Need for discriminating between diagnostic and screening efficacy to estimate a biomarker based on case control and cohort studies

This study proposes the comprehensive index of biomarker (CIB), based on the consistency of a biomarker in case control (Youden index, J) and cohort studies (Crc), to evaluate biomarker efficacy. CIB was calculated as the mean of J and Crc. Analysis of the effect of sensitivity and specificity on CIB and ROC analysis of CIB were performed in simulated and actual datasets. J and CIB had similar values for high-probability events (say probability was 0.50), but there was a significant difference between J and CIB for low-probability events (say probability was 0.05). Therefore, as the subjects considered for diagnosis are usually symptomatic, the occurrence of a disease can be assumed to be a high-probability event. In contrast, as the subjects considered in screening for a disease are usually healthy and asymptomatic, the occurrence of a disease is assumed to be a low-probability event. Although J is the common index used to evaluate the diagnostic effectiveness, unfortunately, the J value is significantly larger than CIB value in a low-probability event, showing overestimation for screening purpose. CIB could have more potential than J for determining the screening efficacy of a biomarker. The efficacy of a biomarker could differ for diagnostic, screening, predictive, and prognostic purposes, and it would be better to evaluate the efficacy of biomarkers for specific systems or contexts.

Low frequency variants associated with leukocyte telomere length in the Singapore Chinese population

The role of low frequency variants associated with telomere length homeostasis in chronic diseases and mortalities is relatively understudied in the East-Asian population. Here we evaluated low frequency variants, including 1,915,154 Asian specific variants, for leukocyte telomere length (LTL) associations among 25,533 Singapore Chinese samples. Three East Asian specific variants in/near POT1, TERF1 and STN1 genes are associated with LTL (Meta-analysis P 2.49×10−14–6.94×10−10). Rs79314063, a missense variant (p.Asp410His) at POT1, shows effect 5.3 fold higher and independent of a previous common index SNP. TERF1 (rs79617270) and STN1 (rs139620151) are linked to LTL-associated common index SNPs at these loci. Rs79617270 is associated with cancer mortality [HR95%CI = 1.544 (1.173, 2.032), PAdj = 0.018] and 4.76% of the association between the rs79617270 and colon cancer is mediated through LTL. Overall, genetically determined LTL is particularly associated with lung adenocarcinoma [HR95%CI = 1.123 (1.051, 1.201), Padj = 0.007]. Ethnicity-specific low frequency variants may affect LTL homeostasis and associate with certain cancers.

Evaluation of Bone Age in Children: A Mini-Review

Bone age represents a common index utilized in pediatric radiology and endocrinology departments worldwide for the definition of skeletal maturity for medical and non-medical purpose. It is defined by the age expressed in years that corresponds to the level of maturation of bones. Although several bones have been studied to better define bone age, the hand and wrist X-rays are the most used images. In fact, the images obtained by hand and wrist X-ray reflect the maturity of different types of bones of the skeletal segment evaluated. This information, associated to the characterization of the shape and changes of bone components configuration, represent an important factor of the biological maturation process of a subject. Bone age may be affected by several factors, including gender, nutrition, as well as metabolic, genetic, and social factors and either acute and chronic pathologies especially hormone alteration. As well several differences can be characterized according to the numerous standardized methods developed over the past decades. Therefore, the complete characterization of the main methods and procedure available and particularly of all their advantages and disadvantages need to be known in order to properly utilized this information for all its medical and non-medical main fields of application.

