233 research outputs found

    Complete mitochondrial genome of the geniculate calcified red alga, Corallina officinalis (Corallinales, Rhodophyta)

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    peerreview_statement: The publishing and review policy for this title is described in its Aims & Scope. aims_and_scope_url: http://www.tandfonline.com/action/journalInformation?show=aimsScope&journalCode=tmdn20© 2016 The Author(s). Published by Taylor & Francis. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/ licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. The attached file is the published pd

    Primordial Black Holes: sirens of the early Universe

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    Primordial Black Holes (PBHs) are, typically light, black holes which can form in the early Universe. There are a number of formation mechanisms, including the collapse of large density perturbations, cosmic string loops and bubble collisions. The number of PBHs formed is tightly constrained by the consequences of their evaporation and their lensing and dynamical effects. Therefore PBHs are a powerful probe of the physics of the early Universe, in particular models of inflation. They are also a potential cold dark matter candidate.Comment: 21 pages. To be published in "Quantum Aspects of Black Holes", ed. X. Calmet (Springer, 2014

    Importance of competing risks in the analysis of anti-epileptic drug failure

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    BACKGROUND: Retention time (time to treatment failure) is a commonly used outcome in antiepileptic drug (AED) studies. METHODS: Two datasets are used to demonstrate the issues in a competing risks analysis of AEDs. First, data collection and follow-up considerations are discussed with reference to information from 15 monotherapy trials. Recommendations for improved data collection and cumulative incidence analysis are then illustrated using the SANAD trial dataset. The results are compared to the more common approach using standard survival analysis methods. RESULTS: A non-significant difference in overall treatment failure time between gabapentin and topiramate (logrank test statistic = 0.01, 1 degree of freedom, p-value = 0.91) masked highly significant differences in opposite directions with gabapentin resulting in fewer withdrawals due to side effects (Gray's test statistic = 11.60, 1 degree of freedom, p = 0.0007) but more due to poor seizure control (Gray's test statistic = 14.47, 1 degree of freedom, p-value = 0.0001). The significant difference in overall treatment failure time between lamotrigine and carbamazepine (logrank test statistic = 5.6, 1 degree of freedom, p-value = 0.018) was due entirely to a significant benefit of lamotrigine in terms of side effects (Gray's test statistic = 10.27, 1 degree of freedom, p = 0.001). CONCLUSION: Treatment failure time can be measured reliably but care is needed to collect sufficient information on reasons for drug withdrawal to allow a competing risks analysis. Important differences between the profiles of AEDs may be missed unless appropriate statistical methods are used to fully investigate treatment failure time. Cumulative incidence analysis allows comparison of the probability of failure between two AEDs and is likely to be a more powerful approach than logrank analysis for most comparisons of standard and new anti-epileptic drugs

    Hyperpolarized 13C-Pyruvate Metabolism as a Surrogate for Tumor Grade and Poor Outcome in Renal Cell Carcinoma-A Proof of Principle Study.

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    Differentiating aggressive clear cell renal cell carcinoma (ccRCC) from indolent lesions is challenging using conventional imaging. This work prospectively compared the metabolic imaging phenotype of renal tumors using carbon-13 MRI following injection of hyperpolarized [1-13C]pyruvate (HP-13C-MRI) and validated these findings with histopathology. Nine patients with treatment-naïve renal tumors (6 ccRCCs, 1 liposarcoma, 1 pheochromocytoma, 1 oncocytoma) underwent pre-operative HP-13C-MRI and conventional proton (1H) MRI. Multi-regional tissue samples were collected using patient-specific 3D-printed tumor molds for spatial registration between imaging and molecular analysis. The apparent exchange rate constant (kPL) between 13C-pyruvate and 13C-lactate was calculated. Immunohistochemistry for the pyruvate transporter (MCT1) from 44 multi-regional samples, as well as associations between MCT1 expression and outcome in the TCGA-KIRC dataset, were investigated. Increasing kPL in ccRCC was correlated with increasing overall tumor grade (ρ = 0.92, p = 0.009) and MCT1 expression (r = 0.89, p = 0.016), with similar results acquired from the multi-regional analysis. Conventional 1H-MRI parameters did not discriminate tumor grades. The correlation between MCT1 and ccRCC grade was confirmed within a TCGA dataset (p < 0.001), where MCT1 expression was a predictor of overall and disease-free survival. In conclusion, metabolic imaging using HP-13C-MRI differentiates tumor aggressiveness in ccRCC and correlates with the expression of MCT1, a predictor of survival. HP-13C-MRI may non-invasively characterize metabolic phenotypes within renal cancer

