A preclinical investigation of the saturation and dosimetry of 153Sm-DOTMP as a bone-seeking radiopharmaceutical

Simón J, Frank RK, Crump DK, Erwin WD, Ueno NT, Wendt RE. A preclinical investigation of the saturation and dosimetry of 153Sm-DOTMP as a bone-seeking radiopharmaceutical. Nuclear Medicine and Biology. 2012/08/01/ 2012;39(6):770-776. doi:https://doi.org/10.1016/j.nucmedbio.2011.12.015https://openworks.mdanderson.org/mdacc_imgphys_pubs/1006/thumbnail.jp

Orbital Instabilities in a Triaxial Cusp Potential

This paper constructs an analytic form for a triaxial potential that describes the dynamics of a wide variety of astrophysical systems, including the inner portions of dark matter halos, the central regions of galactic bulges, and young embedded star clusters. Specifically, this potential results from a density profile of the form $\rho (m) \propto m^{-1}$, where the radial coordinate is generalized to triaxial form so that $m^2 = x^2/a^2 + y^2/b^2 + z^2/c^2$. Using the resulting analytic form of the potential, and the corresponding force laws, we construct orbit solutions and show that a robust orbit instability exists in these systems. For orbits initially confined to any of the three principal planes, the motion in the perpendicular direction can be unstable. We discuss the range of parameter space for which these orbits are unstable, find the growth rates and saturation levels of the instability, and develop a set of analytic model equations that elucidate the essential physics of the instability mechanism. This orbit instability has a large number of astrophysical implications and applications, including understanding the formation of dark matter halos, the structure of galactic bulges, the survival of tidal streams, and the early evolution of embedded star clusters.Comment: 50 pages, accepted for publication in Ap

Secular changes in the progression of clinical markers and patient-reported outcomes in early rheumatoid arthritis

© The Author(s) 2020. Published by Oxford University Press on behalf of the British Society for Rheumatology. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited.OBJECTIVES: To examine secular trends in the progression of clinical and patient-reported outcomes in early RA. METHODS: A total of 2701 patients recruited to the Early Rheumatoid Arthritis Study or Early Rheumatoid Arthritis Network with year of diagnosis from 1986 to 2011. The 5-year progression rates for patients diagnosed at different points in time were modelled using mixed-effects regression; 1990, 2002 and 2010, were compared. Clinical markers of disease included the 28-joint count DAS and the ESR. Patient-reported markers included the HAQ, visual analogue scale of pain and global health, and the Short-Form 36. RESULTS: Statistically significant improvements in both 28-joint count DAS and ESR were seen over the 5 years in patients diagnosed with RA compared with those diagnosed earlier. By 5 years, 59% of patients with diagnosis in 2010 were estimated to reach low disease activity compared with 48% with diagnosis in 2002 and 32% with diagnosis in 1990. Whilst HAQ demonstrated statistically significant improvements, these improvements were small, with similar proportions of patients achieving HAQ scores of ≤1.0 by 5 years with a diagnosis in 1990 compared with 2010. Levels of the visual analogue scale and the Mental Component Scores of the Short-Form 36 indicated similar, statistically non-significant levels over the 5 years, irrespective of year diagnosed. CONCLUSION: This study demonstrates improvements in inflammatory markers over time in early RA, in line with improved treatment strategies. These have not translated into similar improvements in patient-reported outcomes relating to either physical or mental health.Peer reviewedFinal Published versio

Sleep and Pain: A Systematic Review of Studies of Mediation

This is the author accepted manuscript. The final version is available on open access from Lippincott, Williams & Wilkins via the DOI in this recordOBJECTIVES: A relationship between sleep and pain is well established. A better understanding of the mechanisms that link sleep and pain intensity is urgently needed to optimise pain management interventions. The objective of this systematic review was to identify, synthesise and critically appraise studies that have investigated putative mediators on the path between sleep and pain intensity. METHODS: A systematic search of five electronic bibliographic databases (EMBASE, MEDLINE, CINAHL, PsycINFO and the Cochrane Central Register of Controlled Trials) was conducted. Eligible studies had to apply a formal test of mediation to variables on the path between a sleep variable and pain intensity or vice versa. All searches, data extraction and quality assessment were conducted by at least two independent reviewers. RESULTS: The search yielded 2,839 unique articles, nine of which were eligible. Of 13 mediation analyses, 11 investigated pathways from a sleep variable to pain intensity. Putative mediators included affect/mood, depression and/or anxiety, attention to pain, pain helplessness, stress, fatigue, and physical activity. Two analyses investigated pathways from pain intensity to a sleep variable, examining the potentially mediating role of depressive symptoms and mood. While evidence supported a mediating role for psychological and physiological aspects of emotional experiences and attentional processes, methodological limitations were common, including use of cross-sectional data and minimal adjustment for potential confounders. DISCUSSION: A growing body of research is applying mediation analysis to elucidate mechanistic pathways between sleep and pain intensity. Currently sparse evidence would be illuminated by more intensively collected longitudinal data and improvements in analysis.Systematic review registration: PROSPERO registration number CRD42016049240.This is an open access article distributed under the Creative Commons Attribution License 4.0 (CCBY), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. http://creativecommons.org/licenses/by/4.0/.Versus Arthritis Foundatio

