An Implementation of a Decision Support Tool to Assess Treatment of Emerging Contaminants in India

This is the final version. Available on open access from Scientific Research Publishing via the DOI in this recordEmerging contaminants have been increasingly studied over the past decade to improve the understanding of their fate, occurrence and toxicological effects on the environment and human health. Originally wastewater treatment plants were not designed to remove these pollutants of emerging concern. However, research is now focusing on determining which existing treatment unit processes are suited to their removal. This research sets out to determine suitable treatment options for thirty nine emerging contaminants including various Pharmaceuticals and Personal Care products. The treatment options used in this study are taken from a developed decision support tool (WiSDOM) which formulates wastewater trains/packages for treatment of wastewater in India. The tool also evaluates the performance of each optimal solution in terms of removal of conventional pollutants (such as biochemical oxygen demand, chemical oxygen demand, total nitrogen, total phosphorous, faecal coliform etc.), using multi-objective genetic algorithms and multi-criteria decision analysis. An Excel Spreadsheet Program (ESP) was developed as an add-on to the tool, allowing the ESP to take an initial concentration of any of the thirty nine emerging contaminant and pass it through the treatment trains (generated/selected by the WiSDOM tool) to determine the removal efficiency. Three scenarios were developed to analyse the removal of emerging contaminants in India. The scenarios were designed to capture the influence of different socio-economic contexts and wastewater characteristics on the treatment technology selection. The tool generated results suggest that the use of constructed wetlands can remove a large proportion of emerging contaminants, resulting in low energy requirements and operational costs and wildlife habitats. However, the land requirement for this process is not always suited to urban areas in India. Advanced oxidation processes were also efficient at removing emerging contaminants. However, the energy requirements for this process were high. Emerging contaminants have different physical and chemical properties; therefore, future evaluations of each chemical should be monitored separately to generate suitable technologies suited to optimal removal.Engineering and Physical Sciences Research Council (EPSRC)European CommissionNatural Environment Research Council (NERC

Iron deficiency in parkinsonism : region-specific iron dysregulation in Parkinson's disease and multiple system atrophy

Alpha synuclein pathology is widespread and found in diverse cell types in multiple system atrophy (MSA) as compared to Parkinson's disease (PD). The reason for this differential distribution is unknown. Regional differences in the distribution of iron are associated with neurodegenerative diseases, and here we characterize the relationship between iron homeostasis proteins and regional concentration, distribution and form of iron in MSA and PD. In PD substantia nigra, tissue iron and expression of the iron export protein ferroportin increased, while the iron storage protein ferritin expression was unchanged. In the basis pontis of MSA cases, increased total iron concentration coupled with a disproportionate increase in ferritin in dysmorphic microglia and a reduction in ferroportin expression. This is supported by isothermal remanent magnetisation evidence consistent with elevated concentrations of ferritin-bound iron in MSA basis pontis. Conventional opinion holds that excess iron is involved in neurodegeneration. Our data support that this may be the case in PD. While region-specific changes in iron are evident in both PD and MSA, the mechanisms of iron dysregulation appear quite distinct, with a failure to export iron from the MSA basis pontis coupling with significant intracellular accumulation of ferritin iron. This pattern also occurs, to a lesser extent, in the MSA putamen. Despite the excess tissue iron, the manner of iron dysregulation in MSA is reminiscent of changes in anemia of chronic disease, and our preliminary data, coupled with the widespread pathology and involvement of multiple cell types, may evidence a deficit in bioavailabile iron

Optimising wastewater treatment solutions for the removal of contaminants of emerging concern (CECs): A case study for application in India

This is the author accepted manuscript. The final version is available from IWA Publishing via the DOI in this record.The aim of this study was to produce optimal wastewater treatment solutions to calculate the removal of different CECs found in developing countries. A new methodology was developed for a decision support tool (WiSDOM), which focuses on producing treatment solutions suited to treating water for reuse to Indian Water Quality Standards. WiSDOM-CEC analyses the removal of CECs through different treatment solutions and was also used to evaluate the performance of each treatment train solution in terms of removal of conventional pollutants using multi-objective optimisation and multi criteria decision analysis. Information was collected on different CECs across different regions of India, and the removal of eighteen different CECs through 42 wastewater treatment unit processes for five different regions of India was analysed. Comparisons between similar categories of CECs, such as non-steroidal anti-inflammatory showed that emerging contaminants all react differently to individual treatment options. For example, the removal of Ibuprofen (IBP) and Naproxen (NPX) varied from >80% and 0%, respectively, for a solution in Karnataka involving sedimentation, submerged aerated filter, ultra-filtration and Nano filtration. In Tamil Nadu results ranged from 36.8% to 72% for Diclofenac, 10.7% to 66.5% for IBP and 0% for NPX.European CommissionNatural Environment Research Council (NERC)Engineering and Physical Sciences Research Council (EPSRC

