When a γ-ray interacts in a semiconductor detector, the resulting electron–hole charge clouds drift towards their respective electrodes for signal collection. These charge clouds will expand over ...time due to both thermal diffusion and mutual electrostatic repulsion. Solutions to the resulting charge profiles are well understood for the limiting cases accounting for only diffusion and only repulsion, but the general solution including both effects can only be solved numerically. Previous attempts to model these effects have taken into account the broadening of the charge profile due to both effects, but have simplified the shape of the profile by assuming Gaussian distributions. However, the detailed charge profile can have important impacts on charge sharing in multi-electrode strip detectors. In this work, we derive an analytical approximation to the general solution, including both diffusion and repulsion, that closely replicates both the width and the detailed shape of the charge profiles. This analytical solution simplifies the modeling of charge clouds in semiconductor strip detectors.
(R)-N-(3-(6-(4-(1,4-dimethyl-3-oxopiperazin-2-yl)phenylamino)-4-methyl-5-oxo-4,5-dihydropyrazin-2-yl)-2-methylphenyl)-4,5,6,7-tetrahydrobenzobthiophene-2-carboxamide (GDC-0834) is a potent and ...selective inhibitor of Bruton's tyrosine kinase (BTK), investigated as a potential treatment for rheumatoid arthritis. In vitro metabolite identification studies in hepatocytes revealed predominant formation of an inactive metabolite (M1) via amide hydrolysis in human. The formation of M1 appeared to be NADPH-independent in human liver microsomes. M1 was found in only minor to moderate quantities in plasma from preclinical species dosed with GDC-0834. Human clearance predictions using various methodologies resulted in estimates ranging from low to high. In addition, GDC-0834 exhibited low clearance in PXB chimeric mice with humanized liver. Uncertainty in human pharmacokinetic prediction and high interest in a BTK inhibitor for clinical evaluation prompted an investigational new drug strategy, in which GDC-0834 was rapidly advanced to a single-dose human clinical trial. GDC-0834 plasma concentrations in humans were below the limit of quantitation (<1 ng/ml) in most samples from the cohorts dosed orally at 35 and 105 mg. In contrast, substantial plasma concentrations of M1 were observed. In human plasma and urine, only M1 and its sequential metabolites were identified. The formation kinetics of M1 was evaluated in rat, dog, monkey, and human liver microsomes in the absence of NADPH. The maximum rate of M1 formation (V(max)) was substantially higher in human compared with that in other species. In contrast, the Michaelis-Menten constant (K(m)) was comparable among species. Intrinsic clearance (V(max)/K(m)) of GDC-0834 from M1 formation in human was 23- to 169-fold higher than observed in rat, dog, and monkey.
We present 3–50 keV NuSTAR observations of the active galactic nuclei Mrk 335 in a very low flux state. The spectrum is dominated by very strong features at the energies of the iron line at 5–7 keV ...and Compton hump from 10–30 keV. The source is variable during the observation, with the variability concentrated at low energies, which suggesting either a relativistic reflection or a variable absorption scenario. In this work, we focus on the reflection interpretation, making use of new relativistic reflection models that self consistently calculate the reflection fraction, relativistic blurring and angle-dependent reflection spectrum for different coronal heights to model the spectra. We find that the spectra can be well fitted with relativistic reflection, and that the lowest flux state spectrum is described by reflection alone, suggesting the effects of extreme light-bending occurring within ∼2 gravitational radii (R
G) of the event horizon. The reflection fraction decreases sharply with increasing flux, consistent with a point source moving up to above 10 R
G as the source brightens. We constrain the spin parameter to greater than 0.9 at the 3σ confidence level. By adding a spin-dependent upper limit on the reflection fraction to our models, we demonstrate that this can be a powerful way of constraining the spin parameter, particularly in reflection dominated states. We also calculate a detailed emissivity profile for the iron line, and find that it closely matches theoretical predictions for a compact source within a few R
G of the black hole.
