Fatigue behaviour of C-Mn-B steels:effects of heat treatment prestrain and residual stress

The fatigue-crack propagation and threshold behaviour of a C-Mn steel containing boron has been investigated at a range of strength levels suitable for mining chain applications. The heat-treatment variables examined include two austenitizing temperatures (900 degree C and 1250 degree C) and a range of tempering treatments from the as-quenched condition to tempering at 400 degree C. In mining applications the haulage chains undergo a 'calibration' process which has the effect of imposing a tensile prestrain on the chain links before they go into service. Prestrain is shown to reduce threshold values in these steels and this behaviour is related to its effects on the residual stress distribution in the test specimens.

The pre-treatment and pyrolysis of biomass for the production of liquids for fuels and speciality chemicals

Fast pyrolysis of biomass is a significant technology for producing pyrolysis liquids [also known as bio-oil], which contain a number of chemicals. The pyrolysis liquid can be used as a fuel, can be produced solely as a source of chemicals or can have some of the chemicals extracted and the residue used as a fuel. There were two primary objectives of this work. The first was to determine the fast pyrolysis conditions required to maximise the pyrolysis liquid yield from a number of biomass feedstocks. The second objective was to selectively increase the yield of certain chemicals in the pyrolysis liquid by pre-treatment of the feedstock prior to pyrolysis. For a particular biomass feedstock the pyrolysis liquid yield is affected by the reactor process parameters. It has been found that, providing the other process parameters are restricted to the values shown below, reactor temperature is the controlling parameter. The maximum pyrolysis liquid yield and the temperature at which it occurs has been found by a series of pyrolysis experiments over the temperature range 400-600°C. high heating rates > 1000°C/s; pyrolysis vapour residence times <2 seconds; pyrolysis vapour temperatures >400 but <500°C; rapid quenching of the product vapours. Pre-treatment techniques have been devised to modify the chemical composition and/or structure of the biomass in such a way as to influence the chemical composition of the pyrolysis liquid product. The pre-treatments were divided into two groups, those that remove material from the biomass and those which add material to the biomass. Component removal techniques have selectively increased the yield of levoglucosan from 2.45 to 18.58 mf wt.% [dry feedstock basis]. Additive techniques have selectively increased the yield of hydroxyacetaldehyde from 7.26 to 11.63 mf w.% [dry feedstock basis]. Techno-economic assessment has been carried out on an integrated levoglucosan production process [incorporating pre-treatment, pyrolysis and chemical extraction stages] to assess which method of chemical production is the more cost effective. It has been found that it is better to pre-treat the biomass in order to increase the yield of specific chemicals in the pyrolysis liquid and hence improve subsequent chemicals extraction.

Ranibizumab 0.5 mg for diabetic macular edema with bimonthly monitoring after a phase of initial treatment:18-month, multicenter, phase IIIB RELIGHT study

Abstract PURPOSE: To evaluate ranibizumab 0.5 mg using bimonthly monitoring and individualized re-treatment after monthly follow-up for 6 months in patients with visual impairment due to diabetic macular edema (DME). DESIGN: A phase IIIb, 18-month, prospective, open-label, multicenter, single-arm study in the United Kingdom. PARTICIPANTS: Participants (N = 109) with visual impairment due to DME. METHODS: Participants received 3 initial monthly ranibizumab 0.5 mg injections (day 0 to month 2), followed by individualized best-corrected visual acuity (BCVA) and optical coherence tomography-guided re-treatment with monthly (months 3-5) and subsequent bimonthly follow-up (months 6-18). Laser was allowed after month 6. MAIN OUTCOME MEASURES: Mean change in BCVA from baseline to month 12 (primary end point), mean change in BCVA and central retinal thickness (CRT) from baseline to month 18, gain of ≥10 and ≥15 letters, treatment exposure, and incidence of adverse events over 18 months. RESULTS: Of 109 participants, 100 (91.7%) and 99 (90.8%) completed the 12 and 18 months of the study, respectively. The mean age was 63.7 years, the mean duration of DME was 40 months, and 77.1% of the participants had received prior laser treatment (study eye). At baseline, mean BCVA was 62.9 letters, 20% of patients had a baseline BCVA of >73 letters, and mean baseline CRT was 418.1 μm, with 32% of patients having a baseline CRT <300 μm. The mean change in BCVA from baseline to month 6 was +6.6 letters (95% confidence interval [CI], 4.9-8.3), and after institution of bimonthly treatment the mean change in BCVA at month 12 was +4.8 letters (95% CI, 2.9-6.7; P < 0.001) and +6.5 letters (95% CI, 4.2-8.8) at month 18. The proportion of participants gaining ≥10 and ≥15 letters was 24.8% and 13.8% at month 12 and 34.9% and 19.3% at month 18, respectively. Participants received a mean of 6.8 and 8.5 injections over 12 and 18 months, respectively. No new ocular or nonocular safety findings were observed during the study. CONCLUSIONS: The BCVA gain achieved in the initial 6-month treatment period was maintained with an additional 12 months of bimonthly ranibizumab PRN treatment.

