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Increasing the dose intensity of chemotherapy by more frequent administration or sequential scheduling : a patient-level meta-analysis of 37 298 women with early breast cancer in 26 randomised trials

Povzetek: Background: Increasing the dose intensity of cytotoxic therapy by shortening the intervals between cycles, or by giving individual drugs sequentially at full dose rather than in lower-dose concurrent treatment schedules, might enhance efficacy. Methods: To clarify the relative benefits and risks of dose-intense and standard-schedule chemotherapy in early breast cancer, we did an individual patient-level meta-analysis of trials comparing 2-weekly versus standard 3-weekly schedules, and of trials comparing sequential versus concurrent administration of anthracycline and taxane chemotherapy. The primary outcomes were recurrence and breast cancer mortality. Standard intention-to-treat log-rank analyses, stratified by age, nodal status, and trial, yielded dose-intense versus standard-schedule first-event rate ratios (RRs). Findings: Individual patient data were provided for 26 of 33 relevant trials identified, comprising 37,298 (93%) of 40,070 women randomised. Most women were aged younger than 70 years and had node-positive disease. Total cytotoxic drug usage was broadly comparable in the two treatment arms; colony-stimulating factor was generally used in the more dose-intense arm. Combining data from all 26 trials, fewer breast cancer recurrences were seen with dose-intense than with standard-schedule chemotherapy (10-year recurrence risk 28.0% vs 31.4%; RR 0.86, 95% CI 0.82-0.89; p<0.0001). 10-year breast cancer mortality was similarly reduced (18.9% vs 21.3%; RR 0.87, 95% CI 0.83-0.92; p<0.0001), as was all-cause mortality (22.1% vs 24.8%; RR 0.87, 95% CI 0.83-0.91; p<0.0001). Death without recurrence was, if anything, lower with dose-intense than with standard-schedule chemotherapy (10-year risk 4.1% vs 4.6%; RR 0.88, 95% CI 0.78-0.99; p=0.034). Recurrence reductions were similar in the seven trials (n=10,004) that compared 2-weekly chemotherapy with the same chemotherapy given 3-weekly (10-year risk 24.0% vs 28.3%; RR 0.83, 95% CI 0.76-0.91; p<0.0001), in the six trials (n=11,028) of sequential versus concurrent anthracycline plus taxane chemotherapy (28.1% vs 31.3%; RR 0.87, 95% CI 0.80-0.94; p=0.0006), and in the six trials (n=6532) testing both shorter intervals and sequential administration (30.4% vs 35.0%; RR 0.82, 95% CI 0.74-0.90; p<0.0001). The proportional reductions in recurrence with dose-intense chemotherapy were similar and highly significant (p<0.0001) in oestrogen receptor (ER)-positive and ER-negative disease and did not differ significantly by other patient or tumour characteristics. Interpretation: Increasing the dose intensity of adjuvant chemotherapy by shortening the interval between treatment cycles, or by giving individual drugs sequentially rather than giving the same drugs concurrently, moderately reduces the 10-year risk of recurrence and death from breast cancer without increasing mortality from other causes.
Ključne besede: breast neoplasms, women, drug therapy, clinical protocols, meta-analysis, breast cancer, chemotherapy, treatment schedule, randomized trials
DiRROS - Objavljeno: 22.10.2020; Ogledov: 1; Prenosov: 1
URL Celotno besedilo (0,00 KB)

Growth-limiting factors and climate response variability in Norway spruce (Picea abies L.) along an elevation and precipitation gradients in Slovenia
Jernej Jevšenak, Ivan Tychkov, Jožica Gričar, Tom Levanič, Jan Tumajer, Peter Prislan, Domen Arnič, Margarita Popkova, Vladimir V. Shishov, 2020

Povzetek: Norway spruce (Picea abies L.) is among the most sensitive coniferous species to ongoing climate change. However, previous studies on its growth response to increasing temperatures have yielded contrasting results (from stimulation to suppression), suggesting highly site-specific responses. Here, we present the first study that applies two independent approaches, i.e. the nonlinear, process-based Vaganov-Shashkin (VS) model and linear daily response functions. Data were collected at twelve sites in Slovenia differing in climate regimes and ranging elevation between 170 and 1300 m a.s.l. VS model results revealed that drier Norway spruce sites at lower elevations are mostly moisture limited, while moist high-elevation sites are generally more temperature limited. Daily response functions match well the pattern of growth-limiting factors from the VS model and further explain the effect of climate on radial growth: prevailing growth-limiting factors correspond to the climate variable with higher correlations. Radial growth correlates negatively with rising summer temperature and positively with higher spring precipitation. The opposite response was observed for the wettest site at the highest elevation, which positively reacts to increased summer temperature and will most likely benefit from a warming climate. For all other sites, the future radial growth of Norway spruce largely depends on the balance between spring precipitation and summer temperature.
Ključne besede: Vaganov-Shashkin model, climate-growth correlations, tree rings, process-based modelling, dendroTools, dendroclimatology
DiRROS - Objavljeno: 21.10.2020; Ogledov: 14; Prenosov: 13
URL Celotno besedilo (0,00 KB)
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Timeline of leaf and cambial phenology in relation to development of initial conduits in xylem and phloem in three coexisting sub-Mediterranean deciduous tree species
Jožica Gričar, Andreja Vedenik, Gregor Skoberne, Polona Hafner, Peter Prislan, 2020

Povzetek: It is unclear how the anticipated climate change will affect the timing of phenology of different tree organs/tissues and thus the whole-tree functioning. We examined the timing of leaf phenology and secondary growth in three coexisting deciduous tree species (Quercus pubescens Willd., Fraxinus ornus L. and Ostrya carpinifolia Scop) from a sub-Mediterranean region in 2019. In addition, we investigated the relationship between leaf and cambial phenology and the onset of the potential functioning of initial conduits, as determined by the completed differentiation process (vessels) or final size (sieve tubes). For this purpose, leaf development was monitored and the microcores of cambium and the youngest phloem and xylem increments were repeatedly collected at 7-10-day intervals during the growing season. The results revealed differences in the timing of leaf development and seasonal radial growth patterns in spring among the studied tree species, depending on wood porosity. We found that cambial cell production started in all cases in the first half of March. However, in ring-porous Q. pubescens and F. ornus, radial growth in the stem occurred more than a month before buds were swollen, whereas in diffuse-porous O. carpinifolia, these two events were detected at almost the same time. The end of cambial cell production occurred earliest in F. ornus (mid-July) and two weeks later also in the other two species. The widest initial earlywood vessels and early phloem sieve tubes were found in Q. pubescens, the narrowest initial earlywood vessels in O. carpinifolia and the narrowest early phloem sieve tubes in F. ornus. This indicates differences in the e%ciency of conducting systems among the studied species. This novel approach of studying phloem phenology and anatomy in relation to leaf and xylem development contributes to a better understanding of how different tree species adapt their structure of secondary vascular tissues in response to environmental change.
Ključne besede: Quercus pubescens, Fraxinus ornus, Ostrya carpinifolia, earlywood, early phloem, vessel, sieve tube, radial growth
DiRROS - Objavljeno: 21.10.2020; Ogledov: 11; Prenosov: 7
URL Celotno besedilo (0,00 KB)
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