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Reverse Cumulative Distribution Curves (RCDCs) have proven to be a useful tool in summarizing immune response profiles in vaccine studies since their introduction by Reed, Meade, and Steinhoff (RMS) (1995). They are able to display virtually all of the treatment data and characterize summary statistics such as means or even their confidence intervals (CIs) that might be obscure. RMS mentioned their similarity to survival curves often used to summarize time-to-event data which are usually not normally distributed. The RCDCs, while intuitively pleasing and useful, contain important properties which allow for more powerful statistical applications. In this paper, we will suggest several widely used rank-based tests to compare the curves in the context of vaccine studies. These rank-based tests allow for comparisons between treatments, for stratified analyses, weighted analyses, and other modifications that make them the alternative of parametric analyses without the normality assumptions. Clinical trial identification: NCT01712984 and NCT01230957. [ABSTRACT FROM AUTHOR]

• We established cocaine self-administered mice. • We observed microglial activation the brain striatum. • Cocaine differentially modulates microglial functional status in vivo. • NLRP3/IL1β may play critical roles in cocaine-mediated microglial activation. The evidence showing the involvement of microglial activation in the development of drug addiction remain scarce as microglia have not been systematically investigated in self-administered mice, a gold standard rodent model for drug addiction. Here we established the stable cocaine self-administration mice to examine microglial activation levels in various brain regions related to reward circuitry. Immunostaining for Iba1 showed a significant upregulation of intensity in the striatum but not in the medial prefrontal cortex (mPFc), hippocampus or thalamus. Further validation experiments showed that cocaine self-administered mice had significantly increased mRNA expression of ccl2 and IL1β in the striatum but not the mPFc compared to saline controls. Consistently, we found elevated protein levels of Iba1, CCL2, TLR4 and mature IL1β in the striatum, not in the mPFc of cocaine-receiving mice. In addition, cocaine-stimulated microglia had modified morphology including a reduced number of intersections, a shortened length and number of processes in the NAc. In summary, our results demonstrated that cocaine mediated microglial activation in a region-specific manner in vivo. These findings indicate that microglia could be activated in the early stage of cocaine addiction directly supporting the rationale that dysregulation on neuroimmune signaling is inherently involved in the development of drug addiction. [ABSTRACT FROM AUTHOR]

Background: Continuous epidural infusion (CEI) is commonly used for labour analgesia, but concerns over potential motor block, second-stage labour complications, and ineffective analgesia in late labour have prompted examining intermittent epidural bolus (IEB) as an alternative. However, evidence comparing these modalities is conflicting. The meta-analysis evaluates the analgesic efficacy of CEI vs IEB.Methods: Databases were searched for trials comparing CEI to IEB for labour analgesia. The two co-primary outcomes were risk of breakthrough pain and difference in area under the curve (AUC) for pain scores during the first 4 h post-epidural initiation. Local anaesthetic consumption, maternal outcomes (i.e. delivery mode, labour duration, and maternal satisfaction), and side-effects of epidural analgesia were also evaluated. Results were pooled using random-effects modelling. Trial sequential analysis (TSA) was used to evaluate evidence reliability.Results: Twenty-seven studies (3133 patients) were analysed. Compared with CEI, IEB decreased risk of breakthrough pain by 38% (risk ratio [95% confidence interval {CI}] of 0.62 [0.48, 0.81]; P=0.0004; I2=47%; 1164 patients) and reduced AUC of pain during the 4 h interval by 32.9% (mean difference [95% CI] of -16.7 mm h-1 [-18.9, -14.4]; P<0.0001; 1638 patients). Intermittent epidural bolus enhanced maternal satisfaction, shortened labour duration, decreased motor block, and reduced local anaesthetic consumption. The difference between the two groups was not statistically significant for epidural side-effects or mode of delivery. The TSA indicated adequate power for reliable inferences.Conclusions: Intermittent epidural bolus provides improved labour pain control during the first 4 h after epidural initiation with less breakthrough pain. Moderate- to high-quality evidence of intermittent epidural bolus superiority support its use as a safe and effective continuous epidural infusion alternative for labour analgesia. [ABSTRACT FROM AUTHOR]

Abstract: The nonlinear approximations based on trigonometric generating functions are studied. It is shown that, by properly choosing generating functions, such nonlinear approximations to the derivative of the Dirac delta function on [−1,1] are the corresponding Gaussian quadratures applied to its Stieltjes integral representations by the generating functions. Moreover, the approximations are proved to be convergent and the error terms are obtained. [Copyright &y& Elsevier]

