(Ultra) luminous infrared galaxies ((U)LIRGs) are objects characterized by their extreme infrared (8-1000 mu m) luminosities (L sub(LIRG) > 10 super(11) L sub(middot in circle) and L sub(ULIRG) > 10 ...super(12)L sub(middot in circle)). The Herschel Comprehensive ULIRG Emission Survey (PI: van der Werf) presents a representative flux-limited sample of 29 (U)LIRGs that spans the full luminosity range of these objects (10 super(11)L sub(middo t in circle) < or =, slant L sub(IR) < or =, slant 10 super(13) L sub(middot in circle)). With the Herschel Space Observatory, we observe CII 157 mu m, OI 63 mu m, and OI 145 mu m line emission with Photodetector Array Camera and Spectrometer, CO J = 4-3 through J = 13-12, CI 370 mu m, and CI 609 mu m with SPIRE, and low-J CO transitions with ground-based telescopes. The CO ladders of the sample are separated into three classes based on their excitation level. In 13 of the galaxies, the OI 63 mu m emission line is self absorbed. Comparing the CO excitation to the InfraRed Astronomical Satellite 60/100 mu m ratio and to far infrared luminosity, we find that the CO excitation is more correlated to the far infrared colors. We present cooling budgets for the galaxies and find fine-structure line flux deficits in the CII, SiII, OI, and CI lines in the objects with the highest far IR fluxes, but do not observe this for CO 4 < or =, slant J sub(upp) < or =, slant 13. In order to study the heating of the molecular gas, we present a combination of three diagnostic quantities to help determine the dominant heating source. Using the CO excitation, the CO J = 1-0 linewidth, and the active galactic nucleus (AGN) contribution, we conclude that galaxies with large CO linewidths always have high-excitation CO ladders, and often low AGN contributions, suggesting that mechanical heating is important.
Disrupted emotional processing is a common feature of many psychiatric disorders. The authors investigated functional disruptions in neural circuitry underlying emotional processing across a range of ...tasks and across psychiatric disorders through a transdiagnostic quantitative meta-analysis of published neuroimaging data.
A PubMed search was conducted for whole-brain functional neuroimaging findings published through May 2018 that compared activation during emotional processing tasks in patients with psychiatric disorders (including schizophrenia, bipolar or unipolar depression, anxiety, and substance use) to matched healthy control participants. Activation likelihood estimation (ALE) meta-analyses were conducted on peak voxel coordinates to identify spatial convergence.
The 298 experiments submitted to meta-analysis included 5,427 patients and 5,491 control participants. ALE across diagnoses and patterns of patient hyper- and hyporeactivity demonstrated abnormal activation in the amygdala, the hippocampal/parahippocampal gyri, the dorsomedial/pulvinar nuclei of the thalamus, and the fusiform gyri, as well as the medial and lateral dorsal and ventral prefrontal regions. ALE across disorders but considering directionality demonstrated patient hyperactivation in the amygdala and the hippocampal/parahippocampal gyri. Hypoactivation was found in the medial and lateral prefrontal regions, most pronounced during processing of unpleasant stimuli. More refined disorder-specific analyses suggested that these overall patterns were shared to varying degrees, with notable differences in patterns of hyper- and hypoactivation.
These findings demonstrate a pattern of neurocircuit disruption across major psychiatric disorders in regions and networks key to adaptive emotional reactivity and regulation. More specifically, disruption corresponded prominently to the "salience" network, the ventral striatal/ventromedial prefrontal "reward" network, and the lateral orbitofrontal "nonreward" network. Consistent with the Research Domain Criteria initiative, these findings suggest that psychiatric illness may be productively formulated as dysfunction in transdiagnostic neurobehavioral phenotypes such as neurocircuit activation.