    PCR colorimetric dot-blot assay and clinical pretest probability for diagnosis of Pulmonary Tuberculosis in Smear-Negative patients

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    <p>Abstract</p> <p>Background</p> <p>Smear-negative pulmonary tuberculosis (SNPTB) accounts for 30% of Pulmonary Tuberculosis (PTB) cases reported annually in developing nations. Polymerase chain reaction (PCR) may provide an alternative for the rapid detection of <it>Mycobacterium tuberculosis </it>(MTB); however little data are available regarding the clinical utility of PCR in SNPTB, in a setting with a high burden of TB/HIV co-infection.</p> <p>Methods</p> <p>To evaluate the performance of the PCR dot-blot in parallel with pretest probability (Clinical Suspicion) in patients suspected of having SNPTB, a prospective study of 213 individuals with clinical and radiological suspicion of SNPTB was carried out from May 2003 to May 2004, in a TB/HIV reference hospital. Respiratory specialists estimated the pretest probability of active disease into high, intermediate, low categories. Expectorated sputum was examined by direct microscopy (Ziehl-Neelsen staining), culture (Lowenstein Jensen) and PCR dot-blot. Gold standard was based on culture positivity combined with the clinical definition of PTB.</p> <p>Results</p> <p>In smear-negative and HIV subjects, active PTB was diagnosed in 28.4% (43/151) and 42.2% (19/45), respectively. In the high, intermediate and low pretest probability categories active PTB was diagnosed in 67.4% (31/46), 24% (6/25), 7.5% (6/80), respectively. PCR had sensitivity of 65% (CI 95%: 50%–78%) and specificity of 83% (CI 95%: 75%–89%). There was no difference in the sensitivity of PCR in relation to HIV status. PCR sensitivity and specificity among non-previously TB treated and those treated in the past were, respectively: 69%, 43%, 85% and 80%. The high pretest probability, when used as a diagnostic test, had sensitivity of 72% (CI 95%:57%–84%) and specificity of 86% (CI 95%:78%–92%). Using the PCR dot-blot in parallel with high pretest probability as a diagnostic test, sensitivity, specificity, positive and negative predictive values were: 90%, 71%, 75%, and 88%, respectively. Among non-previously TB treated and HIV subjects, this approach had sensitivity, specificity, positive and negative predictive values of 91%, 79%, 81%, 90%, and 90%, 65%, 72%, 88%, respectively.</p> <p>Conclusion</p> <p>PCR dot-blot associated with a high clinical suspicion may provide an important contribution to the diagnosis of SNPTB mainly in patients that have not been previously treated attended at a TB/HIV reference hospital.</p

    Cost-effectiveness analysis of PCR for the rapid diagnosis of pulmonary tuberculosis

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    <p>Abstract</p> <p>Background</p> <p>Tuberculosis is one of the most prominent health problems in the world, causing 1.75 million deaths each year. Rapid clinical diagnosis is important in patients who have co-morbidities such as Human Immunodeficiency Virus (HIV) infection. Direct microscopy has low sensitivity and culture takes 3 to 6 weeks <abbrgrp><abbr bid="B1">1</abbr><abbr bid="B2">2</abbr><abbr bid="B3">3</abbr></abbrgrp>. Therefore, new tools for TB diagnosis are necessary, especially in health settings with a high prevalence of HIV/TB co-infection.</p> <p>Methods</p> <p>In a public reference TB/HIV hospital in Brazil, we compared the cost-effectiveness of diagnostic strategies for diagnosis of pulmonary TB: Acid fast bacilli smear microscopy by Ziehl-Neelsen staining (AFB smear) plus culture and AFB smear plus colorimetric test (PCR dot-blot).</p> <p>From May 2003 to May 2004, sputum was collected consecutively from PTB suspects attending the Parthenon Reference Hospital. Sputum samples were examined by AFB smear, culture, and PCR dot-blot. The gold standard was a positive culture combined with the definition of clinical PTB. Cost analysis included health services and patient costs.</p> <p>Results</p> <p>The AFB smear plus PCR dot-blot require the lowest laboratory investment for equipment (US20,000).Thetotalscreeningcostsare3.8timesforAFBsmearpluscultureversusforAFBsmearplusPCRdotblotcosts(US 20,000). The total screening costs are 3.8 times for AFB smear plus culture versus for AFB smear plus PCR dot blot costs (US 5,635,760 versus US1,498,660).CostspercorrectlydiagnosedcasewereUS 1,498, 660). Costs per correctly diagnosed case were US 50,773 and US13,749forAFBsmearpluscultureandAFBsmearplusPCRdotblot,respectively.AFBsmearplusPCRdotblotwasmorecosteffectivethanAFBsmearplusculture,whenthecostoftreatingallcorrectlydiagnosedcaseswasconsidered.Thecostofreturningpatients,whicharenottreatedduetoanegativeresult,tothehealthservice,washigherinAFBsmearplusculturethanforAFBsmearplusPCRdotblot,US 13,749 for AFB smear plus culture and AFB smear plus PCR dot-blot, respectively. AFB smear plus PCR dot-blot was more cost-effective than AFB smear plus culture, when the cost of treating all correctly diagnosed cases was considered. The cost of returning patients, which are not treated due to a negative result, to the health service, was higher in AFB smear plus culture than for AFB smear plus PCR dot-blot, US 374,778,045 and US$ 110,849,055, respectively.</p> <p>Conclusion</p> <p>AFB smear associated with PCR dot-blot associated has the potential to be a cost-effective tool in the fight against PTB for patients attended in the TB/HIV reference hospital.</p

