Assessment of oxygen plasma ashing as a pre-treatment for radiocarbon dating

This study investigates the potential of low-temperature oxygen plasma ashing as a technique for decontaminating charcoal and wood samples prior to radiocarbon dating. Plasma ashing is demonstrated to be rapid, controllable and surface-specific, and clear differences are identified in the rate of ashing in different organic materials. However, the ability of plasma ashing to selectively remove these different components is limited in heterogeneous sample matrices. This is because oxidation is confined to the immediate sample surface. Comparison of radiocarbon dates obtained from identical aliquots of contaminated ancient charcoal pre-treated by acid-base-acid (ABA), acid-base-oxidation-stepped combustion (ABOx-SC) and plasma ashing suggests that the technique performs as well as the ABA pre-treatment but does not remove as much contamination as the ABOx-SC technique. Plasma-ashing may be particularly useful in cases where sample size is limiting

An investigation of the nature and reactivity of the carbonaceous species deposited on mordenite by reaction with methanol

An investigation of the nature of the carbonaceous species deposited upon mordenite by reaction with methanol has been undertaken. The nature of the species has been shown to be a strong function of both temperature and time on stream. Upon reaction at 300 degrees C a range of alkyl and aromatic species, consistent with the development of an active hydrocarbon pool, are evident and time on stream studies have shown that these are developed within 5 min. Upon reaction at 500 degrees C, a narrower range of hydrogen deficient aromatic species is evident. Thermal volatilisation analysis (TVA), not previously applied to the study of coked zeolites, is shown to be complementary to the more commonly applied C analysis, C-13 MAS NMR and TGA techniques

Impact of the European Clinical Trials Directive on prospective academic clinical trials associated with BMT

The European Clinical Trials Directive (EU 2001; 2001/20/EC) was introduced to improve the efficiency of commercial and academic clinical trials. Concerns have been raised by interested organizations and institutions regarding the potential for negative impact of the Directive on non-commercial European clinical research. Interested researchers within the European Group for Blood and Marrow Transplantation (EBMT) were surveyed to determine whether researcher experiences confirmed this view. Following a pilot study, an internet-based questionnaire was distributed to individuals in key research positions in the European haemopoietic SCT community. Seventy-one usable questionnaires were returned from participants in different EU member states. The results indicate that the perceived impact of the European Clinical Trials Directive has been negative, at least in the research areas of interest to the EBMT

Influence of production variables and starting material on charcoal stable isotopic and molecular characteristics

We present a systematic study on the effect of starting species, gas composition, temperature, particle size and duration of heating upon the molecular and stable isotope composition of high density (mangrove) and low density (pine) wood. In both pine and mangrove, charcoal was depleted in o13C relative to the starting wood by up to 1.6% and 0.8%, respectively. This is attributed predominantly to the progressive loss of isotopically heavier polysaccharides, and kinetic effects of aromatization during heating. However, the pattern of o13C change was dependant upon both starting species and atmosphere, with different structural changes associated with charcoal production from each wood type elucidated by Solid-State o13C Nuclear Magnetic Resonance Spectroscopy. These are particularly evident at lower temperatures, where variation in the oxygen content of the production atmosphere results in differences in the thermal degradation of cellulose and lignin. It is concluded that production of charcoal from separate species in identical conditions, or from a single sample exposed to different production variables, can result in significantly different o13C of the resulting material, relative to the initial wood. These results have implications for the use of charcoal isotope composition to infer past environmental change

Evidence for B cell exhaustion in chronic graft-versus-host disease

Chronic graft-versus-host disease (cGvHD) remains a major complication of allogeneic hematopoietic stem cell transplantation (HSCT). A number of studies support a role for B cells in the pathogenesis of cGvHD. In this study, we report the presence of an expanded population of CD19+CD21− B cells with features of exhaustion in the peripheral blood of patients with cGvHD. CD21− B cells were significantly increased in patients with active cGvHD compared to patients without cGvHD and healthy controls (median 12.2 versus 2.12 versus 3%, respectively; p < 0.01). Compared with naïve (CD27−CD21+) and classical memory (CD27+CD21+) B cells, CD19+CD21− B cells in cGvHD were CD10 negative, CD27 negative and CD20hi, and exhibited features of exhaustion, including increased expression of multiple inhibitory receptors such as FCRL4, CD22, CD85J, and altered expression of chemokine and adhesion molecules such as CD11c, CXCR3, CCR7, and CD62L. Moreover, CD21− B cells in cGvHD patients were functionally exhausted and displayed poor proliferative response and calcium mobilization in response to B-cell receptor triggering and CD40 ligation. Finally, the frequencies of circulating CD21− B cells correlated with cGvHD severity in patients after HSCT. Our study further characterizes B cells in chronic cGVHD and supports the use of CD21−CD27−CD10− B cell frequencies as a biomarker of disease severity

