Baryogenesis in the Two-Higgs Doublet Model

We consider the generation of the baryon asymmetry in the two-Higgs doublet model. Investigating the thermal potential in the presence of CP violation, as relevant for baryogenesis, we find a strong first-order phase transition if the extra Higgs states are heavier than about 300 GeV. The mass of the lightest Higgs can be as large as about 200 GeV. We compute the bubble wall properties, including the profile of the relative complex phase between the two Higgs vevs. The baryon asymmetry is generated by top transport, which we treat in the WKB approximation. We find a baryon asymmetry consistent with observations. The neutron electric dipole moment is predicted to be larger than about 10^{-27}ecm and can reach the current experimental bound. Low values of tan\beta are favored.Comment: 25 pages, 7 figure

Healthcare choice: Discourses, perceptions, experiences and practices

Policy discourse shaped by neoliberal ideology, with its emphasis on marketisation and competition, has highlighted the importance of choice in the context of healthcare and health systems globally. Yet, evidence about how so-called consumers perceive and experience healthcare choice is in short supply and limited to specific healthcare systems, primarily in the Global North. This special issue aims to explore how choice is perceived and utilised in the context of different systems of healthcare throughout the world, where choice, at least in policy and organisational terms, has been embedded for some time. The articles are divided into those emphasising: embodiment and the meaning of choice; social processes associated with choice; the uncertainties, risks and trust involved in making choices; and issues of access and inequality associated with enacting choice. These sociological studies reveal complexities not always captured in policy discourse and suggest that the commodification of healthcare is particularly problematic

The Baryon asymmetry in the Standard Model with a low cut-off

We study the generation of the baryon asymmetry in a variant of the standard model, where the Higgs field is stabilized by a dimension-six interaction. Analyzing the one-loop potential, we find a strong first order electroweak phase transition for Higgs masses up to at least 170 GeV. Dimension-six operators induce also new sources of CP violation. We compute the baryon asymmetry in the WKB approximation. Novel source terms in the transport equations enhance the generated baryon asymmetry. For a wide range of parameters the model predicts a baryon asymmetry close to the observed value.Comment: 22 pages, latex, 6 figure

Distinct and additive effects of calorie restriction and rapamycin in aging skeletal muscle

Preserving skeletal muscle function is essential to maintain life quality at high age. Calorie restriction (CR) potently extends health and lifespan, but is largely unachievable in humans, making "CR mimetics" of great interest. CR targets nutrient-sensing pathways centering on mTORC1. The mTORC1 inhibitor, rapamycin, is considered a potential CR mimetic and is proven to counteract age-related muscle loss. Therefore, we tested whether rapamycin acts via similar mechanisms as CR to slow muscle aging. Here we show that long-term CR and rapamycin unexpectedly display distinct gene expression profiles in geriatric mouse skeletal muscle, despite both benefiting aging muscles. Furthermore, CR improves muscle integrity in mice with nutrient-insensitive, sustained muscle mTORC1 activity and rapamycin provides additive benefits to CR in naturally aging mouse muscles. We conclude that rapamycin and CR exert distinct, compounding effects in aging skeletal muscle, thus opening the possibility of parallel interventions to counteract muscle aging

Distinct and additive effects of calorie restriction and rapamycin in aging skeletal muscle

As global life expectancy continues to climb, maintaining skeletal muscle function is increasingly essential to ensure a good life quality for aging populations. Calorie restriction (CR) is the most potent and reproducible intervention to extend health and lifespan, but is largely unachievable in humans. Therefore, identification of "CR mimetics" has received much attention. CR targets nutrient-sensing pathways centering on mTORC1. The mTORC1 inhibitor, rapamycin, has been proposed as a potential CR mimetic and is proven to counteract age-related muscle loss. Therefore, we tested whether rapamycin acts via similar mechanisms as CR to slow muscle aging. Contrary to our expectation, long-term CR and rapamycin-treated geriatric mice display distinct skeletal muscle gene expression profiles despite both conferring benefits to aging skeletal muscle. Furthermore, CR improved muscle integrity in a mouse with nutrient-insensitive sustained muscle mTORC1 activity and rapamycin provided additive benefits to CR in aging mouse muscles. Therefore, RM and CR exert distinct, compounding effects in aging skeletal muscle, opening the possibility of parallel interventions to counteract muscle aging

