Radiation Metrology of Small Animal Molecular Imaging and Molecular Radiotherapy Using mirco-PET/CT

Genetically engineered animal models of diseases are increasingly recapitulating human diseases. With this, in vivo preclinical imaging of small laboratory animals has emerged as a critical component of biomedical research because of its noninvasive nature allowing serial assay of animal models and monitoring its safety and effectiveness over the history of the disease. The concept of quantitative molecular imaging is to go beyond displaying images in digital form and to consider the image and extract quantitative information that allows for a better understanding of disease progression and treatment. The aim of this work is to demonstrate the need for the metrology of molecular imaging of animal models using micro-PET/CT devices. System characteristics are determined within each subsystem, micro-PET and micro-CT, independent of each other, and as integrated systems. The characterization of tissues, composition and density, by micro-CT was determined along with the noise level of the unit. Moreover, the nominal superficial and deep absorbed doses were estimated to assess the confounding effect of multiple scans in animal studies. The Q value, used to convert counts per milliliter to activity per milliliter, was estimated to assess the observed activity present in the animal. The resolution of the micro-PET subsystem was also estimated using a modified Derenzo phantom to assess the uncertainty of the activity distribution within tissues. Once both modalities were characterized separately the coordinate system of each individual system was checked for spatial accuracy using a cross capillary method. The offset values were then used to establish the same coordinate system for co-registration. Once both micro-PET and micro-CT image data sets had been verified, they were used to generate a voxel image of the subject for use in the Monte Carlo program, MCNP6, where an absorbed dose map was generated for the radiolabeled compound. Two basic examples are given to demonstrate the use of the voxelized absorbed dose maps for calculating the absorbed dose to any segmented organ of interest, across longitudinal studies. In this way, it was shown that an animal-specific model can be used to accurately calculate the absorbed dose for each time point during a study

Radiation Metrology of Small Animal Molecular Imaging and Molecular Radiotherapy Using mirco-PET/CT

Genetically engineered animal models of diseases are increasingly recapitulating human diseases. With this, in vivo preclinical imaging of small laboratory animals has emerged as a critical component of biomedical research because of its noninvasive nature allowing serial assay of animal models and monitoring its safety and effectiveness over the history of the disease. The concept of quantitative molecular imaging is to go beyond displaying images in digital form and to consider the image and extract quantitative information that allows for a better understanding of disease progression and treatment. The aim of this work is to demonstrate the need for the metrology of molecular imaging of animal models using micro-PET/CT devices. System characteristics are determined within each subsystem, micro-PET and micro-CT, independent of each other, and as integrated systems. The characterization of tissues, composition and density, by micro-CT was determined along with the noise level of the unit. Moreover, the nominal superficial and deep absorbed doses were estimated to assess the confounding effect of multiple scans in animal studies. The Q value, used to convert counts per milliliter to activity per milliliter, was estimated to assess the observed activity present in the animal. The resolution of the micro-PET subsystem was also estimated using a modified Derenzo phantom to assess the uncertainty of the activity distribution within tissues. Once both modalities were characterized separately the coordinate system of each individual system was checked for spatial accuracy using a cross capillary method. The offset values were then used to establish the same coordinate system for co-registration. Once both micro-PET and micro-CT image data sets had been verified, they were used to generate a voxel image of the subject for use in the Monte Carlo program, MCNP6, where an absorbed dose map was generated for the radiolabeled compound. Two basic examples are given to demonstrate the use of the voxelized absorbed dose maps for calculating the absorbed dose to any segmented organ of interest, across longitudinal studies. In this way, it was shown that an animal-specific model can be used to accurately calculate the absorbed dose for each time point during a study

Black Holes and Random Matrices

We argue that the late time behavior of horizon fluctuations in large anti-de Sitter (AdS) black holes is governed by the random matrix dynamics characteristic of quantum chaotic systems. Our main tool is the Sachdev-Ye-Kitaev (SYK) model, which we use as a simple model of a black hole. We use an analytically continued partition function $|Z(\beta +it)|^2$ as well as correlation functions as diagnostics. Using numerical techniques we establish random matrix behavior at late times. We determine the early time behavior exactly in a double scaling limit, giving us a plausible estimate for the crossover time to random matrix behavior. We use these ideas to formulate a conjecture about general large AdS black holes, like those dual to 4D super-Yang-Mills theory, giving a provisional estimate of the crossover time. We make some preliminary comments about challenges to understanding the late time dynamics from a bulk point of view.Comment: 73 pages, 15 figures, minor errors correcte

A novel codon insert in protease of clade B HIV type 1.

