Quantum corrections in Higgs inflation: the real scalar case

We present a critical discussion of quantum corrections, renormalisation, and the computation of the beta functions and the effective potential in Higgs inflation. In contrast with claims in the literature, we find no evidence for a disagreement between the Jordan and Einstein frames, even at the quantum level. For clarity of discussion we concentrate on the case of a real scalar Higgs. We first review the classical calculation and then discuss the back reaction of gravity. We compute the beta functions for the Higgs quartic coupling and non-minimal coupling constant. Here, the mid-field regime is non-renormalisable, but we are able to give an upper bound on the 1-loop corrections to the effective potential. We show that, in computing the effective potential, the Jordan and Einstein frames are compatible if all mass scales are transformed between the two frames. As such, it is consistent to take a constant cutoff in either the Jordan or Einstein frame, and both prescriptions yield the same result for the effective potential. Our results are extended to the case of a complex scalar Higgs.Comment: 28 pages, 1 figure. v2: minor changes, updated references, published versio

Application of spectral phase shaping to high resolution CARS spectroscopy

By spectral phase shaping of both the pump and probe pulses in coherent anti-Stokes Raman scattering (CARS) spectroscopy we demonstrate the extraction of the frequencies, bandwidths and relative cross sections of vibrational lines. We employ a tunable broadband Ti:Sapphire laser synchronized to a ps-Nd:YVO mode locked laser. A high resolution spectral phase shaper allows for spectroscopy with a precision better than 1 cm-1 in the high frequency region around 3000 cm-1. We also demonstrate how new spectral phase shaping strategies can amplify the resonant features of isolated vibrations to such an extent that spectroscopy and microscopy can be done at high resolution, on the integrated spectral response without the need for a spectrograph

Cost-effectiveness of infant pneumococcal vaccination in the Netherlands

Objectives: The Dutch National Immunization Program offers the 10-valent pneumococcal conjugate vaccine (PCV10). Also licensed for use in the infant population is the 13-valent PCV (PCV13). To update cost-effectiveness (CE) estimates of PCV13 over PCV10, using current epidemiological and economic data. Methods: We modeled vaccinating a birth cohort with either PCV10 or PCV13 (3+1 dose schedule), and calculated costs and effects linked to resulting disease. We modeled invasive pneumococcal disease (IPD), non-invasive pneumonia and acute otitis media, and considered death and lifetime impairments after IPD. We calculated direct effects in the vaccinated cohort and indirect effects -herd immunity for the vaccine-type (VT) serotypes and replacement for the non-VT serotypes- in the rest of the population. Since no price is available, we use a price difference of € 11 per dose and vary this price difference in sensitivity analyses. Epidemiological and economic data are taken as current as possible. A set of scenarios explore different assumptions, including different sets of epidemiological data, assumptions on vaccine efficacy and indirect effects. Results: Taking only direct effects into account PCV13 cannot be considered cost-effective, unless the price difference is much lower than € 11 per dose. In three scenarios, PCV10 dominates PCV13; in the other scenarios the ICER is between € 89000 and € 153000 per QALY gained. If indirect effects are also taken into account, the ICER of PCV13 compared to PCV10 is below € 20,000 per QALY for all scenarios. Scenarios do not have a large impact on the policy decision, unless we assume extra efficacy of PCV10 against non-typeable Haemophilus influenzae. Conclusions: Replacing PCV10 with PCV13 is not likely to be cost-effective in preventing invasive pneumococcal disease in young children. Taking potential benefits in elderly into account, PCV13 is likely cost-effective. The CE of PCV13 was highly sensitive for indirect effects our analysis

PIN22 Cost-Effectiveness of Hepatitis a Vaccination in Indonesia

Objectives: This study aims to assess the cost-effectiveness of hepatitis A vaccination in Indonesia, including an explicit comparison between one-dose and twodose vaccines. Methods: An age-structured cohort model based on a decision tree was developed for the 2012 Indonesia birth cohort. Using the model, we made a comparison on the use of two-dose and one-dose vaccines. The model involves a 70-year time horizon with 1-month cycles for children less than 2 years old and annually thereafter. Monte Carlo simulations were used to examine the economic acceptability and affordability of the hepatitis A vaccination. Results: With the vaccine price of US$4.49 per dose, the implementation of the hepatitis A vaccine from the societal perspective would yield incremental-cost-effectiveness-ratios (ICERs) at US$ 9,194 and US$4,577 for the two-dose and one-dose vaccine schedules, respectively. Considering the 2012 gross-domestic-product (GDP) per capita in Indonesia of US$ 3,557, the results indicate that hepatitis A vaccination would be a cost-effective intervention, both for the two-dose and one-dose vaccine schedules. Vaccination would be 100% affordable at budgets of US$89,918,000 and US$ 46,778,000 for the implementation of the two-dose and one-dose vaccine schedules, respectively. Conclusions: The implementation of hepatitis A vaccination in Indonesia would be a cost-effective health intervention under the market vaccine prices. Given the budget limitations, the use of a one-dose-vaccine schedule would be more realistic to be applied than a two-dose schedule. The discount rate, vaccine price, vaccine efficacy and mortality rate were the most influential parameters impacting the ICERs

