Use of observed within-person variation of cardiac troponin in emergency department patients for determination of biological variation and percentage and absolute reference change values

BACKGROUND Many patients presenting to the emergency department (ED) for assessment of possible acute coronary syndrome (ACS) have low cardiac troponin concentrations that change very little on repeat blood draw. It is unclear if a lack of change in cardiac troponin concentration can be used to identify acutely presenting patients at low risk of ACS. METHODS We used the hs-cTnI assay from Abbott Diagnostics, which can detect cTnI in the blood of nearly all people. We identified a population of ED patients being assessed for ACS with repeat cTnI measurement who ultimately were proven to have no acute cardiac disease at the time of presentation. We used data from the repeat sampling to calculate total within-person CV (CV(T)) and, knowing the assay analytical CV (CV(A)), we could calculate within-person biological variation (CV(i)), reference change values (RCVs), and absolute RCV delta cTnI concentrations. RESULTS We had data sets on 283 patients. Men and women had similar CV(i) values of approximately 14%, which was similar at all concentrations <40 ng/L. The biological variation was not dependent on the time interval between sample collections (t = 1.5-17 h). The absolute delta critical reference change value was similar no matter what the initial cTnI concentration was. More than 90% of subjects had a critical reference change value <5 ng/L, and 97% had values of <10 ng/L. CONCLUSIONS With this hs-cTnI assay, delta cTnI seems to be a useful tool for rapidly identifying ED patients at low risk for possible ACS.

Characteristics of microbial drug resistance and its correlates in chronic diabetic foot ulcer infections

While virulence factors and the biofilm-forming capabilities of microbes are the key regulators of the wound healing process, the host immune response may also contribute in the events following wound closure or exacerbation of non-closure. We examined samples from diabetic and non-diabetic foot ulcers/wounds for microbial association and tested the microbes for their antibiotic susceptibility and ability to produce biofilms. A total of 1074 bacterial strains were obtained with staphylococci, Pseudomonas, Citrobacter and enterococci as major colonizers in diabetic samples. Though non-diabetic samples had a similar assemblage, the frequency of occurrence of different groups of bacteria was different. Gram-negative bacteria were found to be more prevalent in the diabetic wound environment while Gram-positive bacteria were predominant in non-diabetic ulcers. A higher frequency of monomicrobial infection was observed in samples from non-diabetic individuals when compared to samples from diabetic patients. The prevalence of different groups of bacteria varied when the samples were stratified according to age and sex of the individuals. Several multidrug-resistant strains were observed among the samples tested and most of these strains produced moderate to high levels of biofilms. The weakened immune response in diabetic individuals and synergism among pathogenic micro-organisms may be the critical factors that determine the delicate balance of the wound healing process.

Validity of currently used cutoff values of body mass index as a measure of obesity in Sri Lankan children

The aim of the study was to determine the reliability of body mass index based (BMI) cutoff values in diagnosing obesity among Sri Lankan children. Height, weight, waist circumference (WC) and hip circumference (HC) in 282 children were measured. Total body water was determined by deuterium dilution and fat mass (FM) derived using age and gender specific constants. A percentage FM of 30% for girls and 25% for boys were considered as cutoff levels for obesity. Two hundred and eighty two children (M/F: 158/124) were studied and 99 (80%) girls and 72 (45.5%) boys were obese based on % body fat. Eight (6.4%) girls and nine (5.7%) boys were obese based on International Obesity Task Force (IOTF) cutoff values. Percentage FM and WC centile charts were able to diagnose a significant proportion of children as true obese children. The FM and BMI were closely associated in both girls (r = 0.82, p < 0.001) and boys (r = 0.87, p < 0.001). Percentage FM and BMI had a very low but significant association; girls (r = 0.32, p < 0.001) and boys (r = 0.68, p < 0.001). FM had a significant association with WC and HC. BMI based cutoff values had a specificity of 100% but a very low sensitivity, varying between 8% and 23.6%. BMI is a poor indicator of the percentage fat and the commonly used cutoff values were not sensitive to detect cases of childhood obesity in Sri Lankan children.

