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Introduction: Efficacy of lenalidomide plus rituximab (R-LEN) compared to rituximab monotherapy (R-mono) for patients with previously treated follicular lymphoma (FL) was investigated in AUGMENT (NCT01938001). Our aim was to evaluate the cost-effectiveness of R-LEN versus R-mono in this setting from a Dutch perspective., Areas Covered: Cost-effectiveness was assessed through a partitioned survival model from three perspectives (i.e. societal, healthcare, and societal, including future non-medical costs). Patient-level data from AUGMENT informed effectiveness parameters (i.e. long-term survival) and health state utilities. Resource use and prices were based on AUGMENT and the literature. Clinical experts validated efficacy input parameters and results. Uncertainty was explored through sensitivity and scenario analyses., Expert Opinion: R-LEN resulted in 1.7 incremental discounted quality-adjusted life years (QALYs). Total incremental discounted costs were 67,161 EUR from a societal perspective. In conclusion, R-LEN was cost-effective at a willingness-to-pay (WTP) threshold of 50,000 EUR/QALY in the base-case analyses(incremental cost-effectiveness ratio = 40,493 EUR/QALY). Scenario and sensitivity analyses indicated some level of uncertainty regarding this conclusion, depending on the chosen WTP-threshold and perspective.

Data-driven irrigation planning can optimize crop yield and reduce adverse impacts on surface and ground water quality. We evaluated an irrigation scheduling strategy based on soil matric potentials recorded by wireless Watermark (WM) sensors installed in sandy loam and clay loam soils and soil-water characteristic curve data. Five wireless WM nodes (IRROmesh) were installed at each location, where each node consisted of three WM sensors that were installed at 15, 30, and 60 cm depths in the crop rows. Soil moisture contents, at field capacity and permanent wilting points, were determined from soil-water characteristic curves and were approximately 23% and 11% for a sandy loam, and 35% and 17% for a clay loam, respectively. The field capacity level which occurs shortly after an irrigation event was considered the upper point of soil moisture content, and the lower point was the maximum soil water depletion level at 50% of plant available water capacity in the root zone, depending on crop type, root depth, growth stage and soil type. The lower thresholds of soil moisture content to trigger an irrigation event were 17% and 26% in the sandy loam and clay loam soils, respectively. The corresponding soil water potential readings from the WM sensors to initiate irrigation events were approximately 60 kPa and 105 kPa for sandy loam, and clay loam soils, respectively. Watermark sensors can be successfully used for irrigation scheduling by simply setting two levels of moisture content using soil-water characteristic curve data. Further, the wireless system can help farmers and irrigators monitor real-time moisture content in the soil root zone of their crops and determine irrigation scheduling remotely without time consuming, manual data logging and frequent visits to the field.

Information on the long-term effect of management practices on soil C and N stocks is lacking. An experiment was conducted from 2004 to 2011 in the northern Great Plains, USA to examine the effects of tillage, crop rotation, and cultural practice on annualized crop residue (stems + leaves) returned to the soil and grain yield, and soil total C (STC) and total N (STN) stocks at the 0-120 cm depth. Tillage practices were no-tillage (NT) and conventional tillage (CT) and crop rotations were continuous spring wheat ( Triticum aestivum L.) (CW), spring wheat-pea ( Pisum sativum L.) (W-P), spring wheat-barley ( Hordeum vulgaris L.) hay-pea (W-B-P), and spring wheat-barley hay-corn ( Zea mays L.)-pea (W-B-C-P). Cultural practices were traditional (conventional seed rates and plant spacing, conventional planting date, broadcast N fertilization, and reduced stubble height) and improved (variable seed rates and plant spacing, delayed planting, banded N fertilization, and increased stubble height). Crop residue and grain yield were greater with CW and W-P than W-B-P and grain yield was greater with the traditional than the improved practice. The STC at 10-20 and 90-120 cm was greater with CW or W-P than other crop rotations in CT and greater with CW than W-B-P in NT. The STN at 20-40 cm was greater with W-P than CW and W-B-P in CT. With NT and the improved cultural practice, STN at 0-5, 5-10, 20-40, and 60-90 cm was greater with W-P and W-B-C-P than other crop rotations. The STN at 0-10 cm correlated with annualized crop residue and grain yield (r = 0.94-0.97, P ≤ 0.05). Increased crop residue returned to the soil increased soil C stock with CW and W-P and N stock with W-P, but removal of aboveground crop biomass for hay decreased stocks with W-B-P. Increased soil N stock had a beneficial effect on crop grain yield.

