The Radiation Belt Storm Probes (RBSP)-Energetic Particle, Composition, and Thermal Plasma (ECT) suite contains an innovative complement of particle instruments to ensure the highest quality ...measurements ever made in the inner magnetosphere and radiation belts. The coordinated RBSP-ECT particle measurements, analyzed in combination with fields and waves observations and state-of-the-art theory and modeling, are necessary for understanding the acceleration, global distribution, and variability of radiation belt electrons and ions, key science objectives of NASA’s Living With a Star program and the Van Allen Probes mission. The RBSP-ECT suite consists of three highly-coordinated instruments: the Magnetic Electron Ion Spectrometer (MagEIS), the Helium Oxygen Proton Electron (HOPE) sensor, and the Relativistic Electron Proton Telescope (REPT). Collectively they cover, continuously, the full electron and ion spectra from one eV to 10’s of MeV with sufficient energy resolution, pitch angle coverage and resolution, and with composition measurements in the critical energy range up to 50 keV and also from a few to 50 MeV/nucleon. All three instruments are based on measurement techniques proven in the radiation belts. The instruments use those proven techniques along with innovative new designs, optimized for operation in the most extreme conditions in order to provide unambiguous separation of ions and electrons and clean energy responses even in the presence of extreme penetrating background environments. The design, fabrication and operation of ECT spaceflight instrumentation in the harsh radiation belt environment ensure that particle measurements have the fidelity needed for closure in answering key mission science questions. ECT instrument details are provided in companion papers in this same issue.
In this paper, we describe the science objectives of the RBSP-ECT instrument suite on the Van Allen Probe spacecraft within the context of the overall mission objectives, indicate how the characteristics of the instruments satisfy the requirements to achieve these objectives, provide information about science data collection and dissemination, and conclude with a description of some early mission results.
Neratinib is an irreversible pan-HER tyrosine kinase inhibitor approved for extended adjuvant treatment in early-stage HER2-positive breast cancer based on the phase III ExteNET study. In that trial, ...in which no antidiarrheal prophylaxis was mandated, grade 3 diarrhea was observed in 40% of patients and 17% discontinued due to diarrhea. The international, open-label, sequential-cohort, phase II CONTROL study is investigating several strategies to improve tolerability.
Patients who completed trastuzumab-based adjuvant therapy received neratinib 240 mg/day for 1 year plus loperamide prophylaxis (days 1–28 or 1–56). Sequential cohorts evaluated additional budesonide or colestipol prophylaxis (days 1–28) and neratinib dose escalation (DE; ongoing). The primary end point was the incidence of grade ≥3 diarrhea.
Final data for loperamide (L; n = 137), budesonide + loperamide (BL; n = 64), colestipol + loperamide (CL; n = 136), and colestipol + as-needed loperamide (CL-PRN; n = 104) cohorts, and interim data for DE (n = 60; completed ≥six cycles or discontinued; median duration 11 months) are available. No grade 4 diarrhea was observed. Grade 3 diarrhea rates were lower than ExteNET in all cohorts and lowest in DE (L 31%, BL 28%, CL 21%, CL-PRN 32%, DE 15%). Median number of grade 3 diarrhea episodes was one; median duration per grade 3 episode was 1.0–2.0 days across cohorts. Most grade 3 diarrhea and diarrhea-related discontinuations occurred in month 1. Diarrhea-related discontinuations were lowest in DE (L 20%, BL 8%, CL 4%, CL-PRN 8%, DE 3%). Decreases in health-related quality of life did not cross the clinically important threshold.
Neratinib tolerability was improved with preemptive prophylaxis or DE, which reduced the rate, severity, and duration of neratinib-associated grade ≥3 diarrhea compared with ExteNET. Lower diarrhea-related treatment discontinuations in multiple cohorts indicate that proactive management can allow patients to stay on neratinib for the recommended time period.
NCT02400476.