Voice, deliberation, resistance and persuasion through networked journalism

The pervasive use of the World Wide Web by the general population has created a cultural shift in “our living world”. It has enabled more people to share more information about more events and issues in the world than was possible before its general use. As a consequence, it has transformed traditional news media’s approach to almost every aspect of journalism, with many organisations restructuring their philosophy and practice to include a variety of participatory spaces/forums where people are free to engage in deliberative dialogue about matters of public importance. Moreover, while news media were the traditional gatekeepers of information, today many organisations allow, to different degrees, the general public and other independent journalism entities to participate in the news production process, which may include agenda setting and content production. This paper draws from an international collective case study that showcases various approaches to networked online news journalism. It examines the ways in which different traditional news media models use digital tools and technologies for participatory communication of information about matters of public interest. The research finds differences between the ways in which public service, commercial and independent news media give voice to the public and ultimately their approach to journalism’s role as the Fourth Estate––one of the key institutions of democracy. The work is framed by the notion that journalism in democratic societies has a key role in ensuring citizens are informed and engaged with public affairs. An examination of four media models, the British Broadcasting Corporation (BBC), the Guardian, News Limited and OhmyNews, showcases the various approaches to networked online news journalism and how each provides different avenues for citizen empowerment. The cases are described and analysed in the context of their own social, political and economic setting. Semi-structured in-depth interviews with key senior journalists and editors provide specific information on comparisons between the distinctive practices of their own organisation. In particular these show how the ideal of democracy can be used as a tool of persuasion as much as a method of deliberation.

Measured and predicted total body water in children with myelomeningocele

Objective: Children with myelomeningocele (MMC) have an altered body composition and an atypical distribution of total body water (TBW). The aim of the present study was to determine the accuracy of current predictive equations, based on bioelectrical impedance analysis (BIA), in determining TBW when compared with measured TBW using deuterium dilution. Methods: Fourteen children with MMC were measured for whole body BIA and TBW (using deuterium dilution and the Plateau method). Total body water was predicted using equations based on the resistance and characteristic frequency from BIA measurements and heights of subjects. Results: The mean measured TBW was 15.46 ± 8.28 L and the mean predictions for TBW using equations based on the resistance and characteristic frequency from BIA measurements and heights of subjects were 18.29 ± 8.41 L, 17.72 ± 11.42 L and 12.51 ± 7.59 L, respectively. The best correlation was found using characteristic frequency. The limits of agreement between measured and predicted TBW values using Bland-Altman analysis were large. Conclusions: The present study suggests that the prediction of TBW in children with MMC can be made accurately using the equation of Cornish et al. based on BIA measurements of characteristic frequency.

The emerging role of extracellular vesicle-mediated drug resistance in cancers: Implications in advanced prostate cancer

Emerging evidence has shown that the extracellular vesicles (EVs) regulate various biological processes and can control cell proliferation and survival, as well as being involved in normal cell development and diseases such as cancers. In cancer treatment, development of acquired drug resistance phenotype is a serious issue. Recently it has been shown that the presence of multidrug resistance proteins such as Pgp-1 and enrichment of the lipid ceramide in EVs could have a role in mediating drug resistance. EVs could also mediate multidrug resistance through uptake of drugs in vesicles and thus limit the bioavailability of drugs to treat cancer cells. In this review, we discussed the emerging evidence of the role EVs play in mediating drug resistance in cancers and in particular the role of EVs mediating drug resistance in advanced prostate cancer. The role of EV-associated multidrug resistance proteins, miRNA, mRNA, and lipid as well as the potential interaction(s) among these factors was probed. Lastly, we provide an overview of the current available treatments for advanced prostate cancer, considering where EVs may mediate the development of resistance against these drugs.

