Recent human PET studies with the monoamine oxidase B (MAO B) tracer 11CL-deprenyl show that the rapid rate of radiotracer trapping relative to transport reduces the sensitivity of the tracer in ...regions of high MAO B concentration. This study investigates the use of deuterium substituted L-deprenyl (11CL-deprenyl-D2) to reduce the rate of trapping in tissue and to improve sensitivity.
Five normal subjects (43-64 yr) were studied with 11CL-deprenyl and 11CL-deprenyl-D2 on the same day. Time-activity data from different brain regions and the arterial plasma were analyzed using a three-compartment model as well as graphical analysis for irreversible systems.
For both tracers, maximum radioactivity accumulation occurred at about 5 min. For 11CL-deprenyl, 11C concentration peaked at 5 min and remained constant throughout the study. With 11CL-deprenyl-D2, peak 11C concentration also occurred at about 5 min but was followed by an initial washout. Carbon-11 concentration generally plateaued from 30 to 60 min. The plateau for 11CL-deprenyl was higher than the plateau for 11CL-deprenyl-D2. Data analysis by a three-compartment model and by graphical analysis showed that deuterium substitution: (a) does not affect plasma to tissue transport (K1); (b) reduces the rate of trapping of 11C in all brain regions; (c) facilitates the separation of model terms related to radiotracer delivery from radiotracer trapping in tissue; and (d) improves tracer sensitivity.
This study demonstrates that deuterium substitution causes a significant reduction in the rate of trapping of labeled deprenyl, providing a direct link between radiotracer uptake and MAO B in the human brain and enhancing tracer sensitivity to changes in MAO B concentration.
Recently, resistive random access memory (RRAM) using various metal oxides (i.e., SiO 2 1, HfO 2 , NiO2, Al 2 O 3 , NbO) have attracted a lot of attentions since the current nonvolatile memory (NVM) ...approaching the scaling limits. Meanwhile, the selector devices are essential to address the sneak path issue which causing the reading errors in high-packing-density cross-bar RRAM array. Several types of selector devices with threshold switching (TS) behavior has been investigated, such as rectifying diode3, varistors4, ovonic TS (OTS)5, metal-insulator transition (MIT)6 etc. In this work, the characteristics of electrically driven MIT (E-MIT) in both Nb-doped SrTiO 3 and HfO 2 -based selector devices has been investigated.
Abstract
Objective:
To evaluate changes in healthcare resource use and costs after initiating pregabalin or duloxetine in employees with pain associated with diabetic peripheral neuropathy (pDPN).
...Methods:
Employees (18-64 years old) with a DPN diagnosis and at least one pDPN-related pain medication claim were identified using the MarketScan Commercial Database (2005-2008). Propensity scored matched pregabalin and duloxetine new starts were evaluated in the 6-month pre- and 6-month post-initiation periods. Study outcomes including imputed medically-related work loss, prescription and healthcare utilization, and associated expenditures were analyzed using univariate statistics and multivariate models in a difference-in-difference approach.
Results:
A total of 473 employees in each treatment group were identified. Mean age was 53.6 (SD 7.0) years for pregabalin and 53.5 (SD 7.4) years for duloxetine. There were no pre-index differences between groups. Adjusted marginal effects were not statistically significant for pre-to-post changes in opioid utilization (p = 0.328), number of pDPN-related analgesic medications (p = 0.506), all-cause healthcare costs (p = 0.895), indirect costs (p = 0.324), or pDPN-attributable expenditures (p = 0.359).
Limitations:
Claims analysis is limited in accounting for all patient and plan differences, and by the reliability of medical claims for diagnosis coding. The sample size of the matched cohorts may have limited the power of the analysis to detect differences.
Conclusions:
There were no significant pre-to-post differences between pregabalin and duloxetine treatment groups in pDPN-related analgesic medication use, or pDPN-attributable, all-cause, and indirect expenditures.
In this work, we investigated SiO(x)-based interfacial resistive switching in planar metal-insulator-metal structures using physical/chemical/electrical analyses. This work helps clarify the ...interfacial reaction process and mechanism in SiO(x), and also shows the potential for high temperature operation in future nonvolatile memory applications.
