600 research outputs found

    Amyloid positron emission tomography candidates may focus more on benefits than risks of results disclosure

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    IntroductionGiven mounting calls to disclose biomarker test results to research participants, we explored factors underlying decisions by patients with mild cognitive impairment to receive amyloid imaging results.MethodsProspective, qualitative interviews were conducted with 59 participants (30 = mild cognitive impairment patients, 29 = care partners) from the scan arm of a randomized controlled trial on the effects of amyloid PET results disclosure in an Alzheimer Disease Research Center setting.ResultsSixty‐three percent of the participants were female, with an average age of 72.9 years, and most had greater than a high school level of education (80%). Primary motivations included: (1) better understanding one’s mild cognitive impairment etiology and prognosis to plan ahead, and (2) learning one’s brain amyloid status for knowledge’s sake, regardless of whether the information is actionable. Most participants demonstrated an adequate understanding of the scan’s limitations, yet instances of characterizing amyloid PET as a definitive test for Alzheimer’s disease occurred. Mention of potential drawbacks, such as negative psychological outcomes, was minimal, even among care partners.DiscussionFindings demonstrate a risk of disproportionate focus on possible benefits of testing among amyloid scan candidates and suggest a need to clearly emphasize the limitations of amyloid PET when counseling cognitively impaired patients and their families before testing. Future research should examine whether minimizing drawbacks at the pre‐imaging stage has adverse consequences on results disclosure.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/152635/1/dad2jdadm201805003.pd

    A randomized controlled trial of amyloid positron emission tomography results disclosure in mild cognitive impairment

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    IntroductionRecent studies suggest that Alzheimer’s disease (AD) biomarker disclosure has no discernable psychological impact on cognitively healthy persons. Far less is known about how such results affect symptomatic individuals and their caregivers.MethodsRandomized controlled trial of 82 mild cognitive impairment (MCI) patient and caregiver dyads (total n = 164) to determine the effect of receiving amyloid positron emission tomography results on understanding of, and perceived efficacy to cope with, MCI over 52 weeks of follow‐up.ResultsGains in the primary outcomes were not consistently observed. Amyloid negative patients reported greater perceived ambiguity regarding MCI at follow‐up, while moderate and sustained emotional distress was observed in patients, and to a lesser extent, caregivers, of those who were amyloid positive. There was no corresponding increase in depressive symptoms.DiscussionThese findings point to the possibility that both MCI patients and caregivers may need emotional support after the disclosure of amyloid scan results.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/163444/2/alz12129_am.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/163444/1/alz12129.pd

    TIMED Imaging Photometer Experiment (TIPE)

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    This document contains a summary of the TIMED Imaging Photometer Experiment (TIPE) instrument study at the time of the termination of project due to TIPE being de-selected from the Thermosphere, Ionosphere and Mesosphere Energetics and Dynamics (TIMED) mission

    Comparison of Pittsburgh compound B and florbetapir in cross-sectional and longitudinal studies.

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    IntroductionQuantitative in vivo measurement of brain amyloid burden is important for both research and clinical purposes. However, the existence of multiple imaging tracers presents challenges to the interpretation of such measurements. This study presents a direct comparison of Pittsburgh compound B-based and florbetapir-based amyloid imaging in the same participants from two independent cohorts using a crossover design.MethodsPittsburgh compound B and florbetapir amyloid PET imaging data from three different cohorts were analyzed using previously established pipelines to obtain global amyloid burden measurements. These measurements were converted to the Centiloid scale to allow fair comparison between the two tracers. The mean and inter-individual variability of the two tracers were compared using multivariate linear models both cross-sectionally and longitudinally.ResultsGlobal amyloid burden measured using the two tracers were strongly correlated in both cohorts. However, higher variability was observed when florbetapir was used as the imaging tracer. The variability may be partially caused by white matter signal as partial volume correction reduces the variability and improves the correlations between the two tracers. Amyloid burden measured using both tracers was found to be in association with clinical and psychometric measurements. Longitudinal comparison of the two tracers was also performed in similar but separate cohorts whose baseline amyloid load was considered elevated (i.e., amyloid positive). No significant difference was detected in the average annualized rate of change measurements made with these two tracers.DiscussionAlthough the amyloid burden measurements were quite similar using these two tracers as expected, difference was observable even after conversion into the Centiloid scale. Further investigation is warranted to identify optimal strategies to harmonize amyloid imaging data acquired using different tracers

    Screening for C3 Deficiency in Newborns Using Microarrays

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    BACKGROUND: Dried blood spot samples (DBSS) from newborns are widely used in neonatal screening for selected metabolic diseases and diagnostic possibilities for additional disorders are continuously being evaluated. Primary immunodeficiency disorders comprise a group of more than one hundred diseases, several of which are fatal early in life. Yet, a majority of the patients are not diagnosed due to lack of high-throughput screening methods. METHODOLOGY/PRINCIPAL FINDINGS: We have previously developed a system using reverse phase protein microarrays for analysis of IgA levels in serum samples. In this study, we extended the applicability of the method to include determination of complement component C3 levels in eluates from DBSS collected at birth. Normal levels of C3 were readily detected in 269 DBSS from healthy newborns, while no C3 was detected in sera and DBSS from C3 deficient patients. CONCLUSIONS/SIGNIFICANCE: The findings suggest that patients with deficiencies of specific serum proteins can be identified by analysis of DBSS using reverse phase protein microarrays.QC 20120213</p