Indirect treatment comparison and economic evaluation of novel oral anticoagulants for the prevention of stroke in patients with atrial fibrillation in the Netherlands

Objectives: Management with vitamin K antagonists (VKAs) has been an effective and cost-effective strategy for stroke prevention in atrial fibrillation (AF) but is associated with shortcomings. Novel oral anticoagulants (NOACs) were developed with the aims of no monitoring requirement and improved effectiveness and safety profiles. Economic evaluations require the comparison of all relevant options. However, there are no randomized controlled trials (RCTs) directly comparing these agents. In such cases, indirect treatment comparison (ITC) can be used to synthesize indirect comparative evidence. Through ITC-based evidence synthesis the cost-effectiveness of all available NOACs for stroke prevention in AF patients may be evaluated. Methods: ITC models were based on RCTs data comparing dabigratran, rivaroxaban, or apixaban with VKA treatment. Relative effectiveness was estimated for stroke/systemic embolism, intracranial hemorrhage, myocardial infarction, extracranial hemorrhage, and minor bleeding. A Markov model was developed using ITC-synthesized evidence with VKA as the baseline. Health utilities were collected from international sources whereas costs and mortality data were extracted from Dutch sources. Univariate and probabilistic sensitivity analyses (PSA) were conducted on the base-case incremental cost-effectiveness ratio (ICER). Results: The ICERs for dabigatran, apixaban, and rivaroxaban compared to VKA were € 12,146/QALY, € 12,488/QALY, and € 24,124/QALY, respectively. Sensitivity analysis using the upper and lower limits of the 95% confidence interval for absolute stroke risk with VKA treatment resulted in ICERs that varied drastically from dominance for VKA to being dominated by all NOACs. This is likely due to the large uncertainty observed between the baseline risk profiles of the VKA arms in the three RCTs. The options with the highest probabilities of cost-effectiveness in PSA were VKA at thresholds under € 13,000/QALY and dabigatran or apixaban at thresholds above this mark. Conclusions: Dabigatran and apixaban were shown to be cost-effective options for AF patients in The Netherlands. However, these results were strongly influenced by uncertainty around stroke risk with VKA treatment

Bigger is fitter? Quantitative genetic decomposition of selection reveals an adaptive evolutionary decline of body mass in a wild rodent population

This is the final version of the article. Available from the publisher via the DOI in this record.In natural populations, quantitative trait dynamics often do not appear to follow evolutionary predictions. Despite abundant examples of natural selection acting on heritable traits, conclusive evidence for contemporary adaptive evolution remains rare for wild vertebrate populations, and phenotypic stasis seems to be the norm. This so-called "stasis paradox" highlights our inability to predict evolutionary change, which is especially concerning within the context of rapid anthropogenic environmental change. While the causes underlying the stasis paradox are hotly debated, comprehensive attempts aiming at a resolution are lacking. Here, we apply a quantitative genetic framework to individual-based long-term data for a wild rodent population and show that despite a positive association between body mass and fitness, there has been a genetic change towards lower body mass. The latter represents an adaptive response to viability selection favouring juveniles growing up to become relatively small adults, i.e., with a low potential adult mass, which presumably complete their development earlier. This selection is particularly strong towards the end of the snow-free season, and it has intensified in recent years, coinciding which a change in snowfall patterns. Importantly, neither the negative evolutionary change, nor the selective pressures that drive it, are apparent on the phenotypic level, where they are masked by phenotypic plasticity and a non causal (i.e., non genetic) positive association between body mass and fitness, respectively. Estimating selection at the genetic level enabled us to uncover adaptive evolution in action and to identify the corresponding phenotypic selective pressure. We thereby demonstrate that natural populations can show a rapid and adaptive evolutionary response to a novel selective pressure, and that explicitly (quantitative) genetic models are able to provide us with an understanding of the causes and consequences of selection that is superior to purely phenotypic estimates of selection and evolutionary change.The study was funded by a Swiss National Science Foundation (http://www.snf.ch) project grant (31003A_141110) awarded to EP