The Relationship between Cerebrovascular Reactivity and Cerebral Oxygenation during Hemodialysis

Significance Statement Patients with ESKD have a high burden of ischemic brain lesions related to decline in cerebral blood flow during hemodialysis. Preliminary studies in patients on hemodialysis noted impairment in cerebrovascular reactivity, a mechanism that regulates cerebral perfusion. We found that lower cerebrovascular reactivity was associated with greater decrease in cerebral oxygen saturation during hemodialysis, particularly when accounting for changes in systemic BP. These results suggest that testing cerebrovascular reactivity could be relevant to characterizing risk of cerebral ischemia during hemodialysis and the potential sequelae of brain injury and cognitive impairment over time. Background Patients with kidney failure treated with hemodialysis (HD) may be at risk for cerebral hypoperfusion due to HD-induced BP decline in the setting of impaired cerebral autoregulation. Cerebrovascular reactivity (CVR), the cerebrovascular response to vasoactive stimuli, may be a useful indicator of cerebral autoregulation in the HD population and identify those at risk for cerebral hypoperfusion. We hypothesize that CVR combined with intradialytic BP changes will be associated with declines in cerebral oxygenation saturation (ScO2) during HD. Methods Participants completed the MRI scans on a non-HD day and cerebral oximetry during HD. We measured CVR with resting-state fMRI (rs-fMRI) without a gas challenge and ScO2 saturation with near-infrared spectroscopy. Regression analysis was used to examine the relationship between intradialytic cerebral oxygen desaturation, intradialytic BP, and CVR in different gray matter regions. Results Twenty-six patients on HD had complete data for analysis. Sixteen patients were men, 18 had diabetes, and 20 had hypertension. Mean±SD age was 65.3±7.2 years, and mean±SD duration on HD was 11.5±9.4 months. CVR in the anterior cingulate gyrus (ACG; P=0.03, r2=0.19) and insular cortex (IC; P=0.03, r2=0.19) regions negatively correlated with decline in intradialytic ScO2. Model prediction of intradialytic ScO2 improved when including intradialytic BP change and ultrafiltration rate to the ACG rsCVR (Pr2=0.48) and IC rsCVR (P=0.02, r2=0.35) models, respectively. Conclusions We found significant relationships between regional rsCVR measured in the brain and decline in intradialytic ScO2. Our results warrant further exploration of using CVR in determining a patient’s risk of cerebral ischemic injury during HD

Changes in Cerebral Volume and White Matter Integrity in Adults on Hemodialysis and Relationship to Cognitive Function

Introduction: Patients on hemodialysis (HD) have a significant burden of cognitive impairment. Characterizing the cerebral structural changes in HD patients compared to healthy controls and evaluating the relationship of cerebral structural integrity with cognitive performance in HD patients can help clarify the pathophysiology of the cognitive impairment in HD patients. Methods: In this cross-sectional study, in-center HD patients ≥50 years of age underwent brain structural and diffusion MRIs and cognitive assessment using the NIH Toolbox cognition battery. The cerebral imaging measures of the HD participants were compared to imaging from age-matched controls. Gray matter volume, white matter volume, and white matter integrity determined by diffusion tensor imaging parameters (including fractional anisotropy [FA]) were measured in both cohorts to determine differences in the cerebral structure between HD participants and healthy controls. The association between cognitive performance on the NIH Toolbox cognition battery and cerebral structural integrity was evaluated using multiple linear regression models. Results: We compared imaging measures form 23 HD participants and 15 age-matched controls. The HD participants had decreased gray matter volumes (526.8 vs. 589.5 cm3, p \u3c 0.01) and worsened white matter integrity overall (FA values of 0.2864 vs. 0.3441, p \u3c 0.01) within major white matter tracts compared to healthy controls. Decreases in white matter integrity in the left superior longitudinal fasciculus was associated with lower executive function scores (r2 = 0.24, p = 0.02) and inferior longitudinal fasciculus with lower memory scores (r = 0.25 and p = 0.03 for left and r2 = 0.21 and p = 0.03 for right). Conclusions: HD patients have a pattern of decreased white matter integrity and gray matter atrophy compared to controls. Decreases in white matter integrity were associated with decreased cognitive performance in the HD population

The acheulean handaxe : More like a bird's song than a beatles' tune?

