Effect of Solution pH on the Dual Role of Dissolved Organic Matter in Sensitized Pollutant Photooxidation

[Image: see text] Dissolved organic matter (DOM) has a dual role in indirect phototransformations of aquatic contaminants by acting both as a photosensitizer and an inhibitor. Herein, the pH dependence of the inhibitory effect of DOM and the underlying mechanisms were studied in more than 400 kinetic irradiation experiments over the pH range of 6–11. Experiments employed various combinations of one of three DOM isolates, one of two model photosensitizers, the model antioxidant phenol, and one of nine target compounds (TCs), comprising several aromatic amines, in particular anilines and sulfonamides, and 4-cyanophenol. Using model photosensitizers without antioxidants, the phototransformation of most TCs increased with increasing pH, even for TCs for which pH did not affect speciation. This trend was attributed to pH-dependent formation yields of TC-derived radicals and their re-formation to the parent TC. Analogous trends were observed with DOM as a photosensitizer. Comparison of model and DOM photosensitizer data sets showed increasing inhibitory effects of DOM on TC phototransformation kinetics with increasing pH. In systems with anilines as a TC and phenol as a model antioxidant, pH trends of the inhibitory effect could be rationalized based on the reduction potential difference (ΔE(red)) of phenoxyl/phenol and anilinyl/aniline couples. Our results indicate that the light-induced transformation of aromatic amines in the aquatic environment is governed by the pH-dependent inhibitory effects of antioxidant phenolic moieties of DOM and pH-dependent processes related to the formation of amine oxidation intermediates

Male Norway rats cooperate according to direct but not generalized reciprocity rules

Funding was provided by the Swiss National Science Foundation grants 31003A_156152 and 31003A 176174 to M.T. and P2BEP3 175269 to M.K.S.Reciprocal cooperation may evolve if the costs of help are reliably compensated for by delayed returns provided in future interactions. The associated probabilities and cost–benefit ratios may vary systematically between the sexes, which often display different dispersal strategies and interaction patterns. Whereas female Norway rats, Rattus norvegicus, are known to apply direct and generalized decision rules of reciprocal cooperation, the rules according to which males reciprocate favours are less well understood. Therefore, we investigated the cooperation propensity of male wild-type Norway rats. Male test rats experienced cooperating partners that provided food to them, or defecting partners that refused to provide help. Afterwards, test rats could donate food to previously experienced or unknown partners, resembling direct and generalized reciprocity paradigms, respectively. Male rats cooperated according to direct reciprocity, suggesting that this decision rule is similarly important for both sexes. However, whereas females additionally help according to generalized reciprocity, males did not apply this rule. These results suggest a sex difference in reciprocal decision rules, highlighting the potential importance of different interaction patterns and cost–benefit ratios between the sexes.PostprintPeer reviewe

Comparative evaluation of the MAPlex, Precision ID Ancestry Panel, and VISAGE Basic Tool for biogeographical ancestry inference

Biogeographical ancestry (BGA) inference from ancestry-informative markers (AIMs) has strong potential to support forensic investigations. Over the past two decades, several forensic panels composed of AIMs have been developed to predict ancestry at a continental scale. These panels typically comprise fewer than 200 AIMs and have been designed and tested with a limited set of populations. How well these panels recover patterns of genetic diversity relative to larger sets of markers, and how accurately they infer ancestry of individuals and populations not included in their design remains poorly understood. The lack of comparative studies addressing these aspects makes the selection of appropriate panels for forensic laboratories difficult. In this study, the model-based genetic clustering tool STRUCTURE was used to compare three popular forensic BGA panels: MAPlex, Precision ID Ancestry Panel (PIDAP), and VISAGE Basic Tool (VISAGE BT) relative to a genome-wide reference set of 10k SNPs. The genotypes for all these markers were obtained for a comprehensive set of 3957 individuals from 228 worldwide human populations. Our results indicate that at the broad continental scale (K = 6) typically examined in forensic studies, all forensic panels produced similar genetic structure patterns compared to the reference set (G′ ≈ 90%) and had high classification performance across all regions (average AUC-PR > 97%). However, at K = 7 and K = 8, the forensic panels displayed some region-specific clustering deviations from the reference set, particularly in Europe and the region of East and South-East Asia, which may be attributed to differences in the design of the respective panels. Overall, the panel with the most consistent performance in all regions was VISAGE BT with an average weighted AUC̅W score of 96.26% across the three scales of geographical resolution investigated

Photosensitizing and inhibitory effects of ozonated dissolved organic matter on triplet-induced contaminant transformation

