13 research outputs found
Using Digital Radiography To Image Liquid Nitrogen in Voids
Digital radiography by use of (1) a field-portable x-ray tube that emits low-energy x rays and (2) an electronic imaging x-ray detector has been found to be an effective technique for detecting liquid nitrogen inside voids in thermal-insulation panels. The technique was conceived as a means of investigating cryopumping (including cryoingestion) as a potential cause of loss of thermal insulation foam from space-shuttle external fuel tanks. The technique could just as well be used to investigate cryopumping and cryoingestion in other settings. In images formed by use of low-energy x-rays, one can clearly distinguish between voids filled with liquid nitrogen and those filled with gaseous nitrogen or other gases. Conventional film radiography is of some value, but yields only non-real-time still images that do not show time dependences of levels of liquids in voids. In contrast, the present digital radiographic technique yields a succession of images in real time at a rate of about 10 frames per second. The digitized images can be saved for subsequent analysis to extract data on time dependencies of levels of liquids and, hence, of flow paths and rates of filling and draining. The succession of images also amounts to a real-time motion picture that can be used as a guide to adjustment of test conditions
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Disruption of the homeodomain transcription factor orthopedia homeobox (Otp) is associated with obesity and anxiety.
OBJECTIVE: Genetic studies in obese rodents and humans can provide novel insights into the mechanisms involved in energy homeostasis. METHODS: In this study, we genetically mapped the chromosomal region underlying the development of severe obesity in a mouse line identified as part of a dominant N-ethyl-N-nitrosourea (ENU) mutagenesis screen. We characterized the metabolic and behavioral phenotype of obese mutant mice and examined changes in hypothalamic gene expression. In humans, we examined genetic data from people with severe early onset obesity. RESULTS: We identified an obese mouse heterozygous for a missense mutation (pR108W) in orthopedia homeobox (Otp), a homeodomain containing transcription factor required for the development of neuroendocrine cell lineages in the hypothalamus, a region of the brain important in the regulation of energy homeostasis. OtpR108W/+ mice exhibit increased food intake, weight gain, and anxiety when in novel environments or singly housed, phenotypes that may be partially explained by reduced hypothalamic expression of oxytocin and arginine vasopressin. R108W affects the highly conserved homeodomain, impairs DNA binding, and alters transcriptional activity in cells. We sequenced OTP in 2548 people with severe early-onset obesity and found a rare heterozygous loss of function variant in the homeodomain (Q153R) in a patient who also had features of attention deficit disorder. CONCLUSIONS: OTP is involved in mammalian energy homeostasis and behavior and appears to be necessary for the development of hypothalamic neural circuits. Further studies will be needed to investigate the contribution of rare variants in OTP to human energy homeostasis
O2–01–08: Comparing the impact of a condensed vs extended protocol for disclosure of APOE to relatives of patients with AD: The reveal study
Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/153026/1/alzjjalz200704051.pd
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Validating Biobehavioral Technologies for Use in Clinical Psychiatry
The last decade has witnessed the development of sophisticated biobehavioral and genetic, ambulatory, and other measures that promise unprecedented insight into psychiatric disorders. As yet, clinical sciences have struggled with implementing these objective measures and they have yet to move beyond “proof of concept.” In part, this struggle reflects a traditional, and conceptually flawed, application of traditional psychometrics (i.e., reliability and validity) for evaluating them. This paper focuses on “resolution,” concerning the degree to which changes in a signal can be detected and quantified, which is central to measurement evaluation in informatics, engineering, computational and biomedical sciences. We define and discuss resolution in terms of traditional reliability and validity evaluation for psychiatric measures, then highlight its importance in a study using acoustic features to predict self-injurious thoughts/behaviors (SITB). This study involved tracking natural language and self-reported symptoms in 124 psychiatric patients: (a) over 5–14 recording sessions, collected using a smart phone application, and (b) during a clinical interview. Importantly, the scope of these measures varied as a function of time (minutes, weeks) and spatial setting (i.e., smart phone vs. interview). Regarding reliability, acoustic features were temporally unstable until we specified the level of temporal/spatial resolution. Regarding validity, accuracy based on machine learning of acoustic features predicting SITB varied as a function of resolution. High accuracy was achieved (i.e., ~87%), but only when the acoustic and SITB measures were “temporally-matched” in resolution was the model generalizable to new data. Unlocking the potential of biobehavioral technologies for clinical psychiatry will require careful consideration of resolution
Human loss-of-function variants in the serotonin 2C receptor associated with obesity and maladaptive behavior.
Funder: National Institute for Health Research (NIHR)Serotonin reuptake inhibitors and receptor agonists are used to treat obesity, anxiety and depression. Here we studied the role of the serotonin 2C receptor (5-HT2CR) in weight regulation and behavior. Using exome sequencing of 2,548 people with severe obesity and 1,117 control individuals without obesity, we identified 13 rare variants in the gene encoding 5-HT2CR (HTR2C) in 19 unrelated people (3 males and 16 females). Eleven variants caused a loss of function in HEK293 cells. All people who carried variants had hyperphagia and some degree of maladaptive behavior. Knock-in male mice harboring a human loss-of-function HTR2C variant developed obesity and reduced social exploratory behavior; female mice heterozygous for the same variant showed similar deficits with reduced severity. Using the 5-HT2CR agonist lorcaserin, we found that depolarization of appetite-suppressing proopiomelanocortin neurons was impaired in knock-in mice. In conclusion, we demonstrate that 5-HT2CR is involved in the regulation of human appetite, weight and behavior. Our findings suggest that melanocortin receptor agonists might be effective in treating severe obesity in individuals carrying HTR2C variants. We suggest that HTR2C should be included in diagnostic gene panels for severe childhood-onset obesity
A randomized noninferiority trial of condensed protocols for genetic risk disclosure of Alzheimer's disease
IntroductionConventional multisession genetic counseling is currently recommended when disclosing apolipoprotein E (APOE) genotype for the risk of Alzheimer’s disease (AD) in cognitively normal individuals. The objective of this study was to evaluate the safety of brief disclosure protocols for disclosing APOE genotype for the risk of AD.MethodsA randomized, multicenter noninferiority trial was conducted at four sites. Participants were asymptomatic adults having a firstâ degree relative with AD. A standard disclosure protocol by genetic counselors (SPâ GC) was compared with condensed protocols, with disclosures by genetic counselors (CPâ GC) and by physicians (CPâ MD). Preplanned coâ primary outcomes were anxiety and depression scales 12 months after disclosure.ResultsThree hundred and fortyâ three adults (mean age 58.3, range 33â 86 years, 71% female, 23% African American) were randomly assigned to the SPâ GC protocol (n = 115), CPâ GC protocol (n = 116), or CPâ MD protocol (n = 112). Mean postdisclosure scores on all outcomes were well below cutâ offs for clinical concern across protocols. Comparing CPâ GC with SPâ GC, the 97.5% upper confidence limits at 12 months after disclosure on coâ primary outcomes of anxiety and depression ranged from a difference of 1.2 to 2.0 in means (all P < .001 on noninferiority tests), establishing noninferiority for condensed protocols. Results were similar between European Americans and African Americans.ConclusionsThese data support the safety of condensed protocols for APOE disclosure for those free of severe anxiety or depression who are actively seeking such information