The morphology and mineral chemistry of gold and associated sulphides at Sheba, Fairview, and New Consort gold mines in the Barberton Greenstone Belt (BGB) identify two main types of mineralization. ...The first type occurs associated with sulphides (mainly pyrite), either as inclusions (10–30μm) or as sub-microscopic gold. The second gold type consists of large gold grains (≥100μm) within the silicates (mostly quartz).
LA-ICP-MS studies reveal that some gold and associated sulphide grains contain high values of Cl, Br, Na, and I. The elemental relationships reflect the different chemistry and precipitation processes of possible source fluids, and identify several episodes of mineralisation in the study area, one of them formed due to a boiling process in a supercritical hydrothermal environment. This paper reports on the compositional characteristics of these gold grains, the significance of the halogen contents, and the implications for possible sources of the gold and associated sulphides.
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•Identification of two distinct ore mineral parageneses in the Barberton gold ores•Minerals from the two types distinguishable on basis of composition•Halogens in some minerals characterize mode of ore formation.•Ore forming process pervasive over entire goldfield with local variation
Within Europe, the management of pyridoxine (B6) non-responsive homocystinuria (HCU) may vary but there is limited knowledge about treatment practice.
A comparison of dietetic management practices of ...patients with B6 non-responsive HCU in European centres.
A cross-sectional audit by questionnaire was completed by 29 inherited metabolic disorder (IMD) centres: (14 UK, 5 Germany, 3 Netherlands, 2 Switzerland, 2 Portugal, 1 France, 1 Norway, 1 Belgium).
181 patients (73% >16years of age) with HCU were identified. The majority (66%; n=119) were on dietary treatment (1–10years, 90%; 11–16years, 82%; and >16years, 58%) with or without betaine and 34% (n=62) were on betaine alone. The median natural protein intake (g/day) on diet only was, by age: 1–10years, 12g; 11–16years, 11g; and >16years, 45g. With diet and betaine, median natural protein intake (g/day) by age was: 1–10years, 13g; 11–16years, 20g; and >16years, 38g. Fifty-two percent (n=15) of centres allocated natural protein by calculating methionine rather than a protein exchange system. A methionine-free l-amino acid supplement was prescribed for 86% of diet treated patients. Fifty-two percent of centres recommended cystine supplements for low plasma concentrations. Target treatment concentrations for homocystine/homocysteine (free/total) and frequency of biochemical monitoring varied.
In B6 non-responsive HCU the prescription of dietary restriction by IMD centres declined with age, potentially associated with poor adherence in older patients. Inconsistencies in biochemical monitoring and treatment indicate the need for international consensus guidelines.
•Dietary management practices of B6 non-responsive HCU from 29 European IMD centres•Clinical treatment choice of low methionine diet declined with increasing patient age.•Diet and betaine treated patients had similar protein intakes to those on diet alone.•Almost all patients (86%) were prescribed a methionine-free l-amino acid supplement.•Inconsistencies in monitoring & treatment suggest international guidelines are needed.
Bean plants were grown to maturity in nutrient solutions and soils to study the influence of Cs and K on the growth and the uptake of K and radioactive and stable Cs. The application of K to ...Cs¹³⁷-treated soils relatively high in exchangeable K had only slight effect on the plant uptake of Cs¹³⁷. Increasing additions of K to Cs¹³⁷-treated nutrient solution decreased the uptake of Cs¹³⁷. In both soils and nutrient solutions, the applications of K increased the K-uptake by plants. It may be concluded that when K is readily available to plants, Cs¹³⁷-uptake will be relatively low, but when K is relatively unavailable in the soils, Cs¹³⁷-uptake will be high and can be reduced by the application of K. Small applications of stable Cs to contaminated soils and nutrient solutions caused a greatly increased Cs¹³⁷-uptake by plants, presumably a carries effect. Large applications of Cs reduced the uptake of Cs¹³⁷ because of isotopie dilution. Up to a certain threshold level, the plant uptake of K increased with that of stable Cs and appeared to be partly non-competitive with Cs. Bean plants discriminated against Cs. The discrimination between Cs and K varied with K-and Cs-concentration in the nutrient media. Cesium was toxic to bean plants. Cesium toxicity symptoms were different from K-deficiency symptoms. The toxic effect of Cs was alleviated to some extent by increasing the application of K. In the soils studied, reduction in plant yields occurred when the application of Cs was greater than 8 per cent of the soil cation-exchange capacity.