Dissolved organic matter (DOM) is both a promoter and an inhibitor of triplet-induced organic contaminant oxidation. This dual role was systematically investigated through photochemical experiments with three types of DOM of terrestrial and aquatic origins that were preoxidized to varying extents by ozonation. The inhibitory effect of DOM was assessed by determining the 4-carboxybenzophenone photosensitized transformation rate constants of two sulfonamide antibiotics (sulfamethoxazole and sulfadiazine) in the presence of untreated or preoxidized DOM. The inhibitory effect decreased with the increasing extent of DOM preoxidation, and it was correlated to the loss of phenolic antioxidant moieties, as quantified electrochemically, and to the loss of DOM ultraviolet absorbance. The triplet photosensitizing ability of preoxidized DOM was determined using the conversion of the probe compound 2,4,6-trimethylphenol (TMP), which is unaffected by DOM inhibition effects. The DOM photosensitized transformation rate constants of TMP decreased with increasing DOM preoxidation and were correlated to the concomitant loss of chromophores (i.e., photosensitizing moieties). The combined effects of DOM preoxidation on the inhibiting and photosensitizing properties were assessed by phototransformation experiments of the sulfonamides in DOM-containing solutions. At low extents of DOM preoxidation, the sulfonamide phototransformation rate constants remained either unchanged or slightly increased, indicating that the removal of antioxidant moieties had larger effects than the loss of photosensitizing moieties. At higher extents of DOM preoxidation, transformation rates declined, mainly reflecting the destruction of photosensitizing moieties

Sex differences of vascular brain lesions in patients with atrial fibrillation.

OBJECTIVE To examine sex differences in prevalence, volume and distribution of vascular brain lesions on MRI among patients with atrial fibrillation (AF). METHODS In this cross-sectional analysis, we included 1743 patients with AF (27% women) from the multicentre Swiss Atrial Fibrillation study (SWISS-AF) with available baseline brain MRI. We compared presence and total volume of large non-cortical or cortical infarcts (LNCCIs), small non-cortical infarcts, microbleeds (MB) and white matter hyperintensities (WMH, Fazekas score ≥2 for moderate or severe degree) between men and women with multivariable logistic regression. We generated voxel-based probability maps to assess the anatomical distribution of lesions. RESULTS We found no strong evidence for an association of female sex with the prevalence of all ischaemic infarcts (LNCCI and SNCI combined; adjusted OR 0.86, 95% CI 0.67 to 1.09, p=0.22), MB (adjusted OR 0.91, 95% CI 0.68 to 1.21, p=0.52) and moderate or severe WMH (adjusted OR 1.15, 95% CI 0.90 to 1.48, p=0.27). However, total WMH volume was 17% larger among women than men (multivariable adjusted multiplicative effect 1.17, 95% CI 1.01 to 1.35; p=0.04). Lesion probability maps showed a right hemispheric preponderance of ischaemic infarcts in both men and women, while WMH were distributed symmetrically. CONCLUSION Women had higher white matter disease burden than men, while volume and prevalence of other lesions did not differ. Our findings highlight the importance of controlling risk factors for cerebral small vessel disease in patients with AF, especially among women

Real-world cost-effectiveness of pulmonary vein isolation for atrial fibrillation: a target trial approach.

OBJECTIVES Randomized controlled trials of pulmonary vein isolation (PVI) for treating atrial fibrillation (AF) have proven the procedure's efficacy. Studies assessing its empirical cost-effectiveness outside randomized trial settings are lacking. We aimed to evaluate the effectiveness and cost-effectiveness of PVI versus medical therapy for AF. METHODS We followed a target trial approach using the Swiss AF cohort, a prospective observational cohort study that enrolled AF patients between 2014 and 2017. Resource utilization and cost information was collected through claims data. Quality-of-life was measured with EQ-5D-3L utilities. We estimated incremental cost-effectiveness ratios from the perspective of the Swiss statutory health insurance system. RESULTS Patients undergoing PVI compared to medical therapy had a 5-year overall survival advantage with a hazard ratio of 0.75 (95%CI 0.46-1.21, p=0.69), a 19.8% standard deviation improvement in quality-of-life (95%CI 15.5-22.9%, p<0.001), at an incremental cost of 29,604 (95%CI 16,354-42,855, p<0.001) Swiss Francs (CHF). The estimated incremental cost-effectiveness ratio was CHF 158,612 per quality-adjusted life-year (QALY) gained within a 5-year time horizon. Assuming similar health effects and costs over 5 additional years changed the incremental cost-effectiveness ratio to CHF 82,195 per QALY gained. Results were robust to the sensitivity analyses performed. CONCLUSIONS Our results show that PVI might be a cost-effective intervention within the Swiss healthcare context in a 10-year time horizon, but unlikely to be so at 5-years, if a willingness-to-pay threshold of CHF100,000 per QALY gained is assumed. Given data availability, we find target trial designs are a valuable tool for assessing the cost-effectiveness of healthcare interventions outside of RCT settings

Real-World Cost-Effectiveness of Pulmonary Vein Isolation for Atrial Fibrillation: A Target Trial Approach