Abstract Each fall, bowhead whales in the Bering-Chukchi-Beaufort (BCB) population migrate westward from summering grounds in the Beaufort Sea through the Chukchi Sea to the northern coast of Chukotka, Russia. Routes whales use when crossing the Chukchi Sea vary by year; in some years, whales migrate directly to the northern coast of Chukotka while in other years, whales may pause migration and linger, presumably to feed, in the central Chukchi Sea. To investigate how whale movements may be related to oceanographic variables we examined bowhead whale habitat selection within the Chukchi Sea in autumn (September--November) at two spatial scales. First, at the landscape scale (i.e. the Chukchi Sea), we compare oceanographic variables (e.g. temperature, salinity, and current velocity) at locations within used and randomly available tracks (i.e. paths of travel) to determine how oceanographic features are associated with where whales cross the Chukchi Sea in autumn. Second, at a local scale, we examine how directed travel or lingering within a whale's track is associated with oceanographic variables (e.g. temperature, salinity, and current velocity). Whale location data for 24 bowhead whales were paired with oceanographic data from a pan-arctic coupled ice-ocean model for 2006–2009. At the landscape scale, we found that whales generally followed water of Pacific origin characterized by temperatures <0ºC and salinities between 31.5 and 34.25. Bowhead whales avoided Alaskan Coastal Water and Siberian Shelf Water, the latter of which defines the western limit of their range, likely due to lower intrinsic densities of zooplankton prey. At the local scale, within their tracks, whales were more likely to interrupt directed movements and linger in areas characterized by stronger gradients in bottom salinity. [ABSTRACT FROM AUTHOR]

The Bering–Chukchi–Beaufort (BCB) population of bowhead whales ( Balaena mysticetus ) ranges across the seasonally ice-covered waters of the Bering, Chukchi, and Beaufort seas. We used locations from 54 bowhead whales, obtained by satellite telemetry between 2006 and 2012, to define areas of concentrated use, termed “core-use areas”. We identified six primary core-use areas and describe the timing of use and physical characteristics (oceanography, sea ice, and winds) associated with these areas. In spring, most whales migrated from wintering grounds in the Bering Sea to the Cape Bathurst polynya, Canada (Area 1), and spent the most time in the vicinity of the halocline at depths <75 m, which are within the euphotic zone, where calanoid copepods ascend following winter diapause. Peak use of the polynya occurred between 7 May and 5 July; whales generally left in July, when copepods are expected to descend to deeper depths. Between 12 July and 25 September, most tagged whales were located in shallow shelf waters adjacent to the Tuktoyaktuk Peninsula, Canada (Area 2), where wind-driven upwelling promotes the concentration of calanoid copepods. Between 22 August and 2 November, whales also congregated near Point Barrow, Alaska (Area 3), where east winds promote upwelling that moves zooplankton onto the Beaufort shelf, and subsequent relaxation of these winds promoted zooplankton aggregations. Between 27 October and 8 January, whales congregated along the northern shore of Chukotka, Russia (Area 4), where zooplankton likely concentrated along a coastal front between the southeastward-flowing Siberian Coastal Current and northward-flowing Bering Sea waters. The two remaining core-use areas occurred in the Bering Sea: Anadyr Strait (Area 5), where peak use occurred between 29 November and 20 April, and the Gulf of Anadyr (Area 6), where peak use occurred between 4 December and 1 April; both areas exhibited highly fractured sea ice. Whales near the Gulf of Anadyr spent almost half of their time at depths between 75 and 100 m, usually near the seafloor, where a subsurface front between cold Anadyr Water and warmer Bering Shelf Water presumably aggregates zooplankton. The amount of time whales spent near the seafloor in the Gulf of Anadyr, where copepods (in diapause) and, possibly, euphausiids are expected to aggregate provides strong evidence that bowhead whales are feeding in winter. The timing of bowhead spring migration corresponds with when zooplankton are expected to begin their spring ascent in April. The core-use areas we identified are also generally known from other studies to have high densities of whales and we are confident these areas represent the majority of important feeding areas during the study (2006–2012). Other feeding areas, that we did not detect, likely existed during the study and we expect core-use area boundaries to shift in response to changing hydrographic conditions. [ABSTRACT FROM AUTHOR]

Abstract: Respiratory motion and capnometry monitoring were performed during blood oxygen level-dependent (BOLD) functional magnetic resonance imaging (fMRI) of the brain while a series of paced hyperventilation tasks were performed that caused significant hypocapnia. Respiration volume per time (RVT) and end-tidal carbon dioxide (ETCO2) were determined and compared for their ability to explain BOLD contrast changes in the data. A 35% decrease in ETCO2 was observed along with corresponding changes in RVT. A best-fit ETCO2 response function, with an average initial peak delay time of 12 s, was empirically determined. ETCO2 data convolved with this response function was more strongly and prevalently correlated to BOLD signal changes than RVT data convolved with the corresponding respiration response function. The results suggest that ETCO2 better models BOLD signal fluctuations in fMRI experiments with significant transient hypocapnia. This is due to hysteresis in the ETCO2 response when moving from hypocapnia to normocapnia, compared to moving from normocapnia to hypocapnia. [Copyright &y& Elsevier]

