The role of temozolomide chemotherapy in newly diagnosed 1p/19q non-co-deleted anaplastic gliomas, which are associated with lower sensitivity to chemotherapy and worse prognosis than 1p/19q ...co-deleted tumours, is unclear. We assessed the use of radiotherapy with concurrent and adjuvant temozolomide in adults with non-co-deleted anaplastic gliomas.
This was a phase 3, randomised, open-label study with a 2 × 2 factorial design. Eligible patients were aged 18 years or older and had newly diagnosed non-co-deleted anaplastic glioma with WHO performance status scores of 0–2. The randomisation schedule was generated with the electronic EORTC web-based ORTA system. Patients were assigned in equal numbers (1:1:1:1), using the minimisation technique, to receive radiotherapy (59·4 Gy in 33 fractions of 1·8 Gy) alone or with adjuvant temozolomide (12 4-week cycles of 150–200 mg/m2 temozolomide given on days 1–5); or to receive radiotherapy with concurrent temozolomide 75 mg/m2 per day, with or without adjuvant temozolomide. The primary endpoint was overall survival adjusted for performance status score, age, 1p loss of heterozygosity, presence of oligodendroglial elements, and MGMT promoter methylation status, analysed by intention to treat. We did a planned interim analysis after 219 (41%) deaths had occurred to test the null hypothesis of no efficacy (threshold for rejection p<0·0084). This trial is registered with ClinicalTrials.gov, number NCT00626990.
At the time of the interim analysis, 745 (99%) of the planned 748 patients had been enrolled. The hazard ratio for overall survival with use of adjuvant temozolomide was 0·65 (99·145% CI 0·45–0·93). Overall survival at 5 years was 55·9% (95% CI 47·2–63·8) with and 44·1% (36·3–51·6) without adjuvant temozolomide. Grade 3–4 adverse events were seen in 8–12% of 549 patients assigned temozolomide, and were mainly haematological and reversible.
Adjuvant temozolomide chemotherapy was associated with a significant survival benefit in patients with newly diagnosed non-co-deleted anaplastic glioma. Further analysis of the role of concurrent temozolomide treatment and molecular factors is needed.
Schering Plough and MSD.
Australian Football, the most popular football code in Australia, is a contact sport played by two teams of 18 players who contest play over four 20-minute quarters; the object of the game is to ...score the most points through goal kicking. Sixteen professional senior sides compete against each other in the Australian Football League (AFL) and, similar to other football codes, game demands at the elite level in the AFL have changed considerably in recent years. Early time-motion analysis studies highlighted the long periods of time players spent in low intensity activities (standing and walking). While recent studies utilizing global positioning systems (GPS) technology are somewhat in agreement with earlier findings, available evidence suggests that the game is getting faster. For example, 'playing on' after a mark (a feature of the game where players who catch the ball on the full from a kick longer than 15 m are awarded a free kick) is now much quicker. Indeed, rule changes in recent years have increased the flow and speed of the game; there has been a reduction in the time taken for umpires to restart play, and for players to kick-in (after the opposition kicks a behind) or take a set shot at goal. Nomadic players (a broad term for midfielders and ruckmen because they follow play over the entire playing field) cover slightly greater distances (12,310 m) than both forwards (11,920 m) and backs (11,880 m) in a game. Compared with players in other positions, midfielders are consistently found to spend the most time at higher intensities (running and sprint efforts with movement velocities > 4.44 m/sec), complete more high intensity efforts (approximately 98 per game), sustain them for longer and have shorter recovery periods between high intensity exercise bouts (approximately 90 seconds on average). 'Ruckmen' have similar but less intense running profiles, while forwards and backs generally have less game involvement but have a more intermittent running profile (longer recovery periods with shorter duration high intensity exercise bouts and less time spent in constant pace running). Endurance fitness remains very important for players at the elite level of competition, as does upper and lower body strength and power. In addition, given the increasing speed at which Australian Football is now played, repeated sprint ability of players is arguably more important now than it was in previous years. There are no significant differences in these measures between playing position. Similarly, speed over 10-40 m does not appear to differ between playing position. Establishing the reliability of distance and velocity-derived GPS data in highly specific game-related activities is needed; once achieved, GPS data have the potential to accurately inform coaches of the position-specific demands on their players and to drive the development of training practices that reflect the changing demands of the game.