Pharmacology and therapeutic implications of current drugs for type 2 diabetes mellitus

Type 2 diabetes mellitus (T2DM) is a global epidemic that poses a major challenge to health-care systems. Improving metabolic control to approach normal glycaemia (where practical) greatly benefits long-term prognoses and justifies early, effective, sustained and safety-conscious intervention. Improvements in the understanding of the complex pathogenesis of T2DM have underpinned the development of glucose-lowering therapies with complementary mechanisms of action, which have expanded treatment options and facilitated individualized management strategies. Over the past decade, several new classes of glucose-lowering agents have been licensed, including glucagon-like peptide 1 receptor (GLP-1R) agonists, dipeptidyl peptidase 4 (DPP-4) inhibitors and sodium/glucose cotransporter 2 (SGLT2) inhibitors. These agents can be used individually or in combination with well-established treatments such as biguanides, sulfonylureas and thiazolidinediones. Although novel agents have potential advantages including low risk of hypoglycaemia and help with weight control, long-term safety has yet to be established. In this Review, we assess the pharmacokinetics, pharmacodynamics and safety profiles, including cardiovascular safety, of currently available therapies for management of hyperglycaemia in patients with T2DM within the context of disease pathogenesis and natural history. In addition, we briefly describe treatment algorithms for patients with T2DM and lessons from present therapies to inform the development of future therapies.

Dopamine, empathy and the neurobiology of leadership

Objectives: Organisational Psychologists have long sought after methods by which to train individuals to become more effective leaders. Indeed considerable sums of money are spent on the design of such training programs. Yet it is not clear whether or not leadership skills can be taught or whether they are innate. Social leadership is a varied construct consisting of many diverse aspects, yet the ability to empathise with subordinates is a core skill that underpins effective transformational leadership. This type of leadership consists of four characteristics which are labelled ‘idealized influence’, ‘inspirational motivation’, ‘intellectual stimulation’ and ‘individualized consideration’. This is distinct from the transactional style of leadership, which is based on offering contingent rewards for completion of specific tasks. By identifying a specific gene that mediates distinct leadership traits, more effective training regimes can be designed. Design: There are two likely candidate genes that may mediate empathic leadership. The first is catechol-O-methyltransferase (COMT) which is involved with dopamine synthesis, and the second is the serotonin transporter promoter gene (5-HTTLPR). Both these genes mostly appear in the general population in their heterozygotic form. Thus by comparing phenotypes in leadership traits a measure of base line differences can be examined. Methods: 115 volunteers completed the Multifactor Leadership questionnaire (MLQ), which is a standard 12-item leadership psychometric scale and also underwent buccal swab for subsequent genotyping. Results: Of the 115 subjects 37 were heterozygotic for the COMT gene and 47 heterozygotic for 5-HTTLPR. Of the 12 MLQ subscales, the scores for two of the subscales only differed between the two participant groups. Individuals who were heterozygotic for the COMT gene scored higher on the ‘Inspirational motivation’ t(84)=1.99, p=0.05 and ‘Intellectual stimulation’ t(82)=1.94, p=0.05 scales compared to the carriers for the heterozygotic 5HTPP gene. Conclusions: Given that the behaviours described by these two MLQ subscales require leaders to empathise with subordinates, the current results suggest that dopamine may play a role in this important social task. The fact that both heterozygotic carriers for COMT and 5HTPP were compared allows a comparison to be made between the genotypes most prevalent in the general population.

