A theoretical study of elastic X-ray scattering

Bragg X-ray scattering intensities are defined as scattering by the thermodynamic average electron-charge density. Purely elastic, kinematic X-ray scattering by a target in thermal equilibrium is always larger than Bragg scattering. At low temperatures, the elastic scattering becomes Bragg scattering. For large molecules, such as a crystal, at ordinary temperatures the elastic and Bragg scattering differ in a relative sense by O(N-1), where N is the number of vibrational degrees of freedom. For most practical cases the Bragg scattering is essentially the same as purely elastic scattering of X-rays

Erenumab in chronic migraine: Patient-reported outcomes in a randomized double-blind study.

OBJECTIVE: To determine the effect of erenumab, a human monoclonal antibody targeting the calcitonin gene-related peptide receptor, on health-related quality of life (HRQoL), headache impact, and disability in patients with chronic migraine (CM). METHODS: In this double-blind, placebo-controlled study, 667 adults with CM were randomized (3:2:2) to placebo or erenumab (70 or 140 mg monthly). Exploratory endpoints included migraine-specific HRQoL (Migraine-Specific Quality-of-Life Questionnaire [MSQ]), headache impact (Headache Impact Test-6 [HIT-6]), migraine-related disability (Migraine Disability Assessment [MIDAS] test), and pain interference (Patient-Reported Outcomes Measurement Information System [PROMIS] Pain Interference Scale short form 6b). RESULTS: Improvements were observed for all endpoints in both erenumab groups at month 3, with greater changes relative to placebo observed at month 1 for many outcomes. All 3 MSQ domains were improved from baseline with treatment differences for both doses exceeding minimally important differences established for MSQ-role function-restrictive (≥3.2) and MSQ-emotional functioning (≥7.5) and for MSQ-role function-preventive (≥4.5) for erenumab 140 mg. Changes from baseline in HIT-6 scores at month 3 were -5.6 for both doses vs -3.1 for placebo. MIDAS scores at month 3 improved by -19.4 days for 70 mg and -19.8 days for 140 mg vs -7.5 days for placebo. Individual-level minimally important difference was achieved by larger proportions of erenumab-treated participants than placebo for all MSQ domains and HIT-6. Lower proportions of erenumab-treated participants had MIDAS scores of severe (≥21) or very severe (≥41) or PROMIS scores ≥60 at month 3. CONCLUSIONS: Erenumab-treated patients with CM experienced clinically relevant improvements across a broad range of patient-reported outcomes. CLINICALTRIALSGOV IDENTIFIER: NCT02066415. CLASSIFICATION OF EVIDENCE: This study provides Class II evidence that for patients with CM, erenumab treatment improves HRQoL, headache impact, and disability

Program Management versus Portfolio Management in Defense Acquisition

Symposium PresentationApproved for public release; distribution is unlimited

Program Management Versus Portfolio Management in Defense Acquisition

Excerpt from the Proceedings of the Nineteenth Annual Acquisition Research SymposiumThis research performed a gap analysis on the existing Department of Defense (DoD) program management competency standards to determine if changes are required to fully adopt product portfolio management (PPM) strategies in defense acquisition. Current DoD program management standards are compared to the Project Management Institute’s Portfolio Management Professional certification standards to analyze alignment and gaps between the standards. Barrier to Implementation (BTI) scores are assigned to address the identified gaps in the DoD standard. The study found that the DoD program management competencies are on average 41% aligned with portfolio management industry standards. The DoD program management competencies are least aligned with the portfolio management domains of governance and strategic alignment. The composite BTI score indicates low to medium level of implementation barriers for most of the gaps. Results indicate that the DoD is capable of conducting PPM, and further research is needed to fully align the current competency standards with industry best practices. Defense acquisition senior leaders should consider formulating DoD portfolio management career field functional competencies to address congressional mandates for portfolio management implementation within the DoD.Approved for public release; distribution is unlimited

Scattering and Iron Fluorescence Revealed During Absorption Dips in Circinus X-1

We show that dramatic spectral evolution associated with dips occurring near phase zero in RXTE observations of Cir X-1 is well-fit by variable and at times heavy absorption (N_H > 10^24 cm^-2) of a bright component, plus an underlying faint component which is not attenuated by the variable column and whose flux is ~10% of that of the unabsorbed bright component. A prominent Fe emission line at ~6.5 keV is evident during the dips. The absolute line flux outside the dips is similar to that during the dips, indicating that the line is associated with the faint component. These results are consistent with a model in which the bright component is radiation received directly from a compact source while the faint component may be attributed to scattered radiation. Our results are also generally consistent with those of Brandt et al., who found that a partial- covering model could explain ASCA spectra of a low-to-high transition in Cir X-1. The relative brightness of the two components in our model requires a column density of ~2*10^23 cm^-2 if the faint component is due to Thomson scattering in material that mostly surrounds the source. We find that illumination of such a scattering cloud by the observed direct component would produce an Fe K-alpha fluorescence flux that is in rough agreement with the flux of the observed emission line. We also conclude that if the scattering medium is not highly ionized, our line of sight to the compact source does not pass through it. Finally, we discuss simple pictures of the absorbers responsible for the dips themselves.Comment: Accepted for publication in The Astrophysical Journal (23 pages, including 11 figures

Plasma proteome correlates of lipid and lipoprotein: biomarkers of metabolic diversity and inflammation in children of rural Nepal.

