Cyclicity of singular inner functions from the corona theorem

Carleson's corona theorem is used to obtain two results on cyclicity of singular inner functions in weighted Bergman-type spaces on the unit disk. Our method proof requires no regularity conditions on the weights

2020 Media Futures

What will our media and entertainment be like in 2020

HPA axis related genes and response to psychological therapies: genetics and epigenetics

Background Hypothalamic–pituitary–adrenal (HPA) axis functioning has been implicated in the development of stress-related psychiatric diagnoses and response to adverse life experiences. This study aimed to investigate the association between genetic and epigenetics in HPA axis and response to cognitive behavior therapy (CBT). Methods Children with anxiety disorders were recruited into the Genes for Treatment project (GxT, N = 1,152). Polymorphisms of FKBP5 and GR were analyzed for association with response to CBT. Percentage DNA methylation at the FKBP5 and GR promoter regions was measured before and after CBT in a subset (n = 98). Linear mixed effect models were used to investigate the relationship between genotype, DNA methylation, and change in primary anxiety disorder severity (treatment response). Results Treatment response was not associated with FKBP5 and GR polymorphisms, or pretreatment percentage DNA methylation. However, change in FKBP5 DNA methylation was nominally significantly associated with treatment response. Participants who demonstrated the greatest reduction in severity decreased in percentage DNA methylation during treatment, whereas those with little/no reduction in severity increased in percentage DNA methylation. This effect was driven by those with one or more FKBP5 risk alleles, with no association seen in those with no FKBP5 risk alleles. No significant association was found between GR methylation and response. Conclusions Allele-specific change in FKBP5 methylation was associated with treatment response. This is the largest study to date investigating the role of HPA axis related genes in response to a psychological therapy. Furthermore, this is the first study to demonstrate that DNA methylation changes may be associated with response to psychological therapies in a genotype-dependent manner

Pericytes contribute to airway remodeling in a mouse model of chronic allergic asthma

Myofibroblast accumulation, subepithelial fibrosis, and vascular remodeling are complicating features of chronic asthma, but the mechanisms are not clear. Platelet-derived growth factors (PDGFs) regulate the fate and function of various mesenchymal cells and have been implicated as mediators of lung fibrosis. However, it is not known whether PDGF-BB signaling via PDGFRβ, which is critical for the recruitment of pericytes to blood vessels, plays a role in airway remodeling in chronic asthma. In the present study, we used a selective PDGFRβ inhibitor (CP-673451) to investigate the role of PDGFRβ signaling in the development of airway remodeling and lung dysfunction in an established mouse model of house dust mite-induced chronic allergic asthma. Unexpectedly, we found that pharmacological inhibition of PDGFRβ signaling in the context of chronic aeroallergen exposure led to exacerbated lung dysfunction and airway smooth muscle thickening. Further studies revealed that the inflammatory response to aeroallergen challenge in mice was associated with decreased PDGF-BB expression and the loss of pericytes from the airway microvasculature. In parallel, cells positive for pericyte markers accumulated in the subepithelial region of chronically inflamed airways. This process was exacerbated in animals treated with CP-673451. The results indicate that perturbed PDGF-BB/PDGFRβ signaling and pericyte accumulation in the airway wall may contribute to airway remodeling in chronic allergic asthma

The Provenance, Use and Circulation of Metals in the European Bronze Age: The state of debate

Bronze is the defining metal of the European Bronze Age and has been at the center of archaeological and science-based research for well over a century. Archaeometallurgical studies have largely focused on determining the geological origin of the constituent metals, copper and tin, and their movement from producer to consumer sites. More recently, the effects of recycling, both temporal and spatial, on the composition of the circulating metal stock have received much attention. Also, discussions of the value and perception of bronze, both as individual objects and as hoarded material, continue to be the focus of scholarly debate. Here, we bring together the sometimes diverging views of several research groups on these topics in an attempt to find common ground and set out the major directions of the debate, for the benefit of future research. The paper discusses in turn issues of: geological provenance of new metal entering the system and how to determine and interpret it; the circulation of extant metal across time and space, and how this is seen in changing compositional signatures; and some economic aspects of metal production. These include the role of metal-producing communities within larger economic settings, quantifying the amount of metal present at any one time within a society, and aspects of hoarding, a distinctive European phenomenon that is less prevalent in the Middle Eastern and Asian Bronze Age societies.Funded by the McDonald Institute for Archaeological Researc

Efficiency and safety of varying the frequency of whole blood donation (INTERVAL): a randomised trial of 45 000 donors