© 2016 Wiley Periodicals, Inc. KV is supported by the Netherlands Organization for Scientific Research. MC is supported by the Canada Research Chairs Program, the Social Sciences and Humanities Research of Canada, the Canada Foundation for Innovation, the British Columbia Knowledge Development Fund, and Simon Fraser UniversityPeer reviewedPublisher PD

Using Grizzly Bears to Assess Harvest-Ecosystem Tradeoffs in Salmon Fisheries

Using grizzly bears as surrogates for “salmon ecosystem” function, the authors develop a generalizable ecosystem-based management framework that enables decision-makers to quantify ecosystem-harvest tradeoffs between wild and human recipients of natural resources like fish

Lithic technological responses to Late Pleistocene glacial cycling at Pinnacle Point Site 5-6, South Africa

There are multiple hypotheses for human responses to glacial cycling in the Late Pleistocene, including changes in population size, interconnectedness, and mobility. Lithic technological analysis informs us of human responses to environmental change because lithic assemblage characteristics are a reflection of raw material transport, reduction, and discard behaviors that depend on hunter-gatherer social and economic decisions. Pinnacle Point Site 5-6 (PP5-6), Western Cape, South Africa is an ideal locality for examining the influence of glacial cycling on early modern human behaviors because it preserves a long sequence spanning marine isotope stages (MIS) 5, 4, and 3 and is associated with robust records of paleoenvironmental change. The analysis presented here addresses the question, what, if any, lithic assemblage traits at PP5-6 represent changing behavioral responses to the MIS 5-4-3 interglacial-glacial cycle? It statistically evaluates changes in 93 traits with no a priori assumptions about which traits may significantly associate with MIS. In contrast to other studies that claim that there is little relationship between broad-scale patterns of climate change and lithic technology, we identified the following characteristics that are associated with MIS 4: increased use of quartz, increased evidence for outcrop sources of quartzite and silcrete, increased evidence for earlier stages of reduction in silcrete, evidence for increased flaking efficiency in all raw material types, and changes in tool types and function for silcrete. Based on these results, we suggest that foragers responded to MIS 4 glacial environmental conditions at PP5-6 with increased population or group sizes, 'place provisioning', longer and/or more intense site occupations, and decreased residential mobility. Several other traits, including silcrete frequency, do not exhibit an association with MIS. Backed pieces, once they appear in the PP5-6 record during MIS 4, persist through MIS 3. Changing paleoenvironments explain some, but not all temporal technological variability at PP5-6.Social Science and Humanities Research Council of Canada; NORAM; American-Scandinavian Foundation; Fundacao para a Ciencia e Tecnologia [SFRH/BPD/73598/2010]; IGERT [DGE 0801634]; Hyde Family Foundations; Institute of Human Origins; National Science Foundation [BCS-9912465, BCS-0130713, BCS-0524087, BCS-1138073]; John Templeton Foundation to the Institute of Human Origins at Arizona State Universit

Loss of ATF2 Function Leads to Cranial Motoneuron Degeneration during Embryonic Mouse Development

