Granger causality methods were developed to analyze the flow of information between time series. These methods have become more widely applied in neuroscience. Frequency-domain causality measures, ...such as those of Geweke, as well as multivariate methods, have particular appeal in neuroscience due to the prevalence of oscillatory phenomena and highly multivariate experimental recordings. Despite its widespread application in many fields, there are ongoing concerns regarding the applicability of Granger causality methods in neuroscience. When are these methods appropriate? How reliably do they recover the system structure underlying the observed data? What do frequency-domain causality measures tell us about the functional properties of oscillatory neural systems? In this paper, we analyze fundamental properties of Granger–Geweke (GG) causality, both computational and conceptual. Specifically, we show that (i) GG causality estimates can be either severely biased or of high variance, both leading to spurious results; (ii) even if estimated correctly, GG causality estimates alone are not interpretable without examining the component behaviors of the system model; and (iii) GG causality ignores critical components of a system’s dynamics. Based on this analysis, we find that the notion of causality quantified is incompatible with the objectives of many neuroscience investigations, leading to highly counterintuitive and potentially misleading results. Through the analysis of these problems, we provide important conceptual clarification of GG causality, with implications for other related causality approaches and for the role of causality analyses in neuroscience as a whole.
Inexpensive “base” metals are more affordable and sustainable than precious metals and also offer opportunities to discover new mechanisms for selective catalytic reactions. Base metal complexes can ...have high-spin electronic configurations that are rare in precious metal complexes. This Account describes some concepts relevant to high-spin organometallic complexes, focusing on our recent work with β-diketiminate complexes of iron and cobalt. Even though high-spin organometallic complexes have some unfamiliar spectroscopic properties, they can be studied using NMR spectroscopy as well as techniques that focus on the magnetism brought about by the unpaired electrons. Understanding the mechanisms of reactions using these complexes can be complicated, because complexes with a high-spin electronic configuration may need to change spin states to avoid high barriers for reaction. These spin-state changes can be rapid, and the ability of an excited spin state to “cut through” the barrier for a reaction can lead to spin acceleration. These concepts, originally developed by Poli, Shaik, Schwarz, and Harvey, are applied here to the fundamental organometallic reaction of β-hydride elimination (BHE). Experimentally validated density-functional calculations show spin acceleration in BHE using three-coordinate iron(II) and cobalt(II) complexes. A square-planar transition state is particularly beneficial for accelerating BHE when a high-spin iron(II) complex goes from an S = 2 ground state to an S = 1 transition state or when a high-spin cobalt(II) complex goes from an S = 3/2 ground state to an S = 1/2 transition state. The relative energies of the spin states can be controlled with the choice of the supporting ligand. Using an appropriate ligand, isomerization of 1-alkenes to their Z-2 isomers can be catalyzed in high yields using the cobalt(II) alkyl complexes as catalysts. Though an earlier paper attributed the regioselectivity and stereoselectivity to the preferred geometry of the BHE step, the results of isotope labeling experiments suggest that the selectivity may actually come from the alkene exchange step (again with spin acceleration). In general, the use of multiple intersecting spin states is envisioned as a profitable strategy for bringing about low reaction barriers and high selectivity in catalytic reactions. This effort requires high-accuracy computational models as well as ligand design that gives nearby spin states with appropriate geometries.
Phosphatidylserine (PS) is a major component of membrane bilayers whose change in distribution between inner and outer leaflets is an important physiological signal. Normally, members of the type IV ...P-type ATPases spend metabolic energy to create an asymmetric distribution of phospholipids between the two leaflets, with PS confined to the cytoplasmic membrane leaflet. On occasion, membrane enzymes, known as scramblases, are activated to facilitate transbilayer migration of lipids, including PS. Recently, two proteins required for such randomization have been identified: TMEM16F, a scramblase regulated by elevated intracellular Ca(2+), and XKR8, a caspase-sensitive protein required for PS exposure in apoptotic cells. Once exposed at the cell surface, PS regulates biochemical reactions involved in blood coagulation, and bone mineralization, and also regulates a variety of cell-cell interactions. Exposed on the surface of apoptotic cells, PS controls their recognition and engulfment by other cells. This process is exploited by parasites to invade their host, and in specialized form is used to maintain photoreceptors in the eye and modify synaptic connections in the brain. This review discusses what is known about the mechanism of PS exposure at the surface of the plasma membrane of cells, how actors in the extracellular milieu sense surface exposed PS, and how this recognition is translated to downstream consequences of PS exposure.
