Driving assessment for maintaining mobility and safety in drivers with dementia.

BACKGROUND: Demographic changes are leading to an increase in the number of older drivers: as dementia is an age-related disease, there is also an increase in the numbers of drivers with dementia. Dementia can impact on both the mobility and safety of drivers, and the impact of formal assessment of driving is unknown in terms of either mobility or safety. Those involved in assessment of older drivers need to be aware of the evidence of positive and negative effects of driving assessment. Cognitive tests are felt by some authors to have poor face and construct validity for assessing driving performance; extrapolating from values in one large-scale prospective cohort study, the cognitive test that most strongly predicted future crashes would, if used as a screening tool, potentially prevent six crashes per 1000 people over 65 years of age screened, but at the price of stopping the driving of 121 people who would not have had a crash. PRIMARY OBJECTIVES: 1. to assess whether driving assessment facilitates continued driving in people with dementia;2. to assess whether driving assessment reduces accidents in people with dementia. SECONDARY OBJECTIVE: 1. to assess the quality of research on assessment of drivers with dementia. SEARCH METHODS: ALOIS, the Cochrane Dementia Group's Specialized Register was searched on 13 September 2012 using the terms: driving or driver* or "motor vehicle*" or "car accident*" or "traffic accident*" or automobile* or traffic. This register contains records from major healthcare databases, ongoing trial databases and grey literature sources and is updated regularly. SELECTION CRITERIA: We sought randomised controlled trials prospectively evaluating drivers with dementia for outcomes such as transport mobility, driving cessation or motor vehicle accidents following driving assessment. DATA COLLECTION AND ANALYSIS: Each review author retrieved studies and assessed for primary and secondary outcomes, study design and study quality. MAIN RESULTS: No studies were found that met the inclusion criteria. A description and discussion of the driving literature relating to assessment of drivers with dementia relating to the primary objectives is presented. AUTHORS' CONCLUSIONS: In an area with considerable public health impact for drivers with dementia and other road users, the available literature fails to demonstrate the benefit of driver assessment for either preserving transport mobility or reducing motor vehicle accidents. Driving legislation and recommendations from medical practitioners requires further research that addresses these outcomes in order to provide the best outcomes for both drivers with dementia and the general public.

Driving assessment for maintaining mobility and safety in drivers with dementia.

BACKGROUND: Demographic changes are leading to an increase in the number of older drivers: as dementia is an age-related disease, there is also an increase in the numbers of drivers with dementia. Dementia can impact on both the mobility and safety of drivers, and the impact of formal assessment of driving is unknown in terms of either mobility or safety. Those involved in assessment of older drivers need to be aware of the evidence of positive and negative effects of driving assessment. Cognitive tests are felt by some authors to have poor face and construct validity for assessing driving performance; extrapolating from values in one large-scale prospective cohort study, the cognitive test that most strongly predicted future crashes would, if used as a screening tool, potentially prevent six crashes per 1000 people over 65 years of age screened, but at the price of stopping the driving of 121 people who would not have had a crash. PRIMARY OBJECTIVES: 1. to assess whether driving assessment facilitates continued driving in people with dementia; 2. to assess whether driving assessment reduces accidents in people with dementia. SECONDARY OBJECTIVE: 1. to assess the quality of research on assessment of drivers with dementia. SEARCH METHODS: ALOIS, the Cochrane Dementia Group's Specialized Register was searched on 13 September 2012 using the terms: driving or driver* or "motor vehicle*" or "car accident*" or "traffic accident*" or automobile* or traffic. This register contains records from major healthcare databases, ongoing trial databases and grey literature sources and is updated regularly. SELECTION CRITERIA: We sought randomised controlled trials prospectively evaluating drivers with dementia for outcomes such as transport mobility, driving cessation or motor vehicle accidents following driving assessment. DATA COLLECTION AND ANALYSIS: Each review author retrieved studies and assessed for primary and secondary outcomes, study design and study quality. MAIN RESULTS: No studies were found that met the inclusion criteria. A description and discussion of the driving literature relating to assessment of drivers with dementia relating to the primary objectives is presented. AUTHORS' CONCLUSIONS: In an area with considerable public health impact for drivers with dementia and other road users, the available literature fails to demonstrate the benefit of driver assessment for either preserving transport mobility or reducing motor vehicle accidents. Driving legislation and recommendations from medical practitioners requires further research that addresses these outcomes in order to provide the best outcomes for both drivers with dementia and the general public.