The plasma nutriding of tool and bearing steels

There is some evidence to suggest that nitriding of alloy steels, in particular high speed tool steels, under carefully controlled conditions might sharply increase rolling contact fatigue resistance. However, the subsurface shear stresses developed in aerospace bearing applications tend to occur at depths greater than the usual case depths currently produced by nitriding. Additionally, case development must be limited with certain materials due to case spalling and may not always be sufficient to achieve the current theoretical depths necessary to ensure that peak stresses occur within the case. It was the aim of' this work to establish suitable to overcome this problem by plasma nitriding. To assist this development a study has been made of prior hardening treatment, case development, residual stress and case cracking tendency. M2 in the underhardened, undertempered and fully hardened and tempered conditions all responded similarly to plasma nitriding - maximum surface hardening being achieved by plasma nitriding at 450°C. Case development varied linearly with increasing treatment temperature and also with the square root of the treatment time. Maximum surface hardness of M5O and Tl steels was achieved by plasma nitriding in 15% nitrogen/85% hydrogen and varied logarithmically with atmosphere nitrogen content. The case-cracking contact stress varied linearly with nitriding temperature for M2. Tl and M5O supported higher stresses after nitriding in low nitrogen plasma atmospheres. Unidirectional bending fatigue of M2 has been improved up to three times the strength of the fully hardened and tempered condition by plasma nitriding for 16hrs at 400°C. Fatigue strengths of Tl and M5O have been improved by up to 30% by plasma nitriding for 16hrs at 450°C in a 75% hydrogen/25% nitrogen atmosphere.

The retinopathy of prematurity: a study of incidence and the identification of those babies at risk: myopia associated with prematurity

The ocular problems associated with premature birth have been with us ever since it was discovered that the application of high levels of inspired oxygen provided a reduction in mortality. The consequence of this reduction in mortality has been a rise in morbidity; these mortality and morbidity rates have oscillated during the attempt to find a reasonable balance. The use of contemporary technology during the attempt both to understand the premature baby's delicate physiology and to maintain life to younger and lighter babies has not yet produced stability. The incidence of typical retinal maldevelopment, retinopathy of prematurity (RCP), was analysed by serial weekly ophthalmoscopy examinations in a regional special care baby unit, 579 examinations being made on 138 babies. The best instrument for this examination was found to be a compact indirect ophthalmoscope incorporating an inverting eyepiece - the Reichert Jung monocular indirect ophthalmoscope. The optimum time for ocular examination to discover potential ocular morbidity was at 33 weeks post-conceptual age (PCA) with continued examinations to the age of 37 weeks PCA. The babies that were found to be at risk of a significant grade of RCP were found to be of a birth weight of less than 1251 grams or had an estimated gestational age at birth of 30 weeks or less. A refractive state of myopia was found to be the norm. The myopia reduced as life progressed to attain emmetropia around the age of 50 weeks PCA or 22 weeks survival. The reduction of the myopic state was found to be dependent on birth weight and gestational age at birth, the youngest and therefore the lightest being more predictable in attaining emmetropia. Refractive variations were found to be coincident with the timings of certain medical treatment regimes and a hypothesis is postulated as to the mechanism of this association.

A method for the in-situ determination of the hydraulic conductivity of gravels as used in constructed wetlands for wastewater treatment

A new instrument and method are described that allow the hydraulic conductivities of highly permeable porous materials, such as gravels in constructed wetlands, to be determined in the field. The instrument consists of a Mariotte siphon and a submersible permeameter cell with manometer take-off tubes, to recreate in-situ the constant head permeameter test typically used with excavated samples. It allows permeability to be measured at different depths and positions over the wetland. Repeatability obtained at fixed positions was good (normalised standard deviation of 1–4%), and results obtained for highly homogenous silica sand compared well when the sand was retested in a lab permeameter (0.32 mm.s–1 and 0.31 mm.s–1 respectively). Practical results have a ±30% associated degree of uncertainty because of the mixed effect of natural variation in gravel core profiles, and interstitial clogging disruption during insertion of the tube into the gravel. This error is small, however, compared to the orders of magnitude spatial variations detected. The technique was used to survey the hydraulic conductivity profile of two constructed wetlands in the UK, aged 1 and 15 years respectively. Measured values were high (up to 900 mm.s –1) and varied by three orders of magnitude, reflecting the immaturity of the wetland. Detailed profiling of the younger system suggested the existence of preferential flow paths at a depth of 200 mm, corresponding to the transition between more coarse and less coarse gravel layers (6–12 mm and 3–6 mm respectively), and transverse drift towards the outlet.

