Background
The combination of chemotherapy with thoracic radiotherapy (TRT) compared with TRT alone has been shown to confer a survival advantage for good performance status patients with stage III ...non-small cell lung cancer. However, it is not known whether sequential or concurrent delivery of these therapies is the optimal combination strategy.
Methods
A total of 610 patients were randomly assigned to two concurrent regimens and one sequential chemotherapy and TRT regimen in a three-arm phase III trial. The sequential arm included cisplatin at 100 mg/m2 on days 1 and 29 and vinblastine at 5 mg/m2 per week for 5 weeks with 60 Gy TRT beginning on day 50. Arm 2 used the same chemotherapy regimen as arm 1 with 60 Gy TRT once daily beginning on day 1. Arm 3 used cisplatin at 50 mg/m2 on days 1, 8, 29, and 36 with oral etoposide at 50 mg twice daily for 10 weeks on days 1, 2, 5, and 6 with 69.6 Gy delivered as 1.2 Gy twice-daily fractions beginning on day 1. The primary endpoint was overall survival, and secondary endpoints included tumor response and time to tumor progression. Kaplan-Meier analyses were used to assess survival, and toxic effects were examined using the Wilcoxon rank sum test. All statistical tests were two-sided.
Results
Median survival times were 14.6, 17.0, and 15.6 months for arms 1-3, respectively. Five-year survival was statistically significantly higher for patients treated with the concurrent regimen with once-daily TRT compared with the sequential treatment (5-year survival: sequential, arm 1, 10% 20 patients, 95% confidence interval CI = 7% to 15%; concurrent, arm 2, 16% 31 patients, 95% CI = 11% to 22%, P = .046; concurrent, arm 3, 13% 22 patients, 95% CI = 9% to 18%). With a median follow-up time of 11 years, the rates of acute grade 3-5 nonhematologic toxic effects were higher with concurrent than sequential therapy, but late toxic effects were similar.
Conclusion
Concurrent delivery of cisplatin-based chemotherapy with TRT confers a long-term survival benefit compared with the sequential delivery of these therapies.
With a dayside temperature in excess of 4500 K, comparable to a mid-K-type star, KELT-9b is the hottest planet known. Its extreme temperature makes KELT-9b a particularly interesting test bed for ...investigating the nature and diversity of gas giant planets. We observed the transit of KELT-9b at high spectral resolution (R ∼ 94,600) with the CARMENES instrument on the Calar Alto 3.5 m telescope. Using these data, we detect for the first time ionized calcium (Ca ii triplet) absorption in the atmosphere of KELT-9b; this is the second time that Ca ii has been observed in a hot Jupiter. Our observations also reveal prominent H absorption, confirming the presence of an extended hydrogen envelope around KELT-9b. We compare our detections with an atmospheric model and find that all four lines form between atmospheric temperatures of 6100 and 8000 K and that the Ca ii lines form at pressures between 50 and 100 nbar while the H line forms at a lower pressure (∼10 nbar), higher up in the atmosphere. The altitude that the core of H line forms is found to be ∼1.4 Rp, well within the planetary Roche lobe (∼1.9 Rp). Therefore, rather than probing the escaping upper atmosphere directly, the H line and the other observed Balmer and metal lines serve as atmospheric thermometers enabling us to probe the planet's temperature profile, thus the energy budget.
Observations at 1 au have confirmed that enhancements in measured energetic-particle (EP) fluxes are statistically associated with "rough" magnetic fields, i.e., fields with atypically large spatial ...derivatives or increments, as measured by the Partial Variance of Increments (PVI) method. One way to interpret this observation is as an association of the EPs with trapping or channeling within magnetic flux tubes, possibly near their boundaries. However, it remains unclear whether this association is a transport or local effect; i.e., the particles might have been energized at a distant location, perhaps by shocks or reconnection, or they might experience local energization or re-acceleration. The Parker Solar Probe (PSP), even in its first two orbits, offers a unique opportunity to study this statistical correlation closer to the corona. As a first step, we analyze the separate correlation properties of the EPs measured by the Integrated Science Investigation of the Sun (IS IS) instruments during the first solar encounter. The distribution of time intervals between a specific type of event, i.e., the waiting time, can indicate the nature of the underlying process. We find that the IS IS observations show a power-law distribution of waiting times, indicating a correlated (non-Poisson) distribution. Analysis of low-energy (∼15 - 200 keV/nuc) IS IS data suggests that the results are consistent with the 1 au studies, although we find hints of some unexpected behavior. A more complete understanding of these statistical distributions will provide valuable insights into the origin and propagation of solar EPs, a picture that should become clear with future PSP orbits.