Planar laser-plasma interaction (LPI) experiments at the National Ignition Facility (NIF) have allowed access for the first time to regimes of electron density scale length (∼500 to 700 μm), ...electron temperature (∼3 to 5 keV), and laser intensity (6 to 16×10^{14} W/cm^{2}) that are relevant to direct-drive inertial confinement fusion ignition. Unlike in shorter-scale-length plasmas on OMEGA, scattered-light data on the NIF show that the near-quarter-critical LPI physics is dominated by stimulated Raman scattering (SRS) rather than by two-plasmon decay (TPD). This difference in regime is explained based on absolute SRS and TPD threshold considerations. SRS sidescatter tangential to density contours and other SRS mechanisms are observed. The fraction of laser energy converted to hot electrons is ∼0.7% to 2.9%, consistent with observed levels of SRS. The intensity threshold for hot-electron production is assessed, and the use of a Si ablator slightly increases this threshold from ∼4×10^{14} to ∼6×10^{14} W/cm^{2}. These results have significant implications for mitigation of LPI hot-electron preheat in direct-drive ignition designs.
In this paper we present fluxes in the CI lines of neutral carbon at the centers of some 76 galaxies with far-infrared luminosities ranging from 109 to 1012L, as obtained with the Herschel Space ...Observatory and ground-based facilities, along with the line fluxes of the J = 7-6, J = 4-3, J = 2-112CO, and J = 2-113CO transitions. With this data-set, we determine the behavior of the observed lines with respect to each other and then investigate whether they can be used to characterize the molecular interstellar medium (ISM) of the parent galaxies in simple ways and how the molecular gas properties define the model results. In particular, so-called X(CI) conversion factors are not superior to X(12CO) factors. The methods and diagnostic diagrams outlined in this paper also provide a new and relatively straightforward means of deriving the physical characteristics of molecular gas in high-redshift galaxies up to z = 5, which are otherwise hard to determine.
Abstract
Description
The US Department of Veterans Affairs (VA) and US Department of Defense (DoD) revised the 2010 clinical practice guideline (CPG) for the management of opioid therapy for chronic ...pain, considering the specific needs of the VA and DoD and new evidence regarding prescribing opioid medication for non-end-of-life-related chronic pain. This paper summarizes the major recommendations and compares them with the US Centers for Disease Control and Prevention (CDC) guideline for prescribing opioids.
Patient Population
This Opioid Therapy CPG was developed for VA-DoD service members, veterans, and their families.
Methods
The VA/DoD Evidence-Based Practice Work Group convened a VA/DoD guideline renewal development effort and conformed to the guidelines established by the VA/DoD Joint Executive Council (JEC) and VA/DoD Health Executive Council (HEC). The panel developed questions, searched and evaluated the literature, developed recommendations using GRADE methodology, and developed algorithms. Passage of the CARA Act by Congress compelled consideration and comparison with the CDC opioid therapy guideline mid-development.
Results
There were 18 recommendations made. This article focuses on guideline development and key recommendations with CDC comparisons taken from four major areas, including:
initiation and continuation of opioids;type, dose, follow-up, and taper of opioids;risk mitigation;acute pain.
Conclusions
Guideline development and recommendations are presented. There was substantial overlap with the CDC opioid guideline. Additionally, there were items particularly relevant to the VA-DoD, including risk mitigation, suicide prevention, and preventing opioid use disorder in young patients. Our guideline highlights avoiding opioid therapy longer than 90 days as a critical juncture.
Mutations drive evolution and were assumed to occur by chance: constantly, gradually, roughly uniformly in genomes, and without regard to environmental inputs, but this view is being revised by ...discoveries of molecular mechanisms of mutation in bacteria, now translated across the tree of life. These mechanisms reveal a picture of highly regulated mutagenesis, up-regulated temporally by stress responses and activated when cells/organisms are maladapted to their environments-when stressed-potentially accelerating adaptation. Mutation is also nonrandom in genomic space, with multiple simultaneous mutations falling in local clusters, which may allow concerted evolution-the multiple changes needed to adapt protein functions and protein machines encoded by linked genes. Molecular mechanisms of stress-inducible mutation change ideas about evolution and suggest different ways to model and address cancer development, infectious disease, and evolution generally.