The medial prefrontal cortex (mPFC) plays a major role in both sensory and affective aspects of pain. There is extensive evidence that chronic pain produces functional changes within the mPFC. ...However, our understanding of local circuit changes to defined subpopulations of mPFC neurons in chronic pain models remains unclear. A major subpopulation of mPFC neurons project to the periaqueductal gray (PAG), which is a key midbrain structure involved in endogenous pain suppression and facilitation. Here, we used laser scanning photostimulation of caged glutamate to map cortical circuits of retrogradely labeled cortico-PAG (CP) neurons in layer 5 (L5) of mPFC in brain slices prepared from male mice having undergone chronic constriction injury (CCI) of the sciatic nerve. Whole-cell recordings revealed a significant reduction in excitability for L5 CP neurons contralateral to CCI in the prelimbic (PL), but not infralimbic (IL), region of mPFC. Circuit mapping showed that excitatory inputs to L5 CP neurons in both PL and IL arose primarily from layer 2/3 (L2/3) and were significantly reduced in CCI mice. Glutamate stimulation of L2/3 and L5 elicited inhibitory inputs to CP neurons in both PL and IL, but only L2/3 input was significantly reduced in CP neurons of CCI mice. We also observed significant reduction in excitability and L2/3 inhibitory input to CP neurons ipsilateral to CCI. These results demonstrating region and laminar specific changes to mPFC-PAG neurons suggest that a unilateral CCI bilaterally alters cortical circuits upstream of the endogenous analgesic network, which may contribute to persistence of chronic pain.
Chronic pain is a significant unresolved medical problem that is refractory to traditional analgesics and can negatively affect emotional health. The role of central circuits in mediating the persistent nature of chronic pain remains unclear. Local circuits within the medial prefrontal cortex (mPFC) process ascending pain inputs and can modulate endogenous analgesia via direct projections to the periaqueductal gray (PAG). However, the mechanisms by which chronic pain alters intracortical circuitry of mPFC-PAG neurons are unknown. Here, we report specific changes to local circuits of mPFC-PAG neurons in mice displaying chronic pain behavior after nerve injury. These findings provide evidence for a neural mechanism by which chronic pain disrupts the descending analgesic system via functional changes to cortical circuits.
Several aspects of the interplay between monotone operator theory and convex optimization are presented. The crucial role played by monotone operators in the analysis and the numerical solution of ...convex minimization problems is emphasized. We review the properties of subdifferentials as maximally monotone operators and, in tandem, investigate those of proximity operators as resolvents. In particular, we study new transformations which map proximity operators to proximity operators, and establish connections with self-dual classes of firmly nonexpansive operators. In addition, new insights and developments are proposed on the algorithmic front.
Reef fish spawning aggregations, ranging from small groups to many tens of thousands of individuals, are spectacular but poorly known natural phenomena whereby fish assemble at specific times and ...locations to spawn. For some species these large groups may be the only form of reproduction, the high fish numbers briefly giving a false impression of stability and abundancean illusion of plenty. They are often a focus for intensive seasonal fishing because of their predictability and because many important commercial fishes form them. Highly vulnerable to overexploitation, many aggregations and their associated fisheries, have disappeared or are in decline. Few are effectively managed or incorporated into protected areas. Aggregations are not well understood by fishery scientists, managers and conservationists and their significance little appreciated by fishers or the wider public. To ensure their persistence to replenish important fisheries in coral ecosystems, maintain their ecosystem function and continue to delight divers, a significant change in perspective is needed to foster protection and management. This book provides comprehensive and practical coverage of the biology, study and management of reef fish aggregations, exploring their how, when, where, and why. It explores ways to better protect, study, manage and conserve them, while identifying key data gaps and questions. The text is extensively illustrated with many unique, never before published, photographs and graphics. Case studies on over 20 interesting and important fishes are included, outlining their biology and fisheries and highlighting major concerns and challenges.
