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Climate change is leading to species redistributions. In the tundra biome, shrubs are generally expanding, but not all tundra shrub species will benefit from warming. Winner and loser species, and the characteristics that may determine success or failure, have not yet been fully identified. Here, we investigate whether past abundance changes, current range sizes and projected range shifts derived from species distribution models are related to plant trait values and intraspecific trait variation. We combined 17,921 trait records with observed past and modelled future distributions from 62 tundra shrub species across three continents. We found that species with greater variation in seed mass and specific leaf area had larger projected range shifts, and projected winner species had greater seed mass values. However, trait values and variation were not consistently related to current and projected ranges, nor to past abundance change. Overall, our findings indicate that abundance change and range shifts will not lead to directional modifications in shrub trait composition, since winner and loser species share relatively similar trait spaces. Functional trait data could guide predictions of species responses to environmental change. Here, the authors show that winner and loser shrub species in the warming tundra biome overlap in trait space and may therefore be difficult to predict based on commonly measured traits. [ABSTRACT FROM AUTHOR]

Orchids have symbiotic relationships with ectomycorrhizal or saprotrophic ("rhizoctonia") fungi, which provide plants with nutrients. The extent of plant dependency on fungi for carbon supply is reflected by plant tissue δ13C abundance values. Little is known about how wide-spread partial mycoheterotrophy (PMH) is among orchids in nature and it is debated whether rhizoctonia-associated orchids possess mycoheterotrophy. Using orchids with ectomycorrhizal fungi and rhizoctonia-associated orchid species, we tested one hypothesis: terrestrial green orchids decrease their δ13C values in response to shade less than neighboring non-orchid vascular plants (evidence for PMH). We examined eight pairs of plant species (orchid paired with reference autotrophic plant growing close-by) in well-lit versus shady field conditions in replicated sites across the European part of Russia. In each site illumination level was recorded and plant material was examined for δ13C. We found that all tested orchids showed similar weaker response of tissue δ13C signature to relative light exposure in contrast to the stronger response in control plants, suggesting wide-spread PMH among orchids. There was no significant difference in orchids with ectomycorrhizal fungi and rhizoctonia-associated orchids in response of δ13C to shade, supporting mycoheterotrophic mechanisms of carbon transfer to plants in rhizoctonia-associated orchids. Proportions of fungi-derived carbon for individual orchid species ranged between 3 and 50%. Orchids reduced stomatal density in response to shade less or similarly to autotrophic plants, suggesting that mycoheterotrophic plants might be somewhat less water limited than autotrophic species due to fungal water supply. Our data provide support for broad prevalence of PMH among orchids and of the existence of PMH in rhizoctonia-associated orchids. These findings extend the ecological importance of mycorrhizal associations in belowground food webs. [ABSTRACT FROM AUTHOR]

The soil nitrogen (N) cycle in cold terrestrial ecosystems is slow and organically bound N is an important source of N for plants in these ecosystems. Many plant species can take up free amino acids from these infertile soils, either directly or indirectly via their mycorrhizal fungi. We hypothesized that plant community changes and local plant community differences will alter the soil free amino acid pool and composition; and that long-term warming could enhance this effect. To test this, we studied the composition of extractable free amino acids at five separate heath, meadow, and bog locations in subarctic and alpine Scandinavia, with long-term (13 to 24 years) warming manipulations. The plant communities all included a mixture of ecto-, ericoid-, and arbuscular mycorrhizal plant species. Vegetation dominated by grasses and forbs with arbuscular and non-mycorrhizal associations showed highest soil free amino acid content, distinguishing them from the sites dominated by shrubs with ecto- and ericoid-mycorrhizal associations. Warming increased shrub and decreased moss cover at two sites, and by using redundancy analysis, we found that altered soil free amino acid composition was related to this plant cover change. From this, we conclude that the mycorrhizal type is important in controlling soil N cycling and that expansion of shrubs with ectomycorrhiza (and to some extent ericoid mycorrhiza) can help retain N within the ecosystems by tightening the N cycle. [ABSTRACT FROM AUTHOR]

The majority of variation in six traits critical to the growth, survival and reproduction of plant species is thought to be organised along just two dimensions, corresponding to strategies of plant size and resource acquisition. However, it is unknown whether global plant trait relationships extend to climatic extremes, and if these interspecific relationships are confounded by trait variation within species. We test whether trait relationships extend to the cold extremes of life on Earth using the largest database of tundra plant traits yet compiled. We show that tundra plants demonstrate remarkably similar resource economic traits, but not size traits, compared to global distributions, and exhibit the same two dimensions of trait variation. Three quarters of trait variation occurs among species, mirroring global estimates of interspecific trait variation. Plant trait relationships are thus generalizable to the edge of global trait-space, informing prediction of plant community change in a warming world. It is unclear whether plant trait relationships found at the global scale extend to climatic extremes. Here the authors analyse six major aboveground traits to show that known plant trait relationships extend to the tundra biomes and exhibit the same two dimensions of variation detected at the global scale. [ABSTRACT FROM AUTHOR]

Aims: The effects of litter diversity on litter decomposition remain debated. We tested to what extent the community-weighted means (CWM; functional composition) versus Rao's dissimilarity of litter nitrogen (N)-to-phosphorus (P) ratios explain the non-additive mixture effect on decomposition rate (k) and associated N release.Methods: We carried out a one-year field decomposition experiment with a range of five litter types ranging from three evergreens only (high N/P and low specific leaf area, SLA) to three deciduous species only (low-N/P and high-SLA), with 30:70, 50:50 and 70:30% mixtures of these two extremes in between, in subtropical forest of China.Results: There were tight hump-backed relationships of absolute k-values and N release, respectively, with the CWMSLA. The mixtures with the highest functional evenness in terms of CWMN/P caused the highest positive non-additivity on decomposition (R2 = 0.72) and N release (R2 = 0.95) rates. In contrast, the mixing effect on k or N release was weakly positively correlated with Rao's dissimilarity of N/P (R2 = 0.38 and 0.27 respectively).Conclusions: Our results provide a strong framework for predicting litter decomposition rates and associated N release versus immobilization in mixtures of deciduous versus evergreen species based on their differences in initial stoichiometry. [ABSTRACT FROM AUTHOR]