Background: Trying to simultaneously achieve developmental milestones and cope with a life-threatening disease may place adolescents and young adults (AYAs) at risk for impaired health-related quality of life (HRQoL) later in life. The aim of this study was to examine differences in HRQoL between AYA lymphoma survivors and a normative population and to determine sociodemographic, clinical and long-term symptom-related factors associated with HRQoL., Material and Methods: This study was part of a longitudinal, population-based survey among lymphoma survivors diagnosed between 1999 and 2012. The AYA survivor sample (18-39 years at time diagnosis) was compared to a sex- and age-matched normative population on HRQoL (EORTC-QLQ-C30) and psychological distress (HADS). Multiple linear regression analyses were conducted to determine factors associated with HRQoL among survivors., Results: One hundred and ninety-eight AYA lymphoma survivors (58%) responded to the study invitation. Compared to an age- and sex-matched normative population (N = 380), significantly and clinically relevant poorer HRQoL was observed for AYA lymphoma survivors in seven specific domains of HRQoL: physical, role, cognitive, emotional, social functioning, fatigue and financial difficulties (all p < 0.05). In addition, AYA lymphoma survivors less often had a spouse/partner and more often had a lower educational level compared to the normative population. Linear regression analyses showed that being unemployed, female gender, having one or more comorbid conditions, high levels of fatigue and psychological distress were most strongly associated with HRQoL., Conclusions: These findings identify specific domains of life in which cancer has a significant and long-term impact for AYA lymphoma survivors. Future investigations are needed to identify and test administrations and timing of psychosocial support interventions having potential to reduce long-term late effects in specific HRQoL domains and promote function and adaptability after cancer treatment.

Aims: To investigate the spectrum of mutations in 20 genes involved in B-cell receptor and/or Toll-like receptor signalling resulting in activation of nuclear factor-κB (NF-κB) in 20 nodal marginal zone lymphomas (NMZLs), 20 follicular lymphomas (FLs), and 11 cases of B-cell lymphoma, unclassifiable (BCL-u)., Methods and Results: Nodal marginal zone lymphomas were diagnosed according to strict criteria, including the expression of at least one putative marginal zone marker (MNDA and/or IRTA1). Cases that showed features of NMZL but did not fulfil all criteria were included as BCL-u. All FLs were required to have a BCL2 rearrangement. Mutations were found in: nine NMZLs, with recurrent mutations in TNFAIP3 and CD79B; 12 FLs, with recurrent mutations in TNFRSF14, TNFAIP3, and CARD11; and five cases of BCL-u, with recurrent mutations in TNFRSF14. TNFRSF14 mutations were present in FL and BCL-u, but not in any of the NMZLs. In the BCL-u group, TNFRSF14 mutations clustered with a FL immunophenotype., Conclusions: These results suggest that TNFRSF14 mutations point towards a diagnosis of FL, and can be used in the sometimes difficult distinction between NMZL and FL, but to apply this in diagnostics would require confirmation in an independent cohort. In addition, the presence or absence of specific mutations in pathways converging on NF-κB could be important for decisions regarding targeted treatment., (© 2016 The Authors. Histopathology Published by John Wiley & Sons Ltd.)

