Problems with Using Evolutionary Theory in Philosophy

Does science move toward truths? Are present scientific theories (approximately) true? Should we invoke truths to explain the success of science? Do our cognitive faculties track truths? Some philosophers say yes, while others say no, to these questions. Interestingly, both groups use the same scientific theory, viz., evolutionary theory, to defend their positions. I argue that it begs the question for the former group to do so because their positive answers imply that evolutionary theory is warranted, whereas it is self-defeating for the latter group to do so because their negative answers imply that evolutionary theory is unwarranted

Estimating Effects and Making Predictions from Genome-Wide Marker Data

In genome-wide association studies (GWAS), hundreds of thousands of genetic markers (SNPs) are tested for association with a trait or phenotype. Reported effects tend to be larger in magnitude than the true effects of these markers, the so-called ``winner's curse.'' We argue that the classical definition of unbiasedness is not useful in this context and propose to use a different definition of unbiasedness that is a property of the estimator we advocate. We suggest an integrated approach to the estimation of the SNP effects and to the prediction of trait values, treating SNP effects as random instead of fixed effects. Statistical methods traditionally used in the prediction of trait values in the genetics of livestock, which predates the availability of SNP data, can be applied to analysis of GWAS, giving better estimates of the SNP effects and predictions of phenotypic and genetic values in individuals.Comment: Published in at http://dx.doi.org/10.1214/09-STS306 the Statistical Science (http://www.imstat.org/sts/) by the Institute of Mathematical Statistics (http://www.imstat.org

Chest Physiotherapy for Mechanically Ventilated Children: A Systematic Review

The aim of this study was to appraise and summarize the effects of chest physiotherapy in mechanically ventilated children. A systematic review was completed by searching Medline, Embase, Cinahl Plus, PEDro, and Web of Science from inception to February 9, 2021. Studies investigating chest physiotherapy for mechanically ventilated children (0–18 years), in a pediatric intensive care unit were included. Chest physiotherapy was defined as any intervention performed by a qualified physiotherapist. Measurements of effectiveness and safety were included. Exclusion criteria included preterm infants, children requiring noninvasive ventilation, and those in a nonacute setting. Thirteen studies met the inclusion criteria: two randomized controlled trials, three randomized crossover trials, and eight observational studies. The Cochrane risk of bias and the Critical Appraisal Skills Program tools were used for quality assessment. Oxygen saturations decreased after physiotherapy involving manual hyperinflations (MHI) and chest wall vibrations (CWV). Although statistically significant, these results were not of clinical importance. In contrast, oxygen saturations improved after the expiratory flow increase technique; however, this was not clinically significant. An increase in expiratory tidal volume was demonstrated 30 minutes after MHI and CWV. There was no sustained change in tidal volume following a physiotherapy-led recruitment maneuver. Respiratory compliance and dead-space increased immediately after MHI and CWV. Atelectasis scores improved following intrapulmonary percussive ventilation, and MHI and CWV. Evidence to support chest physiotherapy in ventilated children remains inconclusive. There are few high-quality studies, with heterogeneity in interventions and populations. Future studies are required to investigate multiple physiotherapy interventions and the impact on long-term outcomes

Prediction of individual genetic risk to disease from genome-wide association studies

Empirical studies suggest that the effect sizes of individual causal risk alleles underlying complex genetic diseases are small, with most genotype relative risks in the range of 1.1-2.0. Although the increased risk of disease for a carrier is small for any single locus, knowledge of multiple-risk alleles throughout the genome could allow the identification of individuals that are at high risk. In this study, we investigate the number and effect size of risk loci that underlie complex disease constrained by the disease parameters of prevalence and heritability. Then we quantify the value of prediction of genetic risk to disease using a range of realistic combinations of the number, size, and distribution of risk effects that underlie complex diseases. We propose an approach to assess the genetic risk of a disease in healthy individuals, based on dense genome-wide SNP panels. We test this approach using simulation. When the number of loci contributing to the disease is >50, a large case-control study is needed to identify a set of risk loci for use in predicting the disease risk of healthy people not included in the case-control study. For diseases controlled by 1000 loci of mean relative risk of only 1.04, a case-control study with 10,000 cases and controls can lead to selection of ∼75 loci that explain >50% of the genetic variance. The 5% of people with the highest predicted risk are three to seven times more likely to suffer the disease than the population average, depending on heritability and disease prevalence. Whether an individual with known genetic risk develops the disease depends on known and unknown environmental factors

