The wrong equations: a reply to Gildenhuys

Glymour (2006) claims that classical population genetic models can reliably predict short and medium run population dynamics only given information about future fitnesses those models cannot themselves predict, and that in consequence the causal, ecological models which can predict future fitnesses afford a more foundational description of natural selection than do population genetic models. This paper defends the first claim from objections offered by Gildenhuys (2011)

Reason, Values and Evidence: Rational Dissent from Scientific Authority

We argue that value-based dissent from scientific consensus need not be irrational, as is often supposed. Instead it may commonly be a rational response to information which, if accepted, induces a conflict in core values. We briefly survey normative theories of rationality, drawing specific attention to the role values play in those theories. We then characterize the conditions under which it is rational simply to reject the contextual facts generating conflict among values. We close with some observations about the values to which science communicators may effectively appeal without relinquishing scientific authority

Economic inequalities in the effectiveness of a primary care intervention for depression and suicidal ideation.

BACKGROUND: Economic disadvantage is associated with depression and suicide. We sought to determine whether economic disadvantage reduces the effectiveness of depression treatments received in primary care. METHODS: We conducted differential-effects analyses of the Prevention of Suicide in Primary Care Elderly: Collaborative Trial, a primary-care-based randomized, controlled trial for late-life depression and suicidal ideation conducted between 1999 and 2001, which included 514 patients with major depression or clinically significant minor depression. RESULTS: The intervention effect, defined as change in depressive symptoms from baseline, was stronger among persons reporting financial strain at baseline (differential effect size = -4.5 Hamilton Depression Rating Scale points across the study period [95% confidence interval = -8.6 to -0.3]). We found similar evidence for effect modification by neighborhood poverty, although the intervention effect weakened after the initial 4 months of the trial for participants residing in poor neighborhoods. There was no evidence of substantial differences in the effectiveness of the intervention on suicidal ideation and depression remission by economic disadvantage. CONCLUSIONS: Economic conditions moderated the effectiveness of primary-care-based treatment for late-life depression. Financially strained individuals benefited more from the intervention; we speculate this was because of the enhanced treatment management protocol, which led to a greater improvement in the care received by these persons. People living in poor neighborhoods experienced only temporary benefit from the intervention. Thus, multiple aspects of economic disadvantage affect depression treatment outcomes; additional work is needed to understand the underlying mechanisms

“Liquid Biopsy” of White Matter Hyperintensity in Functionally Normal Elders

Background and Objective: In the aging brain, increased blood-brain barrier (BBB) leakage and white matter hyperintensity (WMH) on MRI are frequently presumed secondary to cerebral small vessel disease (cSVD) or endotheliopathy. We investigate this association in vivo by quantifying protein cargo from endothelial-derived exosomes (EDE), and comparing levels between two groups of functionally normal elders with and without WMH. In addition, we study associations of EDE proteins with upstream and downstream factors, such as inflammation and neurodegenerative changes, respectively.Methods: Twenty six neurologically normal older adults completed general health questionnaires, neuropsychological and physical examinations, and brain MRI. WMH was visually graded with modified Fazekas score of 2 or greater used to classify 11 subjects as cases, and 15 without WMH as controls. Plasma total exosomes were precipitated and EDEs enriched by sequential immuno-precipitations. In addition, we quantified three inflammatory cytokines from plasma and imaging variables on MRI. Group means were compared, the discriminant functions of biomarkers calculated, and the association of EDE biomarkers with plasma inflammatory markers, cognition, and imaging outcomes assessed via regression modeling.Results: Plasma levels of EDE cargo proteins GLUT1, LAT1, P-GP, and NOSTRIN were significantly higher in subjects with WMH in comparison to those without. In contrast, EDE levels of the marker with low expression in brain (VCAM1) were equal between groups. The effect sizes for each of the brain-expressed cargo proteins (GLUT1, LAT1, and P-GP) were such that age-adjusted logistic regressions revealed areas under the curve (AUC) with range of 0.82–0.89, differentiating subjects with WMH from those without. VCAM1 poorly discriminated between groups (AUC:0.55). Higher levels of all brain-expressed EDE proteins were also associated with lower cognitive function, unrelated to burden of WMH. Levels of LAT1 and P-GP were significantly inversely associated with global gray matter volumes, and EDE GLUT1, LAT-1, and P-GP concentrations were significantly associated with systemic IL-6 levels.Conclusion: In a case control study of clinically normal adults with and without WMH, concentrations of EDE proteins were significantly higher in subjects with WMH in comparison to controls. This work is a first step toward in vivo dissection of molecular changes in endothelia of functionally normal subjects with radiographic evidence of age-associated white matter disease

On The Metaphysics of Probabilistic Causation: Lessons from Social Epidemiology

I argue that the orthodox account of probabilistic causation, on which probabilistic causes determine the probability of their effects, is inconsistent with certain ontological assumptions implicit in scientific practice. In particular, scientists recognize the possibility that properties of populations can cause the behavior of members of the populations. Such emergent population level causation is metaphysically impossible on the orthodoxy

Stable Models and Causal Explanation in Evolutionary Biology

Abstract: Models that fail to satisfy the Markov condition are unstable in the sense that changes in state variable values may cause changes in the values of background variables, and these changes in background lead to predictive error. This sort of error arises exactly from the failure of non-Markovian models to track the set of causal relations upon which the values of response variables depend. The result has implications for discussions of the level of selection: under certain plausible conditions the models of selection presented in such debates will not satisfy the Markov condition when fit to data from real populations. Since this is true both for group and individual level models, models of neither sort correctly represent the causal structure generating, nor correctly explain, the phenomena of interest

Reason, Values and Evidence: Rational Dissent from Scientific Authority

We argue that value-based dissent from scientific consensus need not be irrational, as is often supposed. Instead it may commonly be a rational response to information which, if accepted, induces a conflict in core values. We briefly survey normative theories of rationality, drawing specific attention to the role values play in those theories. We then characterize the conditions under which it is rational simply to reject the contextual facts generating conflict among values. We close with some observations about the values to which science communicators may effectively appeal without relinquishing scientific authority.</p