Effect of an extreme flood event on solute transport and resilience of a mine water treatment system in a mineralised catchment.

Extreme rainfall events are predicted to become more frequent with climate change and can have a major bearing on instream solute and pollutant transport in mineralised catchments. The Coledale Beck catchment in north-west England was subject to an extreme rainfall event in December 2015 that equated to a 1 in 200-year event. The catchment contains the UK's first passive metal mine water treatment system, and as such had been subject to intense monitoring of solute dynamics before and after commissioning. Due to this monitoring record, the site provides a unique opportunity to assess the effects of a major storm event on (1) catchment-scale solute transport, and (2) the resilience of the new and novel passive treatment system to extreme events. Monitoring suggests a modest decline in treatment efficiency over time that is not synchronous with the storm event and explained instead by changes in system hydraulic efficiency. There was no apparent flushing of the mine system during the event that could potentially have compromised treatment system performance. Analysis of metal transport in the catchment downstream of the mine suggests relatively subtle changes in instream chemistry with modest but statistically-significant reductions in zinc in the lower catchment irrespective of flow condition after the extreme event, but most parameters of interest show no significant change. Increased export of colloidal iron and aluminium is associated with major landslips in the mid-catchment after the storm and provide fresh sorption sites to attenuate dissolved zinc more rapidly in these locations, corroborated by laboratory experiments utilising site materials to investigate the attenuation/release of metals from stream and terrestrial sediments. The data are important as they show both the resilience of passive mine water treatment systems to extreme events and the importance of catchment-scale monitoring to ensure continued effectiveness of treatment initiatives after major perturbation.

[Breast ductal carcinoma in situ with microinvasion: pathological review and clinical implications]. / Carcinome canalaire in situ avec micro-invasion : spécificités anatomopathologiques et implications cliniques.

PURPOSE: Recent improvements in the detection of breast cancer at an early stage have resulted in a rising incidence of breast ductal carcinoma in situ with microinvasion. So far, there is no consensus regarding its optimal management. We hereby report on our 10-year single institutional experience in breast ductal carcinoma in situ with microinvasion including pathological reviewing. PATIENTS AND METHODS: All consecutive patients treated for a ductal carcinoma in situ with microinvasion at the Institut Claudius-Regaud (Toulouse, France) over a 10-year period were included in this study. We reviewed all available histological materials. RESULTS: Sixty-three patients were eligible for this study. Two patients presented with a lymph node invasion at diagnosis. Each patient benefited from initial surgical management, which consisted either in mastectomy (n=25) or conservative resection (n=37). Axillary exploration was performed in 52 patients (82%). After a median follow-up of 61.3 months [46.9;69], the 5-year overall survival and disease free survival were 98.2 (95% CI=[88.2;99.7]) and 89.5% (95% CI=[76.3;95.6]) respectively. Two delayed invasive relapses occurred leading to one specific death. The pathological review highlighted a trend towards a loss of HR and HER2 expression (9%) in the microinvasive component in comparison with its surrounded in situ carcinoma. CONCLUSION: The risk of initial lymph node involvement and delayed invasive local relapse deserve an optimal locoregional management including lymph node evaluation. The non-negligible discrepancy's rate between in situ and microinvasive components justifies HR status and HER2 expression assessment on the microinvasive component.

Microenvironment mesenchymal cells protect ovarian cancer cell lines from apoptosis by inhibiting XIAP inactivation.

Epithelial ovarian carcinoma is characterized by high frequency of recurrence (70% of patients) and carboplatin resistance acquisition. Carcinoma-associated mesenchymal stem cells (CA-MSC) have been shown to induce ovarian cancer chemoresistance through trogocytosis. Here we examined CA-MSC properties to protect ovarian cancer cells from carboplatin-induced apoptosis. Apoptosis was determined by Propidium Iodide and Annexin-V-FITC labelling and poly-ADP-ribose polymerase cleavage analysis. We showed a significant increase of inhibitory concentration 50 and a 30% decrease of carboplatin-induced apoptosis in ovarian cancer cells incubated in the presence of CA-MSC-conditioned medium (CM). A molecular analysis of apoptosis signalling pathway in response to carboplatin revealed that the presence of CA-MSC CM induced a 30% decrease of effector caspases-3 and -7 activation and proteolysis activity. CA-MSC secretions promoted Akt and X-linked inhibitor of apoptosis protein (XIAP; caspase inhibitor from inhibitor of apoptosis protein (IAP) family) phosphorylation. XIAP depletion by siRNA strategy permitted to restore apoptosis in ovarian cancer cells stimulated by CA-MSC CM. The factors secreted by CA-MSC are able to confer chemoresistance to carboplatin in ovarian cancer cells through the inhibition of effector caspases activation and apoptosis blockade. Activation of the phosphatidylinositol 3-kinase (PI3K)/Akt signalling pathway and the phosphorylation of its downstream target XIAP underlined the implication of this signalling pathway in ovarian cancer chemoresistance. This study reveals the potentialities of targeting XIAP in ovarian cancer therapy.

Dietary restriction delays aging, but not neuronal dysfunction, in Drosophila models of Alzheimer's disease.

