Iron (Fe) oxyhydroxides can be reductively dissolved or transformed under Fe reducing conditions, affecting mineral crystallinity and the sorption capacity for other elements. However, the pathways ...and rates at which these processes occur under natural soil conditions are still poorly understood. Here, we studied Fe oxyhydroxide transformations during reduction-oxidation cycles by incubating mesh bags containing ferrihydrite or lepidocrocite in paddy soil mesocosms for up to 12 weeks. To investigate the influence of close contact with the soil matrix, mesh bags were either filled with pure Fe minerals or with soil mixed with
Fe-labeled Fe minerals. Three cycles of flooding (3 weeks) and drainage (1 week) were applied to induce soil redox cycles. The Fe mineral composition was analyzed with Fe K-edge X-ray absorption fine structure spectroscopy, X-ray diffraction analysis and/or
Fe Mössbauer spectroscopy. Ferrihydrite and lepidocrocite in mesh bags without soil transformed to magnetite and/or goethite, likely catalyzed by Fe(II) released to the pore water by microbial Fe reduction in the surrounding soil. In contrast,
Fe-ferrihydrite in mineral-soil mixes transformed to a highly disordered mixed-valence Fe(II)-Fe(III) phase, suggesting hindered transformation to crystalline Fe minerals. The
Fe-lepidocrocite transformed to goethite and small amounts of the highly disordered Fe phase. The extent of reductive dissolution of minerals in
Fe-mineral-soil mixes during anoxic periods increased with every redox cycle, while ferrihydrite and lepidocrocite precipitated during oxic periods. The results demonstrate that the soil matrix strongly impacts Fe oxyhydroxide transformations when minerals are in close spatial association or direct contact with other soil components. This can lead to highly disordered and reactive Fe phases from ferrihydrite rather than crystalline mineral products and promoted goethite formation from lepidocrocite.
Jarosite is an abundant mineral in acidic environments, often found in acid sulfate soil (ASS) and acid-mine drainage (AMD). As a store of Fe, K, S and acidity, and a scavenger for major and trace ...elements, jarosite plays an important role in the biogeochemistry of acid sulfate environments. When ASS and AMD become anoxic, reducing conditions can set in, producing conditions that are outside the thermodynamic stability field of jarosite. In this study, we investigated the transformation of synthetic and natural jarosite with various degrees of Al-for-Fe substitution under circumneutral anoxic conditions in the presence of Fe(II), to understand the rates and pathways of jarosite and Al-jarosite transformation, the role of competing transformation pathways, the fate of Al during transformation and the different reactivity of natural and synthetic Al-jarosite. Synthetic jarosite (containing 0 %–7 % Al-for-Fe substitution) and a natural Al-substituted jarosite sample from an ASS in Thailand were suspended in solutions of 57Fe(II) at pH 7 for 24 h under anoxic conditions. The chosen experimental conditions mimic the Fe(II) concentrations and pH found in flooded ASS under reducing conditions. Changes in mineral composition of the suspensions were determined by Rietveld analysis of X-ray diffraction patterns at six time points. The fate of Al was determined by XRD, Raman spectroscopy and energy dispersive X-ray spectroscopy analysis of the jarosite and product minerals. Different transformation pathways that occurred simultaneously were traced by using 57Fe Mössbauer spectroscopy and aqueous Fe isotope composition. The analysis showed that 7 % Al-for-Fe substitution in jarosite more than halved the mineral transformation rate compared to unsubstituted jarosite, regardless of the Fe(II) concentrations. Indeed, 7 % Al-for-Fe substitution had a greater effect on the transformation rate than an order-of-magnitude decrease in the Fe(II) concentrations in all Al-for-Fe substitution treatments. The transformation products in all samples were goethite, lepidocrocite and ferrihydrite, with minor amounts of magnetite forming from jarosite with no or low Al-for-Fe substitution reacted with high Fe(II) concentrations. Lepidocrocite was the dominant product in reactors without aluminium, but lepidocrocite was not strongly enriched in 57Fe, suggesting that it may not have formed exclusively from Fe in solution during the Fe(II)-catalysed transformation of other minerals. In high-Al systems, lepidocrocite appeared to be a sink for Al, although its formation in Al-rich samples was suppressed. Natural jarosite reacted more than an order of magnitude more slowly than the synthetic jarosite and Al-jarosite, indicating that the properties of the synthetic jarosite do not completely account for the stability of natural jarosite under anoxic circumneutral conditions. The results provide an important baseline for understanding the drivers of jarosite transformation or stability in ASS and AMD.
