Non-perturbative dynamics of hot non-Abelian gauge fields: beyond leading log approximation

Many aspects of high-temperature gauge theories, such as the electroweak baryon number violation rate, color conductivity, and the hard gluon damping rate, have previously been understood only at leading logarithmic order (that is, neglecting effects suppressed only by an inverse logarithm of the gauge coupling). We discuss how to systematically go beyond leading logarithmic order in the analysis of physical quantities. Specifically, we extend to next-to-leading-log order (NLLO) the simple leading-log effective theory due to Bodeker that describes non-perturbative color physics in hot non-Abelian plasmas. A suitable scaling analysis is used to show that no new operators enter the effective theory at next-to-leading-log order. However, a NLLO calculation of the color conductivity is required, and we report the resulting value. Our NLLO result for the color conductivity can be trivially combined with previous numerical work by G. Moore to yield a NLLO result for the hot electroweak baryon number violation rate.Comment: 20 pages, 1 figur

The 1995 scientific assessment of the atmospheric effects of stratospheric aircraft

This report provides a scientific assessment of our knowledge concerning the impact of proposed high-speed civil transport (HSCT) aircraft on the atmosphere. It comes at the end of Phase 1 of the Atmospheric Effects of Stratospheric Aircraft element of the NASA High-Speed Research Program. The fundamental problem with stratospheric flight is that pollutant residence times are long because the stratosphere is a region of permanent temperature inversion with stable stratification. Using improved two-dimensional assessment models and detailed fleet emissions scenarios, the assessment examines the possible impact of the range of effluents from aircraft. Emphasis is placed on the effects of NO(x) and H2O on the atmospheric ozone content. Measurements in the plume of an in-flight Concorde supersonic transport indicated a large number of small particles. These measurements, coupled with model sensitivity studies, point out the importance of obtaining a more detailed understanding of the fate of sulfur in the HSCT exhaust. Uncertainties in the current understanding of the processes important for determining the overall effects of HSCT's on the atmosphere are discussed and partially quantified. Research directions are identified to improve the quantification of uncertainties and to reduce their magnitude

Lethal Injection for Execution: Chemical Asphyxiation?

Data from executions in the US suggest that current lethal injection protocols do not effect death through the mechanisms intended, and that potentially aware inmates could die through pancuronium-induced asphyxiation

The Genome Sequence of Caenorhabditis briggsae: A Platform for Comparative Genomics

The soil nematodes Caenorhabditis briggsae and Caenorhabditis elegans diverged from a common ancestor roughly 100 million years ago and yet are almost indistinguishable by eye. They have the same chromosome number and genome sizes, and they occupy the same ecological niche. To explore the basis for this striking conservation of structure and function, we have sequenced the C. briggsae genome to a high-quality draft stage and compared it to the finished C. elegans sequence. We predict approximately 19,500 protein-coding genes in the C. briggsae genome, roughly the same as in C. elegans. Of these, 12,200 have clear C. elegans orthologs, a further 6,500 have one or more clearly detectable C. elegans homologs, and approximately 800 C. briggsae genes have no detectable matches in C. elegans. Almost all of the noncoding RNAs (ncRNAs) known are shared between the two species. The two genomes exhibit extensive colinearity, and the rate of divergence appears to be higher in the chromosomal arms than in the centers. Operons, a distinctive feature of C. elegans, are highly conserved in C. briggsae, with the arrangement of genes being preserved in 96% of cases. The difference in size between the C. briggsae (estimated at approximately 104 Mbp) and C. elegans (100.3 Mbp) genomes is almost entirely due to repetitive sequence, which accounts for 22.4% of the C. briggsae genome in contrast to 16.5% of the C. elegans genome. Few, if any, repeat families are shared, suggesting that most were acquired after the two species diverged or are undergoing rapid evolution. Coclustering the C. elegans and C. briggsae proteins reveals 2,169 protein families of two or more members. Most of these are shared between the two species, but some appear to be expanding or contracting, and there seem to be as many as several hundred novel C. briggsae gene families. The C. briggsae draft sequence will greatly improve the annotation of the C. elegans genome. Based on similarity to C. briggsae, we found strong evidence for 1,300 new C. elegans genes. In addition, comparisons of the two genomes will help to understand the evolutionary forces that mold nematode genomes

Impact of the introduction of pneumococcal conjugate vaccination on pneumonia in The Gambia: population-based surveillance and case-control studies.