Multiplex PCR methods are attractive to clinical laboratories wanting to broaden their detection of respiratory viral pathogens in clinical specimens. However, multiplexed assays must be well ...optimized to retain or improve upon the analytic sensitivity of their singleplex counterparts. In this experiment, the lower limit of detection (LOD) of singleplex real-time PCR assays targeting respiratory viruses is compared to an equivalent panel on a multiplex PCR platform, the GenMark eSensor RVP. LODs were measured for each singleplex real-time PCR assay and expressed as the lowest copy number detected 95-100% of the time, depending on the assay. The GenMark eSensor RVP LODs were obtained by converting the TCID50/mL concentrations reported in the package insert to copies/ML using qPCR. Analytical sensitivity between the two methods varied from 1.2-1280.8 copies/ML (0.08-3.11 log differences) for all 12 assays compared. Assays targeting influenza A/H3N2, influenza A/H1N1pdm09, influenza B, and human parainfluenza 1 and 2 were most comparable (1.2-8.4 copies/ML, <1 log difference). Largest differences in LOD were demonstrated for assays targeting adenovirus group E, respiratory syncytial virus subtype A, and a generic assay for all influenza A viruses regardless of subtype (319.4-1280.8 copies/ML, 2.50-3.11 log difference). The multiplex PCR platform, the GenMark eSensor RVP, demonstrated improved analytical sensitivity for detecting influenza A/H3 viruses, influenza B virus, human parainfluenza virus 2, and human rhinovirus (1.6-94.8 copies/ML, 0.20-1.98 logs). Broader detection of influenza A/H3 viruses was demonstrated by the GenMark eSensor RVP. The relationship between TCID50/mL concentrations and the corresponding copy number related to various ATCC cultures is also reported.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
OBJECTIVE: The purpose of this study was to evaluate gender differences
in baseline measures of regional brain metabolism and to assess their
reproducibility. METHOD: Fifteen male and 13 female ...healthy subjects, whose
mean age was 44 years, were tested with positron emission tomography and
18Ffluorodeoxyglucose (FDG) under resting conditions; eight of the men
and 11 of the women underwent a second FDG scan under the same conditions
4-6 weeks later to assess the reproducibility of the previous results.
RESULTS: There were no differences in whole brain metabolism between the
women and the men. In the first evaluation the female subjects showed
significantly higher metabolism in the temporal poles and cerebellum than
the male subjects. During the second evaluation the female subjects had
significantly higher metabolism only in the cerebellum. CONCLUSIONS: This
study documents significant and reproducible gender differences in
cerebellar metabolism; their functional significance merits further
evaluation.
Objective.
To examine the frequency, timing, and factors associated with abnormal cognitive and motor development during the first 30 months of life in infants born to women infected with human ...immunodeficiency virus type 1 (HIV-1).
Methods.
Serial neurodevelopmental assessment was performed with 595 infants born to women infected with HIV-1 in a multicenter, prospective, natural history cohort study. Survival analysis methods were used to evaluate 6 outcome events related to abnormal cognitive and motor growth (time to confirmed drop of 1 SD, time to first score <69, and time to confirmed drop of 2 SD) in Bayley Scales of Infant Development Mental Developmental Index (MDI) and Psychomotor Developmental Index (PDI) scores among infected (n = 114) and uninfected (n = 481) infants. Proportional hazards modeling was used to evaluate the effects of HIV infection status, prematurity, prenatal exposure to illicit drugs, maternal educational attainment, and primary language.
Results.
HIV-1 infection was significantly associated with increased risk for all outcome events related to abnormal mental and motor growth. Differences between infected and uninfected infants were apparent by 4 months of age. Prematurity was associated with increased risk for MDI <69 and PDI <69. Maternal education of <9 completed years was associated with increased risk for MDI <69. Neither prenatal exposure to illicit drugs nor primary language other than English was associated with abnormal development.
Conclusion.
A significant proportion of infants with HIV-1 infection show early and marked cognitive and motor delays or declines that may be important early indicators of HIV disease progression. These abnormalities are independent of other risk factors for developmental delay.
Changes in regional brain glucose metabolism in response to benzodiazepine agonists have been used as indicators of benzodiazepine-GABA receptor function. The purpose of this study was to assess the ...reproducibility of these responses.
Sixteen healthy right-handed men underwent scanning with PET and 18Ffluorodeoxyglucose (FDG) twice: before placebo and before lorazepam (30 micrograms/kg). The same double FDG procedure was repeated 6-8 wk later on the men to assess test-retest reproducibility.