Emerging pollutants in developing countries: Optimising sustainable treatment solutions

This is the author accepted manuscriptOver the past decade the research surrounding the occurrence, source, fate and removal of emerging pollutants has been increasing. The aim of this study was to create an add-on program which analyses the removal of emerging pollutants, to an existing decision support tool (WiSDOM). The tool was also used to evaluate the performance of each optimal solution in terms of removal of conventional pollutants using Multi Objective Genetic Algorithms and Multi Criteria Decision Analysis. Information was collated regarding minimum and maximum concentrations of emerging pollutants for surface water, groundwater, untreated wastewater, drinking water and treated wastewater. This information was used to populate an Excel Spreadsheet Program (ESP) which analysed the removal efficiencies of 13 different emerging pollutants for 42 wastewater treatment unit processes. The ESP is incorporated into the WiSDOM tool to allow the tool to calculate the removal of emerging pollutants. Three main scenarios were created to test the application of the tool and ESP. Scenario 1 focussed on the removal of emerging pollutants from from areas effected by tourism at different scales. Scenario 2 looked at the treatment suited for the removal of emerging pollutants from different socio-economic regions. Lastly, Scenario 3 looked at removing emerging pollutants from hospital and industrial wastewater. The scenarios were focused on wastewater treatment in India and investigated the removal of 13 emerging pollutants commonly found in India.Engineering and Physical Sciences Research Council (EPSRC)European CommissionNatural Environment Research Council (NERC

Sustainable Treatment of Emerging Pollutants in the Context of India

This is the author accepted manuscript.Emerging pollutants have been increasingly studied over the past decade to improve our understanding of their fate, occurrence and toxicological effects on the environment and human health. The aim of this research is to develop a model that calculates the removal of emerging pollutants in India using different treatment unit processes. Different wastewater treatment scenarios based in India were defined considering several variables and factors including: influent water quality, intended use of effluents, available resources, operational envelop and treatment efficiency of technologies. WiSDOM Tool was used to find optimal wastewater trains/packages for treatment keeping in view technical, environmental, social and economic aspects. The tool also evaluates the performance of each optimal solution in terms of removal of current pollutants (such as BOD, COD, TN, TP, FC etc.) using multi-objective genetic algorithms and multi-criteria decision analysis. An Excel spreadsheet model was developed, where the treatment trains (generated/selected by the WiSDOM tool) were passed through to determine the removal efficiency of emerging pollutants. Each emerging pollutant has different physical and chemical properties and therefore, each compound should be monitored separately to generate the optimum removal. Further research is required to bridge the knowledge gap regarding emerging pollutants and their removal during treatment.Part of this study describes work being carried out under EC FP7-funded projects: Grant agreement no: 308672 “Saraswati”. The project sponsors had no involvement in the study design, collection, analysis and interpretation of data or in the writing of the manuscript

Increased markers of cardiac vagal activity in leucine-rich repeat kinase 2-associated Parkinson's disease.

PurposeCardiac autonomic dysfunction manifests as reduced heart rate variability (HRV) in idiopathic Parkinson's disease (PD), but no significant reduction has been found in PD patients who carry the LRRK2 mutation. Novel HRV features have not been investigated in these individuals. We aimed to assess cardiac autonomic modulation through standard and novel approaches to HRV analysis in individuals who carry the LRRK2 G2019S mutation.MethodsShort-term electrocardiograms were recorded in 14 LRRK2-associated PD patients, 25 LRRK2-non-manifesting carriers, 32 related non-carriers, 20 idiopathic PD patients, and 27 healthy controls. HRV measures were compared using regression modeling, controlling for age, sex, mean heart rate, and disease duration. Discriminant analysis highlighted the feature combination that best distinguished LRRK2-associated PD from controls.ResultsBeat-to-beat and global HRV measures were significantly increased in LRRK2-associated PD patients compared with controls (e.g., deceleration capacity of heart rate: p = 0.006) and idiopathic PD patients (e.g., 8th standardized moment of the interbeat interval distribution: p = 0.0003), respectively. LRRK2-associated PD patients also showed significantly increased irregularity of heart rate dynamics, as quantified by Rényi entropy, when compared with controls (p = 0.002) and idiopathic PD patients (p = 0.0004). Ordinal pattern statistics permitted the identification of LRRK2-associated PD individuals with 93% sensitivity and 93% specificity. Consistent results were found in a subgroup of LRRK2-non-manifesting carriers when compared with controls.ConclusionsIncreased beat-to-beat HRV in LRRK2 G2019S mutation carriers compared with controls and idiopathic PD patients may indicate augmented cardiac autonomic cholinergic activity, suggesting early impairment of central vagal feedback loops in LRRK2-associated PD