Expansion of the Conceptual Model for the Accumulation of Selenium in Lentic Food Chains to Include Redox-Controlled Generation and Diffusion of Selenite and Dissolved Organo-Selenium Compounds.

The controls governing the availability of reduced selenium (Se) species, namely selenite (Se[IV]) and dissolved organo-Se (DOSe), to primary producers at the sediment-water interface in depositional environments (i.e., lentic systems) were assessed through consideration of theoretical principles and field data. Selenite is generated in suboxic sediment porewater via the microbially mediated reduction of selenate (Se[IV]) and/or reductive dissolution of Se-bearing iron oxides. Field data for lentic environments demonstrate that the production of DOSe in sediment porewaters can also be redox- and depth-dependent. In this manner, the remobilization depths of Se(IV) and DOSe in depositional environments are dependent on the vertical redox gradient (dEh/dz), where deeper depths of remobilization are observed in less reducing sedimentary environments (lower dEh/dz). In turn, remobilization depth has a direct bearing on the concentration of dissolved Se(IV) and DOSe that may be realized at the sediment-water interface because the depth of reaction governs the diffusive path length, concentration gradient, and rate of diffusional transport toward the sediment-water interface. The principles that link sediment redox gradients, depth of remobilization, diffusive transport processes, and concentration of reduced Se species at the sediment-water interface have a direct bearing on the potential for Se uptake by primary producers in lentic food chains (e.g., phytoplankton, biofilms, bacteria). Overall, these processes complement the current conceptual "benthic detrital food chain" model that describes the accumulation of Se in lentic systems. Environ Toxicol Chem 2022;41:2859-2869. © 2022 SETAC.

Biogeochemical mechanisms of selenium exchange between water and sediments in two contrasting lentic environments.

The biogeochemical mechanisms of Se exchange between water and sediments in two contrasting lentic environments were assessed through examination of Se speciation in the water column, porewater, and sediment. High-resolution (7 mm) vertical profiles of <0.45 µm Se species across the sediment-water interface demonstrate that the behavior of dissolved Se(VI), Se(IV), and organo-Se are closely linked to redox conditions as revealed by porewater profiles of redox-sensitive species (dissolved O2, NO3-, Fe, Mn, SO4(2-), and ΣH2S). At both sites Se(VI) is removed from solution in suboxic near-surface porewaters demonstrating that the sediments are serving as diffusive sinks for Se. X-ray absorption near edge spectroscopy (XANES) of sediments suggests that elemental Se and organo-Se represent the dominant sedimentary sinks for dissolved Se. Dissolved Se(IV) and organo-Se are released to porewaters in the near-surface sediments resulting in the diffusive transport of these species into the water column, where between-site differences in the depths of release can be linked to differences in redox zonation. The presence or absence of emergent vegetation is proposed to present a dominant control on sedimentary redox conditions as well as on the recycling and persistence of reduced Se species in bottom waters.

Quantifying the Association Between Psychotherapy Content and Clinical Outcomes Using Deep Learning.