Dietary restriction (DR) extends lifespan in diverse organisms and, in animal and cellular models, can delay a range of aging-related diseases including Alzheimer's disease (AD). A better understanding of the mechanisms mediating these interactions, however, may reveal novel pathways involved in AD pathogenesis, and potential targets for disease-modifying treatments and biomarkers for disease progression. Drosophila models of AD have recently been developed and, due to their short lifespan and susceptibility to genetic manipulation, we have used the fly to investigate the molecular connections among diet, aging and AD pathology. DR extended lifespan in both Arctic mutant Aß42 and WT 4R tau over-expressing flies, but the underlying molecular pathology was not altered and neuronal dysfunction was not prevented by dietary manipulation. Our data suggest that DR may alter aging through generalised mechanisms independent of the specific pathways underlying AD pathogenesis in the fly, and hence that lifespan-extending manipulations may have varying effects on aging and functional declines in aging-related diseases. Alternatively, our analysis of the specific effects of DR on neuronal toxicity downstream of Aß and tau pathologies with negative results may simply confirm that the neuro-protective effects of DR are upstream of the initiating events involved in the pathogenesis of AD.

Hydraulic residence time and iron removal in a wetland receiving ferruginous mine water over a 4 year period from commissioning.

Analysis of residence time distribution (RTD) has been conducted for the UK Coal Authority's mine water treatment wetland at Lambley, Northumberland, to determine the hydraulic performance of the wetland over a period of approximately 4 years since site commissioning. The wetland RTD was evaluated in accordance with moment analysis and modelled based on a tanks-in-series (TIS) model to yield the hydraulic characteristics of system performance. Greater hydraulic performance was seen during the second site monitoring after 21 months of site operation i.e. longer hydraulic residence time to reflect overall system hydraulic efficiency, compared to wetland performance during its early operation. Further monitoring of residence time during the third year of wetland operation indicated a slight reduction in hydraulic residence time, thus a lower system hydraulic efficiency. In contrast, performance during the fourth year of wetland operation exhibited an improved overall system hydraulic efficiency, suggesting the influence of reed growth over the lifetime of such systems on hydraulic performance. Interestingly, the same pattern was found for iron (which is the primary pollutant of concern in ferruginous mine waters) removal efficiency of the wetland system from the second to fourth year of wetland operation. This may therefore, reflect the maturity of reeds for maintaining efficient flow distribution across the wetland to retain a longer residence time and significant fractions of water involved to enhance the extent of treatment received for iron attenuation. Further monitoring will be conducted to establish whether such performance is maintained, or whether efficiency decreases over time due to accumulation of dead plant material within the wetland cells.

Attenuation of mining-derived pollutants in the hyporheic zone: a review.

Mine water pollution is a major cause of surface- and groundwater pollution in former mining districts throughout Europe. It is a potential barrier to achieving good status water bodies, which is a requirement of the EU Water Framework Directive. In the UK, a concerted effort has been made over the last decade or so to address the scientific and practical challenges relating to the remediation of mine water pollution. However, most of this work has focused on remediation of point sources of pollution (typically arising from abandoned mines and shafts), while the behaviour of mine water at the groundwater-surface water interface (the "hyporheic zone") has received far less attention in relevant scientific and engineering literature. The extent of mine water pollution and capacity for its attenuation at the hyporheic zone has not been well quantified while, furthermore, the complex chemical and microbial processes occurring there (specifically with reference to mining-derived pollutants) have not been investigated in any depth. The absence of such data may relate, in a large part, to the difficulty in physically measuring volumes and concentrations associated with these river inputs/exports. A far greater body of literature addresses biogeochemical processes at the hyporheic zone (especially relating to manganese), albeit many such articles relate to aqueous metal dynamics in general, rather than mine water specifically. This paper presents a review of the natural attenuation processes that may limit the movement and availability of mining-derived pollutants at the groundwater-surface water (GW-SW) interface, and specifically within the hyporheic zone. A substantial part focuses on precipitation and adsorption processes at the hyporheic zone, as well as discussing the role of microbial processes in governing metal ion mobility.

Intra-operative injection of Patent Blue V dye to facilitate nodal staging in colorectal cancer.

OBJECTIVES: Routine histopathology may understage colorectal cancer by failing to detect involved lymph nodes. This study examined the feasibility of dye staining those lymph nodes most likely to harbour metastases. PATIENTS AND METHODS: Patent Blue V dye 2.5% was injected intra-operatively into left-sided colorectal carcinomas prior to resection in 19 patients. RESULTS: Blue-stained nodes were found in 12/19 patients (63%). Examination of blue-stained nodes alone correctly identified overall nodal status in 11 (92%) of these 12 patients. CONCLUSION: The technique needs to be refined further. Nonetheless, intra-operative lymph node staining using blue dye offers the prospect of improving the ease and accuracy of nodal staging in colorectal cancer.

Anesthesia for Dupuytren's contracture.

Despite the potential complications of brachial plexus blockade, it remains a reliable and safe form of anesthesia for surgery of the upper extremity. The site of the surgery dictates which of the four approaches to the brachial plexus should be used. When the choice matches the site of surgery, the blocks should be successful in approximately 80% of cases. When supplemented with an additional peripheral block, the success rate is greater than 90% using the axillary and supraclavicular approaches. The duration of the blocks varies from 1 to 12 hours, depending on the choice of anesthetic agent. The addition of epinephrine to the anesthetic agent decreases the rate of tissue uptake of the drug, thereby both lengthening the duration of the block and decreasing the toxicity of the agent. Alkalinizing lidocaine with sodium bicarbonate decreases the latency time and increases the intensity and spread of the block. Surgeons should be aware of the advantages and capabilities of regional anesthesia and should discuss anesthesia options with patients and anesthesiologists.