Northern peatlands are very sensitive to changes in climate. Impacts of increased temperatures on hydrology, vegetation structure and soil carbon are already well documented from northern peatlands. In contrast, effects of global warming on soil mites, and seasonal effects in particular, have received less attention, even though soil mites are an important component in ecosystems as they contribute to nutrient dynamics and decomposition. We investigated the impacts of long-term (16 years) experimental seasonal climate manipulations (summer warming, winter warming with snow accumulation, and year-round warming) on oribatid (Oribatida) and mesostigmatid (Mesostigmata) mite communities in a peat bog underlain by discontinuous permafrost, in Abisko, Northern Sweden. We found that (1) Year-round warming treatment had neither impact on life-history trait compositions nor on total abundances of oribatid mites, possibly because of opposite effects of summer and winter warming; (2) Small-bodied oribatid mites, in particular those belonging to genera Suctobelba, increased in abundance under the summer warming treatment; (3) The species richness of oribatid mites was negative affected by year-round warming; (4) Mesostigmatid mites, which were not identified to species level, were found to decrease in abundance under year-round warming. Because different mite taxa with different body sizes and diets play distinct roles in carbon and nutrient dynamics, the observed changes in mite communities may impact ecosystem functions in northern peatlands. [ABSTRACT FROM AUTHOR]

The tundra is warming more rapidly than any other biome on Earth, and the potential ramifications are far-reaching because of global feedback effects between vegetation and climate. A better understanding of how environmental factors shape plant structure and function is crucial for predicting the consequences of environmental change for ecosystem functioning. Here we explore the biome-wide relationships between temperature, moisture and seven key plant functional traits both across space and over three decades of warming at 117 tundra locations. Spatial temperature-trait relationships were generally strong but soil moisture had a marked influence on the strength and direction of these relationships, highlighting the potentially important influence of changes in water availability on future trait shifts in tundra plant communities. Community height increased with warming across all sites over the past three decades, but other traits lagged far behind predicted rates of change. Our findings highlight the challenge of using space-for-time substitution to predict the functional consequences of future warming and suggest that functions that are tied closely to plant height will experience the most rapid change. They also reveal the strength with which environmental factors shape biotic communities at the coldest extremes of the planet and will help to improve projections of functional changes in tundra ecosystems with climate warming. Analyses of the relationships between temperature, moisture and seven key plant functional traits across the tundra and over time show that community height increased with warming across all sites, whereas other traits lagged behind predicted rates of change. [ABSTRACT FROM AUTHOR]

In the karst landscape, widespread in the world including southern China, soil nutrient supply is strongly constrained. In such environments, arbuscular mycorrhizal (AM) fungi may facilitate plant nutrient uptake. However, the possible role of different AM fungal species, and their interactions, especially in transferring nitrogen (N) from litter to plant, is poorly understood. We conducted two microcosm experiments to investigate the role that two karst soil AM fungi, Glomus etunicatum and Glomus mosseae, play in the transfer of N from decomposing litter to the host plant and to determine how N availability influences these processes. In experiment 1, Cinnamomum camphora tree seedlings were grown in compartments inoculated with G. etunicatum. Lolium perenne leaf litter labeled with δN was added to the soil in unplanted compartments. Compartments containing the δN labeled litter were either accessible to hyphae but not to seedling roots or were not accessible to hyphae or roots. The addition of mineral N to one of the host compartments at the start of the experiment significantly increased the biomass of the C. camphora seedlings, N content and N:P ratio, AM mycelium length, and soil microbial biomass carbon and N. However, significantly, more δN was acquired, from the leaf litter by the AM hyphae and transferred to the host when mineral N was not added to the soil. In experiment 2, in which C. camphora seedlings were inoculated with both G. etunicatum and G. mosseae rather than with G. mosseae alone, there was a significant increase in mycelial growth (50.21%), in soil microbial biomass carbon (417.73%) in the rhizosphere, and in the amount of δN that was transferred to the host. These findings suggest that maintaining AM fungal diversity in karst soils could be important for mediating N transfer from organic material to host plants in N-poor soils. [ABSTRACT FROM AUTHOR]

The promise of 'trait-based' plant ecology is one of generalized prediction across organizational and spatial scales, independent of taxonomy. This promise is a major reason for the increased popularity of this approach. Here, we argue that some important foundational assumptions of trait-based ecology have not received sufficient empirical evaluation. We identify three such assumptions and, where possible, suggest methods of improvement: (i) traits are functional to the degree that they determine individual fitness, (ii) intraspecific variation in functional traits can be largely ignored, and (iii) functional traits show general predictive relationships to measurable environmental gradients. [ABSTRACT FROM AUTHOR]

Allogeneic hematopoietic transplantation is increasingly used in patients aged 55 years or more with AML. The question of whether outcomes can be improved with an allele-level 8/8 HLA-matched unrelated donor (MUD) rather than an older HLA-matched sibling (MSD, more than 55 years) is still unanswered. We thus analyzed outcomes in 714 patients aged 55 years and older with AML in first CR (CR1) who received PBSCs after a reduced-intensity conditioning hematopoietic cell transplant from a MUD (n=310) or a MSD (n=404) in a recent period (2005-2010). The 3-year cumulative incidences (CIs) of non-relapse mortality were 17% and 23% with MSD and MUD, respectively (P=0.17). The 3-year CIs of relapse were 37% and 30%, respectively (P=0.12), resulting in a 3-year CI of leukemia-free survival of 46% and 47%, respectively (P=0.51). The 3-year overall survival was 49% with both MSD and MUD. In conclusion, HLA-identical sibling donors aged 55 years or more should not be excluded because of age for patients aged 55 years and older with AML in CR1. [ABSTRACT FROM AUTHOR]