Applied sport science of rugby league Johnston, Rich D; Gabbett, Tim J; Jenkins, David G
Sports medicine (Auckland),
08/2014, Letnik:
44, Številka:
8
Journal Article
Recenzirano
Rugby league is a team sport in which players engage in repeated high-intensity exercise involving frequent collisions. Recent research, much of which has involved global positioning system (GPS) ...technology, has provided coaches and sport scientists with a deeper understanding of match demands, particularly at the elite level. This has allowed for the development of training programmes that prepare players for the most intense contact and running demands likely to be experienced in competition. At the elite level, rugby league players have well-developed aerobic and anaerobic endurance, muscular strength and power, reactive agility, and speed. Upper- and lower-body strength and aerobic power are associated with a broad range of technical and sport-specific skills, in addition to a lower risk of injury. Significant muscle damage (as estimated from creatine kinase concentrations) and fatigue occurs as a result of match-play; while muscle function and perceptual fatigue generally return to baseline 48 h following competition, increases in plasma concentrations of creatine kinase can last for up to 5 days post-match. Well-developed physical qualities may minimise post-match fatigue and facilitate recovery. Ultimately, the literature highlights that players require a broad range of physical and technical skills developed through specific training. This review evaluates the demands of the modern game, drawing on research that has used GPS technology. These findings highlight that preparing players based on the average demands of competition is likely to leave them underprepared for the most demanding passages of play. As such, coaches should incorporate drills that replicate the most intense repeated high-intensity demands of competition in order to prepare players for the worst-case scenarios expected during match-play.
Ophiocordyceps fungi manipulate the behaviour of their ant hosts to produce a summit disease phenotype, thereby establishing infected ant cadavers onto vegetation at elevated positions suitable for ...fungal growth and transmission. Multiple environmental and ecological factors have been proposed to shape the timing, positioning and outcome of these manipulations.
We conducted a long‐term field study of Ophiocordyceps camponoti‐floridani infections of Camponotus floridanus ants—the Florida zombie ants. We propose and refine hypotheses on the factors that shape infection outcomes by tracking the occurrence of and fungal growth from hundreds of ant cadavers. We modelled and report these data in relation to weather, light, vegetation and attack by hyperparasites.
We investigated environmental factors that could affect the occurrence and location of newly manipulated ant cadavers. New cadaver occurrence was preferentially biased towards epiphytic Tillandsia bromeliads, canopy openness and summer weather conditions (an interactive effect of temperature, humidity and precipitation). Furthermore, we suggest that incident light at the individual cadaver level reflects microhabitat choice by manipulated ants or selective pressure on cadaver maintenance for conditions that improve fungal survival.
We also asked which environmental conditions affect fungal fitness. Continued fungal development of reproductive structures and putative transmission increased with moist weather conditions (interaction of humidity and precipitation) and canopy openness, while being reduced by hyperparasitic mycoparasite infections. Moreover, under the most open canopy conditions, we found an atypical Ophiocordyceps growth morphology that could represent a plastic response to conditions influenced by high light levels.
Taken together, we explore general trends and the effects of various ecological conditions on host and parasite disease outcomes in the Florida zombie ant system. These insights from the field can be used to inform experimental laboratory setups that directly test the effects of biotic and abiotic factors on fungus–ant interactions or aim to uncover underlying molecular mechanisms.
Read the free Plain Language Summary for this article on the Journal blog.
Read the free Plain Language Summary for this article on the Journal blog.
Although ecology and biogeography had common origins in the natural history of the nineteenth century, they diverged substantially during the early twentieth century as ecology became increasingly ...hypothesis-driven and experimental. This mechanistic focus narrowed ecology's purview to local scales of time and space, and mostly excluded large-scale phenomena and historical explanations. In parallel, biogeography became more analytical with the acceptance of plate tectonics and the development of phylogenetic systematics, and began to pay more attention to ecological factors that influence large-scale distributions. This trend towards unification exposed problems with terms such as 'community' and 'niche,' in part because ecologists began to view ecological communities as open systems within the contexts of history and geography. The papers in this issue represent biogeographic and ecological perspectives and address the general themes of (i) the niche, (ii) comparative ecology and macroecology, (iii) community assembly, and (iv) diversity. The integration of ecology and biogeography clearly is a natural undertaking that is based on evolutionary biology, has developed its own momentum, and which promises novel, synthetic approaches to investigating ecological systems and their variation over the surface of the Earth. We offer suggestions on future research directions at the intersection of biogeography and ecology.
