Field theory for a reaction-diffusion model of quasispecies dynamics

RNA viruses are known to replicate with extremely high mutation rates. These rates are actually close to the so-called error threshold. This threshold is in fact a critical point beyond which genetic information is lost through a second-order phase transition, which has been dubbed the ``error catastrophe.'' Here we explore this phenomenon using a field theory approximation to the spatially extended Swetina-Schuster quasispecies model [J. Swetina and P. Schuster, Biophys. Chem. {\bf 16}, 329 (1982)], a single-sharp-peak landscape. In analogy with standard absorbing-state phase transitions, we develop a reaction-diffusion model whose discrete rules mimic the Swetina-Schuster model. The field theory representation of the reaction-diffusion system is constructed. The proposed field theory belongs to the same universality class than a conserved reaction-diffusion model previously proposed [F. van Wijland {\em et al.}, Physica A {\bf 251}, 179 (1998)]. From the field theory, we obtain the full set of exponents that characterize the critical behavior at the error threshold. Our results present the error catastrophe from a new point of view and suggest that spatial degrees of freedom can modify several mean field predictions previously considered, leading to the definition of characteristic exponents that could be experimentally measurable.Comment: 13 page

Current cosmological bounds on neutrino masses and relativistic relics

We combine the most recent observations of large-scale structure (2dF and SDSS galaxy surveys) and cosmic microwave anisotropies (WMAP and ACBAR) to put constraints on flat cosmological models where the number of massive neutrinos and of massless relativistic relics are both left arbitrary. We discuss the impact of each dataset and of various priors on our bounds. For the standard case of three thermalized neutrinos, we find an upper bound on the total neutrino mass sum m_nu < 1.0 (resp. 0.6) eV (at 2sigma), using only CMB and LSS data (resp. including priors from supernovae data and the HST Key Project), a bound that is quite insensitive to the splitting of the total mass between the three species. When the total number of neutrinos or relativistic relics N_eff is left free, the upper bound on sum m_nu (at 2sigma, including all priors) ranges from 1.0 to 1.5 eV depending on the mass splitting. We provide an explanation of the parameter degeneracy that allows larger values of the masses when N_eff increases. Finally, we show that the limit on the total neutrino mass is not significantly modified in the presence of primordial gravitational waves, because current data provide a clear distinction between the corresponding effects.Comment: 13 pages, 6 figure

Effect of interventions to reduce potentially inappropriate use of drugs in nursing homes: a systematic review of randomised controlled trials

Background Studies have shown that residents in nursing homes often are exposed to inappropriate medication. Particular concern has been raised about the consumption of psychoactive drugs, which are commonly prescribed for nursing home residents suffering from dementia. This review is an update of a Norwegian systematic review commissioned by the Norwegian Directorate of Health. The purpose of the review was to identify and summarise the effect of interventions aimed at reducing potentially inappropriate use or prescribing of drugs in nursing homes. Methods We searched for systematic reviews and randomised controlled trials in the Cochrane Library, MEDLINE, EMBASE, ISI Web of Knowledge, DARE and HTA, with the last update in April 2010. Two of the authors independently screened titles and abstracts for inclusion or exclusion. Data on interventions, participants, comparison intervention, and outcomes were extracted from the included studies. Risk of bias and quality of evidence were assessed using the Cochrane Risk of Bias Table and GRADE, respectively. Outcomes assessed were use of or prescribing of drugs (primary) and the health-related outcomes falls, physical limitation, hospitalisation and mortality (secondary). Results Due to heterogeneity in interventions and outcomes, we employed a narrative approach. Twenty randomised controlled trials were included from 1631 evaluated references. Ten studies tested different kinds of educational interventions while seven studies tested medication reviews by pharmacists. Only one study was found for each of the interventions geriatric care teams, early psychiatric intervening or activities for the residents combined with education of health care personnel. Several reviews were identified, but these either concerned elderly in general or did not satisfy all the requirements for systematic reviews. Conclusions Interventions using educational outreach, on-site education given alone or as part of an intervention package and pharmacist medication review may under certain circumstances reduce inappropriate drug use, but the evidence is of low quality. Due to poor quality of the evidence, no conclusions may be drawn about the effect of the other three interventions on drug use, or of either intervention on health-related outcomes

Costs of potentially inappropriate medication use in residential aged care facilities

