ECB Unconventional Monetary Policy and SME Access to Finance

Small- and medium-sized enterprises (SMEs) account for two-thirds of employment in the euro area which makes them a priority for the transmission of monetary policy to the real economy. SMEs in Europe experienced a credit crunch following the sovereign debt crisis. Over the period 2014–2019, the European Central Bank (ECB) engaged in unconventional monetary policy (UMP) to restore funding conditions in the euro area, to support stronger economic growth and higher inflation. We use the ECB/EC Survey on the Access to Finance of Enterprises to examine the relationship between monetary policy and SME access to finance in countries that were most affected by the crisis as follows: Greece, Ireland, Italy, Portugal and Spain. We show that the implementation of UMP increases the probability that firms with higher debt-to-assets ratio remain credit constrained in stressed countries, although this effect becomes insignificant in non-stressed countries. Our findings suggest that monetary policy is transmitted unevenly to leveraged SMEs across jurisdictions. Additionally, we find little evidence that risky firms are credit constrained during periods of UMP, when risk is measured from the firms’ own viewpoint. However, our heterogenous analysis shows that smaller and younger firms—which are also considered to be risky—remain credit constrained over this period. Policy should ensure that UMP trickles down to SMEs regardless of their size, age or location. Tweetable line: Leveraged SMEs in stressed countries are more likely to remain credit constrained even when monetary policy is expansionary. Policy must do more to support small and young firms’ access to credit to facilitate higher investment and growth

A computational study of whole-brain connectivity in resting state and task fMRI

Background: We compared the functional brain connectivity produced during resting-state in which subjects were not actively engaged in a task with that produced while they actively performed a visual motion task (task-state). Material/Methods In this paper we employed graph-theoretical measures and network statistics in novel ways to compare, in the same group of human subjects, functional brain connectivity during resting-state fMRI with brain connectivity during performance of a high level visual task. We performed a whole-brain connectivity analysis to compare network statistics in resting and task states among anatomically defined Brodmann areas to investigate how brain networks spanning the cortex changed when subjects were engaged in task performance. Results: In the resting state, we found strong connectivity among the posterior cingulate cortex (PCC), precuneus, medial prefrontal cortex (MPFC), lateral parietal cortex, and hippocampal formation, consistent with previous reports of the default mode network (DMN). The connections among these areas were strengthened while subjects actively performed an event-related visual motion task, indicating a continued and strong engagement of the DMN during task processing. Regional measures such as degree (number of connections) and betweenness centrality (number of shortest paths), showed that task performance induces stronger inter-regional connections, leading to a denser processing network, but that this does not imply a more efficient system as shown by the integration measures such as path length and global efficiency, and from global measures such as small-worldness. Conclusions: In spite of the maintenance of connectivity and the “hub-like” behavior of areas, our results suggest that the network paths may be rerouted when performing the task condition

Scale Changes Provide an Alternative Cue For the Discrimination of Heading, But Not Object Motion

Background: Understanding the dynamics of our surrounding environments is a task usually attributed to the detection of motion based on changes in luminance across space. Yet a number of other cues, both dynamic and static, have been shown to provide useful information about how we are moving and how objects around us move. One such cue, based on changes in spatial frequency, or scale, over time has been shown to be useful in conveying motion in depth even in the absence of a coherent, motion-defined flow field (optic flow). Material/Methods 16 right handed healthy observers (ages 18–28) participated in the behavioral experiments described in this study. Using analytical behavioral methods we investigate the functional specificity of this cue by measuring the ability of observers to perform tasks of heading (direction of self-motion) and 3D trajectory discrimination on the basis of scale changes and optic flow. Results: Statistical analyses of performance on the test-experiments in comparison to the control experiments suggests that while scale changes may be involved in the detection of heading, they are not correctly integrated with translational motion and, thus, do not provide a correct discrimination of 3D object trajectories. Conclusions: These results have the important implication for the type of visual guided navigation that can be done by an observer blind to optic flow. Scale change is an important alternative cue for self-motion