The autonomic adjustments to exercise are mediated by central signals from the higher brain (central command) and by a peripheral
reflex arising from working skeletal muscle (exercise pressor ...reflex), with further modulation provided by the arterial baroreflex.
Although it is clear that central command, the exercise pressor reflex and the arterial baroreflex are all requisite for eliciting
appropriate cardiovascular adjustments to exercise, this review will be limited primarily to discussion of central command.
Central modulation of the cardiovascular system via descending signals from higher brain centres has been well recognized
for over a century, yet the specific regions of the human brain involved in this exercise-related response have remained speculative.
Brain mapping studies during exercise as well as non-exercise conditions have provided information towards establishing the
cerebral cortical structures in the human brain specifically involved in cardiovascular control. The purpose of this review
is to provide an update of current concepts on central command in humans, with a particular emphasis on the regions of the
brain identified to alter autonomic outflow and result in cardiovascular adjustments.
Reperfusion is a key factor for clinical outcome in patients with acute ischemic stroke (AIS) treated with endovascular thrombectomy (EVT) for large-vessel intracranial occlusion. However, data are ...scarce on the association between the time from onset and reperfusion results.
To analyze the rate of reperfusion after EVT started at different intervals after symptom onset in patients with AIS.
We conducted a meta-analysis of individual patient data from 7 randomized trials of the Highly Effective Reperfusion Using Multiple Endovascular Devices (HERMES) group. This is a multicenter cohort study of the intervention arm of randomized clinical trials included in the HERMES group. Patients with anterior circulation AIS who underwent EVT for M1/M2 or intracranial carotid artery occlusion were included. Each trial enrolled patients according to its specific inclusion and exclusion criteria. Data on patients eligible but not enrolled (eg, refusals or exclusions) were not available. All analyses were performed by the HERMES biostatistical core laboratory using the pooled database. Data were analyzed between December 2010 and April 2015.
Successful reperfusion was defined as a modified thrombolysis in cerebral infarction score of 2b/3 at the end of the EVT procedure adjusted for age, occlusion location, pretreatment intravenous thrombolysis, and clot burden score and was analyzed in relation to different intervals (onset, emergency department arrival, imaging, and puncture) using mixed-methods logistic regression.
Among the 728 included patients, with a mean (SD) age of 65.4 (13.5) years and of whom 345 were female (47.4%), decreases in rates of successful reperfusion defined as a thrombolysis in cerebral infarction score of 2b/3 were observed with increasing time from admission or first imaging to groin puncture. The magnitude of effect was a 22% relative reduction (odds ratio, 0.78; 95% CI, 0.64-0.95) per additional hour between admission and puncture and a 26% relative reduction (odds ratio, 0.74; 95% CI, 0.59-0.93) per additional hour between imaging and puncture.
Because the probability of reperfusion declined significantly with time between hospital arrival and groin puncture, we provide additional arguments for minimizing the intervals after symptom onset in anterior circulation acute ischemic stroke.
First results of a cosmic-ray electron and positron spectrum from 10 GeV to 3 TeV is presented based upon observations with the CALET instrument on the International Space Station starting in ...October, 2015. Nearly a half million electron and positron events are included in the analysis. CALET is an all-calorimetric instrument with total vertical thickness of 30 X_{0} and a fine imaging capability designed to achieve a large proton rejection and excellent energy resolution well into the TeV energy region. The observed energy spectrum over 30 GeV can be fit with a single power law with a spectral index of -3.152±0.016 (stat+syst). Possible structure observed above 100 GeV requires further investigation with increased statistics and refined data analysis.