Importance: Compared with the treatment of physical conditions, the quality of care of mental health disorders remains poor and the rate of improvement in treatment is slow, a primary reason being the lack of objective and systematic methods for measuring the delivery of psychotherapy. Objective: To use a deep learning model applied to a large-scale clinical data set of cognitive behavioral therapy (CBT) session transcripts to generate a quantifiable measure of treatment delivered and to determine the association between the quantity of each aspect of therapy delivered and clinical outcomes. Design, Setting, and Participants: All data were obtained from patients receiving internet-enabled CBT for the treatment of a mental health disorder between June 2012 and March 2018 in England. Cognitive behavioral therapy was delivered in a secure online therapy room via instant synchronous messaging. The initial sample comprised a total of 17 572 patients (90 934 therapy session transcripts). Patients self-referred or were referred by a primary health care worker directly to the service. Exposures: All patients received National Institute for Heath and Care Excellence-approved disorder-specific CBT treatment protocols delivered by a qualified CBT therapist. Main Outcomes and Measures: Clinical outcomes were measured in terms of reliable improvement in patient symptoms and treatment engagement. Reliable improvement was calculated based on 2 severity measures: Patient Health Questionnaire (PHQ-9) and Generalized Anxiety Disorder 7-item scale (GAD-7), corresponding to depressive and anxiety symptoms respectively, completed by the patient at initial assessment and before every therapy session (see eMethods in the Supplement for details). Results: Treatment sessions from a total of 14 899 patients (10 882 women) aged between 18 and 94 years (median age, 34.8 years) were included in the final analysis. We trained a deep learning model to automatically categorize therapist utterances into 1 or more of 24 feature categories. The trained model was applied to our data set to obtain quantifiable measures of each feature of treatment delivered. A logistic regression revealed that increased quantities of a number of session features, including change methods (cognitive and behavioral techniques used in CBT), were associated with greater odds of reliable improvement in patient symptoms (odds ratio, 1.11; 95% CI, 1.06-1.17) and patient engagement (odds ratio, 1.20, 95% CI, 1.12-1.27). The quantity of nontherapy-related content was associated with reduced odds of symptom improvement (odds ratio, 0.89; 95% CI, 0.85-0.92) and patient engagement (odds ratio, 0.88, 95% CI, 0.84-0.92). Conclusions and Relevance: This work demonstrates an association between clinical outcomes in psychotherapy and the content of therapist utterances. These findings support the principle that CBT change methods help produce improvements in patients' presenting symptoms. The application of deep learning to large clinical data sets can provide valuable insights into psychotherapy, informing the development of new treatments and helping standardize clinical practice.

Driving assessment for maintaining mobility and safety in drivers with dementia.

BACKGROUND: Demographic changes are leading to an increase in the number of older drivers: as dementia is an age-related disease, there is also an increase in the numbers of drivers with dementia. Dementia can impact on both the mobility and safety of drivers, and the impact of formal assessment of driving is unknown in terms of either mobility or safety. Those involved in assessment of older drivers need to be aware of the evidence of positive and negative effects of driving assessment. Although cognitive tests are felt by some authors to have poor face and construct validity for assessing driving performance, extrapolating from values in one large-scale prospective cohort study, the cognitive test that most strongly predicted future crashes would, if used as a screening tool, potentially prevent six crashes per 1000 people over 65 screened, but at the price of stopping the driving of 121 people who would not have had a crash. PRIMARY OBJECTIVES: 1. To assess whether driving assessment facilitates continued driving in people with dementia 2. To assess whether driving assessment reduces accidents in people with dementia. SECONDARY OBJECTIVE: To assess the quality of research on assessment of drivers with dementia. SEARCH STRATEGY: The Cochrane Dementia Group's Specialized Register was searched on 30 October 2007 using the terms: driving or driver* or "motor vehicle*" or "car accident*" or "traffic accident*" or automobile* or traffic. This register contains records from major healthcare databases, ongoing trial databases and grey literature sources and is updated regularly. SELECTION CRITERIA: We sought randomized controlled trials prospectively evaluating drivers with dementia for outcomes such as transport mobility, driving cessation or motor vehicle accidents following driving assessment. DATA COLLECTION AND ANALYSIS: Each author retrieved studies and assessed for primary and secondary outcomes, study design and study quality. MAIN RESULTS: No studies were found that met the inclusion criteria. A description and discussion of the driving literature relating to assessment of drivers with dementia relating to the primary objectives is presented. AUTHORS' CONCLUSIONS: In an area with considerable public health impact for drivers with dementia and other road users, the available literature fails to demonstrate the benefit of driver assessment for either preserving transport mobility or reducing motor vehicle accidents. Driving legislation and recommendations from medical practitioners requires further research that addresses these outcomes in order to provide the best outcomes for both drivers with dementia and the general public.

Controls governing the spatial distribution of sediment arsenic concentrations and solid-phase speciation in a lake impacted by legacy mining pollution.

Forty-seven sediment cores were collected as part of a spatial survey of Long Lake, Yellowknife, NWT, Canada to elucidate the physical and geochemical controls on the distribution of arsenic (As) in sediments impacted by the aerial deposition of arsenic trioxide (As2O3) from ore roasting at legacy gold mines. High-resolution profiles of dissolved As in bottom water and porewater were also collected to determine As remobilization and diffusion rates across the sediment-water interface. Arsenic concentrations in Long Lake sediments ranged from 2.2 to 3420 mg kg-1 (dry weight). Two distinct types of sediment As concentration profiles were identified and are interpreted to represent erosional and depositional areas. Water depth is the best predictor of As concentration in the top 5 cm of sediments due to the inferred focusing of fine-grained As2O3 into deeper water. At greater sediment depths, iron (Fe) concentration, as a likely indicator of As, Fe, and sulphur (S) co-diagenesis, was the best predictor of As concentration. The sediments are a source of dissolved As to surface waters through diffusion-controlled release to bottom water. Arsenic concentrations, solid-phase speciation, and diffusive efflux varied laterally across the lake bottom and with sediment depth due to the interplay between sediment-focusing processes and redox reactions, which has implications for human health and ecological risk assessments.