A novel combination of three codon inserts in the pol coding region of HIV-1 RNA was identified in a highly antiretroviral experienced study subject with HIV-1 infection. A one codon insert was observed in the protease region between codon 40 and 41 simultaneously with a two codon insert present in the reverse transcriptase region at codon 69

Underflight calibration of SOHO/CDS and Hinode/EIS with EUNIS-07

Flights of Goddard Space Flight Center's Extreme-Ultraviolet Normal-Incidence Spectrograph (EUNIS) sounding rocket in 2006 and 2007 provided updated radiometric calibrations for SOHO/CDS and Hinode/EIS. EUNIS carried two independent imaging spectrographs covering wavebands of 300-370 A in first order and 170-205 A in second order. After each flight, end-to-end radiometric calibrations of the rocket payload were carried out in the same facility used for pre-launch calibrations of CDS and EIS. During the 2007 flight, EUNIS, SOHO CDS and Hinode EIS observed the same solar locations, allowing the EUNIS calibrations to be directly applied to both CDS and EIS. The measured CDS NIS 1 line intensities calibrated with the standard (version 4) responsivities with the standard long-term corrections are found to be too low by a factor of 1.5 due to the decrease in responsivity. The EIS calibration update is performed in two ways. One is using the direct calibration transfer of the calibrated EUNIS-07 short wavelength (SW) channel. The other is using the insensitive line pairs, in which one member was observed by EUNIS-07 long wavelength (LW) channel and the other by EIS in either LW or SW waveband. Measurements from both methods are in good agreement, and confirm (within the measurement uncertainties) the EIS responsivity measured directly before the instrument's launch. The measurements also suggest that the EIS responsivity decreased by a factor of about 1.2 after the first year of operation. The shape of the EIS SW response curve obtained by EUNIS-07 is consistent with the one measured in laboratory prior to launch. The absolute value of the quiet-Sun He II 304 A intensity measured by EUNIS-07 is consistent with the radiance measured by CDS NIS in quiet regions near the disk center and the solar minimum irradiance obtained by CDS NIS and SDO/EVE recently.Comment: 16 pages, 14 figures, 5 tables, accepted by ApJ Supplement (Sep. 2011

Translational treatment paradigm for managing non‐unions secondary to radiation injury utilizing adipose derived stem cells and angiogenic therapy

BackgroundBony non‐unions arising in the aftermath of collateral radiation injury are commonly managed with vascularized free tissue transfers. Unfortunately, these procedures are invasive and fraught with attendant morbidities. This study investigated a novel, alternative treatment paradigm utilizing adipose‐derived stem cells (ASCs) combined with angiogenic deferoxamine (DFO) in the rat mandible.MethodsRats were exposed to a bioequivalent dose of radiation and mandibular osteotomy. Those exhibiting non‐unions were subsequently treated with surgical debridement alone or debridement plus combination therapy. Radiographic and biomechanical outcomes were assessed after healing.ResultsSignificant increases in biomechanical strength and radiographic metrics were observed in response to combination therapy (p < .05). Importantly, combined therapy enabled a 65% reduction in persisting non‐unions when compared to debridement alone.ConclusionWe support the continued investigation of this promising combination therapy in its potential translation for the management of radiation‐induced bony pathology. © 2015 Wiley Periodicals, Inc. Head Neck 38: E837–E843, 2016Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/137613/1/hed24110.pd

PRimary Care Opioid Use Disorders treatment (PROUD) trial protocol: a pragmatic, cluster-randomized implementation trial in primary care for opioid use disorder treatment

