Uncontrolled proliferation is a hallmark of cancer. In breast cancer, immunohistochemical assessment of the proportion of cells staining for the nuclear antigen Ki67 has become the most widely used ...method for comparing proliferation between tumor samples. Potential uses include prognosis, prediction of relative responsiveness or resistance to chemotherapy or endocrine therapy, estimation of residual risk in patients on standard therapy and as a dynamic biomarker of treatment efficacy in samples taken before, during, and after neoadjuvant therapy, particularly neoadjuvant endocrine therapy. Increasingly, Ki67 is measured in these scenarios for clinical research, including as a primary efficacy endpoint for clinical trials, and sometimes for clinical management. At present, the enormous variation in analytical practice markedly limits the value of Ki67 in each of these contexts. On March 12, 2010, an international panel of investigators with substantial expertise in the assessment of Ki67 and in the development of biomarker guidelines was convened in London by the cochairs of the Breast International Group and North American Breast Cancer Group Biomarker Working Party to consider evidence for potential applications. Comprehensive recommendations on preanalytical and analytical assessment, and interpretation and scoring of Ki67 were formulated based on current evidence. These recommendations are geared toward achieving a harmonized methodology, create greater between-laboratory and between-study comparability, and allow earlier valid applications of this marker in clinical practice.
The Jupiter Energetic Particle Detector Instruments (JEDI) on the Juno Jupiter polar-orbiting, atmosphere-skimming, mission to Jupiter will coordinate with the several other space physics instruments ...on the Juno spacecraft to characterize and understand the space environment of Jupiter’s polar regions, and specifically to understand the generation of Jupiter’s powerful aurora. JEDI comprises 3 nearly-identical instruments and measures at minimum the energy, angle, and ion composition distributions of ions with energies from H:20 keV and O: 50 keV to >1 MeV, and the energy and angle distribution of electrons from <40 to >500 keV. Each JEDI instrument uses microchannel plates (MCP) and thin foils to measure the times of flight (TOF) of incoming ions and the pulse height associated with the interaction of ions with the foils, and it uses solid state detectors (SSD’s) to measure the total energy (
E
) of both the ions and the electrons. The MCP anodes and the SSD arrays are configured to determine the directions of arrivals of the incoming charged particles. The instruments also use fast triple coincidence and optimum shielding to suppress penetrating background radiation and incoming UV foreground. Here we describe the science objectives of JEDI, the science and measurement requirements, the challenges that the JEDI team had in meeting these requirements, the design and operation of the JEDI instruments, their calibrated performances, the JEDI inflight and ground operations, and the initial measurements of the JEDI instruments in interplanetary space following the Juno launch on 5 August 2011. Juno will begin its prime science operations, comprising 32 orbits with dimensions 1.1×40 RJ, in mid-2016.
The neutron-rich nucleus Ba-144 (t(1/2) = 11.5 s) is expected to exhibit some of the strongest octupole correlations among nuclei with mass numbers A less than 200. Until now, indirect evidence for ...such strong correlations has been inferred from observations such as enhanced E1 transitions and interleaving positive- and negative-parity levels in the ground-state band. In this experiment, the octupole strength was measured directly by sub-barrier, multistep Coulomb excitation of a post-accelerated 650-MeV Ba-144 beam on a 1.0-mg/cm(2) Pb-208 target. The measured value of the matrix element, < 3(1)(-)parallel to M(E3)parallel to 0(1)(+)> = 0.65((+17)(-23)) eb(3/2,) corresponds to a reduced Bd(E3) transition probability of 48((+25)(-34)) W.u. This result represents an unambiguous determination of the octupole collectivity, is larger than any available theoretical prediction, and is consistent with octupole deformation.
The Energetic Particle Detector (EPD) Investigation is one of 5 fields-and-particles investigations on the Magnetospheric Multiscale (MMS) mission. MMS comprises 4 spacecraft flying in close ...formation in highly elliptical, near-Earth-equatorial orbits targeting understanding of the fundamental physics of the important physical process called magnetic reconnection using Earth’s magnetosphere as a plasma laboratory. EPD comprises two sensor types, the Energetic Ion Spectrometer (EIS) with one instrument on each of the 4 spacecraft, and the Fly’s Eye Energetic Particle Spectrometer (FEEPS) with 2 instruments on each of the 4 spacecraft. EIS measures energetic ion energy, angle and elemental compositional distributions from a required low energy limit of 20 keV for protons and 45 keV for oxygen ions, up to >0.5 MeV (with capabilities to measure up to >1 MeV). FEEPS measures instantaneous all sky images of energetic electrons from 25 keV to >0.5 MeV, and also measures total ion energy distributions from 45 keV to >0.5 MeV to be used in conjunction with EIS to measure all sky ion distributions. In this report we describe the EPD investigation and the details of the EIS sensor. Specifically we describe EPD-level science objectives, the science and measurement requirements, and the challenges that the EPD team had in meeting these requirements. Here we also describe the design and operation of the EIS instruments, their calibrated performances, and the EIS in-flight and ground operations. Blake et al. (The Flys Eye Energetic Particle Spectrometer (FEEPS) contribution to the Energetic Particle Detector (EPD) investigation of the Magnetospheric Magnetoscale (MMS) Mission,
this issue
) describe the design and operation of the FEEPS instruments, their calibrated performances, and the FEEPS in-flight and ground operations. The MMS spacecraft will launch in early 2015, and over its 2-year mission will provide comprehensive measurements of magnetic reconnection at Earth’s magnetopause during the 18 months that comprise orbital phase 1, and magnetic reconnection within Earth’s magnetotail during the about 6 months that comprise orbital phase 2.
