Indiana Consortium for Innovation in Biomedical Imaging

poster abstractThe Indiana Consortium for Innovation in Biomedical Imaging (Indiana-CIBI) has been established to leverage the biomedical imaging strengths of several major academic institutions throughout Indiana. This initiative provides the environment, infrastructure, and resources necessary for establishing one of the premier translational, research and educational imaging networks in the United States. The Indiana-CIBI will facilitate the identification of crucial clinical problems and unmet research needs; stimulate the development of innovative solutions; and help translate optimized patient care services into practice at partner health-care delivery facilities. The objectives of the Indiana-CIBI include: Providing national leadership in translation from concept to practice. Encouraging targeted problem-driven technology development. Nurturing innovation and progress through facile access to advanced resources. Focusing Indiana state-wide interdisciplinary partnerships in the development of new, innovative imaging technologies and the utilization of imaging resources. Cultivating investigator engagement and channeling intrinsic motivation. The stated objectives of the Indiana-CIBI define the operational model for the consortium. Key steps in the innovation-focused process include: 1) Identification of critical clinical or biomedical research needs by physician or biomedical investigator(s); 2) Creation of innovative solutions through innovation incubator teams, imaging innovation marathons, and crowdsourcing solicitations; 3) Translation to practice through a large medical physics/radiology network; and 4) Translation to advanced core services through the Indiana-CTSI core resource network. Critical success factors for the Indiana-CIBI include tight integration within academic health care facilities, consolidation of fragmented resources, and expansion of critical support resources, eliminating the need to duplicate some types of services across multiple sites in Indiana. For further information regarding the Indiana Consortium for Innovation in Biomedical Imaging and its programs please contact Mark Holland or Gary Hutchins at [email protected]. The Indiana-CIBI is supported, in part, by contributions from the IUPUI Office of the Vice Chancellor for Research

Research Center for Quantitative Renal Imaging

poster abstractMission: The mission of the Research Center for Quantitative Renal Imaging is to provide a focused research environment and resource for the development, implementation, and dissemination of innovative, quantitative imaging methods designed to assess the status of and mechanisms associated with acute and chronic kidney disease and evaluate efficacy of therapeutic interventions. Nature of the Center: This Research Center provides a formal mechanism to link research programs focused on understanding the fundamental mechanisms associated with kidney diseases with those associated with the development of advanced imaging methods and quantitative analyses into a focused effort dedicated toward the development and implementation of quantitative renal imaging methods. Goals of the IUPUI Research Center for Quantitative Renal Imaging: Identify, develop, and implement innovative imaging methods that provide quantitative imaging biomarkers for assessing and inter-relating renal structure, function, hemodynamics and underlying tissue micro-environmental factors contributing to kidney disease. Establish an environment that facilitates and encourages interdisciplinary collaborations among investigators and offers research support to investigators focused on developing and utilizing innovative quantitative imaging methods in support of kidney disease research. Provide a resource to inform the greater research and healthcare communities of advances in quantitative renal imaging and its potential for enhanced patient management and care. Offer an imaging research resource to companies engaged in product development associated with the diagnosis and treatment of kidney diseases. Further Information: For further information regarding the IUPUI Research Center for Quantitative RenalImaging and its funding programs please visit http://www.renalimaging.iupui.edu/ or contact the Center at [email protected]. Acknowledgments: The IUPUI Research Center for Quantitative Renal Imaging is supported by contributions from the IUPUI Signature Center Initiative, the Department of Radiology & Imaging Sciences; the Division of Nephrology, the IUPUI School of Science, the IUPUI School of Engineering & Technology, and the Indiana Clinical and Translational Sciences Institute (CTSI)