Measuring the assessment and counselling provided with the supply of non-prescription asthma reliever medication: a simulated patient study

BACKGROUND: Over one quarter of asthma reliever medications are provided without prescription by community pharmacies in Australia. Evidence that community pharmacies provide these medications with sufficient patient assessment and medication counseling to ensure compliance with the government's Quality Use of Medicines principles is currently lacking. OBJECTIVE: To assess current practice when asthma reliever medication is provided in the community pharmacy setting and to identify factors that correlate with assessment of asthma control. METHODS: Researchers posing as patients visited a sample of Perth metropolitan community pharmacies in May 2007. During the visit, the simulated patient enacted a standardized scenario of someone with moderately controlled asthma who wished to purchase a salbutamol (albuterol) inhaler without prescription. Results of the encounter were recorded immediately after the visit. Regression analysis was performed, with medication use frequency (a marker of asthma control) as the dependent variable. RESULTS: One hundred sixty community pharmacies in the Perth metropolitan area were visited in May 2007. Pharmacists and/or pharmacy assistants provided some form of assessment in 84% of the visits. Counseling was provided to the simulated patients in 24% of the visits. Only 4 pharmacy staff members asked whether the simulated patient knew how to use the inhaler. Significant correlation was found between assessment and/or counseling of reliever use frequency and 3 independent variables: visit length (p < 0.001), number of assessment questions asked (p < 0.001), and the simulated patient who conducted the visit (p < 0.02). CONCLUSIONS: Both patient assessment and medication counseling were suboptimal compared with recommended practice when nonprescription asthma reliever medication was supplied in the community pharmacy setting. Pharmacy and pharmacist demographic variables do not appear to affect assessment of asthma control. This research indicates the need for substantial improvements in practice in order to provide reliever medication in line with Quality Use of Medication principles of ensuring safe and effective use of medication.

Team working in intensive care:current evidence and future endeavors

Purpose of review: It has recently been argued that the future of intensive care medicine will rely on high quality management and teamwork. Therefore, this review takes an organizational psychology perspective to examine the most recent research on the relationship between teamwork, care processes, and patient outcomes in intensive care. Recent findings: Interdisciplinary communication within a team is crucial for the development of negotiated shared treatment goals and short-team patient outcomes. Interventions for maximizing team communication have received substantial interest in recent literature. Intensive care coordination is not a linear process, and intensive care teams often fail to discuss how to implement goals, trigger and align activities, or reflect on their performance. Despite a move toward interdisciplinary team working, clinical decision-making is still problematic and continues to be perceived as a top-down and authoritative process. The topic of team leadership in intensive care is underexplored and requires further research. Summary: Based on findings from the most recent research evidence in medicine and management, four principles are identified for improving the effectiveness of team working in intensive care: engender professional efficacy, create stable teams and leaders, develop trust and participative safety, and enable frequent team reflexivity.

Describing and communicating uncertainty within the semantic web

The Semantic Web relies on carefully structured, well defined, data to allow machines to communicate and understand one another. In many domains (e.g. geospatial) the data being described contains some uncertainty, often due to incomplete knowledge; meaningful processing of this data requires these uncertainties to be carefully analysed and integrated into the process chain. Currently, within the SemanticWeb there is no standard mechanism for interoperable description and exchange of uncertain information, which renders the automated processing of such information implausible, particularly where error must be considered and captured as it propagates through a processing sequence. In particular we adopt a Bayesian perspective and focus on the case where the inputs / outputs are naturally treated as random variables. This paper discusses a solution to the problem in the form of the Uncertainty Markup Language (UncertML). UncertML is a conceptual model, realised as an XML schema, that allows uncertainty to be quantified in a variety of ways i.e. realisations, statistics and probability distributions. UncertML is based upon a soft-typed XML schema design that provides a generic framework from which any statistic or distribution may be created. Making extensive use of Geography Markup Language (GML) dictionaries, UncertML provides a collection of definitions for common uncertainty types. Containing both written descriptions and mathematical functions, encoded as MathML, the definitions within these dictionaries provide a robust mechanism for defining any statistic or distribution and can be easily extended. Universal Resource Identifiers (URIs) are used to introduce semantics to the soft-typed elements by linking to these dictionary definitions. The INTAMAP (INTeroperability and Automated MAPping) project provides a use case for UncertML. This paper demonstrates how observation errors can be quantified using UncertML and wrapped within an Observations & Measurements (O&M) Observation. The interpolation service uses the information within these observations to influence the prediction outcome. The output uncertainties may be encoded in a variety of UncertML types, e.g. a series of marginal Gaussian distributions, a set of statistics, such as the first three marginal moments, or a set of realisations from a Monte Carlo treatment. Quantifying and propagating uncertainty in this way allows such interpolation results to be consumed by other services. This could form part of a risk management chain or a decision support system, and ultimately paves the way for complex data processing chains in the Semantic Web.

