The speed, tight timing requirements packaging and complicated error behavior of DDR2 and DDR3 SDRAMs pose significant challenges for single-event testing. Often, each new generation will require an ...expensive new tester with a state-of-the-art controller for the memory. We explore the trade-offs in the use of commercial FPGA based evaluation boards for radiation testing DDR2 and DDR3 SDRAMs. We evaluate the resulting data quality and discuss tester performance while also elucidating and comparing SEE susceptibilities in DDR2 and DDR3 SDRAMs.
High-density lipoprotein plays a key role in reverse cholesterol transport. In addition, high-density lipoprotein particles may be cardioprotective and reduce infarct size in the setting of ...myocardial injury. Lecithin-cholesterol acyltransferase is a rate-limiting enzyme in reverse cholesterol transport. MEDI6012 is a recombinant human lecithin-cholesterol acyltransferase that increases high-density lipoprotein cholesterol. Administration of lecithin-cholesterol acyltransferase has the potential to reduce infarct size and regress coronary plaque in acute ST-segment-elevation myocardial infarction.
REAL-TIMI 63B (A Randomized, Placebo‑controlled Phase 2b Study to Evaluate the Safety and Efficacy of MEDI6012 in Acute ST Elevation Myocardial Infarction) was a phase 2B multinational, placebo-controlled, randomized trial. Patients with ST-segment-elevation myocardial infarction within 6 hours of symptom onset and planned for percutaneous intervention were randomly assigned 2:1 to MEDI6012 (2- or 6-dose regimen) or placebo and followed for 12 weeks. The primary outcome was infarct size as a percentage of left ventricular mass by cardiac MRI at 10 to 12 weeks, with the primary analysis in patients with TIMI Flow Grade 0 to 1 before percutaneous intervention who received at least 2 doses of MEDI6012. The secondary outcome was change in noncalcified plaque volume on coronary computed tomographic angiography from baseline to 10 to 12 weeks with the primary analysis in patients who received all 6 doses of MEDI6012.
A total of 593 patients were randomly assigned. Patients were a median of 62 years old, 77.9% male, and 95.8% statin naive. Median time from symptom onset to randomization was 146 (interquartile range IQR, 103-221) minutes and from hospitalization to randomization was 12.7 (IQR, 6.6-24.0) minutes, and the first dose of drug was administered a median of 8 (IQR, 3-13) minutes before percutaneous intervention. The index myocardial infarction was anterior in 69.6% and TIMI Flow Grade 0 to 1 in 65.1% of patients. At 12 weeks, infarct size did not differ between treatment groups (MEDI6012: 9.71%, IQR 4.79-16.38; placebo: 10.48%, IQR, 4.92-16.61, 1-sided
=0.79. There was also no difference in noncalcified plaque volume (geometric mean ratio, 0.96 95% CI, NA-1.10, 1-sided
=0.30). There was no significant difference in treatment emergent serious adverse events.
Administration of MEDI6012 in patients with acute ST-segment-elevation myocardial infarction did not result in a significant reduction in infarct size or noncalcified plaque volume at 12 weeks. MEDI6012 was well tolerated with no excess in overall serious adverse events.
URL: https://www.
gov; Unique identifier: NCT03578809.
