Dotted and Undotted Algebraic Spinor Fields in General Relativity

We investigate using Clifford algebra methods the theory of algebraic dotted and undotted spinor fields over a Lorentzian spacetime and their realizations as matrix spinor fields, which are the usual dotted and undotted two component spinor fields. We found that some ad hoc rules postulated for the covariant derivatives of Pauli sigma matrices and also for the Dirac gamma matrices in General Relativity cover important physical meaning, which is not apparent in the usual matrix presentation of the theory of two components dotted and undotted spinor fields. We also discuss some issues related to the the previous one and which appear in a proposed "unified" theory of gravitation and electromagnetism which use two components dotted and undotted spinor fields and also paravector fields, which are particular sections of the even subundle of the Clifford bundle of spacetime.Comment: some new misprints have been correcte

Quark mixing from softly broken symmetries

Quark flavor mixing may originate in the soft breaking of horizontal symmetries. Those symmetries, which in the simplest case are three family U(1) groups, are obeyed only by the dimension-4 Yukawa couplings and lead, when unbroken, to the absence of mixing. Their breaking may arise from the dimension-3 mass terms of SU(2)-singlet vector-like quarks. Those gauge-singlet mass terms break the horizontal symmetries at a scale much higher than the Fermi scale, yet softly, leading to quark mixing while the quark masses remain unsuppressed.Comment: 9 pages, plain Latex, no figure

RNA-seq and Tn-seq reveal fitness determinants of vancomycin-resistant Enterococcus faecium during growth in human serum

BACKGROUND: The Gram-positive bacterium Enterococcus faecium is a commensal of the human gastrointestinal tract and a frequent cause of bloodstream infections in hospitalized patients. The mechanisms by which E. faecium can survive and grow in blood during an infection have not yet been characterized. Here, we identify genes that contribute to growth of E. faecium in human serum through transcriptome profiling (RNA-seq) and a high-throughput transposon mutant library sequencing approach (Tn-seq). RESULTS: We first sequenced the genome of E. faecium E745, a vancomycin-resistant clinical isolate, using a combination of short- and long read sequencing, revealing a 2,765,010 nt chromosome and 6 plasmids, with sizes ranging between 9.3 kbp and 223.7 kbp. We then compared the transcriptome of E. faecium E745 during exponential growth in rich medium and in human serum by RNA-seq. This analysis revealed that 27.8% of genes on the E. faecium E745 genome were differentially expressed in these two conditions. A gene cluster with a role in purine biosynthesis was among the most upregulated genes in E. faecium E745 upon growth in serum. The E. faecium E745 transposon mutant library was then used to identify genes that were specifically required for growth of E. faecium in serum. Genes involved in de novo nucleotide biosynthesis (including pyrK_2, pyrF, purD, purH) and a gene encoding a phosphotransferase system subunit (manY_2) were thus identified to be contributing to E. faecium growth in human serum. Transposon mutants in pyrK_2, pyrF, purD, purH and manY_2 were isolated from the library and their impaired growth in human serum was confirmed. In addition, the pyrK_2 and manY_2 mutants were tested for their virulence in an intravenous zebrafish infection model and exhibited significantly attenuated virulence compared to E. faecium E745. CONCLUSIONS: Genes involved in carbohydrate metabolism and nucleotide biosynthesis of E. faecium are essential for growth in human serum and contribute to the pathogenesis of this organism. These genes may serve as targets for the development of novel anti-infectives for the treatment of E. faecium bloodstream infections

The Minimal Phantom Sector of the Standard Model: Higgs Phenomenology and Dirac Leptogenesis

We propose the minimal, lepton-number conserving, SU(3)xSU(2)xU(1) gauge-singlet, or phantom, extension of the Standard Model. The extension is natural in the sense that all couplings are of O(1) or forbidden due to a phantom sector global U(1)_D symmetry, and basically imitates the standard Majorana see-saw mechanism. Spontaneous breaking of the U(1)_D symmetry triggers consistent electroweak gauge symmetry breaking only if it occurs at a scale compatible with small Dirac neutrino masses and baryogenesis through Dirac leptogenesis. Dirac leptogenesis proceeds through the usual out-of-equilibrium decay scenario, leading to left and right-handed neutrino asymmetries that do not fully equilibrate after they are produced. The model contains two physical Higgs bosons and a massless Goldstone boson. The existence of the Goldstone boson suppresses the Higgs to bb branching ratio and instead the Higgs bosons will mainly decay to invisible Goldstone and/or to visible vector boson pairs. In a representative scenario, we estimate that with 30 fb^-1 integrated luminosity, the LHC could discover this invisibly decaying Higgs, with mass ~120 GeV. At the same time a significantly heavier, partner Higgs boson with mass ~210 GeV could be found through its vector boson decays. Electroweak constraints as well as astrophysical and cosmological implications are analysed and discussed.Comment: 21 pages, 4 figures. Corrected typos and added references. To appear in JHE