In recipients of allogeneic hematopoietic stem cell transplantation with AML in CR1, reduced intensity (RIC) conditioning regimens are usually given to older patients and myeloablative regimens (MAC) to younger patients. We analyzed whether in middle-aged patients aged 40-60 years, MAC was superior to RIC in cytogenetically higher risk AML. Among 2974 patients, 1638 had MAC and 1336 RIC transplants. Cytogenetics were high risk in 508, intermediate risk in 2297 and low risk in 169. Overall survival (OS) was higher in patients with RIC with low-risk cytogenetics but not in the intermediate- or poor-risk AML. Relapse incidence was lower with MAC in poor- and intermediate-risk AML. Nonrelapse mortality (NRM) was higher in MAC in all cytogenetic risk groups. Multivariate analysis confirmed a significant leukemia-free survival and OS advantage for RIC in low risk but no advantage of MAC in intermediate- and poor-risk leukemia. In patients aged 40-60 years, MAC has no advantage over RIC. We confirm lower relapse but higher NRM risks with MAC. MAC is not superior in patients with higher risk cytogenetics, but is inferior to RIC in the small cohort of AML patients with low-risk cytogenetics. [ABSTRACT FROM AUTHOR]

The preferred type of post-remission therapy (PRT) in patients with acute myeloid leukemia (AML) in first complete remission (CR1) is a subject of continued debate, especially in patients at higher risk of nonrelapse mortality (NRM), including patients >40 years of age. We report results of a time-dependent multivariable analysis of allogenic hematopoietic stem cell transplantation (alloHSCT) (n=337) versus chemotherapy (n=271) or autologous HSCT (autoHSCT) (n=152) in 760 patients aged 40-60 years with AML in CR1. Patients receiving alloHSCT showed improved overall survival (OS) as compared with chemotherapy (respectively, 57±3% vs 40±3% at 5 years, P<0.001). Comparable OS was observed following alloHSCT and autoHSCT in patients with intermediate-risk AML (60±4 vs 54±5%). However, alloHSCT was associated with less relapse (hazard ratio (HR) 0.51, P<0.001) and better relapse-free survival (RFS) (HR 0.74, P=0.029) as compared with autoHSCT in intermediate-risk AMLs. AlloHSCT was applied following myeloablative conditioning (n=157) or reduced intensity conditioning (n=180), resulting in less NRM, but comparable outcome with respect to OS, RFS and relapse. Collectively, these results show that alloHSCT is to be preferred over chemotherapy as PRT in patients with intermediate- and poor-risk AML aged 40-60 years, whereas autoHSCT remains a treatment option to be considered in patients with intermediate-risk AML. [ABSTRACT FROM AUTHOR]

We determined whether assessment of the immunogenicity of individual donor-recipient HLA mismatches based on differences in their amino-acid sequence and physiochemical properties predicts clinical outcome following haematopoietic SCT (HSCT). We examined patients transplanted with 9/10 single HLA class I-mismatched grafts (n=171) and 10/10 HLA-A-, -B-, -C-, -DRB1- and -DQB1-matched grafts (n=168). A computer algorithm was used to determine the physiochemical disparity (electrostatic mismatch score (EMS) and hydrophobic mismatch score (HMS)) of mismatched HLA class I specificities in the graft-versus-host direction. Patients transplanted with HLA-mismatched grafts with high EMS/HMS had increased incidence of ⩾grade II acute GVHD (aGVHD) compared with patients transplanted with low EMS/HMS grafts; patients transplanted with low and medium EMS/HMS grafts had similar incidence of aGVHD to patients transplanted with 10/10 HLA-matched grafts. Mortality was higher following single HLA-mismatched HSCT but was not correlated with HLA physiochemical disparity. Assessment of donor-recipient HLA incompatibility based on physiochemical HLA disparity may enable better selection of HLA-mismatched donors in HSCT. [ABSTRACT FROM AUTHOR]

Non-relapse mortality (NRM) after allogeneic hematopoietic stem cell transplantation (alloHSCT) can be predicted by the hematopoietic cell transplantation comorbidity index (HCT-CI) and the European Group for Blood and Marrow Transplantation (EBMT) score, which are composed of different parameters. We set out to integrate the parameters of both scores in patients with acute myeloid leukemia (AML) in first complete remission (CR1) receiving reduced intensity conditioning (RIC) alloHSCT. All parameters from the HCT-CI and the EBMT-score with the addition of patient and donor cytomegalovirus serology were evaluated in 812 patients by multivariable analysis with end-point NRM at 2 years. Subsequently, 16 parameters were selected based on hazard ratio >1.2, and were incorporated into a novel score, which was further internally validated by bootstrapping. Both the HCT-CI and the EBMT-score showed relatively weak predictive value, whereas the integrated score allowed to identify three clearly distinct risk groups with 2-year NRM estimates of 8±2% (low-risk), 17±2% (intermediate-risk) and 38±4% (high-risk), which also translated in prediction of overall survival. Collectively, integration of the most dominant parameters from the HCT-CI and the EBMT-score allowed to develop a simple and robust, integrated score with improved prediction of NRM for AML patients proceeding to RIC alloHSCT in CR1. [ABSTRACT FROM AUTHOR]