Architectural changes of the biceps femoris after concentric or eccentric training

Purpose To determine i) the architectural adaptations of the biceps femoris long head (BFlf) following concentric or eccentric strength training interventions; ii) the time course of adaptation during training and detraining. Methods Participants in this randomized controlled trial (control [n=28], concentric training group [n=14], eccentric training group [n=14], males) completed a 4-week control period, followed by 6 weeks of either concentric- or eccentric-only knee flexor training on an isokinetic dynamometer and finished with 28 days of detraining. Architectural characteristics of BFlf were assessed at rest and during graded isometric contractions utilizing two-dimensional ultrasonography at 28 days pre-baseline, baseline, days 14, 21 and 42 of the intervention and then again following 28 days of detraining. Results BFlf fascicle length was significantly longer in the eccentric training group (p<0.05, d range: 2.65 to 2.98) and shorter in the concentric training group (p<0.05, d range: -1.62 to -0.96) after 42 days of training compared to baseline at all isometric contraction intensities. Following the 28-day detraining period, BFlf fascicle length was significantly reduced in the eccentric training group at all contraction intensities compared to the end of the intervention (p<0.05, d range: -1.73 to -1.55). There was no significant change in fascicle length of the concentric training group following the detraining period. Conclusions These results provide evidence that short term resistance training can lead to architectural alterations in the BFlf. In addition, the eccentric training-induced lengthening of BFlf fascicle length was reversed and returned to baseline values following 28 days of detraining. The contraction mode specific adaptations in this study may have implications for injury prevention and rehabilitation.

Growth hormone resistance and somatomedins in children with end-stage liver disease awaiting transplantation

Background: The success of orthotopic liver transplantation as treatment for end-stage liver disease has prompted investigation of strategies to maintain or improve nutrition and growth in children awaiting transplantation, because malnutrition is an adverse prognostic factor. The purpose of this study was to evaluate the effect of recombinant human growth hormone therapy on body composition and indices of liver function in patients awaiting transplant. Methods: The study was designed as a placebo- controlled, double-blind, crossover trial. Patients received 0.2 U/kg growth hormone, subcutaneously, or placebo daily for 28 days during two treatment periods, separated by a 2-week washout period. Ten patients (mean age, 3.06 ± 1.15 years; range, 0.51-11.65 years, five men), with extrahepatic biliary atresia (n = 8) or two with Alagille's syndrome (n = 2), with end-stage liver disease, completed the trial while awaiting orthotopic liver transplantation. Height, weight, total body potassium, total body fat, resting energy expenditure, respiratory quotient, hematologic and multiple biochemical profile, number of albumin infusions, insulin-like growth factor-1 and 1, growth hormone binding protein (GHBP), and insulin-like growth factor binding protein-1 (IGFBP-1) and insulin-like growth factor binding protein (IGFBP-3) were measured at the beginning and end of each treatment period. Results: Growth hormone treatment was associated with a significant decline in serum bilirubin (-34.6 ± 16.5 μmol/l vs. 18.2 ± 11.59 μmol/l; p < 0.02) but there was no significant effect on any anthropometric or body composition measurements, or on any biochemical or hematologic parameters. Conclusions: These children with end-stage liver disease displayed growth hormone resistance, particularly in relation to the somatomedin axis. Exogenous growth hormone administration may be of limited value in these patients

