Comparative pharmacodynamic and pharmacokinetic characteristics of subcutaneous insulin glulisine and insulin aspart prior to a standard meal in obese subjects with type 2 diabetes

Aims: A multinational, randomized, double-blind, two-way crossover trial to compare the pharmacokinetic and pharmacodynamic properties of bolus, subcutaneously administered insulin glulisine (glulisine) and insulin aspart (aspart) in insulin-naÏve, obese subjects with type 2 diabetes

Dirac field in topologically massive gravity

We consider a Dirac field coupled minimally to the Mielke-Baekler model of gravity and investigate cosmological solutions in three dimensions. We arrive at a family of solutions which exists even in the limit of vanishing cosmological constant.Comment: 12 pages. Title changed. Conclusion extended. Appendix added. To appear in Gen. Rel. Gra

Yeast biota of naturally fermented black olives in different brines made from cv. Gemlik grown in various districts of the Cukurova region of Turkey

In this study, the yeast microbiota of naturally fermented black olives made from cv. Gemlik, grown in three different districts of the Çukurova region of Turkey, were investigated. Fermentations were conducted for 180 days in three different brines, including NaCl 10% w/v, NaCl 8% w/v and NaCl 8% w/v added with glucose 0.5%. In total, 223 yeasts were isolated and then identified by PCR–RFLP analysis of the 5.8S ITS rRNA region and sequence information for the D1/D2 domains of the 26S rRNA gene. A broad range of yeast biodiversity was identified, including eight genera and nine species. Candida boidinii (41%), Wickerhamomyces anomalus (32%) and Saccharomyces sp. (18%) were predominant yeasts throughout the fermentations. To a lesser extent, the other species, Candida aaseri, Meyerozyma sp., Zygoascus hellenicus, Pichia kudriavzevii, Schwanniomyces etchellsii and Candida atlantica were also members of the olive-fermenting microbiota. In Tarsus and Bahçe districts C. boidinii and in Serinyol district Saccharomyces sp. were the most frequently identified species. W. anomalus was the most frequently isolated species (by 48% of total yeasts) in NaCl 10% brines. C. boidinii was the most dominant species in the brines, including NaCl 8% and NaCl 8% + glucose 0.5%, with frequencies of 42% and 61%, respectively. At the end of the 180 days of fermentation, total acidity values of the brines were in the range 1.04–8.1 g/l lactic acid. Copyright © 2016 John Wiley & Sons, Ltd

Anti-nausea effects and pharmacokinetics of ondansetron, maropitant and metoclopramide in a low-dose cisplatin model of nausea and vomiting in the dog: a blinded crossover study

Nausea is a subjective sensation which is difficult to measure in non-verbal species. The aims of this study were to determine the efficacy of three classes of antiemetic drugs in a novel low dose cisplatin model of nausea and vomiting and measure change in potential nausea biomarkers arginine vasopressin (AVP) and cortisol. A four period cross-over blinded study was conducted in eight healthy beagle dogs of both genders. Dogs were administered 18 mg/m2 cisplatin intravenously, followed 45 min later by a 15 min infusion of either placebo (saline) or antiemetic treatment with ondansetron (0.5 mg/kg; 5-HT3 antagonist), maropitant (1 mg/kg; NK1 antagonist) or metoclopramide (0.5 mg/kg; D2 antagonist). The number of vomits and nausea associated behaviours, scored on a visual analogue scale, were recorded every 15 min for 8 h following cisplatin administration. Plasma samples were collected to measure AVP, cortisol and antiemetic drug concentrations

Enhanced He-alpha emission from "smoked" Ti targets irradiated with 400nm, 45 fs laser pulses

We present a study of He-like 1s(2)-1s2p line emission from solid and low-density Ti targets under similar or equal to 45 fs laser pulse irradiation with a frequency doubled Ti: Sapphire laser. By varying the beam spot, the intensity on target was varied from 10(15) W/cm(2) to 10(19) W/cm(2). At best focus, low density "smoked" Ti targets yield similar to 20 times more He-alpha than the foil targets when irradiated at an angle of 45 degrees with s-polarized pulses. The duration of He-alpha emission from smoked targets, measured with a fast streak camera, was similar to that from Ti foils

Cisplatin-induced emesis: systematic review and meta-analysis of the ferret model and the effects of 5-HT3 receptor antagonists

PURPOSE: The ferret cisplatin emesis model has been used for ~30 years and enabled identification of clinically used anti-emetics. We provide an objective assessment of this model including efficacy of 5-HT(3) receptor antagonists to assess its translational validity. METHODS: A systematic review identified available evidence and was used to perform meta-analyses. RESULTS: Of 182 potentially relevant publications, 115 reported cisplatin-induced emesis in ferrets and 68 were included in the analysis. The majority (n = 53) used a 10 mg kg(−1) dose to induce acute emesis, which peaked after 2 h. More recent studies (n = 11) also used 5 mg kg(−1), which induced a biphasic response peaking at 12 h and 48 h. Overall, 5-HT(3) receptor antagonists reduced cisplatin (5 mg kg(−1)) emesis by 68% (45–91%) during the acute phase (day 1) and by 67% (48–86%) and 53% (38–68%, all P < 0.001), during the delayed phase (days 2, 3). In an analysis focused on the acute phase, the efficacy of ondansetron was dependent on the dosage and observation period but not on the dose of cisplatin. CONCLUSION: Our analysis enabled novel findings to be extracted from the literature including factors which may impact on the applicability of preclinical results to humans. It reveals that the efficacy of ondansetron is similar against low and high doses of cisplatin. Additionally, we showed that 5-HT(3) receptor antagonists have a similar efficacy during acute and delayed emesis, which provides a novel insight into the pharmacology of delayed emesis in the ferret