The feasibility and effectiveness of a web-based personalised feedback and social norms alcohol intervention in UK university students: A randomised control trial

OBJECTIVE Alcohol misuse amongst University students is a serious concern, and research has started to investigate the feasibility of using e-health interventions. This study aimed to establish the effectiveness of an electronic web-based personalised feedback intervention through the use of a randomised control trial (RCT). METHODS 506 participants were stratified by gender, age group, year of study, self-reported weekly consumption of alcohol and randomly assigned to either a control or intervention condition. Intervention participants received electronic personalised feedback and social norms information on their drinking behaviour which they could access by logging onto the website at any time during the 12-week period. CAGE score, average number of alcoholic drinks consumed per drinking occasion, and alcohol consumption over the last week were collected from participants at pre- and post-survey. RESULTS A significant difference in pre- to post-survey mean difference of alcohol consumed per occasion was found, with those in the intervention condition displaying a larger mean decrease when compared to controls. No intervention effect was found for units of alcohol consumed per week or for CAGE scores. Sixty-three percent of intervention participants agreed that the feedback provided was useful. Those intervention participants who were above the CAGE cut off were more likely to report that the website would make them think more about the amount they drank. CONCLUSIONS Delivering an electronic personalised feedback intervention to students via the World Wide Web is a feasible and potentially effective method of reducing student alcohol intake. Further research is needed to replicate this outcome, evaluate maintenance of any changes, and investigate the process of interaction with web-based interventions

Fosciclopirox suppresses growth of high-grade urothelial cancer by targeting the γ-secretase complex

Ciclopirox (CPX) is an FDA-approved topical antifungal agent that has demonstrated preclinical anticancer activity in a number of solid and hematologic malignancies. Its clinical utility as an oral anticancer agent, however, is limited by poor oral bioavailability and gastrointestinal toxicity. Fosciclopirox, the phosphoryloxymethyl ester of CPX (Ciclopirox Prodrug, CPX-POM), selectively delivers the active metabolite, CPX, to the entire urinary tract following parenteral administration. We characterized the activity of CPX-POM and its major metabolites in in vitro and in vivo preclinical models of high-grade urothelial cancer. CPX inhibited cell proliferation, clonogenicity and spheroid formation, and increased cell cycle arrest at S and G0/G1 phases. Mechanistically, CPX suppressed activation of Notch signaling. Molecular modeling and cellular thermal shift assays demonstrated CPX binding to γ-secretase complex proteins Presenilin 1 and Nicastrin, which are essential for Notch activation. To establish in vivo preclinical proof of principle, we tested fosciclopirox in the validated N-butyl-N-(4-hydroxybutyl) nitrosamine (BBN) mouse bladder cancer model. Once-daily intraperitoneal administration of CPX-POM for four weeks at doses of 235 mg/kg and 470 mg/kg significantly decreased bladder weight, a surrogate for tumor volume, and resulted in a migration to lower stage tumors in CPX-POM treated animals. This was coupled with a reduction in the proliferation index. Additionally, there was a reduction in Presenilin 1 and Hes-1 expression in the bladder tissues of CPX-POM treated animals. Following the completion of the first-in-human Phase 1 trial (NCT03348514), the pharmacologic activity of fosciclopirox is currently being characterized in a Phase 1 expansion cohort study of muscle-invasive bladder cancer patients scheduled for cystectomy (NCT04608045) as well as a Phase 2 trial of newly diagnosed and recurrent urothelial cancer patients scheduled for transurethral resection of bladder tumors (NCT04525131)

Baryon Washout, Electroweak Phase Transition, and Perturbation Theory

We analyze the conventional perturbative treatment of sphaleron-induced baryon number washout relevant for electroweak baryogenesis and show that it is not gauge-independent due to the failure of consistently implementing the Nielsen identities order-by-order in perturbation theory. We provide a gauge-independent criterion for baryon number preservation in place of the conventional (gauge-dependent) criterion needed for successful electroweak baryogenesis. We also review the arguments leading to the preservation criterion and analyze several sources of theoretical uncertainties in obtaining a numerical bound. In various beyond the standard model scenarios, a realistic perturbative treatment will likely require knowledge of the complete two-loop finite temperature effective potential and the one-loop sphaleron rate.Comment: 25 pages, 9 figures; v2 minor typos correcte