The serine protease urokinase-type plasminogen activator (uPA) promotes matrix degradation by many cell types, including the invasive extravillous trophoblast (EVT) of the human placenta. The ...noncatalytic amino-terminal end of uPA binds to uPA receptors (uPARs) expressed by these cells. A highly polarized expression of uPAR-bound uPA at the migration front of EVT cells in situ suggests a functional role of uPA:uPAR interaction in EVT cell migration. The present study examined whether uPA stimulates EVT cell migration, independent of proteolytic function, and investigated some of the signaling pathways involved. Using in vitro-propagated EVT cells in Transwell migration assays, both uPA and its noncatalytic amino-terminal fragment (ATF) were shown to stimulate migration through multiporous polycarbonate (pore size 8 μm) membranes. A uPAR-blocking antibody inhibited basal and ATF-stimulated migration. Migration was found to be stimulated by hypoxic conditions, which upregulates uPAR expression; this stimulation was abrogated with the uPAR-blocking antibody, indicating the role of endogenous uPA in EVT cell migration. Spectrofluorometric measurement of cytosolic calcium in cells treated with uPA and ATF demonstrated a rapid rise in Ca
2+
i, which was prevented by pretreatment of cells with thapsigargin, indicating a release from intracellular stores. Both basal and ATF-mediated migratory responses were suppressed in the presence of selective pharmacological inhibitors LY294002, U73122, and U0126, implicating the respective roles of phosphatidinylinositol 3-kinase (PI 3-K), phospholipase C (PLC), and MEK1/2 in basal and ATF-stimulated migratory capacity. Taken together, these results demonstrate that uPA:uPAR interaction stimulates EVT cell migration, independent of uPA enzymatic activity, using the mitogen-activated protein kinase pathway and calcium signaling events including the participation of PI 3-K and PLC. These findings are relevant to clinical conditions of aberrant trophoblast migration, including spontaneous abortion, preeclampsia, and choriocarcinoma.
Hypotension after traumatic brain injury (TBI) worsens outcome. We published the first report of TBI plus hemorrhagic shock (HS) in mice using a volume-controlled approach and noted increased ...neuronal death. To rigorously control blood pressure during HS, a pressure-controlled HS model is required. Our hypothesis was that a brief, severe period of pressure-controlled HS after TBI in mice will exacerbate functional deficits and neuropathology versus TBI or HS alone. C57BL6 male mice were randomized into four groups (n=10/group): sham, HS, controlled cortical impact (CCI), and CCI+HS. We used a pressure-controlled shock phase (mean arterial pressure MAP=25-27 mm Hg for 35 min) and its treatment after mild to moderate CCI including, a 90 min pre-hospital phase, during which lactated Ringer's solution was given to maintain MAP >70 mm Hg, and a hospital phase, when the shed blood was re-infused. On days 14-20, the mice were evaluated in the Morris water maze (MWM, hidden platform paradigm). On day 21, the lesion and hemispheric volumes were quantified. Neuropathology and hippocampal neuron counts (hematoxylin and eosin H&E, Fluoro-Jade B, and NeuN) were evaluated in the mice (n=60) at 24 h, 7 days, or 21 days (n=5/group/time point). HS reduced MAP during the shock phase in the HS and CCI+HS groups (p<0.05). Fluid requirements during the pre-hospital phase were greatest in the CCI+HS group (p<0.05), and were increased in HS versus sham and CCI animals (p<0.05). MWM latency was increased on days 14 and 15 after CCI+HS (p<0.05). Swim speed and visible platform latency were impaired in the CCI+HS group (p<0.05). CCI+HS animals had increased contusion volume versus the CCI group (p<0.05). Hemispheric volume loss was increased 33.3% in the CCI+HS versus CCI group (p<0.05). CA1 cell loss was seen in CCI+HS and CCI animals at 24 h and 7 days (p<0.05). CA3 cell loss was seen after CCI+HS (p<0.05 at 24 h and 7 days). CA1 cell loss at 21 days was seen only in CCI+HS animals (p<0.05). Brief, severe, pressure-controlled HS after CCI produces robust functional deficits and exacerbates neuropathology versus CCI or HS alone.
Ampullary adenocarcinoma (AAC) is a rare malignancy with great morphological heterogeneity, which complicates the prediction of survival and, therefore, clinical decision-making. The aim of this ...study was to develop and externally validate a prediction model for survival after resection of AAC.
An international multicenter cohort study was conducted, including patients who underwent pancreatoduodenectomy for AAC (2006–2017) from 27 centers in 10 countries spanning three continents. A derivation and validation cohort were separately collected. Predictors were selected from the derivation cohort using a LASSO Cox proportional hazards model. A nomogram was created based on shrunk coefficients. Model performance was assessed in the derivation cohort and subsequently in the validation cohort, by calibration plots and Uno's C-statistic. Four risk groups were created based on quartiles of the nomogram score.
Overall, 1007 patients were available for development of the model. Predictors in the final Cox model included age, resection margin, tumor differentiation, pathological T stage and N stage (8th AJCC edition). Internal cross-validation demonstrated a C-statistic of 0.75 (95% CI 0.73–0.77). External validation in a cohort of 462 patients demonstrated a C-statistic of 0.77 (95% CI 0.73–0.81). A nomogram for the prediction of 3- and 5-year survival was created. The four risk groups showed significantly different 5-year survival rates (81%, 57%, 22% and 14%, p < 0.001). Only in the very-high risk group was adjuvant chemotherapy associated with an improved overall survival.
A prediction model for survival after curative resection of AAC was developed and externally validated. The model is easily available online via www.pancreascalculator.com.
•A prediction model for survival after resection of ampullary adenocarcinoma was created•The model was externally validated with a C-statistic of 0.77•The model may be used to predict 3- and 5-year overall survival in individual patients•Four risk groups were created with statistically significant differences in survival•Only in the very high risk group was adjuvant chemotherapy associated with an improved overall survival
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