The AP-1 family transcription factor ATF2 is essential for development and tissue maintenance in mammals. In particular, ATF2 is highly expressed and activated in the brain and previous studies using mouse knockouts have confirmed its requirement in the cerebellum as well as in vestibular sense organs. Here we present the analysis of the requirement for ATF2 in CNS development in mouse embryos, specifically in the brainstem. We discovered that neuron-specific inactivation of ATF2 leads to significant loss of motoneurons of the hypoglossal, abducens and facial nuclei. While the generation of ATF2 mutant motoneurons appears normal during early development, they undergo caspase-dependent and independent cell death during later embryonic and foetal stages. The loss of these motoneurons correlates with increased levels of stress activated MAP kinases, JNK and p38, as well as aberrant accumulation of phosphorylated neurofilament proteins, NF-H and NF-M, known substrates for these kinases. This, together with other neuropathological phenotypes, including aberrant vacuolisation and lipid accumulation, indicates that deficiency in ATF2 leads to neurodegeneration of subsets of somatic and visceral motoneurons of the brainstem. It also confirms that ATF2 has a critical role in limiting the activities of stress kinases JNK and p38 which are potent inducers of cell death in the CNS

The Neural Basis of Following Advice

Learning by following explicit advice is fundamental for human cultural evolution, yet the neurobiology of adaptive social learning is largely unknown. Here, we used simulations to analyze the adaptive value of social learning mechanisms, computational modeling of behavioral data to describe cognitive mechanisms involved in social learning, and model-based functional magnetic resonance imaging (fMRI) to identify the neurobiological basis of following advice. One-time advice received before learning had a sustained influence on people's learning processes. This was best explained by social learning mechanisms implementing a more positive evaluation of the outcomes from recommended options. Computer simulations showed that this “outcome-bonus” accumulates more rewards than an alternative mechanism implementing higher initial reward expectation for recommended options. fMRI results revealed a neural outcome-bonus signal in the septal area and the left caudate. This neural signal coded rewards in the absence of advice, and crucially, it signaled greater positive rewards for positive and negative feedback after recommended rather than after non-recommended choices. Hence, our results indicate that following advice is intrinsically rewarding. A positive correlation between the model's outcome-bonus parameter and amygdala activity after positive feedback directly relates the computational model to brain activity. These results advance the understanding of social learning by providing a neurobiological account for adaptive learning from advice

Collective consciousness and its pathologies: Understanding the failure of AIDS control and treatment in the United States

We address themes of distributed cognition by extending recent formal developments in the theory of individual consciousness. While single minds appear biologically limited to one dynamic structure of linked cognitive submodules instantiating consciousness, organizations, by contrast, can support several, sometimes many, such constructs simultaneously, although these usually operate relatively slowly. System behavior remains, however, constrained not only by culture, but by a developmental path dependence generated by organizational history, in the context of market selection pressures. Such highly parallel multitasking – essentially an institutional collective consciousness – while capable of reducing inattentional blindness and the consequences of failures within individual workspaces, does not eliminate them, and introduces new characteristic malfunctions involving the distortion of information sent between workspaces and the possibility of pathological resilience – dysfunctional institutional lock-in. Consequently, organizations remain subject to canonical and idiosyncratic failures analogous to, but more complicated than, those afflicting individuals. Remediation is made difficult by the manner in which pathological externalities can write images of themselves onto both institutional function and corrective intervention. The perspective is applied to the failure of AIDS control and treatment in the United States

A basic theory of inheritance: How bad practice prevails

This paper develops an inheritance theory explaining the diffusion and persistence of detrimental management practice. Received wisdom, in both management theory and practice, would suggest that a practice that lowers the life expectancy of adopting firms, over time, will vanish because it puts those firms at a competitive disadvantage. In this paper, I challenge this view. I develop a conceptual model that details how a practice that lowers the survival chances of adopting organizations may still spread and continue to exist across a population of firms. I propose that a combination of three basic conditions is sufficient to bring about this phenomenon: if the practice is somehow associated with success, if there exists causal ambiguity, and if the rate of its diffusion is high compared with the rate at which it accelerates firms’ demise, the practice may continue to thrive and become a widespread and persistent feature in an industry. A pivotal conceptual insight is that the endurance of particular management practices and strategies is not merely a corollary of the competitiveness of the organizations that use them but that they have fitness levels of their own