Hydrological and biogeochemical controls governing the speciation and accumulation of selenium in a wetland influenced by mine drainage.

Controls governing the speciation and accumulation of Se in a 3.7-ha marsh influenced by mine drainage were assessed through examination of water balance, water quality, sediment, and plant tissue components. Over the 8-mo study period (April through November, 2009), mean monthly flows ranged from 1600 to 2300 m3 d-1 (hydraulic retention time of 1-3 d). Total Se concentrations in the marsh outflow were lower than the inflow by 0.4 to 6.2 µg L-1 (mean difference = 3.3 µg L-1 ), illustrating Se removal. The Se accumulation pathways are illustrated by elevated concentrations of Se in sediments (3-35 mg kg-1 dry wt) as well as in below-ground (2-41 mg kg-1 dry wt; mean = 10 mg kg-1 dry wt) and above-ground (0.8-6.3 mg kg-1 dry wt; mean = 2 mg kg-1 dry wt) emergent plant tissues. Redox stratification in the shallow water column had a marked effect on Se speciation and behavior, illustrating bottom water removal of dissolved selenate in suboxic horizons and increased mobility of dissolved organo-Se. Mass balance data yielded inflow and outflow loading rates for Se of 27 and 23 g d-1 , respectively (net accumulation rate of 4 g d-1 or 0.11 mg m2 d-1 ). The rate of accumulation as calculated from the mass balance agrees with independently measured rates of Se accumulation in sediments for the site (3.6-8.1 g d-1 or 0.10-0.22 mg m-2 d-1 ). Environ Toxicol Chem 2018;37:1824-1838. © 2018 SETAC.

Speciation, behavior, and bioavailability of copper downstream of a mine-impacted lake.

A combination of Cu speciation analysis and toxicity testwork was conducted to assess the behavior, speciation, and bioavailability of Cu in a stream system rich in dissolved organic carbon (DOC) downstream of a mine-impacted lake (East Lake, ON, Canada). Elevated levels (approximately 50 microg/L) of Cu exist in the lake due to the release of dissolved Cu to the water column from underlying sediments. Most of the Cu present in East Lake and downstream is present as filterable species that represent 74 to 100% of the total. Measurements of labile Cu as measured by diffusive gradients in thin films (DGT) suggest that most of the Cu is unavailable to aquatic biota. The DGT results indicate that 9 to 24% of Cu within the receiving environment is biologically available. Decreases in the labile Cu fraction with distance downstream of East Lake correlate well with increases in the concentration of DOC (r(2) = 0.79-0.95), presumably due to the progressive importance of Cu-organic complexes. The relationship between filterable Cu and SO(4)(2-) downstream of East Lake was linear (r(2) = 0.99) for all sampling periods, suggesting that decreases in filterable Cu concentration downstream of East Lake could be attributed solely to dilution (i.e., conservative behavior). Variations in the filterable Cu concentration resulting in 50% mortality (LC50 = 96-203 microg/L) and the concentration resulting in an inhibition of reproduction by 25% (IC25 = 75-156 microg/L) with respect to Ceriodaphnia dubia (7-d incubation) in Cu-spiked solutions could be explained by differences in labile-Cu concentrations as determined by DGT. The considerable complexation capacity afforded by lake and stream waters can be attributed to complexation of Cu with abundant DOC (7-17 mg/L). The relevance of the toxicity data to water-effect ratio testwork, and the associated development of site-specific water quality objectives, are discussed.

The Menkes and Wilson disease genes counteract in copper toxicosis in Labrador retrievers: a new canine model for copper-metabolism disorders.