Pharmacogenomic studies of the anticancer and immunosuppressive thiopurines mercaptopurine and azathioprine

WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT • 6-Mercaptopurine (6-MP) and azathioprine (AZA) are both inactive prodrugs that require intracellular activation into the active 6-thioguanine nucleotides (6-TGNs). • This metabolic process undergoes three different competitive pathways that are catalysed by three different enzymes; xanthine oxidase (XO), thiopurine methyltransferase (TPMT) and inosine triphosphatase (ITPA), all of which exhibit genetic polymorphisms. • Although the impact of genetic variation in the TPMT gene on treatment outcome and toxicity has been demonstrated, the role of other polymorphisms remains less well known. WHAT THIS STUDY ADDS • New information on the allelic variation of these three enzymes (XO, TPMT and ITPA) and their influence on 6-MP/AZA metabolism and toxicity. • Confirmation of the association of TPMT polymorphism with haematological toxicity. • Identified potential genetic characteristics that may contribute to higher risk of adverse events (such as ITPA IVS2+21A→C mutation). AIMS - To examine the allelic variation of three enzymes involved in 6-mercaptopurine/azathioprine (6-MP/AZA) metabolism and evaluate the influence of these polymorphisms on toxicity, haematological parameters and metabolite levels in patients with acute lymphoblastic leukaemia (ALL) or inflammatory bowel disease (IBD). METHODS - Clinical data and blood samples were collected from 19 ALL paediatric patients and 35 IBD patients who were receiving 6-MP/AZA therapy. All patients were screened for seven genetic polymorphisms in three enzymes involved in mercaptopurine metabolism [xanthine oxidase, inosine triphosphatase (C94→A and IVS2+21A→C) and thiopurine methyltransferase]. Erythrocyte and plasma metabolite concentrations were also determined. The associations between the various genotypes and myelotoxicity, haematological parameters and metabolite concentrations were determined. RESULTS - Thiopurine methyltransferase variant alleles were associated with a preferential metabolism away from 6-methylmercaptopurine nucleotides (P = 0.008 in ALL patients, P = 0.038 in IBD patients) favouring 6-thioguanine nucleotides (6-TGNs) (P = 0.021 in ALL patients). Interestingly, carriers of inosine triphosphatase IVS2+21A→C variants among ALL and IBD patients had significantly higher concentrations of the active cytotoxic metabolites, 6-TGNs (P = 0.008 in ALL patients, P = 0.047 in IBD patients). The study confirmed the association of thiopurine methyltransferase heterozygosity with leucopenia and neutropenia in ALL patients and reported a significant association between inosine triphosphatase IVS2+21A→C variants with thrombocytopenia (P = 0.012). CONCLUSIONS - Pharmacogenetic polymorphisms in the 6-MP pathway may help identify patients at risk for associated toxicities and may serve as a guide for dose individualization.

How drug metabolism influences treatment outcomes

Recent developments within the National Health Service have led to an increase in personnel 'qualified' to prescribe a wide range of pharmacological agents. A short (38-day) Continuing Professional Development course in prescribing is deemed adequate to fully train individuals for practice. A sound understanding of prescribing medicines has important implications for patient benefit. For example, a prescriber would require some knowledge of drug absorption, distribution, metabolism and excretion, as well as aspects of drug delivery and drug-drug interactions. Drug metabolism in particular exerts a powerful influence on drug action; this can range from complete failure of efficacy through to life-threatening toxicity. Moreover, it is conservatively estimated that there may be several thousand deaths each year in the UK arising from an inadequate knowledge of drug metabolism when prescribing medicines. This one-day course focused on the importance of understanding drug metabolism on treatment strategies and outcomes, and was accessed by a range of healthcare professionals in the West Midlands area of the UK. © 2007 Informa UK Ltd.

