Repeated, fuel-specific, emission measurements in Denver (2005/2013), Los Angeles (LA) (2008/2013), and Tulsa (2005/2013) provide long-term trends in on-road reactive nitrogen emissions from three ...light-/medium-duty U.S. fleets. Reductions in oxides of nitrogen (NO x ) emissions ranged from 21% in Denver (from 5.6 ± 1.3 to 4.4 ± 0.2 g of NO x /kg of fuel) to 43% in Tulsa (from 4.4 ± 0.3 to 2.5 ± 0.1 g of NO x /kg of fuel) since 2005, while decreases in fleet ammonia (NH3) emissions ranged from no change in Denver (from 0.45 ± 0.09 to 0.44 ± 0.02 g of NH3/kg of fuel) since 2005 to a 28% decrease in LA (from 0.80 ± 0.02 to 0.58 ± 0.02 g of NH3/kg of fuel) since 2008. The majority of the reduction in gasoline vehicle NO x emissions occurred prior to the full implementation of the Tier II emission standards in 2009. High in-use NO x emissions from small-engine diesel passenger vehicles produced a significant contribution to the fleet means despite their small numbers. NH3 emissions decreased at a slower rate than NO x emissions as a result of modest NH3 emission reduction among the newest vehicles and increased emissions from a growing number of older vehicles with active catalytic converters. In addition, the reactive nitrogen emissions from many new model year vehicles are now dominated by NH3.
Introduction
The COVID‐19 pandemic has transformed lives across the world. In the UK, a public health driven policy of population “lockdown” has had enormous personal and economic impact.
Methods
We ...compare UK response and outcomes with European countries of similar income and healthcare resources. We calibrate estimates of the economic costs as different % loss in Gross Domestic Product (GDP) against possible benefits of avoiding life years lost, for different scenarios where current COVID‐19 mortality and comorbidity rates were used to calculate the loss in life expectancy and adjusted for their levels of poor health and quality of life. We then apply a quality‐adjusted life years (QALY) value of £30,000 (maximum under national guidelines).
Results
There was a rapid spread of cases and significant variation both in severity and timing of both implementation and subsequent reductions in social restrictions. There was less variation in the trajectory of mortality rates and excess deaths, which have fallen across all countries during May/June 2020. The average age at death and life expectancy loss for non‐COVID‐19 was 79.1 and 11.4 years, respectively, while COVID‐19 were 80.4 and 10.1 years; including adjustments for life‐shortening comorbidities and quality of life plausibly reduces this to around 5 QALY lost for each COVID‐19 death. The lowest estimate for lockdown costs incurred was 40% higher than highest benefits from avoiding the worst mortality case scenario at full life expectancy tariff and in more realistic estimations they were over 5 times higher. Future scenarios showed in the best case a QALY value of £220k (7xNICE guideline) and in the worst‐case £3.7m (125xNICE guideline) was needed to justify the continuation of lockdown.
Conclusion
This suggests that the costs of continuing severe restrictions are so great relative to likely benefits in lives saved that a rapid easing in restrictions is now warranted.
Abstract Background & Aims Patients with chronic hepatitis C virus (HCV) infection have high rates of sustained virologic response (SVR) following 12 weeks of treatment with the nucleotide polymerase ...inhibitor sofosbuvir combined with the NS5A inhibitor velpatasvir. We assessed the efficacy of 8 weeks of treatment with sofosbuvir and velpatasvir plus the pangenotypic NS3/4A protease inhibitor voxilaprevir (sofosbuvir-velpatasvir-voxilaprevir). Methods In 2 phase 3, open-label trials, patients with HCV infection who had not previously been treated with a direct-acting antiviral agent were randomly assigned to groups given sofosbuvir-velpatasvir-voxilaprevir for 8 weeks or sofosbuvir-velpatasvir for 12 weeks. POLARIS-2, which enrolled patients infected with all HCV genotypes with or without cirrhosis, except patients with genotype 3 and cirrhosis, was designed to test the non-inferiority of 8 weeks of sofosbuvir-velpatasvir-voxilaprevir to 12 weeks of sofosbuvir-velpatasvir using a non-inferiority margin of 5%. POLARIS-3, which enrolled patients infected with HCV genotype 3 who had cirrhosis, compared rates of SVR in both groups to a performance goal of 83%. Results In POLARIS-2, 95% (95% CI, 93%–97%) of patients had an SVR to 8 weeks of sofosbuvir-velpatasvir-voxilaprevir; this did not meet the criterion to establish non-inferiority to 12 weeks of sofosbuvir-velpatasvir, which produced an SVR in 98% of patients (95% CI, 96%–99%; difference in the stratum-adjusted Mantel-Haenszel proportions of 3.4%; 95% CI, –6.2% to –0.6%). The difference in the efficacy was primarily due to a lower rate of SVR (92%) among patients with HCV genotype 1a infection receiving 8 weeks of sofosbuvir-velpatasvir-voxilaprevir. In POLARIS-3, 96% of patients (95% CI, 91%–99%) achieved an SVR in both treatment groups, which was significantly superior to the performance goal. Overall, the most common adverse events were headache, fatigue, diarrhea, and nausea; diarrhea and nausea were reported more frequently by patients receiving voxilaprevir. In both trials, the proportions of patients who discontinued treatment owing to adverse events were low (0–1%). Conclusions In phase 3 trials of patients with HCV infection, we did not establish that sofosbuvir-velpatasvir-voxilaprevir for 8 weeks was non-inferior to sofosbuvir-velpatasvir for 12 weeks, but the 2 regimens had similar rates of SVR in patients with HCV genotype 3 and cirrhosis. Mild gastrointestinal adverse events were associated with treatment regimens that included voxilaprevir. ClinicalTrials.gov numbers: POLARIS-2, NCT02607800 and POLARIS-3, NCT02639338
The protein dystrophin, normally found on the cytoplasmic surface of skeletal muscle cell membranes, is absent in patients with Duchenne muscular dystrophy as well as mdx (X-linked muscular ...dystrophy) mice. Although its primary structure has been determined, the precise functional role of dystrophin remains the subject of speculation. In the present study, we demonstrate that dystrophin-deficient muscle fibers of the mdx mouse exhibit an increased susceptibility to contraction-induced sarcolemmal rupture. The level of sarcolemmal damage is directly correlated with the magnitude of mechanical stress placed upon the membrane during contraction rather than the number of activations of the muscle. These findings strongly support the proposition that the primary function of dystrophin is to provide mechanical reinforcement to the sarcolemma and thereby protect it from the membrane stresses developed during muscle contraction. Furthermore, the methodology used in this study should prove useful in assessing the efficacy of dystrophin gene therapy in the mdx mouse.