Deposits of disease-associated alpha-synuclein may be present in the dura mater in Lewy body disorders: implications for potential inadvertent transmission by surgery

Deposition of alpha-synuclein in the brain is a hallmark of Lewy body disorders. Alpha-synuclein has been considered to show prion-like properties. Prion diseases can be transmitted by the transplantation of cadaveric dura mater causing iatrogenic Creutzfeldt-Jakob disease. Recent observations of amyloid-β deposition in dural grafts support the seeding properties of amyloid-β. Here we assessed the presence of alpha-synuclein in dura mater samples as a potential transmissible seed source. We immunostained 32 postmortem dura mater samples; 16 cases with Lewy-body disorder (LBD) showing different pathology stages and 16 non-LBD cases for phosphorylated (Ser129) and disease-associated (5G4) alpha-synuclein. Disease-associated alpha-synuclein aggregates were identified in intradural nerve fibres and associated with a vessel in a single LBD-Braak stage 4 case. We conclude that alpha-synuclein is detectable, although rarely, in dura mater samples in patients with LBD. The risk of potential transmissibility of dural alpha-synuclein deserves assessment by complementary experimental studies

Tumor necrosis factor‐α underlies loss of cortical dendritic spine density in a mouse model of congestive heart failure

BACKGROUND: Heart failure (HF) is a progressive disorder characterized by reduced cardiac output and increased peripheral resistance, ultimately leading to tissue perfusion deficits and devastating consequences for several organs including the brain. We previously described a tumor necrosis factor-α (TNF-α)-dependent enhancement of posterior cerebral artery tone and concomitant reduced cerebral blood flow in a mouse model of early HF in which blood pressure remains minimally affected. HF is often associated with cognitive impairments such as memory deficits, even before any overt changes in brain structure and function occur. The pathophysiology underlying the development of cognitive impairments in HF is unknown, and appropriate treatment strategies are lacking.METHODS AND RESULTS: We used a well-established mouse model in which HF was induced by experimental myocardial infarction produced by permanent surgical ligation of the left anterior descending coronary artery (infarct size ≈25% of the left ventricular wall). Ligated mice developed enlarged hearts, congested lungs, and reduced cardiac output and blood pressure, with elevated peripheral resistance within 6 to 8 weeks after ligation. In this study, we demonstrated the significance of the proinflammatory cytokine TNF-α during HF-mediated neuroinflammation and associated impaired hippocampus-independent nonspatial episodic memory function. Augmented cerebral TNF-α expression and microglial activation in HF mice, indicative of brain inflammation, were accompanied by morphological changes and significant reduction of cortical dendritic spines (61.39±8.61% for basal and 61.04±9.18% for apical spines [P<0.001]). The significance of TNF-α signaling during the observed HF-mediated neurodegenerative processes is supported by evidence showing that sequestration or genetic deletion of TNF-α ameliorates the observed reduction of cortical dendritic spines (33.51±7.63% for basal and 30.13±6.98% for apical spines in wild-type mice treated with etanercept; 17.09±6.81% for basal and 17.21±7.29% for apical spines in TNF-α(-/-)). Moreover, our data suggest that alterations in cerebral serum and glucocorticoid-inducible kinase 1 (SgK1) expression and phosphorylation during HF may be TNF-α dependent and that an increase of SgK1 phosphorylation potentially plays a role in the HF-associated reduction of dendritic spine density.CONCLUSIONS: Our findings demonstrate that TNF-α plays a pivotal role in HF-mediated neuroinflammation and associated alterations of cortical dendritic spine density and has the potential to reveal novel treatment strategies for HF-associated memory deficits

Investigating Voice as a Biomarker for Leucine-Rich Repeat Kinase 2-Associated Parkinson's Disease

We investigate the potential association between leucine-rich repeat kinase 2 (LRRK2) mutations and voice. Sustained phonations ('aaah' sounds) were recorded from 7 individuals with LRRK2-associated Parkinson's disease (PD), 17 participants with idiopathic PD (iPD), 20 non-manifesting LRRK2-mutation carriers, 25 related non-carriers, and 26 controls. In distinguishing LRRK2-associated PD and iPD, the mean sensitivity was 95.4% (SD 17.8%) and mean specificity was 89.6% (SD 26.5%). Voice features for non-manifesting carriers, related non-carriers, and controls were much less discriminatory. Vocal deficits in LRRK2-associated PD may be different than those in iPD. These preliminary results warrant longitudinal analyses and replication in larger cohorts