•CONTROL trial investigated antidiarrheal strategies including dose escalation in neratinib-treated patients with early HER2+ breast cancer.•Preemptive prophylaxis and dose escalation reduced the rate, severity, and duration of grade 3 diarrhea compared with ExteNET.•Lower diarrhea-related discontinuations and dose reductions in multiple cohorts compared with ExteNET suggested improved tolerability.•Neratinib dose escalation is a particularly promising strategy as it eliminates mandatory prophylaxis and related side-effects.
This paper proposes a two-phase scheme for removing salt-and-pepper impulse noise. In the first phase, an adaptive median filter is used to identify pixels which are likely to be contaminated by ...noise (noise candidates). In the second phase, the image is restored using a specialized regularization method that applies only to those selected noise candidates. In terms of edge preservation and noise suppression, our restored images show a significant improvement compared to those restored by using just nonlinear filters or regularization methods only. Our scheme can remove salt-and-pepper-noise with a noise level as high as 90%.
Chronic inflammation has been associated with increased risk for developing gastrointestinal cancer. Interleukin-23 (IL-23) receptor signaling has been correlated with inflammatory bowel disease ...pathogenesis, as well as promotion of tumor growth. However, little is known about the relative potential for IL-23-directed causality in gut tumorigenesis. We report that IL-23 transgene expression was sufficient to induce rapid (3-4 weeks) de novo development of intestinal adenomas with 100% incidence. Initiation of tumorigenesis was independent of exogenous carcinogens, Helicobacter colonization, or pre-existing tumor-suppressor gene mutations. Tumorigenesis was mediated by Thy1(+)IL-23R(+) innate lymphoid cells (ILC3), in part, through IL-17 responses as tumor development was inhibited in RAG(-/-) × IL-17(-/-) double knockout mice. Remarkably, IL-23 initiation of tumorigenesis by resident ILCs consistently occurred before recruitment of conspicuous inflammatory infiltrates. Our results reveal an explicit role for IL-23-mediated initiation of gut tumorigenesis and implicate a key role for IL-23R(+) ILC3 in the absence of overt cellular infiltrate recruitment.
Background
Postoperative colorectal anastomotic strictures are quite common. As such, many techniques have been available to address such a problem, one of which is endoscopic dilation. The aim of ...the present study was to evaluate the long-term outcomes following endoscopic dilation using a multidiameter balloon.
Methods
A retrospective study was conducted on patients with postoperative anastomotic stenosis treated with endoscopic dilation using a multidiameter balloon at our institution, in January 2005–December 2019 were retrospectively reviewed, excluding those with tumor recurrence. Perioperative factors, complications, and recurrence rates were analyzed.
Results
There were 40 patients, (22 males and 18 females, mean age 64.6 ± 10.7 years, range 33–84 years). The median follow-up period was 56 months (interquartile range 22.5–99 months). Only 1 complication occurred, micro-perforation due to guided wire injury, which was managed conservatively. Five (12.5%) patients developed restenosis and underwent repeat balloon dilation. None of the five recurrences required more aggressive management, such as redo anastomosis.
Conclusions
Endoscopic multidiameter balloon dilation is a safe and effective method for treating benign colorectal anastomotic strictures.
The near-term progression of ocean acidification (OA) is projected to bring about sharp changes in the chemistry of coastal upwelling ecosystems. The distribution of OA exposure across these ...early-impact systems, however, is highly uncertain and limits our understanding of whether and how spatial management actions can be deployed to ameliorate future impacts. Through a novel coastal OA observing network, we have uncovered a remarkably persistent spatial mosaic in the penetration of acidified waters into ecologically-important nearshore habitats across 1,000 km of the California Current Large Marine Ecosystem. In the most severe exposure hotspots, suboptimal conditions for calcifying organisms encompassed up to 56% of the summer season, and were accompanied by some of the lowest and most variable pH environments known for the surface ocean. Persistent refuge areas were also found, highlighting new opportunities for local adaptation to address the global challenge of OA in productive coastal systems.
