Mutations in the guinea pig preproglucagon gene are restricted to a specific portion of the prohormone sequence

AbstractA cDNA clone encoding guinea pig preproglucagon has been isolated from a pancreatic cDNA library. The predicted amino acid sequence of proglucagon is highly conserved in all regions, in comparison to other mammals, except for the C-terminal portion of the 29-residue glucagon region, in which 5 amino acid substitutions have occurred. These changes may serve to offset the reduced receptor-binding potency of the highly mutated insulin in this New World species.GlucagonEvolutionHystricomorphcDNAGlycogenolytic hormon

Neutrino Emission from Goldstone Modes in Dense Quark Matter

We calculate neutrino emissivities from the decay and scattering of Goldstone bosons in the color-flavor-locked (CFL) phase of quarks at high baryon density. Interactions in the CFL phase are described by an effective low-energy theory. For temperatures in the tens of keV range, relevant to the long-term cooling of neutron stars, the emissivities involving Goldstone bosons dominate over those involving quarks, because gaps in the CFL phase are $\sim 100$ MeV while the masses of Goldstone modes are on the order of 10 MeV. For the same reason, the specific heat of the CFL phase is also dominated by the Goldstone modes. Notwithstanding this, both the emissivity and the specific heat from the massive modes remain rather small, because of their extremely small number densities. The values of the emissivity and the specific heat imply that the timescale for the cooling of the CFL core in isolation is $\sim 10^{26}$ y, which makes the CFL phase invisible as the exterior layers of normal matter surrounding the core will continue to cool through significantly more rapid processes. If the CFL phase appears during the evolution of a proto-neutron star, neutrino interactions with Goldstone bosons are expected to be significantly more important since temperatures are high enough ($\sim 20-40$ MeV) to admit large number densities of Goldstone modes.Comment: 29 pages, no figures. slightly modified text, one new eqn. and new refs. adde

"Just Going Through the Motions.…": A Qualitative Exploration of Athlete Perceptions of Social Loafing in Training and Competition Contexts - Implications for Team Sport Coaches

Semi-structured interviews were conducted with twenty team sport athletes representing a range of different sports with the aim of investigating their views relating to social loafing in training and competition. General themes investigated and subsequent content analysis highlighted factors that promote or reduce the extent of social loafing. Determinants of self-loafing were grouped according to three distinct categories: Group processes; Task characteristics and Individual perceptions. Social loafing among others was perceived to be prevalent in both the training and competition scenarios with more examples of social loafing provided in the training situation. The signs of social loafing were grouped according to the following themes: Cognitive & Emotional, Behavioural, Communication and Player Intuition. Consequences of social loafing were found to be detrimental to the effort and performance of both the individual and the team. Athletes were also able to differentiate between perceived social loafing and the perceived use of ‘strategic rest’ in team sports. Implications for the coaching process are far reaching with the need to develop an effective team culture and to provide training sessions that are interesting, engaging and relevant

Nuclear Structure Functions in the Large x Large Q^2 Kinematic Region in Neutrino Deep Inelastic Scattering

Data from the CCFR E770 Neutrino Deep Inelastic Scattering (DIS) experiment at Fermilab contain events with large Bjorken x (x>0.7) and high momentum transfer (Q^2>50 (GeV/c)^2). A comparison of the data with a model based on no nuclear effects at large x, shows a significant excess of events in the data. Addition of Fermi gas motion of the nucleons in the nucleus to the model does not explain the excess. Adding a higher momentum tail due to the formation of ``quasi-deuterons'' makes some improvement. An exponentially falling F_2 \propto e^-s(x-x_0) at large x, predicted by ``multi-quark clusters'' and ``few-nucleon correlations'', can describe the data. A value of s=8.3 \pm 0.7(stat.)\pm 0.7(sys.) yields the best agreement with the data.Comment: 4 pages, 4 figures, 1 table. Sibmitted to PR

Early in-hospital exposure to statins and outcome after intracerebral haemorrhage - Results from the Virtual International Stroke Trials Archive