ABSTRACT We present the results from sensitive, multi-epoch NuSTAR observations of the late-type star-forming galaxy M83 (d = 4.6 Mpc). This is the first investigation to spatially resolve the hard ( ...E > 10 keV) X-ray emission of this galaxy. The nuclear region and ∼20 off-nuclear point sources, including a previously discovered ultraluminous X-ray source, are detected in our NuSTAR observations. The X-ray hardnesses and luminosities of the majority of the point sources are consistent with hard X-ray sources resolved in the starburst galaxy NGC 253. We infer that the hard X-ray emission is most likely dominated by intermediate accretion state black hole binaries and neutron star low-mass X-ray binaries (Z-sources). We construct the X-ray binary luminosity function (XLF) in the NuSTAR band for an extragalactic environment for the first time. The M83 XLF has a steeper XLF than the X-ray binary XLF in NGC 253, which is consistent with previous measurements by Chandra at softer X-ray energies. The NuSTAR integrated galaxy spectrum of M83 drops quickly above 10 keV, which is also seen in the starburst galaxies NGC 253, NGC 3310, and NGC 3256. The NuSTAR observations constrain any active galactic nucleus (AGN) to be either highly obscured or to have an extremely low luminosity of 1038 erg s−1 (10-30 keV), implying that it is emitting at a very low Eddington ratio. An X-ray point source that is consistent with the location of the nuclear star cluster with an X-ray luminosity of a few times 1038 erg s−1 may be a low-luminosity AGN but is more consistent with being an X-ray binary.
Background and Objectives: Orthopedic surgeons commonly prescribe opioids, surpassing all medical specialties. Our objective was to develop a pain management scale that captures medication use, ...patient-reported pain scores, and helps orthopedic surgeons evaluate their post-operative prescribing practice. Materials and Methods: An IRB-approved prospective study followed 502 post-operative orthopedic surgery patients over a six-month period. All patients were surveyed in an orthopedic clinic at a Level 1 US Trauma Center, during a routine follow-up. Patient pain satisfaction was assessed using the validated Interventional Pain Assessment (IPA) scale, which uses three categories: 0 (no pain), 1 (tolerable pain), and 2 (intolerable pain). Daily narcotic use was translated to morphine milligram equivalents (MMEs) using the Michigan Automated Prescription System (MAPS) narcotics registry. When patient pain satisfaction and narcotic usage were combined, this scale was called the Detroit Interventional Pain Assessment (DIPA) scale. Results: The five classes based on common prescription and usage of narcotics in this cohort include the following: A (no pain medication), B (over-the-counter medication), C (occasional use of short-acting narcotics 1–30 MMEs), D (consistent/regular use of short-acting narcotics 31–79 MMEs), and E (long-duration or stronger short-acting narcotics 80+ MMEs). Patients were most satisfied with their pain management at six weeks (80.5%) and three months (75.65%), and least satisfied at two weeks (62.5%) and six months (60.9%). Additional information displayed on the DIPA graph revealed there was a significant decrease in the percentage of patients on narcotics at two weeks (65.2%) to six months (32.6%) at p < 0.001. Conclusions: The DIPA pain scale shows the relationship between patient pain perception and opioid prescription/usage, while also tracking prescriber tendencies. Providers were able to visualize their post-operative pain management progression at each designated clinic visit with corresponding alphabetical daily MME categories. In this study, results suggest that surgeons were not effective at managing the pain of patients at two weeks post-operative, which is attributed to an inadequate number of pain pills prescribed upon discharge. Overall, the DIPA graph signaled that better pain management interventions are necessitated in periods with lower efficiency scores.
In light of the large number of studies published since the 2004 update of Schizophrenia Patient Outcomes Research Team psychopharmacological treatment recommendations, we conducted an extensive ...literature review to determine whether the current psychopharmacological treatment recommendations required revision and whether there was sufficient evidence to warrant new treatment recommendations for prespecified outcomes of interest. We reviewed over 400 articles, which resulted in 16 treatment recommendations: the revision of 11 previous treatment recommendations and 5 new treatment recommendations. Three previous treatment recommendations were eliminated. There were 13 interventions and/or outcomes for which there was insufficient evidence for a treatment recommendation, and a statement was written to summarize the current level of evidence and identify important gaps in our knowledge that need to be addressed. In general, there was considerable consensus among the Psychopharmacology Evidence Review Group and the expert consultants. Two major areas of contention concerned whether there was sufficient evidence to recommend specific dosage ranges for the acute and maintenance treatment of first-episode and multi-episode schizophrenia and to endorse the practice of switching antipsychotics for the treatment of antipsychotic-related weight gain. Finally, there continue to be major gaps in our knowledge, including limited information on (1) the use of adjunctive pharmacological agents for the treatment of persistent positive symptoms or other symptom domains of psychopathology, including anxiety, cognitive impairments, depressive symptoms, and persistent negative symptoms and (2) the treatment of co-occurring substance or medical disorders that occur frequently in individuals with schizophrenia.
