Control of Coulomb blockade in a mesoscopic Josephson junction using single electron tunneling

We study a circuit where a mesoscopic Josephson junction (JJ) is embedded in an environment consisting of a large bias resistor and a normal metal - superconductor tunnel junction (NIS). The effective Coulomb blockade of the JJ can be controlled by the tunneling current through the NIS junction leading to transistor-like characteristics. We show using phase correlation theory and numerical simulations that substantial current gain with low current noise ($i_{n}\lesssim 1$ fA/$\sqrt{\text{Hz}}$) and noise temperature ($\lesssim$ 0.1 K) can be achieved. Good agreement between our numerical simulations and experimental results is obtained.Comment: 5 pages, 4 figures, RevTE

Description of self-synchronization effects in distributed Josephson junction arrays using harmonic analysis and power balance

Power generation and synchronisation in Josephson junction arrays have attracted attention for a long time. This stems from fundamental interest in nonlinear coupled systems as well as from potential in practical applications. In this paper we study the case of an array of junctions coupled to a distributed transmission line either driven by an external microwave or in a self-oscillating mode. We simplify the theoretical treatment in terms of harmonic analysis and power balance. We apply the model to explain the large operation margins of SNS- and SINIS-junction arrays. We show the validity of the approach by comparing with experiments and simulations with self-oscillating es-SIS junction arrays.Comment: 5 pages, 3 figure

Noninvasive Cardiorespiratory Signals Analysis for Asthma Evolution Monitoring in Preschool Children

OBJECTIVE: Despite its increasing prevalence, diagnosis of asthma in children remains problematic due to their difficulties in producing repeatable spirometric maneuvers. Moreover, low adherence to inhaled corticosteroids (ICS) treatment could result in permanent airway remodeling. The growing interest in a noninvasive and objective way for monitoring asthma, together with the apparent role of autonomic nervous system (ANS) in its pathogenesis, have attracted interest towards heart rate variability (HRV) and cardiorespiratory coupling (CRC) analyses. METHODS: HRV and CRC were analyzed in 70 children who were prescribed ICS treatment due to recurrent obstructive bronchitis. They underwent three different electrocardiogram and respiratory signals recordings, during and after treatment period. After treatment completion, they were followed up during 6 months and classified attending to their current asthma status. RESULTS: Vagal activity, as measured from HRV, and CRC, were reduced after treatment in those children at lower risk of asthma, whereas it kept unchanged in those with a worse prognosis. CONCLUSION: Results suggest that HRV analysis could be useful for the continuous monitoring of ANS anomalies present in asthma, thus contributing to evaluate the evolution of the disease, which is especially challenging in young children. SIGNIFICANCE: Noninvasive ANS assessment using HRV analysis could be useful in the continuous monitoring of asthma in children

Can screening and brief intervention lead to population-level reductions in alcohol-related harm?

A distinction is made between the clinical and public health justifications for screening and brief intervention (SBI) against hazardous and harmful alcohol consumption. Early claims for a public health benefit of SBI derived from research on general medical practitioners' (GPs') advice on smoking cessation, but these claims have not been realized, mainly because GPs have not incorporated SBI into their routine practice. A recent modeling exercise estimated that, if all GPs in England screened every patient at their next consultation, 96% of the general population would be screened over 10 years, with 70-79% of excessive drinkers receiving brief interventions (BI); assuming a 10% success rate, this would probably amount to a population-level effect of SBI. Thus, a public health benefit for SBI presupposes widespread screening; but recent government policy in England favors targeted versus universal screening, and in Scotland screening is based on new registrations and clinical presentation. A recent proposal for a national screening program was rejected by the UK National Health Service's National Screening Committee because 1) there was no good evidence that SBI led to reductions in mortality or morbidity, and 2) a safe, simple, precise, and validated screening test was not available. Even in countries like Sweden and Finland, where expensive national programs to disseminate SBI have been implemented, only a minority of the population has been asked about drinking during health-care visits, and a minority of excessive drinkers has been advised to cut down. Although there has been research on the relationship between treatment for alcohol problems and population-level effects, there has been no such research for SBI, nor have there been experimental investigations of its relationship with population-level measures of alcohol-related harm. These are strongly recommended. In this article, conditions that would allow a population-level effect of SBI to occur are reviewed, including their political acceptability. It is tentatively concluded that widespread dissemination of SBI, without the implementation of alcohol control measures, might have indirect influences on levels of consumption and harm but would be unlikely on its own to result in public health benefits. However, if and when alcohol control measures were introduced, SBI would still have an important role in the battle against alcohol-related harm

Estimating the potential survival gains by eliminating socioeconomic and sex inequalities in stage at diagnosis of melanoma.