    Flying Squirrel–associated Typhus, United States

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    In March 2002, typhus fever was diagnosed in two patients residing in West Virginia and Georgia. Both patients were hospitalized with severe febrile illnesses, and both had been recently exposed to or had physical contact with flying squirrels or flying squirrel nests. Laboratory results indicated Rickettsia prowazekii infection

    The Legionella effector WipB is a translocated Ser/Thr phosphatase that targets the host lysosomal nutrient sensing machinery

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    Legionella pneumophila infects human alveolar macrophages and is responsible for Legionnaire’s disease, a severe form of pneumonia. L. pneumophila encodes more than 300 putative effectors, which are translocated into the host cell via the Dot/Icm type IV secretion system. These effectors highjack the host’s cellular processes to allow bacterial intracellular growth and replication. Here we adopted a multidisciplinary approach to investigate WipB, a Dot/Icm effector of unknown function. The crystal structure of the N-terminal domain at 1.7 Å resolution comprising residues 25 to 344 revealed that WipB harbours a Ser/Thr phosphatase domain related to the eukaryotic phospho-protein phosphatase (PPP) family. The C-terminal domain (residues 365–524) is sufficient to pilot the effector to acidified LAMP1-positive lysosomal compartments, where WipB interacts with the v-ATPase and the associated LAMTOR1 phosphoprotein, key components of the lysosomal nutrient sensing (LYNUS) apparatus that controls the mammalian target of rapamycin (mTORC1) kinase complex at the lysosomal surface. We propose that WipB is a lysosome-targeted phosphatase that modulates cellular nutrient sensing and the control of energy metabolism during Legionella infection

    Metal Hydrides Form Halogen Bonds: Measurement of Energetics of Binding

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    The formation of halogen bonds from iodopentafluorobenzene and 1-iodoperfluorohexane to a series of bis(η5-cyclopentadienyl)metal hydrides (Cp2TaH3, 1; Cp2MH2, M = Mo, 2, M = W, 3; Cp2ReH, 4; Cp2Ta(H)CO, 5; Cp = η5-cyclopentadienyl) is demonstrated by 1H NMR spectroscopy. Interaction enthalpies and entropies for complex 1 with C6F5I and C6F13I are reported (ΔH° = −10.9 ± 0.4 and −11.8 ± 0.3 kJ/mol; ΔS° = −38 ± 2 and −34 ± 2 J/(mol·K), respectively) and found to be stronger than those for 1 with the hydrogen-bond donor indole (ΔH° = −7.3 ± 0.1 kJ/mol, ΔS° = −24 ± 1 J/(mol·K)). For the more reactive complexes 2–5, measurements are limited to determination of their low-temperature (212 K) association constants with C6F5I as 2.9 ± 0.2, 2.5 ± 0.1, <1.5, and 12.5 ± 0.3 M–1, respectively

    The aries auroral modelling campaign: characterization and modelling of an evening auroral arc observed from a rocket and a ground-based line of meridian scanners

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    An auroral arc system excited by soft electrons was studied with a combination of in situ rocket measurements and optical tomographic techniques, using data from a photometer on a horizontal, spinning rocket and a line of three meridian scanning photometers. The ground-based scanner data at 4709, 5577, 8446 and 6300 A were successfully inverted to provide a set of volume emission rate distributions in the plane of the rocket trajectory, with a basic time resolution of 24 s. Volume emission rate profiles, derived from these distributions peaked at about 150 km for 5577 and 4709 A, while the 8446 A emission peaked at about 170 km with a more extended height distribution. The rocket photometer gave comparable volume emission rate distributions for the 3914 A emission as reported in a separate paper by McDade et al. (1991, Planet. Space Sci. 39, 895). Instruments on the rocket measured the primary electron flux during the flight and, in particular, the flux precipitating into the auroral arc overflown at apogee (McEwen et al., 1991; in preparation). The local electron density and temperature were measured by probes on the rocket (Margot and McNamara (1991; Can. J. Phys. 69, 950). The electron density measurements on the downleg were modelled using ion production rate data derived from the optical results. Model calculations of the emission height profile based on the measured electron flux agree with the observed profiles. The height distribution of the N2+ emission in the equatorward band, through which the rocket passed during the descent, was measured by both the rocket and the ground-based tomographic techniques and the results are in good agreement. Comparison of these profiles with model profiles indicates that the exciting primary spectrum may be represented by an accelerated Maxwellian or a Gaussian distribution centered at about 3 keV. This distribution is close to what would be obtained if the electron flux exciting the poleward form were accelerated by a 1-2 kV upward potential drop. The relative height profiles for the volume emission rate of the 5577 A OI emission and the 4709 A N2+ emission were almost indistinguishable from each other for both the forms measured, with ratios in the range 38-50; this is equivalent to I(5577)/I(4278) ratios of 8-10. The auroral intensities and intensity ratios measured in the magnetic zenith from the ground during the period before and during the rocket flight are consistent with the primary electron fluxes and height distributions measured from the rocket. Values of I(5577)/I(4278) in the range 8-10 were also measured directly by the zenith ground photometers over which the arc system passed. These values are slightly higher than those reported by Gattinger and Vallance-Jones (1972) and this may possibly indicate an enhancement of the atomic oxygen concentration at the time of the flight. Such an enhancement would be consistent with our result, that the observed values of I(5577) and I(8446) are also significantly higher than those modelled on the basis of the electron flux spectrum measured at apogee.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/29020/1/0000050.pd
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