Human disease biomarkers: challenges, advances, and trends in their validation

Biomarkers are important tools in the medical field, once they allow better prediction, characterization, and treatment of diseases. In this scenario, it is essential that biomarkers are highly accurate. Thus, biomarker validation is an essential part of ensuring the effectiveness of a biomarker. Validation of biomarkers is the process by which biomarkers are evaluated for accuracy and consistency, as well as their ability to inform the condition of health or disease. Although, there is no unique measure that can be used to determine the validity for all biomarkers, there are general criteria that all biomarkers must meet to be useful. In this work, we review the definition of biomarkers and discuss the validity components. We then critically discuss the main methods used to validate biomarkers and consider some examples of biomarkers of the diseases which most killer in the world (cardiovascular diseases, cancer, and viral infections), highlighting the potential biochemical pathways of these biomarkers in the biological system. In addition, we also comment on the omic strategies used in the biomarker discovery process and conclude with information about perspectives in biomarker validation through imaging techniques.

Dynamical behavior of alternate base expansions

We generalize the greedy and lazy $\beta $ -transformations for a real base $\beta $ to the setting of alternate bases ${\boldsymbol {\beta }}=(\beta _0,\ldots ,\beta _{p-1})$ , which were recently introduced by the first and second authors as a particular case of Cantor bases. As in the real base case, these new transformations, denoted $T_{{\boldsymbol {\beta }}}$ and $L_{{\boldsymbol {\beta }}}$ respectively, can be iterated in order to generate the digits of the greedy and lazy ${\boldsymbol {\beta }}$ -expansions of real numbers. The aim of this paper is to describe the measure-theoretical dynamical behaviors of $T_{{\boldsymbol {\beta }}}$ and $L_{{\boldsymbol {\beta }}}$ . We first prove the existence of a unique absolutely continuous (with respect to an extended Lebesgue measure, called the p-Lebesgue measure) $T_{{\boldsymbol {\beta }}}$ -invariant measure. We then show that this unique measure is in fact equivalent to the p-Lebesgue measure and that the corresponding dynamical system is ergodic and has entropy $({1}/{p})\log (\beta _{p-1}\cdots \beta _0)$ . We give an explicit expression of the density function of this invariant measure and compute the frequencies of letters in the greedy ${\boldsymbol {\beta }}$ -expansions. The dynamical properties of $L_{{\boldsymbol {\beta }}}$ are obtained by showing that the lazy dynamical system is isomorphic to the greedy one. We also provide an isomorphism with a suitable extension of the $\beta $ -shift. Finally, we show that the ${\boldsymbol {\beta }}$ -expansions can be seen as $(\beta _{p-1}\cdots \beta _0)$ -representations over general digit sets and we compare both frameworks.

Excursions to the cusps for geometrically finite hyperbolic orbifolds and equidistribution of closed geodesics in regular covers

We give a finitary criterion for the convergence of measures on non-elementary geometrically finite hyperbolic orbifolds to the unique measure of maximal entropy. We give an entropy criterion controlling escape of mass to the cusps of the orbifold. Using this criterion, we prove new results on the distribution of collections of closed geodesics on such an orbifold, and as a corollary, we prove the equidistribution of closed geodesics up to a certain length in amenable regular covers of geometrically finite orbifolds.

Fathers’ and mothers’ enjoyment of childcare: the role of multitasking

Using data from the latest edition of the Italian Time Use Survey (ITUS, 2013–2014), we analyse 31,309 childcare episodes to investigate the relationship betweenmultitasking (i.e., the combination of childcare with housework tasks) and parents’enjoyment of the time they spent on childcare, with a gender perspective. To this end,we rely on information from the episode enjoyment scores the respondents used toevaluate the degree of (un)pleasantness associated with the different activities theyrecorded in a daily diary. These episode enjoyment scores are a novelty in the ITUS,and provide a unique measure of the respondents’ momentary assessments of theirsubjective well-being. Our results highlight the existence of a negative relationshipbetween multitasking and parental well-being when spending time on childcare forboth mothers and fathers, regardless of the nature of the childcare activity theywere performing (i.e., routine or recreational childcare). Our findings add to priorresearch by shedding new light on the role of multitasking as a relevant contextualcharacteristic of care that affects the well-being of fathers, as well as of mothers.

