On Whitham theory for perturbed integrable equations

Whitham theory of modulations is developed for periodic waves described by nonlinear wave equations integrable by the inverse scattering transform method associated with $2\times2$ matrix or second order scalar spectral problems. The theory is illustrated by derivation of the Whitham equations for perturbed Korteweg-de Vries equation and nonlinear Schr\"odinger equation with linear damping.Comment: 17 pages, no figure

Albiglutide and cardiovascular outcomes in patients with type 2 diabetes and cardiovascular disease (Harmony Outcomes): a double-blind, randomised placebo-controlled trial

Background: Glucagon-like peptide 1 receptor agonists differ in chemical structure, duration of action, and in their effects on clinical outcomes. The cardiovascular effects of once-weekly albiglutide in type 2 diabetes are unknown. We aimed to determine the safety and efficacy of albiglutide in preventing cardiovascular death, myocardial infarction, or stroke. Methods: We did a double-blind, randomised, placebo-controlled trial in 610 sites across 28 countries. We randomly assigned patients aged 40 years and older with type 2 diabetes and cardiovascular disease (at a 1:1 ratio) to groups that either received a subcutaneous injection of albiglutide (30–50 mg, based on glycaemic response and tolerability) or of a matched volume of placebo once a week, in addition to their standard care. Investigators used an interactive voice or web response system to obtain treatment assignment, and patients and all study investigators were masked to their treatment allocation. We hypothesised that albiglutide would be non-inferior to placebo for the primary outcome of the first occurrence of cardiovascular death, myocardial infarction, or stroke, which was assessed in the intention-to-treat population. If non-inferiority was confirmed by an upper limit of the 95% CI for a hazard ratio of less than 1·30, closed testing for superiority was prespecified. This study is registered with ClinicalTrials.gov, number NCT02465515. Findings: Patients were screened between July 1, 2015, and Nov 24, 2016. 10 793 patients were screened and 9463 participants were enrolled and randomly assigned to groups: 4731 patients were assigned to receive albiglutide and 4732 patients to receive placebo. On Nov 8, 2017, it was determined that 611 primary endpoints and a median follow-up of at least 1·5 years had accrued, and participants returned for a final visit and discontinuation from study treatment; the last patient visit was on March 12, 2018. These 9463 patients, the intention-to-treat population, were evaluated for a median duration of 1·6 years and were assessed for the primary outcome. The primary composite outcome occurred in 338 (7%) of 4731 patients at an incidence rate of 4·6 events per 100 person-years in the albiglutide group and in 428 (9%) of 4732 patients at an incidence rate of 5·9 events per 100 person-years in the placebo group (hazard ratio 0·78, 95% CI 0·68–0·90), which indicated that albiglutide was superior to placebo (p<0·0001 for non-inferiority; p=0·0006 for superiority). The incidence of acute pancreatitis (ten patients in the albiglutide group and seven patients in the placebo group), pancreatic cancer (six patients in the albiglutide group and five patients in the placebo group), medullary thyroid carcinoma (zero patients in both groups), and other serious adverse events did not differ between the two groups. There were three (<1%) deaths in the placebo group that were assessed by investigators, who were masked to study drug assignment, to be treatment-related and two (<1%) deaths in the albiglutide group. Interpretation: In patients with type 2 diabetes and cardiovascular disease, albiglutide was superior to placebo with respect to major adverse cardiovascular events. Evidence-based glucagon-like peptide 1 receptor agonists should therefore be considered as part of a comprehensive strategy to reduce the risk of cardiovascular events in patients with type 2 diabetes. Funding: GlaxoSmithKline

Problematizing `empowerment' in education and work An exploration of the GNVQ

Available from British Library Document Supply Centre-DSC:6226.290(7) / BLDSC - British Library Document Supply CentreSIGLEGBUnited Kingdo

Reversal of imbalance between kynurenic acid and 3-hydroxykynurenine by antipsychotics in medication-na\uefve and medication-free schizophrenic patients