The valsalva manoeuvre (VM), used as an autonomic function test, can detect sympathetic and/or parasympathetic autonomic dysfunction. This study investigated the value of VM in patients with ...different Parkinsonian syndromes (PS). We continuously recorded blood pressure, ECG and respiration among 38 patients with multiple system atrophy (MSA), 32 patients with progressive supranuclear palsy (PSP), 26 patients with idiopathic Parkinson’s disease (PD) and in 27 healthy subjects matched in age and sex (Con). VM was performed in addition to metronomic breathing and tilt-table testing. VM could not be analysed in 26% of the ES patients. Valsalva ratio (VR), as a parameter of cardiovagal function, was pathologically decreased in all patient groups. Valsalva ratio (VR) was not able to discriminate parasympathetic dysfunction between patients and controls as well as E/I ratio of metronomic breathing. As a parameter of sympathetic dysfunction during VM, the physiological increase of blood pressure was more often missing during phase IV than phase II especially in PD and MSA patients. Correlation with orthostatic hypotension during tilt-table testing was only moderate. Although VM can demonstrate sympathetic and parasympathetic autonomic dysfunction, we cannot recommend VM as a first line autonomic test in PS patients. Metronomic breathing and tilt-table test seem more capable as parasympathetic resp. and sympathetic function tests to identify cardiovascular abnormalities in PS patients.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Next to α-synuclein deposition, microglial activation is a prominent pathological feature in the substantia nigra (SN) of Parkinson's disease (PD) patients. Little is known, however, about the ...different phenotypes of microglia and how they change during disease progression, in the SN or in another brain region, like the hippocampus (HC), which is implicated in dementia and depression, important non-motor symptoms in PD. We studied phenotypes and activation of microglia in the SN and HC of established PD patients (Braak PD stage 4–6), matched controls (Braak PD stage 0) and of incidental Lewy Body disease (iLBD) cases (Braak PD stage 1–3) that are considered a prodromal state of PD. As recent experimental studies suggested that toll-like receptor 2 (TLR2) mediates α-synuclein triggered microglial activation, we also studied whether TLR2 expression is indeed related to pathology in iLBD and PD patients. A clear α-synuclein pathology-related increase in amoeboid microglia was present in the HC and SN in PD. Also, morphologically primed/reactive microglial cells, and a profound increase in microglial TLR2 expression were apparent in iLBD, but not PD, cases, indicative of an early activational response to PD pathology. Moreover, TLR2 was differentially expressed between the SN and HC, consistent with a region-specific pattern of microglial activation. In conclusion, the regional changes in microglial phenotype and TLR2 expression in primed/reactive microglia in the SN and HC of iLBD cases indicate that TLR2 may play a prominent role in the microglial-mediated responses that could be important for PD progression.
Single-event effects testing (heavy-ion and proton) is presented for 96- and 176-layer commercially-available 3D NAND flash memory, with emphasis on SEFI detection and recovery.
We have created a clinical molecular diagnostic assay to test for microsatellite instability (MSI) at multiple loci simultaneously in paraffin-embedded surgical pathology colon resection specimens. ...This fluorescent multiplex polymerase chain reaction (PCR) assay analyzes the five primary microsatellite loci recommended at the 1997 National Cancer Institute-sponsored conference on MSI for the identification of MSI or replication errors in colorectal cancer: Bat-25, Bat-26, D2S123, D5S346, and D17S250. Amplicon detection is accomplished by capillary electrophoresis using the ABI 310 Genetic Analyzer. Assay validation compared 18 specimens previously assessed by radioactive PCR and polyacrylamide gel electrophoresis detection to results generated by the reported assay. Germline and tumor DNA samples were amplified in separate multiplex PCR reactions, sized in separate capillary electrophoresis runs, and compared directly to identify novel length alleles in tumor tissue. A concordance of 100% between the two modalities was achieved. The multiplex assay routinely detected a subpopulation of 10% tumor alleles in the presence of 90% normal alleles. A novel statistical model was generated that corroborates the validity of using results generated by analysis of five independent microsatellites to achieve a single overall MSI diagnosis. The assay presented is superior to standard radioactive monoplex PCR, polyacrylamide gel electrophoretic analysis, primarily due to the multiplex PCR format.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
It is unknown if simultaneous stimulation of the respiratory and locomotor muscle afferents via inspiratory loading (IL) and locomotor subsystolic cuff inflation (CUFF) influences the cardiovascular ...responses during exercise. We hypothesized that combined IL and CUFF (IL + CUFF) will result in greater increases in blood pressure (MAP) and systemic vascular resistance (SVR) than IL and CUFF alone during exercise. Eight adults (6 males/2 females) were enrolled and performed four 10-min bouts of constant-load cycling eliciting 40% maximal oxygen uptake on a single day. For each exercise bout, the first 5 min consisted of spontaneous breathing. The second 5 min consisted of voluntary hyperventilation (i.e., breathing frequency of 40 breaths/min) with IL (30% maximum inspiratory pressure), CUFF (80 mmHg), IL + CUFF, or no intervention (CTL) in randomized order. During exercise, cardiac output and MAP were determined via open-circuit acetylene wash-in and manual sphygmomanometry, respectively, and SVR was calculated. Across CTL, IL, CUFF, and IL + CUFF, MAP was greater with each condition (CTL: 97 ± 14; IL: 106 ± 13; CUFF: 114 ± 14; IL + CUFF: 119 ± 15 mmHg, all
< 0.02). Furthermore, SVR was greater with IL + CUFF compared with IL, CUFF, and CTL (CTL: 6.6 ± 1.1; IL: 7.5 ± 1.4; CUFF: 7.5 ± 1.3; IL + CUFF: 8.2 ± 1.4 mmHg·L
·min
, all
< 0.02). Cardiac output was not different across conditions (CTL: 15.2 ± 3.8; IL: 14.8 ± 3.7; CUFF: 15.6 ± 3.5; IL + CUFF: 14.7 ± 4.3 L/min, all
> 0.05). These data demonstrate that simultaneous stimulation of respiratory and locomotor muscle afferent feedback results in additive MAP and SVR responses than IL and CUFF alone during submaximal exercise. These findings have important clinical implications for populations with exaggerated locomotor and respiratory muscle reflex feedbacks.