    The reliability of side to side measurements of upper extremity activity levels in healthy subjects

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    <p>Abstract</p> <p>Background</p> <p>In both clinical and occupational settings, ambulatory sensors are becoming common for assessing all day measurements of arm motion. In order for the motion of a healthy, contralateral side to be used as a control for the involved side, the inherent side to side differences in arm usage must be minimal. The goal of the present study was to determine the reliability of side to side measurements of upper extremity activity levels in healthy subjects.</p> <p>Methods</p> <p>Thirty two subjects with no upper extremity pathologies were studied. Each subject wore a triaxial accelerometer on both arms for three and a half hours. Motion was assessed using parameters previously reported in the literature. Side to side differences were compared with the intraclass correlation coefficient, standard error of the mean, minimal detectable change scores and a projected sample size analysis.</p> <p>Results</p> <p>The variables were ranked based on their percentage of minimal detectable change scores and sample sizes needed for paired t-tests. The order of these rankings was found to be identical and the top ranked parameters were activity counts per hour (MDC% = 9.5, n = 5), jerk time (MDC% = 15.8, n = 8) and percent time above 30 degrees (MDC% = 34.7, n = 9).</p> <p>Conclusions</p> <p>In general, the mean activity levels during daily activities were very similar between dominant and non-dominant arms. Specifically, activity counts per hour, jerk time, and percent time above 30 degrees were found to be the variables most likely to reveal significant difference or changes in both individuals and groups of subjects. The use of ambulatory measurements of upper extremity activity has very broad uses for occupational assessments, musculoskeletal injuries of the shoulder, elbow, wrist and hand as well as neurological pathologies.</p

    Design and baseline characteristics of the ParkFit study, a randomized controlled trial evaluating the effectiveness of a multifaceted behavioral program to increase physical activity in Parkinson patients

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    <p>Abstract</p> <p>Background</p> <p>Many patients with Parkinson's disease (PD) lead a sedentary lifestyle. Promotion of physical activities may beneficially affect the clinical presentation of PD, and perhaps even modify the course of PD. However, because of physical and cognitive impairments, patients with PD require specific support to increase their level of physical activity.</p> <p>Methods</p> <p>We developed the ParkFit Program: a PD-specific and multifaceted behavioral program to promote physical activity. The emphasis is on creating a behavioral change, using a combination of accepted behavioral motivation techniques. In addition, we designed a multicentre randomized clinical trial to investigate whether this ParkFit Program increases physical activity levels over two years in sedentary PD patients. We intended to include 700 sedentary patients. Primary endpoint is the time spent on physical activities per week, which will be measured every six months using an interview-based 7-day recall.</p> <p>Results</p> <p>In total 3453 PD patients were invited to participate. Ultimately, 586 patients - with a mean (SD) age of 64.1 (7.6) years and disease duration of 5.3 (4.5) years - entered the study. Study participants were younger, had a shorter disease duration and were less sedentary compared with eligible PD patients not willing to participate.</p> <p>Discussion</p> <p>The ParkFit trial is expected to yield important new evidence about behavioral interventions to promote physical activity in sedentary patients with PD. The results of the trial are expected in 2012.</p> <p>Trial registration</p> <p><url>http://clinicaltrials.gov</url> (nr NCT00748488).</p
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