We describe the construction and characterization of the 280 GHz bolometric focal plane units (FPUs) to be deployed on the second flight of the balloon-borne
Spider
instrument. These FPUs are vital ...to
Spider
’s primary science goal of detecting or placing an upper limit on the amplitude of the primordial gravitational wave signature in the cosmic microwave background (CMB) by constraining the
B
-mode contamination in the CMB from Galactic dust emission. Each 280 GHz focal plane contains a
16
×
16
grid of corrugated silicon feedhorns coupled to an array of aluminum–manganese transition-edge sensor (TES) bolometers fabricated on 150 mm diameter substrates. In total, the three 280 GHz FPUs contain 1530 polarization-sensitive bolometers (765 spatial pixels) optimized for the low loading environment in flight and read out by time-division SQUID multiplexing. In this paper, we describe the mechanical, thermal, and magnetic shielding architecture of the focal planes and present cryogenic measurements which characterize yield and the uniformity of several bolometer parameters. The assembled FPUs have high yields, with one array as high as 95% including defects from wiring and readout. We demonstrate high uniformity in device parameters, finding the median saturation power for each TES array to be
∼
3 pW at 300 mK with a less than 6% variation across each array at
1
σ
. These focal planes will be deployed alongside the 95 and 150 GHz telescopes in the
Spider
-2 instrument, slated to fly from McMurdo Station in Antarctica in December 2018.
Dentists may be faced with the challenge of restoring unfavorably placed implants. In some instances, previously integrated implants may be from different manufacturers. This clinical report ...describes the rehabilitation of a patient with a maxillary CAD/CAM implant bar-supported overdenture that presented with malpositioned implants, from different manufacturers, including one from a discontinued implant system.
The thermal conductivity of bridgmanite, the primary constituent of the Earth's lower mantle, has been investigated using diamond anvil cells at pressures up to 85 GPa and temperatures up to 3,100 K. ...We report the results of time‐domain optical laser flash heating and X‐ray Free Electron Laser heating experiments from a variety of bridgmanite samples with different Al and Fe contents. The results demonstrate that Fe or Fe,Al incorporation in bridgmanite reduces thermal conductivity by about 50% in comparison to end‐member MgSiO3 at the pressure‐temperature conditions of Earth's lower mantle. The effect of temperature on the thermal conductivity at 28–60 GPa is moderate, well described as k=k300(300/T)a ${k={k}_{300}(300/T)}^{a}$, where a is 0.2–0.5. The results yield thermal conductivity of 7.5–15 W/(m × K) in the thermal boundary layer of the lowermost mantle composed of Fe,Al‐bearing bridgmanite.
Plain Language Summary
Heat transport from the Earth's core and mantle to the surface drives plate tectonics and is crucial for sustaining the magnetic field which shields the surface from the solar wind. To quantify the heat transport process across the core‐mantle boundary layer, it is important to know thermal conductivity of major constituent minerals of the lower mantle in the region. Bridgmanite, which was called silicate perovskite, is the most abundant mineral in the lower mantle. Here we measured thermal conductivity on lab‐grown bridgmanite with different Fe and Al compositions compressed at the tips of two opposing diamonds to reproduce relevant pressures in the mantle. To obtain thermal conductivity, we applied optical and X‐ray Free Electron Lasers combined with optical spectroscopy and X‐ray diffraction to heat and measure time‐dependent temperature distributions of the sample. Our study provides relevant high pressure‐temperature data sets to better constrain the heat flux across the core‐mantle boundary.