NASA's Astronant Family Support Office

During the NASAMir program of the 1990s and due to the challenges inherent in the International Space Station training schedule and operations tempo, it was clear that a special focus on supporting families was a key to overall mission success for the ISS crewmembers pre, in and postflight. To that end, in January 2001 the first Family Services Coordinator was hired by the Behavioral Health and Performance group at NASA JSC and matrixed from Medical Operations into the Astronaut Office's organization. The initial roles and responsibilities were driven by critical needs, including facilitating family communication during training deployments, providing missionspecific and other relevant trainings for spouses, serving as liaison for families with NASA organizations such as Medical Operations, NASA management and the Astronaut Office, and providing assistance to ensure success of an Astronaut Spouses Group. The role of the Family Support Office (FSO) has modified as the ISS Program matured and the needs of families changed. The FSO is currently an integral part of the Astronaut Office's ISS Operations Branch. It still serves the critical function of providing information to families, as well as being the primary contact for US and international partner families with resources at JSC. Since crews launch and return on Russian vehicles, the FSO has the added responsibility for coordinating with Flight Crew Operations, the families, and their guests for Soyuz launches, landings, and Direct Return to Houston postflight. This presentation will provide a summary of the family support services provided for astronauts, and how they have changed with the Program and families the FSO serves. Considerations for future FSO services will be discussed briefly as NASA proposes one year missions and beyond ISS missions. Learning Objective: 1) Obtain an understanding of the reasons a Family Support Office was important for NASA. 2) Become familiar with the services provided for astronauts and their families and how they changed with the Program and family needs

Lipidomic QTL in Diversity Outbred mice identifies a novel function for α/β hydrolase domain 2 (Abhd2) as an enzyme that metabolizes phosphatidylcholine and cardiolipin.

We and others have previously shown that genetic association can be used to make causal connections between gene loci and small molecules measured by mass spectrometry in the bloodstream and in tissues. We identified a locus on mouse chromosome 7 where several phospholipids in liver showed strong genetic association to distinct gene loci. In this study, we integrated gene expression data with genetic association data to identify a single gene at the chromosome 7 locus as the driver of the phospholipid phenotypes. The gene encodes α/β-hydrolase domain 2 (Abhd2), one of 23 members of the ABHD gene family. We validated this observation by measuring lipids in a mouse with a whole-body deletion of Abhd2. The Abhd2KO mice had a significant increase in liver levels of phosphatidylcholine and phosphatidylethanolamine. Unexpectedly, we also found a decrease in two key mitochondrial lipids, cardiolipin and phosphatidylglycerol, in male Abhd2KO mice. These data suggest that Abhd2 plays a role in the synthesis, turnover, or remodeling of liver phospholipids

Inhibition of De Novo Ceramide Synthesis Reverses Diet-Induced Insulin Resistance and Enhances Whole-Body Oxygen Consumption

OBJECTIVE - It has been proposed that skeletal muscle insulin resistance arises from the accumulation of intramyocellular lipid metabolites that impede insulin signaling, including diacylglycerol and ceramide. We determined the role of de novo ceramide synthesis in mediating muscle insulin resistance. RESEARCH DESIGN AND METHODS - Mice were subjected to 12 weeks of diet-induced obesity (DIO), and then treated for 4 weeks with myriocin, an inhibitor of serine palmitoyl transferase-1 (SPT1), the rate-limiting enzyme of de novo ceramide synthesis. RESULTS - After 12 weeks of DIO, C57BL/6 mice demonstrated a doubling in gastrocnemius ceramide content, which was completely reversed (141.5 ± 15.8 vs. 94.6 ± 10.2 nmol/g dry wt) via treatment with myriocin, whereas hepatic ceramide content was unaffected by DIO. Interestingly, myriocin treatment did not alter the DIO-associated increase in gastrocnemius diacyglycerol content, and the only correlation observed between lipid metabolite accumulation and glucose intolerance occurred with ceramide (R = 0.61). DIO mice treated with myriocin showed a complete reversal of glucose intolerance and insulin resistance which was associated with enhanced insulin-stimulated Akt and glycogen synthase kinase 3β phosphorylation. Furthermore, myriocin treatment also decreased intramyocellular ceramide content and prevented insulin resistance development in db/db mice. Finally, myriocin-treated DIO mice displayed enhanced oxygen consumption rates (3,041 ± 124 vs. 2,407 ± 124 ml/kg/h) versus their control counterparts. CONCLUSIONS - Our results demonstrate that the intramyocellular accumulation of ceramide correlates strongly with the development of insulin resistance, and suggests that inhibition of SPT1 is a potentially promising target for the treatment of insulin resistance. © 2010 by the American Diabetes Association.link_to_subscribed_fulltex