Black microcolonial fungi as deteriogens of two famous marble statues in Florence, Italy

Blackened areas on outdoor marble statues are a significant esthetic problem due to the presence of deteriorating agents. Microcolonial black fungi, which have their natural ecological niche on rocks, play an important role in deterioration of stones used in monuments, such as marble and limestone. Black fungi were isolated from two very valuable statues exposed to the outdoor environment in Florence, Italy, the "Ratto delle Sabineâ" and the "Copia del David", and these fungi were demonstrated to be responsible for the blackening areas on the statues. The black strains showed many features common to members of rock-inhabitants dematiaceous fungi. Morphological and molecular characterization, including phylogenetic analysis, indicated that the strains isolated from both statues and in different times belong to the same species and can be assigned to the rock-inhabitant genera Sarcinomyces and Phaeococcomyces. Red yeasts growing in close proximity to the black ones, with no visible effect on the statues, were also characterized on the morphological and molecular level and identified as Sporobolomyces yunnanensis

Z' Bosons at Colliders: a Bayesian Viewpoint

We revisit the CDF data on di-muon production to impose constraints on a large class of Z' bosons occurring in a variety of E_6 GUT based models. We analyze the dependence of these limits on various factors contributing to the production cross-section, showing that currently systematic and theoretical uncertainties play a relatively minor role. Driven by this observation, we emphasize the use of the Bayesian statistical method, which allows us to straightforwardly (i) vary the gauge coupling strength, g', of the underlying U(1)'; (ii) include interference effects with the Z' amplitude (which are especially important for large g'); (iii) smoothly vary the U(1)' charges; (iv) combine these data with the electroweak precision constraints as well as with other observables obtained from colliders such as LEP 2 and the LHC; and (v) find preferred regions in parameter space once an excess is seen. We adopt this method as a complementary approach for a couple of sample models and find limits on the Z' mass, generally differing by only a few percent from the corresponding CDF ones when we follow their approach. Another general result is that the interference effects are quite relevant if one aims at discriminating between models. Finally, the Bayesian approach frees us of any ad hoc assumptions about the number of events needed to constitute a signal or exclusion limit for various actual and hypothetical reference energies and luminosities at the Tevatron and the LHC.Comment: PDFLaTeX, 24 pages, 7 figures. Version with improved tables and figure

Differential hypoglycaemic, anorectic, autonomic and emetic effects of the glucagon-like peptide receptor agonist, exendin-4, in the conscious telemetered ferret.

Background: Rodents are incapable of emesis and consequently the emetic potential of glucagon-like peptide-1 receptor (GLP-1R) agonists in studies designed to assess a potential blood glucose lowering action of the compound was missed. Therefore, we investigated if the ferret, a carnivore with demonstrated translation capability in emesis research, would identify the emetic potential of the GLP-1R agonist, exendin-4, and any associated effects on gastric motor function, appetite and cardiovascular homeostasis. Methods: The biological activity of the GLP-1R ligands was investigated in vivo using a glucose tolerance test in pentobarbitone-anesthetised ferrets and in vitro using organ bath studies. Radiotelemetry was used to investigate the effect of exendin-4 on gastric myoelectric activity (GMA) and cardiovascular function in conscious ferrets; behaviour was also simultaneously assessed. Western blot was used to characterize GLP-1R distribution in the gastrointestinal and brain tissues. Results: In anesthetised ferrets, exendin-4 (30 nmol/kg, s.c.) reduced experimentally elevated blood glucose levels by 36.3%, whereas the GLP-1R antagonist, exendin (9–39) (300 nmol/kg, s.c.) antagonised the effect and increased AUC0–120 by 31.0% when injected alone (P < 0.05). In animals with radiotelemetry devices, exendin-4 (100 nmol/kg, s.c.) induced emesis in 1/9 ferrets, but inhibited food intake and decreased heart rate variability (HRV) in all animals (P < 0.05). In the animals not exhibiting emesis, there was no effect on GMA, mean arterial blood pressure, heart rate, or core body temperature. In the ferret exhibiting emesis, there was a shift in the GMA towards bradygastria with a decrease in power, and a concomitant decrease in HRV. Western blot revealed GLP-1R throughout the gastrointestinal tract but exendin-4 (up to 300 nM) and exendin (9–39), failed to contract or relax isolated ferret gut tissues. GLP-1R were found in all major brain regions and the levels were comparable those in the vagus nerve. Conclusions: Peripherally administered exendin-4 reduced blood glucose and inhibited feeding with a low emetic potential similar to that in humans (11% vs 12.8%). A disrupted GMA only occurred in the animal exhibiting emesis raising the possibility that disruption of the GMA may influence the probability of emesis occurring in response to treatment with GLP-1R agonists

Authoritarian Neoliberalism and Democratic Backsliding in Turkey: Beyond the Narratives of Progress

Unpacking the core themes that are discussed in this collection, this article both offers a research agenda to re-analyse Turkey’s ‘authoritarian turn’ and mounts a methodological challenge to the conceptual frameworks that reinforce a strict analytical separation between the ‘economic’ and the ‘political’ factors. The paper problematises the temporal break in scholarly analyses of the AKP period and rejects the argument that the party’s methods of governance have shifted from an earlier ‘democratic’ model – defined by ‘hegemony’ – to an emergent ‘authoritarian’ one. In contrast, by retracing the mechanisms of the state-led reproduction of neoliberalism since 2003, the paper demonstrates that the party’s earlier ‘hegemonic’ activities were also shaped by authoritarian tendencies which manifested at various levels of governance