The deleterious effects of a disrupted copper metabolism are illustrated by hereditary diseases caused by mutations in the genes coding for the copper transporters ATP7A and ATP7B. Menkes disease, involving ATP7A, is a fatal neurodegenerative disorder of copper deficiency. Mutations in ATP7B lead to Wilson disease, which is characterized by a predominantly hepatic copper accumulation. The low incidence and the phenotypic variability of human copper toxicosis hamper identification of causal genes or modifier genes involved in the disease pathogenesis. The Labrador retriever was recently characterized as a new canine model for copper toxicosis. Purebred dogs have reduced genetic variability, which facilitates identification of genes involved in complex heritable traits that might influence phenotype in both humans and dogs. We performed a genome-wide association study in 235 Labrador retrievers and identified two chromosome regions containing ATP7A and ATP7B that were associated with variation in hepatic copper levels. DNA sequence analysis identified missense mutations in each gene. The amino acid substitution ATP7B:p.Arg1453Gln was associated with copper accumulation, whereas the amino acid substitution ATP7A:p.Thr327Ile partly protected against copper accumulation. Confocal microscopy indicated that aberrant copper metabolism upon expression of the ATP7B variant occurred because of mis-localization of the protein in the endoplasmic reticulum. Dermal fibroblasts derived from ATP7A:p.Thr327Ile dogs showed copper accumulation and delayed excretion. We identified the Labrador retriever as the first natural, non-rodent model for ATP7B-associated copper toxicosis. Attenuation of copper accumulation by the ATP7A mutation sheds an interesting light on the interplay of copper transporters in body copper homeostasis and warrants a thorough investigation of ATP7A as a modifier gene in copper-metabolism disorders. The identification of two new functional variants in ATP7A and ATP7B contributes to the biological understanding of protein function, with relevance for future development of therapy.

A Multi-Center Prospective Derivation and Validation of a Clinical Prediction Tool for Severe Clostridium difficile Infection.

BACKGROUND AND AIMS: Prediction of severe clinical outcomes in Clostridium difficile infection (CDI) is important to inform management decisions for optimum patient care. Currently, treatment recommendations for CDI vary based on disease severity but validated methods to predict severe disease are lacking. The aim of the study was to derive and validate a clinical prediction tool for severe outcomes in CDI. METHODS: A cohort totaling 638 patients with CDI was prospectively studied at three tertiary care clinical sites (Boston, Dublin and Houston). The clinical prediction rule (CPR) was developed by multivariate logistic regression analysis using the Boston cohort and the performance of this model was then evaluated in the combined Houston and Dublin cohorts. RESULTS: The CPR included the following three binary variables: age ≥ 65 years, peak serum creatinine ≥ 2 mg/dL and peak peripheral blood leukocyte count of ≥ 20,000 cells/µL. The Clostridium difficile severity score (CDSS) correctly classified 76.5% (95% CI: 70.87-81.31) and 72.5% (95% CI: 67.52-76.91) of patients in the derivation and validation cohorts, respectively. In the validation cohort, CDSS scores of 0, 1, 2 or 3 were associated with severe clinical outcomes of CDI in 4.7%, 13.8%, 33.3% and 40.0% of cases respectively. CONCLUSIONS: We prospectively derived and validated a clinical prediction rule for severe CDI that is simple, reliable and accurate and can be used to identify high-risk patients most likely to benefit from measures to prevent complications of CDI.

Alteration to lake trophic status as a means to control arsenic mobility in a mine-impacted lake.

The relationship between lake trophic status, sedimentary redox conditions and As mobility was examined in mine-impacted Balmer Lake, Canada. Under the current redox regime, the reductive dissolution of As-bearing Fe(III) oxyhydroxides occurs in close proximity to the sediment-water interface, resulting in the remobilization of dissolved As in the shallow porewaters to values as high as 8.5 mg L(-1). The shallow depth of the oxic zone limits the extent to which As can be re-sorbed in the interfacial horizons, and as a result, a proportion of the remobilized As escapes into the water column where it poses a water quality concern. Examination of the relationship between summer average chlorophyll a and total P at spring overturn in the lake water column demonstrates that Balmer Lake is currently eutrophic as a result of mining-derived inputs of P (domestic waters) and N (blasting residues and cyanide breakdown products). The results suggest that actively pushing the system towards oligotrophy by reducing non-natural P loadings to the system will decrease rates of in situ production and associated sediment oxygen demand, which will in turn result in increased thickness of the aerobic zone and enhanced As scavenging. Such conclusions are supported by porewater data which indicate that the flux of As to the water column is significantly reduced when the Fe(III) redox cline is situated at deeper sediment depths. In the absence of detailed P-loading data, it is recommended that P inputs be reduced to approximately 10% of the estimated pre-mining P loading of approximately 200 kg yr(-1). This implies reducing the collective P-loadings from the two mine sites adjacent to the lake from the approximate current value (approximately 150 kg yr(-1)) to approximately 20 kg yr(-1). It is proposed that establishment of oligotrophy in the lake should significantly mitigate the current level of dissolved As in lake waters.