BACKGROUND: Pneumococcal conjugate vaccines (PCVs) are used in many low-income countries but their impact on the incidence of pneumonia is unclear. The Gambia introduced PCV7 in August, 2009, and PCV13 in May, 2011. We aimed to measure the impact of the introduction of these vaccines on pneumonia incidence. METHODS: We did population-based surveillance and case-control studies. The primary endpoint was WHO-defined radiological pneumonia with pulmonary consolidation. Population-based surveillance was for suspected pneumonia in children aged 2-59 months (minimum age 3 months in the case-control study) between May 12, 2008, and Dec 31, 2015. Surveillance for the impact study was limited to the Basse Health and Demographic Surveillance System (BHDSS), whereas surveillance for the case-control study included both the BHDSS and Fuladu West Health and Demographic Surveillance System. Nurses screened all outpatients and inpatients at all health facilities in the surveillance area using standardised criteria for referral to clinicians in Basse and Bansang. These clinicians recorded clinical findings and applied standardised criteria to identify patients with suspected pneumonia. We compared the incidence of pneumonia during the baseline period (May 12, 2008, to May 11, 2010) and the PCV13 period (Jan 1, 2014, to Dec 31, 2015). We also investigated the effectiveness of PCV13 using case-control methods between Sept 12, 2011, and Sept 31, 2014. Controls were aged 90 days or older, and were eligible to have received at least one dose of PCV13; cases had the same eligibility criteria with the addition of having WHO-defined radiological pneumonia. FINDINGS: We investigated 18 833 children with clinical pneumonia and identified 2156 cases of radiological pneumonia. Among children aged 2-11 months, the incidence of radiological pneumonia fell from 21·0 cases per 1000 person-years in the baseline period to 16·2 cases per 1000 person-years (23% decline, 95% CI 7-36) in 2014-15. In the 12-23 month age group, radiological pneumonia decreased from 15·3 to 10·9 cases per 1000 person-years (29% decline, 12-42). In children aged 2-4 years, incidence fell from 5·2 to 4·1 cases per 1000 person-years (22% decline, 1-39). Incidence of all clinical pneumonia increased by 4% (-1 to 8), but hospitalised cases declined by 8% (3-13). Pneumococcal pneumonia declined from 2·9 to 1·2 cases per 1000 person-years (58% decline, 22-77) in children aged 2-11 months and from 2·6 to 0·7 cases per 1000 person-years (75% decline, 47-88) in children aged 12-23 months. Hypoxic pneumonia fell from 13·1 to 5·7 cases per 1000 person-years (57% decline, 42-67) in children aged 2-11 months and from 6·8 to 1·9 cases per 1000 person-years (72% decline, 58-82) in children aged 12-23 months. In the case-control study, the best estimate of the effectiveness of three doses of PCV13 against radiological pneumonia was an adjusted odds ratio of 0·57 (0·30-1·08) in children aged 3-11 months and vaccine effectiveness increased with greater numbers of doses (p=0·026). The analysis in children aged 12 months and older was underpowered because there were few unvaccinated cases and controls. INTERPRETATION: The introduction of PCV in The Gambia was associated with a moderate impact on the incidence of radiological pneumonia, a small reduction in cases of hospitalised pneumonia, and substantial reductions of pneumococcal and hypoxic pneumonia in young children. Low-income countries that introduce PCV13 with reasonable coverage can expect modest reductions in hospitalised cases of pneumonia and a marked impact on the incidence of severe childhood pneumonia. FUNDING: GAVI's Pneumococcal vaccines Accelerated Development and Introduction Plan, Bill & Melinda Gates Foundation, and UK Medical Research Council

EurOP2E – the European Open Platform for Prescribing Education, a consensus study among clinical pharmacology and therapeutics teachers

Purpose Sharing and developing digital educational resources and open educational resources has been proposed as a way to harmonize and improve clinical pharmacology and therapeutics (CPT) education in European medical schools. Previous research, however, has shown that there are barriers to the adoption and implementation of open educational resources. The aim of this study was to determine perceived opportunities and barriers to the use and creation of open educational resources among European CPT teachers and possible solutions for these barriers. Methods CPT teachers of British and EU medical schools completed an online survey. Opportunities and challenges were identified by thematic analyses and subsequently discussed in an international consensus meeting. Results Data from 99 CPT teachers from 95 medical schools were analysed. Thirty teachers (30.3%) shared or collaboratively produced digital educational resources. All teachers foresaw opportunities in the more active use of open educational resources, including improving the quality of their teaching. The challenges reported were language barriers, local differences, lack of time, technological issues, difficulties with quality management, and copyright restrictions. Practical solutions for these challenges were discussed and include a peer review system, clear indexing, and use of copyright licenses that permit adaptation of resources. Conclusion Key challenges to making greater use of CPT open educational resources are a limited applicability of such resources due to language and local differences and quality concerns. These challenges may be resolved by relatively simple measures, such as allowing adaptation and translation of resources and a peer review system

