Inductive parsimony and the Methodological Argument

a b s t r a c t Studies on so-called Change Blindness and Inattentional Blindness have been taken to establish the claim that conscious perception of a stimulus requires the attentional processing of that stimulus. One might contend, against this claim, that the evidence only shows attention to be necessary for the subject to have access to the contents of conscious perception and not for conscious perception itself. This ''Methodological Argument'' is gaining ground among philosophers who work on attention and consciousness, such as Christopher Mole. I find that, without the supporting evidence of inaccessible consciousness, this argument collapses into an indefensible form of inductive parsimony. The Methodological Argument is thus shown to be unsuccessful when used against the claim that attention is required for conscious perception, though I suggest that it may be successful against the more ambitious claim that attention is necessary for all conscious experience

Biomechanical forces promote embryonic haematopoiesis

Biomechanical forces are emerging as critical regulators of embryogenesis, particularly in the developing cardiovascular system. After initiation of the heartbeat in vertebrates, cells lining the ventral aspect of the dorsal aorta, the placental vessels, and the umbilical and vitelline arteries initiate expression of the transcription factor Runx1 (refs 3-5), a master regulator of haematopoiesis, and give rise to haematopoietic cells. It remains unknown whether the biomechanical forces imposed on the vascular wall at this developmental stage act as a determinant of haematopoietic potential. Here, using mouse embryonic stem cells differentiated in vitro, we show that fluid shear stress increases the expression of Runx1 in CD41(+)c-Kit(+) haematopoietic progenitor cells, concomitantly augmenting their haematopoietic colony-forming potential. Moreover, we find that shear stress increases haematopoietic colony-forming potential and expression of haematopoietic markers in the para-aortic splanchnopleura/aorta-gonads-mesonephros of mouse embryos and that abrogation of nitric oxide, a mediator of shear-stress-induced signalling, compromises haematopoietic potential in vitro and in vivo. Collectively, these data reveal a critical role for biomechanical forces in haematopoietic development

Mid-life sleep is associated with cognitive performance later in life in aging American Indians: data from the Strong Heart Study

BackgroundSleep-related disorders have been associated with cognitive decline and neurodegeneration. American Indians are at increased risk for dementia. Here, we aim to characterize, for the first time, the associations between sleep characteristics and subsequent cognitive performance in a sample of aging American Indians.MethodsWe performed analyses on data collected in two ancillary studies from the Strong Heart Study, which occurred approximately 10 years apart with an overlapping sample of 160 American Indians (mean age at follow-up 73.1, standard deviation 5.6; 69.3% female and 80% with high school completion). Sleep measures were derived by polysomnography and self-reported questionnaires, including sleep timing and duration, sleep latency, sleep stages, indices of sleep-disordered breathing, and self-report assessments of poor sleep and daytime sleepiness. Cognitive assessment included measures of general cognition, processing speed, episodic verbal learning, short and long-delay recall, recognition, and phonemic fluency. We performed correlation analyses between sleep and cognitive measures. For correlated variables, we conducted separate linear regressions. We analyzed the degree to which cognitive impairment, defined as more than 1.5 standard deviations below the average Modified Mini Mental State Test score, is predicted by sleep characteristics. All regression analyses were adjusted for age, sex, years of education, body mass index, study site, depressive symptoms score, difference in age from baseline to follow-up, alcohol use, and presence of APOE e4 allele.ResultsWe found that objective sleep characteristics measured by polysomnography, but not subjective sleep characteristics, were associated with cognitive performance approximately 10 years later. Longer sleep latency was associated with worse phonemic fluency (β = −0.069, p = 0.019) and increased likelihood of being classified in the cognitive impairment group later in life (odds ratio 1.037, p = 0.004). Longer duration with oxygen saturation < 90% was associated with better immediate verbal memory, and higher oxygen saturation with worse total learning, short and long-delay recall, and processing speed.ConclusionIn a sample of American Indians, sleep characteristics in midlife were correlated with cognitive performance a decade later. Sleep disorders may be modifiable risk factors for cognitive impairment and dementia later in life, and suitable candidates for interventions aimed at preventing neurodegenerative disease development and progression

The incidence of stroke in Indigenous populations of countries with a Very High Human Development Index: a systematic review protocol