Reflexes arising from the respiratory and locomotor muscles influence cardiovascular regulation during exercise. However, it is unclear how the respiratory and locomotor muscle reflexes interact when simultaneously stimulated. Herein, we demonstrate that stimulation of the respiratory and locomotor muscle reflexes yielded additive cardiovascular responses during submaximal exercise.
Colorectal cancer screening has been shown to prevent or detect early colorectal cancer and reduce mortality; yet, adherence to screening recommendations remains low, particularly in rural settings.
...RCT.
Adults (n=7,812) aged 50–75 years and due for colorectal cancer screening in a largely rural health system were randomly assigned to either the intervention (n=3,906) or the control (n=3,906) group in September 2016, with analysis following through 2018.
A mailed motivational messaging screening reminder letter with an option to call and request a free at-home fecal immunochemical screening test (intervention) or the standard invitation letter detailing that the individual was due for screening (control). Multifaceted motivational messaging emphasized colorectal cancer preventability and the ease and affordability of screening, and communicated a limited supply of test kits.
Colorectal cancer screening participation within 6 months after mailed invitation was ascertained from the electronic medical record.
Colorectal cancer screening participation was significantly improved in the intervention (30.1%) vs the usual care control group (22.5%; p<0.001). Individuals randomized to the intervention group had 49% higher odds of being screened over follow-up than those randomized to the control group (OR=1.49, 95% CI=1.34, 1.65). A total of 13.2 screening invitations were needed to accomplish 1 additional screening over the usual care. Of the 233 fecal immunochemical test kits mailed to participants, 154 (66.1%) were returned, and 18 (11.7%) tested positive.
A mailed motivational messaging letter with a low-cost screening alternative increased colorectal cancer screening in this largely rural community with generally poor adherence to screening recommendations. Mailed colorectal cancer screening reminders using motivational messaging may be an effective method for increasing screening and reducing rural colorectal cancer disparities.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Neuronal membrane components that bind alpha-bungarotoxin with high affinity have only recently been shown unambiguously to function as nicotinic receptors. Activation of the receptors increases ...intracellular levels of free calcium in neurons. In the chick ciliary ganglion, where the receptors have been studied in some detail, they have been shown to have a predominantly nonsynaptic location on neurons and may be concentrated on pseudodendrites emerging from the somata. This has raised questions about the physiological significance of the receptors for the neurons. Here we show that activation of the receptors on isolated ciliary ganglion neurons in cell culture produces neurite retraction. Focal application of either nicotine or ACh at low concentrations induces the retraction, and alpha-bungarotoxin blocks the effect. The retraction requires external calcium and is confined to the individual neurite stimulated with agonist. Brief exposure to elevated concentrations of K+ also induces neurite retraction, and both the K(+)-induced and the nicotine-induced retractions can be prevented by the calcium channel blocker omega-conotoxin. The results suggest that activation of the alpha-bungarotoxin-binding nicotinic receptors on neurites triggers activation of voltage-gated calcium channels presumably by depolarizing the membrane, and that together they permit sufficient calcium to enter the neurite to prevent further outgrowth and induce retraction.
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