Ten-year mortality, disease progression, and treatment-related side effects in men with localised prostate cancer from the ProtecT randomised controlled trial according to treatment received

Background The ProtecT trial reported intention-to-treat analysis of men with localised prostate cancer randomly allocated to active monitoring (AM), radical prostatectomy, and external beam radiotherapy. Objective To report outcomes according to treatment received in men in randomised and treatment choice cohorts. Design, setting, and participants This study focuses on secondary care. Men with clinically localised prostate cancer at one of nine UK centres were invited to participate in the treatment trial comparing AM, radical prostatectomy, and radiotherapy. Intervention Two cohorts included 1643 men who agreed to be randomised and 997 who declined randomisation and chose treatment. Outcome measurements and statistical analysis Analysis was carried out to assess mortality, metastasis and progression and health-related quality of life impacts on urinary, bowel, and sexual function using patient-reported outcome measures. Analysis was based on comparisons between groups defined by treatment received for both randomised and treatment choice cohorts in turn, with pooled estimates of intervention effect obtained using meta-analysis. Differences were estimated with adjustment for known prognostic factors using propensity scores. Results and limitations According to treatment received, more men receiving AM died of PCa (AM 1.85%, surgery 0.67%, radiotherapy 0.73%), whilst this difference remained consistent with chance in the randomised cohort (p = 0.08); stronger evidence was found in the exploratory analyses (randomised plus choice cohort) when AM was compared with the combined radical treatment group (p = 0.003). There was also strong evidence that metastasis (AM 5.6%, surgery 2.4%, radiotherapy 2.7%) and disease progression (AM 20.35%, surgery 5.87%, radiotherapy 6.62%) were more common in the AM group. Compared with AM, there were higher risks of sexual dysfunction (95% at 6 mo) and urinary incontinence (55% at 6 mo) after surgery, and of sexual dysfunction (88% at 6 mo) and bowel dysfunction (5% at 6 mo) after radiotherapy. The key limitations are the potential for bias when comparing groups defined by treatment received and changes in the protocol for AM during the lengthy follow-up required in trials of screen-detected PCa. Conclusions Analyses according to treatment received showed increased rates of disease-related events and lower rates of patient-reported harms in men managed by AM compared with men managed by radical treatment, and stronger evidence of greater PCa mortality in the AM group. Patient summary More than 95 out of every 100 men with low or intermediate risk localised prostate cancer do not die of prostate cancer within 10 yr, irrespective of whether treatment is by means of monitoring, surgery, or radiotherapy. Side effects on sexual and bladder function are better after active monitoring, but the risks of spreading of prostate cancer are more common

A randomized, double-blind, placebo-controlled trial of deprenyl and thioctic acid in human immunodeficiency virus-associated cognitive impairment