Can electronic monitoring with a digital smart spacer support personalised medication adherence and inhaler technique education in patients with asthma?:Protocol of the randomised controlled OUTERSPACE trial

INTRODUCTION: Medication adherence and inhaler technique in patients with asthma remain suboptimal. A digital, smart spacer may support personalised adherence and inhaler technique education. The aim of this study is to assess the feasibility of undertaking a definitive randomised controlled trial of personalised, smart spacer data-driven education and explore clinical benefits. METHODS AND ANALYSIS: We present the design of the multicentre, randomised controlled OUtcomes following Tailored Education and Retraining: Studying Performance and AdherenCE feasibility trial of 2 months. Patients will be recruited from four Dutch general practices. At t=-1, patients with asthma ≥18 years using inhaled corticosteroids±long-acting beta-agonists±short-acting beta-agonists administered with a pressurised-metered-dose-inhaler and spacer (n=40) will use a smart spacer for 1 month. The rechargeable CE-marked smart spacer (Aerochamber Plus with Flow Vu) includes a sensor that monitors adherence and inhalation technique to prescribed dosing regimen of both maintenance and reliever inhalers. After 1 month (t=0), patients are 1:1 randomised into two groups: control group (usual care) versus intervention group (personalised education). At t=-1, t=0 and t=1 month, the Asthma Control Questionnaire (ACQ), Work Productivity and Activity Impairment (WPAI) questionnaire and Test of Adherence to Inhalers (TAI) are administered and fractional exhaled nitric oxide (FeNO) is assessed. At t=0 and t=1, spirometry is performed. At t=1, usability and satisfaction will be analysed using the System Usability Scale and interviews with patients and healthcare providers. Primary outcome is the overall feasibility of a definitive trial assessed by patient recruitment speed, participation and drop-out rate. Secondary outcomes are patient and healthcare provider satisfaction and exploratory clinical outcomes are adherence, inhaler technique, TAI score, FeNO, lung function, ACQ and WPAI. ETHICS AND DISSEMINATION: Ethical approval was obtained from the RTPO in Leeuwarden, Netherlands (number: NL78361.099.21). Patients will provide written informed consent. Study findings will be disseminated through conferences and peer-reviewed scientific and professional journals. TRIAL REGISTRATION NUMBER: NL9637

Electronic monitoring with a digital smart spacer to support personalized inhaler use education in patients with asthma:The randomized controlled OUTERSPACE trial

BACKGROUND: Poor adherence to inhaled medication has been associated with poor outcomes. Smart spacers can monitor inhaler use and technique, yet their feasibility in adults with asthma and their potential benefits are unknown.OBJECTIVE: Assessing the feasibility of undertaking a definitive randomized controlled trial (RCT) of smart spacer-based inhaler education and explore potential clinical benefits in adults with asthma.METHODS: Two-month randomized controlled feasibility OUtcomes following Tailored Education and Retraining: Studying Performance and AdherenCE (OUTERSPACE) trial comparing personalized smart spacer-based inhaler education versus usual care. Patients were recruited in four Dutch primary care centres. Outcomes were feasibility (inclusion speed, patient acceptance), medication adherence, inhaler technique, clinical effects (lung function, ACQ, FeNO) and usability (System Usability Scale [SUS]).RESULTS: 42 patients were randomized and all completed the study. The feasibility of performing a larger trial focusing on asthma patient education using a smart spacer was demonstrated with all patients included in four months and a participation rate of 86%. In the intervention group, inhalation errors per day decreased by 26.2% while in the usual care group inhalation errors increased by 14.6% (p = 0.021). Adherence decreased slightly in the intervention group as opposed to improvement in the control group (difference 12%, p = 0.028). No changes in lung function, ACQ or FeNO were observed. Usability was deemed high (SUS patients 71, nurses 89).CONCLUSION: This RCT showed that smart spacer-driven education in patients with asthma is feasible and in this short-term study reduced inhaler errors. Longer-term and larger studies are required to assess clinical effects.</p

