Liraglutide vs insulin glargine and placebo in combination with metformin and sulfonylurea therapy in type 2 diabetes mellitus (LEAD-5 met+SU): a randomised controlled trial

Udgivelsesdato: 2009-OctAIMS/HYPOTHESIS: The aim of the study was to compare the efficacy and safety of liraglutide in type 2 diabetes mellitus vs placebo and insulin glargine (A21Gly,B31Arg,B32Arg human insulin), all in combination with metformin and glimepiride. METHODS: This randomised (using a telephone or web-based randomisation system), parallel-group, controlled 26 week trial of 581 patients with type 2 diabetes mellitus on prior monotherapy (HbA(1c) 7.5-10%) and combination therapy (7.0-10%) was conducted in 107 centres in 17 countries. The primary endpoint was HbA(1c). Patients were randomised (2:1:2) to liraglutide 1.8 mg once daily (n = 232), liraglutide placebo (n = 115) and open-label insulin glargine (n = 234), all in combination with metformin (1 g twice daily) and glimepiride (4 mg once daily). Investigators, participants and study monitors were blinded to the treatment status of the liraglutide and placebo groups at all times. RESULTS: The number of patients analysed as intention to treat were: liraglutide n = 230, placebo n = 114, insulin glargine n = 232. Liraglutide reduced HbA(1c) significantly vs glargine (1.33% vs 1.09%; -0.24% difference, 95% CI 0.08, 0.39; p = 0.0015) and placebo (-1.09% difference, 95% CI 0.90, 1.28; p < 0.0001). There was greater weight loss with liraglutide vs placebo (treatment difference -1.39 kg, 95% CI 2.10, 0.69; p = 0.0001), and vs glargine (treatment difference -3.43 kg, 95% CI 4.00, 2.86; p < 0.0001). Liraglutide reduced systolic BP (-4.0 mmHg) vs glargine (+0.5 mmHg; -4.5 mmHg difference, 95% CI 6.8, -2.2; p = 0.0001) but not vs placebo (p = 0.0791). Rates of hypoglycaemic episodes (major, minor and symptoms only, respectively) were 0.06, 1.2 and 1.0 events/patient/year, respectively, in the liraglutide group (vs 0, 1.3, 1.8 and 0, 1.0, 0.5 with glargine and placebo, respectively). A slightly higher number of adverse events (including nausea at 14%) were reported with liraglutide, but only 9.8% of participants in the group receiving liraglutide developed anti-liraglutide antibodies. CONCLUSIONS/INTERPRETATION: Liraglutide added to metformin and sulfonylurea produced significant improvement in glycaemic control and bodyweight compared with placebo and insulin glargine. The difference vs insulin glargine in HbA(1c) was within the predefined non-inferiority margin. TRIAL REGISTRATION: ClinicalTrials.gov NCT00331851. FUNDING: The study was funded by Novo Nordisk A/S

ARTreat Project: Three-Dimensional Numerical Simulation of Plaque Formation and Development in the Arteries

Atherosclerosis is a progressive disease characterized by the accumulation of lipids and fibrous elements in arteries. It is characterized by dysfunction of endothelium and vasculitis, and accumulation of lipid, cholesterol, and cell elements inside blood vessel wall. In this study, a continuum-based approach for plaque formation and development in 3-D is presented. The blood flow is simulated by the 3-D Navier-Stokes equations, together with the continuity equation while low-density lipoprotein (LDL) transport in lumen of the vessel is coupled with Kedem-Katchalsky equations. The inflammatory process was solved using three additional reaction-diffusion partial differential equations. Transport of labeled LDL was fitted with our experiment on the rabbit animal model. Matching with histological data for LDL localization was achieved. Also, 3-D model of the straight artery with initial mild constriction of 30% plaque for formation and development is presented

Accelerator Testing of the General Antiparticle Spectrometer, a Novel Approach to Indirect Dark Matter Detection

We report on recent accelerator testing of a prototype general antiparticle spectrometer (GAPS). GAPS is a novel approach for indirect dark matter searches that exploits the antideuterons produced in neutralino-neutralino annihilations. GAPS captures these antideuterons into a target with the subsequent formation of exotic atoms. These exotic atoms decay with the emission of X-rays of precisely defined energy and a correlated pion signature from nuclear annihilation. This signature uniquely characterizes the antideuterons. Preliminary analysis of data from a prototype GAPS in an antiproton beam at the KEK accelerator in Japan has confirmed the multi-X-ray/pion star topology and indicated X-ray yields consistent with prior expectations. Moreover our success in utilizing solid rather than gas targets represents a significant simplification over our original approach and offers potential gains in sensitivity through reduced dead mass in the target area.Comment: 18 pages, 9 figures, submitted to JCA

