623 research outputs found

    Outcome Report of Roundtable on International Investment Regime and Access to Justice

    Get PDF
    On October 18, 2017, the UN Working Group on Business and Human Rights and the CCSI co-hosted a one-day roundtable on the impacts of the international investment regime on access to justice for investment-affected individuals and communities. Held at Columbia University in New York, the roundtable brought together 32 individuals from civil society organizations, communities affected by investments at the heart of investor-state claims, governments, academia, donor organizations, UN mandate holders, and other stakeholder groups. The roundtable provided an opportunity for participants to: (i) explore and assess the specific impacts of international investment agreements and investor-state dispute settlement on access to justice, both within and outside the investment regime; (ii) discuss and analyze options for reform of the international investment regime and improvement of human rights enforcement mechanisms to determine whether they address the specific impacts explored; and (iii) identify a preliminary set of recommendations to address implications of the current investment regime for access to justice. Following the roundtable, key takeaways from the discussion were discussed during a session at the 6th UN Forum on Business and Human Rights on November 29th, 2017. This outcome document summarizes roundtable discussions. A shorter briefing note provides an overview of key points

    Regenerable DNA-Functionalized Hydrogels for Ultrasensitive, Instrument-Free Mercury(II) Detection and Removal in Water

    Get PDF
    This document is the Accepted Manuscript version of a Published Work that appeared in final form in Journal of the American Chemical Society, copyright © American Chemical Society after peer review and technical editing by publisher. To access the final edited and published work see Dave, N., Chan, M. Y., Huang, P.-J. J., Smith, B. D., & Liu, J. (2010). Regenerable DNA-Functionalized Hydrogels for Ultrasensitive, Instrument-Free Mercury(II) Detection and Removal in Water. Journal of the American Chemical Society, 132(36), 12668–12673. https://doi.org/10.1021/ja106098jMercury is a highly toxic environmental pollutant with bioaccumulative properties. Therefore, new materials are required to not only detect but also effectively remove mercury from environmental sources such as water. We herein describe a polyacrylamide hydrogel-based sensor functionalized with a thymine-rich DNA that can simultaneously detect and remove mercury from water. Detection is achieved by selective binding of Hg2+ between two thymine bases, inducing a hairpin structure where, upon addition of SYBR Green I dye, green fluorescence is observed. In the absence of Hg2+, however, addition of the dye results in yellow fluorescence. Using the naked eye, the detection limit in a 50 mL water sample is 10 nM Hg2+. This sensor can be regenerated using a simple acid treatment and can remove Hg2+ from water at a rate of ∼1 h−1. This sensor was also used to detect and remove Hg2+ from samples of Lake Ontario water spiked with mercury. In addition, these hydrogel-based sensors are resistant to nuclease and can be rehydrated from dried gels for storage and DNA protection. Similar methods can be used to functionalize hydrogels with other nucleic acids, proteins, and small molecules for environmental and biomedical applications.University of Waterloo || Natural Sciences and Engineering Research Council |

    Joint modelling of mental health markers through pregnancy: a Bayesian semi-parametric approach

    Get PDF
    Maternal depression and anxiety through pregnancy have lasting societal impacts. It is thus crucial to understand the trajectories of its progression from preconception to postnatal period, and the risk factors associated with it. Within the Bayesian framework, we propose to jointly model seven outcomes, of which two are physiological and five non-physiological indicators of maternal depression and anxiety over time. We model the former two by a Gaussian process and the latter by an autoregressive model, while imposing a multidimensional Dirichlet process prior on the subject-specific random effects to account for subject heterogeneity and induce clustering. The model allows for the inclusion of covariates through a regression term. Our findings reveal four distinct clusters of trajectories of the seven health outcomes, characterising women's mental health progression from before to after pregnancy. Importantly, our results caution against the loose use of hair corticosteroids as a biomarker, or even a causal factor, for pregnancy mental health progression. Additionally, the regression analysis reveals a range of preconception determinants and risk factors for depressive and anxiety symptoms during pregnancy

    Discovery of a Novel Prolactin in Non-Mammalian Vertebrates: Evolutionary Perspectives and Its Involvement in Teleost Retina Development

    Get PDF
    BACKGROUND:The three pituitary hormones, viz. prolactin (PRL), growth hormone (GH) and somatolactin (SL), together with the mammalian placental lactogen (PL), constitute a gene family of hormones with similar gene structure and encoded protein sequences. These hormones are believed to have evolved from a common ancestral gene through several rounds of gene duplication and subsequent divergence. PRINCIPAL FINDINGS:In this study, we have identified a new PRL-like gene in non-mammalian vertebrates through bioinformatics and molecular cloning means. Phylogenetic analyses showed that this novel protein is homologous to the previously identified PRL. A receptor transactivation assay further showed that this novel protein could bind to PRL receptor to trigger the downstream post-receptor event, indicating that it is biologically active. In view of its close phylogenetic relationship with PRL and also its ability to activate PRL receptor, we name it as PRL2 and the previously identified PRL as PRL1. All the newly discovered PRL2 sequences possess three conserved disulfide linkages with the exception of the shark PRL2 which has only two. In sharp contrast to the classical PRL1 which is predominantly expressed in the pituitary, PRL2 was found to be mainly expressed in the eye and brain of the zebrafish but not in the pituitary. A largely reduced inner nuclear layer of the retina was observed after morpholino knockdown of zebrafish PRL2, indicating its role on retina development in teleost. SIGNIFICANCE:The discovery of this novel PRL has revitalized our understanding on the evolution of the GH/PRL/SL/PL gene family. Its unique expression and functions in the zebrafish eye also provide a new avenue of research on the neuroendocrine control of retina development in vertebrates

    The coronary CT angiography vision protocol : a prospective observational imaging cohort study in patients undergoing non-cardiac surgery