Environmental mercury (Hg) pollution is a matter of global concern. Mercury speciation controls its environmental behaviour, and stable isotope ratios can potentially trace Hg movement through ...environmental compartments. Here we investigated Hg in industrially contaminated soils and sediments (Visp, Valais, Switzerland) using concentration and stable isotope analysis (CV-MC-ICP-MS) of total digests, and a four-step sequential extraction procedure. The sequential extraction employed (1) water (labile Hg species), (2) NaOH or Na4P2O7 (organically-bound Hg), (3) hydroxylamine-HCl (Hg bound to Mn and Fe (oxyhydr)oxides), and (4) aqua regia (residual Hg pools). The majority of Hg was extracted in step 4 and up to 36% in step 2. Mercury bound to organic matter was the dominant source of Hg in water, NaOH and Na4P2O7 extracts. Sulfides and colloidal oxide minerals were possible additional sources of Hg in some samples. The inconsistent comparative performance of NaOH and Na4P2O7 extractions showed that these classical extractants may not extract Hg exclusively from the organically-bound pool. Samples taken at the industrial facility displayed the greatest isotopic variation (δ202Hg: −0.80‰ ± 0.14‰ to 0.25‰ ± 0.13‰, Δ199Hg: −0.10‰ ± 0.03‰ to 0.02‰ ± 0.03‰; all 2SD) whereas downstream of the facility there was much less variation around average values of δ202Hg = −0.47‰ ± 0.11‰ and Δ199Hg = −0.05‰ ± 0.03‰ (1SD, n = 19). We interpret the difference as the result of homogenisation by mixing of canal sediments containing Hg from the various sources at the industrial facility with preservation of the mixed industrial Hg signature downstream. In contrast to previous findings, Hg isotopes in the sequential extracts were largely similar to one another (2SD < 0.14‰), likely demonstrating that the Hg speciation was similar among the extracts. Our results reveal that Hg resides in relatively stable soil pools which record an averaged isotope signature of the industrial sources, potentially facilitating source tracing studies with Hg isotope signatures at larger spatial scales further downstream.
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•Variable Hg isotope ratios in contaminated soils and sediments at chemical facility•Soils and sediments downstream exhibited narrow range of mercury isotope ratios.•Sequential extractions demonstrated the dominance of very stable Hg forms in soils.•Isotopic homogeneity of extracts revealed absence of fractionation between Hg pools.•Industry source Hg signatures are mixed and preserved during release and transport.
Treatment options are limited for patients with relapsed/refractory diffuse large B-cell lymphoma (DLBCL). Tumor cells can exploit the programmed death-1 checkpoint pathway to evade immune ...surveillance. In the current study, we evaluated the efficacy and safety of programmed death-1 blockade by nivolumab in patients with relapsed/refractory DLBCL.
In this phase II, open-label study, patients with relapsed/refractory DLBCL who were ineligible for autologous hematopoietic cell transplantation (auto-HCT) or who had experienced failure with auto-HCT received nivolumab 3 mg/kg every 2 weeks. We assessed the efficacy and safety of nivolumab as well as genetic alterations of 9p24.1.
Among 121 treated patients, patients in the auto-HCT-failed cohort (n = 87) received a median of four nivolumab doses and a median of three doses were administered to those in the auto-HCT-ineligible cohort (n = 34). At a median follow-up of 9 months in the auto-HCT-failed cohort and 6 months in the auto-HCT-ineligible cohort, independently assessed objective response rates were 10% and 3%, and median durations of response were 11 and 8 months, respectively. Median progression-free survival and overall survival were 1.9 and 12.2 months in the auto-HCT-failed cohort and 1.4 and 5.8 months in the auto-HCT-ineligible cohort respectively. All three patients with complete remission-3% of the auto-HCT-failed cohort-had durable response (11 or more, 14 or more, and 17 months). Treatment-related grade 3 and 4 adverse events were reported in 24% of patients. The most common were neutropenia (4%), thrombocytopenia (3%), and increased lipase (3%). Of all evaluable samples for 9p24.1 analysis, 16% exhibited low-level copy gain and 3% had amplification.
Nivolumab monotherapy is associated with a favorable safety profile but a low overall response rate among patients with DLBCL who are ineligible for auto-HCT or who experienced failure with auto-HCT. Genetic alterations of 9p24.1 are infrequent in DLBCL.