Background: Limits on the frequency of whole blood donation exist primarily to safeguard donor health. However, there is substantial variation across blood services in the maximum frequency of donations allowed. We compared standard practice in the UK with shorter inter-donation intervals used in other countries. Methods: In this parallel group, pragmatic, randomised trial, we recruited whole blood donors aged 18 years or older from 25 centres across England, UK. By use of a computer-based algorithm, men were randomly assigned (1:1:1) to 12-week (standard) versus 10-week versus 8-week inter-donation intervals, and women were randomly assigned (1:1:1) to 16-week (standard) versus 14-week versus 12-week intervals. Participants were not masked to their allocated intervention group. The primary outcome was the number of donations over 2 years. Secondary outcomes related to safety were quality of life, symptoms potentially related to donation, physical activity, cognitive function, haemoglobin and ferritin concentrations, and deferrals because of low haemoglobin. This trial is registered with ISRCTN, number ISRCTN24760606, and is ongoing but no longer recruiting participants. Findings: 45 263 whole blood donors (22 466 men, 22 797 women) were recruited between June 11, 2012, and June 15, 2014. Data were analysed for 45 042 (99·5%) participants. Men were randomly assigned to the 12-week (n=7452) versus 10-week (n=7449) versus 8-week (n=7456) groups; and women to the 16-week (n=7550) versus 14-week (n=7567) versus 12-week (n=7568) groups. In men, compared with the 12-week group, the mean amount of blood collected per donor over 2 years increased by 1·69 units (95% CI 1·59–1·80; approximately 795 mL) in the 8-week group and by 0·79 units (0·69–0·88; approximately 370 mL) in the 10-week group (p<0·0001 for both). In women, compared with the 16-week group, it increased by 0·84 units (95% CI 0·76–0·91; approximately 395 mL) in the 12-week group and by 0·46 units (0·39–0·53; approximately 215 mL) in the 14-week group (p<0·0001 for both). No significant differences were observed in quality of life, physical activity, or cognitive function across randomised groups. However, more frequent donation resulted in more donation-related symptoms (eg, tiredness, breathlessness, feeling faint, dizziness, and restless legs, especially among men [for all listed symptoms]), lower mean haemoglobin and ferritin concentrations, and more deferrals for low haemoglobin (p<0·0001 for each) than those observed in the standard frequency groups. Interpretation: Over 2 years, more frequent donation than is standard practice in the UK collected substantially more blood without having a major effect on donors' quality of life, physical activity, or cognitive function, but resulted in more donation-related symptoms, deferrals, and iron deficiency. Funding: NHS Blood and Transplant, National Institute for Health Research, UK Medical Research Council, and British Heart Foundation

Investigating the melt pool properties and thermal effects of multi-laser diode area melting

Diode area melting (DAM) is a new additive manufacturing process that utilises customised architectural arrays of low-power laser diode emitters for high-speed parallel processing of metallic feedstock. The laser diodes operate at shorter laser wavelengths (808 nm) than conventional SLM fibre lasers (1064 nm) theoretically enabling more efficient energy absorption for specific materials. This investigation presents the first work investigating the melt pool properties and thermal effects of the multi-laser DAM process, modelling generated melt pools the unique thermal profiles created along a powder bed during processing. Using this approach process, optimisation can be improved by analysing this thermal temperature distribution, targeting processing conditions that induce full melting for variable powder layer thicknesses. In this work, the developed thermal model simulates the DAM processing of 316L stainless steel and is validated with experimental trials. The simulation indicates that multi-laser DAM methodology can reduce residual stress formation compared to the single point laser scanning methods used during selective laser melting

Impact of stochastic physics and model resolution on the simulation of tropical cyclones in climate GCMs

The role of model resolution in simulating geophysical vortices with the characteristics of realistic Tropical Cyclones (TCs) is well established. The push for increasing resolution continues, with General Circulation Models (GCMs) starting to use sub-10km grid spacing. In the same context it has been suggested that the use of Stochastic Physics (SP) may act as a surrogate for high resolution, providing some of the benefits at a fraction of the cost. Either technique can reduce model uncertainty, and enhance reliability, by providing a more dynamic environment for initial synoptic disturbances to be spawned and to grow into TCs. We present results from a systematic comparison of the role of model resolution and SP in the simulation of TCs, using EC-Earth simulations from project Climate-SPHINX, in large ensemble mode, spanning five different resolutions. All tropical cyclonic systems, including TCs, were tracked explicitly. As in previous studies, the number of simulated TCs increases with the use of higher resolution, but SP further enhances TC frequencies by � 30%, in a strikingly similar way. The use of SP is beneficial for removing systematic climate biases, albeit not consistently so for interannual variability; conversely, the use of SP improves the simulation of the seasonal cycle of TC frequency. An investigation of the mechanisms behind this response indicates that SP generates both higher TC (and TC seed) genesis rates, and more suitable environmental conditions, enabling a more efficient transition of TC seeds into TCs. These results were confirmed by the use of equivalent simulations with the HadGEM3-GC31 GCM