In this study we examine the anthropogenically forced climate response over the historical period, 1860 to present, and projected response to 2100, using updated emissions scenarios and an improved ...coupled model (HadCM3) that does not use flux adjustments. We concentrate on four new Special Report on Emission Scenarios (SRES) namely (A1FI, A2, B2, B1) prepared for the Intergovernmental Panel on Climate Change Third Assessment Report, considered more self-consistent in their socio-economic and emissions structure, and therefore more policy relevant, than older scenarios like IS92a. We include an interactive model representation of the anthropogenic sulfur cycle and both direct and indirect forcings from sulfate aerosols, but omit the second indirect forcing effect through cloud lifetimes. The modelled first indirect forcing effect through cloud droplet size is near the centre of the IPCC uncertainty range. We also model variations in tropospheric and stratospheric ozone. Greenhouse gas-forced climate change response in B2 resembles patterns in IS92a but is smaller. Sulfate aerosol and ozone forcing substantially modulates the response, cooling the land, particularly northern mid-latitudes, and altering the monsoon structure. By 2100, global mean warming in SRES scenarios ranges from 2.6 to 5.3 K above 1900 and precipitation rises by 1%/K through the twenty first century (1.4%/K omitting aerosol changes). Large-scale patterns of response broadly resemble those in an earlier model (HadCM2), but with important regional differences, particularly in the tropics. Some divergence in future response occurs across scenarios for the regions considered, but marked drying in the mid-USA and southern Europe and significantly wetter conditions for South Asia, in June-July-August, are robust and significant.PUBLICATION ABSTRACT
Quantum materials display rich and myriad types of magnetic, electronic, and structural ordering, often with these ordering modes either competing with one another or “intertwining,” that is, ...reinforcing one another. Low-dimensional quantum materials influenced strongly by competing interactions and/or geometric frustration are particularly susceptible to such ordering phenomena and thus offer fertile ground for understanding the consequent emergent collective quantum phenomena. Such is the case of the quasi-2D materials R4Ni3O10 (R=La, Pr), in which intertwined charge- and spin-density waves (CDW and SDW) on the Ni sublattice have been identified and characterized. Not unexpectedly, these density waves are largely quasi-2D as a result of weak coupling between planes, compounded with magnetic frustration. In the case of R=Pr, however, we show here that exchange coupling between the transition-metal and rare-earth sublattices upon cooling overcomes both obstacles, leading to a dimensional crossover into a fully 3D-ordered and coupled SDW state on both sublattices, as an induced moment on notionally nonmagnetic Pr3+ opens exchange pathways in the third dimension. In the process, the structure of the SDW on the Ni sublattice is irreversibly altered, an effect that survives reheating of the material until the underlying CDW melts. This “bootstrapping” mechanism linking incommensurate SDWs on the two sublattices illustrates a new member of the multitude of quantum states that low-dimensional magnets can express, driven by coupled orders and modulated by frustrated exchange pathways.
Nine-banded armadillos (Dasypus novemcinctus) are naturally infected with Mycobacterium leprae and have been implicated in zoonotic transmission of leprosy. Early studies found this disease mainly in ...Texas and Louisiana, but armadillos in the southeastern United States appeared to be free of infection. We screened 645 armadillos from 8 locations in the southeastern United States not known to harbor enzootic leprosy for M. leprae DNA and antibodies. We found M. leprae-infected armadillos at each location, and 106 (16.4%) animals had serologic/PCR evidence of infection. Using single-nucleotide polymorphism variable number tandem repeat genotyping/genome sequencing, we detected M. leprae genotype 3I-2-v1 among 35 armadillos. Seven armadillos harbored a newly identified genotype (3I-2-v15). In comparison, 52 human patients from the same region were infected with 31 M. leprae types. However, 42.3% (22/52) of patients were infected with 1 of the 2 M. leprae genotype strains associated with armadillos. The geographic range and complexity of zoonotic leprosy is expanding.
PDF
