We provide an overview of the design and capabilities of the near-infrared spectrograph (NIRSpec) onboard the
James Webb
Space Telescope. NIRSpec is designed to be capable of carrying out ...low-resolution (
R
= 30−330) prism spectroscopy over the wavelength range 0.6–5.3 μm and higher resolution (
R
= 500−1340 or
R
= 1320−3600) grating spectroscopy over 0.7–5.2 μm, both in single-object mode employing any one of five fixed slits, or a 3.1 × 3.2 arcsec
2
integral field unit, or in multiobject mode employing a novel programmable micro-shutter device covering a 3.6 × 3.4 arcmin
2
field of view. The all-reflective optical chain of NIRSpec and the performance of its different components are described, and some of the trade-offs made in designing the instrument are touched upon. The faint-end spectrophotometric sensitivity expected of NIRSpec, as well as its dependency on the energetic particle environment that its two detector arrays are likely to be subjected to in orbit are also discussed.
Clinical and Laboratory Standards Institute (CLSI) conditions for testing the susceptibilities of pathogenic
species to antifungal agents are based on a collaborative study that evaluated five ...clinically relevant isolates of
and some antifungal agents. With the advent of molecular identification, there are two basic needs: to confirm the suitability of these testing conditions for all agents and
species and to establish species-specific epidemiologic cutoff values (ECVs) or breakpoints (BPs) for the species. We collected available CLSI MICs/minimal effective concentrations (MECs) of amphotericin B, five triazoles, terbinafine, flucytosine, and caspofungin for 301
, 486
, 75
, and 13
molecularly identified isolates. Data were obtained in 17 independent laboratories (Australia, Europe, India, South Africa, and South and North America) using conidial inoculum suspensions and 48 to 72 h of incubation at 35°C. Sufficient and suitable data (modal MICs within 2-fold concentrations) allowed the proposal of the following ECVs for
and
, respectively: amphotericin B, 4 and 4 μg/ml; itraconazole, 2 and 2 μg/ml; posaconazole, 2 and 2 μg/ml; and voriconazole, 64 and 32 μg/ml. Ketoconazole and terbinafine ECVs for
were 2 and 0.12 μg/ml, respectively. Insufficient or unsuitable data precluded the calculation of ketoconazole and terbinafine (or any other antifungal agent) ECVs for
, as well as ECVs for
and
These ECVs could aid the clinician in identifying potentially resistant isolates (non-wild type) less likely to respond to therapy.
No systemic therapies have been approved for the treatment of advanced cutaneous squamous-cell carcinoma. This cancer may be responsive to immune therapy, because the mutation burden of the tumor is ...high and the disease risk is strongly associated with immunosuppression. In the dose-escalation portion of the phase 1 study of cemiplimab, a deep and durable response was observed in a patient with metastatic cutaneous squamous-cell carcinoma.
We report the results of the phase 1 study of cemiplimab for expansion cohorts of patients with locally advanced or metastatic cutaneous squamous-cell carcinoma, as well as the results of the pivotal phase 2 study for a cohort of patients with metastatic disease (metastatic-disease cohort). In both studies, the patients received an intravenous dose of cemiplimab (3 mg per kilogram of body weight) every 2 weeks and were assessed for a response every 8 weeks. In the phase 2 study, the primary end point was the response rate, as assessed by independent central review.
In the expansion cohorts of the phase 1 study, a response to cemiplimab was observed in 13 of 26 patients (50%; 95% confidence interval CI, 30 to 70). In the metastatic-disease cohort of the phase 2 study, a response was observed in 28 of 59 patients (47%; 95% CI, 34 to 61). The median follow-up was 7.9 months in the metastatic-disease cohort of the phase 2 study. Among the 28 patients who had a response, the duration of response exceeded 6 months in 57%, and 82% continued to have a response and to receive cemiplimab at the time of data cutoff. Adverse events that occurred in at least 15% of the patients in the metastatic-disease cohort of the phase 2 study were diarrhea, fatigue, nausea, constipation, and rash; 7% of the patients discontinued treatment because of an adverse event.
Among patients with advanced cutaneous squamous-cell carcinoma, cemiplimab induced a response in approximately half the patients and was associated with adverse events that usually occur with immune checkpoint inhibitors. (Funded by Regeneron Pharmaceuticals and Sanofi; ClinicalTrials.gov numbers, NCT02383212 and NCT02760498 .).