The British Society of Gastroenterology guidelines on the management of cholangiocarcinoma were originally published in 2002. This is the first update since then and is based on a comprehensive ...review of the recent literature, including data from randomised controlled trials, systematic reviews, meta-analyses, cohort, prospective and retrospective studies.
The physics of dusty plasmas in high magnetic field is an area of current interest, spurred by the development of experiments in this area. Dust acoustic (or dust density) waves have been observed in ...many laboratory dusty plasmas where there is either no or weak magnetic field. These waves may be excited by the flow of ions relative to dust. The effects of high magnetic field on the excitation of dust waves have been considered in the theoretical literature, including instabilities driven by ions streaming either along or across the magnetic field. We review and extend prior theory work on such instabilities, exploring their behavior as the magnetization of the ions is varied, while the electrons are strongly magnetized and the dust is unmagnetized. It is shown that when the ions are magnetized, there can be structure in the unstable wavenumber spectrum under certain conditions. Application to possible experimental parameters is discussed.
Paclitaxel is a commonly used chemotherapeutic agent with a broad spectrum of activity against cancers in humans. In 1992, paclitaxel was approved by the U.S. Food and Drug Administration (FDA) as ...Taxol® for use in advanced ovarian cancer. Two years later, it was approved for the treatment of metastatic breast cancer. Paclitaxel was originally isolated from the bark of the Pacific yew tree, Taxus brevifolia in 1971. Taxanes are a family of microtubule inhibitors. As a member of this family, paclitaxel suppresses spindle microtubule dynamics. This activity results in the blockage of the metaphase‐anaphase transitions, and ultimately in the inhibition of mitosis, and induction of apoptosis in a wide spectrum of cancer cells. Additional anticancer activities of paclitaxel have been defined that are independent of these effects on the microtubules and may include the suppression of cell proliferation as well as antiangiogenic effects. Based on its targeting of a fundamental feature of the cancer phenotype, the mitotic complex, it is not surprising that paclitaxel has been found to be active in a wide variety of cancers in humans. This review summarizes the evidence in support of paclitaxel's broad anticancer activity and introduces the rationale for, and the progress in development of novel formulations of paclitaxel that may preferentially target cancers and that are not associated with the risks for hypersensitivity in dogs. Of note, a novel nanoparticle formulation of paclitaxel that substantially limits hypersensitivity was recently given conditional approval by the FDA Center for Veterinary Medicine for use in dogs with resectable and nonresectable squamous cell carcinoma and nonresectable stage III, IV and V mammary carcinoma.
Bacteria can rapidly evolve resistance to antibiotics via the SOS response, a state of high-activity DNA repair and mutagenesis. We explore here the first steps of this evolution in the bacterium ...Escherichia coli . Induction of the SOS response by the genotoxic antibiotic ciprofloxacin changes the E. coli rod shape into multichromosome-containing filaments. We show that at subminimal inhibitory concentrations of ciprofloxacin the bacterial filament divides asymmetrically repeatedly at the tip. Chromosome-containing buds are made that, if resistant, propagate nonfilamenting progeny with enhanced resistance to ciprofloxacin as the parent filament dies. We propose that the multinucleated filament creates an environmental niche where evolution can proceed via generation of improved mutant chromosomes due to the mutagenic SOS response and possible recombination of the new alleles between chromosomes. Our data provide a better understanding of the processes underlying the origin of resistance at the single-cell level and suggest an analogous role to the eukaryotic aneuploidy condition in cancer.
Significance Understanding how bacteria rapidly evolve under antibiotic selective pressure is crucial to controlling the development of resistant organisms. We show that initial resistance emerges from successful segregation of mutant chromosomes at the tips of filaments followed by budding of resistant progeny. We propose that the first stages of emergence of resistance occur via the generation of multiple chromosomes within the filament and are achieved by mutation and possibly recombination between the chromosomes.
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