Why my disease is important: metrics of disease occurrence used in the introductory sections of papers in three leading general medical journals in 1993 and 2003.

BACKGROUND: We assessed the metrics used in claims about disease importance made in the introductory sections of scientific papers published in 1993 and 2003. We were interested in the choice of metric in circumstances where establishing the relative social importance of a disease was, presumptively, a primary objective. METHODS: This study consisted of a textual examination of the introductory statements from papers retrieved from MEDLINE. Papers were published in the New England Journal of Medicine, The Lancet, and the Journal of the American Medical Association during the first halves of 1993 and 2003, and were selected on the basis of keywords found in a pilot study to be associated with claims about disease importance. RESULTS: We found 143 papers in 1993 and 264 papers in 2003 included claims about disease importance in their introductory sections, and characteristics of these claims were abstracted. Of the quotes identified in the papers and articles examined, most used counts, prevalence, or incidence measurements. Some also used risk estimates and economic quantities to convey the importance of the disease. There was no change in the types of metrics used between 1993 and 2003. Very few articles, even in 2003, used metrics that weighted disease onsets by the expected consequent loss of healthy time -- such as years of life lost, quality-adjusted life years, and/or disability-adjusted life years. CONCLUSIONS: Claims about the relative importance of diseases continued to be overwhelmingly expressed in terms of counts (of deaths and disease onsets) and comparisons of counts, rates, and risks. Where the aim is to convey the burden that a given disease imposes on a society, "event-based" metrics might be less fit for the purpose than "time-based" metrics. More attention is needed to how the choice of metric should relate to the purpose at hand.RIGHTS : This article is licensed under the BioMed Central licence at http://www.biomedcentral.com/about/license which is similar to the 'Creative Commons Attribution Licence'. In brief you may : copy, distribute, and display the work; make derivative works; or make commercial use of the work - under the following conditions: the original author must be given credit; for any reuse or distribution, it must be made clear to others what the license terms of this work are

Directed Explicit Model Checking with HSF-SPIN

We present the explicit state model checker HSF-SPIN which is based on the model checker SPIN and its Promela modeling language. HSF-SPIN incorporates directed search algorithms for checking safety and a large class of LTL-specified liveness properties. We start off from the A* algorithm and define heuristics to accelerate the search into the direction of a specified failure situation. Next we propose an improved nested depth-first search algorithm that exploits the structure of Promela Never-Claims. As a result of both improvements, counterexamples will be shorter and the explored part of the state space will be smaller than with classical approaches, allowing to analyze larger state spaces. We evaluate the impact of the new heuristics and algorithms on a set of protocol models, some of which are real-world industrial protocols

Why choice of metric matters in public health analyses: a case study of the attribution of credit for the decline in coronary heart disease mortality in the US and other populations

RIGHTS : This article is licensed under the BioMed Central licence at http://www.biomedcentral.com/about/license which is similar to the 'Creative Commons Attribution Licence'. In brief you may : copy, distribute, and display the work; make derivative works; or make commercial use of the work - under the following conditions: the original author must be given credit; for any reuse or distribution, it must be made clear to others what the license terms of this work are.Abstract Background Reasons for the widespread declines in coronary heart disease (CHD) mortality in high income countries are controversial. Here we explore how the type of metric chosen for the analyses of these declines affects the answer obtained. Methods The analyses we reviewed were performed using IMPACT, a large Excel based model of the determinants of temporal change in mortality from CHD. Assessments of the decline in CHD mortality in the USA between 1980 and 2000 served as the central case study. Results Analyses based in the metric of number of deaths prevented attributed about half the decline to treatments (including preventive medications) and half to favourable shifts in risk factors. However, when mortality change was expressed in the metric of life-years-gained, the share attributed to risk factor change rose to 65%. This happened because risk factor changes were modelled as slowing disease progression, such that the hypothetical deaths averted resulted in longer average remaining lifetimes gained than the deaths averted by better treatments. This result was robust to a range of plausible assumptions on the relative effect sizes of changes in treatments and risk factors. Conclusions Time-based metrics (such as life years) are generally preferable because they direct attention to the changes in the natural history of disease that are produced by changes in key health determinants. The life-years attached to each death averted will also weight deaths in a way that better reflects social preferences.Peer Reviewe

Porphyrins profile by high performance liquid chromatography/electrospray ionization tandem mass spectrometry for the diagnosis of porphyria