Performance analysis for industrial wireless networks

This thesis is the result of the project “Norwegian, Bosnian, and Serbian cooperation platform for university and industry ICT R&D – NORBAS”.Industrial wireless networks operate in harsher and noisier environments compared to traditional wireless networks, while demanding high reliability and low latency. These requirements, combined with the constant need for better coverage, higher data rates and overall seamless user experience call for a paradigm shift in communication in regards to the previous generations of technologies used. Cooperative diversity is one such approach. The main focus of this thesis is on the performance analysis of cooperative wireless networks set in industrial environments – where the network, apart from additive white Gaussian noise, is subject to multipath fading and shadowing, and/or temporary random blockage effects. In these scenarios, in order to achieve specific performance metrics such as error rates or outage probabilities, existing cooperative strategies are aided by protocols in the channel between the cooperating nodes. Moreover, pair-wise analysis investigates the correlation of multiple data flows. Building upon existing repetition protocols, outage performance of a network subject to fading and shadowing is observed, and the effects of fading and shadowing severity, network dimension, average signal-to-noise ratio values and packet length are discussed. Special cases are also observed, in which the composite fading channel is reduced to several familiar propagation environments, unifying the analysis. Afterwards, the analysis of more complex protocols is presented, taking into account random blockage in the channels between cooperating nodes. A novel, threshold-based internode protocol is introduced, which improves performance by listening to the transmissions and choosing whether to send a packet immediately or after a waiting period. As these two periods are close, the effect of temporal correlation is also investigated. Apart from the exact outage probability expressions, simpler asymptotic expressions, with and without blockage, are derived as well, giving a better insight on the network behaviour at high average signal-to-noise ratio regimes. Both outage probability and packet error rate can be also improved by adding automatic repeat request schemes in the channel between cooperating nodes, which again utilize the internode channels by re-sending data until it can be successfully decoded. Error-free communication can be achieved, but at a delay cost. Nevertheless, a trade-off between performance gains and delays remains, and can therefore be used for designing wireless networks with different requirements – error-free or low-latency. Finally, joint outage performance is investigated. Using a generic approach, which can be applied to any sort of data where multiple sources are communicating over wireless networks, pair-wise behaviour is investigated. As a result, any multi-route diversity type of scheme will have this sort of behaviour, since particular point-to-point relay links are being shared by source nodes. This in turn means that the performance of those flows will be correlated. For higher layers, there is a difference in the behaviour, meaning that when errors are correlated, data flows start behaving correlated as well. As a result, negative acknowledgements may start to correlate as well. All of this contributes to the network behaving in a correlated way, i.e., when something happens, it tends to happen to more than one data flow.Rezime: Industrijske bežične mreže zahtevaju rad u težim i bučnijim uslovima u odnosu na tradicionalne bežične mreže, dok takođe zadržavaju zahteve visoke pouzdanosti i malog kašnjenja. Ovi zahtevi, zajedno sa konstantnom potrebom za većim propusnim opsegom, boljom pokrivenošću, većom brzinom prenosa podataka i generalno boljom i neprekidnom vezom poziva na promenu paradigme u komunikaciji u odnosu na tehnologije ranijih generacija. Kooperativni diverziti predstavlja jedan pristup kojim je to moguće postići. Glavna tema ove disertacije jeste analiza performansi kooperativnih bežičnih mreža smeštenih u industrijskom okruženju – gde je mreža, pored aditivnog Gausovog šuma podložna i fedingu usled višestruke propagacije, efektima senki i/ili privremenim slučajnim efektima blokade. U ovakvim scenarijima, da bi se postigle određene perfomanse, izražene preko verovatnoće greške ili verovatnoće prekida, postojećim kooperativnin strategijama pomažu i protokoli u kanalu između kooperirajućih čvorova. Takođe, analiza para čvorova govori nam o korelaciji više tokova podataka. Polazeći od postojećih protokola koji koriste ponavljanje paketa, posmatra se verovatnoća prekida čvora u bežičnoj mreži koja je podložna efektima fedinga i senki, i istražuje se uticaj efekata dubine fedinga i senke, dimenzije mreže, srednjeg odnosa signal-šum, kao i dužine paketa na verovatnoću prekida. Posmatraju se takođe i specijalni slučajevi, kada se kompozitni feding kanal svodi na nekoliko poznatih propagacionih modela, i na taj način se analiza upotpunjuje. Nakon toga, predstavljena je analiza kompleksnijeg protokola, koja uzima u obzir blokadu u kanalu između kooperirajućih čvorova. Uveden je novi protokol u komunikaciji između čvorova baziran na pragu odlučivanja, koji poboljšava performanse tako što osluškuje kanal, i na osnovu stanja kanala šalje svoj paket ili odmah, ili posle čekanja. Budući da su ova dva vremenska intervala bliska, efekat vremenske korelacije je takođe razmatran. Pored izvedenih tačnih izraza za verovatnoću prekida, jednostavniji asimptotski izrazi su takođe izvedeni za slučajeve sa i bez blokade, dajući bolji uvid u ponašanje mreže u režimu velikog odnosa signal-šum. Performanse kao što su verovatnoća prekida i verovatnoća greške po paketu se takođe mogu poboljšati uvođenjem procedura automatske retransmisije, tako što se u kanalu između čvorova ponovo šalju paketi dok se uspešno ne dekoduju. Komunikacija bez greške se može ostvariti ali po ceni većeg kašnjenja. U svakom slučaju, kompromis između performansi i kašnjenja se može ostvariti, i može se iskoristiti za projektovanje bežičnih mreža različitih namena – mrežama sa komunikacijom bez grešaka ili sa malim kašnjenjem. Konačno, istražena je istovremena verovatnoća prekida više čvorova. Koristeći jednostavan pristup koji se može primeniti na bilo koji tip komunikacije sa više čvorova unutar bežične mreže, istraženo je ponašanje grupe od dva čvora. Bilo koji tip diverziti šeme sa više putanja pokazaće ovakvo ponašanje, jer više izvorišnih čvorova dele pojedinačne linkove od tačke do tačke. To znači da će performanse tokova podataka koji potiču od ovih izvorišnih čvorova biti korelisane. Na višim slojevima, javlja se promena u ponašanju mreže, jer kada su greške korelisane, onda i tokovi podataka od različitih izvorišnih čvorova postaju korelisani. Sve ovo doprinosi da se mreža ponaša korelisano, tj. kada se nešto desi, desiće se istovremeno za više tokova podataka

