Dimensionality of Carbon Nanomaterials Determines the Binding and Dynamics of Amyloidogenic Peptides: Multiscale Theoretical Simulations

Experimental studies have demonstrated that nanoparticles can affect the rate of protein self-assembly, possibly interfering with the development of protein misfolding diseases such as Alzheimer's, Parkinson's and prion disease caused by aggregation and fibril formation of amyloid-prone proteins. We employ classical molecular dynamics simulations and large-scale density functional theory calculations to investigate the effects of nanomaterials on the structure, dynamics and binding of an amyloidogenic peptide apoC-II(60-70). We show that the binding affinity of this peptide to carbonaceous nanomaterials such as C60, nanotubes and graphene decreases with increasing nanoparticle curvature. Strong binding is facilitated by the large contact area available for π-stacking between the aromatic residues of the peptide and the extended surfaces of graphene and the nanotube. The highly curved fullerene surface exhibits reduced efficiency for π-stacking but promotes increased peptide dynamics. We postulate that the increase in conformational dynamics of the amyloid peptide can be unfavorable for the formation of fibril competent structures. In contrast, extended fibril forming peptide conformations are promoted by the nanotube and graphene surfaces which can provide a template for fibril-growth

Quantification of Trace-Level DNA by Real-Time Whole Genome Amplification

Quantification of trace amounts of DNA is a challenge in analytical applications where the concentration of a target DNA is very low or only limited amounts of samples are available for analysis. PCR-based methods including real-time PCR are highly sensitive and widely used for quantification of low-level DNA samples. However, ordinary PCR methods require at least one copy of a specific gene sequence for amplification and may not work for a sub-genomic amount of DNA. We suggest a real-time whole genome amplification method adopting the degenerate oligonucleotide primed PCR (DOP-PCR) for quantification of sub-genomic amounts of DNA. This approach enabled quantification of sub-picogram amounts of DNA independently of their sequences. When the method was applied to the human placental DNA of which amount was accurately determined by inductively coupled plasma-optical emission spectroscopy (ICP-OES), an accurate and stable quantification capability for DNA samples ranging from 80 fg to 8 ng was obtained. In blind tests of laboratory-prepared DNA samples, measurement accuracies of 7.4%, −2.1%, and −13.9% with analytical precisions around 15% were achieved for 400-pg, 4-pg, and 400-fg DNA samples, respectively. A similar quantification capability was also observed for other DNA species from calf, E. coli, and lambda phage. Therefore, when provided with an appropriate standard DNA, the suggested real-time DOP-PCR method can be used as a universal method for quantification of trace amounts of DNA

Definition of strategies for the reduction of operational inefficiencies in a stroke unit

Stroke disease is the second common cause of death in the world and is then of particular concern to policy-makers. Additionally, it is a meaningful problem leaving a high number of people with severe disabilities, placing a heavy burden on society and incurring prolonged length of stay. In this respect, it is necessary to develop analytic models providing information on care system behavior in order to detect potential operational inefficiencies along the stroke patient journey and subsequently design improvement strategies. However, modeling stroke care is highly complex due to the multiple clinical outcomes and different pathways. Therefore, this paper presents an integrated approach between Discrete-event Simulation (DES) and Markov models so that integrated planning of healthcare services relating to stroke care and the evaluation of potential improvement scenarios can be facilitated, made more logically robust and easy to understand. First, a stroke care system from Colombia was characterized by identifying the exogenous and endogenous variables of the process. Afterward, an input analysis was conducted to define the probability distributions of the aforementioned variables. Then, both DES and Markov models were designed and validated to provide deeper analysis of the entire patient journey. Finally, the possible adoption of thrombolytic treatment on patients with stroke disease was assessed based on the proposed approaches within this paper. The results evidenced that the length of stay (LOS) decreased by 12,89% and the mortality ratio was diminished by 21,52%. Evaluation of treatment cost per patient is also carried out

Protocol for an economic evaluation alongside the University Health Network Whiplash Intervention Trial: cost-effectiveness of education and activation, a rehabilitation program, and the legislated standard of care for acute whiplash injury in Ontario

Background: Whiplash injury affects 83% of persons in a traffic collision and leads to whiplash-associated disorders (WAD). A major challenge facing health care decision makers is identifying cost-effective interventions due to lack of economic evidence. Our objective is to compare the cost-effectiveness of: 1) physician-based education and activation, 2) a rehabilitation program developed by Aviva Canada (a group of property and casualty insurance providers), and 3) the legislated standard of care in the Canadian province of Ontario: the Pre-approved Framework Guideline for Whiplash developed by the Financial Services Commission of Ontario. Methods/Design. The economic evaluation will use participant-level data from the University Health Network Whiplash Intervention Trial and will be conducted from the societal perspective over the trial's one-year follow-up. Resource use (costs) will include all health care goods and services, and benefits provided during the trial's 1-year follow-up. The primary health effect will be the quality-adjusted life year. We will identify the most cost-effective intervention using the incremental cost-effectiveness ratio and incremental net-benefit. Confidence ellipses and cost-effectiveness acceptability curves will represent uncertainty around these statistics, respectively. A budget impact analysis will assess the total annual impact of replacing the current legislated standard of care with each of the other interventions. An expected value of perfect information will determine the maximum research expenditure Canadian society should be willing to pay for, and inform priority setting in, research of WAD management. Discussion. Results will provide health care decision makers with much needed economic evidence on common interventions for acute whiplash management. © 2011 van der Velde et al; licensee BioMed Central Ltd