Elevated temperature mechanical properties of hollow flange channel sections

The fire performance of cold-formed steel members is an important criterion to be verified for their successful use in structural applications. However, lack of clear design guidance on their fire performance has inhibited their usage in buildings. Their elevated temperature mechanical properties, i.e., yield strengths, elastic moduli and stress–strain relationships, are imperative for the fire design. In the past many researchers have proposed elevated temperature mechanical property reduction factors for cold-formed steels, however, large variations exist among them. The LiteSteel Beam (LSB), a hollow flange channel section, is manufactured by a combined cold-forming and electric resistance welding process. Its web, inner and outer flange elements have different yield strengths due to varying levels of cold-working caused by their manufacturing process. Elevated temperature mechanical properties of LSBs are not the same even within their cross-sections. Therefore an experimental study was undertaken to determine the elevated temperature mechanical properties of steel plate elements in LSBs. Elevated temperature tensile tests were performed on web, inner and outer flange specimens taken from LSBs, and their results are presented in this paper including their comparisons with previous studies. Based on the test results and the proposed values from previous studies and fire design standards, suitable predictive equations are proposed for the determination of elevated temperature mechanical properties of LSB web and flange elements. Suitable stress–strain models are also proposed for the plate elements of this cold-formed and welded hollow flange channel section.

Engineering cellulose nanofibre suspensions to control filtration resistance and sheet permeability

This study examines and quantifies the effect of adding polyelectrolytes to cellulose nanofibre suspensions on the gel point of cellulose nanofibre suspensions, which is the lowest solids concentration at which the suspension forms a continuous network. The lower the gel point, the faster the drainage time to produce a sheet and the higher the porosity of the final sheet formed. Two new techniques were designed to measure the dynamic compressibility and the drainability of nanocellulose–polyelectrolyte suspensions. We developed a master curve which showed that the independent variable controlling the behaviour of nanocellulose suspensions and its composite is the structure of the flocculated suspension which is best quantified as the gel point. This was independent of the type of polyelectrolyte used. At an addition level of 2 mg/g of nanofibre, a reduction in gel point over 50 % was achieved using either a high molecular weight (13 MDa) linear cationic polyacrylamide (CPAM, 40 % charge), a dendrimer polyethylenimine of high molecular weight of 750,000 Da (HPEI) or even a low molecular weight of 2000 Da (LPEI). There was no significant difference in the minimum gel point achieved, despite the difference in polyelectrolyte morphology and molecular weight. In this paper, we show that the gel point controls the flow through the fibre suspension, even when comparing fibre suspensions with solids content above the gel point. A lower gel point makes it easier for water to drain through the fibre network,reducing the pressure required to achieve a given dewatering rate and reducing the filtering time required to form a wet laid sheet. We further show that the lower gel point partially controls the structure of the wet laid sheet after it is dried. Halving the gel point increased the air permeability of the dry sheet by 37, 46 and 25 %, when using CPAM, HPEI and LPEI, respectively. The resistance to liquid flow was reduced by 74 and 90 %, when using CPAM and LPEI. Analysing the paper formed shows that sheet forming process and final sheet properties can be engineered and controlled by adding polyelectrolytes to the nanofibre suspension.

Robust estimation using the Huber function with a data-dependent tuning constant

Robust estimation often relies on a dispersion function that is more slowly varying at large values than the square function. However, the choice of tuning constant in dispersion functions may impact the estimation efficiency to a great extent. For a given family of dispersion functions such as the Huber family, we suggest obtaining the "best" tuning constant from the data so that the asymptotic efficiency is maximized. This data-driven approach can automatically adjust the value of the tuning constant to provide the necessary resistance against outliers. Simulation studies show that substantial efficiency can be gained by this data-dependent approach compared with the traditional approach in which the tuning constant is fixed. We briefly illustrate the proposed method using two datasets.

Voice, deliberation, resistance and persuasion through participatory journalism business models

The pervasive use of the World Wide Web by the general population has created a cultural shift throughout the world. It has enabled more people to share more information about more events and issues than was possible before its general use. As a consequence, it has transformed traditional news media’s approach to almost every aspect of journalism, with many organisations restructuring their philosophy and practice to include a variety of participatory spaces/forums where people are free to engage in deliberative dialogue about matters of public importance. This paper draws from an international collective case study that showcases various approaches to participatory online news journalism during the period 1997–2011 (Adams, 2013). The research finds differences in the ways in which public service, commercial, and independent news media give voice to the public, and ultimately in their approach to journalism’s role as the Fourth Estate––one of the key institutions of democracy. The work is framed by the notion that journalism in democratic societies has a crucial role in ensuring citizens are informed and engaged with public affairs. An examination of four media models, OhmyNews International, News Corp Australia (formerly News Limited), the Guardian and the British Broadcasting Corporation (BBC), showcases the various approaches to participatory online news journalism and how each provides different avenues for citizen engagement. Semistructured in-depth interviews with some of the key senior journalists and editors provide specific information on comparisons between the distinctive practices in each of their employer organisations.

