Risk assessments for quality-assured, source-segregated composts and anaerobic digestates for a circular bioeconomy in the UK

A circular economy relies on demonstrating the quality and environmental safety of wastes that are recovered and reused as products. Policy-level risk assessments, using generalised exposure scenarios, and informed by stakeholder communities have been used to appraise the acceptability of necessary changes to legislation, allowing wastes to be valued, reused and marketed. Through an extensive risk assessment exercise, summarised in this paper, we explore the burden of proof required to offer safety assurance to consumer and brand-sensitive food sectors in light of attempts to declassify, as wastes, quality-assured, source-segregated compost and anaerobic digestate products in the United Kingdom. We report the residual microbiological and chemical risks estimated for both products in land application scenarios and discuss these in the context of an emerging UK bioeconomy worth £52bn per annum. Using plausible worst case assumptions, as demanded by the quality food sector, risk estimates and hazard quotients were estimated to be low or negligible. For example, the human health risk of E. coli 0157 illness from exposure to microbial residuals in quality-assured composts, through a ready-to-eat vegetable consumption exposure route, was estimated at ~10-8 per person per annum. For anaerobic digestion residues, 7 x10-3 cases of E. coli 0157 were estimated per annum, a potential contribution of 0.0007 percent of total UK cases. Hazard quotients for potential chemical contaminants in both products were insufficient in magnitude to merit detailed quantitative risk assessments. Stakeholder engagement and expert review was also a substantive feature of this study. We conclude that quality assured, source-segregated products applied to land, under UK quality protocols and waste processing standards, pose negligible risks to human, animal, environmental and crop receptors, providing that risk management controls set within the standards and protocols are adhered to

An original phylogenetic approach identified mitochondrial haplogroup T1a1 as inversely associated with breast cancer risk in BRCA2 mutation carriers

Introduction: Individuals carrying pathogenic mutations in the BRCA1 and BRCA2 genes have a high lifetime risk of breast cancer. BRCA1 and BRCA2 are involved in DNA double-strand break repair, DNA alterations that can be caused by exposure to reactive oxygen species, a main source of which are mitochondria. Mitochondrial genome variations affect electron transport chain efficiency and reactive oxygen species production. Individuals with different mitochondrial haplogroups differ in their metabolism and sensitivity to oxidative stress. Variability in mitochondrial genetic background can alter reactive oxygen species production, leading to cancer risk. In the present study, we tested the hypothesis that mitochondrial haplogroups modify breast cancer risk in BRCA1/2 mutation carriers. Methods: We genotyped 22,214 (11,421 affected, 10,793 unaffected) mutation carriers belonging to the Consortium of Investigators of Modifiers of BRCA1/2 for 129 mitochondrial polymorphisms using the iCOGS array. Haplogroup inference and association detection were performed using a phylogenetic approach. ALTree was applied to explore the reference mitochondrial evolutionary tree and detect subclades enriched in affected or unaffected individuals. Results: We discovered that subclade T1a1 was depleted in affected BRCA2 mutation carriers compared with the rest of clade T (hazard ratio (HR) = 0.55; 95% confidence interval (CI), 0.34 to 0.88; P = 0.01). Compared with the most frequent haplogroup in the general population (that is, H and T clades), the T1a1 haplogroup has a HR of 0.62 (95% CI, 0.40 to 0.95; P = 0.03). We also identified three potential susceptibility loci, including G13708A/rs28359178, which has demonstrated an inverse association with familial breast cancer risk. Conclusions: This study illustrates how original approaches such as the phylogeny-based method we used can empower classical molecular epidemiological studies aimed at identifying association or risk modification effects.Peer reviewe

Robust estimation of bacterial cell count from optical density

Optical density (OD) is widely used to estimate the density of cells in liquid culture, but cannot be compared between instruments without a standardized calibration protocol and is challenging to relate to actual cell count. We address this with an interlaboratory study comparing three simple, low-cost, and highly accessible OD calibration protocols across 244 laboratories, applied to eight strains of constitutive GFP-expressing E. coli. Based on our results, we recommend calibrating OD to estimated cell count using serial dilution of silica microspheres, which produces highly precise calibration (95.5% of residuals <1.2-fold), is easily assessed for quality control, also assesses instrument effective linear range, and can be combined with fluorescence calibration to obtain units of Molecules of Equivalent Fluorescein (MEFL) per cell, allowing direct comparison and data fusion with flow cytometry measurements: in our study, fluorescence per cell measurements showed only a 1.07-fold mean difference between plate reader and flow cytometry data