Introduction Recent data suggest that statin use after intracerebral haemorrhage might be beneficial. However, data on the effects of early in-hospital statin exposure are lacking. Therefore, we sought to assess whether (1) early statin exposure during the acute phase after intracerebral haemorrhage and (2) early continuation of prevalent statin use are associated with favourable functional outcome. Patients and methods Data were obtained from the Virtual International Stroke Trials Archive. Patients were categorised according to use patterns of statins during this early in-hospital phase (continuation, discontinuation or new initiation of statins). Univariate and multivariable analyses were conducted to explore the association between early statin exposure and functional outcome. Results A total of 919 patients were included in the analysis. Early in-hospital statin exposure (n = 89, 9.7%) was associated with better functional outcome (modified Rankin Scale <= 3) compared with 790 patients without statin exposure before or early after the event (66% versus 47%, adjusted OR 2.1, 95% confidence interval 1.3-3.6). Compared with patients without exposure to statins before and early after the event, early continuation of statin therapy (n = 57) was associated with favourable functional outcome (adjusted odds ratio 2.6, 95% confidence interval 1.3-5.2). The association between early continuation of statins and outcome remained robust in sensitivity analyses restricted to patients able to take oral medication within 72 h and one-week survivors. Discussion It is possible that part of the observed associations are not due to a protective effect of statins but are confounded by indication bias. Conclusion Statin exposure and continuation of prevalent statin therapy early after intracerebral haemorrhage are associated with favourable functional outcome after 90 days

A novel formulation of inhaled sodium cromoglicate (PA101) in idiopathic pulmonary fibrosis and chronic cough: a randomised, double-blind, proof-of-concept, phase 2 trial

Background Cough can be a debilitating symptom of idiopathic pulmonary fibrosis (IPF) and is difficult to treat. PA101 is a novel formulation of sodium cromoglicate delivered via a high-efficiency eFlow nebuliser that achieves significantly higher drug deposition in the lung compared with the existing formulations. We aimed to test the efficacy and safety of inhaled PA101 in patients with IPF and chronic cough and, to explore the antitussive mechanism of PA101, patients with chronic idiopathic cough (CIC) were also studied. Methods This pilot, proof-of-concept study consisted of a randomised, double-blind, placebo-controlled trial in patients with IPF and chronic cough and a parallel study of similar design in patients with CIC. Participants with IPF and chronic cough recruited from seven centres in the UK and the Netherlands were randomly assigned (1:1, using a computer-generated randomisation schedule) by site staff to receive PA101 (40 mg) or matching placebo three times a day via oral inhalation for 2 weeks, followed by a 2 week washout, and then crossed over to the other arm. Study participants, investigators, study staff, and the sponsor were masked to group assignment until all participants had completed the study. The primary efficacy endpoint was change from baseline in objective daytime cough frequency (from 24 h acoustic recording, Leicester Cough Monitor). The primary efficacy analysis included all participants who received at least one dose of study drug and had at least one post-baseline efficacy measurement. Safety analysis included all those who took at least one dose of study drug. In the second cohort, participants with CIC were randomly assigned in a study across four centres with similar design and endpoints. The study was registered with ClinicalTrials.gov (NCT02412020) and the EU Clinical Trials Register (EudraCT Number 2014-004025-40) and both cohorts are closed to new participants. Findings Between Feb 13, 2015, and Feb 2, 2016, 24 participants with IPF were randomly assigned to treatment groups. 28 participants with CIC were enrolled during the same period and 27 received study treatment. In patients with IPF, PA101 reduced daytime cough frequency by 31·1% at day 14 compared with placebo; daytime cough frequency decreased from a mean 55 (SD 55) coughs per h at baseline to 39 (29) coughs per h at day 14 following treatment with PA101, versus 51 (37) coughs per h at baseline to 52 (40) cough per h following placebo treatment (ratio of least-squares [LS] means 0·67, 95% CI 0·48–0·94, p=0·0241). By contrast, no treatment benefit for PA101 was observed in the CIC cohort; mean reduction of daytime cough frequency at day 14 for PA101 adjusted for placebo was 6·2% (ratio of LS means 1·27, 0·78–2·06, p=0·31). PA101 was well tolerated in both cohorts. The incidence of adverse events was similar between PA101 and placebo treatments, most adverse events were mild in severity, and no severe adverse events or serious adverse events were reported. Interpretation This study suggests that the mechanism of cough in IPF might be disease specific. Inhaled PA101 could be a treatment option for chronic cough in patients with IPF and warrants further investigation