Porphyrias are a group of inherited or acquired disorders of certain enzymes in the heme bio-synthetic pathway. Most porphyria symptoms are nonspecific and occur intermittently; resulting frequently in missed diagnosis since the disease itself is a rare one. The aim of the study is toestablish a new reliable and accurate laboratory method for separation, identification and quantitation of urinary porphyrins by liquid chromatography tandem mass spectrometry (LC/MS/MS) and thereby the diagnosis of different porphyria types for the first time in Egypt. Screening by plasma fluorescence and quantitative determination of urinary porphyrins by high performance liquid chromatography electrospray ionization tandem mass spectrometry (HPLC/ESI/MS/MS) of 50 clinically suspected patients revealed one case of variegate porphyria and five cases of porphyria cutanea tarda. Plasma fluorescence scanning is a simple procedure that can be used as screening test to detect porphyria patients that require quantitation of urinary porphyrins as a second step. Quantitative determination of urinary porphyrins using HPLC/ESI/MS/MS and ion mapping techniques are applicable for the differential diagnosis of porphyria types, since each type has a characteristic porphyrins excretion profile. Quantitative determination of urinary porphyrins by HPLC/ESI/MS/MS used in this study is a modification for the method Stoev et al. while ion mapping technique is a new technique invented by the research team at the Biochemical Genetics Department

Lactatemia during treatment of status asthmaticus in children

Background: Transient increase of lactate levels with or without metabolic acidosis has been seldom reported as a complication of β2-adrenergic therapy administered during asthma attacks in children. Objective: The study is aimed to investigate the frequency of lactatemia in children with acute asthma treated with nebulized β2-agonists, and to delineate its causes and effects on prognosis. Methods: We studied 32 asthmatic children; 68.8% had intermittent asthma, and 31.2% had mild persistent asthma. Their ages ranged from 6 to 8 years with a mean of 6.48±0.68 years. Patients were enrolled during acute asthma exacerbation (62.5% had severe and 37.5% had moderate attacks)from the Cairo University Children's Hospital. Patients underwent clinical evaluation, and routine investigations (CBC, PEFR, and total serum IgE) then received nebulized salbutamol at 0.1 mg/kg/dose (minimum 2.5 mg) every 20 min for three doses together with O2. Plasma lactate was determined before, 1 h after, and 24 h following the inhalation therapy. Blood gases were also evaluated before and after the β2-agonist treatment. Results: At 1 h post-treatment, all patients had appreciable lactatemia (4.44±0.78 mmol/L, p < 0.001) compared to the pre-treatment level with a rise of 257±121.5%. Patients with severe attacks demonstrated a higher mean value compared to those with moderate attacks (4.69±0.8 mmol/L versus 4.02±0.6 mmol/L, p < 0.05). At 24 h post-treatment, lactate levels returned to the normal values in most patients (1.91±0.59 mmol/L, p < 0.001) as compared to the 1 h post-treatment level. None of our patients developed metabolic acidosis and all of them showed significant clinical improvement. Our results strongly accuse nebulized salbutamol as the possible pathogenetic factor for lactatemia during therapy of acute asthma attacks, while overworked respiratory muscles and hypoxemia have been excluded as contributing factors. Conclusion: Transient lactatemia is not uncommon during β2-agonist therapy in asthmatic children with acute exacerbation, and is harmless in most cases. Prediction of lactic acidosis prevents inappropriate intensification of therapy especially in patients with more severe attacks or impending respiratory failure.Keywords: Asthma, exacerbation, lactate, lactatemia, β2-agonist, salbutamolEgypt J Pediatr Allergy Immunol 2004; 2(2): 83-8

Breast cancer resistance protein (BCRP) gene expression in a cohort of adult Egyptian patients with acute myeloid leukemia

Background: Acute myeloid leukemia (AML), an aggressive clonal disease, is genetically heterozygous. The prognostic role of expression of Breast Cancer Resistance Protein (BCRP) gene, which behaves as a multidrug transporter, in adult AML is ambiguous. Objective: The objective is to assess the level of mRNA expression of BCRP gene in newly diagnosed cytogenetically normal adult Egyptian AML patients; and to clarify its potential influence and association between therapeutic responsiveness and disease free survival.Methods: The BCRP gene expression was evaluated by quantifying its mRNA using real time RT-PCR in fifty newly diagnosed cytogenetically normal adult AML patients and 20 healthy normal controls. The expression was evaluated in relation to clinical and prognostic factors, response to treatment and the survival rate. Results: BCRP mRNA was over expressed in adult AML patients compared to controls. This study showed a positive statistical correlation between BCRP gene expression and the percent of CD34 expression. Statistical analysis did not reveal  any association between BCRP expression level and chemotherapeutic responsiveness or disease free survival rate. Conclusion: The significance of BCRP gene expression and its function in AML is very complicated, therefore more standardized clinical studies are needed.Keywords: BCRP, adult AML, gene expression, prognosis, Egypt