    Get PDF
    INTRODUCTION: At present, physicians have a limited ability to predict major cardiovascular complications after non-cardiac surgery and little is known about the anatomy of coronary arteries associated with perioperative myocardial infarction. We have initiated the Coronary CT Angiography (CTA) VISION Study to (1) establish the predictive value of coronary CTA for perioperative myocardial infarction and death and (2) describe the coronary anatomy of patients that have a perioperative myocardial infarction. METHODS AND ANALYSIS: The Coronary CTA VISION Study is prospective observational study. Preoperative coronary CTA will be performed in 1000–1500 patients with a history of vascular disease or at least three cardiovascular risk factors who are undergoing major elective non-cardiac surgery. Serial troponin will be measured 6–12 h after surgery and daily for the first 3 days after surgery. Major vascular outcomes at 30 days and 1 year after surgery will be independently adjudicated. ETHICS AND DISSEMINATION: Coronary CTA results in a measurable radiation exposure that is similar to a nuclear perfusion scan (10–12 mSV). Treating physicians will be blinded to the CTA results until 30 days after surgery in order to provide the most unbiased assessment of its prognostic capabilities. The only exception will be the presence of a left main stenosis >50%. This approach is supported by best available current evidence that, excluding left main disease, prophylatic revascularisation prior to non-cardiac surgery does not improve outcomes. An external safety and monitoring committee is overseeing the study and will review outcome data at regular intervals. Publications describing the results of the study will be submitted to major peer-reviewed journals and presented at international medical conferences

    Epidemiology, prehospital care and outcomes of patients arriving by ambulance with dyspnoea: An observational study

    Get PDF
    Background: This study aimed to determine epidemiology and outcome for patients presenting to emergency departments (ED) with shortness of breath who were transported by ambulance. Methods: This was a planned sub-study of a prospective, interrupted time series cohort study conducted at three time points in 2014 and which included consecutive adult patients presenting to the ED with dyspnoea as a main symptom. For this sub-study, additional inclusion criteria were presentation to an ED in Australia or New Zealand and transport by ambulance. The primary outcomes of interest are the epidemiology and outcome of these patients. Analysis was by descriptive statistics and comparisons of proportions. Results: One thousand seven patients met inclusion criteria. Median age was 74 years (IQR 61-68) and 46.1 % were male. There was a high rate of co-morbidity and chronic medication use. The most common ED diagnoses were lower respiratory tract infection (including pneumonia, 22.7 %), cardiac failure (20.5%) and exacerbation of chronic obstructive pulmonary disease (19.7 %). ED disposition was hospital admission (including ICU) for 76.4 %, ICU admission for 5.6 % and death in ED in 0.9 %. Overall in-hospital mortality among admitted patients was 6.5 %. Discussion: Patients transported by ambulance with shortness of breath make up a significant proportion of ambulance caseload and have high comorbidity and high hospital admission rate. In this study, >60 % were accounted for by patients with heart failure, lower respiratory tract infection or COPD, but there were a wide range of diagnoses. This has implications for service planning, models of care and paramedic training. Conclusion: This study shows that patients transported to hospital by ambulance with shortness of breath are a complex and seriously ill group with a broad range of diagnoses. Understanding the characteristics of these patients, the range of diagnoses and their outcome can help inform training and planning of services

    Dopamine Induced Neurodegeneration in a PINK1 Model of Parkinson's Disease

    Get PDF
    Parkinson's disease is a common neurodegenerative disease characterised by progressive loss of dopaminergic neurons, leading to dopamine depletion in the striatum. Mutations in the PINK1 gene cause an autosomal recessive form of Parkinson's disease. Loss of PINK1 function causes mitochondrial dysfunction, increased reactive oxygen species production and calcium dysregulation, which increases susceptibility to neuronal death in Parkinson's disease. The basis of neuronal vulnerability to dopamine in Parkinson's disease is not well understood

    The effects of anticholinergic medications on cognition in children: a systematic review and meta-analysis

    Get PDF
    Cognitive side effects of anticholinergic medications in older adults are well documented. Whether these poor cognitive outcomes are observed in children has not been systematically investigated. We aimed to conduct a systematic review and meta-analysis on the associations between anticholinergic medication use and cognitive performance in children. Systematic review was conducted using Medline, PsychInfo, and Embase, identifying studies testing cognitive performance relative to the presence versus absence of anticholinergic medication(s) in children. We assessed effects overall, as well as relative to drug class, potency (low and high), cognitive domain, and duration of administration. The systematic search identified 46 articles suitable for meta-analysis. For the most part, random effects meta-analyses did not identify statistically significant associations between anticholinergic exposure and cognitive performance in children; the one exception was a small effect of anticholinergic anti-depressants being associated with better cognitive function (Hedges’ g = 0.24, 95% CI 0.06–0.42, p = 0.01). Anticholinergic medications do not appear to be associated with poor cognitive outcomes in children, as they do in older adults. The discrepancy in findings with older adults may be due to shorter durations of exposure in children, differences in study design (predominantly experimental studies in children rather than predominantly epidemiological in older adults), biological ageing (e.g. blood brain barrier integrity), along with less residual confounding due to minimal polypharmacy and comorbidity in children

    The influence of atrial fibrillation on the levels of NT-proBNP versus GDF-15 in patients with heart failure

    Get PDF
    In heart failure (HF), levels of NT-proBNP are influenced by the presence of concomitant atrial fibrillation (AF), making it difficult to distinguish between HF versus AF in patients with raised NT-proBNP. It is unknown whether levels of GDF-15 are also influenced by AF in patients with HF. In this study we compared the plasma levels of NT-proBNP versus GDF-15 in patients with HF in AF versus sinus rhythm (SR)
    corecore