OBJECTIVES Randomized controlled trials of pulmonary vein isolation (PVI) for treating atrial fibrillation (AF) have proven the procedure's efficacy. Studies assessing its empirical cost-effectiveness outside randomized trial settings are lacking. We aimed to evaluate the effectiveness and cost-effectiveness of PVI versus medical therapy for AF. METHODS We followed a target trial approach using the Swiss-AF cohort, a prospective observational cohort study that enrolled patients with AF between 2014 and 2017. Resource utilization and cost information were collected through claims data. Quality of life was measured with EQ-5D-3L utilities. We estimated incremental cost-effectiveness ratios (ICERs) from the perspective of the Swiss statutory health insurance system. RESULTS Patients undergoing PVI compared with medical therapy had a 5-year overall survival advantage with a hazard ratio of 0.75 (95% CI 0.46-1.21; P = .69) and a 19.8% SD improvement in quality of life (95% CI 15.5-22.9; P < .001), at an incremental cost of 29 604 Swiss francs (CHF) (95% CI 16 354-42 855; P < .001). The estimated ICER was CHF 158 612 per quality-adjusted life-year (QALY) gained within a 5-year time horizon. Assuming similar health effects and costs over 5 additional years changed the ICER to CHF 82 195 per QALY gained. Results were robust to the sensitivity analyses performed. CONCLUSIONS Our results show that PVI might be a cost-effective intervention within the Swiss healthcare context in a 10-year time horizon, but unlikely to be so at 5 years, if a willingness-to-pay threshold of CHF 100 000 per QALY gained is assumed. Given data availability, we find target trial designs are a valuable tool for assessing the cost-effectiveness of healthcare interventions outside of randomized controlled trial settings

Omega-3 Fatty Acids and Heart Rhythm, Rate, and Variability in Atrial Fibrillation.

Background Previous randomized control trials showed mixed results concerning the effect of omega-3 fatty acids (n-3 FAs) on atrial fibrillation (AF). The associations of n-3 FA blood levels with heart rhythm in patients with established AF are unknown. The goal of this study was to assess the associations of total and individual n-3 FA blood levels with AF type (paroxysmal versus nonparoxysmal), heart rate (HR), and HR variability in patients with AF. Methods and Results Total n-3 FAs, eicosapentaenoic acid, docosahexaenoic acid, docosapentaenoic acid, and alpha-linolenic acid blood levels were determined in 1969 patients with known AF from the SWISS-AF (Swiss Atrial Fibrillation cohort). Individual and total n-3 FAs were correlated with type of AF, HR, and HR variability using standard logistic and linear regression, adjusted for potential confounders. Only a mild association with nonparoxysmal AF was found with total n-3 FA (odds ratio [OR], 0.97 [95% CI, 0.89-1.05]) and docosahexaenoic acid (OR, 0.93 [95% CI, 0.82-1.06]), whereas other individual n-3 FAs showed no association with nonparoxysmal AF. Higher total n-3 FAs (estimate 0.99 [95% CI, 0.98-1.00]) and higher docosahexaenoic acid (0.99 [95% CI, 0.97-1.00]) tended to be associated with slower HR in multivariate analysis. Docosapentaenoic acid was associated with a lower HR variability triangular index (0.94 [95% CI, 0.89-0.99]). Conclusions We found no strong evidence for an association of n-3 FA blood levels with AF type, but higher total n-3 FA levels and docosahexaenoic acid might correlate with lower HR, and docosapentaenoic acid with a lower HR variability triangular index

Neurocognitive function in patients with atrial fibrillation undergoing pulmonary vein isolation.

BACKGROUND Atrial fibrillation (AF) is associated with cognitive dysfunction. However, neurocognitive function in AF patients undergoing pulmonary vein isolation (PVI) has not been well studied. The aim of this analysis is to compare neurocognitive function in patients who did or did not undergo PVI. MATERIALS AND METHODS We used data from the Swiss Atrial Fibrillation Cohort study (Swiss-AF), a prospective, observational, multicenter study in Switzerland. Patients with documented AF were enrolled and data of 1,576 patients without history of PVI and with complete information on PVI status and neurocognitive function were used. Information on PVI was collected at baseline and during 1 year of follow-up. Neurocognitive testing was performed at baseline and after 1 year of follow-up, using the Montreal Cognitive Assessment (MoCA), trail making test (TMT) A and B, digit symbol substitution test (DSST) and semantic fluency test (SFT). To investigate the association of PVI with neurocognitive function, we use propensity score matching (1:3) and inverse probability of treatment weighting (IPTW). RESULTS The mean age of this population was 74 ± 8 years, 27.1% were women. Overall, 88 (5.5%) patients underwent PVI during 1 year of follow-up. Using ITPW (n = 1576), PVI was weakly associated with the MoCA score after adjusting for time since PVI, baseline MoCA score and other covariates (β (95%CI) 1.19 (0.05; 2.32), p = 0.04). In the propensity matched comparison (n = 352), there was no significant association between PVI and the MoCA score (β (95%CI) 1.04 (-0.19; 2.28), p = 0.1). There were no significant associations between PVI and cognitive function when using the TMT A and B, DSST or SFT independent of the method used. CONCLUSION In this population of AF patients, there was no consistent evidence of an association between PVI and neurocognitive function. CLINICAL TRIAL REGISTRATION [https://clinicaltrials.gov/], identifier [NCT02105844]