This work reports on the current status of the global modeling of iron (Fe)
deposition fluxes and atmospheric concentrations and the analyses of the
differences between models, as well as between ...models and observations. A
total of four global 3-D chemistry transport (CTMs) and general circulation
(GCMs) models participated in this intercomparison, in the framework of
the United Nations Joint Group of Experts on the Scientific Aspects of Marine
Environmental Protection (GESAMP) Working Group 38, “The Atmospheric Input
of Chemicals to the Ocean”. The global total Fe (TFe) emission strength in
the models is equal to ∼72 Tg Fe yr−1 (38–134 Tg Fe yr−1)
from mineral dust sources and around 2.1 Tg Fe yr−1 (1.8–2.7 Tg Fe yr−1)
from combustion processes (the sum of anthropogenic
combustion/biomass burning and wildfires). The mean global labile Fe (LFe)
source strength in the models, considering both the primary emissions and the
atmospheric processing, is calculated to be 0.7 (±0.3) Tg Fe yr−1,
accounting for both mineral dust and combustion aerosols. The
mean global deposition fluxes into the global ocean are estimated to be in the range
of 10–30 and 0.2–0.4 Tg Fe yr−1 for TFe and LFe, respectively,
which roughly corresponds to a respective 15 and 0.3 Tg Fe yr−1 for the multi-model ensemble model mean. The model intercomparison analysis indicates that the representation of the
atmospheric Fe cycle varies among models, in terms of both the magnitude of
natural and combustion Fe emissions as well as the complexity of atmospheric
processing parameterizations of Fe-containing aerosols. The model comparison
with aerosol Fe observations over oceanic regions indicates that most models
overestimate surface level TFe mass concentrations near dust source
regions and tend to underestimate the low concentrations observed in remote
ocean regions. All models are able to simulate the tendency of higher Fe
concentrations near and downwind from the dust source regions, with the mean
normalized bias for the Northern Hemisphere (∼14), larger
than that of the Southern Hemisphere (∼2.4) for the ensemble model
mean. This model intercomparison and model–observation comparison study
reveals two critical issues in LFe simulations that require further
exploration: (1) the Fe-containing aerosol size distribution and (2) the
relative contribution of dust and combustion sources of Fe to labile Fe in
atmospheric aerosols over the remote oceanic regions.
The Dark Energy Survey Image Processing Pipeline Morganson, E.; Gruendl, R. A.; Menanteau, F. ...
Publications of the Astronomical Society of the Pacific,
07/2018, Letnik:
130, Številka:
989
Journal Article
Recenzirano
Odprti dostop
The Dark Energy Survey (DES) is a five-year optical imaging campaign with the goal of understanding the origin of cosmic acceleration. DES performs a ∼5000 deg2 survey of the southern sky in five ...optical bands (g, r, i, z, Y) to a depth of ∼24th magnitude. Contemporaneously, DES performs a deep, time-domain survey in four optical bands (g, r, i, z) over ∼27 deg2. DES exposures are processed nightly with an evolving data reduction pipeline and evaluated for image quality to determine if they need to be retaken. Difference imaging and transient source detection are also performed in the time domain component nightly. On a bi-annual basis, DES exposures are reprocessed with a refined pipeline and coadded to maximize imaging depth. Here we describe the DES image processing pipeline in support of DES science, as a reference for users of archival DES data, and as a guide for future astronomical surveys.
Separating organics without distillation
Hydrocarbon distillation is a widespread and energy-intensive process. Membranes might offer an alternative approach, but few can survive immersion in organic ...solvents nor are they able to extract relatively small molecules. Thompson
et al.
developed a series of polymers of intrinsic microporosity that they used for membrane-based separations of organic compounds in an organic solvent (see the Perspective by Brennecke and Freeman). The new membrane has a molecular weight cutoff of 253 daltons, far lower than existing ones closer to 600 daltons. The polymers were used to separate light shale crude oil and succeeded in fractionation of molecular weights of about 170 daltons.
Science
this issue p.
310
; see also p.
254
Polymers enable nonthermal separation of crude oil components.
The fractionation of crude-oil mixtures through distillation is a large-scale, energy-intensive process. Membrane materials can avoid phase changes in such mixtures and thereby reduce the energy intensity of these thermal separations. With this application in mind, we created spirocyclic polymers with
N
-aryl bonds that demonstrated noninterconnected microporosity in the absence of ladder linkages. The resulting glassy polymer membranes demonstrated nonthermal membrane fractionation of light crude oil through a combination of class- and size-based “sorting” of molecules. We observed an enrichment of molecules lighter than 170 daltons corresponding to a carbon number of 12 or a boiling point less than 200°C in the permeate. Such scalable, selective membranes offer potential for the hybridization of energy-efficient technology with conventional processes such as distillation.
