO(x) emissions in lean premixed gas turbine combustors

NASA Technical Reports Server (NTRS)

Shih, W.-P.; Lee, J. G.; Santavicca, D. A.

1994-01-01

Gas turbine engines for both land-based and aircraft propulsion applications are facing regulations on NOx emissions which cannot be met with current combustor technology. A number of alternative combustor strategies are being investigated which have the potential capability of achieving ultra-low NOx emissions, including lean premixed combustors, direct injection combustors, rich burn-quick quench-lean burn combustors and catalytic combustors. The research reported in this paper addresses the effect of incomplete fuel-air mixing on the lean limit performance and the NOx emissions characteristics of lean premixed combustors.

Effects of intranasal insulin on endogenous glucose production in insulin-resistant men.

PubMed

Xiao, Changting; Dash, Satya; Stahel, Priska; Lewis, Gary F

2018-03-14

The effects of intranasal insulin on the regulation of endogenous glucose production (EGP) in individuals with insulin resistance were assessed in a single-blind, crossover study. Overweight or obese insulin-resistant men (n = 7; body mass index 35.4 ± 4.4 kg/m 2 , homeostatic model assessment of insulin resistance 5.6 ± 1.6) received intranasal spray of either 40 IU insulin lispro or placebo in 2 randomized visits. Acute systemic spillover of intranasal insulin into the circulation was matched with a 30-minute intravenous infusion of insulin lispro in the nasal placebo arm. EGP was assessed under conditions of a pancreatic clamp with a primed, constant infusion of glucose tracer. Under these experimental conditions, compared with placebo, intranasal administration of insulin did not significantly affect plasma glucose concentrations, EGP or glucose disposal in overweight/obese, insulin-resistant men, in contrast to our previous study, in which an equivalent dose of intranasal insulin significantly suppressed EGP in lean, insulin-sensitive men. Insulin resistance is probably associated with impairment in centrally mediated insulin suppression of EGP. © 2018 John Wiley & Sons Ltd.

Interaction of a vortex and a premixed flame

NASA Technical Reports Server (NTRS)

Ferziger, Joel H.; Rutland, Christopher J.

1989-01-01

The interaction of a vortex structure and a premixed flame is studied. The presence of pressure gradients in the vortex and density gradients in the flame result in a complicated interaction. This interaction has been examined when the flame and vortex are fully coupled and in two special cases where they are decoupled: a frozen flame case and a frozen vortex case. In the frozen flame case the main effect of the flame on the vortex is through the barocline torque term. This has been modeled for high Damkoehler numbers. In the frozen vortex case the main effect, at moderate Damkoehler numbers, is to convect the flame around the vortex. At low Damkoehler numbers, depending on the length scales, pockets of unburned gas can form or the flame structure can be significantly changed. The two frozen cases provide a basis for understanding the full interaction.

Impaired Insulin Secretion and Enhanced Insulin Sensitivity in Cholecystokinin-Deficient Mice

PubMed Central

Lo, Chun-Min; Obici, Silvana; Dong, H. Henry; Haas, Michael; Lou, Dawnwen; Kim, Dae Hyun; Liu, Min; D’Alessio, David; Woods, Stephen C.; Tso, Patrick