DC Priming by M. vaccae Inhibits Th2 Responses in Contrast to Specific TLR2 Priming and Is Associated with Selective Activation of the CREB Pathway

The environmental mycobacterium, M. vaccae has been used in mouse models to support the contemporary hygiene hypothesis that non-pathogenic microorganisms reduce allergy associated T helper (Th)2 responses and inflammatory diseases by augmenting regulatory T cells. However, data for human models and possible mechanisms are limited. We tested the effect of innate immune interactions between human DC and M. vaccae on DC-dependent T cell responses. M. vaccae activation of DC via Toll like receptor (TLR)2 was compared to a specific TLR2 ligand (Pam(3)CSK4) and alternative stimulation with a TLR4 ligand (LPS). M. vaccae induced DC dependent inhibition of Th2 responses, in contrast to Pam(3)CSK4, which had the opposite effect and LPS, which had no polarizing effect. DC maturation, gene expression and cytokine production, in response to each stimulus did not correlate with the specific functional effects. Comparable DC transcriptional responses to M. vaccae and Pam(3)CSK4 suggested that TLR2 mediated transcriptional regulation was not sufficient for inhibition of Th2 responses. Transcription factor enrichment analysis and assessment of signaling events, implicated a role for selective early activation of the CREB pathway by M. vaccae. Further study of the CREB pathway may provide novel insight into the molecular mechanisms of DC-dependent T cell polarization

Il trovatore

Orquestra Simfònica del Gran Teatre del Liceu, dirigida per Lamberto Gardelli, i Cor del Gran Teatre del Liceu, dirigit per Romano GandolfiPrograma de mà de l'òpera Il trovatore, de Verdi, representada entre abril i maig del 1993, que va comptar amb el següent repartiment: Vicens Sardinero i Joan Pons (Conte di Luna) ; Aprile Millo, Michèle Crider i Sharon Sweet (Leonora) ; Nina Terentieva i Dolora Zajick (Azucena) ; Dennis O'Neill, Kristian Johannsson i Vladimir Popov (Manrico) ; Stefano palatchi (Ferrando9 ; Maria Uiz (Ines) ; Alfredo heilbron (Ruiz) ; Joan Tomàs (zíngar) ; Antoni Lluch (missatger). L'orquestra estava dirigida per Lamberto Gardelli, i el cor per Romano Gandolf

Perceived Cognition after Percutaneous Coronary Intervention: Association with Quality of Life, Mood and Fatigue in the THORESCI Study

Purpose: Percutaneous coronary intervention (PCI) is a common invasive procedure for the treatment of coronary artery diseases. Long-term cognitive functioning after PCI and its association with health-related quality of life (HRQL) and psychological factors is relatively unknown. The aim of this study is to examine whether perceived cognitive functioning during the year after PCI is associated with HRQL over this time period, and whether mood, fatigue, and age are associated with changes in perceived cognition and HRQL. Methods: Patients undergoing PCI (n = 384, 79% male, mean age = 63, SD = 10) were recruited in the observational Tilburg Health Outcome Registry of Emotional Stress after Coronary Intervention (THORESCI) cohort study. Perceived concentration and attention problems, HRQL, mood, and fatigue were assessed at baseline, at 1-month and 12-month follow-up. Results: General linear mixed modeling analysis showed that across time, between- and within-subject differences in perceived concentration problems were associated with a reduced HRQL in all domains independent of clinical and demographic covariates. Only a part of this association could be explained by negative mood, fatigue, and older age. Similar findings were found for between-subject differences in perceived attention problems. Conclusions: Between-subject differences and within-subject changes in perceived cognition in PCI patients were strongly associated with HRQL across time, such that poorer perceived cognition was associated with poorer HRQL, independent of demographic and clinical variables. Most of the associations were also independent of mood and fatigue. The results should increase the awareness of clinicians for the role of cognition in the cardiac rehabilitation and recovery post-PCI