Molecular recognition of metabotropic glutamate receptor type 1 (mGluR1): synergistic understanding with free energy perturbation and linear response modeling.

Metabotropic glutamate receptors (mGluRs) constitute an important family of the G-protein coupled receptors. Due to their widespread distribution in the central nervous system (CNS), these receptors are attractive candidates for understanding the molecular basis of various cognitive processes as well as for designing inhibitors for relevant psychiatric and neurological disorders. Despite many studies on drugs targeting the mGluR receptors to date, the molecular level details on the ligand binding dynamics still remain unclear. In this study, we performed in silico experiments for mGluR1 with 29 different ligands including known synthetic agonists and antagonists as well as natural amino acids. The ligand-receptor binding affinities were estimated by the use of atomistic simulations combined with the mathematically rigorous, Free Energy Perturbation (FEP) method, which successfully recognized the native agonist l-glutamate among the highly favorable binders, and also accurately distinguished antagonists from agonists. Comparative contact analysis also revealed the binding mode differences between natural and non-natural amino acid-based ligands. Several factors potentially affecting the ligand binding affinity and specificity were identified including net charges, dipole moments, and the presence of aromatic rings. On the basis of these findings, linear response models (LRMs) were built for different sets of ligands that showed high correlations (R(2) > 0.95) to the corresponding FEP binding affinities. These results identify some key factors that determine ligand-mGluR1 binding and could be used for future inhibitor designs and support a role for in silico modeling for understanding receptor ligand interactions.

Genome wide analysis indicates genes for basement membrane and cartilage matrix proteins as candidates for hip dysplasia in Labrador Retrievers.

Hip dysplasia, an abnormal laxity of the hip joint, is seen in humans as well as dogs and is one of the most common skeletal disorders in dogs. Canine hip dysplasia is considered multifactorial and polygenic, and a variety of chromosomal regions have been associated with the disorder. We performed a genome-wide association study in Dutch Labrador Retrievers, comparing data of nearly 18,000 single nucleotide polymorphisms (SNPs) in 48 cases and 30 controls using two different statistical methods. An individual SNP analysis based on comparison of allele frequencies with a χ(2) statistic was used, as well as a simultaneous SNP analysis based on Bayesian variable selection. Significant association with canine hip dysplasia was observed on chromosome 8, as well as suggestive association on chromosomes 1, 5, 15, 20, 25 and 32. Next-generation DNA sequencing of the exons of genes of seven regions identified multiple associated alleles on chromosome 1, 5, 8, 20, 25 and 32 (p<0.001). Candidate genes located in the associated regions on chromosomes 1, 8 and 25 included LAMA2, LRR1 and COL6A3, respectively. The associated region on CFA20 contained candidate genes GDF15, COMP and CILP2. In conclusion, our study identified candidate genes that might affect susceptibility to canine hip dysplasia. These genes are involved in hypertrophic differentiation of chondrocytes and extracellular matrix integrity of basement membrane and cartilage. The functions of the genes are in agreement with the notion that disruptions in endochondral bone formation in combination with soft tissue defects are involved in the etiology of hip dysplasia.

Mortality in patients with Clostridium difficile infection correlates with host pro-inflammatory and humoral immune responses.

