Economic outcomes of percutaneous coronary intervention with drug-eluting stents versus bypass surgery for patients with left main or three-vessel coronary artery disease: One-year results from the SYNTAX trial

Objectives: To evaluate the cost-effectiveness of alternative approaches to revascularization for patients with three-vessel or left main coronary artery disease (CAD). Background: Previous studies have demonstrated that, despite higher initial costs, long-term costs with bypass surgery (CABG) in multivessel CAD are similar to those for percutaneous coronary intervention (PCI). The impact of drug-eluting stents (DES) on these results is unknown. Methods: The SYNTAX trial randomized 1,800 patients with left main or three-vessel CAD to either CABG (n = 897) or PCI using paclitaxel-eluting stents (n = 903). Resource utilization data were collected prospectively for all patients, and cumulative 1-year costs were assessed from the perspective of the U.S. healthcare system. Results: Total costs for the initial hospitalization were $5,693/patient higher with CABG, whereas follow-up costs were$2,282/patient higher with PCI due mainly to more frequent revascularization procedures and higher outpatient medication costs. Total 1-year costs were thus $3,590/patient higher with CABG, while quality-adjusted life expectancy was slightly higher with PCI. Although PCI was an economically dominant strategy for the overall population, cost-effectiveness varied considerably according to angiographic complexity. For patients with high angiographic complexity (SYNTAX score > 32), total 1-year costs were similar for CABG and PCI, and the incremental cost-effectiveness ratio for CABG was$43,486 per quality-adjusted life-year gained. Conclusions: Among patients with three-vessel or left main CAD, PCI is an economically attractive strategy over the first year for patients with low and moderate angiographic complexity, while CABG is favored among patients with high angiographic complexity

Defining the Critical Hurdles in Cancer Immunotherapy

ABSTRACT: Scientific discoveries that provide strong evidence of antitumor effects in preclinical models often encounter significant delays before being tested in patients with cancer. While some of these delays have a scientific basis, others do not. We need to do better. Innovative strategies need to move into early stage clinical trials as quickly as it is safe, and if successful, these therapies should efficiently obtain regulatory approval and widespread clinical application. In late 2009 and 2010 the Society for Immunotherapy of Cancer (SITC), convened an "Immunotherapy Summit" with representatives from immunotherapy organizations representing Europe, Japan, China and North America to discuss collaborations to improve development and delivery of cancer immunotherapy. One of the concepts raised by SITC and defined as critical by all parties was the need to identify hurdles that impede effective translation of cancer immunotherapy. With consensus on these hurdles, international working groups could be developed to make recommendations vetted by the participating organizations. These recommendations could then be considered by regulatory bodies, governmental and private funding agencies, pharmaceutical companies and academic institutions to facilitate changes necessary to accelerate clinical translation of novel immune-based cancer therapies. The critical hurdles identified by representatives of the collaborating organizations, now organized as the World Immunotherapy Council, are presented and discussed in this report. Some of the identified hurdles impede all investigators, others hinder investigators only in certain regions or institutions or are more relevant to specific types of immunotherapy or first-in-humans studies. Each of these hurdles can significantly delay clinical translation of promising advances in immunotherapy yet be overcome to improve outcomes of patients with cancer

A Liquid-Hydrogen Cerenkov Counter

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Sea Surface Temperature Trends in the Coastal Zone of British Columbia, Canada

Coastal sea surface temperature (SST), measured daily at the British Columbia (BC) Lighthouse network of stations, has been analyzed in this paper. A network of 14 of the 27 stations had (near) continuous data sets. These stations were clustered previously into exposed (northern/outer) and sheltered (southern/inner) sites. SST trends, evaluated between 1973 and 2010, show that the temperature contrast between these clusters is becoming greater: The northern/exposed stations are strongly influenced by interdecadal (Pacific Decadal oscillation [PDO]) and multidecadal oscillations in the north Pacific that are coherent with HadISST1.1 data for the region. There is no statistically significant warming trend for this region. The stations in the Strait of Georgia are much less influenced by the PDO and show a statistically significant mean increase in SST of up to 0.56°C/decade (Anomaly 1). This is higher than the global average and contrasts markedly with the trends from the northern stations. The warming trends of the southern stations are significant at all months of the year but are most evident during summer (July–September). The summertime anomalies in temperature at Active Pass are significantly correlated (p < 0.001) with the temperature of the Fraser River water. Temperature differences between the Strait of Georgia and the outer shelf (Anomaly 2) are increasing in time; this is particularly evident since 2000. Monthly averaged MODIS satellite data (4×4-km resolution) show that trends in SST at two selected sites in the Strait of Georgia are very similar to the BC Lighthouse measurements and support the spatial extrapolation of the Lighthouse measurements. At present rates of SST rise, the southern coastal waters of BC will be about 3°C warmer by the end of the 21st century

Does allelopathy explain the invasiveness of Campuloclinium macrocephalum (pompom weed) in the South African grassland biome?

