The (F)utility of the thallium-201 quantitative lung/myocardial ratio in the detection of coronary artery disease

Exercise-induced increases in pulmonary uptake of thallium-201 ( 201 Tl) have been associated with exercise-induced myocardial dysfunction. To evaluate this phenomenon more replicably, a quantitative semi-automated computer program was used to generate, from anterior exercise and delayed views, lung-myocardial ratios (LMR) of 201 Tl uptake in 78 patients [40 normal, 38 with coronary artery disease (CAD)]. Patients with CAD had a significantly higher mean exercise lung myocardial ratio (EXLMR) than normals (30.8 vs. 27.3; P < 0.003). In patients with adequate exercise (≥85% of an age-adjusted maximal heart rate), the EXLMRs of CAD patients were significantly higher than those of normals (29.7 vs. 25.5; P =0.003). However, this difference between CAD and normal patients was not apparent in a patient subgroup with submaximal exercise levels (< 85% of an age-adjusted maximal heart rate). In both normal and CAD patients, EXLMR decreased with increasing exercise levels ( r =-0.555; P =0.007). In patients with 201 Tl scans lacking visually defined perfusion defects (visually normal), an elevated LMR detected 60% of CAD cases with 81% specificity. A considerably elevated EXLMR in patients achieving adequate exercise should suggest the presence of CAD, even if there are no visually apparent cardiac perfusion defects. With submaximal exercise, however, the EXLMR is not a useful discriminator between CAD patients and normals.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/46823/1/259_2004_Article_BF00638787.pd

Tandem mass spectrometry data quality assessment by self-convolution

<p>Abstract</p> <p>Background</p> <p>Many algorithms have been developed for deciphering the tandem mass spectrometry (MS) data sets. They can be essentially clustered into two classes. The first performs searches on theoretical mass spectrum database, while the second based itself on <it>de novo </it>sequencing from raw mass spectrometry data. It was noted that the quality of mass spectra affects significantly the protein identification processes in both instances. This prompted the authors to explore ways to measure the quality of MS data sets before subjecting them to the protein identification algorithms, thus allowing for more meaningful searches and increased confidence level of proteins identified.</p> <p>Results</p> <p>The proposed method measures the qualities of MS data sets based on the symmetric property of b- and y-ion peaks present in a MS spectrum. Self-convolution on MS data and its time-reversal copy was employed. Due to the symmetric nature of b-ions and y-ions peaks, the self-convolution result of a good spectrum would produce a highest mid point intensity peak. To reduce processing time, self-convolution was achieved using Fast Fourier Transform and its inverse transform, followed by the removal of the "DC" (Direct Current) component and the normalisation of the data set. The quality score was defined as the ratio of the intensity at the mid point to the remaining peaks of the convolution result. The method was validated using both theoretical mass spectra, with various permutations, and several real MS data sets. The results were encouraging, revealing a high percentage of positive prediction rates for spectra with good quality scores.</p> <p>Conclusion</p> <p>We have demonstrated in this work a method for determining the quality of tandem MS data set. By pre-determining the quality of tandem MS data before subjecting them to protein identification algorithms, spurious protein predictions due to poor tandem MS data are avoided, giving scientists greater confidence in the predicted results. We conclude that the algorithm performs well and could potentially be used as a pre-processing for all mass spectrometry based protein identification tools.</p

Efect of maleated anhydride on mechanical properties of rice husk filler reinforced PLA Matrix Polymer Composite

Polylactic acid (PLA) formulated from corn starch has a bright potential to replace the non-renewable petroleum-based plastics. The combination of PLA and natural fbre has gained interest due to its unique performance, as reported in many researches and industries. Meanwhile, rice husk produced as the by-product of rice milling can be utilised, unless it is turned completely into waste. Therefore, in the present study, the rice husk powder (RHP) was used as a fller in the PLA, so to determine the infuence of the fller loading on the mechanical properties of the PLA composite. A coupling agent was selected for treatment from two options, i.e., maleic anhydride polypropylene (MAPP) and maleic anhydride polyethylene (MAPE), by applying the agents with various loading contents, such as 2, 4 and 6 wt%. The composite was fabricated by using the hot compression machine. Both the treated and untreated RHP–PLA composites were characterised via the tensile, fexural and impact strength tests. The increase in the RHP loading content led to the decrease in the tensile and fexural strengths. The applications of the coupling agents (MAPE and MAPP) did not improve the tensile and impact strengths, but the fexural strength was enhanced

