Casimir force in discrete scalar fields I: 1D and 2D cases

We calculate the Casimir force between parallel plates for a discrete massless scalar field. The scalar field forms a periodic lattice in continuous spacetime. The dispersion relation for both the square and triangular lattices allows for the accurate reproduction of the subtle Casimir effect without encountering infinite quantities. Our findings demonstrate that the Casimir force is independent of the type of periodic lattice used. At low frequencies, we observe a high level of rotational symmetry in both lattices. However, at high frequencies, both lattices lose their rotational symmetry, although the propagation of high-frequency waves becomes significantly limited as their group velocity approaches zero. We claim that the behavior of physics in discrete fields becomes similar to that in the continuous case, with the exception that we now have a natural and smooth cutoff mechanism that proves useful in cases requiring regularization. It appears that we have found an alternative approach to regularization using lattices with different symmetries in the background of continuous spacetime.Comment: 10 pages, 9 figure

An accurate calculation of the nucleon axial charge with lattice QCD

We report on a lattice QCD calculation of the nucleon axial charge, $g_A$, using M\"{o}bius Domain-Wall fermions solved on the dynamical $N_f=2+1+1$ HISQ ensembles after they are smeared using the gradient-flow algorithm. The calculation is performed with three pion masses, $m_\pi\sim\{310,220,130\}$ MeV. Three lattice spacings ($a\sim\{0.15,0.12,0.09\}$ fm) are used with the heaviest pion mass, while the coarsest two spacings are used on the middle pion mass and only the coarsest spacing is used with the near physical pion mass. On the $m_\pi\sim220$ MeV, $a\sim0.12$ fm point, a dedicated volume study is performed with $m_\pi L \sim \{3.22,4.29,5.36\}$. Using a new strategy motivated by the Feynman-Hellmann Theorem, we achieve a precise determination of $g_A$ with relatively low statistics, and demonstrable control over the excited state, continuum, infinite volume and chiral extrapolation systematic uncertainties, the latter of which remains the dominant uncertainty. Our final determination at 2.6\% total uncertainty is $g_A = 1.278(21)(26)$, with the first uncertainty including statistical and systematic uncertainties from fitting and the second including model selection systematics related to the chiral and continuum extrapolation. The largest reduction of the second uncertainty will come from a greater number of pion mass points as well as more precise lattice QCD results near the physical pion mass.Comment: 17 pages + 11 pages of references and appendices. 15 figures. Interested readers can download the Python analysis scripts and an hdf5 data file at https://github.com/callat-qcd/project_gA_v

Cassini observations of ionospheric plasma in Saturn's magnetotail lobes

Studies of Saturn's magnetosphere with the Cassini mission have established the importance of Enceladus as the dominant mass source for Saturn's magnetosphere. It is well known that the ionosphere is an important mass source at Earth during periods of intense geomagnetic activity but lesser attention has been dedicated to study the ionospheric mass source at Saturn. In this paper we describe a case study of data from Saturn's magnetotail, when Cassini was located at ∼2200 hours Saturn local time at 36 RS from Saturn. During several entries into the magnetotail lobe, tailward-flowing cold electrons and a cold ion beam were observed directly adjacent to the plasma sheet and extending deeper into the lobe. The electrons and ions appear to be dispersed, dropping to lower energies with time. The composition of both the plasma sheet and lobe ions show very low fluxes (sometimes zero within measurement error) of water group ions. The magnetic field has a swept-forward configuration which is atypical for this region and the total magnetic field strength larger than expected at this distance from the planet. Ultraviolet auroral observations show a dawn brightening and upstream heliospheric models suggest that the magnetosphere is being compressed by a region of high solar wind ram pressure. We interpret this event as the observation of ionospheric outflow in Saturn's magnetotail. We estimate a number flux between 2.95±0.43×109 1.43±0.21×1010 cm-2 s-1, one or about two orders magnitude larger than suggested by steady state MHD models, with a mass source between 1.4×102 and 1.1×103 kg/s. After considering several configurations for the active atmospheric regions, we consider as most probable the main auroral oval, with associated mass source between 49.7±13.4 and 239.8±64.8 kg/s for an average auroral oval, and 10±4 and 49±23 kg/s for the specific auroral oval morphology found during this event. It is not clear how much of this mass is trapped within the magnetosphere and how much is lost to the solar wind

Novel formulations of oral bisphosphonates in the treatment of osteoporosis.