We performed a retrospective analysis on 421 adult patients who underwent unrelated cord blood transplantation (UCBT) for ALL. Median age was 32 years; 46% were in first CR (CR1), 32% in CR2 and 22% had advanced disease. Double UCBT was performed in 173 patients (41%). Myeloablative conditioning (MAC) was given to 314 patients (75%). Cumulative incidence (CI) of 60-day neutrophil recovery was 78%. CI of acute and chronic GVHD was 33 and 26%, respectively. Non-relapse mortality (NRM) at 2 years was 42%. Age⩾35 years (P<0.0001), advanced disease at UCBT (P<0.0001) and use of MAC (P<0.0001) were associated with increased NRM. Relapse incidence (RI) at 2 years was 28%; use of reduced intensity conditioning (RIC) (P=0.0002) was associated with increased RI. Two-year leukemia-free survival (LFS) was 39% for patients in CR1, 31% for CR2 and 8% for advanced disease. In multivariate analysis, factors associated with decreased LFS rate were: age ⩾35 years (P=0.034), use of MAC (P=0.032) and advanced disease (P<0.0001). These results show that UCBT is a valuable option to treat high-risk adult ALL when in remission. Strategies to decrease toxicity and relapse are needed to improve final outcomes. [ABSTRACT FROM AUTHOR]

Hematopoietic SCT (HSCT) is often complicated by viral reactivations. In this retrospective cohort study (January 2004-August 2008), predictors for human herpes virus 6 (HHV6)-reactivation and associations between HHV6-reactivation and clinical outcomes after allogeneic HSCT were studied. HHV6 DNA load in plasma was monitored weekly by quantitative real-time PCR. Associations between the main end point HHV6-reactivation and other end points, that is, acute GVHD (aGVHD) and NRM were analyzed using Cox proportional hazard models. In total, 108 patients receiving either a myeloablative (MA; n=60) or non-myeloablative (NMA; n=48) conditioning regimen were included. Median age was 40 years (range 17-65); median follow-up was 20 months (range 3-36). In 16/60 (27%) patients with MA conditioning regimen, a HHV6 reactivation was observed (mean viral load 50 323 cp/mL) compared with 2/48 (4%) patients with a NMA conditioning regimen with low viral load (mean 1100 cp/mL). In multivariate analysis, MA conditioning was the only predictor for HHV6 reactivation (P=0.02). In addition, HHV6 reactivation was associated with grades 2-4 aGVHD (P<0.001) and NRM (P=0.03). Regular monitoring of HHV6 reactivation after HSCT might be important in MA HSCT patients to enable early initiation of antiviral treatment or to anticipate aGVHD, all of which may improve clinical outcome. [ABSTRACT FROM AUTHOR]

The MHC region on chromosome 6 contains a large number of non-HLA genes next to the HLA genes. Matching for HLA in unrelated hematopoietic SCT (HSCT) does not necessarily mean that these non-HLA genes are also matched. We selected 348 Northwest European patients transplanted with an HLA-A-, -B-, -C-, -DRB1-, -DQB1-matched unrelated donor (MUD) between 1987 and 2008. Patients' haplotypes were identified via descend. We were unable to determine the haplotypes of the donor; therefore we used frequent haplotypes (FH) in high linkage disequilibrium (LD) as a proxy for haplotype matching. Presence of a FH in a patient positively affected the probability and speed of identifying a matched unrelated donor. Competing risk survival analysis showed that patients with one or two FH have a statistically significantly decreased probability of developing grade II acute GVDH (aGVHD) without increased risk of relapse compared to patients without FH (HR (95% CI): 0.53 (0.31-0.91)). This association was strongest for those FH with the highest LD between both HLA-A and -C or -B, and HLA-C or -B and -DRB1 (HR (95% CI): 0.49 (0.26-0.92)). These results extend evidence that non-HLA allele coding regions have a significant impact on development of grade II aGVHD. We conclude that there is more to successful HSCT than matching for HLA genes. [ABSTRACT FROM AUTHOR]

Allogeneic hematopoietic SCT with reduced-intensity conditioning (RIC-HSCT) is increasingly adopted for the treatment of older adults with AML. Our goal was to verify for the first time, if center experience influences outcome of RIC-HSCT. Results of 1413 transplantations from HLA-matched related or unrelated donors for adult patients with AML in first CR were analyzed according to the level of center activity. Transplants were performed in 203 European centers between 2001 and 2007. The 2-year probability of leukemia-free survival (LFS) after RIC-HSCT performed in centers with the lowest activity (15 procedures/7 years) was 43±3% compared with 55±2% in the remainder (P<0.001). The incidence of non-relapse mortality (NRM) was 24±3% and 15±1% (P=0.004), whilst relapse rate was 33±3% and 31±1% (P=0.33), respectively. In a multivariate model, adjusted for other prognostic factors, low RIC-HSCT activity was associated with decreased chance of LFS (hazard ratio (HR)=0.64; P<0.001) and increased risk of NRM (HR=1.47, P=0.04) and relapse (HR=1.41, P=0.01). Center experience is a very important predictor of outcome and should be considered in future analyses evaluating the results of RIC-HSCT. The reasons why centers with low RIC-HSCT activity have worse outcomes should be further investigated. [ABSTRACT FROM AUTHOR]

