Plasma neurofilament heavy chain levels and disease progression in amyotrophic lateral sclerosis: insights from a longitudinal study

Objective To investigate the role of longitudinal plasma neurofilament heavy chain protein (NfH) levels as an indicator of clinical progression and survival in amyotrophic lateral sclerosis (ALS). Methods A cross-sectional study involving 136 clinically heterogeneous patients with ALS and 104 healthy and neurological controls was extended to include a prospective analysis of 74 of these ALS cases, with samplings at approximately 3-month intervals in a follow-up period of up to 3 years. We analysed the correlation between longitudinal NfH-phosphoform levels and disease progression. Temporal patterns of NfH changes were evaluated using multilevel linear regression. Results Baseline plasma NfH levels were higher than controls only in patients with ALS with short disease duration to baseline sampling. Compared with controls, fast-progressing patients with ALS, particularly those with a short diagnostic latency and disease duration, had higher plasma NfH levels at an early stage and lower levels closer to end-stage disease. Lower NfH levels between visits were associated with rapid functional deterioration. We also detected antibodies against NfH, NfH aggregates and NfH cleavage products. Conclusions Disease progression in ALS involves defined trajectories of plasma NfH levels, reflecting speed of neurological decline and survival. Intervisit plasma NfH changes are also indicative of disease progression. This study confirms that longitudinal measurements of NfH plasma levels are more informative than cross-sectional studies, where the time of sampling may represent a bias in the interpretation of the results. Autoantibodies against NfH aggregates and NfH cleavage products may explain the variable expression of plasma NfH with disease progressionThis project was funded by The Motor Neurone Disease Association (Malaspina/Apr13/6097) and Barts and The London Charities (468/1714). LG is the Graham Watts Senior Research Fellow, funded by The Brain Research Trust and the European Community’s Seventh Framework Programme (FP7/2007-2013)

Membrane independent limiting flux for RO and NF membranes fouled by humic acid

The flux decline of reverse osmosis and nanofiltration membranes was investigated under constant pressure conditions during humic acid fouling tests. For a given membrane type under a given feedwater composition, increasing pressure resulted in increased flux reduction and foulant accumulation. A limiting flux seems to exist beyond which the membrane flux cannot be sustained. Membranes with initial fluxes greater than the limiting flux experienced severe fouling and their pseudo stable fluxes approached the limiting flux. Flux reduction was much milder when the initial flux was lower than the limiting flux. Furthermore, the limiting flux seems to be independent of membrane properties, probably due to the dominance of foulant-deposited-foulant interaction upon complete foulant coverage over membrane surfaces. On the other hand, strong dependence of the limiting flux on the feedwater composition was observed. The limiting flux was reduced at higher proton, calcium, and/or background electrolytes concentrations, likely due to reduced electrostatic repulsion under these conditions. © 2007 American Chemical Society.link_to_subscribed_fulltex

Nickel aluminate spinel formation during sintering of simulated Ni-laden sludge and kaolinite

Incorporating Ni-laden waste sludge into kaolinite-based construction ceramic materials appears promising based on the identified nickel bearing phases, evaluated incorporation efficiency and nickel leachability of the products. Nickel aluminate spinel (NiAl2O4) results from sintering kaolinite and nickel oxide between 990 and 1480 °C, with more than 90% incorporation efficiency achieved at 1250 °C and 3 h sintering. At lower temperature (990 °C), NiAl2O4 formed from the reaction between nickel oxide and the defect spinel generated from the kaolinite-mullite reaction series. In addition to sintering temperature and time, four raw material mixing procedures were employed, and the ball-milled slurry samples had the highest nickel incorporation efficiency. Prolonged leach testing of NiO, NiAl2O4 and the product from sintered kaolinite + NiO mixtures was carried out using the TCLP extraction fluid #1 (pH 4.9) to evaluate the product stability, and the results revealed the superiority of spinel products over NiO in stabilizing nickel. © 2006 Elsevier Ltd. All rights reserved.link_to_subscribed_fulltex