Towards improving adaptability of capability driven development methodology in complex environment

We are triggered to incorporate adaptability in information system designs and methodologies corresponding to complex and unpredictable environment of today and tomorrow and to complex adaptive systems they are aimed for. Adaptability as non-functional requirement is being portrayed and investigated from broad multidisciplinary perspective that influences how dynamic business-IT alignment can be accomplished. Capability Driven Development methodology has supported delivering dynamic capabilities by providing context-aware self-adaptive platform in the CaaS project implementations, as our case study. Along with the already incorporated mechanisms, components that enable adaptability, there is open space for further evolutionary and deliberate change towards becoming truly appropriate methodology for dynamic reconfigurations of capabilities in organizations and business ecosystems that operate in complexity and uncertainty. The analysis and evaluation of adaptability of the CDD methodology through three dimensions (complexity of the external and internal environment, managerial profiling and artifact-integrated components) in this paper conclude with instigation of starting points towards achieving higher adaptability for complexity of the CDD methodology

The change of phytochemical profile in beet juice and the influence of different storage conditions during one year

Many scientific researches proved the antioxidative impact of beet and its products. The use of vegetable juices is getting more popular in human diet. The way of storage plays an important role in preservation, long life and minimal variability of phytonutrients. The storage of products, usually in inappropriate conditions, leads to additional loss of phytonutrients, which have already been decreased by processing. In this research, we studied the impact of three ways of storage of pasteurised beet juice during one year, on content of some nutrients (total sugars, vitamin C, phenols and total antioxidative capacity). Pasteurised juice was stored in three ways: in light, at room temperature, in dark, at room temperature and in dark, at temperature of 4 °C. The change of content and differences have been followed during one month and confirmed with ANOVA and Tukey's test. The lowest changes of total sugars have been recorded in storage in dark at 4 °C, while in storage in light, the sugar content increased. The losses of vitamin C during one year of storage had linear trend of decrease. Antioxidative capacity of beet juice depends on concentration of phenol compounds and loss of these parameters was similar during period of one year. The best way of storage was dark place at low temperature