The regional absolute brain metabolic values obtained during the second evaluation were significantly lower than those obtained from the first evaluation regardless of condition (p < or = 0.001). Lorazepam significantly and consistently decreased both whole-brain metabolism and the magnitude. The regional pattern of the changes were comparable for both studies (12.3% +/- 6.9% and 13.7% +/- 7.4%). Lorazepam effects were the largest in the thalamus (22.2% +/- 8.6% and 22.4% +/- 6.9%) and occipital cortex (19% +/- 8.9% and 21.8% +/- 8.9%). Relative metabolic measures were highly reproducible both for pharmacologic and replication condition.
This study measured the test-retest reproducibility in regional brain metabolic responses, and although the global and regional metabolic values were significantly lower for the repeated evaluation, the response to lorazepam was highly reproducible.
Carbon-11-d-threo-methylphenidate, the active enantiomer of methylphenidate (ritalin), has been shown to bind uniquely to the dopamine transporter in the baboon brain. This study characterizes its ...binding in the human brain and measures its test-retest reproducibility.
Studies were done in seven normal controls, each of whom was scanned with 11Cd-threomethylphenidate on two different occasions. Six subjects were scanned twice 3-5 wk apart without intervention to assess reproducibility. One subject was scanned sequentially before and after treatment with methylphenidate to assess binding saturability. Graphical analysis was used to obtain tissue distribution volumes (DV). The ratio of the DV in the basal ganglia (BG) to that in cerebellum (CB) (DVBG/DVCB), which corresponds to (Bmax/Kd) + 1 was used to estimate dopamine transporter availability.
Highest tracer uptake occurred in the basal ganglia, where activity peaked 7-11 min postinjection. The half-clearance time for the tracer in brain regions other than the basal ganglia was 74 min. In the basal ganglia, only 10%-15% of the activity had cleared at 74 min. Time-activity curves for 11Cd-threo-methylphenidate in the basal ganglia and cerebellum were highly reproducible. The average percent change for the absolute value for DVBG/DVCB was 6.5% +/- 4% (range 0-12%). Methylphenidate pretreatment decreased basal ganglia uptake but not cortical or cerebellar binding and reduced DVBG/DVCB by 62% and Bmax/Kd by 91%.
These studies demonstrate that 11Cd-threo-methylphenidate binding in the human brain is reversible, highly reproducible and saturable. Thus, it is an appropriate PET ligand to measure dopamine transporter availability.
Objective: To evaluate changes in health‐care resource use and costs after initiating pregabalin or duloxetine in employees with fibromyalgia (FM).
Methods: Employees (18 to 64 years old) with at ...least one claim for an FM‐attributable medication within 60 days following an FM diagnosis were identified using the Thomson Reuters MarketScan® Commercial Database (2006 to 2008). Patients newly initiated on pregabalin were propensity score matched to patients newly initiated on duloxetine. These treatment cohorts were evaluated for changes between the 6‐month pre‐ and post‐initiation periods in health‐care utilization including prescriptions, imputed medically related work loss and expenditures. Pre‐ to post‐initiation changes were compared between pregabalin and duloxetine using a difference‐in‐difference approach based on univariate statistics and multivariable models.
Results: A total of 731 employees with FM initiated on pregabalin (89.9% female, mean age 47.1 ± 9.7 years) were matched with 731 employees initiated on duloxetine (89.5% female, mean age 47.1 ± 9.8 years); other demographic and clinical characteristics were also comparable between cohorts. The adjusted marginal effects were not statistically significant for pre‐ to post‐changes in opioid utilization (P = 0.856), number of FM‐attributable (P = 0.151) or FM‐related medications (P = 0.462), and all‐cause (P = 0.323) or FM‐attributable (P = 0.991) expenditures. Pregabalin was associated with a significantly lower probability of any medically related work loss of 3.2 percentage points (P = 0.030) compared with duloxetine, but changes in indirect costs were not significantly different (P = 0.600).
Conclusions: The changes in health resource utilization and costs after initiation of pregabalin were not significantly different than the changes observed after initiation of duloxetine. These results not only demonstrate an overall similarity of resource utilization, but also suggest cost neutrality between pregabalin and duloxetine.
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