Haematopoietic stem cell transplantation (SCT) is an expensive lifesaving procedure, which is increasingly performed in patients with haematological diseases. Developments in the protocol for SCT have resulted in cost estimates that require updating. We aimed to calculate actual costs for SCT and to identify major cost drivers by means of a daily practice cost study. We randomly selected 191 patients, treated at three university hospitals, who underwent an autologous (auto) SCT or allogeneic (allo) SCT in 2007, 2008 or 2009. Allo-SCT included sibling donors, matched unrelated donors (MUD) and umbilical cord blood (UCB). Resource use was collected from the hospital registration systems and medical files. The total costs included selection and harvesting of stem cells, transplantation and 1-year follow-up. The average costs per patient were 45,670 € for auto-SCT and 101,919 € for sibling allo-SCT. The costs of transplantations from unrelated donors were much higher: 171,478 € for allo-SCT-MUD and 254,689 € for allo-SCT-UCB. Hospital inpatient days together with laboratory and other activities were the main cost drivers across all types of SCT. Besides, donor search costs were a large cost component in allo-SCT-sib (18 %) and allo-SCT-MUD (12 %). Real-world costs were above routine reimbursement and appropriate financing is necessary to guarantee the continuation of SCT. The costs calculated in this study provide reliable up-to-date input for cost-effectiveness studies and budget revision. [ABSTRACT FROM AUTHOR]

This report investigated the impact of graft-versus-host disease (GVHD) on transplantation outcomes in 1859 acute myeloid leukemia patients given allogeneic peripheral blood stem cells after reduced-intensity conditioning (RIC allo-SCT). Grade I acute GVHD was associated with a lower risk of relapse (hazards ratio (HR)=0.7, P=0.02) translating into a trend for better overall survival (OS; HR=1.3; P=0.07). Grade II acute GVHD had no net impact on OS, while grade III-IV acute GVHD was associated with a worse OS (HR=0.4, P<0.0.001) owing to high risk of nonrelapse mortality (NRM; HR=5.2, P<0.0001). In time-dependent multivariate Cox analyses, limited chronic GVHD tended to be associated with a lower risk of relapse (HR=0.72; P=0.07) translating into a better OS (HR=1.8; P<0.001), while extensive chronic GVHD was associated with a lower risk of relapse (HR=0.65; P=0.02) but also with higher NRM (HR=3.5; P<0.001) and thus had no net impact on OS. In-vivo T-cell depletion with antithymocyte globulin (ATG) or alemtuzumab was successful at preventing extensive chronic GVHD (P<0.001), but without improving OS for ATG and even with worsening OS for alemtuzumab (HR=0.65; P=0.001). These results highlight the role of the immune-mediated graft-versus-leukemia effect in the RIC allo-SCT setting, but also the need for improving the prevention and treatment of severe GVHD. [ABSTRACT FROM AUTHOR]

Litter decomposition and nutrient mineralization in high-latitude peatlands are constrained by low temperatures. So far, little is known about the effects of seasonal components of climate change (higher spring and summer temperatures, more snow which leads to higher winter soil temperatures) on these processes. In a 4-year field experiment, we manipulated these seasonal components in a sub-arctic bog and studied the effects on the decomposition and N and P dynamics of leaf litter of Calamagrostis lapponica, Betula nana, and Rubus chamaemorus, incubated both in a common ambient environment and in the treatment plots. Mass loss in the controls increased in the order Calamagrostis < Betula < Rubus. After 4 years, overall mass loss in the climate-treatment plots was 10 % higher compared to the ambient incubation environment. Litter chemistry showed within each incubation environment only a few and species-specific responses. Compared to the interspecific differences, they resulted in only moderate climate treatment effects on mass loss and these differed among seasons and species. Neither N nor P mineralization in the litter were affected by the incubation environment. Remarkably, for all species, no net N mineralization had occurred in any of the treatments during 4 years. Species differed in P-release patterns, and summer warming strongly stimulated P release for all species. Thus, moderate changes in summer temperatures and/or winter snow addition have limited effects on litter decomposition rates and N dynamics, but summer warming does stimulate litter P release. As a result, N-limitation of plant growth in this sub-arctic bog may be sustained or even further promoted. [ABSTRACT FROM AUTHOR]

So far the impact of cytogenetics risk on outcome in the context of reduced intensity conditioning (RIC) allo-SCT has been poorly studied. We have identified 378 AML patients in first CR who underwent RIC allo-SCT from an HLA-matched sibling donor between 2000 and 2007 reported to the European Group for Bone and Marrow Transplantation and for whom detailed cytogenetics data were available (good risk: n=21; intermediate risk: n=304; and poor risk: n=53). With a median follow-up of 24 months (range: 1-93), 2-year non-relapse mortality, relapse rate (RR), leukemia-free survival (LFS) and OS were 14%, 31%, 55% and 61%, respectively. Cytogenetics was significantly associated with RR (good risk: 10%; intermediate risk: 28%; and poor risk: 55% at 2 years, P<0.0001) and LFS (good risk: 64%; intermediate risk: 57%; and poor risk: 38% at 2 years, P=0.003). In a multivariate analysis, RR and LFS were significantly higher and lower, respectively, in the high-risk cytogenetics group (P=0.001, P=0.004) and in patients with a higher WBC at diagnosis (>10 × 109/L) (P<0.001, P=0.004). As documented in the setting of myeloablative allo-SCT, patients with poor cytogenetics had increased RR and decreased LFS after RIC allo-SCT, requiring new prospective strategies to improve results in this subgroup. [ABSTRACT FROM AUTHOR]

Background and aims: We ask how productivity responses of alpine plant communities to increased nutrient availability can be predicted from abiotic regime and initial functional type composition. Methods: We compared four Caucasian alpine plant communities (lichen heath, Festuca varia grassland, Geranium-Hedysarum meadow, snow bed community) forming a toposequence and contrasting in productivity and dominance structure for biomass responses to experimental fertilization (N, P, NP, Ca) and irrigation for 4-5 years. Results: The dominant plants in more productive communities monopolized added N and P, at the expense of their neighbors. In three out of four communities, N and P fertilizations gave greater aboveground biomass increase than N or P fertilization alone, indicating overall co-limitation of N and P, with N being most limiting. Relative biomass increase in NP treatment was negatively related to biomass in control plots across the four communities. Grasses often responded more vigorously to P, but sedges to N alone. Finally, we present one of the rare examples of a forb showing a strong N or NP response. Conclusion: Our findings will help improve our ability to predict community composition and biomass dynamics in cool ecosystems subject to changing nutrient availability as induced by climate or land-use changes. [ABSTRACT FROM AUTHOR]

The article presents a study which examines the feasibility and effectiveness of intensive chemotherapy in acute lymphoblastic leukemia (ALL) patients over the age of 40. It notes that the study was participated by 60 patients with ALL who were treated with intensive chemotherapeutic regimen. It concludes that the regimen of intensive chemotherapy is feasible and demonstrated efficacy in patients with ALL up to 70 years of age.