Analysis of human immunodeficiency virus type 1 drug resistance in children receiving nucleoside analogue reverse-transcriptase inhibitors plus nevirapine, nelfinavir, or ritonavir (Pediatric AIDS Clinical Trials Group 377)

In Pediatric AIDS Clinical Trials Group 377, antiretroviral therapy-experienced children were randomized to 4 treatment arms that included different combinations of stavudine, lamivudine (3TC), nevirapine (Nvp), nelfinavir (Nfv), and ritonavir (Rtv). Previous treatment with zidovudine (Zdv), didanosine (ddI), or zalcitabine (ddC) was acceptable. Drug resistance ((R)) mutations were assessed before study treatment (baseline) and at virologic failure. Zdv(R), ddI(R), and ddC(R) mutations were detected frequently at baseline but were not associated with virologic failure. Children with drug resistance mutations at baseline had greater reductions in virus load over time than did children who did not. Nvp(R) and 3TC(R) mutations were detected frequently at virologic failure, and Nvp(R) mutations were more common among children receiving 3-drug versus 4-drug Nvp-containing regimens. Children who were maintained on their study regimen after virologic failure accumulated additional Nvp(R) and 3TC(R) mutations plus Rtv(R) and Nfv(R) mutations. However, Rtv(R) and Nfv(R) mutations were detected at unexpectedly low rates.

Limitations of the manual supination resistance test

The aim of this study was to asses results obtained from a range of commonly performed lower extremity “open and closed” chain kinetic tests used for predicting foot function and correlate these test findings to data obtained from the Zebris WinFDM-T system®. When performed correctly these tests are thought to be indicators of lower extremity function. Podiatrists frequently perform examinations of joint and muscle structures to understand biomechanical function; however the relationship between these routine tests and forces generated during the gait cycle are not always well understood. This can introduce a degree of variability in clinical interpretation which creates conjecture regarding the value of these tests.

Inter-lamellar shear resistance confers compressive stiffness in the intervertebral disc: An image-based modelling study on the bovine caudal disc

The intervertebral disc withstands large compressive loads (up to nine times bodyweight in humans) while providing flexibility to the spinal column. At a microstructural level, the outer sheath of the disc (the annulus fibrosus) comprises 12–20 annular layers of alternately crisscrossed collagen fibres embedded in a soft ground matrix. The centre of the disc (the nucleus pulposus) consists of a hydrated gel rich in proteoglycans. The disc is the largest avascular structure in the body and is of much interest biomechanically due to the high societal burden of disc degeneration and back pain. Although the disc has been well characterized at the whole joint scale, it is not clear how the disc tissue microstructure confers its overall mechanical properties. In particular, there have been conflicting reports regarding the level of attachment between adjacent lamellae in the annulus, and the importance of these interfaces to the overall integrity of the disc is unknown. We used a polarized light micrograph of the bovine tail disc in transverse cross-section to develop an image-based finite element model incorporating sliding and separation between layers of the annulus, and subjected the model to axial compressive loading. Validation experiments were also performed on four bovine caudal discs. Interlamellar shear resistance had a strong effect on disc compressive stiffness, with a 40% drop in stiffness when the interface shear resistance was changed from fully bonded to freely sliding. By contrast, interlamellar cohesion had no appreciable effect on overall disc mechanics. We conclude that shear resistance between lamellae confers disc mechanical resistance to compression, and degradation of the interlamellar interface structure may be a precursor to macroscopic disc degeneration.