MINERALOGICAL AND TEXTURAL EVOLUTION OF THE ECONOMIC MANGANESE MINERALIZATION IN WESTERN RHODOPE MASSIF, N GREECE

The western Rhodope massif contains a significant number of 'battery grade' Mn-oxide deposits which are best developed in the area near Kato Nevrokopi, Drama district, N. Greece. Economic Mn-oxide ore concentrations are confined to fault zones and related karsts in marbles. The mineralisation has formed by weathering of hydrothermal veins that were genetically related to Oligocene magmatism. At Kato Nevrokopi, progressive and continuous weathering of primary, hydrothermal veins of rhodochrosite, mixed sulphide, quartz and 'black calcite' (calcite and todorokite) has resulted in the formation of the assemblage MnO-gel-(amorphous Mn-oxide)-todorokite-azurite-goethite-cerussite in the veins and the assemblage MnO-gel-nsutite-chalcophanite-birnessite-cryptomelane-pyrolusite and malachite and amorphous Fe-oxides in karstic cavities. The f(S)2 and f(O)2 of the hydrothermal fluids increased with time. The breakdown of the hypogene Mn-carbonate was aided by the production of an acidic fluid due to the oxidation of sulphides. Precipitation of the supergene ores was caused by neutralisation of the fluids due to reaction with the host marble and to mixing of relatively reduced fluids with oxygenated surface water in a fluctuation water table regime. Zinc was also mobile during weathering and became concentrated in the intermediate Mn-oxides, effectively stabilising their structures. The mineral paragenesis records the progressive oxidation of the ore and the appearance of less hydrated Mn-oxides, low in alkalis and alkaline earths

A controlled study of hand function in nodal and erosive osteoarthritis.

Hand function using a standardised test of activities of daily living was assessed in (a) 57 patients (53 female, four male; mean age 69 years) with established (that is, symptom onset greater than 10 years before) nodal generalised osteoarthritis (NGOA); (b) 10 patients (nine female, one male; mean age 70 years) with established erosive osteoarthritis (EOA); and (c) 52 matched controls (48 female, four male; mean age 71 years) with asymptomatic, clinically normal hands. Although significant differences between controls and patient groups were observed for individual tasks, only minor global impairment was seen, the worst function occurring in patients with EOA. There was no consistent correlation between tested aspects of hand function and extent of radiographic change assessed by summated graded score for separate osteoarthritic features in individual joints. In controls increasing age correlated with longer time to complete all tasks and weaker power grip; a similar, less pronounced correlation occurred in patients. Differences between controls and patients with NGOA were most apparent in younger subjects; in the elderly (greater than 80 years) hand function was essentially the same. This study shows good functional outcome for patients with NGOA, and suggests that the OA process is of little functional importance to the aging hand

Fine scale depth regulation of invertebrate larvae around coastal fronts

Vertical migrations of zooplankters have been widely described, but their active movements through shallow, highly dynamic water columns within the inner shelf may be more complex and difficult to characterize. In this study, invertebrate larvae, currents, and hydrographic variables were sampled at different depths during and after the presence of fronts on three different cruises off the southern coast of South Africa. Internal wave dynamics were observed in the hydrographic data set but also through satellite imagery, although strong surface convergent currents were absent and thermal stratification was weak. During the first two cruises, fronts were more conspicuous and they preceded strong onshore currents at depth which developed with the rising tide. Vertical distributions of larvae changed accordingly, with higher abundances at these deep layers once the front disappeared. The third cruise was carried out during slack tides, the front was not conspicuous, deep strong onshore currents did not occur afterward and larval distributions did not change consistently through time. Overall, the vertical distributions of many larval taxa matched the vertical profiles of shoreward currents and multivariate analyses revealed that these flows structured the larval community, which was neither influenced by temperature nor chlorophyll. Thus, the ability to regulate active vertical positioning may enhance shoreward advection and determine nearshore larval distributions

Clinical Utility of Random Anti–Tumor Necrosis Factor Drug–Level Testing and Measurement of Antidrug Antibodies on the Long-Term Treatment Response in Rheumatoid Arthritis

Objective: To investigate whether antidrug antibodies and/or drug non-trough levels predict the long-term treatment response in a large cohort of patients with rheumatoid arthritis (RA) treated with adalimumab or etanercept and to identify factors influencing antidrug antibody and drug levels to optimize future treatment decisions.  Methods: A total of 331 patients from an observational prospective cohort were selected (160 patients treated with adalimumab and 171 treated with etanercept). Antidrug antibody levels were measured by radioimmunoassay, and drug levels were measured by enzyme-linked immunosorbent assay in 835 serial serum samples obtained 3, 6, and 12 months after initiation of therapy. The association between antidrug antibodies and drug non-trough levels and the treatment response (change in the Disease Activity Score in 28 joints) was evaluated.  Results: Among patients who completed 12 months of followup, antidrug antibodies were detected in 24.8% of those receiving adalimumab (31 of 125) and in none of those receiving etanercept. At 3 months, antidrug antibody formation and low adalimumab levels were significant predictors of no response according to the European League Against Rheumatism (EULAR) criteria at 12 months (area under the receiver operating characteristic curve 0.71 [95% confidence interval (95% CI) 0.57, 0.85]). Antidrug antibody–positive patients received lower median dosages of methotrexate compared with antidrug antibody–negative patients (15 mg/week versus 20 mg/week; P = 0.01) and had a longer disease duration (14.0 versus 7.7 years; P = 0.03). The adalimumab level was the best predictor of change in the DAS28 at 12 months, after adjustment for confounders (regression coefficient 0.060 [95% CI 0.015, 0.10], P = 0.009). Etanercept levels were associated with the EULAR response at 12 months (regression coefficient 0.088 [95% CI 0.019, 0.16], P = 0.012); however, this difference was not significant after adjustment. A body mass index of ≥30 kg/m2 and poor adherence were associated with lower drug levels.  Conclusion: Pharmacologic testing in anti–tumor necrosis factor–treated patients is clinically useful even in the absence of trough levels. At 3 months, antidrug antibodies and low adalimumab levels are significant predictors of no response according to the EULAR criteria at 12 months

