Earth system modeling with endogenous and dynamic human societies: the copan:CORE open World-Earth modeling framework

Analysis of Earth system dynamics in the Anthropocene requires to explicitly take into account the increasing magnitude of processes operating in human societies, their cultures, economies and technosphere and their growing feedback entanglement with those in the physical, chemical and biological systems of the planet. However, current state-of-the-art Earth System Models do not represent dynamic human societies and their feedback interactions with the biogeophysical Earth system and macroeconomic Integrated Assessment Models typically do so only with limited scope. This paper (i) proposes design principles for constructing World-Earth Models (WEM) for Earth system analysis of the Anthropocene, i.e., models of social (World) - ecological (Earth) co-evolution on up to planetary scales, and (ii) presents the copan:CORE open simulation modeling framework for developing, composing and analyzing such WEMs based on the proposed principles. The framework provides a modular structure to flexibly construct and study WEMs. These can contain biophysical (e.g. carbon cycle dynamics), socio-metabolic/economic (e.g. economic growth) and socio-cultural processes (e.g. voting on climate policies or changing social norms) and their feedback interactions, and are based on elementary entity types, e.g., grid cells and social systems. Thereby, copan:CORE enables the epistemic flexibility needed for contributions towards Earth system analysis of the Anthropocene given the large diversity of competing theories and methodologies used for describing socio-metabolic/economic and socio-cultural processes in the Earth system by various fields and schools of thought. To illustrate the capabilities of the framework, we present an exemplary and highly stylized WEM implemented in copan:CORE that illustrates how endogenizing socio-cultural processes and feedbacks could fundamentally change macroscopic model outcomes

Mycobacterial infection aggravates Helicobacter pylori-induced gastric preneoplastic pathology by redirection of de novo induced Treg cells.

The two human pathogens Helicobacter pylori and Mycobacterium tuberculosis (Mtb) co-exist in many geographical areas of the world. Here, using a co-infection model of H. pylori and the Mtb relative M. bovis bacillus Calmette-Guérin (BCG), we show that both bacteria affect the colonization and immune control of the respective other pathogen. Co-occurring M. bovis boosts gastric Th1 responses and H. pylori control and aggravates gastric immunopathology. H. pylori in the stomach compromises immune control of M. bovis in the liver and spleen. Prior antibiotic H. pylori eradication or M. bovis-specific immunization reverses the effects of H. pylori. Mechanistically, the mutual effects can be attributed to the redirection of regulatory T cells (Treg cells) to sites of M. bovis infection. Reversal of Treg cell redirection by CXCR3 blockade restores M. bovis control. In conclusion, the simultaneous presence of both pathogens exacerbates the problems associated with each individual infection alone and should possibly be factored into treatment decisions

Climate change drives loss of bacterial gut mutualists at the expense of host survival in wild meerkats

Climate change and climate‐driven increases in infectious disease threaten wildlife populations globally. Gut microbial responses are predicted to either buffer or exacerbate the negative impacts of these twin pressures on host populations. However, examples that document how gut microbial communities respond to long‐term shifts in climate and associated disease risk, and the consequences for host survival, are rare. Over the past two decades, wild meerkats inhabiting the Kalahari have experienced rapidly rising temperatures, which is linked to the spread of tuberculosis (TB). We show that over the same period, the faecal microbiota of this population has become enriched in Bacteroidia and impoverished in lactic acid bacteria (LAB), a group of bacteria including Lactococcus and Lactobacillus that are considered gut mutualists. These shifts occurred within individuals yet were compounded over generations, and were better explained by mean maximum temperatures than mean rainfall over the previous year. Enriched Bacteroidia were additionally associated with TB exposure and disease, the dry season and poorer body condition, factors that were all directly linked to reduced future survival. Lastly, abundances of LAB taxa were independently and positively linked to future survival, while enriched taxa did not predict survival. Together, these results point towards extreme temperatures driving an expansion of a disease‐associated pathobiome and loss of beneficial taxa. Our study provides the first evidence from a longitudinally sampled population that climate change is restructuring wildlife gut microbiota, and that these changes may amplify the negative impacts of climate change through the loss of gut mutualists. While the plastic response of host‐associated microbiotas is key for host adaptation under normal environmental fluctuations, extreme temperature increases might lead to a breakdown of coevolved host–mutualist relationships

Ionized outflows in local luminous AGN : what are the real densities and outflow rates?