Nanostructure of cellulose microfibrils in spruce wood

The structure of cellulose microfibrils in wood is not known in detail, despite the abundance of cellulose in woody biomass and its importance for biology, energy, and engineering. The structure of the microfibrils of spruce wood cellulose was investigated using a range of spectroscopic methods coupled to small-angle neutron and wide-angle X-ray scattering. The scattering data were consistent with 24-chain microfibrils and favored a “rectangular” model with both hydrophobic and hydrophilic surfaces exposed. Disorder in chain packing and hydrogen bonding was shown to increase outwards from the microfibril center. The extent of disorder blurred the distinction between the I alpha and I beta allomorphs. Chains at the surface were distinct in conformation, with high levels of conformational disorder at C-6, less intramolecular hydrogen bonding and more outward-directed hydrogen bonding. Axial disorder could be explained in terms of twisting of the microfibrils, with implications for their biosynthesis

Melphalan 140mg/m2 or 200mg/m2 for autologous transplantation in myeloma: results from the Collaboration to Collect Autologous Transplant Outcomes in Lymphoma and Myeloma (CALM) study. A report by the EBMT Chronic Malignancies Working Party

Melphalan at a dose of 200mg/m2 is standard conditioning prior to autologous haematopoietic stem cell transplantation for multiple myeloma, but a dose of 140mg/m2 is often used in clinical practice in patients perceived to be at risk of excess toxicity. To determine if melphalan 200 and melphalan 140 are equally effective and tolerable in clinically relevant patient subgroups we analysed 1964 first single autologous transplantation episodes using a series of Cox proportional-hazards models. Overall survival, progression-free survival, cumulative incidence of relapse, non-relapse mortality, haematopoietic recovery and second primary malignancy rates were not significantly different between the melphalan 140 (n=245) and melphalan 200 (n=1719) groups. Multivariable subgroup analysis showed that disease status at transplantation interacted with overall survival, progression-free survival, and cumulative incidence of relapse, with a significant advantage associated with melphalan 200 in patients transplanted in less than partial response (adjusted hazard ratios for melphalan 200 versus melphalan 140: 0.5, 0.54, and 0.56). In contrast, transplantation in very good partial or complete response significantly favoured melphalan 140 for overall survival (adjusted hazard ratio: 2.02). Age, renal function, prior proteasome inhibitor treatment, gender, or Karnofsky score did not interact with overall/progression-free survival or relapse rate in the melphalan dose groups. There were no significant survival or relapse rate differences between melphalan 200 and melphalan 140 patients with high-risk or standard-risk chromosomal abnormalities. In conclusion, remission status at the time of transplantation may favour melphalan 200 or melphalan 140 for key transplant outcomes (NCT01362972)

Eradication of chronic myeloid leukemia stem cells: a novel mathematical model predicts no therapeutic benefit of adding G-CSF to imatinib

Imatinib mesylate induces complete cytogenetic responses in patients with chronic myeloid leukemia (CML), yet many patients have detectable BCR-ABL transcripts in peripheral blood even after prolonged therapy. Bone marrow studies have shown that this residual disease resides within the stem cell compartment. Quiescence of leukemic stem cells has been suggested as a mechanism conferring insensitivity to imatinib, and exposure to the Granulocyte-Colony Stimulating Factor (G-CSF), together with imatinib, has led to a significant reduction in leukemic stem cells in vitro. In this paper, we design a novel mathematical model of stem cell quiescence to investigate the treatment response to imatinib and G-CSF. We find that the addition of G-CSF to an imatinib treatment protocol leads to observable effects only if the majority of leukemic stem cells are quiescent; otherwise it does not modulate the leukemic cell burden. The latter scenario is in agreement with clinical findings in a pilot study administering imatinib continuously or intermittently, with or without G-CSF (GIMI trial). Furthermore, our model predicts that the addition of G-CSF leads to a higher risk of resistance since it increases the production of cycling leukemic stem cells. Although the pilot study did not include enough patients to draw any conclusion with statistical significance, there were more cases of progression in the experimental arms as compared to continuous imatinib. Our results suggest that the additional use of G-CSF may be detrimental to patients in the clinic