Proteins involved in lipoprotein metabolism can modulate cardiovascular health. While often measured to assess adult metabolic diseases, little is known about the proteomes of lipoproteins and their relation to metabolic dysregulation and underlying inflammation in undernourished child populations. The objective of this population study was to globally characterize plasma proteins systemically associated with HDL, LDL, and triglycerides in 500 Nepalese children. Abnormal lipid profiles characterized by elevated plasma triglycerides and low HDL-cholesterol (HDL-C) concentrations were common, especially in children with subclinical inflammation. Among 982 proteins analyzed, the relative abundance of 11, 12, and 52 plasma proteins was correlated with LDL-cholesterol (r = -0.43∼0.70), triglycerides (r = -0.39∼0.53), and HDL-C (r = -0.49∼0.79) concentrations, respectively. These proteins included apolipoproteins and numerous unexpected intracellular and extracellular matrix binding proteins, likely originating in hepatic and peripheral tissues. Relative abundance of two-thirds of the HDL proteome varied with inflammation, with acute phase reactants higher by 4∼40%, and proteins involved in HDL biosynthesis, cholesterol efflux, vitamin transport, angiogenesis, and tissue repair lower by 3∼20%. Untargeted plasma proteomics detects comprehensive sets of both known and novel lipoprotein-associated proteins likely reflecting systemic regulation of lipoprotein metabolism and vascular homeostasis. Inflammation-altered distributions of the HDL proteome may be predisposing undernourished populations to early chronic disease

Inhibiting tryptophan metabolism enhances interferon therapy in kidney cancer.

Renal cell carcinoma (RCC) is increasing in incidence, and a complete cure remains elusive. While immune-checkpoint antibodies are promising, interferon-based immunotherapy has been disappointing. Tryptophan metabolism, which produces immunosuppressive metabolites, is enhanced in RCC. Here we show indolamine-2,3-dioxygenase-1 (IDO1) expression, a kynurenine pathway enzyme, is increased not only in tumor cells but also in the microenvironment of human RCC compared to normal kidney tissues. Neither kynurenine metabolites nor IDO inhibitors affected the survival or proliferation of human RCC or murine renal cell adenocarcinoma (RENCA) cells in vitro. However, interferon-gamma (IFNγ) induced high levels of IDO1 in both RCC and RENCA cells, concomitant with enhanced kynurenine levels in conditioned media. Induction of IDO1 by IFNα was weaker than by IFNγ. Neither the IDO1 inhibitor methyl-thiohydantoin-DL-tryptophan (MTH-trp) nor IFNα alone inhibited RENCA tumor growth, however the combination of MTH-trp and IFNα reduced tumor growth compared to IFNα. Thus, the failure of IFNα therapy for human RCC is likely due to its inability to overcome the immunosuppressive environment created by increased IDO1. Based on our data, and given that IDO inhibitors are already in clinical trials for other malignancies, IFNα therapy with an IDO inhibitor should be revisited for RCC

Multi-Focal, Multi-Centric Angiosarcoma of Bone

A multi-focal multi-centric, malignant tumour of vascular origin arising in bone in a 55-year-old man is described. The presenting symptoms were pain and weight loss. Radiologically, multiple lytic lesions were demonstrated in the long bones of both legs and throughout the pelvis. Histological examination demonstrated an angiosarcoma which was predominantly low grade in nature but with focal areas of intermediate grade. Turnout cells expressed the endothelial markers CD31, CD34 and von Willebrand's factor. There was rapid radiological progression of disease with no response to radiotherapy. Pain abated within a few days of institution of doxorubicin, 75 mg m-2, but the patient died of massive pulmonary thromboembolism 14 days later, 11 months after the first symptoms

Assessment of sampling methods to estimate horseshoe crab (Limulus polyphemus L.) egg density in Delaware Bay

Each spring horseshoe crabs (Limulus polyphemus L.) emerge from Delaware Bay to spawn and deposit their eggs on the foreshore of sandy beaches (Shuster and Botton, 1985; Smith et al., 2002a). From mid-May to early June, migratory shorebirds stopover in Delaware Bay and forage heavily on horseshoe crab eggs that have been transported up onto the beach (Botton et al., 1994; Burger et al., 1997; Tsipoura and Burger, 1999). Thus, estimating the quantity of horseshoe crab eggs in Delaware Bay beaches can be useful for monitoring spawning activity and assessing the amount of forage available to migratory shorebirds