Key Points
We measured thermal conductivity of Fe,Al‐bearing bridgmanite, the most abundant mineral in the Earth's lower mantle, up to 85 GPa and 3,100 K
Finite‐element calculations to temperatures obtained from laser flash and X‐ray Free Electron Laser heating measurements are fitted to evaluate temperature effect on conductivity
We assessed pressure, temperature, composition effects on thermal conductivity of bridgmanite at the thermal boundary layer of the lowermost mantle
We studied selected tissues from ewes and their lambs that were grazing pastures fertilized with either sewage sludge (treated) or inorganic fertilizer (control) and determined concentrations of ...alkylphenols and phthalates in these tissues. Mean tissue concentrations of alkylphenols were relatively low (< 10-400 μg/kg) in all animals and tissues. Phthalates were detected in tissues of both control and treated animals at relatively high concentrations (> 20,000 μg/kg in many tissue samples). The use of sludge as a fertilizer was not associated with consistently increased concentrations of either alkylphenols or phthalates in the tissues of animals grazing treated pastures relative to levels in control animal tissues. Concentrations of the two classes of chemicals differed but were of a similar order of magnitude in liver and muscle as well as in fat. Concentrations of each class of compound were broadly similar in tissues derived from ewes and lambs. Although there were significant differences (p < 0.01 or p < 0.001) between years (cohorts) in mean tissue concentrations of both nonylphenol (NP) and phthalate in each of the tissues from both ewes and lambs, the differences were not attributable to either the age (6 months or 5 years) of the animal or the duration of exposure to treatments. Octylphenol concentrations were generally undetectable. There was no consistent cumulative outcome of prolonged exposure on the tissue concentrations of either class of pollutant in any ewe tissue. Mean tissue concentrations of phthalate were higher (p < 0.001) in the liver and kidney fat of male compared with female lambs. We suggest that the addition of sewage sludge to pasture is unlikely to cause large increases in tissue concentrations of NP and phthalates in sheep and other animals with broadly similar diets and digestive systems (i.e., domestic ruminants) grazing such pasture.
Celotno besedilo
Dostopno za:
BFBNIB, DOBA, IZUM, KILJ, NMLJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Neurofibromatosis type 2 (NF2) is an autosomal dominant condition with high spontaneous mutation rate which predisposes to the development of multiple nerve sheath tumours (schwannomas), meningiomas ...and ependymoma. The cardinal feature and main diagnostic criterion for the diagnosis of NF2 remains the development of bilateral vestibular schwannoma (BVS). With increasing use of MRI screening the possibility of a 'chance' diagnosis of BVS has been mooted with a potential frequency of one in two million people in their lifetime. Until now, however, no evidence for such an event has been published. We aimed to demonstrate that chance occurrence can occur and to estimate its frequency among those with just BVS late in life.
Two vestibular schwannomas from the same patient were DNA sequenced and underwent loss of heterozygosity analysis.
We show that a man who developed BVS, at ages 52 and 67 years developed these tumours sporadically by demonstrating that there were no molecular events in common between the two tumours. Furthermore from a database of over 1200 patients with NF2, we have estimated that ~25% of cases of BVS over 50 years and 50% over 70 years of age where no other features of NF2 are present represent a chance occurrence rather than due to an underlying mosaic or constitutional NF2 mutation.
Patients presenting with BVS later in life should be appraised of the potential likelihood they may not have NF2 and the resultant further reduction in risks of transmission to offspring.
Abstract Background Opioids are commonly used to manage chronic pain. Although traditional μ-opioids are effective in reducing pain, they are often associated with opioid-induced side effects (OISEs) ...that can limit treatment effectiveness. Studies have shown that tapentadol extended release (ER) has a lower incidence of gastrointestinal adverse events than oxycodone controlled release (CR) at equianalgesic doses. Objective A model was developed to estimate the budget impact of placing tapentadol ER on a hypothetical US health plan formulary of Schedule II long-acting opioids. Methods We estimated annual direct health care costs for patients who received 6-month therapy with long-acting formulations of tapentadol, oxycodone, morphine, hydromorphone, oxymorphone, or fentanyl. Costs included medications, copayments, OISE management, and switching/discontinuation. Published estimates of incidence/prevalence, OISEs, and pain management resources and costs were used. The base case analysis assumed a 10% formulary share of tapentadol ER with a 10% decrease of oxycodone CR. The resulting per-member per-month (PMPM) formulary cost differences and results of a 1-way sensitivity analysis are reported. Results In a health plan of 500,000 members, 2600 (0.52%) are estimated to experience chronic pain annually. Adding tapentadol ER to the formulary was associated with an annual budget savings of $148,945 ($0.0248 PMPM). This savings was achieved through a decrease in both pharmacy costs ($144,062; $0.0240 PMPM) and medical costs ($4883; $0.0008 PMPM). Cost decreases were driven by lower daily average consumption and fewer OISEs with tapentadol ER versus oxycodone CR, leading to reduced resource utilization over 6 months of treatment. Sensitivity analyses showed results were most sensitive to drug acquisition costs. Conclusions Our results suggest that replacing 10% of oxycodone CR's formulary share with tapentadol ER would decrease the overall budget of a health plan with 500,000 members. Placing tapentadol ER on a health plan formulary may result in a reduction in both pharmacy and medical costs.