A new arenavirus in a cluster of fatal transplant-associated diseases

Three patients who received visceral-organ transplants from a single donor on the same day died of a febrile illness 4 to 6 weeks after transplantation. Culture, polymerase-chain-reaction (PCR) and serologic assays, and oligonucleotide microarray analysis for a wide range of infectious agents were not informative. We evaluated RNA obtained from the liver and kidney transplant recipients. Unbiased high-throughput sequencing was used to identify microbial sequences not found by means of other methods. The specificity of sequences for a new candidate pathogen was confirmed by means of culture and by means of PCR, immunohistochemical, and serologic analyses. High-throughput sequencing yielded 103,632 sequences, of which 14 represented an Old World arenavirus. Additional sequence analysis showed that this new arenavirus was related to lymphocytic choriomeningitis viruses. Specific PCR assays based on a unique sequence confirmed the presence of the virus in the kidneys, liver, blood, and cerebrospinal fluid of the recipients. Immunohistochemical analysis revealed arenavirus antigen in the liver and kidney transplants in the recipients. IgM and IgG antiviral antibodies were detected in the serum of the donor. Seroconversion was evident in serum specimens obtained from one recipient at two time points

A novel albumin gene mutation (R222I) in familial dysalbuminemic hyperthyroxinemia

Context: Familial dysalbuminemic hyperthyroxinemia, characterized by abnormal circulating albuminwith increased T4 affinity, causes artefactual elevation of free T4 concentrations in euthyroid individuals. Objective: Four unrelated index cases with discordant thyroid function tests in different assay platforms were investigated. Design and Results: Laboratory biochemical assessment, radiolabeled T4 binding studies, and ALB sequencing were undertaken. 125I-T4 binding to both serum and albumin in affected individuals was markedly increased, comparable with known familial dysalbuminemic hyperthyroxinemia cases. Sequencing showed heterozygosity for a novel ALB mutation (arginine to isoleucine at codon 222, R222I) in all four cases and segregation of the genetic defect with abnormal biochemical phenotype in one family. Molecular modeling indicates that arginine 222 is located within a high-affinity T4 binding site in albumin, with substitution by isoleucine, which has a smaller side chain predicted to reduce steric hindrance, thereby facilitating T 4 and rT3 binding. When tested in current immunoassays, serum free T4 values from R222I heterozygotes were more measurably abnormal in one-step vs two-step assay architectures. Total rT3 measurements were also abnormally elevated. Conclusions: A novel mutation (R222I) in the ALB gene mediates dominantly inherited dysalbuminemic hyperthyroxinemia. Susceptibility of current free T4 immunoassays to interference by this mutant albumin suggests likely future identification of individuals with this variant binding protein

A new arenavirus in a cluster of fatal transplant-associated diseases

Three patients who received visceral-organ transplants from a single donor on the same day died of a febrile illness 4 to 6 weeks after transplantation. Culture, polymerase-chain-reaction (PCR) and serologic assays, and oligonucleotide microarray analysis for a wide range of infectious agents were not informative. We evaluated RNA obtained from the liver and kidney transplant recipients. Unbiased high-throughput sequencing was used to identify microbial sequences not found by means of other methods. The specificity of sequences for a new candidate pathogen was confirmed by means of culture and by means of PCR, immunohistochemical, and serologic analyses. High-throughput sequencing yielded 103,632 sequences, of which 14 represented an Old World arenavirus. Additional sequence analysis showed that this new arenavirus was related to lymphocytic choriomeningitis viruses. Specific PCR assays based on a unique sequence confirmed the presence of the virus in the kidneys, liver, blood, and cerebrospinal fluid of the recipients. Immunohistochemical analysis revealed arenavirus antigen in the liver and kidney transplants in the recipients. IgM and IgG antiviral antibodies were detected in the serum of the donor. Seroconversion was evident in serum specimens obtained from one recipient at two time points

Modeling Hemispheric Detonation Experiments in 2-Dimensions

Experiments have been performed with LX-17 (92.5% TATB and 7.5% Kel-F 800 binder) to study scaling of detonation waves using a dimensional scaling in a hemispherical divergent geometry. We model these experiments using an arbitrary Lagrange-Eulerian (ALE3D) hydrodynamics code, with reactive flow models based on the thermo-chemical code, Cheetah. The thermo-chemical code Cheetah provides a pressure-dependent kinetic rate law, along with an equation of state based on exponential-6 fluid potentials for individual detonation product species, calibrated to high pressures ({approx} few Mbars) and high temperatures (20000K). The parameters for these potentials are fit to a wide variety of experimental data, including shock, compression and sound speed data. For the un-reacted high explosive equation of state we use a modified Murnaghan form. We model the detonator (including the flyer plate) and initiation system in detail. The detonator is composed of LX-16, for which we use a program burn model. Steinberg-Guinan models5 are used for the metal components of the detonator. The booster and high explosive are LX-10 and LX-17, respectively. For both the LX-10 and LX-17, we use a pressure dependent rate law, coupled with a chemical equilibrium equation of state based on Cheetah. For LX-17, the kinetic model includes carbon clustering on the nanometer size scale