We report on the determination of electron densities, and their impact on the outflow masses and rates, measured in the central few hundred parsecs of 11 local luminous active galaxies. We show that the peak of the integrated line emission in the active galactic nuclei (AGN) is significantly offset from the systemic velocity as traced by the stellar absorption features, indicating that the profiles are dominated by outflow. In contrast, matched inactive galaxies are characterized by a systemic peak and weaker outflow wing. We present three independent estimates of the electron density in these AGN, discussing the merits of the different methods. The electron density derived from the [S II] doublet is significantly lower than that found with a method developed in the last decade using auroral and transauroral lines, as well as a recently introduced method based on the ionization parameter. The reason is that, for gas photoionized by an AGN, much of the [S II] emission arises in an extended partially ionized zone where the implicit assumption that the electron density traces the hydrogen density is invalid. We propose ways to deal with this situation and we derive the associated outflow rates for ionized gas, which are in the range 0.001–0.5 M yr−1 for our AGN sample. We compare these outflow rates to the relation between M˙ out and LAGN in the literature, and argue that it may need to be modified and rescaled towards lower mass outflow rates

Silent brain infarcts impact on cognitive function in atrial fibrillation

Aims: We aimed to investigate the association of clinically overt and silent brain lesions with cognitive function in atrial fibrillation (AF) patients. Methods and results: We enrolled 1227 AF patients in a prospective, multicentre cohort study (Swiss-AF). Patients underwent standardized brain magnetic resonance imaging (MRI) at baseline and after 2 years. We quantified new small non-cortical infarcts (SNCIs) and large non-cortical or cortical infarcts (LNCCIs), white matter lesions (WML), and microbleeds (Mb). Clinically, silent infarcts were defined as new SNCI/LNCCI on follow-up MRI in patients without a clinical stroke or transient ischaemic attack (TIA) during follow-up. Cognition was assessed using validated tests. The mean age was 71 years, 26.1% were females, and 89.9% were anticoagulated. Twenty-eight patients (2.3%) experienced a stroke/TIA during 2 years of follow-up. Of the 68 (5.5%) patients with ≥1 SNCI/LNCCI, 60 (88.2%) were anticoagulated at baseline and 58 (85.3%) had a silent infarct. Patients with brain infarcts had a larger decline in cognition [median (interquartile range)] changes in Cognitive Construct score [-0.12 (-0.22; -0.07)] than patients without new brain infarcts [0.07 (-0.09; 0.25)]. New WML or Mb were not associated with cognitive decline. Conclusion: In a contemporary cohort of AF patients, 5.5% had a new brain infarct on MRI after 2 years. The majority of these infarcts was clinically silent and occurred in anticoagulated patients. Clinically, overt and silent brain infarcts had a similar impact on cognitive decline. Clinical trial registration: ClinicalTrials.gov Identifier: NCT02105844, https://clinicaltrials.gov/ct2/show/NCT02105844. Keywords: Atrial fibrillation; Brain infarction; Cognitive function; Magnetic resonance imaging; Oral anticoagulation

Measurement of the cosmic ray spectrum above 4×10184{\times}10^{18} eV using inclined events detected with the Pierre Auger Observatory

A measurement of the cosmic-ray spectrum for energies exceeding $4{\times}10^{18}$ eV is presented, which is based on the analysis of showers with zenith angles greater than $60^{\circ}$ detected with the Pierre Auger Observatory between 1 January 2004 and 31 December 2013. The measured spectrum confirms a flux suppression at the highest energies. Above $5.3{\times}10^{18}$ eV, the "ankle", the flux can be described by a power law $E^{-\gamma}$ with index $\gamma=2.70 \pm 0.02 \,\text{(stat)} \pm 0.1\,\text{(sys)}$ followed by a smooth suppression region. For the energy ($E_\text{s}$) at which the spectral flux has fallen to one-half of its extrapolated value in the absence of suppression, we find $E_\text{s}=(5.12\pm0.25\,\text{(stat)}^{+1.0}_{-1.2}\,\text{(sys)}){\times}10^{19}$ eV.Comment: Replaced with published version. Added journal reference and DO

Genome-Wide Association Study Identifies Two Novel Regions at 11p15.5-p13 and 1p31 with Major Impact on Acute-Phase Serum Amyloid A

Elevated levels of acute-phase serum amyloid A (A-SAA) cause amyloidosis and are a risk factor for atherosclerosis and its clinical complications, type 2 diabetes, as well as various malignancies. To investigate the genetic basis of A-SAA levels, we conducted the first genome-wide association study on baseline A-SAA concentrations in three population-based studies (KORA, TwinsUK, Sorbs) and one prospective case cohort study (LURIC), including a total of 4,212 participants of European descent, and identified two novel genetic susceptibility regions at 11p15.5-p13 and 1p31. The region at 11p15.5-p13 (rs4150642; p = 3.20×10−111) contains serum amyloid A1 (SAA1) and the adjacent general transcription factor 2 H1 (GTF2H1), Hermansky-Pudlak Syndrome 5 (HPS5), lactate dehydrogenase A (LDHA), and lactate dehydrogenase C (LDHC). This region explains 10.84% of the total variation of A-SAA levels in our data, which makes up 18.37% of the total estimated heritability. The second region encloses the leptin receptor (LEPR) gene at 1p31 (rs12753193; p = 1.22×10−11) and has been found to be associated with CRP and fibrinogen in previous studies. Our findings demonstrate a key role of the 11p15.5-p13 region in the regulation of baseline A-SAA levels and provide confirmative evidence of the importance of the 1p31 region for inflammatory processes and the close interplay between A-SAA, leptin, and other acute-phase proteins