BACKGROUND: Although inequalities in cancer survival are thought to reflect inequalities in stage at diagnosis, little evidence exists about the size of potential survival gains from eliminating inequalities in stage at diagnosis. METHODS: We used data on patients diagnosed with malignant melanoma in the East of England (2006-2010) to estimate the number of deaths that could be postponed by completely eliminating socioeconomic and sex differences in stage at diagnosis after fitting a flexible parametric excess mortality model. RESULTS: Stage was a strong predictor of survival. There were pronounced socioeconomic and sex inequalities in the proportion of patients diagnosed at stages III-IV (12 and 8% for least deprived men and women and 25 and 18% for most deprived men and women, respectively). For an annual cohort of 1025 incident cases in the East of England, eliminating sex and deprivation differences in stage at diagnosis would postpone approximately 24 deaths to beyond 5 years from diagnosis. Using appropriate weighting, the equivalent estimate for England would be around 215 deaths, representing 11% of all deaths observed within 5 years from diagnosis in this population. CONCLUSIONS: Reducing socioeconomic and sex inequalities in stage at diagnosis would result in substantial reductions in deaths within 5 years of a melanoma diagnosis.This article is an independent research supported by different funding bodies, beyond the authors’ own employing organisations. MJR was partially funded by a Cancer Research UK Postdoctoral Fellowship (CRUK_A13275). GL is supported by a Postdoctoral Fellowship award by the National Institute for Health Research (NIHR PDF-2011-04-047) to end of 2014 and a Cancer Research UK Clinician Scientist Fellowship award (A18180) from January 2015. The views expressed in this publication are those of the authors and not necessarily those of the National Health Service (NHS), the National Institute for Health Research, the Department of Health, Cancer Research UK, or any other organisation. We thank all staff at the National Cancer Registration Service, Public Health England, Eastern Office, who helped collect and code data used in this study. We particularly acknowledge the help of Dr Clement H Brown and Dr Brian A Rous who were responsible for staging.This is the final published version. It first appeared at http://www.nature.com/bjc/journal/v112/n1s/full/bjc201550a.html

Europe's lost forests: a pollen-based synthesis for the last 11,000 years

8000 years ago, prior to Neolithic agriculture, Europe was mostly a wooded continent. Since then, its forest cover has been progressively fragmented, so that today it covers less than half of Europe’s land area, in many cases having been cleared to make way for fields and pasture-land. Establishing the origin of Europe’s current, more open land-cover mosaic requires a long-term perspective, for which pollen analysis offers a key tool. In this study we utilise and compare three numerical approaches to transforming pollen data into past forest cover, drawing on >1000 14C-dated site records. All reconstructions highlight the different histories of the mixed temperate and the northern boreal forests, with the former declining progressively since ~6000 years ago, linked to forest clearance for agriculture in later prehistory (especially in northwest Europe) and early historic times (e.g. in north central Europe). In contrast, extensive human impact on the needle-leaf forests of northern Europe only becomes detectable in the last two millennia and has left a larger area of forest in place. Forest loss has been a dominant feature of Europe’s landscape ecology in the second half of the current interglacial, with consequences for carbon cycling, ecosystem functioning and biodiversity

Improving guideline adherence for cardiac rehabilitation in the Netherlands

Background In 2004, the Netherlands Society of Cardiology released the current guideline on cardiac rehabilitation. Given its complexity and the involvement of various healthcare disciplines, it was supplemented with a clinical algorithm, serving to facilitate its implementation in daily practice. Although the algorithm was shown to be effective for improving guideline adherence, several shortcomings and deficiencies were revealed. Based on these findings, the clinical algorithm has now been updated. This article describes the process and the changes that were made. Methods The revision consisted of three phases. First, the reliability of the measurement instruments included in the 2004 Clinical Algorithm was investigated by evaluating between-centre variations of the baseline assessment data. Second, based on the available evidence, a multidisciplinary expert advisory panel selected items needing revision and provided specific recommendations. Third, a guideline development group decided which revisions were finally included, also taking practical considerations into account. Results A total of nine items were revised: three because of new scientific insights and six because of the need for more objective measurement instruments. In all revised items, subjective assessment methods were replaced by more objective assessment tools (e.g. symptom-limited exercise instead of clinical judgement). In addition, four new key items were added: screening for anxiety/depression, stress, cardiovascular risk profile and alcohol consumption. Conclusion Based on previously determined shortcomings, the Clinical Algorithm for Cardiac Rehabilitation was thoroughly revised mainly by incorporating more objective assessment methods and by adding several new key area

Effect of pH of amine fluoride containing toothpastes on enamel remineralization in vitro