In hematological malignancies complex interactions exist between the immune system, microorganisms and malignant cells. On one hand, microorganisms can induce cancer, as illustrated by specific infection-induced lymphoproliferative diseases such as Helicobacter pylori-associated gastric mucosa-associated lymphoid tissue lymphoma. On the other hand, malignant cells create an immunosuppressive environment for their own benefit, but this also results in an increased risk of infections. Disrupted innate immunity contributes to the neoplastic transformation of blood cells by several mechanisms, including the uncontrolled clearance of microbial and autoantigens resulting in chronic immune stimulation and proliferation, chronic inflammation, and defective immune surveillance and anti-cancer immunity. Restoring dysfunction or enhancing responsiveness of the innate immune system might therefore represent a new angle for the prevention and treatment of hematological malignancies, in particular lymphoid malignancies and associated infections. Recently, it has been shown that cells of the innate immune system, such as monocytes/macrophages and natural killer cells, harbor features of immunological memory and display enhanced functionality long-term after stimulation with certain microorganisms and vaccines. These functional changes rely on epigenetic reprogramming and have been termed 'trained immunity'. In this review the concept of 'trained immunity' is discussed in the setting of lymphoid malignancies. Amelioration of infectious complications and hematological disease progression can be envisioned to result from the induction of trained immunity, but future studies are required to prove this exciting new hypothesis., (Copyright© Ferrata Storti Foundation.)

Purpose: The purpose of the study is to examine differences in perceived impact of cancer (IOC) between adolescents and young adults (AYAs; 18-35 years at cancer diagnosis), adults (36-64 years) and elderly (65-84 years) with a history of (non-)Hodgkin lymphoma. Furthermore, to investigate the association of socio-demographic, clinical and psychological characteristics with IOC; and the association between IOC and health-related quality of life (HRQoL) among AYAs only., Methods: This study is part of a population-based PROFILES registry survey among lymphoma patients diagnosed between 1999 and 2009. Patients (n = 1.281) were invited to complete the IOCv1 and EORTC-QLQ-C30 questionnaires. Response rate was 67 % (n = 861)., Results: AYA lymphoma survivors scored higher on the positive IOC summary scale, compared to adult and elderly patients (p < 0.001), while no significant differences were observed for negative IOC. Among AYAs, females, survivors with a partner, and survivors with elevated psychological distress levels scored significantly higher on the negative IOC summary scale. The negative IOC summary scale was negatively associated with all EORTC QLQ-C30 functioning scales (β ranging from -0.39 to -0.063; p < 0.05). The positive IOC summary scale was negatively associated with the EORTC QLQ-C30 subscale 'Emotional functioning' (β = -0.24; p < 0.05)., Conclusion: AYA, adult and elderly with a history of (non-)Hodgkin lymphoma experienced different types of IOC in terms of positive and negative aspects., Implications for Cancer Survivors: Although AYAs experience a more positive IOC compared to older survivors, some AYAs experience more negative IOC and may require developmentally appropriate interventions to address their specific concerns.

Nodal marginal zone lymphoma (NMZL) is a rare type of B-cell non-Hodgkin lymphoma. This study assessed the clinical features of 56 patients with NMZL in comparison to 46 patients with follicular lymphoma (FL). Patients with NMZL and FL had a largely similar clinical presentation, but patients with FL had a higher disease stage at presentation, more frequent abdominal lymphadenopathy and bone marrow involvement, and showed more common transformation into diffuse large B-cell lymphoma (DLBCL) during the course of disease. Overall survival and event-free survival were similar for patients with NMZL and FL, but factors associated with worse prognosis differed between the two groups. Transformation into DLBCL was associated with a significantly poorer outcome in both groups, but the phenotypes were different: DLBCL arising in FL was mainly of germinal center B-cell phenotype, whereas DLBCL arising in NMZL was mainly of non-germinal center B-cell phenotype.

Little information exists about how global warming potential (GWP) is affected by management practices in agroecosystems. We evaluated the effects of irrigation, tillage, crop rotation, and N fertilization on net GWP and greenhouse gas intensity (GHGI or GWP per unit crop yield) calculated by soil respiration (GWP and GHGI) and organic C (SOC) (GWP and GHGI) methods after accounting for CO emissions from all sources (irrigation, farm operations, N fertilization, and greenhouse gas [GHG] fluxes) and sinks (crop residue and SOC) in a Lihen sandy loam from 2008 to 2011 in western North Dakota. Treatments were two irrigation practices (irrigated vs. nonirrigated) and five cropping systems (conventional-till malt barley [ L.] with N fertilizer [CTBN], conventional-till malt barley with no N fertilizer [CTBO], no-till malt barley-pea [ L.] with N fertilizer [NTB-P], no-till malt barley with N fertilizer, and no-till malt barley with no N fertilizer [NTBO]). While CO equivalents were greater with irrigation, tillage, and N fertilization than without, NO and CH fluxes were 2 to 218 kg CO eq. ha greater in nonirrigated NTBN and irrigated CTBN than in other treatments. Previous year's crop residue and C sequestration rate were 202 to 9316 kg CO eq. ha greater in irrigated NTB-P than in other treatments. Compared with other treatments, GWP and GWP were 160 to 9052 kg CO eq. ha lower in irrigated and nonirrigated NTB-P. Similarly, GHGI and GHGI were lower in nonirrigated NTB-P than in other treatments. Regardless of irrigation practices, NTB-P may lower net GHG emissions more than other treatments in the northern Great Plains., (Copyright © by the American Society of Agronomy, Crop Science Society of America, and Soil Science Society of America, Inc.)