Insensitivity of chronic myeloid leukemia (CML) hematopoietic stem cells to tyrosine kinase inhibitors (TKIs) prevents eradication of the disease and may be involved in clinical resistance. For improved treatment results more knowledge about CML stem cells is needed. We here present a new flow cytometric approach enabling prospective discrimination of CML stem cells from their normal counterparts within single-patient samples. In 24 of 40 newly diagnosed CML patients residual normal CD34+CD38− stem cells could be identified by lower CD34 and CD45 expression, lower forward/sideward light scatter and by differences of lineage marker expression (CD7, CD11b and CD56) and of CD90. fluorescent in situ hybridization (FISH) analysis on Fluorescence-activated cell sorting sorted cells proved that populations were BCR-ABL positive or negative and long-term liquid culture assays with subsequent colony forming unit assays and FISH analysis proved their stem cell character. Patients with residual non-leukemic stem cells had lower clinical risk scores (Sokal, Euro), lower hematological toxicity of imatinib (IM) and better molecular responses to IM than patients without. This new approach will expand our possibilities to separate CML and normal stem cells, present in a single bone marrow or peripheral blood sample, thereby offering opportunities to better identify new CML stem-cell-specific targets. Moreover, it may guide optimal clinical CML management. [ABSTRACT FROM AUTHOR]

Aims: The purpose of this study was to test the hypotheses that soil nutrient patchiness can differentially benefit the decomposition of root and shoot litters and that this facilitation depends on plant genotypes. Methods: We grew 15 cultivars (i.e. genotypes) of winter wheat ( Triticum aestivum L.) under uniform and patchy soil nutrients, and contrasted their biomass and the subsequent mass, carbon (C) and nitrogen (N) dynamics of their root and shoot litters. Results: Under equal amounts of nutrients, patchy distribution increased root biomass and had no effects on shoot biomass and C:N ratios of roots and shoots. Roots and shoots decomposed more rapidly in patchy nutrients than in uniform nutrients, and reductions in root and shoot C:N ratios with decomposition were greater in patchy nutrients than uniform nutrients. Soil nutrient patchiness facilitated shoot decomposition more than root decomposition. The changes in C:N ratios with decomposition were correlated with initial C:N ratios of litter, regardless of roots or shoots. Litter potential yield, quality and decomposition were also affected by T. aestivum cultivars and their interactions with nutrient patchiness. Conclusions: Soil nutrient patchiness can enhance C and N cycling and this effect depends strongly on genotypes of T. aestivum. Soil nutrient heterogeneity in plant communities also can enhance diversity in litter decomposition and associated biochemical and biological dynamics in the soil. [ABSTRACT FROM AUTHOR]

Event-free survival (EFS) at 5 years in pediatric acute lymphoblastic leukemia (ALL) is >80%. Outcome in adult ALL is still unsatisfactory, which is due to less cumulative dosing of chemotherapy and less strict adherence to timing of successive cycles. In the present phase II trial, we evaluated a pediatric regimen in adult patients with ALL under the age of 40. Treatment was according to the pediatric FRALLE approach for high-risk ALL patients and characterized by increased dosages of asparaginase, steroids, methotrexate and vincristin. However, allogeneic stem cell transplantation was offered to standard risk patients with a sibling donor and to all high-risk patients in contrast to the pediatric protocol. Feasibility was defined by achieving complete remission (CR) and completion of treatment within a strict timeframe in at least 60% of patients. In all, 54 patients were included with a median age of 26. CR was achieved in 49 patients (91%), of whom 33 completed treatment as scheduled (61%). Side effects primarily consisted of infections and occurred in 40% of patients. With a median follow-up of 32 months, EFS estimated 66% at 24 months and overall survival 72%. These data show that a dose-intensive pediatric regimen is feasible in adult ALL patients up to the age of 40. [ABSTRACT FROM AUTHOR]

Many parameters predict for outcome after unrelated donor (URD) allogeneic hematopoietic stem cell transplantation (alloSCT). High-resolution HLA-matching significantly impacts outcome and also the European Group of Blood and Marrow Transplantation (EBMT) risk score, based on patient age, disease stage, donor type, time from diagnosis to SCT and gender combination, may predict for non-relapse mortality and overall survival (OS). We evaluated the individual and combined effects of allele-matching and the EBMT risk score in 327 patients with poor-risk acute leukemia or myelodysplasia, who received a T-cell depleted URD alloSCT. Matching for HLA-A, -B, -C and -DRB1 alleles (8/8 match) was associated with a 5-year OS of 40% compared with 30% for mismatched (7/8) pairs (P=0.02). Patients with EBMT risk scores of 1-2, 3, 4 and 5-7 had 5-year OS estimates of 53, 43, 30 and 20%, respectively (P<0.001). The favorable prognostic impact of an 8/8 donor was most pronounced if the EBMT risk score was low (1-2). Five-year OS was 74±8% vs 39±11% for fully matched patients with a low-risk EBMT score as compared with EBMT low-risk patients with 7/8 donors. These data underscore the importance of incorporating both the EBMT risk score and the degree of high-resolution HLA-matching in the risk assessment prior to URD alloSCT. [ABSTRACT FROM AUTHOR]