Most patients with chronic myeloid leukemia (CML) treated with imatinib will relapse if treatment is withdrawn. We conducted a prospective clinical trial of imatinib withdrawal in 40 chronic-phase ...CML patients who had sustained undetectable minimal residual disease (UMRD) by conventional quantitative polymerase chain reaction (PCR) on imatinib for at least 2 years. Patients stopped imatinib and were monitored frequently for molecular relapse. At 24 months, the actuarial estimate of stable treatment-free remission was 47.1%. Most relapses occurred within 4 months of stopping imatinib, and no relapses beyond 27 months were seen. In the 21 patients treated with interferon before imatinib, a shorter duration of interferon treatment before imatinib was significantly associated with relapse risk, as was slower achievement of UMRD after switching to imatinib. Highly sensitive patient-specific BCR-ABL DNA PCR showed persistence of the original CML clone in all patients with stable UMRD, even several years after imatinib withdrawal. No patients with molecular relapse after discontinuation have progressed or developed BCR-ABL mutations (median follow-up, 42 months). All patients who relapsed remained sensitive to imatinib re-treatment. These results confirm the safety and efficacy of a trial of imatinib withdrawal in stable UMRD with frequent, sensitive molecular monitoring and early rescue of molecular relapse.
•Approximately 40% of patients with undetectable minimal residual disease on imatinib can stop treatment without loss of molecular response.•Patients in treatment-free remission still have detectable BCR-ABL DNA several years after stopping imatinib.
Many parts of the world are experiencing a drying climatic trend with significant implications for water resources, especially where there is interaction between surface water and groundwater. Where ...drying leads to a shift in a catchment's hydrological regime, hydrological models may display bias in predictions and therefore degradation in their predictive capacity. We present two modifications to GR4J, a commonly used rainfall–run‐off model, that (a) allow the sensitivity of storage dependant evaporation and streamflow production to differ significantly, effectively mimicking “catchment memory” and (b) account for temporal variation in catchment vegetation cover, for example, due to land use change. We test the original and two modified models on a forested headwater catchment in the south‐west of Australia. In this catchment, a data set of more than 21,000 individual groundwater records collected over a period of more than 40 years chronicles a significant decline in catchment groundwater storage, resulting in a nonstationary streamflow regime. These longer‐term changes were overlaid with a shorter‐term hydrological response to clearing for bauxite mining and subsequent revegetation. The model structural modifications led to substantially improved streamflow prediction when compared with the original model, related to improved ability in the revised models' production store to match changes in the observed groundwater storage within the catchment. The performance of all three models and hence the apparent effectiveness of the modified models was dependent on the hydrological conditions in the calibration period. Best model fits were obtained when the calibration period encompassed both wetter and drier conditions in the hydrological record. The modified models presented here may reduce prediction bias for catchments in other parts of the world where long‐term shifts in hydrologic regime are being experienced and improve prediction for catchments with significant changes in vegetation cover.
Diffuse large B-cell lymphoma (DLBCL) is a heterogeneous disease with variable outcomes. Despite the majority of patients being cured with combination chemoimmunotherapy, up to 30% eventually succumb ...to the disease. Until recently, baseline prognostic assessment has centred on the International Prognostic Index (IPI), although this index is yet to impact strongly on treatment choice. Molecular features such as cell of origin, MYC and BCL-2 genetic alterations and protein overexpression were identified over a decade ago, yet their prognostic value is still not fully elucidated. Adding complexity are the plethora of new clinical, biological and molecular prognostic markers described in the recent literature, most of which lack independent validation, likely act as surrogate markers for those already in common use and have yet to substantially impact on therapeutic decision making. This review comprehensively assesses the value of individual prognostic markers in the clinical setting and their potential to predict response to novel agents, and ways to optimise their use in future research.
We evaluated early disease progression and its impact on overall survival (OS) in previously untreated follicular lymphoma patients in GALLIUM (
), and investigated the effect on early disease ...progression of the two randomization arms: obinutuzumab-based
rituximab-based immunochemotherapy. Cause-specific Cox regression was used to estimate the effect of treatment on the risk of disease progression or death due to disease progression within 24 months of randomization and to analyze OS in patients with or without disease progression after 24 months. Mortality in both groups was analyzed 6, 12, and 18 months post randomization (median follow up, 41 months). Fewer early disease progression events occurred in obinutuzumab (57 out of 601)
rituximab (98 out of 601) immunochemotherapy patients, with an average risk reduction of 46.0% (95%CI: 25.0-61.1%; cumulative incidence rate 10.1%
17.4%). At a median post-progression follow up of 22.6 months, risk of mortality increased markedly following a progression event HR of time-varying progression status, 25.5 (95%CI: 16.2-40.3). Mortality risk was higher the earlier patients progressed within the first 24 months. Age-adjusted HR for OS after 24 months in surviving patients with disease progression
those without was 12.2 (95%CI: 5.6-26.5). Post-progression survival was similar by treatment arm. In conclusion, obinutuzumab plus chemotherapy was associated with a marked reduction in the rate of early disease progression events relative to rituximab plus chemotherapy. Early disease progression in patients with follicular lymphoma was associated with poor prognosis, with mortality risk higher after earlier progression. Survival post progression did not seem to be influenced by treatment arm.
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