Campuloclinium macrocephalum is an Asteraceous alien weed that invades roadside vegetation and grassland in South Africa. The role of allelopathy and competition in its invasiveness was investigated using Eragrostis curvula (weeping lovegrass, an indigenous grass), E. tef and Lactuca sativa (lettuce) as test species. Trials were conducted in Petri-dishes, pots and in the field. Root and shoot extracts of adult C. macrocephalum plants did not inhibit seed germination in any test species. The greatest effect was radicle stunting produced by leaf extracts at 10 and 25% w/v. Eragrostis curvula was less tolerant of the extracts than E. tef. Allelopathic effects could however not be confirmed in pot trials evaluating the interference potential of the weed or weed residue effects against E. curvula. E. curvula growth and biomass was not affected by plant densities of one or five C. macrocephalum per pot, whereas C. macrocephalum suffered a 17% mortality and density-dependant trade-offs of size and biomass for survival. Under field conditions C. macrocephalum had a broader ecological niche than E. curvula, invading hygrophilous and undisturbed grasslands not amenable for E. curvula establishment, this included well drained disturbed soils on which the latter proliferated. Evidence of competitive exclusion of E. curvula by C. macrocephalum or vice versa was not detected. The coexistence of both species irrespective of relative density suggested these species have different resource requirements. Allelopathy was not an adequate causal mechanism to explain invasiveness in Campuloclinium macrocephalum. A more traditional hypothesis such as the absence of natural enemies, at this stage, better justifies the weed’s invasion success

The mass settling flux of suspended particulate matter in Venice Lagoon, Italy

A multi-disciplinary study of the stability of the tidal flats of Venice Lagoon has provided field and laboratory data on the factors influencing the mass settling rates of material in suspension. This work was carried out using two in situ benthic flumes (Sea Carousel and Mini Flume) in association with a wide range of physical and biological measurements undertaken during the summer of 1998 and the subsequent winter. Also, controlled experiments on erosion/sedimentation of prepared beds were carried out using Lab Carousel, a laboratory equivalent of Sea Carousel. Particle size and mass settling rates were found to be largely independent of suspended sediment concentration but strongly controlled by the antecedent bed shear stresses that led to the suspension. Results between the three flume types differed because of differences in the induced stress history created in each case. Comparable results were obtained by normalizing mass settling rate to the mean friction velocity of the flow during settling i.e. the Rouse parameter (Ws/U* ) and by use of the mean dimensionless particle diameter (D*). Results fell in line with results on carbonate and silica sands of the inlets of the lagoon. The mean particle diameter (df) varied in proportion to the applied shear stress and shear rate (G), suggesting that the suspended particles were eroded aggregates not floccules. The effective density of these aggregates was least (~16 kgm-3) at the largest sizes (df > 1 x 10-4 m) and greatest (~160-1600 kgm-3) at the smallest sizes (df < 1 x 10-4 m). The lack of an increase in df at low shear rates suggests that flocculation was not taking place. The mean deposition threshold (all experiments) was 0.68 Pa, which is less than the mean erosion threshold from these sites (0.78 Pa)

Glial cell changes in the central auditory system through the lifespan of rhesus macaques – a potential mechanism for inflammation in the progression of age-related hearing loss

Age-related hearing loss (ARHL) is a common condition, affecting half of adults over the age of 75. It has a large impact on quality of life, contributing to social isolation and depression. Despite ARHL being common, it is not universal, suggesting that its progression may be amenable to modulation or therapy - this would allow a level of hearing adequate for social interaction to be maintained for longer. Pathology in the cochlea is the main focus of current presbycusis (ARHL) research. Due to a loss of input from the cochlea, there is also degeneration of the central auditory system, which causes auditory processing to be impaired. An association between raised inflammatory status and decreased hearing ability has been shown in an aging human population. It is feasible that systemic inflammation could be contributing to hearing loss by increasing degeneration of the central auditory pathway. During aging there are changes to the immune system, including a tendency towards chronic low grade inflammation.The link between systemic inflammation and neurodegenerative diseases is well established. Given that there is also neurodegeneration occurring in ARHL, it is possible that hearing loss progression could be intensified by systemic inflammation via interaction with the glia. Perineuronal nets (PNN) are specialised extracellular matrix structures and have an important role in the auditory system as they aid intregration of sound inputs. Therefore, alongside glial changes, an alteration in PNN structure could contribute to hearing impairment. The rhesus macaque is an important model in understanding a possible role for inflammation in ARHL: similar to humans, non-human primates have an unusually long lifespan compared to mammals of a similar size, they develop chronic inflammation with age and they variably develop ARHL