Background: Autologous stem-cell transplantation (autoSCT) is considered a standard treatment of non-frail patients with mantle cell lymphoma (MCL), but little is known about outcome of MCL patients relapsing after autoSCT. We therefore sought to analyse the outcome after autoSCT failure and the efficacy of a rescue stem-cell transplantation (SCT) in this setting., Patients and Methods: Patients with MCL were eligible if they had relapsed after autoSCT performed between 2000 and 2009. A total of 1054 patients could be identified in the EBMT registry. By contacting the transplant centres, a full dataset could be retrieved for 360 patients., Results: Median overall survival (OS) after relapse of the whole study group was 19 months. A long (>12 months) interval between autoSCT and relapse [P < 0.001, hazard ratio (HR) 0.62], primary refractory disease (P < 0.02, HR 1.92), prior high-dose ARA-C treatment (P = 0.04, HR 1.43), and the year of relapse (P = 0.02, HR 0.92) significantly influenced OS from relapse in multivariate analysis. Eighty patients (22%) received a rescue allogeneic SCT (alloSCT). Relapse incidence, non-relapse mortality, and OS 2 years after alloSCT was 33% [confidence interval (95% CI 21% to 45%)], 30% (95% CI 19% to 42%), and 46% (95% CI 33% to 59%), respectively. Remission duration after autoSCT was the only variable significantly affecting the outcome of salvage alloSCT. In contrast, rescue autoSCT was not associated with long-term disease control. However, individual patients survived long term even without salvage transplantation., Conclusions: MCL recurrence within 1 year after autoSCT has an extremely dismal outcome, while the prognosis of patients with longer remission durations after autoSCT is significantly better. AlloSCT may offer the possibility of durable survival when performed for patients with a remission duration of more than 12 months after first autoSCT, but the favourable effect of a salvage alloSCT in this setting needs further validation.

The mortality associated with post-transplant lymphoproliferative disorder (PTLD) induced by EBV infection can be reduced by monitoring EBV by polymerase-chain-reaction and rituximab given pre-emptively. We performed a retrospective analysis of the risk factors for the occurrence of EBV infection/disease and EBV-related mortality among 273 consecutive recipients of a T-cell-depleted allo-SCT during two periods: (a) before the implementation of a comprehensive protocol (2006-2008) and (b) afterwards (2009-2011). EBV infection was detected in 61 (22%) cases, and 28 cases were considered to have had EBV disease. Treatment with antithymocyte globulin was the most important risk factor (odds ratio (OR) 2.4; 95% confidence interval (CI) 1.3-4.2, P=0.001). After implementation of the protocol, in patients experiencing EBV infection, pre-emptive therapy was started more often and sooner (median 3 vs 6 days, P=0.002). Moreover, there were fewer cases of monomorphic PTLD (4/33 (12%) vs 11/28 (39%), P=0.01), and the EBV-related mortality was lower for patients experiencing EBV infection (2/33 (6%) vs 8/28 (29%), OR 0.2; 95% CI 0.05-0.9, P=0.03). The EBV protocol proved feasible and resulted in faster initiation of pre-emptive therapy, the diagnosis in an earlier stage of EBV disease, and decreased EBV-related mortality.