Knowledge, attitudes and other factors associated with assessment of tobacco smoking among pregnant Aboriginal women by health care providers: a cross-sectional survey

<p>Abstract</p> <p>Background</p> <p>As with many Indigenous peoples, smoking rates among Aboriginal Australians are considerably higher than those of the non-Indigenous population. Approximately 50% of Indigenous women smoke during pregnancy, a time when women are more motivated to quit. Antenatal care providers are potentially important change agents for reducing the harms associated with smoking, yet little is known about their knowledge, attitudes or skills, or the factors associated with providing smoking cessation advice.</p> <p>Methods</p> <p>This paper aimed to explore the knowledge and attitudes of health care providers caring for pregnant Australian Aboriginal women with regard to smoking risks and cessation; and to identify factors associated with self-reported assessment of smoking. A cross-sectional survey was undertaken with 127 staff providing antenatal care to Aboriginal women from two jurisdictions: the Northern Territory and New South Wales, Australia. Measures included respondents' estimate of the prevalence of smoking among pregnant women; optimal and actual assessment of smoking status; knowledge of risks associated with antenatal smoking; knowledge of smoking cessation; attitudes to providing cessation advice to pregnant women; and perceived barriers and motivators for cessation for pregnant women.</p> <p>Results</p> <p>The median provider estimate of the smoking prevalence was 69% (95%CI: 60,70). The majority of respondents considered assessment of smoking status to be integral to antenatal care and a professional responsibility. Most (79%) indicated that they assess smoking status in 100% of clients. Knowledge of risks was generally good, but knowledge of cessation was poor. Factors independently associated with assessing smoking status among all women were: employer service type (<it>p </it>= 0.025); cessation knowledge score (<it>p </it>= 0.011); and disagreeing with the statement that giving advice is not worth it given the low level of success (<it>p </it>= 0.011).</p> <p>Conclusions</p> <p>Addressing knowledge of smoking risks and cessation counselling is a priority and should improve both confidence and ability, and increase the frequency and effectiveness of counselling. The health system must provide supports to providers through appropriate policy and resourcing, to enable them to address this issue.</p

Measuring emotional and social wellbeing in Aboriginal and Torres Strait Islander populations: an analysis of a Negative Life Events Scale

Aboriginal and Torres Strait Islander Australians experience widespread socioeconomic disadvantage and health inequality. In an attempt to make Indigenous health research more culturally-appropriate, Aboriginal and Torres Strait Islander Australians have called for more attention to the concept of emotional and social wellbeing (ESWB). Although it has been widely recognised that ESWB is of crucial importance to the health of Aboriginal and Torres Strait Islander peoples, there is little consensus on how to measure in Indigenous populations, hampering efforts to better understand and improve the psychosocial determinants of health. This paper explores the policy and political context to this situation, and suggests ways to move forward. The second part of the paper explores how scales can be evaluated in a health research setting, including assessments of endorsement, discrimination, internal and external reliability

Dynamics of Disks and Warps

This chapter reviews theoretical work on the stellar dynamics of galaxy disks. All the known collective global instabilities are identified, and their mechanisms described in terms of local wave mechanics. A detailed discussion of warps and other bending waves is also given. The structure of bars in galaxies, and their effect on galaxy evolution, is now reasonably well understood, but there is still no convincing explanation for their origin and frequency. Spiral patterns have long presented a special challenge, and ideas and recent developments are reviewed. Other topics include scattering of disk stars and the survival of thin disks.Comment: Chapter accepted to appear in Planets, Stars and Stellar Systems, vol 5, ed G. Gilmore. 32 pages, 17 figures. Includes minor corrections made in proofs. Uses emulateapj.st

Five insights from the Global Burden of Disease Study 2019

The Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2019 provides a rules-based synthesis of the available evidence on levels and trends in health outcomes, a diverse set of risk factors, and health system responses. GBD 2019 covered 204 countries and territories, as well as first administrative level disaggregations for 22 countries, from 1990 to 2019. Because GBD is highly standardised and comprehensive, spanning both fatal and non-fatal outcomes, and uses a mutually exclusive and collectively exhaustive list of hierarchical disease and injury causes, the study provides a powerful basis for detailed and broad insights on global health trends and emerging challenges. GBD 2019 incorporates data from 281 586 sources and provides more than 3.5 billion estimates of health outcome and health system measures of interest for global, national, and subnational policy dialogue. All GBD estimates are publicly available and adhere to the Guidelines on Accurate and Transparent Health Estimate Reporting. From this vast amount of information, five key insights that are important for health, social, and economic development strategies have been distilled. These insights are subject to the many limitations outlined in each of the component GBD capstone papers.Peer reviewe