We present a method that self-consistently tracks the growth of supermassive black holes (BHs) and the feedback from active galactic nuclei (AGN) in cosmological, hydrodynamical simulations. Our ...model is a substantially modified version of the one introduced by Springel, Di Matteo & Hernquist implemented in a significantly expanded version of the gadget III code, which contains new prescriptions for star formation, supernova feedback, radiative cooling and chemodynamics. We simulate the growth of BHs from an initial seed state via Eddington-limited accretion of the surrounding gas, and via mergers with other BHs. Because cosmological simulations at present lack both the resolution and the physics to model the multiphase interstellar medium, they tend to strongly underestimate the Bondi–Hoyle accretion rate. To allow low-mass BHs to grow, it is therefore necessary to increase the predicted Bondi–Hoyle rates in star-forming gas by large factors, either by explicitly multiplying the accretion rate by a numerical correction factor or by using an unresolved, subgrid model for the gas close to the BH. We explore the physical regimes where the use of such multiplicative factors is reasonable, and through this introduce a new prescription for gas accretion by BHs. Feedback from AGN is modelled by coupling a fraction of the rest-mass energy of the accreted gas thermally into the surrounding medium. We describe the implementation as well as the limitations of the model in detail and motivate all the changes relative to previous work. We demonstrate how general physical considerations can be used to choose many of the parameters of the model and demonstrate that the fiducial model reproduces observational constraints. We employ a large suite of cosmological simulations, in which the parameters of the BH model are varied away from their fiducial values, to investigate the robustness of the predictions for the cosmic star formation history and the redshift zero cosmic BH density, BH scaling relations and galaxy-specific star formation rates. We find that the freedom introduced by the need to increase the predicted accretion rates by hand, the standard procedure in the literature, is the most significant source of uncertainty. Our simulations demonstrate that supermassive BHs are able to regulate their growth by releasing a fixed amount of energy for a given halo mass, independent of the assumed efficiency of AGN feedback, which sets the normalization of the BH scaling relations. Regardless of whether BH seeds are initially placed above or below the BH scaling relations, they grow on to the same scaling relations. AGN feedback efficiently suppresses star formation in high-mass galaxies.
The ER-mitochondrial interface is central to calcium signaling, organellar dynamics, and lipid biosynthesis. The ER and mitochondrial membranes also host sources and targets of reactive oxygen ...species (ROS), but their local dynamics and relevance remained elusive since measurement and perturbation of ROS at the organellar interface has proven difficult. Employing drug-inducible synthetic ER-mitochondrial linkers, we overcame this problem and demonstrate that the ER-mitochondrial interface hosts a nanodomain of H2O2, which is induced by cytoplasmic Ca2+ spikes and exerts a positive feedback on calcium oscillations. H2O2 nanodomains originate from the mitochondrial cristae, which are compressed upon calcium signal propagation to the mitochondria, likely due to Ca2+-induced K+ and concomitant water influx to the matrix. Thus, ER-mitochondrial H2O2 nanodomains represent a component of inter-organelle communication, regulating calcium signaling and mitochondrial activities.
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•The ER-mitochondrial interface hosts a dynamic H2O2 nanodomain•ER-mitochondrial Ca2+ transfer stimulates ROS mobilization from mitochondria•The oxidized cristae volume is the source of interface H2O2 transients•H2O2 transients sensitize ER Ca2+ release to maintain Ca2+ oscillations
During Ca2+ signals, elevated Ca2+ microdomains form at the ER-mitochondrial interface. Booth et al. demonstrate that a nanodomain of H2O2 is also present. This is produced by Ca2+-induced mobilization of ROS from the mitochondrial cristae and functions to sensitize ER Ca2+ channels.
Synthetic polymer-based materials are ubiquitous in aquatic environments, where weathering processes lead to their progressive fragmentation and the leaching of additive chemicals. The current study ...assessed the chemical content of freshwater and marine leachates produced from car tire rubber (CTR), polypropylene (PP), polyethylene terephthalate (PET), polystyrene (PS) and polyvinyl chloride (PVC) microplastics, and their adverse effects on the microalgae Raphidocelis subcapitata (freshwater) and Skeletonema costatum (marine) and the Mediterranean mussel Mytilus galloprovincialis. A combination of non-target and target chemical analysis revealed a number of organic and metal compounds in the leachates, including representing plasticizers, antioxidants, antimicrobials, lubricants, and vulcanizers. CTR and PVC materials and their corresponding leachates had the highest content of tentatively identified organic additives, while PET had the lowest. The metal content varied both between polymer leachates and between freshwater and seawater. Notable additives identified in high concentrations were benzothiazole (CTR), phthalide (PVC), acetophenone (PP), cobalt (CTR, PET), zinc (CTR, PVC), lead (PP) and antimony (PET). All leachates, except PET, inhibited algal growth with EC50 values ranging from 0.5% (CTR) and 64% (PP) of the total leachate concentration. Leachates also affected mussel endpoints, including the lysosomal membrane stability and early stages endpoints as gamete fertilization, embryonic development and larvae motility and survival. Embryonic development was the most sensitive parameter in mussels, with EC50 values ranging from 0.8% (CTR) to 65% (PET) of the total leachate. The lowest impacts were induced on D-shell larvae survival, reflecting their ability to down-regulate motility and filtration in the presence of chemical stressors. This study provides evidence of the relationship between chemical composition and toxicity of plastic/rubber leachates. Consistent with increasing contamination by organic and inorganic additives, the leachates ranged from slightly to highly toxic to mussels and algae, highlighting the need for a better understanding of the overall impact of plastic-associated chemicals on aquatic ecosystems.