BACKGROUND: Most people with opioid use disorder (OUD) never receive treatment. Medication treatment of OUD in primary care is recommended as an approach to increase access to care. The PRimary Care Opioid Use Disorders treatment (PROUD) trial tests whether implementation of a collaborative care model (Massachusetts Model) using a nurse care manager (NCM) to support medication treatment of OUD in primary care increases OUD treatment and improves outcomes. Specifically, it tests whether implementation of collaborative care, compared to usual primary care, increases the number of days of medication for OUD (implementation objective) and reduces acute health care utilization (effectiveness objective). The protocol for the PROUD trial is presented here. METHODS: PROUD is a hybrid type III cluster-randomized implementation trial in six health care systems. The intervention consists of three implementation strategies: salary for a full-time NCM, training and technical assistance for the NCM, and requiring that three primary care providers have DEA waivers to prescribe buprenorphine. Within each health system, two primary care clinics are randomized: one to the intervention and one to Usual Primary Care. The sample includes all patients age 16-90 who visited the randomized primary care clinics from 3 years before to 2 years after randomization (anticipated to be \u3e 170,000). Quantitative data are derived from existing health system administrative data, electronic medical records, and/or health insurance claims ( electronic health records, [EHRs]). Anonymous staff surveys, stakeholder debriefs, and observations from site visits, trainings and technical assistance provide qualitative data to assess barriers and facilitators to implementation. The outcome for the implementation objective (primary outcome) is a clinic-level measure of the number of patient days of medication treatment of OUD over the 2 years post-randomization. The patient-level outcome for the effectiveness objective (secondary outcome) is days of acute care utilization [e.g. urgent care, emergency department (ED) and/or hospitalizations] over 2 years post-randomization among patients with documented OUD prior to randomization. DISCUSSION: The PROUD trial provides information for clinical leaders and policy makers regarding potential benefits for patients and health systems of a collaborative care model for management of OUD in primary care, tested in real-world diverse primary care settings

Development of an improved blood-stage malaria vaccine targeting the essential RH5-CyRPA-RIPR invasion complex

Reticulocyte-binding protein homologue 5 (RH5), a leading blood-stage Plasmodium falciparum malaria vaccine target, interacts with cysteine-rich protective antigen (CyRPA) and RH5-interacting protein (RIPR) to form an essential heterotrimeric “RCR-complex”. We investigate whether RCR-complex vaccination can improve upon RH5 alone. Using monoclonal antibodies (mAbs) we show that parasite growth-inhibitory epitopes on each antigen are surface-exposed on the RCR-complex and that mAb pairs targeting different antigens can function additively or synergistically. However, immunisation of female rats with the RCR-complex fails to outperform RH5 alone due to immuno-dominance of RIPR coupled with inferior potency of anti-RIPR polyclonal IgG. We identify that all growth-inhibitory antibody epitopes of RIPR cluster within the C-terminal EGF-like domains and that a fusion of these domains to CyRPA, called “R78C”, combined with RH5, improves the level of in vitro parasite growth inhibition compared to RH5 alone. These preclinical data justify the advancement of the RH5.1 + R78C/Matrix-M™ vaccine candidate to Phase 1 clinical trial

Research priorities in the field of posttraumatic pain and disability: Results of a transdisciplinary consensus-generating workshop

© Copyright 2016 David M.Walton et al. Background. Chronic or persistent pain and disability following noncatastrophic \u27musculoskeletal\u27 (MSK) trauma is a pervasive public health problem. Recent intervention trials have provided little evidence of benefit from several specific treatments for preventing chronic problems. Such findings may appear to argue against formal targeted intervention for MSK traumas. However, these negative findings may reflect a lack of understanding of the causal mechanisms underlying the transition from acute to chronic pain, rendering informed and objective treatment decisions difficult. The Canadian Institutes of Health Research (CIHR) Institute ofMusculoskeletalHealth and Arthritis (IMHA) has recently identified better understanding of causalmechanisms as one of three priority foci of their most recent strategic plan. Objectives. A 2-day invitation-only active participation workshop was held inMarch 2015 that included 30 academics, clinicians, and consumers with the purpose of identifying consensus research priorities in the field of trauma-relatedMSK pain and disability, prediction, and prevention. Methods. Conversations were recorded, explored thematically, and member-checked for accuracy. Results. From the discussions, 13 themes were generated that ranged from a focus on identifying causal mechanisms and models to challenges with funding and patient engagement. Discussion. Novel priorities included the inclusion of consumer groups in research from the early conceptualization and design stages and interdisciplinary longitudinal studies that include evaluation of integrated phenotypes and mechanisms