Conditional Loss of Engrailed 1/2 in Rhombic Lip-Derived Neurons Increases Intrinsic Rhythmicity and Decreases Overall Variability of Eupneic Respiration

Evidence for a cerebellar role during cardiopulmonary challenges has long been established, but investigation into cerebellar involvement in eupneic breathing has been inconclusive. Given the view of the cerebellum (CRB) as a temporally coordinating structure, any investigation into the CRB during respiration must evaluate rhythm and variability of the respiratory sequence. In this study, we chose an elegant model of cerebellar neuropathology, Atoh1-En1/2 CKO, where mutant animals have conditional loss of the developmental patterning gene Engrailed 1/2 in rhombic lip-lineage neurons and exhibit a proportional scaling-down of neuron number in hypoplastic lobules of the CRB. We utilized whole-body unrestrained plethysmography to measure respiration during eupnea, and evaluated the respiratory sequence of mutant animals and their control littermates using the average rate, the coefficient of variation (CV), and a unique measure of intrinsic rhythmicity called CV2. Linear regression analyses revealed that mutant animals had decreased overall variability and increased intrinsic rhythmicity (as measured by CV and CV2, respectively) compared to their control littermates, but we found no effect of strain on average respiratory rate. Analysis also revealed modestly decreased respiratory rates, increased CV, and increased CV2 in female animals, independent of strain. These results align well with previously reported studies and add new insight into CRB involvement in eupneic respiratory rhythmicity. Although not investigated in this study, future works should consider the coordination of breathing, licking, swallowing, and whisking in order to build a more complete understanding of the relationship between the CRB and respiration.

Dynamics of Cohomological Expanding Mappings I: First and Second Main Results

Let $f:V\rightarrow V $ be a Cohomological Expanding Mapping1 of a smooth complex compact homogeneous manifold with dimC(V) = k ≥ 1 and Kodaira Dimension $\leq 0$. We study the dynamics of such mapping from a probabilistic point of view, that is, we describe the asymptotic behavior of the orbit $ O_{f} (x) = \{f^{n} (x), n \in \mathbb{N} \quad \mbox{or}\quad \mathbb{Z}\}$ of a generic point. Using pluripotential methods, we construct a natural invariant canonical probability measure of maximum Cohomological Entropy $ \mu_{f} $ such that ${\chi_{2l}^{-m}} (f^m)^\ast \Omega \to \mu_f \qquad \mbox{as} \quad m\to\infty$ for each smooth probability measure $\Omega $ on V . Then we study the main stochastic properties of $ \mu_{f}$ and show that $ \mu_{f}$ is a measure of equilibrium, smooth, ergodic, mixing, K-mixing, exponential-mixing and the unique measure with maximum Cohomological Entropy. We also conjectured that $\mu_f:=T_l^+ \wedge T_{k-l}^-$, $\dim_\H(\mu_f)= \Psi h_{\chi}(f) $ and $\dim_\H( \mbox{Supp} T_l^+) \geq 2(k-l) + \frac{\log \chi_{2l}}{\psi_l}.$

Nymphs of Ixodes ricinus Are More Sensitive to Deet Than Adult Females

ABSTRACT The use of repellents is a unique measure of personal protection, which can avoid tick attachment and thus reduce the risk of tick-borne infections. In the European Union, the efficacy of the repellents coming onto the market has to be evaluated according to the guidelines published by the European Chemical Agency before registration. The United States Environmental Protection Agency has a similar role. Despite obvious differences in morphology and behavior, both these guidelines allow the use of nymph or adult female ticks for laboratory testing. Here, we provide evidence that sensitivity to diethyltoluamide (deet) (P < 0.0001) of Ixodes ricinus nymphs within the in vitro trial was significantly higher than in adult females. In the experiment, we also observed that feral ticks were less sensitive to repellent than were laboratory-reared ticks (P < 0.01) and that mobility decreased when the trial was repeated (P < 0.05). This study showed that the results of efficacy tests could vary significantly even when the protocol was conducted in accordance with the recommended methods. To refine the results of efficacy tests, we recommend a reevaluation of the guidelines, with emphasis on the developmental stage and origin of ticks.

Beyond Greenwash

Modern consumers are confronted by a growing array of colorful eco-labels on everything from coffee to computers. Yet, not all of these eco-labels are trustworthy. Despite the existence of well-established best practices for eco-labeling, many labels remain little more than superficial exercises in “greenwash.” How can consumers separate greenwash from genuine attempts to address environmental challenges? Beyond Greenwash? systematically investigates the credibility of transnational eco-labeling in a global and cross-sectoral context. It brings original data, an innovative mixed-method research design, and a unique measure of procedural credibility in transnational governance to bear on one of the most salient questions in contemporary global environmental politics. In doing so, it reaches the important conclusion that the rigor and credibility of transnational governance depends as much on who is being governed as who is doing the governing. Beyond Greenwash? offers practical insights into the viability of eco-labeling as a form of transnational governance and makes a timely contribution to broader debates in political science and international relations about when and how emergent forms of transnational governance can succeed in achieving their stated objectives.

Geodesic Flows Modelled by Expansive Flows

Given a smooth compact surface without focal points and of higher genus, it is shown that its geodesic flow is semi-conjugate to a continuous expansive flow with a local product structure such that the semi-conjugation preserves time parametrization. It is concluded that the geodesic flow has a unique measure of maximal entropy.