In this large clinical trial, aspirin plus extended-release dipyridamole was found to have an efficacy similar to that of clopidogrel in the prevention of recurrent stroke. However, aspirin plus ...extended-release dipyridamole resulted in more bleeding, including intracranial bleeding. The results will help guide therapy for secondary stroke prevention.
Aspirin plus extended-release dipyridamole was found to have an efficacy similar to that of clopidogrel in the prevention of recurrent stroke. However, aspirin plus extended-release dipyridamole resulted in more bleeding, including intracranial bleeding.
Recurrent stroke is an important vascular event affecting the life of survivors of ischemic stroke.
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Multiple randomized trials have proved the efficacy of antiplatelet agents for the prevention of recurrent stroke after noncardioembolic stroke.
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Antiplatelet options for the prevention of recurrent stroke include aspirin (50 mg to 325 mg per day), the combination of low-dose aspirin and extended-release dipyridamole, and clopidogrel alone.
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Aspirin has been shown to reduce the risk of stroke recurrence by about 23% as compared with placebo.
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Studies of clopidogrel have suggested an 8% relative risk reduction of stroke recurrence, as compared with aspirin, among . . .
In a multicenter trial, 20,332 patients who had recently had an ischemic stroke were randomly assigned to receive either telmisartan or placebo. All patients also received medications for ...blood-pressure control at the investigators' discretion. At a mean follow-up of 2.5 years, there was no significant difference between the two study groups in the rates of recurrent stroke or major cardiovascular events.
Patients who had recently had an ischemic stroke were randomly assigned to receive either telmisartan or placebo. At a mean follow-up of 2.5 years, there was no significant difference between the study groups in the rates of recurrent stroke or major cardiovascular events.
Stroke is the second most frequent cause of death in the world and is responsible for about 5 million deaths each year.
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An additional 15 million persons have nonfatal strokes, with about a third having disabling consequences. Elevated blood pressure is the strongest risk factor for stroke, and lowering of blood pressure, especially in patients with substantially elevated levels (e.g., systolic pressure, >160 mm Hg), reduces the risk of stroke.
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After a stroke, lowering blood pressure with a combination of an angiotensin-converting–enzyme (ACE) inhibitor and a diuretic reduced rates of recurrent stroke in the Perindopril Protection against Recurrent Stroke Study . . .
Satellite-based passive microwave remote sensing has been shown to be a valuable tool in mapping and monitoring global soil moisture. The Advanced Microwave Scanning Radiometer on the Aqua platform ...(AMSR-E) has made significant contributions to this application. As the result of agency and individual initiatives, several approaches for the retrieval of soil moisture from AMSR-E have been proposed and implemented. Although the majority of these are based on the same Radiative Transfer Equation, studies have shown that the resulting soil moisture estimates can differ significantly. A primary goal of this investigation is to understand these differences and develop a suitable approach to potentially improve the algorithm currently used by NASA in producing its operational soil moisture product. In order to achieve this goal, the theoretical basis of several alternative soil moisture retrieval algorithms are examined. Analysis has focused on five established approaches: the operational algorithm adopted by NASA, which is referred to as the Normalized Polarization Difference algorithm, the Single Channel Algorithm, the Land Parameter Retrieval Model, the University of Montana soil moisture algorithm, and the HydroAlgo Artificial Neural Network algorithm. Previous comparisons of these algorithms in the literature have typically focused on the retrieved soil moisture products, and employed different metrics and data sets, and have resulted in differing conclusions. In this investigation we attempt to provide a more thorough understanding of the fundamental differences between the algorithms and how these differences affect their performance in terms of range of soil moisture provided. The comparative overview presented in the paper is based on the operating versions of the source codes of the individual algorithms. Analysis has indicated that the differences between algorithms lie in the specific parameterizations and assumptions of each algorithm. The comparative overview of the theoretical basis of the approaches is linked to differences found in the soil moisture retrievals, leading to suggestions for improvements and increased reliability in these algorithms.
•Theoretical inter-comparison of several passive-based microwave retrieval algorithms•Algorithm's performance depends on the vegetation and roughness parameterization.•Interchange of parameterization units between the algorithms might not be possible.
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