Rapid adaptation in response to novel environments can facilitate species invasions and range expansions. Understanding how invasive disease vectors rapidly evolve to novel conditions—particularly at ...the edge of its non‐native range—has important implications for mitigating the prevalence and spread of disease.
Here, we evaluate the role of local adaptation in overwintering capability of the Asian tiger mosquito, Aedes albopictus. This species invaded the Southern United States in the 1980s and rapidly spread northward into novel climate compared to its native range. Photoperiodically induced egg diapause is a key trait contributing to the establishment and spread of Ae. albopictus in temperate latitudes, and diapause incidence rapidly developed a cline along a latitudinal gradient in the United States shortly after its initial invasion. However, variation in overwintering survival of diapause‐induced eggs along this gradient is not known, but is critical to the fitness‐related role of diapause evolution in the establishment of Ae. albopictus in its northern US range.
Using reciprocal transplants, we detected local adaptation in overwinter survival of diapausing Aedes albopictus eggs. In northern range‐edge winters, eggs produced by range‐edge individuals survived better than those produced by range‐core individuals. Diapause eggs from range‐edge and range‐core locations survived equally well in range‐core winters, and no eggs survived a winter beyond the current northern range limit in the United States.
Synthesis and applications. These results demonstrate rapid (~3 decades) local adaptation of egg diapause, a key trait facilitating overwinter survival and range expansion for the invasive Asian tiger mosquito. In light of these results, control efforts could shift from targeting satellite populations to a focus on preventing dispersal into locally adapted, range‐edge locations and to aim removal efforts towards areas surrounding locally adapted populations. Adopting new approaches to target rapidly adapting populations will require large‐scale collaboration among control agencies and research institutions, and should begin in the northern US range to better control Aedes albopictus mosquito populations in the face of rapid adaptation.
Background
Pulmonary endarterectomy (PEA), pulmonary arterial hypertension (PAH) therapy and balloon pulmonary angioplasty (BPA) are currently accepted therapies for chronic thromboembolic pulmonary ...hypertension (CTEPH). This international CTEPH Registry identifies clinical characteristics of patients, diagnostic algorithms and treatment decisions in a global context.
Methods
1010 newly diagnosed consecutive patients were included in the registry between February 2015 and September 2016. Diagnosis was confirmed by right heart catheterisation, ventilation–perfusion lung scan, computerised pulmonary angiography and/or invasive pulmonary angiography after at least 3 months on anticoagulation.
Results
Overall, 649 patients (64.3%) were considered for PEA, 193 (19.1%) for BPA, 20 (2.0%) for both PEA and BPA, and 148 (14.7%) for PAH therapy only. Reasons for PEA inoperability were technical inaccessibility (n=235), comorbidities (n=63) and patient refusal (n=44). In Europe and America and other countries (AAO), 72% of patients were deemed suitable for PEA, whereas in Japan, 70% of patients were offered BPA as first choice. Sex was evenly balanced, except in Japan where 75% of patients were female. A history of acute pulmonary embolism was reported for 65.6% of patients. At least one PAH therapy was initiated in 35.8% of patients (26.2% of PEA candidates, 54.5% of BPA candidates and 54.1% of those not eligible for either PEA or BPA). At the time of analysis, 39 patients (3.9%) had died of pulmonary hypertension-related causes (3.5% after PEA and 1.8% after BPA).
Conclusions
The registry revealed noticeable differences in patient characteristics (rates of pulmonary embolism and sex) and therapeutic approaches in Japan compared with Europe and AAO.
Chronic thromboembolic pulmonary hypertension results from incomplete resolution of pulmonary emboli. Pulmonary endarterectomy (PEA) is potentially curative, but residual pulmonary hypertension ...following surgery is common and its impact on long-term outcome is poorly understood. We wanted to identify factors correlated with poor long-term outcome after surgery and specifically define clinically relevant residual pulmonary hypertension post-PEA.