P783 Clinical, Humanistic, and Economic Burden in Patients with PNH Receiving C5 Inhibition Treatment across UK, Germany, and France. Insights from the Commodore Burden of Illness Study

Paroxysmal nocturnal hemoglobinuria (PNH) is a rare, life-threatening blood disorder. In the UK, Germany, and France, C5 complement inhibitors, such as eculizumab and ravulizumab, both of which are intravenously (IV) infused, are the standard of care for PNH

The comparative institutional analysis of energy transitions

The discussion on ‘The comparative institutional analysis of energy transitions’ gives us a state-of-the-art overview of the main theoretical and conceptual developments within the field of political economy. It invites us to broaden our knowledge on the changing realities of different geographical regions in energy transition. In this discussion forum, Finnegan discusses emerging themes in the comparative political economy literature of climate change. He identifies gaps and offers an outline for further research. Allen, Allen, Cumming and Johan take a closer look at the links between different types of capitalism and the natural environment. The authors stress the importance of adopting an institutional perspective to explain differences in environmental outcomes. Wood compares the transitions of energy usage and mixes between liberal and coordinated market economies from a historical perspective. He looks for parallels between the energy transition from coal to oil and gas to the current renewables. Nicklich and Endo answer the question ‘Do globalization and globally perceived occurrences of environmental problems lead to a convergence of energy supply?’. They compare the fields of German and Japanese wind power with a particular focus on Greenpeace after the Fukushima disaster in 2011. Finally, Lim and Tanaka focus on the question ‘When do energy transition policies enjoy broad-based acceptance?’. They conclude that the public acceptance of energy transition varies between Western and non-Western societies

BioDeepTime : a database of biodiversity time series for modern and fossil assemblages

We thank the Paleosynthesis Project and the Volkswagen Stiftung for funding that supported this project (Az 96 796). M.C.R. acknowledges the German Research Foundation (DFG) for funding through the Cluster of Excellence ‘The Ocean Floor – Earth's Uncharted Interface’ (EXC 2077, grant no. 390741603). E.E.S. acknowledges funding from Leverhulme Trust grant RPG-201170, the Leverhulme Prize and the National Science Research Council grant NE/V011405/1. Q.J.L. and L.N. acknowledge support from the Youth Innovation Promotion Association (2019310) and the Chinese Academy of Sciences (CAS-WX2021SF-0205). A.M.P. acknowledges funding from the Leverhulme Trust through research grant RPG-2019-402. M.D. acknowledges funding from Leverhulme Trust through the Leverhulme Centre for Anthropocene Biodiversity (RC-2018-021) and a research grant (RPG-2019-402), and the European Union (ERC coralINT, 101044975). L. H. L. acknowledges funding from the European Research Council (macroevolution.abc ERC grant no. 724324). K.H.P acknowledges funding from the National Science Foundation Graduate Research Fellowship Program (DGE-2139841). H.H.M.H. acknowledges support from Peter Buck Postdoc Fellowship, Smithsonian Institution. A.T. acknowledges funding from the Slovak Research and Development Agency (APVV 22-0523) and the Slovak Scientific Grant Agency (VEGA 02/0106/23).Motivation We have little understanding of how communities respond to varying magnitudes and rates of environmental perturbations across temporal scales. BioDeepTime harmonizes assemblage time series of presence and abundance data to help facilitate investigations of community dynamics across timescales and the response of communities to natural and anthropogenic stressors. BioDeepTime includes time series of terrestrial and aquatic assemblages of varying spatial and temporal grain and extent from the present-day to millions of years ago. Main Types of Variables Included BioDeepTime currently contains 7,437,847 taxon records from 10,062 assemblage time series, each with a minimum of 10 time steps. Age constraints, sampling method, environment and taxonomic scope are provided for each time series. Spatial Location and Grain The database includes 8752 unique sampling locations from freshwater, marine and terrestrial ecosystems. Spatial grain represented by individual samples varies from quadrats on the order of several cm2 to grid cells of ~100 km2. Time Period and Grain BioDeepTime in aggregate currently spans the last 451?million years, with the 10,062 modern and fossil assemblage time series ranging in extent from years to millions of years. The median extent of modern time series is 18.7?years and for fossil series is 54,872?years. Temporal grain, the time encompassed by individual samples, ranges from days to tens of thousands of years. Major Taxa and Level of Measurement The database contains information on 28,777 unique taxa with 4,769,789 records at the species level and another 271,218 records known to the genus level, including time series of benthic and planktonic foraminifera, coccolithophores, diatoms, ostracods, plants (pollen), radiolarians and other invertebrates and vertebrates. There are to date 7012 modern and 3050 fossil time series in BioDeepTime. Software Format SQLite, Comma-separated values.Publisher PDFPeer reviewe