Management practices, such as irrigation, tillage, cropping system, and N fertilization, may influence soil greenhouse gas (GHG) emissions. We quantified the effects of irrigation, tillage, crop rotation, and N fertilization on soil CO, NO, and CH emissions from March to November, 2008 to 2011 in a Lihen sandy loam in western North Dakota. Treatments were two irrigation practices (irrigated and nonirrigated) and five cropping systems (conventional-tilled malt barley [ L.] with N fertilizer [CT-N], conventional-tilled malt barley with no N fertilizer [CT-C], no-tilled malt barley-pea [ L.] with N fertilizer [NT-PN], no-tilled malt barley with N fertilizer [NT-N], and no-tilled malt barley with no N fertilizer [NT-C]). The GHG fluxes varied with date of sampling and peaked immediately after precipitation, irrigation, and/or N fertilization events during increased soil temperature. Both CO and NO fluxes were greater in CT-N under the irrigated condition, but CH uptake was greater in NT-PN under the nonirrigated condition than in other treatments. Although tillage and N fertilization increased CO and NO fluxes by 8 to 30%, N fertilization and monocropping reduced CH uptake by 39 to 40%. The NT-PN, regardless of irrigation, might mitigate GHG emissions by reducing CO and NO emissions and increasing CH uptake relative to other treatments. To account for global warming potential for such a practice, information on productions associated with CO emissions along with NO and CH fluxes is needed., (Copyright © by the American Society of Agronomy, Crop Science Society of America, and Soil Science Society of America, Inc.)

Among greenhouse gases, carbon dioxide (CO(2)) is one of the most significant contributors to regional and global warming as well as climatic change. A field study was conducted to (i) determine the effect of soil characteristics resulting from changes in soil management practices on CO(2) flux from the soil surface to the atmosphere in transitional land from perennial forages to annual crops, and (ii) develop empirical relationships that predict CO(2) flux from soil temperature and soil water content. The CO(2) flux, soil temperature (T(s)), volumetric soil water content (theta(v)) were measured every 1-2 weeks in no-till (NT) and conventional till (CT) malt barley and undisturbed soil grass-alfalfa (UGA) systems in a Lihen sandy loam soil (sandy, mixed, frigid Entic Haplustoll) under irrigated and non-irrigated conditions in western North Dakota. Soil air-filled porosity (epsilon) was calculated from total soil porosity and theta(v) measurements. Significant differences in CO(2) fluxes between land management practices (irrigation and tillage) were observed on some measurement dates. Higher CO(2) fluxes were detected in CT plots than in NT and UGA treatments immediately after rainfall or irrigation. Soil CO(2) fluxes increased with increasing soil moisture (R(2)=0.15, P<0.01) while an exponential relationship was found between CO(2) emission and T(s) (R(2)=0.59). Using a stepwise regression analysis procedure, a significant multiple regression equation was developed between CO(2) flux and theta(v), T(s) (CO(2) flux = e(-3.477+0.123T(s)+6.381theta)(v); R(2)=0.68, P

Management practices can influence soil CO(2) emission and C content in cropland, which can effect global warming. We examined the effects of combinations of irrigation, tillage, cropping systems, and N fertilization on soil CO(2) flux, temperature, water, and C content at the 0- to 20-cm depth from May to November 2005 at two sites in the northern Great Plains. Treatments were two irrigation systems (irrigated vs. non-irrigated) and six management practices that contained tilled and no-tilled malt barley (Hordeum vulgaris L.) with 0 to 134 kg N ha(-1), no-tilled pea (Pisum sativum L.), and a conservation reserve program (CRP) planting applied in Lihen sandy loam (sandy, mixed, frigid, Entic Haplustolls) in western North Dakota. In eastern Montana, treatments were no-tilled malt barley with 78 kg N ha(-1), no-tilled rye (Secale cereale L.), no-tilled Austrian winter pea, no-tilled fallow, and tilled fallow applied in dryland Williams loam (fine-loamy, mixed Typic Argiborolls). Irrigation increased CO(2) flux by 13% compared with non-irrigation by increasing soil water content in North Dakota. Tillage increased CO(2) flux by 62 to 118% compared with no-tillage at both places. The flux was 1.5- to 2.5-fold greater with tilled than with non-tilled treatments following heavy rain or irrigation in North Dakota and 1.5- to 2.0-fold greater with crops than with fallow following substantial rain in Montana. Nitrogen fertilization increased CO(2) flux by 14% compared with no N fertilization in North Dakota and cropping increased the flux by 79% compared with fallow in no-till and 0 kg N ha(-1) in Montana. The CO(2) flux in undisturbed CRP was similar to that in no-tilled crops. Although soil C content was not altered, management practices influenced CO(2) flux within a short period due to changes in soil temperature, water, and nutrient contents. Regardless of irrigation, CO(2) flux can be reduced from croplands to a level similar to that in CRP planting using no-tilled crops with or without N fertilization compared with other management practices.