The effectiveness of a low-intensity problem-solving intervention for common adolescent mental health problems in New Delhi, India: protocol for a school-based, individually randomized controlled trial with an embedded stepped-wedge cluster randomized controlled recruitment trial

Background Conduct, anxiety and depressive disorders account for over 75% of the adolescent mental health burden globally. The current protocol will test a low-intensity problem-solving intervention for school-going adolescents with common mental health problems in India. The protocol also tests the effects of a classroom-based sensitization intervention on the demand for counselling services in an embedded recruitment trial. Methods We will conduct a two-arm individually randomized controlled trial in six Government-run secondary schools in New Delhi. The targeted sample is 240 adolescents in grades 9-12 with persistent, elevated mental health symptoms and associated impact. Participants will receive either a brief problem-solving intervention delivered over 3 weeks by lay counsellors (intervention), or enhanced usual care comprised of problem-solving booklets (control). Self-reported adolescent mental health symptoms and idiographic problems will be assessed at 6 weeks (co-primary outcomes) and again at 12 weeks post-randomization. In addition, adolescent-reported impact of mental health difficulties, perceived stress, mental wellbeing and clinical remission, as well as parent-reported adolescent mental health symptoms and impact scores, will be assessed at 6 and 12 weeks post-randomization. We will also complete a parallel process evaluation, including estimations of the costs of delivering the interventions. An embedded recruitment trial will apply a stepped-wedge, cluster (class)-randomized controlled design in 70 classes across the six schools. This will evaluate the added impact of a classroom-based sensitization intervention over school-level recruitment sensitization activities on the primary outcome of referral rate into the host trial (i.e. the proportion of adolescents referred as a function of the total sampling frame in each condition of the embedded recruitment trial). Other outcomes will be the proportion of referrals eligible to participate in the host trial, proportion of self-generated referrals, and severity and pattern of symptoms among referred adolescents in each condition. Power calculations were undertaken separately for each trial. A detailed statistical analysis plan will be developed separately for each trial prior to unblinding. Discussion Both trials were initiated on 20 August 2018. A single research protocol for both trials offers a resource-efficient methodology for testing the effectiveness of linked procedures to enhance uptake and outcomes of a school-based psychological intervention for common adolescent mental health problems

Left ventricular shape variation in asymptomatic populations: the multi-ethnic study of atherosclerosis

BACKGROUND: Although left ventricular cardiac geometric indices such as size and sphericity characterize adverse remodeling and have prognostic value in symptomatic patients, little is known of shape distributions in subclinical populations. We sought to quantify shape variation across a large number of asymptomatic volunteers, and examine differences among sub-cohorts. METHODS: An atlas was constructed comprising 1,991 cardiovascular magnetic resonance (CMR) cases contributed from the Multi-Ethnic Study of Atherosclerosis baseline examination. A mathematical model describing regional wall motion and shape was used to establish a coordinate map registered to the cardiac anatomy. The model was automatically customized to left ventricular contours and anatomical landmarks, corrected for breath-hold mis-registration between image slices. Mathematical techniques were used to characterize global shape distributions, after removal of translations, rotations, and scale due to height. Differences were quantified among ethnicity, sex, smoking, hypertension and diabetes sub-cohorts. RESULTS: The atlas construction process yielded accurate representations of global shape (errors between manual and automatic surface points in 244 validation cases were less than the image pixel size). After correction for height, the dominant shape component was associated with heart size, explaining 32% of the total shape variance at end-diastole and 29% at end-systole. After size, the second dominant shape component was sphericity at end-diastole (13%), and concentricity at end-systole (10%). The resulting shape components distinguished differences due to ethnicity and risk factors with greater statistical power than traditional mass and volume indices. CONCLUSIONS: We have quantified the dominant components of global shape variation in the adult asymptomatic population. The data and results are available at cardiacatlas.org. Shape distributions were principally explained by size, sphericity and concentricity, which are known correlates of adverse outcomes. Atlas-based global shape analysis provides a powerful method for quantifying left ventricular shape differences in asymptomatic populations. TRIAL REGISTRATION: ClinicalTrials.gov NCT0000548