The association between the pro-inflammatory state of schizophrenia and increased tryptophan degradation into kynurenine has been reported. However, the relationship between metabolites from subdivisions of the kynurenine pathway, kynurenic acid and 3-hydroxykynurenine, remains unknown. The present study tested the relationship between these kynurenine metabolites in the plasma of medication-naive (n = 35) or medication-free (n = 18) patients with schizophrenia at admission and following 6-week antipsychotic treatment compared to healthy controls (n = 48). The plasma concentrations of kynurenic acid (nmol/l) were lower (difference = -8.44 (-13.22 to -3.65); p = 0.001) and of 3-hydroxykynurenine (nmol/l) were higher (difference = 11.24 (8.11-14.37); p <0.001) in the patients compared with the healthy controls. The kynurenic acid/kynurenine (difference = -2.75 (-5.115 to -0.336); p = 0.026) and kynurenic acid/3-hydroxykynurenine (difference = -1.08 (-1.431 to -0.729); p <0.001) ratios were also lower in the patients. After the 6-week treatment, the patients' plasma kynurenic acid levels (difference = 3.85 (-0.23 to 7.94); p = 0.064) showed a trend towards an increase, whereas plasma 3-hydroxykynurenine levels (difference = 22.41 (19.76-25.07); p <0.001) decreased. As a consequence, the kynurenic acid/3-hydroxykynurenine ratio (difference = -4.41 (-5.51 to -3.3); p <0.001) increased. Higher initial plasma kynurenic acid levels on admission or increased kynurenic acid/kynurenine ratio after treatment were associated with reduction of clinical symptoms scores upon discharge although higher kynurenic acid/kynurenine on admission may induce higher positive symptoms score. In contrast, higher 3-hydroxykynurenine is associated with lower positive symptoms score. These results indicate that there is an imbalance in the kynurenine pathway in schizophrenia. The 6-week antipsychotic treatment may partially reverse the imbalance in kynurenine metabolism and that in turn induces clinical response

Study of viremic profile in febrile specimens of chikungunya in Bandung, Indonesia

BACKGROUND: Data regarding the viremia profile of chikungunya virus (CHIKV) infected patients especially during the pre-febrile period is limited. OBJECTIVE: To obtain virological kinetic data on CHIKV infections. STUDY DESIGN: A two-week community observation for dengue transmission was conducted in Bandung, Indonesia, from 2005 to 2009. Acute specimens from non-dengue febrile patients were screened by pan-alphavirus conventional RT-PCR. The positives were confirmed for CHIKV RNA by a specific RT-PCR followed by sequencing. Simultaneously these specimens were also cultured in Vero cells and tested for anti-CHIK IgM MAC-ELISA. All the available serial specimens,including the pre-febrile specimens, from confirmed CHIK cases, were tested by virus isolation, RT-PCR, qRT-PCR, and CHIK IgM ELISA. RESULTS: There were five laboratory confirmed CHIK cases identified and studied. Among these, viremia was determined to extend from as early as 6 days prior to until 13 days post fever onset. Quantitative RT-PCR showed viremia peaked at or near onset of illness. CONCLUSION: In this study, individuals were identified with viremia prior to fever onset and extending beyond the febrile phase. This extended viremic phase has the potential to impact transmission dynamics and thus the public health response to CHIK outbreaks

Quality of life, social position and occupational groups in Brazil: evidence from a population-based survey

This study investigates whether occupation, variable that reflects social position, is associated with good quality of life among Brazilians. It is a cross-sectional study based on data obtained from a population-based survey carried out in Brazil in 2008. The sample composed of 12,423 Brazilians, older than 20 years. Physical and mental quality of life were both measured by SF-36 and scores were grouped in "above the mean" and "below the mean" to set binary outcomes. Logistic regression analysis was carried out to verify the impact of occupational position on the chances of better physical and mental quality of life, controlling it by socio-demographic and health variables. Results showed that Brazilians included on the labour market have better chances of a good physical and mental quality of life, even if controlled by other variables