Emergence of Fermi pockets in an excitonic CDW melted novel superconductor

A superconducting (SC) state (Tc ~ 4.2K) has very recently been observed upon successful doping of the CDW ordered triangular lattice TiSe$_2$, with copper. Using high resolution photoemission spectroscopy we identify, for the first time, the momentum space locations of the doped electrons that form the Fermi sea of the parent superconductor. With doping, we find that the kinematic nesting volume increases whereas the coherence of the CDW order sharply drops. In the superconducting doping, we observe the emergence of a large density of states in the form of a narrow electron pocket near the \textit{L}-point of the Brillouin Zone with \textit{d}-like character. The \textit{k}-space electron distributions highlight the unconventional interplay of CDW to SC cross-over achieved through non-magnetic copper doping.Comment: 4+ pages, 5 figures; Accepted for publication in Phys. Rev. Lett. (2007

Bi2Te1.6S1.4 - a Topological Insulator in the Tetradymite Family

We describe the crystal growth, crystal structure, and basic electrical properties of Bi2Te1.6S1.4, which incorporates both S and Te in its Tetradymite quintuple layers in the motif -[Te0.8S0.2]-Bi-S-Bi-[Te0.8S0.2]-. This material differs from other Tetradymites studied as topological insulators due to the increased ionic character that arises from its significant S content. Bi2Te1.6S1.4 forms high quality crystals from the melt and is the S-rich limit of the ternary Bi-Te-S {\gamma}-Tetradymite phase at the melting point. The native material is n-type with a low resistivity; Sb substitution, with adjustment of the Te to S ratio, results in a crossover to p-type and resistive behavior at low temperatures. Angle resolved photoemission study shows that topological surface states are present, with the Dirac point more exposed than it is in Bi2Te3 and similar to that seen in Bi2Te2Se. Single crystal structure determination indicates that the S in the outer chalcogen layers is closer to the Bi than the Te, and therefore that the layers supporting the surface states are corrugated on the atomic scale.Comment: To be published in Physical Review B Rapid Communications 16 douuble spaced pages. 4 figures 1 tabl

Complete d-Band Dispersion and the Mobile Fermion Scale in NaxCoO2

We utilize fine-tuned polarization selection coupled with excitation-energy variation of photoelectron signal to image the \textit{complete d}-band dispersion relation in sodium cobaltates. A hybridization gap anticrossing is observed along the Brillouin zone corner and the full quasiparticle band is found to emerge as a many-body entity lacking a pure orbital polarization. At low dopings, the quasiparticle bandwidth (Fermion scale, many-body \textit{E$_F$} $\sim$ 0.25 eV) is found to be smaller than most known oxide metals. The low-lying density of states is found to be in agreement with bulk-sensitive thermodynamic measurements for nonmagnetic dopings where the 2D Luttinger theorem is also observed to be satisfied.Comment: 4+ pages, 5 Fig

Low-lying quasiparticle states and hidden collective charge instabilities in parent cobaltate superconductors (NaxCoO2)

We report a state-of-the-art photoemission (ARPES) study of high quality single crystals of the NaxCoO2 series focusing on the fine details of the low-energy states. The Fermi velocity is found to be small (< 0.5 eV.A) and only weakly anisotropic over the Fermi surface at all dopings setting the size of the pair wavefunction to be on the order of 10-20 nanometers. In the low doping regime the exchange inter-layer splitting vanishes and two dimensional collective instabilities such as 120-type fluctuations become kinematically allowed. Our results suggest that the unusually small Fermi velocity and the unique symmetry of kinematic instabilities distinguish cobaltates from other unconventional oxide superconductors such as the cuprates or the ruthenates.Comment: Accepted for publication in Phys. Rev. Lett. (2006

The epigenetic clock is correlated with physical and cognitive fitness in the Lothian Birth Cohort 1936

Background: The DNA methylation-based 'epigenetic clock' correlates strongly with chronological age, but it is currently unclear what drives individual differences. We examine cross-sectional and longitudinal associations between the epigenetic clock and four mortality-linked markers of physical and mental fitness: lung function, walking speed, grip strength and cognitive ability. Methods: DNA methylation-based age acceleration (residuals of the epigenetic clock estimate regressed on chronological age) were estimated in the Lothian Birth Cohort 1936 at ages 70 (n=920), 73 (n=299) and 76 (n=273) years. General cognitive ability, walking speed, lung function and grip strength were measured concurrently. Cross-sectional correlations between age acceleration and the fitness variables were calculated. Longitudinal change in the epigenetic clock estimates and the fitness variables were assessed via linear mixed models and latent growth curves. Epigenetic age acceleration at age 70 was used as a predictor of longitudinal change in fitness. Epigenome-wide association studies (EWASs) were conducted on the four fitness measures. Results: Cross-sectional correlations were significant between greater age acceleration and poorer performance on the lung function, cognition and grip strength measures (r range: -0.07 to -0.05, P range: 9.7 x 10 to 0.024). All of the fitness variables declined over time but age acceleration did not correlate with subsequent change over 6 years. There were no EWAS hits for the fitness traits. Conclusions: Markers of physical and mental fitness are associated with the epigenetic clock (lower abilities associated with age acceleration). However, age acceleration does not associate with decline in these measures, at least over a relatively short follow-up