Evolutionary Dynamics of the Ty3/Gypsy LTR Retrotransposons in the Genome of Anopheles gambiae

Ty3/gypsy elements represent one of the most abundant and diverse LTR-retrotransposon (LTRr) groups in the Anopheles gambiae genome, but their evolutionary dynamics have not been explored in detail. Here, we conduct an in silico analysis of the distribution and abundance of the full complement of 1045 copies in the updated AgamP3 assembly. Chromosomal distribution of Ty3/gypsy elements is inversely related to arm length, with densities being greatest on the X, and greater on the short versus long arms of both autosomes. Taking into account the different heterochromatic and euchromatic compartments of the genome, our data suggest that the relative abundance of Ty3/gypsy LTRrs along each chromosome arm is determined mainly by the different proportions of heterochromatin, particularly pericentric heterochromatin, relative to total arm length. Additionally, the breakpoint regions of chromosomal inversion 2La appears to be a haven for LTRrs. These elements are underrepresented more than 7-fold in euchromatin, where 33% of the Ty3/gypsy copies are associated with genes. The euchromatin on chromosome 3R shows a faster turnover rate of Ty3/gypsy elements, characterized by a deficit of proviral sequences and the lowest average sequence divergence of any autosomal region analyzed in this study. This probably reflects a principal role of purifying selection against insertion for the preservation of longer conserved syntenyc blocks with adaptive importance located in 3R. Although some Ty3/gypsy LTRrs show evidence of recent activity, an important fraction are inactive remnants of relatively ancient insertions apparently subject to genetic drift. Consistent with these computational predictions, an analysis of the occupancy rate of putatively older insertions in natural populations suggested that the degenerate copies have been fixed across the species range in this mosquito, and also are shared with the sibling species Anopheles arabiensis

Fish oil administration in older adults: is there potential for adverse events? A systematic review of the literature

ackground: Omega-3 (n-3) fatty acid supplementation is becoming increasingly popular. However given its antithrombotic properties the potential for severe adverse events (SAE) such as bleeding has safety implications, particularly in an older adult population. A systematic review of randomized control trials (RCT) was conducted to explore the potential for SAE and non-severe adverse events (non-SAE) associated with n-3 supplementation in older adults. Methods: A comprehensive search strategy using Medline and a variety of other electronic sources was conducted. Studies investigating the oral administration of n-3 fish oil containing eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA) or both against a placebo were sourced. The primary outcome of interest included reported SAE associated with n-3 supplementation. Chi-square analyses were conducted on the pooled aggregate of AEs. Results: Of the 398 citations initially retrieved, a total of 10 studies involving 994 older adults aged ≥60 years were included in the review. Daily fish oil doses ranged from 0.03 g to 1.86 g EPA and/or DHA with study durations ranging from 6 to 52 weeks. No SAE were reported and there were no significant differences in the total AE rate between groups (n-3 intervention group: 53/540; 9.8%; placebo group: 28/454; 6.2%; p= 0.07). Non-SAE relating to gastrointestinal (GI) disturbances were the most commonly reported however there was no significant increase in the proportion of GI disturbances reported in participants randomized to the n-3 intervention (n-3 intervention group: 42/540 (7.8%); placebo group: 24/454 (5.3%); p= 0.18). Conclusions: The potential for AEs appear mild-moderate at worst and are unlikely to be of clinical significance. The use of n-3 fatty acids and the potential for SAE should however be further researched to investigate whether this evidence is consistent at higher doses and in other populations. These results also highlight that well-documented data outlining the potential for SAE following n-3 supplementation are limited nor adequately reported to draw definitive conclusions concerning the safety associated with n-3 supplementation. A more rigorous and systematic approach for monitoring and recording AE data in clinical settings that involve n-3 supplementation is required.The authors would like to acknowledge funding provided for the ongoing ATLANTIC randomized controlled trial supported by the National Health and Medical Research Council (NHMRC), Australia