A symmetric property in the enhanced common index jump theorem with applications to the closed geodesic problem

<p style='text-indent:20px;'>In this paper, we prove a symmetric property for the indices for symplectic paths in the enhanced common index jump theorem (cf. Theorem 3.5 in [<xref ref-type="bibr" rid="b6">6</xref>]). As an application of this property, we prove that on every compact Finsler manifold <inline-formula><tex-math id="M1">\begin{document}$ (M, \, F) $\end{document}</tex-math></inline-formula> with reversibility <inline-formula><tex-math id="M2">\begin{document}$ \lambda $\end{document}</tex-math></inline-formula> and flag curvature <inline-formula><tex-math id="M3">\begin{document}$ K $\end{document}</tex-math></inline-formula> satisfying <inline-formula><tex-math id="M4">\begin{document}$ \left(\frac{\lambda}{\lambda+1}\right)^2&lt;K\le 1 $\end{document}</tex-math></inline-formula>, there exist two elliptic closed geodesics whose linearized Poincaré map has an eigenvalue of the form <inline-formula><tex-math id="M5">\begin{document}$ e^{\sqrt {-1}\theta} $\end{document}</tex-math></inline-formula> with <inline-formula><tex-math id="M6">\begin{document}$ \frac{\theta}{\pi}\notin{\bf Q} $\end{document}</tex-math></inline-formula> provided the number of closed geodesics on <inline-formula><tex-math id="M7">\begin{document}$ M $\end{document}</tex-math></inline-formula> is finite.</p>

Muscle wasting diseases has two distinct trajectories on the 3-dimensional age-BMI-peak VO2 scatterplot

Background: Frailty and sarcopenia are age-related morbid states, and a low body mass index (BMI) is a characteristic of frailty and cachexia. However, no common index for assessing these three muscle wasting states is available, making it difficult to understand the relationship among them. Peak oxygen uptake (peak VO2), an index of life expectancy, may be a useful common index. Therefore, this study aimed to investigate the relationship among sarcopenia, frailty, and cachexia using age, BMI, and peak VO2. Methods: Participants were 175 Japanese community dwelling older adults (58 men, 117 women; 77.6 years). We assessed biochemical, physiological, and physical factors, and symptoms associated with frailty, and cachexia. Peak VO2 was assessed with a cardiopulmonary exercise test. Participants were classified into five groups: robust, pre-frail, frail, sarcopenia, and cachexia. We compared the groups by age, BMI, and peakVO2 with average values and 95% confidence intervals (CIs).Results: 17% (n=30) of participants were classified as robust, 40% (n=70) as pre-frail, 12% (n=21) as sarcopenia, 25% (n=44) as frail, and 6% (n=10) as cachexia. Significant differences were found in age (robust vs. frail, pre-frail vs. frail), BMI (robust vs. cachexia, pre-frail vs. cachexia, frail vs. cachexia), and peak VO2 (robust vs. frail, robust vs. cachexia, pre-frail vs. cachexia) with average values and 95% CIs. Three dimensions among age, BMI and peak VO2 revealed two trajectories (from robust to frailty via pre-frailty, and from robust to cachexia via sarcopenia) among muscle wasting diseases.Conclusions: This study revealed two trajectories among muscle wasting diseases.

Assessment and Forecast of Socio-Demographic Threats to Global Security

The article studies and analyzes typical regularities of correlation between quantitative characteristics of social systems (indicators) and correlation between the structure and dynamics of threats on the basis of expert estimation in points. It identifies and grounds the necessity of using the obtained forecast of socio-demographic threats in order to develop and pursue new global demographic policy. A long-term scientifically grounded strategy is necessary to meet efficiently new serious challenges to global security that jeopardize civilization on the Earth. But this strategy has not been developed yet. In order to manage living processes or social systems it is needed to have their quantitative characteristics (indicators). For physical and economic processes and systems the system of gauges in the form of natural or value indexes can be used. In this case methods of expert assessment will allow us to reduce non-comparable indexes to their common index showing them in points. Such methods of quantitative assessment are used widely in public science. To assess threats to global security the authors propose to use strategic matrix in two modifications: for quantitative measuring the level of threat dynamic to global security by 6 elements of civilization genotype (genotype of civilization) and more detail matrix for each of 6 elements and estimation of their concrete indexes. Its novelty is the use of information for 60 years, including those of forecast by the optimistic scenario. The basis of matrix is formed by estimation of the system of socio-demographic element in genotype. The use of multi-factor matrix can provide an opportunity to range by their importance technological, informational and economic threats to global security in the 1-st half of the 21st century