Eight hundred eighty consecutive patients (mean age, 57 years) underwent PEA for chronic thromboembolic pulmonary hypertension. Patients routinely underwent detailed reassessment with right heart catheterization and noninvasive testing at 3 to 6 months and annually thereafter with discharge if they were clinically stable at 3 to 5 years and did not require pulmonary vasodilator therapy. Cox regressions were used for survival (time-to-event) analyses. Overall survival was 86%, 84%, 79%, and 72% at 1, 3, 5, and 10 years for the whole cohort and 91% and 90% at 1 and 3 years for the recent half of the cohort. The majority of patient deaths after the perioperative period were not attributable to right ventricular failure (chronic thromboembolic pulmonary hypertension). At reassessment, a mean pulmonary artery pressure of ≥30 mm Hg correlated with the initiation of pulmonary vasodilator therapy post-PEA. A mean pulmonary artery pressure of ≥38 mm Hg and pulmonary vascular resistance ≥425 dynes·s(-1)·cm(-5) at reassessment correlated with worse long-term survival.
Our data confirm excellent long-term survival and maintenance of good functional status post-PEA. Hemodynamic assessment 3 to 6 months and 12 months post-PEA allows stratification of patients at higher risk of dying of chronic thromboembolic pulmonary hypertension and identifies a level of residual pulmonary hypertension that may guide the long-term management of patients postsurgery.
Explaining the mechanisms underlying spatial and temporal variation in community composition is a major challenge. Nevertheless, the processes controlling temporal variation at a site (i.e. temporal ...β‐diversity, including its turnover and nestedness components) are less understood than those affecting variation among sites (i.e. spatial β‐diversity). Short‐term temporal turnover (e.g. throughout an annual cycle) is expected to correlate positively with seasonal environmental variability and landscape connectivity, but also species pool size (γ‐diversity). We use the megadiverse Amazonian freshwater ichthyofauna as a model to ask whether seasonality and landscape connectivity drive variation in temporal species turnover among geomorphological habitat types, while accounting for between‐habitat variation in γ‐diversity. We collected 11 397 fish representing 260 species during a year‐long sampling program from an area containing the lowland Amazon's four major geomorphological habitat types: rivers, floodplains, terra firme streams, and shield streams. River‐floodplain systems exhibit strong but predictable seasonality (via a high‐amplitude annual flood pulse), high connectivity, and high species richness with many rare species. Terra firme and shield streams exhibit low seasonality, low connectivity, and low species richness with proportionally fewer rare species. Based on these parameters we predicted that river‐floodplain systems should have higher temporal turnover than stream systems. Using a null model approach combined with β‐deviation calculations, we confirmed that rivers and floodplains do exhibit higher turnover (but not nestedness) than terra firme and shield streams, even when controlling for the potentially confounding effect of higher species richness in river‐floodplain systems. All habitats exhibit low temporal nestedness, indicating that short‐term changes in community composition result primarily from temporal species turnover. Our results provide a timely reminder that efforts to conserve the Amazon's threatened aquatic biodiversity should account for the distinct temporal dynamics of habitat types and variation in hydrological seasonality.
Beta diversity (β) is used in biogeography, ecology, and conservation to assess the heterogeneity of local communities. Ideally, researchers could include sensitivity to error in the list of reasons ...to choose a β index. However, only numerical undersampling has been rigorously studied. This study compared multiple β indices to determine which are most robust to geographic undersampling, numerical undersampling, and taxonomic error using simulated landscapes. For these landscapes, eight β indices were chosen to represent families of β and used to measure real and errant data. Six indices used both presence–absence and abundance data, while two more used only abundance data. Six of the abundance‐based indices had adjusted versions for individual undersampling, and these versions were also evaluated (total = 14 indices). Presence–absence‐ and abundance‐based indices were comparable in sensitivity to total method error. Numerical undersampling and taxonomic error generally caused more error in β than randomly distributed geographic undersampling. Among presence–absence‐based indices, Jaccard's dissimilarity was the most robust to error overall, while β‐3 was the most robust among narrow‐sense measures. Among abundance‐based indices, Bray‐Curtis and BDTOTAL were the most robust to error. Some commonly used β indices (e.g., Sorensen, Simpson) are relatively unreliable given errors of taxonomy or numerical undersampling. Future studies of β should focus on using more robust indices (Jaccard, Bray‐Curtis, BDTOTAL), and past studies based on error‐sensitive indices should be considered with caution. Studies of β should emphasize adequate numerical sampling and taxonomic accuracy to minimize errors in β.
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