Abstract: This study quantified the impact of the well-known physiologic noise correction algorithm RETROICOR applied to a pain functional magnetic resonance imaging (FMRI) experiment at two field strengths: 1.5 and 3.0 T. In the 1.5-T acquisition, there was an 8.2% decrease in time course variance (σ) and a 227% improvement in average model fit (increase in mean R 2 a). In the 3.0-T acquisition, significantly greater improvements were seen: a 10.4% decrease in σ and a 240% increase in mean R 2 a. End-tidal carbon dioxide data were also collected during scanning and used to account for low-frequency changes in cerebral blood flow; however, the impact of this correction was trivial compared to applying RETROICOR. Comparison between two implementations of RETROICOR demonstrated that oversampled physiologic data can be applied by either downsampling or modification of the timing in the RETROICOR algorithm, with equivalent results. Furthermore, there was no significant effect from manually aligning the physiologic data with corresponding image slices from an interleaved acquisition, indicating that RETROICOR accounts for timing differences between physiologic changes and MR signal changes. These findings suggest that RETROICOR correction, as it is commonly implemented, should be included as part of the data analysis for pain FMRI studies performed at 1.5 and 3.0 T. [Copyright &y& Elsevier]

Abstract: Springer et al. [Springer, A.M., Estes, J.A., van Vliet, G.B., Williams, T.M., Doak, D.F., Danner, E.M., Forney, K.A., Pfister, B., 2003. Sequential megafaunal collapse in the North Pacific Ocean: an ongoing legacy of industrial whaling? Proceedings of the National Academy of Sciences 100 (21), 12,223–12,228] hypothesized that great whales were an important prey resource for killer whales, and that the removal of fin and sperm whales by commercial whaling in the region of the Bering Sea/Aleutian Islands (BSAI) in the late 1960s and 1970s led to cascading trophic interactions that caused the sequential decline of populations of harbor seal, northern fur seal, Steller sea lion and northern sea otter. This hypothesis, referred to as the Sequential Megafaunal Collapse (SMC), has stirred considerable interest because of its implication for ecosystem-based management. The SMC has the following assumptions: (1) fin whales and sperm whales were important as prey species in the Bering Sea; (2) the biomass of all large whale species (i.e., North Pacific right, fin, humpback, gray, sperm, minke and bowhead whales) was in decline in the Bering Sea in the 1960s and early 1970s; and (3) pinniped declines in the 1970s and 1980s were sequential. We concluded that the available data are not consistent with the first two assumptions of the SMC. Statistical tests of the timing of the declines do not support the assumption that pinniped declines were sequential. We propose two alternative hypotheses for the declines that are more consistent with the available data. While it is plausible, from energetic arguments, for predation by killer whales to have been an important factor in the declines of one or more of the three populations of pinnipeds and the sea otter population in the BSAI region over the last 30 years, we hypothesize that the declines in pinniped populations in the BSAI can best be understood by invoking a multiple factor hypothesis that includes both bottom–up forcing (as indicated by evidence of nutritional stress in the western Steller sea lion population) and top–down forcing (e.g., predation by killer whales, mortality incidental to commercial fishing, directed harvests). Our second hypothesis is a modification of the top–down forcing mechanism (i.e., killer whale predation on one or more of the pinniped populations and the sea otter population is mediated via the recovery of the eastern North Pacific population of the gray whale). We remain skeptical about the proposed link between commercial whaling on fin and sperm whales, which ended in the mid-1960s, and the observed decline of populations of northern fur seal, harbor seal, and Steller sea lion some 15 years later. [Copyright &y& Elsevier]

Chemical mechanical planarization (CMP) of copper, a key processing step in the rapid development of copper interconnect technology, requires the use of a chemical system that can oxidize and complex copper. Hydroxylamine, because of its redox properties and copper complexation ability, is being actively tested for use in copper CMP. Fundamental investigations have been carried out to characterize the dissolution of electroplated copper thin films in hydroxylamine-based solutions. Based on potential-pH diagrams and the data on dependence of copper etch rate on pH, a mechanism for copper dissolution based on the auto-oxidation/reduction of hydroxylamine has been proposed. The effectiveness of benzotriazole (BTA) and salicylhydroxamic acid (SHA) as corrosion inhibitors for copper in hydroxylamine-based chemistries is discussed. [Copyright &y& Elsevier]