Cognitive impairment is a frequent manifestation of advanced human immunodeficiency virus (HIV) infection. The response to antiretroviral medication is often partial and poorly sustained. Recent studies suggest that free radical production within the CNS and neuronal apoptosis may play important roles in the pathogenesis of HIV dementia. We conducted a randomized double-blind, placebo-controlled trial using a parallel group, 2× 2 factorial design evaluating deprenyl, a monoamine oxidase B inhibitor and putative anti-apoptotic agent, and thioctic acid, an antioxidant, in 36 patients with HIV-associated cognitive impairment. Both deprenyl and thioctic acid were well tolerated with few adverse events. Deprenyl recipients showed significant improvement on tests of verbal memory compared with patients not taking deprenyl. Thioctic acid treatment did not improve cognitive function. These results suggest that deprenyl treatment is associated with cognitive improvement in subjects with mild HIV-associated cognitive impairment, whereas thioctic acid has no benefit. A larger efficacy trial is needed to assess the long-term effect of deprenyl on cognitive performance in patients with HIV infection. Human immunodeficiency virus type 1 (HIV-1)-associated dementia complex(HIV dementia) occurs in 15 to 20% of acquired immunodeficiency syndrome(AIDS) patients and is characterized by cognitive impairment, motor dysfunction, and behavioral changes.1-5 The cognitive impairment includes mental slowing, forgetfulness, and poor concentration. Motor symptoms include loss of fine motor control, clumsiness, unsteady gait, and tremor. Behavioral changes include apathy, lethargy, and depression.2,3,6 HIV dementia is usually a rapidly progressive disorder with a mean survival of about 6 months,2 although recently, patients with slower progression or a stable course have been identified.7 HIV-1-associated minor cognitive motor disorder, a milder syndrome, is estimated to occur in 25% of patients with symptomatic HIV infection.8 Few available antiretroviral agents have been studied for the treatment of HIV dementia. Open label studies with zidovudine (ZDV) in demented patients showed improvements in clinical functioning, neuropsychological performance, and neuroimaging studies.9 ZDV, in a placebo-controlled blinded study, also improved neuropsychological function in AIDS or AIDS-related complex patients without dementia.10 The only placebo-controlled trial of ZDV in HIV dementia demonstrated the greatest neurocognitive improvement only with very high dosages (i.e., 2,000 mg/day).11 Unfortunately, the response to ZDV treatment may be short-lived or associated with intolerable side effects and therefore often unsatisfactory. There is very limited information about the therapeutic effects of other antiretroviral medications (e.g., dideoxynucleosides)12 or protease inhibitors. Neurotoxins from HIV-infected activated macrophages or microglia interacting with astrocytes may play a central pathogenetic role in HIV dementia.13,14 Putative neurotoxins include cytokines (tumor necrosis factor alpha [TNF-α]) and oxygen radicals.2,15 Both TNF-α and hydroxyl free radicals may stimulate apoptosis (programmed cell death), and apoptotic neurons have been demonstrated in the cerebral cortex and basal ganglia of both children and adults with HIV encephalitis.16,17 We hypothesized that these indirect mechanisms of neuronal injury could be modified by deprenyl and thioctic acid to improve or even prevent HIV-associated cognitive impairment. Deprenyl, a selective monoamine oxidase type B inhibitor, at very low dosages in in vitro and in vivo systems has a trophic effect on injured neurons.18-21 Thioctic acid is a naturally occurring enzymatic cofactor for pyruvate dehydrogenase and alpha oxoglutarate dehydrogenase and scavenges harmful hydroxyl radicals and other reactive oxygen species.22,23 We conducted a randomized, double-blind, placebo-controlled clinical trial of deprenyl and thioctic acid to assess their safety and tolerability and to assess their impact on HIV-associated cognitive impairment in HIV seropositive (HIV+) patients

Effect of the introduction of pneumococcal conjugate vaccination on invasive pneumococcal disease in The Gambia: a population-based surveillance study.

BACKGROUND: Little information is available about the effect of pneumococcal conjugate vaccines (PCVs) in low-income countries. We measured the effect of these vaccines on invasive pneumococcal disease in The Gambia where the 7-valent vaccine (PCV7) was introduced in August, 2009, followed by the 13-valent vaccine (PCV13) in May, 2011. METHODS: We conducted population-based surveillance for invasive pneumococcal disease in individuals aged 2 months and older who were residents of the Basse Health and Demographic Surveillance System (BHDSS) in the Upper River Region, The Gambia, using standardised criteria to identify and investigate patients. Surveillance was done between May, 2008, and December, 2014. We compared the incidence of invasive pneumococcal disease between baseline (May 12, 2008-May 11, 2010) and after the introduction of PCV13 (Jan 1, 2013-Dec 31, 2014), adjusting for changes in case ascertainment over time. FINDINGS: We investigated 14 650 patients, in whom we identified 320 cases of invasive pneumococcal disease. Compared with baseline, after the introduction of the PCV programme, the incidence of invasive pneumococcal disease decreased by 55% (95% CI 30-71) in the 2-23 months age group, from 253 to 113 per 100 000 population. This decrease was due to an 82% (95% CI 64-91) reduction in serotypes covered by the PCV13 vaccine. In the 2-4 years age group, the incidence of invasive pneumococcal disease decreased by 56% (95% CI 25-75), from 113 to 49 cases per 100 000, with a 68% (95% CI 39-83) reduction in PCV13 serotypes. The incidence of non-PCV13 serotypes in children aged 2-59 months increased by 47% (-21 to 275) from 28 to 41 per 100 000, with a broad range of serotypes. The incidence of non-pneumococcal bacteraemia varied little over time. INTERPRETATION: The Gambian PCV programme reduced the incidence of invasive pneumococcal disease in children aged 2-59 months by around 55%. Further surveillance is needed to ascertain the maximum effect of the vaccine in the 2-4 years and older age groups, and to monitor serotype replacement. Low-income and middle-income countries that introduce PCV13 can expect substantial reductions in invasive pneumococcal disease. FUNDING: GAVI's Pneumococcal vaccines Accelerated Development and Introduction Plan (PneumoADIP), Bill & Melinda Gates Foundation, and the UK Medical Research Council