Residue-specific investigation of the relationship between oxidation and activity of a dual specificity phosphatase by mass spectrometry

Redox regulation of signalling pathways is critical in proliferation and apoptosis; redox imbalance can lead to pathologies such as inflammation and cancer. Vaccinia H1-related protein (VHR; DUSP3) is a dual-specificity phosphatase important in controlling MAP kinase activity during cell cycle. the active-site motif contains a cysteine that acts as a nucleophile during catalysis. We used VHR to investigate the effect of oxidation in vitro on phosphatase activity, with the aim of determining how the profile of site-specific modification related to catalytic activity. Recombinant human VHR was expressed in E. coli and purified using a GST-tag. Protein was subjected to oxidation with various concentrations of SIN-1 or tetranitromethane (TNM) as nitrating agents, or HOCl. the activity was assayed using either 3-O-methylfluorescein phosphate with fluorescence detection or PIP3 by phosphate release with malachite green. the sites of oxidation were mapped using HPLC coupled to tandem mass spectrometry on an ABSciex 5600TripleTOF following in-gel digestion. More than 25 different concentration-dependent oxidative modifications to the protein were detected, including oxidations of methionine, cysteine, histidine, lysine, proline and tyrosine, and the % oxidized peptide (versus unmodified peptide) was determined from the extracted ion chromatograms. Unsurprisingly, methionine residues were very susceptible to oxidation, but there was a significant different in the extent of their oxidation. Similarly, tyrosine residues varied greatly in their modifications: Y85 and Y138 were readily nitrated, whereas Y38, Y78 and Y101 showed little modification. Y138 must be phosphorylated for MAPK phosphatase activity, so this susceptibility impacts on signalling pathways. Di- and tri- oxidations of cysteine residues were observed, but did not correlate directly with loss of activity. Overall, the catalytic activity did not correlate with redox state of any individual residue, but the total oxidative load correlated with treatment concentration and activity. This study provides the first comprehensive analysis of oxidation modifications of VHR, and demonstrates both heterogenous oxidant effects and differential residue susceptibility in a signalling phosphatase.

Relationship between changes in postprandial glucagon, patient characteristics, and response to lixisenatide as add-on to oral antidiabetics

Background and aims: Lixisenatide, a once-daily prandial glucagon-like peptide-1 receptor agonist, reduces postprandial (PP) glycaemic excursions and HbA 1c . We report an exploratory analysis of the GetGoal-M and S trials in patients with type 2 diabetes mellitus (T2DM) with different changes in PP glucagon levels in response to lixisenatide treatment. Materials and methods: Patients (n=423) were stratified by their change in 2 hour PP glucagon level between baseline evaluation and Week 24 of treat - ment with lixisenatide as add-on to oral antidiabetics (OADs) into groups of Greater Change (GC; n=213) or Smaller Change (SC; n=210) in plasma glucagon levels (median change -23.57 ng/L). ANOVA and Chi-squared tests were used for the comparison of continuous and categorical variables, respec - tively. Baseline and endpoint continuous measurements in each group were compared using paired t -tests. Results: Mean change from baseline in 2 hour PP glucagon levels for the GC vs SC groups was -47.19 vs -0.59 ng/L (p<0.0001), respectively. Patients in the GC group had a shorter mean duration of diabetes (7.3 vs 9.0 years; p=0.0036) and lesser OAD use (4.5 vs 5.7 years; p=0.0092) than those in the SC group. Patients in the GC group had a greater mean reduction in HbA 1c (-1.10 vs -0.67%; p<0.0001), fasting plasma glucose (FPG; -25.20 vs -9.30 mg/dL [p<0.0001]), PP plasma glucose (PPG; -129.40 vs -78.22 mg/dL [p<0.0001]), and a greater drop in weight (-2.27 vs -1.17 kg; p=0.0002) and body mass index (-0.84 vs -0.44 kg/m 2 ; p=0.0002) than those in the SC group. More patients in the GC group also achieved composite endpoints, including HbA 1c <7% with no symptomatic hypoglycaemia and no weight gain (40.38 vs 19.52%; p<0.0001), than in the SC group. Conclusion: Greater reductions in PP glucagon associated with lixisenatide as add-on to OADs in patients with T2DM are also associated with greater reductions in HbA1c, FPG, PPG, and greater weight loss, highlighting the importance of glucagon suppression on therapeutic response. Clinical Trial Registration Number: NCT00712673; NCT00713830 Supported by: Sanof