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•Synthetic polymers in the environment can release potentially toxic additives.•Leachates showed polymer-specific mixtures of metals and organic chemicals.•Identified additives include plasticizers, antioxidants and antimicrobial agents.•Acute and sub-lethal responses to leachates were observed in microalgae and mussels.•Differences in toxicity were observed for different plastic materials.
Feedback from energy liberated by gas accretion on to black holes (BHs) is an attractive mechanism to explain the exponential cut-off at the massive end of the galaxy stellar mass function. Most ...previous implementations of BH accretion in hydrodynamical simulations of galaxy formation have assumed that BHs grow at an accretion rate that is proportion to the Bondi rate. A major concern is that the Bondi accretion rate is inappropriate when the accreting material has significant angular momentum. We present an improved accretion model that takes into account the circularization and subsequent viscous transport of infalling material, and implemented as a ‘subgrid’ model in hydrodynamic simulations. The resulting accretion rates are generally low in low mass (≲ 1011.5 M⊙) haloes, but show outbursts of Eddington-limited accretion during galaxy mergers. During outbursts these objects strongly resemble quasars. In higher mass haloes, gas accretion peaks at ∼10 per cent of the Eddington rate, which is thought to be conducive to the formation of radio jets. The resulting accretion rate depends strongly on the effective pressure of the gas surrounding the BH, which in turn depends strongly on halo mass. This induces a sharp transition in the importance of BH feedback. In small haloes, the growth of galaxies is regulated by star formation and supernova feedback, but above a halo mass of 1011.5 M⊙, rapid BH growth leads to the suppression of star formation and reduced growth of stellar mass with increasing halo mass.
Upcoming weak lensing surveys, such as LSST, EUCLID and WFIRST, aim to measure the matter power spectrum with unprecedented accuracy. In order to fully exploit these observations, models are needed ...that, given a set of cosmological parameters, can predict the non-linear matter power spectrum at the level of 1 per cent or better for scales corresponding to comoving wavenumbers 0.1 ≲k≲ 10 h Mpc−1. We have employed the large suite of simulations from the OverWhelmingly Large Simulations (OWLS) project to investigate the effects of various baryonic processes on the matter power spectrum. In addition, we have examined the distribution of power over different mass components, the back-reaction of the baryons on the cold dark matter and the evolution of the dominant effects on the matter power spectrum. We find that single baryonic processes are capable of changing the power spectrum by up to several tens of per cent. Our simulation that includes AGN feedback, which we consider to be our most realistic simulation as, unlike those used in previous studies, it has been shown to solve the overcooling problem and to reproduce optical and X-ray observations of groups of galaxies, predicts a decrease in power relative to a dark matter only simulation ranging, at z= 0, from 1 per cent at k≈ 0.3 h Mpc−1 to 10 per cent at k≈ 1 h Mpc−1 and to 30 per cent at k≈ 10 h Mpc−1. This contradicts the naive view that baryons raise the power through cooling, which is the dominant effect only for k≳ 70 h Mpc−1. Therefore, baryons, and particularly AGN feedback, cannot be ignored in theoretical power spectra for k≳ 0.3 h Mpc−1. It will thus be necessary to improve our understanding of feedback processes in galaxy formation, or at least to constrain them through auxiliary observations, before we can fulfil the goals of upcoming weak lensing surveys.
To quantify the association of cancer treatment delay and mortality for each four week increase in delay to inform cancer treatment pathways.
Systematic review and meta-analysis.
Published studies in ...Medline from 1 January 2000 to 10 April 2020.
Curative, neoadjuvant, and adjuvant indications for surgery, systemic treatment, or radiotherapy for cancers of the bladder, breast, colon, rectum, lung, cervix, and head and neck were included. The main outcome measure was the hazard ratio for overall survival for each four week delay for each indication. Delay was measured from diagnosis to first treatment, or from the completion of one treatment to the start of the next. The primary analysis only included high validity studies controlling for major prognostic factors. Hazard ratios were assumed to be log linear in relation to overall survival and were converted to an effect for each four week delay. Pooled effects were estimated using DerSimonian and Laird random effect models.