In two phase 3 trials involving patients with hepatitis C virus infection, including those with cirrhosis, 12 weeks of sofosbuvir–velpatasvir resulted in a sustained virologic response in 99% of ...patients with genotype 2 and 95% of those with genotype 3.
Hepatitis C virus (HCV) genotypes 2 and 3 account for an estimated 35% of global HCV infections, affecting up to 58 million persons.
1
,
2
Unlike HCV genotype 1, genotypes 2 and 3 are common in low-income regions in Asia, sub-Saharan Africa, Latin America, and Eastern Europe.
1
Before the advent of direct-acting antiviral agents, HCV genotypes 2 and 3 were grouped together in treatment guidelines as “easy-to-treat” genotypes. However, recent studies have shown that HCV genotype 3 is associated with more rapid disease progression and lower rates of response to treatment than is HCV genotype 2, especially in patients with cirrhosis . . .
ObjectivesWhile there is good evidence for associations between short-term exposure to ozone and a range of adverse health outcomes, the evidence from narrative reviews for long-term exposure is ...suggestive of associations with respiratory mortality only. We conducted a systematic, quantitative evaluation of the evidence from cohort studies, reporting associations between long-term exposure to ozone and mortality.MethodsCohort studies published in peer-reviewed journals indexed in EMBASE and MEDLINE to September 2015 and PubMed to October 2015 and cited in reviews/key publications were identified via search strings using terms relating to study design, pollutant and health outcome. Study details and estimate information were extracted and used to calculate standardised effect estimates expressed as HRs per 10 ppb increment in long-term ozone concentrations.Results14 publications from 8 cohorts presented results for ozone and all-cause and cause-specific mortality. We found no evidence of associations between long-term annual O3 concentrations and the risk of death from all causes, cardiovascular or respiratory diseases, or lung cancer. 4 cohorts assessed ozone concentrations measured during the warm season. Summary HRs for cardiovascular and respiratory causes of death derived from 3 cohorts were 1.01 (95% CI 1.00 to 1.02) and 1.03 (95% CI 1.01 to 1.05) per 10 ppb, respectively.ConclusionsOur quantitative review revealed a paucity of independent studies regarding the associations between long-term exposure to ozone and mortality. The potential impact of climate change and increasing anthropogenic emissions of ozone precursors on ozone levels worldwide suggests further studies of the long-term effects of exposure to high ozone levels are warranted.
In a study involving more than 5.9 million persons in a Danish registry, the presence of a mental disorder (in 11.8% of the population) was associated with subsequent medical conditions encompassing ...31 specific diagnoses, with hazard ratios that ranged from 0.82 to 3.62 and varied greatly over time.
Background and Aim: The etiology of autoimmune hepatitis (AIH) is unknown, and limited epidemiological data are available. Our aim was to perform a population based epidemiological study of AIH in ...Canterbury, New Zealand.
Methods: To calculate point prevalence, all adult and pediatric outpatient clinics and hospital discharge summaries were searched to identify all cases of AIH in the Canterbury region. Incident cases were recruited prospectively in 2008. Demographic and clinical data were extracted from case notes. Both the original revised AIH criteria and the simplified criteria were applied and cases were included in the study if they had definite or probable AIH.
Results: When the original revised criteria were used, 138 cases (123 definite and 14 probable AIH), were identified. Prospective incidence in 2008 was 2.0/100 000 (95% confidence interval CI 0.8–3.3/100 000). Point prevalence on 31 December 2008 was 24.5/100 000 (95% CI 20.1–28.9). Age‐standardized (World Health Organization standard population) incidence and prevalence were 1.7 and 18.9 per 100 000, respectively. Gender‐specific prevalence confirmed a female predominance, while ethnicity‐specific prevalence showed higher prevalence in Caucasians. 72% of cases presented after 40 years of age and the peak age of presentation was in the sixth decade of life.
Conclusions: This is the first and largest population‐based epidemiology study of AIH in a geographically defined region using standardized inclusion criteria. The observed incidence and prevalence rates are among the highest reported. The present study confirms that AIH presents predominantly in older women, with a peak in the sixth decade, contrary to the classical description of the disease.
PDF