Obeticholic acid for the treatment of non-alcoholic steatohepatitis: interim analysis from a multicentre, randomised, placebo-controlled phase 3 trial

Background Non-alcoholic steatohepatitis (NASH) is a common type of chronic liver disease that can lead to cirrhosis. Obeticholic acid, a farnesoid X receptor agonist, has been shown to improve the histological features of NASH. Here we report results from a planned interim analysis of an ongoing, phase 3 study of obeticholic acid for NASH. Methods In this multicentre, randomised, double-blind, placebo-controlled study, adult patients with definite NASH,non-alcoholic fatty liver disease (NAFLD) activity score of at least 4, and fibrosis stages F2–F3, or F1 with at least oneaccompanying comorbidity, were randomly assigned using an interactive web response system in a 1:1:1 ratio to receive oral placebo, obeticholic acid 10 mg, or obeticholic acid 25 mg daily. Patients were excluded if cirrhosis, other chronic liver disease, elevated alcohol consumption, or confounding conditions were present. The primary endpointsfor the month-18 interim analysis were fibrosis improvement (≥1 stage) with no worsening of NASH, or NASH resolution with no worsening of fibrosis, with the study considered successful if either primary endpoint was met. Primary analyses were done by intention to treat, in patients with fibrosis stage F2–F3 who received at least one dose of treatment and reached, or would have reached, the month 18 visit by the prespecified interim analysis cutoff date. The study also evaluated other histological and biochemical markers of NASH and fibrosis, and safety. This study is ongoing, and registered with ClinicalTrials.gov, NCT02548351, and EudraCT, 20150-025601-6. Findings Between Dec 9, 2015, and Oct 26, 2018, 1968 patients with stage F1–F3 fibrosis were enrolled and received at least one dose of study treatment; 931 patients with stage F2–F3 fibrosis were included in the primary analysis (311 in the placebo group, 312 in the obeticholic acid 10 mg group, and 308 in the obeticholic acid 25 mg group). The fibrosis improvement endpoint was achieved by 37 (12%) patients in the placebo group, 55 (18%) in the obeticholic acid 10 mg group (p=0·045), and 71 (23%) in the obeticholic acid 25 mg group (p=0·0002). The NASH resolution endpoint was not met (25 [8%] patients in the placebo group, 35 [11%] in the obeticholic acid 10 mg group [p=0·18], and 36 [12%] in the obeticholic acid 25 mg group [p=0·13]). In the safety population (1968 patients with fibrosis stages F1–F3), the most common adverse event was pruritus (123 [19%] in the placebo group, 183 [28%] in the obeticholic acid 10 mg group, and 336 [51%] in the obeticholic acid 25 mg group); incidence was generally mild to moderate in severity. The overall safety profile was similar to that in previous studies, and incidence of serious adverse events was similar across treatment groups (75 [11%] patients in the placebo group, 72 [11%] in the obeticholic acid 10 mg group, and 93 [14%] in the obeticholic acid 25 mg group). Interpretation Obeticholic acid 25 mg significantly improved fibrosis and key components of NASH disease activity among patients with NASH. The results from this planned interim analysis show clinically significant histological improvement that is reasonably likely to predict clinical benefit. This study is ongoing to assess clinical outcomes