Reasons for Performing Study: Structural changes in articular cartilage associated with the ageing process require definition for investigators performing developmental and age-related studies, for which information is lacking., Objectives: To 1) determine the onset and end of puberty as defined by serum insulin like growth factor (IGF-I) and IGF-binding protein-3 (IGFBP-3) concentrations and 2) correlate articular-epiphyseal cartilage complex structural changes with the onset and end of puberty., Methods: IGF-I and IGFBP-3 were measured in serum samples from normal female and male horses age 9-715 days to determine peak and steady-state values for horses transitioning through puberty. Osteochondral tissue sections were obtained from horses age 120-840 days (4-28 months) and examined histologically for cartilage canals and tidemark formation., Results: In male and female horses, serum IGF-I/IGFBP-3 concentrations peaked at approximately 225 days, defining the onset of puberty. Cartilage canals were absent from articular cartilage just prior to this time point. IGF-I/IGFBP-3 concentrations declined to steady-state levels at approximately age 450 days, signalling exit from puberty and therefore the beginning of ageing. This time point correlated to initial formation of a tidemark in the osteochondral tissue sections., Conclusions: Horses may be considered pubescent at age 225-450 days, and post pubescent and ageing after age 450 days., Potential Relevance: Defining the normal post natal to post pubescent concentrations for serum IGF-I and serum IGFBP-3 establishes subsets of animals for age-related studies and may be used to monitor horses for abnormally high IGF-I concentrations due to natural disease or subsequent to systemic growth hormone administration.

Simple methods are described that permit the use of either H3BO3 indicator solution or acidified filter disks to collect NH3 liberated by treatment of Kjeldahl digests with NaOH. These methods incorporate modifications to improve reliability, analytical capacity, and convenience. A semimicro digest was diluted to 25 mL with deionized water, and a 10 mL aliquot, containing up to 4 mg N (150 microg N for diffusions into acidified disks), was transferred to a shell vial, which was placed inside a 473 mL (1 pint) Mason jar containing 10 mL 10N NaOH. The NH3 liberated by overturning the vial was collected after 12 to 48 h at ambient temperature, or after 4 h at 45 to 50 degrees C on a hotplate, for quantitative and/or isotope-ratio analyses. With either H3BO3 indicator solution or acidified filter disks, recovery of diffused N was quantitative. Isotope-ratio analyses of diffused N from 15N-labeled chemical, plant, and soil samples were within 3% of analyses using steam distillation.

An apparatus that operates with an isotope-ratio mass spectrometer to automatically perform nitrogen isotope analyses by the Rittenberg technique was modified to permit the use of nitrous oxide (N(2)O) instead of Freon (CCl(2)F(2) or CHClF(2)) for the purging of air prior to hypobromite oxidation of ammonium-N to N(2) in a plastic microplate. Analytical performance was unaffected by the modifications. Up to 768 samples can be processed in a single loading, at a rate of 6 to 12 samples/h. Within the range of 0.2 to 20 atom % (15)N, isotope-ratio analyses of 50 to 200 mug of N using the automated Rittenberg apparatus (ARA) with a double-collector mass spectrometer were accurate to within 0.7%, as compared to manual Rittenberg analyses of 1 mg of N using the same mass spectrometer with a dual-inlet system. Automated analyses of 20mug of N were accurate to within 2%, and automated analyses of 10 mug of N were accurate to within 7%. The relative standard deviation for measurements at the natural abundance level (10 analyses, 20-200 mug of N) was < 0.04 %.