Nickel aluminate spinel formation during sintering of simulated Ni-laden sludge and kaolinite

Incorporating Ni-laden waste sludge into kaolinite-based construction ceramic materials appears promising based on the identified nickel bearing phases, evaluated incorporation efficiency and nickel leachability of the products. Nickel aluminate spinel (NiAl2O4) results from sintering kaolinite and nickel oxide between 990 and 1480 °C, with more than 90% incorporation efficiency achieved at 1250 °C and 3 h sintering. At lower temperature (990 °C), NiAl2O4 formed from the reaction between nickel oxide and the defect spinel generated from the kaolinite-mullite reaction series. In addition to sintering temperature and time, four raw material mixing procedures were employed, and the ball-milled slurry samples had the highest nickel incorporation efficiency. Prolonged leach testing of NiO, NiAl2O4 and the product from sintered kaolinite + NiO mixtures was carried out using the TCLP extraction fluid #1 (pH 4.9) to evaluate the product stability, and the results revealed the superiority of spinel products over NiO in stabilizing nickel. © 2006 Elsevier Ltd. All rights reserved.link_to_subscribed_fulltex

Spinel formation for stabilizing simulated nickel-laden sludge with aluminum-rich ceramic precursors

The feasibility of stabilizing nickel-laden sludge from commonly available Al-rich ceramic precursors was investigated and accomplished with high nickel incorporation efficiency. To simulate the process, nickel oxide was mixed alternatively with γ-alumina, corundum, kaolinite, and mullite and was sintered from 800 to 1480 °C. The nickel aluminate spinel (NiAl 2O 4) was confirmed as the stabilization phase for nickel and crystallized with efficiencies greater than 90% for all precursors above 1250 °C and 3-h sintering. The nickel-incorporation reaction pathways with these precursors were identified, and the microstructure and spinel yield were investigated as a function of sintering temperature with fixed sintering time. This study has demonstrated a promising process for forming nickel spinel to stabilize nickel-laden sludge from a wide range of inexpensive ceramic precursors, which may provide an avenue for economically blending waste metal sludges via the building industry processes to reduce the environmental hazards of toxic metals. The correlation of product textures and nickel incorporation efficiencies through selection of different precursors also provides the option of tailoring property-specific products. © 2006 American Chemical Society.link_to_subscribed_fulltex

Formation of copper aluminate spinel and cuprous aluminate delafossite to thermally stabilize simulated copper-laden sludge

The study reported herein indicated the stabilization mechanisms at work when copper-laden sludge is thermally treated with γ-alumina and kaolinite precursors, and evaluated the prolonged leachability of their product phases. Four copper-containing phases - copper oxide (CuO), cuprous oxide (Cu2O), copper aluminate spinel (CuAl2O4), and cuprous aluminate delafossite (CuAlO2) - were found in the thermal reactions of the investigated systems. These phases were independently synthesized for leaching by 0.1M HCl aqueous solution, and the relative leachabilities were found to be CuAl2O4<CuAlO2≪≪Cu2O<CuO. The sintering condition and formation mechanism employed to stabilize copper into CuAl2O4 and CuAlO2 are extensively discussed here. With a 3h of short sintering, it was found that CuAl2O4 could be effectively formed between 850 and 950°C by the γ-alumina precursor. Although kaolinite had a lower incorporation capability than γ-alumina, it was found to transform a considerable amount of copper into CuAl2O4 between 950 and 1000°C. At higher temperatures, CuAlO2 was produced only in the γ-alumina system as the occurrence of Cu2O-cristobalite solution in the kaolinite system precluded the production of CuAlO2. The hypothesis that the spinel formation mechanism has two stages was supported by the results of the changing Cu/Al mole ratio in the system, and the rate-limiting step was identified as the diffusion process in the second stage. © 2010 Elsevier B.V.link_to_subscribed_fulltex