Simultaneous ALS and SCA2 associated with an intermediate-length ATXN2 CAG-repeat expansion

Spinocerebellar ataxia type 2 (SCA2) and amyotrophic lateral sclerosis (ALS) share a common molecular basis: both are associated with CAG-repeat expansion of ATXN2 and TDP-43-positive neuronal cytoplasmic inclusions. To date, the two disorders are viewed as clinically distinct with ALS resulting from 30-33 CAG-repeats and SCA2 from >34 CAG-repeats. We describe a 67-year old with a 32 CAG-repeat expansion of ATXN2 who presented with simultaneous symptoms of ALS and SCA2. Our case demonstrates that the clinical dichotomy between SCA2 and ATXN2-ALS is false. We suggest instead that CAG-repeat expansion length determines the timing of SCA2 clinical symptoms relative to onset of ALS; consistent with this age of onset of SCA2 but not ATXN2-ALS, is dependent upon expansion length. Review of the literature and our local cohort provides evidence for occurrence of ALS in late stage SCA2, which may be under-recognised by clinicians who think of the two diseases as distinct

Control of nanoparticle size, reactivity and magnetic properties during the bioproduction of magnetite by Geobacter sulfurreducens

The bioproduction of nano-scale magnetite by Fe(III)-reducing bacteria offers a potentially tunable, environmentally benign route to magnetic nanoparticle synthesis. Here, we demonstrate that it is possible to control the size of magnetite nanoparticles produced by Geobacter sulfurreducens, by adjusting the total biomass introduced at the start of the process. The particles have a narrow size distribution and can be controlled within the range of 10-50 nm. X-ray diffraction analysis indicates that controlled production of a number of different biominerals is possible via this method including goethite, magnetite and siderite, but their formation is strongly dependent upon the rate of Fe(III) reduction and total concentration and rate of Fe(II) produced by the bacteria during the reduction process. Relative cation distributions within the structure of the nanoparticles has been investigated by X-ray magnetic circular dichroism and indicates the presence of a highly reduced surface layer which is not observed when magnetite is produced through abiotic methods. The enhanced Fe(II)-rich surface, combined with small particle size, has important environmental applications such as in the reductive bioremediation of organics, radionuclides and metals. In the case of Cr(VI), as a model high-valence toxic metal, optimised biogenic magnetite is able to reduce and sequester the toxic hexavalent chromium very efficiently in the less harmful trivalent form

Genome-Wide Association Study in BRCA1 Mutation Carriers Identifies Novel Loci Associated with Breast and Ovarian Cancer Risk

BRCA1-associated breast and ovarian cancer risks can be modified by common genetic variants. To identify further cancer risk-modifying loci, we performed a multi-stage GWAS of 11,705 BRCA1 carriers (of whom 5,920 were diagnosed with breast and 1,839 were diagnosed with ovarian cancer), with a further replication in an additional sample of 2,646 BRCA1 carriers. We identified a novel breast cancer risk modifier locus at 1q32 for BRCA1 carriers (rs2290854, P = 2.7×10, HR = 1.14, 95% CI: 1.09-1.20). In addition, we identified two novel ovarian cancer risk modifier loci: 17q21.31 (rs17631303, P = 1.4×10, HR = 1.27, 95% CI: 1.17-1.38) and 4q32.3 (rs4691139, P = 3.4×10, HR = 1.20, 95% CI: 1.17-1.38). The 4q32.3 locus was not associated with ovarian cancer risk in the general population or BRCA2 carriers, suggesting a BRCA1-specific association. The 17q21.31 locus was also associated with ovarian cancer risk in 8,211 BRCA2 carriers (P = 2×10). These loci may lead to an improved understanding of the etiology of breast and ovarian tumors in BRCA1 carriers. Based on the joint distribution of the known BRCA1 breast cancer risk-modifying loci, we estimated that the breast cancer lifetime risks for the 5% of BRCA1 carriers at lowest risk are 28%-50% compared to 81%-100% for the 5% at highest risk. Similarly, based on the known ovarian cancer risk-modifying loci, the 5% of BRCA1 carriers at lowest risk have an estimated lifetime risk of developing ovarian cancer of 28% or lower, whereas the 5% at highest risk will have a risk of 63% or higher. Such differences in risk may have important implications for risk prediction and clinical management for BRCA1 carriers. © 2013 Couch et al