The European Group for Blood and Marrow Transplantation regularly publishes special reports on the current practice of haematopoietic SCT for haematological diseases, solid tumours and immune disorders in Europe. Major changes have occurred since the first report was published. HSCT today includes grafting with allogeneic and autologous stem cells derived from BM, peripheral blood and cord blood. With reduced-intensity conditioning regimens in allogeneic transplantation, the age limit has increased, permitting the inclusion of older patients. New indications have emerged, such as autoimmune disorders and AL amyloidosis for autologous HSCT and solid tumours, myeloproliferative syndromes and specific subgroups of lymphomas for allogeneic transplants. The introduction of alternative therapies, such as imatinib for CML, has challenged well-established indications. An updated report with revised tables and operating definitions is presented. [ABSTRACT FROM AUTHOR]

In autologous and allogeneic hematopoietic SCT (HSCT) neutropenia may be associated with severe infection. Immunodeficiency associated with GVHD and its treatment in allogeneic HSCT is also a risk for severe infection. In both periods, patients may develop severe sepsis with organ failure. To gain insights into treatment possibilities, HISTORY, a multicenter retrospective study reviewed HSCT patient records on mortality, organ dysfunction, platelet count and bleeding events. All transplantation records from 16 European centers were reviewed for 1.5 years. Of 2092 patients screened, 160 were documented for HSCT with respiratory and/or cardiovascular organ dysfunction because of sepsis and/or GVHD. Mortality was 53.1% at 28 days and 65.6% at 100 days. HSCT patients with sepsis and organ dysfunction are at highest risk of death (49.5%). Death from refractory septic shock was 15.2%, and it was 20% from respiratory failure and 64.7% from sepsis. Fewer than 3% of HSCT patients died from bleeding complications; however, individuals at increased risk of bleeding were excluded. Despite low platelet counts, an increased risk of bleeding could be established only if thrombocytopenia dropped below 13 × 109/l. Thus, there might be a therapeutic window for treatment strategies for severe sepsis in HSCT, such as drotrecogin alfa (activated).Bone Marrow Transplantation (2009) 43, 491–497; doi:10.1038/bmt.2008.337; published online 15 December 2008 [ABSTRACT FROM AUTHOR]

A fully major histocompatilbility complex (MHC) matched donor is not available for the majority of patients in need of a haematopoietic stem cell transplantation (SCT), which illustrates the need for a tool to define acceptable MHC disparities. Previously, we noticed that a variety of single MHC class I mismatched allogeneic donor–recipient pairs did not elicit an allogeneic cytotoxic-lymphocyte (CTL) response in vitro if the MHC amino-acid sequences had five or more differences in the α-helices plus five or more differences in the β-sheet (5α5β) (7). To address the clinical relevance of this observation, we analysed CTL precursor (CTLp) assay outcome and SCT outcome in 53 Dutch recipients of a single MHC class I mismatched graft from an unrelated donor. Overall patient survival was 44% after 4 years. In multivariate analysis, recipients of a 5α5β mismatched graft with negative CTLp frequencies in vitro before transplantation demonstrated superior survival: survival at 4 years was 80% as compared to 47% in recipients of other mismatched grafts with negative CTLp frequencies (hazard ratio=0.131; 95% CI=(0.03–0.61); P=0.009). This option of acceptable mismatches may enlarge the pool of potentially acceptable stem cell donors.Bone Marrow Transplantation (2007) 40, 193–200; doi:10.1038/sj.bmt.1705721; published online 28 May 2007 [ABSTRACT FROM AUTHOR]

A prospective randomized phase III study was performed to evaluate whether intensified cytarabine would induce a higher response rate and longer event-free interval as compared to low-dose cytarabine in chronic myeloid leukemia (CML). One hundred and eighteen patients with CML in early chronic phase entered the study. Twenty-eight out of 32 patients assigned to group A received two cycles of a combination of intensified cytarabine and idarubicin followed by interferon alfa (IFN-alpha) maintenance, 28 patients in group B received standard treatment by a combination of low-dose cytarabine and IFN-alpha. Forty-nine patients with a human leukocyte antigen-identical sibling donor proceeded to allogeneic stem cell transplantation (allo-SCT) and nine patients were excluded from the analysis. Hematological response was observed in 97% of the patients in group A vs 86% of the patients in group B during the first year of treatment. In group A, 16 patients (50%) achieved a major cytogenetic response, which compared to seven patients (25%) with a major cytogenetic response in group B. With a median follow-up of 58 months (range 34-76), event-free survival was not significantly different between arms A and B. The estimated 5-year survival rate was 56% in the intensified arm and 77% in the low-dose arm (P = 0.05). Recipients of allo-SCT showed a 5-year estimated survival rate of 55%. Although intensified cytarabine induced a higher initial percentage of major and complete cytogenetic responses, responses were not sustained by IFN-alpha maintenance therapy. [ABSTRACT FROM AUTHOR]

Nutrient resorption from senescing plant tissues is an important determinant of the fitness of plant populations in nutrient-poor ecosystems, because it makes plants less dependent on current nutrient uptake. Moreover, it can have significant “afterlife” effects through its impact on litter chemistry and litter decomposability. Little is known about the effects of climate change on nutrient resorption. We studied the effects of climate change treatments (including winter snow addition, and spring and/or summer warming) on nutrient resorption of four dominant species in a nutrient-poor subarctic peatland. These species were Betula nana (woody deciduous), Vaccinium uliginosum (woody deciduous), Calamagrostis lapponica (graminoid) and Rubus chamaemorus (forb). After five years of treatments both mature and senesced leaf N concentrations showed a small but significant overall reduction in response to the climate treatments. However, the effects were species-specific. For example, in the controls the N concentration in senesced leaves of Calamagrostis (3.0±0.2 mg N g−1) was about four times lower than for Rubus (11.2±0.2 mg N g−1). There were no significant treatment effects on N resorption efficiency (% of the N pool in mature leaves that is resorbed during senescence). The nitrogen resorption efficiency of Calamagrostis (about 80%) was higher than in the other three species (about 60%). Thus, climate change has only a minor impact on nutrient resorption parameters. However, given the substantial interspecific differences in these parameters, substantial changes in plant–soil feedbacks may be expected as a result of the observed changes in the species composition of high-latitude vegetation. These changes are species-specific and thus difficult to predict. [ABSTRACT FROM AUTHOR]