The malaria parasite, which is transmitted by several Anopheles mosquito species, requires more time to reach its human-transmissible stage than the average lifespan of mosquito vectors. Monitoring ...the species-specific age structure of mosquito populations is critical to evaluating the impact of vector control interventions on malaria risk. We present a rapid, cost-effective surveillance method based on deep learning of mid-infrared spectra of mosquito cuticle that simultaneously identifies the species and age class of three main malaria vectors in natural populations. Using spectra from over 40, 000 ecologically and genetically diverse An. gambiae, An. arabiensis, and An. coluzzii females, we develop a deep transfer learning model that learns and predicts the age of new wild populations in Tanzania and Burkina Faso with minimal sampling effort. Additionally, the model is able to detect the impact of simulated control interventions on mosquito populations, measured as a shift in their age structures. In the future, we anticipate our method can be applied to other arthropod vector-borne diseases.
The purpose of this work was to develop an end-to-end patient-specific quality assurance (QA) technique for spot-scanned proton therapy that is more sensitive and efficient than traditional ...approaches. The patient-specific methodology relies on independently verifying the accuracy of the delivered proton fluence and the dose calculation in the heterogeneous patient volume. A Monte Carlo dose calculation engine, which was developed in-house, recalculates a planned dose distribution on the patient CT data set to verify the dose distribution represented by the treatment planning system. The plan is then delivered in a pre-treatment setting and logs of spot position and dose monitors, which are integrated into the treatment nozzle, are recorded. A computational routine compares the delivery log to the DICOM spot map used by the Monte Carlo calculation to ensure that the delivered parameters at the machine match the calculated plan. Measurements of dose planes using independent detector arrays, which historically are the standard approach to patient-specific QA, are not performed for every patient. The nozzle-integrated detectors are rigorously validated using independent detectors in regular QA intervals. The measured data are compared to the expected delivery patterns. The dose monitor reading deviations are reported in a histogram, while the spot position discrepancies are plotted vs. spot number to facilitate independent analysis of both random and systematic deviations. Action thresholds are linked to accuracy of the commissioned delivery system. Even when plan delivery is acceptable, the Monte Carlo second check system has identified dose calculation issues which would not have been illuminated using traditional, phantom-based measurement techniques. The efficiency and sensitivity of our patient-specific QA program has been improved by implementing a procedure which independently verifies patient dose calculation accuracy and plan delivery fidelity. Such an approach to QA requires holistic integration and maintenance of patient-specific and patient-independent QA.
Anti-programmed cell death protein 1 (PD-1) antibodies (PD1) prolong recurrence-free survival in high-risk resected melanoma; however, approximately 25%–30% of patients recur within 1 year. This ...study describes the pattern of recurrence, management and outcomes of patients who recur with adjuvant PD1 therapy.
Consecutive patients from 16 centres who recurred having received adjuvant PD1 therapy for resected stage III/IV melanoma were studied. Recurrence characteristics, management and outcomes were examined; patients with mucosal melanoma were analysed separately.
Melanoma recurrence occurred in 147 (17%) of ∼850 patients treated with adjuvant PD1. In those with cutaneous melanoma (n = 136), median time to recurrence was 4.6 months (range 0.3–35.7); 104 (76%) recurred during (ON) adjuvant PD1 after a median 3.2 months and 32 (24%) following (OFF) treatment cessation after a median 12.5 months, including in 21 (15%) who ceased early for toxicity. Fifty-nine (43%) recurred with locoregional disease only and 77 (57%) with distant disease. Of those who recurred locally, 22/59 (37%) subsequently recurred distantly. Eighty-nine (65%) patients received systemic therapy after recurrence. Of those who recurred ON adjuvant PD1, none (0/6) responded to PD1 alone; 8/33 assessable patients (24%) responded to ipilimumab (alone or in combination with PD1) and 18/23 (78%) responded to BRAF/MEK inhibitors. Of those who recurred OFF adjuvant PD1, two out of five (40%) responded to PD1 monotherapy, two out of five (40%) responded to ipilimumab-based therapy and 9/10 (90%) responded to BRAF/MEK inhibitors.
Most patients who recur early despite adjuvant PD1 develop distant metastases. In those who recur ON adjuvant PD1, there is minimal activity of further PD1 monotherapy, but ipilimumab (alone or in combination with PD1) and BRAF/MEK inhibitors have clinical utility. Retreatment with PD1 may have activity in select patients who recur OFF PD1.
•Melanoma recurrence occurred in 147 (17%) of 850 patients, after a median 4.6 months after starting adjuvant PD1.•At initial recurrence, 57% had distant metastases, mostly detected on imaging while asymptomatic.•Some 38% of patients with initial local recurrence then recurred distantly within short follow-up (median 8.3 months).•PD1 monotherapy was not active in those who recurred ON adjuvant PD1, but had activity in those who recurred OFF adjuvant PD1.•BRAF/MEK inhibitors and ipilimumab (alone or in combination with PD1) had the highest activity in this setting.
PDF