Oral bisphosphonates are a key intervention in the treatment of osteoporosis and in reducing the risk of fragility fractures. Their use is supported by over 3 decades of evidence; however, patient adherence to oral bisphosphonates remains poor in part due to complex dosing instructions and adverse events, including upper gastrointestinal symptoms. This problem has led to the development of novel oral bisphosphonate formulations. Buffered, effervescent alendronate is dissolved in water and so seeks to reduce upper gastro-intestinal adverse events, and gastro-resistant risedronate aims to reduce the complexity of dosing procedure (e.g. fasting prior to consumption) whilst still maintaining the efficacy of fracture risk reduction. Clinical trials and real-world data have been employed to demonstrate some benefits in terms of reduced upper gastro-intestinal adverse events, adherence, persistence and health economic outcomes. This report describes the result of an ESCEO (European Society for Clinical and Economic Aspects of Osteoporosis and Osteoarthritis) expert working group, which explores where oral bisphosphonates sit in current clinical practice guidelines, review their risk-benefit profile and the consequences of poor adherence before exploring novel oral bisphosphonate formulations and their potential clinical and health economic impact. Further research is required but there are signs that these novel, oral bisphosphonate formulations may lead to improved tolerance of oral bisphosphonates and thus, improved adherence and fracture outcomes

Enceladus and Titan: Emerging Worlds of the Solar System (ESA Voyage 2050 White Paper)

Some of the major discoveries of the recent Cassini-Huygens mission have put Titan and Enceladus firmly on the Solar System map. The mission has revolutionised our view of Solar System satellites, arguably matching their scientific importance with that of their planet. While Cassini-Huygens has made big surprises in revealing Titan's organically rich environment and Enceladus' cryovolcanism, the mission's success naturally leads us to further probe these findings. We advocate the acknowledgement of Titan and Enceladus science as highly relevant to ESA's long-term roadmap, as logical follow-on to Cassini-Huygens. In this white paper, we will outline important science questions regarding these satellites and identify the pertinent science themes we recommend ESA cover during the Voyage 2050 planning cycle. Addressing these science themes would make major advancements to the present knowledge we have about the Solar System, its formation, evolution and likelihood that other habitable environments exist outside the Earth's biosphere

Cystatin C is glucocorticoid responsive, directs recruitment of Trem2+ macrophages, and predicts failure of cancer immunotherapy

Cystatin C (CyC), a secreted cysteine protease inhibitor, has unclear biological functions. Many patients exhibit elevated plasma CyC levels, particularly during glucocorticoid (GC) treatment. This study links GCs with CyC’s systemic regulation by utilizing genome-wide association and structural equation modeling to determine CyC production genetics in the UK Biobank. Both CyC production and a polygenic score (PGS) capturing predisposition to CyC production were associated with increased all-cause and cancer-specific mortality. We found that the GC receptor directly targets CyC, leading to GC-responsive CyC secretion in macrophages and cancer cells. CyC-knockout tumors displayed significantly reduced growth and diminished recruitment of TREM2+ macrophages, which have been connected to cancer immunotherapy failure. Furthermore, the CyC-production PGS predicted checkpoint immunotherapy failure in 685 patients with metastatic cancer from combined clinical trial cohorts. In conclusion, CyC may act as a GC effector pathway via TREM2+ macrophage recruitment and may be a potential target for combination cancer immunotherapy.publishedVersio

Twenty-five years of end-user searching, Part 1: Research findings

This is the first part of a two-part article that reviews 25 years of published research findings on end-user searching in online information retrieval (IR) systems. In Part 1 (Markey, 2007 ), the author seeks to answer the following questions: What characterizes the queries that end users submit to online IR systems? What search features do people use? What features would enable them to improve on the retrievals they have in hand? What features are hardly ever used? What do end users do in response to the system's retrievals? Are end users satisfied with their online searches? Summarizing searches of online IR systems by the search features people use everyday makes information retrieval appear to be a very simplistic one-stop event. In Part 2, the author examines current models of the information retrieval process, demonstrating that information retrieval is much more complex and involves changes in cognition, feelings, and/or events during the information seeking process. She poses a host of new research questions that will further our understanding about end-user searching of online IR systems.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/56093/1/20462_ftp.pd

Migraine, inflammatory bowel disease and celiac disease:A Mendelian randomization study

