Instability of (1+1) de sitter space in the presence of interacting fields

Instabilities of two dimensional (1+1) de Sitter space induced by interacting fields are studied. As for the case of flat Minkowski space, several interacting fermion models can be translated into free boson ones and vice versa. It is found that interacting fermion theories do not lead to any instabilities, while the interacting bosonic sine-Gordon model does lead to a breakdown of de Sitter symmetry and to the vanishing of the vacuum expectation value of the S matrix.Comment: 7 page

Analgosedatives in the PICU – more than sleep alone?

Up to 70 % of drugs administered to children in the pediatric intensive care unit (PICU) are used unlicensed or off-label. This means, without regulatory review of information about safety and efficacy and without appropriate dosages or formulations. The aims of this thesis are: __1)__ To review existing knowledge on PK, PD and ethical challenges in critically ill children with a focus on analgosedatives. __2)__ To study complex PICU pharmacokinetics using as examples: _a)_ The pharmacokinetics of clonidine in ECMO patients _b)_ Oral bioavailability of paracetamol in critically ill patients __3)__ To study hemodynamic efficacy and safety outcomes of analgosedatives _a)_ Is hemodynamic stability similar in tailored sedation versus pre-emptive sedation after heart surgery in young infants? _b)_ What is the impact of clonidine on hemodynamic stability in neonates after heart surgery and in a general mixed PICU populatio

In vivo E2F reporting reveals efficacious schedules of MEK1/2–CDK4/6 targeting and mTOR–s6 resistance mechanisms

Targeting cyclin-dependent kinases 4/6 (CDK4/6) represents a therapeutic option in combination with BRAF inhibitor and/or MEK inhibitor (MEKi) in melanoma; however, continuous dosing elicits toxicities in patients. Using quantitative and temporal in vivo reporting, we show that continuous MEKi with intermittent CDK4/6 inhibitor (CDK4/6i) led to more complete tumor responses versus other combination schedules. Nevertheless, some tumors acquired resistance that was associated with enhanced phosphorylation of ribosomal S6 protein. These data were supported by phospho-S6 staining of melanoma biopsies from patients treated with CDK4/6i plus targeted inhibitors. Enhanced phospho-S6 in resistant tumors provided a therapeutic window for the mTORC1/2 inhibitor AZD2014. Mechanistically, upregulation or mutation of NRAS was associated with resistance in in vivo models and patient samples, respectively, and mutant NRAS was sufficient to enhance resistance. This study utilizes an in vivo reporter model to optimize schedules and supports targeting mTORC1/2 to overcome MEKi plus CDK4/6i resistance. SIGnIFICAnCE: Mutant BRAF and NRAS melanomas acquire resistance to combined MEK and CDK4/6 inhibition via upregulation of mTOR pathway signaling. This resistance mechanism provides the preclinical basis to utilize mTORC1/2 inhibitors to improve MEKi plus CDK4/6i drug regimens

Unusual Spread of a Penicillin-Susceptible Methicillin-Resistant Staphylococcus aureus Clone in a Geographic Area of Low Incidence

We describe the unusual spread of a penicillin-susceptible methicillin-resistant Staphylococcus aureus (MRSA) clone in hospitals in western Switzerland, where the incidence of MRSA is usually low. During a 2-year period, this clone had been responsible for several outbreaks and had been isolated from >156 persons in 21 institutions. Molecular typing by pulsed-field gel electrophoresis (PFGE) demonstrated that all of these isolates belonged to the same clone. In 1 of the outbreaks, involving 30 cases, the clone was responsible for at least 17 secondary cases. In contrast, during the period of the latter outbreak, 9 other patients harboring different MRSA strains, as assessed by PFGE, were hospitalized in the same wards, but no secondary cases occurred. These observations suggest that this clone, compared with other MRSA strains, had some intrinsic factor(s) that contributed to its ability to disseminate and could thus be considered epidemi

Developing Dementia-Friendly Tourism Destinations: An Exploratory Analysis

Dementia is emerging as a global issue. Increases in life expectancy create an older population structure with accompanying health needs but also high lifestyle expectations. For example existing generations have come to expect to be able to participate in leisure and tourism activities in later life, which can be constrained by the onset of dementia. Leading healthy lifestyles and engaging in tourism activities are viewed as fundamental to remaining active and contributing to slowing the progress of dementia. This study is the first to examine the challenges and implications of the growing scale of dementia and the business opportunities this may create for destinations wishing to achieve dementia-friendly status. The paper reports results from an initial scoping study with tourism businesses in a coastal resort in the United Kingdom with such ambitions to assess the nature of the issues that arose from a series of face-to-face interviews

Size-Dependency of Income Distributions and Its Implications

This paper highlights the size-dependency of income distributions, i.e. the income distribution curves versus the population of a country systematically. By using the generalized Lotka-Volterra model to fit the empirical income data in the United States during 1996-2007, we found an important parameter $\lambda$ can scale with a $\beta$ power of the size (population) of U.S. in that year. We pointed out that the size-dependency of the income distributions, which is a very important property but seldom addressed by previous studies, has two non-trivial implications: (1) the allometric growth pattern, i.e. the power law relationship between population and GDP in different years, which can be mathematically derived from the size-dependent income distributions and also supported by the empirical data; (2) the connection with the anomalous scaling for the probability density function in critical phenomena since the re-scaled form of the income distributions has the exactly same mathematical expression for the limit distribution of the sum of many correlated random variables asymptotically.Comment: 4 figures, 4 page

Different effects of alpine woody plant expansion on domestic and wild ungulates

Changes in land-use and climate affect the distribution and diversity of plant and animal species at different spatiotemporal scales. The extent to which species-specific phenotypic plasticity and biotic interactions mediate organismal adaptation to changing environments, however, remains poorly understood. Woody plant expansion is threatening the extent of alpine grasslands worldwide, and evaluating and predicting its effects on herbivores is of crucial importance. Here, we explore the impact of shrubification on the feeding efficiency of Pyrenean chamois (Rupicapra p. pyrenaica), as well as on the three most abundant coexisting domestic ungulate species: cattle, sheep and horses. We use observational diet composition from May to October and model different scenarios of vegetation availability where shrubland and woodland proliferate at the expense of grassland. We then predicted if the four ungulate species could efficiently utilize their food landscapes with their current dietary specificities measuring their niche breath in each scenario. We observed that the wild counterpart, due to a higher trophic plasticity, is less disturbed by shrubification compared to livestock, which rely primarily on herbaceous plants and will be affected 3.6 times more. Our results suggest that mixed feeders, such as chamois, could benefit from fallow landscapes, and that mountain farmers are at a growing economic risk worldwide due to changing land-use practices and climate conditions