The review included 34 studies for 17 indications (n=1 272 681 patients). No high validity data were found for five of the radiotherapy indications or for cervical cancer surgery. The association between delay and increased mortality was significant (P<0.05) for 13 of 17 indications. Surgery findings were consistent, with a mortality risk for each four week delay of 1.06-1.08 (eg, colectomy 1.06, 95% confidence interval 1.01 to 1.12; breast surgery 1.08, 1.03 to 1.13). Estimates for systemic treatment varied (hazard ratio range 1.01-1.28). Radiotherapy estimates were for radical radiotherapy for head and neck cancer (hazard ratio 1.09, 95% confidence interval 1.05 to 1.14), adjuvant radiotherapy after breast conserving surgery (0.98, 0.88 to 1.09), and cervix cancer adjuvant radiotherapy (1.23, 1.00 to 1.50). A sensitivity analysis of studies that had been excluded because of lack of information on comorbidities or functional status did not change the findings.
Cancer treatment delay is a problem in health systems worldwide. The impact of delay on mortality can now be quantified for prioritisation and modelling. Even a four week delay of cancer treatment is associated with increased mortality across surgical, systemic treatment, and radiotherapy indications for seven cancers. Policies focused on minimising system level delays to cancer treatment initiation could improve population level survival outcomes.
The ubiquitous pollution of the environment with microplastics, a diverse suite of contaminants, is of growing concern for science and currently receives considerable public, political, and academic ...attention. The potential impact of microplastics in the environment has prompted a great deal of research in recent years. Many diverse methods have been developed to answer different questions about microplastic pollution, from sources, transport, and fate in the environment, and about effects on humans and wildlife. These methods are often insufficiently described, making studies neither comparable nor reproducible. The proliferation of new microplastic investigations and cross-study syntheses to answer larger scale questions are hampered. This diverse group of 23 researchers think these issues can begin to be overcome through the adoption of a set of reporting guidelines. This collaboration was created using an open science framework that we detail for future use. Here, we suggest harmonized reporting guidelines for microplastic studies in environmental and laboratory settings through all steps of a typical study, including best practices for reporting materials, quality assurance/quality control, data, field sampling, sample preparation, microplastic identification, microplastic categorization, microplastic quantification, and considerations for toxicology studies. We developed three easy to use documents, a detailed document, a checklist, and a mind map, that can be used to reference the reporting guidelines quickly. We intend that these reporting guidelines support the annotation, dissemination, interpretation, reviewing, and synthesis of microplastic research. Through open access licensing (CC BY 4.0), these documents aim to increase the validity, reproducibility, and comparability of studies in this field for the benefit of the global community.
Wastewater treatment plants (WWTPs) serve as an important route of microplastics (MPs) to the environment. Therefore, more effective MPs sampling and detection methodologies, as well as a better ...understanding of their influence on MPs occurrence and distributions in WWTP effluents, are needed for better removal and control. In this work, the efficiency of a municipal WWTP to remove MPs was assessed by collecting samples from raw to tertiary effluent during a 12-month sampling campaign (season-based) using different sampling methods (containers, 24-h composite and large grab samples). MPs retrieved from different treatment units within the WWTP were identified and quantified using plastic/non-plastic staining followed by optical microscopy, SEM and μ-Raman microscopy. Overall, the mean removal efficiency of MPs in the WWTP was 97%, with most MPs removed by the secondary stage and a mean effluent concentration of 1.97 MPs L−1 after sand filtration. The relative abundance of particles was lower than fibers in treated effluent compared with the raw wastewater, with MP fibers constituting 74% of the total MPs in raw wastewater and 91% in treated effluent. Taking seasonal variations into account is important as total MPs concentration in the effluent was notably higher in winter compared with the other seasons. Increasing the sampled volume using large samples or 24-h composite samples significantly reduced the variability between replicates. However, MPs concentration post the tertiary stage was significantly lower using morning sampling (9 am) by large grab sampling method (1.2 MPs L−1) compared to 24-h composite sampling (3.2 MPs L−1) possibly due to intra-daily changes. Using a finer mesh size (0.45 μm) to capture MPs beyond the size range typically studied (≥20 μm) effectively doubled the number of MPs detected in the tertiary effluent and highlights the importance of standardizing sampling procedures.
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•Sampling method affects the amount of identifiable microplastics in wastewater.•Microplastics concentrations were higher in winter compared with other seasons.•Large or 24 h composite samples contributed to minimize variability between samples.•Lower cut off mesh size (0.45 μm vs ≥20 μm) doubled the number of detected MPs.•Despite removal efficiency of 97%, annual microplastics emissions are considerable.
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