Exploring the Levinthal limit in protein folding

According to the thermodynamic hypothesis, the native state of proteins is uniquely defined by their amino acid sequence. On the other hand, according to Levinthal, the native state is just a local minimum of the free energy and a given amino acid sequence, in the same thermodynamic conditions, can assume many, very different structures that are as thermodynamically stable as the native state. This is the Levinthal limit explored in this work. Using computer simulations, we compare the interactions that stabilize the native state of four different proteins with those that stabilize three non-native states of each protein and find that the nature of the interactions is very similar for all such 16 conformers. Furthermore, an enhancement of the degree of fluctuation of the non-native conformers can be explained by an insufficient relaxation to their local free energy minimum. These results favor Levinthal's hypothesis that protein folding is a kinetic non-equilibrium process.FCT - Foundation for Science and Technology, Portugal [UID/Multi/04326/2013]; Fundacao de Amparo a Pesquisa do Estado de Sao Paulo (FAPESP); Conselho Nacional de Desenvolvimento Cientia co e Tecnologico (CNPq

Inverting the Sachs-Wolfe Formula: an Inverse Problem Arising in Early-Universe Cosmology

The (ordinary) Sachs-Wolfe effect relates primordial matter perturbations to the temperature variations $\delta T/T$ in the cosmic microwave background radiation; $\delta T/T$ can be observed in all directions around us. A standard but idealised model of this effect leads to an infinite set of moment-like equations: the integral of $P(k) j_\ell^2(ky)$ with respect to k ($0<k<\infty$) is equal to a given constant, $C_\ell$, for $\ell=0,1,2,...$. Here, P is the power spectrum of the primordial density variations, $j_\ell$ is a spherical Bessel function and y is a positive constant. It is shown how to solve these equations exactly for ~$P(k)$. The same solution can be recovered, in principle, if the first ~m equations are discarded. Comparisons with classical moment problems (where $j_\ell^2(ky)$ is replaced by $k^\ell$) are made.Comment: In Press Inverse Problems 1999, 15 pages, 0 figures, Late

Preparation and Characterization of Some Nanometal Oxides Using Microwave Technique and Their Application to Cotton Fabrics

The objective of this paper is the synthesis of some nanometal oxides via microwave irradiation technique and their application to augment multifunctional properties of cotton fabric. Cotton fabrics containing nanometal oxides were prepared via a thiol-modification of cotton fabric samples and then dipped into the metal salt solutions precursors and transferred to the microwave oven. The surface morphology and quantitative analysis of the obtained modified cotton fabrics containing nanometal oxides were studied by scanning electron microscopy coupled with high energy dispersive X-ray (SEM-EDX). The shape and distribution of nanometal oxide inside the fabric samples were analyzed by transmission electron microscopy of cross-section fabric samples. The iron oxide nanoparticles had a nanosphere with particle size diameter 15–20 nm, copper oxide nanoparticles had a nanosphere with particle size diameter 25–30 nm, and cobalt oxide nanoparticles had a nanotube-like shape with a length of 100–150 nanometer and a diameter of ~58 nanometer, whereas the manganese oxide nanoparticles had a linear structure forming nanorods with a diameter of 50–55 nanometer and a length of 70–80 nanometers. Antibacterial activity was evaluated quantitatively against gram-positive bacteria such as Staphylococcus aureus and gram-negative bacteria such as Escherichia coli, UV-protection activity was analyzed using UV-DRS spectroscopy, and flame retardation of prepared fabric samples was evaluated according to the limiting oxygen index (LOI). Results revealed that the prepared fabric sample containing nanometal oxide possesses improved antibacterial, LOI, and UV-absorbing efficiency. Moreover, the metal oxide nanoparticles did not leach out the fabrics by washing even after 30 laundering washing cycles

Gauge-ready formulation of the cosmological kinetic theory in generalized gravity theories

We present cosmological perturbations of kinetic components based on relativistic Boltzmann equations in the context of generalized gravity theories. Our general theory considers an arbitrary number of scalar fields generally coupled with the gravity, an arbitrary number of mutually interacting hydrodynamic fluids, and components described by the relativistic Boltzmann equations like massive/massless collisionless particles and the photon with the accompanying polarizations. We also include direct interactions among fluids and fields. The background FLRW model includes the general spatial curvature and the cosmological constant. We consider three different types of perturbations, and all the scalar-type perturbation equations are arranged in a gauge-ready form so that one can implement easily the convenient gauge conditions depending on the situation. In the numerical calculation of the Boltzmann equations we have implemented four different gauge conditions in a gauge-ready manner where two of them are new. By comparing solutions solved separately in different gauge conditions we can naturally check the numerical accuracy.Comment: 26 pages, 9 figures, revised thoroughly, to appear in Phys. Rev.