We compared the kinetics of T-cell recovery after extensive ex vivo and in vivo T-cell depleted autologous stem cell transplantation (SCT) for multiple sclerosis (MS; n=8) with unmodified SCT for hematological malignancies (HM; n=39). Both patient group showed a very protracted recovery of ‘naive’ CD4+, 45R0− (≈CD45RA+) T-cells. Within the ‘primed’ CD4+, 45R0+ T-cells, the ‘central memory’ cells expressing the CD62L and CD27 markers were the slowest to recover. The repopulating T-cells were highly activated, as shown by increased expression of HLA-DR and the apoptosis marker CD95. The capability of CD4+ and CD8+ T-cells to produce IFN-γ, IL-2 and TNF-α had reached normal ranges from 2 months post SCT onwards. Unexpectedly, the kinetics of T-cell recovery between 3 and 12 months post transplant was similar in T-depleted and unmodified SCT. Before SCT, the HM patients showed lymphopenia of all T-cell subsets, upregulated HLA-DR and CD95 expression and increased cytokine responses. We suggest that the similar kinetics of T-cell recovery in the two patient groups may be explained by the susceptibility to apoptosis of the activated CD4+ T-cells in the autografts of the HM patients. This susceptibility to apoptosis would interfere with a swift and sustained CD4+ T-cell regeneration post SCT.Bone Marrow Transplantation (2006) 37, 763–772. doi:10.1038/sj.bmt.1705333; published online 6 March 2006 [ABSTRACT FROM AUTHOR]

Plant traits have become popular as predictors of interspecific variation in important ecosystem properties and processes. Here we introduce foliar pH as a possible new plant trait, and tested whether (1) green leaf pH or leaf litter pH correlates with biochemical and structural foliar traits that are linked to biogeochemical cycling; (2) there is consistent variation in green leaf pH or leaf litter pH among plant types as defined by nutrient uptake mode and higher taxonomy; (3) green leaf pH can predict a significant proportion of variation in leaf digestibility among plant species and types; (4) leaf litter pH can predict a significant proportion of variation in leaf litter decomposability among plant species and types. We found some evidence in support of all four hypotheses for a wide range of species in a subarctic flora, although cryptogams (fern allies and a moss) tended to weaken the patterns by showing relatively poor leaf digestibility or litter decomposability at a given pH. Among seed plant species, green leaf pH itself explained only up to a third of the interspecific variation in leaf digestibility and leaf litter up to a quarter of the interspecific variation in leaf litter decomposability. However, foliar pH substantially improved the power of foliar lignin and/or cellulose concentrations as predictors of these processes when added to regression models as a second variable. When species were aggregated into plant types as defined by higher taxonomy and nutrient uptake mode, green-specific leaf area was a more powerful predictor of digestibility or decomposability than any of the biochemical traits including pH. The usefulness of foliar pH as a new predictive trait, whether or not in combination with other traits, remains to be tested across more plant species, types and biomes, and also in relation to other plant or ecosystem traits and processes. [ABSTRACT FROM AUTHOR]

During the past three decades the Earth has warmed with a rate unprecedented during the past 1000 years. There is already ample evidence that this fast climate warming has affected a broad range of organisms, including plants. Plants from high-latitude and high-altitude sites (‘cold biomes’) are especially sensitive to climate warming. In this paper we (1) review the response in the phenology of plants, changes in their range and distribution, soil nutrient availability, and the effects on the structure and dynamics of plant communities for cold, northern biomes; and (2) we show, by using data from an ongoing snow and temperature manipulation experiment in northern Sweden, that also winter and spring events have a profound influence on plant performance. Both long-term phenological data sets, experimental warming studies (performed in summer or year-round), natural gradient studies and satellite images show that key phenological events are responsive to temperature increases and that recent climate warming does indeed lead to changes in plant phenology. However, data from a warming and snow manipulation study that we are conducting in northern Sweden show that plants respond differently to the various climatic scenarios that we had imposed on these species and that especially winter and spring events have a profound impact. This indicates that it is necessary to include several scenarios of both summer and winter climate change in experimental climate change studies, and that we need detailed projections of future climate at a regional scale to be able to assess their impacts on natural ecosystems. There is also ample evidence that the range shift of herbs and shrubs to more northern regions is for the vast majority of species mainly caused by changes in the climate. This is in line with the observed ‘up-greening’ of northern tundra sites. These rapid northern shifts in distribution of plants as a result of climate warming may have substantial consequences for the structure and dynamics of high-latitude ecosystems. An analysis of warming studies at 9 tundra sites shows that heating during at least 3 years increased net N-mineralization from 0.32±0.31 (SE) g N m−2 yr−1 in the controls to 0.53±0.31 (SE) g N m−2 yr−1 in the heated plots ( p<0.05), an increase of about 70%. Thus, warming leads to higher N availability in high-latitude northern tundra sites, but the variability is substantial. Higher nutrient availability affects in turn the species composition of high-latitude sites, which has important consequences for the carbon and water balance of these systems. [ABSTRACT FROM AUTHOR]