The potential harms of some medications may outweigh their potential benefits (inappropriate medication use). Despite recommendations to avoid the use of potentially inappropriate medications (PIMs) in older adults, the prevalence of PIM use is high in different settings including residential aged care. However, it remains unclear what the costs of these medications are in this setting. The main objective of this study was to determine the costs of PIMs in older adults living in residential care. A secondary objective was to examine if there was a difference in costs of PIMs in a home-like model of residential care compared to an Australian standard model of care.Participants included 541 participants from the Investigation Services Provided in the Residential Environment for Dementia (INSPIRED) Study. The INSPIRED study is a cross-sectional study of 17 residential aged care facilities in Australia. 12 month medication costs were determined for the participants and PIMs were identified using the 2015 updated Beers Criteria for older adults.Of all of the medications dispensed in 1 year, 15.9% were PIMs and 81.4% of the participants had been exposed to a PIM. Log-linear models showed exposure to a PIM was associated with higher total medication costs (Adjusted β = 0.307, 95% CI 0.235 to 0.379, p < 0.001). The mean proportion (±SD) of medication costs that were spent on PIMs in 1 year was 17.5% (±17.8) (AUD$410.89 ± 479.45 per participant exposed to a PIM). The largest PIM costs arose from proton-pump inhibitors (34.4%), antipsychotics (21.0%) and benzodiazepines (18.7%). The odds of incurring costs from PIMs were 52% lower for those residing in a home-like model of care compared to a standard model of care.The use of PIMs for older adults in residential care facilities is high and these medications represent a substantial cost which has the potential to be lowered. Further research should investigate whether medication reviews in this population could lead to potential cost savings and improvement in clinical outcomes. Adopting a home-like model of residential care may be associated with reduced prevalence and costs of PIMs.S. L. Harrison, L. Kouladjian O’Donnell, R. Milte, S. M. Dyer, E. S. Gnanamanickam, C. Bradley, E. Liu, S. N. Hilmer and M. Crott

Optimisation of medications used in residential aged care facilities: a systematic review and meta-analysis of randomised controlled trials

Background: Frail older adults living in residential aged care facilities (RACFs) usually experience comorbidities and are frequently prescribed multiple medications. This increases the potential risk of inappropriate prescribing and its negative consequences. Thus, optimising prescribed medications in RACFs is a challenge for healthcare providers. Objective: Our aim was to systematically review interventions that increase the appropriateness of medications used in RACFs and the outcomes of these interventions. Methods: Systematic review and meta-analysis of randomised control trials (RCTs) and cluster randomised control trials (cRCTs) were performed by searching specified databases (MEDLINE, PubMed, Google scholar, PsycINFO) for publications from inception to May 2019 based on defined inclusion criteria. Data were extracted, study quality was assessed and statistically analysed using RevMan v5.3. Medication appropriateness, hospital admissions, mortality, falls, quality of life (QoL), Behavioural and Psychological Symptoms of Dementia (BPSD), adverse drug events (ADEs) and cognitive function could be meta-analysed. Results: A total of 25 RCTs and cRCTs comprising 19,576 participants met the inclusion criteria. The studies tested various interventions including medication review (n = 13), staff education (n = 9), multi-disciplinary case conferencing (n = 4) and computerised clinical decision support systems (n = 2). There was an effect of interventions on medication appropriateness (RR 0.71; 95% confidence interval (CI): 0.60,0.84) (10 studies), and on medication appropriateness scales (standardised mean difference = − 0.67; 95% CI: − 0.97, − 0.36) (2 studies). There were no apparent effects on hospital admission (RR 1.00; 95% CI: 0.93, 1.06), mortality (RR 0.98; 95% CI: 0.86, 1.11), falls (RR 1.06; 95% CI: 0.89,1.26), ADEs (RR 1.04; 95% CI: 0.96,1.13), QoL (standardised mean difference = 0.16; 95% CI:-0.13, 0.45), cognitive function (weighted mean difference = 0.69; 95% CI: − 1.25, 2.64) and BPSD (RR 0.68; 95% CI: 0.44,1.06) (2 studies). Conclusion: Modest improvements in medication appropriateness were observed in the studies included in this systematic review. However, the effect on clinical measures was limited to drive strong conclusions