Background and Aims: Despite known Indigenous health and socioeconomic disadvantage in countries with a Very High Human Development Index, data on the incidence of stroke in these populations are sparse. With oversight from an Indigenous Advisory Board, we will undertake a systematic review of the incidence of stroke in Indigenous populations of developed countries or regions, with comparisons between Indigenous and non-Indigenous populations of the same region, though not between different Indigenous populations. Methods: Using PubMed, OVID-EMBASE, and Global Health databases, we will examine population-based incidence studies of stroke in Indigenous adult populations of developed countries published 1990-current, without language restriction. Non-peer-reviewed sources, studies including <10 Indigenous People, or with insufficient data to determine incidence, will be excluded. Two reviewers will independently validate the search strategies, screen titles and abstracts, and record reasons for rejection. Relevant articles will undergo full-text screening, with standard data extracted for all studies included. Quality assessment will include Sudlow and Warlow's criteria for population-based stroke incidence studies, the Newcastle-Ottawa Scale for risk of bias, and the CONSIDER checklist for Indigenous research. Results: Primary outcomes include crude, age-specific and/or age-standardized incidence of stroke. Secondary outcomes include overall stroke rates, incidence rate ratio and case-fatality. Results will be synthesized in figures and tables, describing data sources, populations, methodology, and findings. Within-population meta-analysis will be performed if, and where, methodologically sound and comparable studies allow this. Conclusion: We will undertake the first systematic review assessing disparities in stroke incidence in Indigenous populations of developed countries. Data outputs will be disseminated to relevant Indigenous stakeholders to inform public health and policy research.Anna H. Balabanski, Angela Dos Santos, John A. Woods, Amanda G. Thrift, Timothy J. Kleinig, Astrid Suchy-Dicey, Susanna Ragnhild Siri, Bernadette Boden-Albala, Rita Krishnamurthi, Valery L. Feigin, Dedra Buchwald, Annemarei Ranta, Christina S. Mienna, Carol Zavaleta, Leonid Churilov, Luke Burchill, Deborah Zion, W.T. Longstreth Jr., David L. Tirschwell, Sonia Anand, Mark W. Parsons, Alex Brown, Donald K. Warne, Matire Harwood, and Judith M. Katzenellenboge

The transcriptional landscape of age in human peripheral blood

Disease incidences increase with age, but the molecular characteristics of ageing that lead to increased disease susceptibility remain inadequately understood. Here we perform a whole-blood gene expression meta-analysis in 14,983 individuals of European ancestry (including replication) and identify 1,497 genes that are differentially expressed with chronological age. The age-associated genes do not harbor more age-associated CpG-methylation sites than other genes, but are instead enriched for the presence of potentially functional CpG-methylation sites in enhancer and insulator regions that associate with both chronological age and gene expression levels. We further used the gene expression profiles to calculate the 'transcriptomic age' of an individual, and show that differences between transcriptomic age and chronological age are associated with biological features linked to ageing, such as blood pressure, cholesterol levels, fasting glucose, and body mass index. The transcriptomic prediction model adds biological relevance and complements existing epigenetic prediction models, and can be used by others to calculate transcriptomic age in external cohorts.Peer reviewe

Renal tubular secretion in chronic kidney disease: description, determinants, and outcomes

Thesis (Ph.D.)--University of Washington, 2014Background The presence and severity of chronic kidney disease are currently assessed by glomerular filtration rate and urinary albumin excretion. Other kidney functions, such as proximal tubular secretion, are not typically quantified. Tubular secretion is capable of clearing metabolites from the blood more efficiently than filtration, suggesting important clinical consequences of secretion dysfunction. Measuring tubular secretion as an independent marker of kidney function may provide insight into kidney disease etiology and prediction of adverse outcomes. Methods We developed and validated mass spectrometry assays to measure hippurate and cinnamoylglycine, which are primarily cleared by renal tubular secretion. We estimated secretion function in a prospective cohort study of 298 CKD patients using timed urinary clearance of these molecules. We examined associations between renal secretion and estimated filtration (average of creatinine and urea clearance), related clinical characteristics, and mortality. Results Tubular secretion correlated with glomerular filtration, but considerable residual variability remained. Tubular secretion was significantly greater among men. For a given level of filtration function, diminished hippurate clearance was associated with increased risk of death (hazard ratio comparing low to high secretion groups: 2.3, 95% confidence interval: 1.1-4.7). Diminished cinnamoylglycine clearance, for a given level of filtration, was associated with increased risk of starting dialysis (hazard ratio comparing low to high secretion groups: 4.5, 95% confidence interval: 1.4-14.4). Conclusion Proximal tubular secretion function comprises a measurement of kidney function that modestly correlates with filtration function and may be associated with mortality and starting dialysis