Equilibrium Molecular Structures Jean Demaison, James E. Boggs, Attila G. Csaszar / Jean Demaison, James E. Boggs, Attila G. Csaszar
2016, 2011, 2010, 2010-12-02
eBook
Molecular structure is the most basic information about a substance, determining most of its properties. Determination of accurate structures is hampered in that every method applies its own ...definition of "structure" and thus results from different sources can yield significantly different results. Sophisticated protocols exist to account for these
The majority of ultraluminous X-ray sources are point sources that are spatially offset from the nuclei of nearby galaxies and whose X-ray luminosities exceed the theoretical maximum for spherical ...infall (the Eddington limit) onto stellar-mass black holes. Their X-ray luminosities in the 0.5-10 kiloelectronvolt energy band range from 10(39) to 10(41) ergs per second. Because higher masses imply less extreme ratios of the luminosity to the isotropic Eddington limit, theoretical models have focused on black hole rather than neutron star systems. The most challenging sources to explain are those at the luminous end of the range (more than 10(40) ergs per second), which require black hole masses of 50-100 times the solar value or significant departures from the standard thin disk accretion that powers bright Galactic X-ray binaries, or both. Here we report broadband X-ray observations of the nuclear region of the galaxy M82 that reveal pulsations with an average period of 1.37 seconds and a 2.5-day sinusoidal modulation. The pulsations result from the rotation of a magnetized neutron star, and the modulation arises from its binary orbit. The pulsed flux alone corresponds to an X-ray luminosity in the 3-30 kiloelectronvolt range of 4.9 × 10(39) ergs per second. The pulsating source is spatially coincident with a variable source that can reach an X-ray luminosity in the 0.3-10 kiloelectronvolt range of 1.8 × 10(40) ergs per second. This association implies a luminosity of about 100 times the Eddington limit for a 1.4-solar-mass object, or more than ten times brighter than any known accreting pulsar. This implies that neutron stars may not be rare in the ultraluminous X-ray population, and it challenges physical models for the accretion of matter onto magnetized compact objects.
Broad X-ray emission lines from neutral and partially ionized iron observed in active galaxies have been interpreted as fluorescence produced by the reflection of hard X-rays off the inner edge of an ...accretion disk. In this model, line broadening and distortion result from rapid rotation and relativistic effects near the black hole, the line shape being sensitive to its spin. Alternative models in which the distortions result from absorption by intervening structures provide an equally good description of the data, and there has been no general agreement on which is correct. Recent claims that the black hole (2 × 10(6) solar masses) at the centre of the galaxy NGC 1365 is rotating at close to its maximum possible speed rest on the assumption of relativistic reflection. Here we report X-ray observations of NGC 1365 that reveal the relativistic disk features through broadened Fe-line emission and an associated Compton scattering excess of 10-30 kiloelectronvolts. Using temporal and spectral analyses, we disentangle continuum changes due to time-variable absorption from reflection, which we find arises from a region within 2.5 gravitational radii of the rapidly spinning black hole. Absorption-dominated models that do not include relativistic disk reflection can be ruled out both statistically and on physical grounds.
Observations of the afterglows of γ-ray bursts (GRBs) have revealed that they lie at cosmological distances, and so correspond to the release of an enormous amount of energy. The nature of the ...central engine that powers these events and the prompt γ-ray emission mechanism itself remain enigmatic because, once a relativistic fireball is created, the physics of the afterglow is insensitive to the nature of the progenitor. Here we report the discovery of linear polarization in the prompt γ-ray emission from GRB021206, which indicates that it is synchrotron emission from relativistic electrons in a strong magnetic field. The polarization is at the theoretical maximum, which requires a uniform, large-scale magnetic field over the γ-ray emission region. A large-scale magnetic field constrains possible progenitors to those either having or producing organized fields. We suggest that the large magnetic energy densities in the progenitor environment (comparable to the kinetic energy densities of the fireball), combined with the large-scale structure of the field, indicate that magnetic fields drive the GRB explosion.
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