Association between COVID-19 lockdown measures and the incidence of iatrogenic versus spontaneous very preterm births in the Netherlands:a retrospective study

Background: The COVID-19 pandemic led to regional or nationwide lockdowns as part of risk mitigation measurements in many countries worldwide. Recent studies suggest an unexpected and unprecedented decrease in preterm births during the initial COVID-19 lockdowns in the first half of 2020. The objective of the current study was to assess the effects of the two months of the initial national COVID-19 lockdown period on the incidence of very and extremely preterm birth in the Netherlands, stratified by either spontaneous or iatrogenic onset of delivery, in both singleton and multiple pregnancies. Methods: Retrospective cohort study using data from all 10 perinatal centers in the Netherlands on very and extremely preterm births during the initial COVID-19 lockdown from March 15 to May 15, 2020. Incidences of very and extremely preterm birth were calculated using an estimate of the total number of births in the Netherlands in this period. As reference, we used data from the corresponding calendar period in 2015–2018 from the national perinatal registry (Perined). We differentiated between spontaneous versus iatrogenic onset of delivery and between singleton versus multiple pregnancies. Results: The incidence of total preterm birth < 32 weeks in singleton pregnancies was 6.1‰ in the study period in 2020 versus 6.5‰ in the corresponding period in 2015–2018. The decrease in preterm births in singletons was solely due to a significant decrease in iatrogenic preterm births, both < 32 weeks (OR 0.71; 95%CI 0.53 to 0.95) and < 28 weeks (OR 0.53; 95%CI 0.29 to 0.97). For multiple pregnancies, an increase in preterm births < 28 weeks was observed (OR 2.43; 95%CI 1.35 to 4.39). Conclusion: This study shows a decrease in iatrogenic preterm births during the initial COVID-19-related lockdown in the Netherlands in singletons. Future studies should focus on the mechanism of action of lockdown measures and reduction of preterm birth and the effects of perinatal outcome

Digital spacer data driven COPD inhaler adherence education:The OUTERSPACE proof-of-concept study

Pressurized metered dose inhalers are recommended to be used in combination with spacers, yet inhaler technique and adherence are poor. A novel digital "smart" spacer can record spacer use and technique errors and could facilitate personalized education. In this proof-of-concept study, we assessed the usability of the digital spacer and explored its effects on inhaler technique, adherence, long-term systemic drug exposure and clinical outcomes in COPD. Usability was deemed high. One month after personalized digital spacer inhaler education, the mean number of errors per patient per day decreased with 36%, from 6.40 errors/day to 4.07 errors/day (p = 0.038). Drug exposure was confirmed by bioanalytical scalp hair analysis of formoterol. No significant change in clinical outcomes was observed. This study demonstrates the digital spacer's potential value in inhaler education, but larger, longer-term studies are required

Smoke-free legislation and child health

In this paper, we aim to present an overview of the scientific literature on the link between smoke-free legislation and early-life health outcomes. Exposure to second-hand smoke is responsible for an estimated 166 ,000 child deaths each year worldwide. To protect people from tobacco smoke, the World Health Organization recommends the implementation of comprehensive smoke-free legislation that prohibits smoking in all public indoor spaces, including workplaces, bars and restaurants. The implementation of such legislation has been found to reduce tobacco smoke exposure, encourage people to quit smoking and improve adult health outcomes. There is an increasing body of evidence that shows that children also experience health benefits after implementation of smoke-free legislation. In addition to protecting children from tobacco smoke in public, the link between smoke-free legislation and improved child health is likely to be mediated via a decline in smoking during pregnancy and reduced exposure in the home environment. Recent studies have found that the implementation of smoke-free legislation is associated with a substantial decrease in the number of perinatal deaths, preterm births and hospital attendance for respiratory tract infections and asthma in children, although such benefits are not found in each study. With over 80% of the world’s population currently unprotected by comprehensive smoke-free laws, protecting (unborn) children from the adverse impact of tobacco smoking and SHS exposure holds great potential to benefit public health and should therefore be a key priority for policymakers and health workers alike