Tubulointerstitial kidney disease is an important cause of progressive renal failure whose aetiology is incompletely understood. We analysed a large pedigree with maternally inherited ...tubulointerstitial kidney disease and identified a homoplasmic substitution in the control region of the mitochondrial genome (m.547A>T). While mutations in mtDNA coding sequence are a well recognised cause of disease affecting multiple organs, mutations in the control region have never been shown to cause disease. Strikingly, our patients did not have classical features of mitochondrial disease. Patient fibroblasts showed reduced levels of mitochondrial tRNAPhe, tRNALeu1 and reduced mitochondrial protein translation and respiration. Mitochondrial transfer demonstrated mitochondrial transmission of the defect and in vitro assays showed reduced activity of the heavy strand promoter. We also identified further kindreds with the same phenotype carrying a homoplasmic mutation in mitochondrial tRNAPhe (m.616T>C). Thus mutations in mitochondrial DNA can cause maternally inherited renal disease, likely mediated through reduced function of mitochondrial tRNAPhe.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
The therapeutic effects of centrally acting pharmaceuticals can manifest gradually and unreliably in patients, making the drug discovery process slow and expensive. Biological markers providing early ...evidence for clinical efficacy could help prioritize development of the more promising drug candidates. A potential source of such markers is functional magnetic resonance imaging (fMRI), a noninvasive imaging technique that can complement molecular imaging. fMRI has been used to characterize how drugs cause changes in brain activity. However, variation in study protocols and analysis techniques has made it difficult to identify consistent associations between subtle modulations of brain activity and clinical efficacy. We present and validate a general protocol for functional imaging-based assessment of drug activity in the central nervous system. The protocol uses machine learning methods and data from multiple published studies to identify reliable associations between drug-related activity modulations and drug efficacy, which can then be used to assess new data. A proof-of-concept version of this approach was developed and is shown here for analgesics (pain medication), and validated with eight separate studies of analgesic compounds. Our results show that the systematic integration of multistudy data permits the generalized inferences required for drug discovery. Multistudy integrative strategies of this type could help optimize the drug discovery and validation pipeline.
Although delirium is a common medical comorbidity with altered cognition as its defining feature, few publications have addressed the neuropsychological prodrome, profile, and recovery of patients ...tested during delirium. We characterize neuropsychological performance in 54 hemapoietic stem cell/bone marrow transplantation (BMT) patients shortly before, during, and after delirium and in BMT patients without delirium and 10 healthy adults. Patients were assessed prospectively before and after transplantation using a brief battery. BMT patients with delirium performed more poorly than comparisons and those without delirium on cross-sectional and trend analyses. Deficits were in expected areas of attention and memory, but also in psychomotor speed and learning. The patients with delirium did not return to normative "average" on any test during observation. Most tests showed a mild decline in the visit before delirium, a sharp decline with delirium onset, and variable performance in the following days. This study adds to the few investigations of neuropsychological performance surrounding delirium and provides targets for monitoring and early detection; Trails A and B, RBANS Coding, and List Recall may be useful for delirium assessment.
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