Iron Behaving Badly: Inappropriate Iron Chelation as a Major Contributor to the Aetiology of Vascular and Other Progressive Inflammatory and Degenerative Diseases

The production of peroxide and superoxide is an inevitable consequence of aerobic metabolism, and while these particular "reactive oxygen species" (ROSs) can exhibit a number of biological effects, they are not of themselves excessively reactive and thus they are not especially damaging at physiological concentrations. However, their reactions with poorly liganded iron species can lead to the catalytic production of the very reactive and dangerous hydroxyl radical, which is exceptionally damaging, and a major cause of chronic inflammation. We review the considerable and wide-ranging evidence for the involvement of this combination of (su)peroxide and poorly liganded iron in a large number of physiological and indeed pathological processes and inflammatory disorders, especially those involving the progressive degradation of cellular and organismal performance. These diseases share a great many similarities and thus might be considered to have a common cause (i.e. iron-catalysed free radical and especially hydroxyl radical generation). The studies reviewed include those focused on a series of cardiovascular, metabolic and neurological diseases, where iron can be found at the sites of plaques and lesions, as well as studies showing the significance of iron to aging and longevity. The effective chelation of iron by natural or synthetic ligands is thus of major physiological (and potentially therapeutic) importance. As systems properties, we need to recognise that physiological observables have multiple molecular causes, and studying them in isolation leads to inconsistent patterns of apparent causality when it is the simultaneous combination of multiple factors that is responsible. This explains, for instance, the decidedly mixed effects of antioxidants that have been observed, etc...Comment: 159 pages, including 9 Figs and 2184 reference

Guidelines for the use and interpretation of assays for monitoring autophagy (4th edition)1.

In 2008, we published the first set of guidelines for standardizing research in autophagy. Since then, this topic has received increasing attention, and many scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Thus, it is important to formulate on a regular basis updated guidelines for monitoring autophagy in different organisms. Despite numerous reviews, there continues to be confusion regarding acceptable methods to evaluate autophagy, especially in multicellular eukaryotes. Here, we present a set of guidelines for investigators to select and interpret methods to examine autophagy and related processes, and for reviewers to provide realistic and reasonable critiques of reports that are focused on these processes. These guidelines are not meant to be a dogmatic set of rules, because the appropriateness of any assay largely depends on the question being asked and the system being used. Moreover, no individual assay is perfect for every situation, calling for the use of multiple techniques to properly monitor autophagy in each experimental setting. Finally, several core components of the autophagy machinery have been implicated in distinct autophagic processes (canonical and noncanonical autophagy), implying that genetic approaches to block autophagy should rely on targeting two or more autophagy-related genes that ideally participate in distinct steps of the pathway. Along similar lines, because multiple proteins involved in autophagy also regulate other cellular pathways including apoptosis, not all of them can be used as a specific marker for bona fide autophagic responses. Here, we critically discuss current methods of assessing autophagy and the information they can, or cannot, provide. Our ultimate goal is to encourage intellectual and technical innovation in the field

Time-varying managerial overconfidence and pecking order preference

This paper examines whether managerial overconfidence enhances or weakens pecking order preference. We construct time-varying managerial words-based (i.e. tone of Chairman’s Statement) and action-based (i.e. firm investment and directors’ trading) overconfidence measures. Both optimistic tone and industry-adjusted investment have significant and negative impacts on the pecking order coefficient in the Shyam-Sunder and Myers (J Financ Econ 51:219–244, 1999) regression framework. Overconfident managers tend to use more equity than debt to finance deficits. This new evidence is consistent with the proposition that overconfident managers who underestimate the riskiness of future earnings believe that their debt (equity) is undervalued (overvalued) and therefore prefer equity to debt financing. Thus, managerial overconfidence can lead to a reverse pecking order preference. We also find that managerial overconfidence significantly weakens pecking order preference especially in firms with high earnings volatility and small firms