Objective: To assess whether migraine may be genetically and/or causally associated with inflammatory bowel disease (IBD) or celiac disease. Background: Migraine has been linked to IBD and celiac disease in observational studies, but whether this link may be explained by a shared genetic basis or could be causal has not been established. The presence of a causal association could be clinically relevant, as treating one of these medical conditions might mitigate the symptoms of a causally linked condition. Methods:Linkage disequilibrium score regression and two-sample bidirectional Mendelian randomization analyses were performed using summary statistics from cohort-based genome-wide association studies of migraine (59,674 cases; 316,078 controls), IBD (25,042 cases; 34,915 controls) and celiac disease (11,812 or 4533 cases; 11,837 or 10,750 controls). Migraine with and without aura were analyzed separately, as were the two IBD subtypes Crohn's disease and ulcerative colitis. Positive control analyses and conventional Mendelian randomization sensitivity analyses were performed.Results: Migraine was not genetically correlated with IBD or celiac disease. No evidence was observed for IBD (odds ratio [OR] 1.00, 95% confidence interval [CI] 0.99–1.02, p = 0.703) or celiac disease (OR 1.00, 95% CI 0.99–1.02, p = 0.912) causing migraine or migraine causing either IBD (OR 1.08, 95% CI 0.96–1.22, p = 0.181) or celiac disease (OR 1.08, 95% CI 0.79–1.48, p = 0.614) when all participants with migraine were analyzed jointly. There was some indication of a causal association between celiac disease and migraine with aura (OR 1.04, 95% CI 1.00–1.08, p = 0.045), between celiac disease and migraine without aura (OR 0.95, 95% CI 0.92–0.99, p = 0.006), as well as between migraine without aura and ulcerative colitis (OR 1.15, 95% CI 1.02–1.29, p = 0.025). However, the results were not significant after multiple testing correction. Conclusions: We found no evidence of a shared genetic basis or of a causal association between migraine and either IBD or celiac disease, although we obtained some indications of causal associations with migraine subtypes.</p

The eClinical Care Pathway Framework: A novel structure for creation of online complex clinical care pathways and its application in the management of sexually transmitted infections.

Despite considerable international eHealth impetus, there is no guidance on the development of online clinical care pathways. Advances in diagnostics now enable self-testing with home diagnosis, to which comprehensive online clinical care could be linked, facilitating completely self-directed, remote care. We describe a new framework for developing complex online clinical care pathways and its application to clinical management of people with genital chlamydia infection, the commonest sexually transmitted infection (STI) in England.Using the existing evidence-base, guidelines and examples from contemporary clinical practice, we developed the eClinical Care Pathway Framework, a nine-step iterative process. Step 1: define the aims of the online pathway; Step 2: define the functional units; Step 3: draft the clinical consultation; Step 4: expert review; Step 5: cognitive testing; Step 6: user-centred interface testing; Step 7: specification development; Step 8: software testing, usability testing and further comprehension testing; Step 9: piloting. We then applied the Framework to create a chlamydia online clinical care pathway (Online Chlamydia Pathway).Use of the Framework elucidated content and structure of the care pathway and identified the need for significant changes in sequences of care (Traditional: history, diagnosis, information versus Online: diagnosis, information, history) and prescribing safety assessment. The Framework met the needs of complex STI management and enabled development of a multi-faceted, fully-automated consultation.The Framework provides a comprehensive structure on which complex online care pathways such as those needed for STI management, which involve clinical services, public health surveillance functions and third party (sexual partner) management, can be developed to meet national clinical and public health standards. The Online Chlamydia Pathway's standardised method of collecting data on demographics and sexual behaviour, with potential for interoperability with surveillance systems, could be a powerful tool for public health and clinical management.UKCRC Translational Infection Research (TIR) Initiative supported by the Medical Research Council, eSTI2 Consortium (Grant Number G0901608)

Understanding of Coupled Terrestrial Carbon, Nitrogen and Water Dynamics—An Overview

Coupled terrestrial carbon (C), nitrogen (N) and hydrological processes play a crucial role in the climate system, providing both positive and negative feedbacks to climate change. In this review we summarize published research results to gain an increased understanding of the dynamics between vegetation and atmosphere processes. A variety of methods, including monitoring (e.g., eddy covariance flux tower, remote sensing, etc.) and modeling (i.e., ecosystem, hydrology and atmospheric inversion modeling) the terrestrial carbon and water budgeting, are evaluated and compared. We highlight two major research areas where additional research could be focused: (i) Conceptually, the hydrological and biogeochemical processes are closely linked, however, the coupling processes between terrestrial C, N and hydrological processes are far from well understood; and (ii) there are significant uncertainties in estimates of the components of the C balance, especially at landscape and regional scales. To address these two questions, a synthetic research framework is needed which includes both bottom-up and top-down approaches integrating scalable (footprint and ecosystem) models and a spatially nested hierarchy of observations which include multispectral remote sensing, inventories, existing regional clusters of eddy-covariance flux towers and CO2 mixing ratio towers and chambers