The JCMT Gould Belt Survey: Evidence for radiative heating in Serpens MWC 297 and its influence on local star formation

We present SCUBA-2 450micron and 850micron observations of the Serpens MWC 297 region, part of the JCMT Gould Belt Survey of nearby star-forming regions. Simulations suggest that radiative feedback influences the star-formation process and we investigate observational evidence for this by constructing temperature maps. Maps are derived from the ratio of SCUBA-2 fluxes and a two component model of the JCMT beam for a fixed dust opacity spectral index of beta = 1.8. Within 40 of the B1.5Ve Herbig star MWC 297, the submillimetre fluxes are contaminated by free-free emission with a spectral index of 1.03+-0.02, consistent with an ultra-compact HII region and polar winds/jets. Contamination accounts for 73+-5 per cent and 82+-4 per cent of peak flux at 450micron and 850micron respectively. The residual thermal disk of the star is almost undetectable at these wavelengths. Young Stellar Objects are confirmed where SCUBA-2 850micron clumps identified by the fellwalker algorithm coincide with Spitzer Gould Belt Survey detections. We identify 23 objects and use Tbol to classify nine YSOs with masses 0.09 to 5.1 Msun. We find two Class 0, one Class 0/I, three Class I and three Class II sources. The mean temperature is 15+-2K for the nine YSOs and 32+-4K for the 14 starless clumps. We observe a starless clump with an abnormally high mean temperature of 46+-2K and conclude that it is radiatively heated by the star MWC 297. Jeans stability provides evidence that radiative heating by the star MWC 297 may be suppressing clump collapse.Comment: 24 pages, 13 figures, 7 table

Heterogeneity of primary outcome measures used in clinical trials of treatments for intermediate, posterior, and panuveitis

BACKGROUND: Uveitis describes a heterogeneous group of conditions characterized by intraocular inflammation. Since most of the sight-threatening forms of uveitis are individually rare, there has been an increasing tendency for clinical trials to group distinct uveitis syndromes together despite clear variations in phenotype which may reflect real aetiological and pathogenetic differences. Furthermore this grouping of distinct syndromes, and the range of manifestations within each uveitis syndrome, leads to a wide range of possible outcome measures. In this study we wished to review the degree of consensus or otherwise in the choice of primary outcome measures for registered clinical trials related to uveitis. METHODS: Systematic review of data provided in clinical trial registries describing clinical trials dealing with medical treatment of intermediate, posterior, or panuveitis through 01 October 2013. We reviewed 15 on-line clinical trial registries approved by the International Committee of Medical Journal Editors. We identified all that met the following inclusion criteria: prospective, interventional design; target populations with intermediate, posterior or panuveitis; and one or more pre-specified outcome measures that were related to uveitis. Primary outcome measures were classified in terms of type (efficacy or safety or both; single, composite, or multiple); dimension (disease activity, disease damage, measured or patient-reported visual function); and domain (the specific study variable being measured). RESULTS: Of 195 registered uveitis studies, we identified 104 clinical trials that met inclusion criteria. There were 14 different domains used as primary outcome measures. Among clinical trials that utilized primary outcome measures of treatment efficacy (n = 94), 70 (74 %) used a measure of disease activity (vitreous haze in 40/70 [57 %]; macular oedema in 19/70 [27 %]) and 49 (70 %) used a measure of visual function (visual acuity in all cases). Multiple primary outcome measures were used in 23 (22 %) of 104 clinical trials. With regard to quality, in 12 (12 %) of 104 clinical trials, outcome measures were poorly defined. No clinical trial utilized a patient-reported study variable as primary outcome measure. CONCLUSIONS: This systematic review highlights the heterogeneity of outcome measures used in recent clinical trials for intermediate, posterior, and panuveitis. Current designs prioritize clinician-observed measures of disease activity and measurement of visual function as outcome measures. This apparent lack of consensus regarding outcome measures for the study of uveitis is a concern, as it prevents comparison of studies and meta-analyses, and weakens the evidence available to stake-holders, from patients to clinicians to regulators, regarding the efficacy and value of a given treatment