Abstract Weather and climate play important roles in determining patterns of air quality over multiple scales in time and space, owing to the fact that emissions, transport, dilution, chemical ...transformation, and eventual deposition of air pollutants all can be influenced by meteorologic variables such as temperature, humidity, wind speed and direction, and mixing height. There is growing recognition that development of optimal control strategies for key pollutants like ozone and fine particles now requires assessment of potential future climate conditions and their influence on the attainment of air quality objectives. In addition, other air contaminants of relevance to human health, including smoke from wildfires and airborne pollens and molds, may be influenced by climate change. In this study, the focus is on the ways in which health-relevant measures of air quality, including ozone, particulate matter, and aeroallergens, may be affected by climate variability and change. The small but growing literature focusing on climate impacts on air quality, how these influences may play out in future decades, and the implications for human health is reviewed. Based on the observed and anticipated impacts, adaptation strategies and research needs are discussed.
Purpose of Review
I review literature on the impacts of climate change on air quality and human health, with a focus on articles published from 2013 on ozone and airborne particles. Selected previous ...literature is discussed where relevant in tracing the origins of our current knowledge.
Recent Findings
Climate and weather have strong influences on the spatial and temporal distribution of air pollution concentrations. Emissions of ozone and PM
2.5
precursors increase at higher ambient temperatures. The reactions that form ozone occur faster with greater sunlight and higher temperatures. Weather systems influence the movement and dispersion of air pollutants in the atmosphere through the action of winds, vertical mixing, and precipitation, all of which are likely to alter in a changing climate. Recent studies indicate that, holding anthropogenic air pollution emissions constant, ozone concentrations in populated regions will tend to increase in future climate scenarios. For the USA, the climate impact on ozone is most consistently seen in north-central and north-eastern states, with the potential for many thousands of additional ozone-related deaths. The sensitivity of anthropogenic PM
2.5
to climate is more variable across studies and regions, owing to the varied nature of PM constituents, as well as to less complete characterization of PM reaction chemistry in available atmospheric models. However, PM emitted by wildland fires is likely to become an increasing health risk in many parts of the world as climate continues to change.
Summary
The complex interactions between climate change and air quality imply that future policies to mitigate these twin challenges will benefit from greater coordination. Assessing the health implications of alternative policy approaches towards climate and pollution mitigation will be a critical area of future work.
We propose new primal-dual decomposition algorithms for solving systems of inclusions involving sums of linearly composed maximally monotone operators. The principal innovation in these algorithms is ...that they are block-iterative in the sense that, at each iteration, only a subset of the monotone operators needs to be processed, as opposed to all operators as in established methods. Flexible strategies are used to select the blocks of operators activated at each iteration. In addition, we allow lags in operator processing, permitting asynchronous implementation. The decomposition phase of each iteration of our methods is to generate points in the graphs of the selected monotone operators, in order to construct a half-space containing the Kuhn–Tucker set associated with the system. The coordination phase of each iteration involves a projection onto this half-space. We present two related methods: the first method provides weakly convergent primal and dual sequences under general conditions, while the second is a variant in which strong convergence is guaranteed without additional assumptions. Neither algorithm requires prior knowledge of bounds on the linear operators involved or the inversion of linear operators. Our algorithmic framework unifies and significantly extends the approaches taken in earlier work on primal-dual projective splitting methods.
Background Content validity is the most important measurement property of a patient-reported outcome measure (PROM) and the most challenging to assess. Our aims were to: (1) develop standards for ...evaluating the quality of PROM development; (2) update the original COSMIN standards for assessing the quality of content validity studies of PROMs; (3) develop criteria for what constitutes good content validity of PROMs, and (4) develop a rating system for summarizing the evidence on a PROM's content validity and grading the quality of the evidence in systematic reviews of PROMs. Methods An online 4-round Delphi study was performed among 159 experts from 21 countries. Panelists rated the degree to which they (dis)agreed to proposed standards, criteria, and rating issues on 5-point rating scales ('strongly disagree' to 'strongly agree'), and provided arguments for their ratings. Results Discussion focused on sample size requirements, recording and field notes, transcribing cognitive interviews, and data coding. After four rounds, the required 67% consensus was reached on all standards, criteria, and rating issues. After pilot-testing, the steering committee made some final changes. Ten criteria for good content validity were defined regarding item relevance, appropriateness of response options and recall period, comprehensiveness, and comprehensibility of the PROM. Discussion The consensus-based COSMIN methodology for content validity is more detailed, standardized, and transparent than earlier published guidelines, including the previous COSMIN standards. This methodology can contribute to the selection and use of high-quality PROMs in research and clinical practice.
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