On the gravitational production of superheavy dark matter

The dark matter in the universe can be in the form of a superheavy matter species (WIMPZILLA). Several mechanisms have been proposed for the production of WIMPZILLA particles during or immediately following the inflationary epoch. Perhaps the most attractive mechanism is through gravitational particle production, where particles are produced simply as a result of the expansion of the universe. In this paper we present a detailed numerical calculation of WIMPZILLA gravitational production in hybrid-inflation models and natural-inflation models. Generalizing these findings, we also explore the dependence of the gravitational production mechanism on various models of inflation. We show that superheavy dark matter production seems to be robust, with Omega_X h^2 ~ (M_X / (10^11 GeV))^2 (T_RH / (10^9 GeV)), so long as M_X < H_I, where M_X is the WIMPZILLA mass, T_RH is the reheat temperature, and H_I is the expansion rate of the universe during inflation.Comment: 26 pages, 7 figures; LaTeX; submitted to Physical Review D; minor typographical error correcte

Probing Kaluza-Klein Dark Matter with Neutrino Telescopes

In models in which all of the Standard Model fields live in extra universal dimensions, the lightest Kaluza-Klein (KK) particle can be stable. Calculations of the one-loop radiative corrections to the masses of the KK modes suggest that the identity of the lightest KK particle (LKP) is mostly the first KK excitation of the hypercharge gauge boson. This LKP is a viable dark matter candidate with an ideal present-day relic abundance if its mass is moderately large, between 600 to 1200 GeV. Such weakly interacting dark matter particles are expected to become gravitationally trapped in large bodies, such as the Sun, and annihilate into neutrinos or other particles that decay into neutrinos. We calculate the annihilation rate, neutrino flux and the resulting event rate in present and future neutrino telescopes. The relatively large mass implies that the neutrino energy spectrum is expected to be well above the energy threshold of AMANDA and IceCube. We find that the event rate in IceCube is between a few to tens of events per year.Comment: 13 pages, 3 figures, LaTeX; typos fixed, version to appear in PR

Neutrino masses and the number of neutrino species from WMAP and 2dFGRS

We have performed a thorough analysis of the constraints which can be put on neutrino parameters from cosmological observations, most notably those from the WMAP satellite and the 2dF galaxy survey. For this data we find an upper limit on the sum of active neutrino mass eigenstates of \sum m_nu < 1.0 eV (95% conf.), but this limit is dependent on priors. We find that the WMAP and 2dF data alone cannot rule out the evidence from neutrinoless double beta decay reported by the Heidelberg-Moscow experiment. In terms of the relativistic energy density in neutrinos or other weakly interacting species we find, in units of the equivalent number of neutrino species, N_nu, that N_nu = 4.0+3.0-2.1 (95% conf.). When BBN constraints are added, the bound on N_\nu is 2.6+0.4-0.3 (95% conf.), suggesting that N_nu could possibly be lower than the standard model value of 3. This can for instance be the case in models with very low reheating temperature and incomplete neutrino thermalization. Conversely, if N_nu is fixed to 3 then the data from WMAP and 2dFGRS predicts that 0.2458 < Y_P < 0.2471, which is significantly higher than the observationally measured value. The limit on relativistic energy density changes when a small $\nu_e$ chemical potential is present during BBN. In this case the upper bound on N_nu from WMAP, 2dFGRS and BBN is N_nu < 6.5. Finally, we find that a non-zero \sum m_nu can be compensated by an increase in N_nu. One result of this is that the LSND result is not yet ruled out by cosmological observations.Comment: 10 pages, 6 figure

Complete Genome Sequence of <em>Vibrio parahaemolyticus</em> Environmental Strain UCM-V493

Vibrio parahaemolyticus is the leading bacterial cause of seafood-related gastroenteritis in the world. Here, we report the complete genome sequence and annotation of an environmental strain of V. parahaemolyticus, UCM-V493, with the aim of understanding the differences between the clinical and environmental isolates of the bacteria. We also make some preliminary sequence comparisons with the clinical strain RIMD2210633

Scale in education research: towards a multi-scale methodology

This article explores some theoretical and methodological problems concerned with scale in education research through a critique of a recent mixed-method project. The project was framed by scale metaphors drawn from the physical and earth sciences and I consider how recent thinking around scale, for example in ecosystems and human geography might offer helpful points and angles of view on the challenges of thinking spatially in education research. Working between the spatial metaphors of ecology scholars and the critiques of the human geographers, for example the hypercomplex social space in Lefebvre’s political-economic thinking and the fluid, simultaneous, multiple spatialities of Massey’s post-structuralism, I problematize space and scale in education research. Interweaving these geographical ideas with Giddens’ structuration and Bourdieu’s theory of practice, both of which employed what might be termed scale-bridging to challenge social science’s entrenched paradigms, leads me to reconsider what is possible and desirable in the study of education systems. Following the spatial turn in the social sciences generally, there is an outstanding need to theorise multi-scale methodology for education research