<p>Abstract</p> <p>Background</p> <p>One of the important factors of the demineralization and remineralization equilibrium of enamel is the pH of the surrounding solutions. Effort has been laid in the formulation of different fluoride compounds and the fluoride content in toothpastes but much less is known about the influence of the pH of the toothpastes on their effectiveness. It was therefore the aim of this study to investigate the influence of different pH levels on enamel remineralization in an in vitro experiment using polarization light microscopy and EDX quantitative element analysis.</p> <p>Methods</p> <p>A 5 × 5 mm window on the enamel surface of 40 caries free extracted human premolars was demineralized in a hydroxyethylcellulose solution at pH 4.8. The teeth were divided into 8 groups and the lower half of the window was covered with varnish serving as control. Each group was then immersed in toothpaste slurry containing amine fluoride (1400 ppm) at pH 4.1, 4.5, 5.1 and 6.9 or control toothpaste slurry without fluoride at pH 4.3, 4.7, 5.3 and 7.0. Serial sections were cut through the lesions and investigated with polarization light microscopy and quantitative EDX element analysis.</p> <p>Results</p> <p>The PLM results showed a decreased porous volume of the body of the lesion after incubation with fluoridated toothpaste at pH 4.53 and 5.16. No differences between the experimental window and the control window were found in the other groups. The quantitative element analysis showed no differences in the element content of any of the groups.</p> <p>Conclusion</p> <p>From the results it can be concluded that slightly acidified fluoridated dentifrices may have a certain positive effect on enamel remineralization.</p

Nanofibrous Scaffolds Incorporating PDGF-BB Microspheres Induce Chemokine Expression and Tissue Neogenesis In Vivo

Platelet-derived growth factor (PDGF) exerts multiple cellular effects that stimulate wound repair in multiple tissues. However, a major obstacle for its successful clinical application is the delivery system, which ultimately controls the in vivo release rate of PDGF. Polylactic-co-glycolic acid (PLGA) microspheres (MS) in nanofibrous scaffolds (NFS) have been shown to control the release of rhPDGF-BB in vitro. In order to investigate the effects of rhPDGF-BB release from MS in NFS on gene expression and enhancement of soft tissue engineering, rhPDGF-BB was incorporated into differing molecular weight (MW) polymeric MS. By controlling the MW of the MS over a range of 6.5 KDa–64 KDa, release rates of PDGF can be regulated over periods of weeks to months in vitro. The NFS-MS scaffolds were divided into multiple groups based on MS release characteristics and PDGF concentration ranging from 2.5–25.0 µg and evaluated in vivo in a soft tissue wound repair model in the dorsa of rats. At 3, 7, 14 and 21 days post-implantation, the scaffold implants were harvested followed by assessments of cell penetration, vasculogenesis and tissue neogenesis. Gene expression profiles using cDNA microarrays were performed on the PDGF-releasing NFS. The percentage of tissue invasion into MS-containing NFS at 7 days was higher in the PDGF groups when compared to controls. Blood vessel number in the HMW groups containing either 2.5 or 25 µg PDGF was increased above those of other groups at 7d (p<0.01). Results from cDNA array showed that PDGF strongly enhanced in vivo gene expression of the CXC chemokine family members such as CXCL1, CXCL2 and CXCL5. Thus, sustained release of rhPDGF-BB, controlled by slow-releasing MS associated with the NFS delivery system, enhanced cell migration and angiogenesis in vivo, and may be related to an induced expression of chemokine-related genes. This approach offers a technology to accurately control growth factor release to promote soft tissue engineering in vivo

Effect of fluoride toothpastes on enamel demineralization

BACKGROUND: It was the aim of this study to investigate the effect of four different toothpastes with differing fluoride compounds on enamel remineralization. METHODS: A 3 × 3 mm window on the enamel surface of 90 human premolars was demineralized in a hydroxyethylcellulose solution at pH 4.8. The teeth were divided into 6 groups and the lower half of the window was covered with varnish serving as control. The teeth were immersed in a toothpaste slurry containing: placebo tooth paste (group 1); remineralization solution (group 2); Elmex Anticaries (group 3); Elmex Sensitive (group 4); Blend-a-med Complete (group 5) and Colgate GRF (group 6). Ten teeth of each group were used for the determination of the F(- )content in the superficial enamel layer and acid solubility of enamel expressed in soluble phosphorus. Of 6 teeth of each group serial sections were cut and investigated with polarization light microscopy (PLM) and quantitative energy dispersive X-ray analysis (EDX). RESULTS: The PLM results showed an increased remineralization of the lesion body in the Elmex Anticaries, Elmex Sensitive and Colgate GRF group but not in the Blend-a-med group. A statistically significant higher Ca content was found in the Elmex Anticaries group. The fluoride content in the superficial enamel layer was significantly increased in both Elmex groups and the Blend-a-med group. Phosphorus solubility was significantly decreased in both Elmex groups and the Blend-a-med group. CONCLUSION: It can be concluded that amine fluoride compounds in toothpastes result in a clearly marked remineralization of caries like enamel lesions followed by sodium fluoride and sodium monofluorophosphate formulations