Host anti-toxin immune responses play important roles in Clostridium difficile disease and outcome. The relationship between host immune and inflammatory responses during severe C. difficile infection (CDI) and the risk of mortality has yet to be defined. We aimed to investigate the host systemic IgG anti-toxin immune responses, the in vitro cytotoxicity of the infecting C. difficile ribotyped strain, and the host inflammatory markers and their relationship to CDI disease severity and risk of mortality. Inflammatory markers, co-morbidities and CDI outcomes were recorded in a prospective cohort of 150 CDI cases. Serum anti-cytotoxin A (TcdA) and anti-TcdB IgG titres were measured by ELISA and the infecting C. difficile isolate was ribotyped and the in vitro cytotoxin titre assessed. A low median anti-TcdA IgG titre was significantly associated with 30-day all-cause mortality (P<0.05). Ribotype 027 isolates were significantly more toxinogenic than other ribotypes (P<0.00001). High cytotoxin titres correlated with increased inflammatory markers but also higher anti-TcdA and -TcdB (P<0.05) IgG responses resulting in a lower risk of mortality. On multivariate analysis, predictors of mortality were peak white cell count >20 × 10(9) l(-1) [odds ratio (OR) 11.53; 95 % confidence interval (CI) 2.38-55.92], creatinine concentration >133 µmol l(-1) (OR 6.54; 95 % CI 1.47-29.07), Horn's index >3 (OR 4.09; 95 % CI 0.76-22.18) and low anti-TcdA IgG (OR 0.97; 95 % CI 0.95-0.99), but not ribotype, cytotoxin titre or anti-TcdB IgG. Thus, host pro-inflammatory and humoral responses correlate with the cytotoxin titre of the infecting strain and effective anti-toxin immune responses reduce the risk of mortality.

Seasonal and interannual mobility of arsenic in a lake impacted by metal mining.

Detailed examination of the water column, sediments, and interstitial waters was conducted in Balmer Lake, Ontario, Canada, in 1993-1994 and 1999 in order to assess the seasonal and interannual controls governing the behavior of As. High-resolution profiles of dissolved (<0.45 microm) Fe, Mn, SO4(2-), and sigmaH2S across the sediment-water interface indicate the presence of reducing conditions in close proximity to the benthic boundary during ice-free periods, which are characterized by fully oxygenated bottom waters. Dissolved As is remobilized as As(III) in suboxic sediment horizons via the redox-controlled dissolution of Fe (and perhaps Mn) oxide phases. During 1993-1994, As fluxes to the water column were relatively low (2-15 microg cm(-2) year(-1)) and contributed between 2 and 18% of the water column inventory. Dissolved As in the lake waters was derived primarily from external mining-related loadings during this period. Between 1993 and 1999, external loadings of As to Balmer Lake decreased while [As]aq within the lake increased, suggesting an increase in the proportion of sediment-derived As. Indeed, benthic dissolved As fluxes in 1999 ranged from 179 to 380 microg cm(-2) year(-1), representing approximately 33-60% of the water column burden. The relatively recent importance of sedimentary arsenic sources is suggested to reflect changes to sediment redox conditions associated with a postulated increase in lake primary productivity. Ironically, the increased contribution of dissolved arsenic to the water column appears to have resulted from an otherwise improvement in water quality. Reduced loadings of Cu, Zn, and Ni to the lake since 1994 appear to have allowed increased phytoplankton production that has stimulated arsenic release.

Post-depositional behavior of Cu in a metal-mining polishing pond (East Lake, Canada).

The post-depositional behavior of Cu in a gold-mining polishing pond (East Lake, Canada) was assessed after mine closure by examination of porewater chemistry and mineralogy. The near-surface (upper 1.5 cm) sediments are enriched in Cu, with values ranging from 0.4 to 2 wt %. Mineralogical examination revealed that the bulk of the Cu inventory is present as authigenic copper sulfides. Optical microscopy, energy-dispersion spectra, and X-ray data indicate that the main Cu sulfide is covellite (CuS). The formation of authigenic Cu-S phases is supported by the porewater data, which demonstrate that the sediments are serving as a sink for dissolved Cu below sub-bottom depths of 1-2 cm. The zone of Cu removal is consistent with the occurrence of detectable sulfide and the consumption of sulfate. The sediments can be viewed as a passive bioreactorthat permanently removes Cu as insoluble copper sulfides. This process is not unlike that which occurs in other forms of bioremediation, such as wetlands and permeable reactive barriers. Above the zone of Cu removal, dissolved Cu maxima in the interfacial porewaters range from 150 to 450 microg L(-1) and reflect the dissolution of a Cu-bearing phase in the surface sediments. The reactive phase is thought to be a component of treatment sludges delivered to the lake as part of cyanide treatment. Flux calculations indicate that the efflux of dissolved Cu from the sediments to the water column (14-51 microg cm(-2) yr(-1)) can account for the elevated levels of dissolved Cu in lake waters (approximately 50 microg L(-1)). Implications for lake recovery are discussed.