Abstract
We present a transit-timing variation (TTV) and planetary atmosphere analysis of the Neptune-mass planet HAT-P-26 b. We present a new set of 13 transit light curves from optical ground-based ...observations and combine them with light curves from the Wide Field Camera 3 on the Hubble Space Telescope, the Transiting Exoplanet Survey Satellite, and previously published ground-based data. We refine the planetary parameters of HAT-P-26 b and undertake a TTV analysis using 33 transits obtained over seven years. The TTV analysis shows an amplitude signal of 1.98 ± 0.05 minutes, which could result from the presence of an additional ∼0.02
M
Jup
planet at a 1:2 mean-motion resonance orbit. Using a combination of transit depths spanning optical to near-infrared wavelengths, we find that the atmosphere of HAT-P-26 b contains
2.4
−
1.6
+
2.9
% H
2
O with a derived temperature of
590
−
50
+
60
K.
ABSTRACT
This study investigated the main factors contributing to boron toxicity in plants. Growth was rapidly inhibited by internal B concentrations in the range 1–5 m m across a range of plant ...types that included monocot, dicot and algal species. In contrast, mature cells were able to withstand up to 60 m m B for several days. In wheat, rapid inhibition of root growth occurred if high B was applied to the root tip, but not if high B was applied to mature sections of the root. In leaves, there were gradations in B concentrations that correlated with visible symptoms of toxicity. However, there was no evidence to support the hypothesis that toxicity in leaves is due to osmotic stress induced by the accumulation of B. Analysis of the sensitivity to B of a range of metabolic processes including photosynthesis, respiration and protein synthesis leads to the conclusion that growth is not restricted by effects of B on energy supply and not directly by inhibition of protein synthesis. At higher B concentrations, many cellular activities were found to be partially inhibited and the toxicity to mature tissues was therefore considered not to arise from the disruption of a single process, but from the accumulated retardation of many cellular processes, exacerbated in light by photo‐oxidative stress.
The Radiation Belt Storm Probes Ion Composition Experiment (RBSPICE) on the two Van Allen Probes spacecraft is the magnetosphere ring current instrument that will provide data for answering the three ...over-arching questions for the Van Allen Probes Program: RBSPICE will determine “how space weather creates the storm-time ring current around Earth, how that ring current supplies and supports the creation of the radiation belt populations,” and how the ring current is involved in radiation belt losses. RBSPICE is a time-of-flight versus total energy instrument that measures ions over the energy range from ∼20 keV to ∼1 MeV. RBSPICE will also measure electrons over the energy range ∼25 keV to ∼1 MeV in order to provide instrument background information in the radiation belts. A description of the instrument and its data products are provided in this chapter.
The relationships between the initial opioid prescription characteristics and pain etiology with the probability of opioid discontinuation were explored in this retrospective cohort study using ...health insurance claims data from a nationally representative database of commercially insured patients in the United States. We identified 1,353,902 persons aged 14 years and older with no history of cancer or substance abuse, with new opioid use episodes and categorized them into 11 mutually exclusive pain etiologies. Cox proportional hazards models were estimated to identify factors associated with time to opioid discontinuation. After accounting for losses to follow-up, the probability of continued opioid use at 1 year was 5.3% across all subjects. Patients with chronic pain had the highest probability for continued opioid use followed by patients with inpatient admissions. Patients prescribed doses ≥90 morphine milligram equivalents (hazard ratio HR = .91; 95% confidence interval CI, .91-.92), initiated with tramadol (HR = .89; 95% CI, .89-.90) or long-acting opioids (HR = .79; 95% CI, .77-.82) were less likely to discontinue opioids. Increasing days' supply of the first prescription was consistently associated with a lower likelihood of opioid discontinuation (HRs, CIs: 3-4 days' supply = .70, .70-.71; 5-7 days' supply = .48, .47-.48; 8-10 days' supply = .37, .37-.38; 11-14 days' supply = .32, .31-.33; 15-21 days' supply = .29, .28-.29; ≥22 days supplied = .20, .19-.20). The direction of this relationship was consistent across all pain etiologies. Clinicians should initiate patients with the lowest supply of opioids to mitigate unintentional long-term opioid use.
This study shows that characteristics of the first opioid prescription, particularly duration of the prescription, are significant predictors of continued opioid use irrespective of the indication for an opioid prescription. These data should encourage prescribers to initiate patients using the minimum effective opioid dose and duration to reduce unintended long-term use and could motivate policies that restrict the initial supply of opioids.
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