We present an investigation of the optical spectra of 264 low-redshift (z < 0.2) Type Ia supernovae (SNe Ia) discovered by the Palomar Transient Factory, an untargeted transient survey. We focus on ...velocity and pseudo-equivalent width measurements of the Si ii 4130, 5972, and 6355 Å lines, as well those of the Ca ii near-infrared (NIR) triplet, up to +5 days relative to the SN B-band maximum light. We find that a high-velocity component of the Ca ii NIR triplet is needed to explain the spectrum in ∼95 per cent of SNe Ia observed before −5 days, decreasing to ∼80 per cent at maximum. The average velocity of the Ca ii high-velocity component is ∼8500 km s−1 higher than the photospheric component. We confirm previous results that SNe Ia around maximum light with a larger contribution from the high-velocity component relative to the photospheric component in their Ca ii NIR feature have, on average, broader light curves and lower Ca ii NIR photospheric velocities. We find that these relations are driven by both a stronger high-velocity component and a weaker contribution from the photospheric Ca ii NIR component in broader light curve SNe Ia. We identify the presence of C ii in very-early-time SN Ia spectra (before −10 days), finding that >40 per cent of SNe Ia observed at these phases show signs of unburnt material in their spectra, and that C ii features are more likely to be found in SNe Ia having narrower light curves.
Neoadjuvant chemotherapy improves outcome in osteosarcoma. Determination of optimum regimens for survival, toxicity and prognostic factors requires randomised controlled trials to be conducted.
...Between 1983 and 2002, the European Osteosarcoma Intergroup recruited 1067 patients with localised extremity osteosarcoma to three randomised controlled trials. Standard treatment in each was doxorubicin 75 mg/m2 and cisplatin 100 mg/m2. Comparators were addition of methotrexate (BO02/80831), a multidrug regimen (BO03/80861) and a dose-intense schedule (BO06/80931). Standard survival analysis methods were used to identify prognostic factors, temporal and other influences on outcome.
Five- and 10-year survival were 56% (95% confidence interval 53% to 59%) and 52%, respectively (49% to 55%), with no difference between trials or treatment arms. Median follow-up was 9.4 years. Age range was 3–40 years (median 15). Limb salvage was achieved in 69%. Five hundred and thirty-three patients received the standard arm, 79% completing treatment. Good histological response to preoperative chemotherapy, distal tumour location (all sites other than proximal humerus/femur) and female gender were associated with improved survival.
Localised osteosarcoma will be cured in 50% of patients with cisplatin and doxorubicin. Large randomised trials can be conducted in this rare cancer. Failure to improve survival over 20 years argues for concerted collaborative international efforts to identify and rapidly test new treatments.
This manuscript describes the experience from registration until randomisation for a cohort of 2260 patients with osteosarcoma who joined the EURAMOS-1 trial. This includes pre-operative chemotherapy ...and surgery. It sets out the practical issues in collaboration and in achieving randomisation.
Four international study groups undertook a large study in resectable osteosarcoma, which included two randomised controlled trials, to determine the effect on survival of changing post-operative chemotherapy based on histological response.
Patients with resectable osteosarcoma aged ≤40 years were treated with the MAP regimen, comprising pre-operatively of two 5-week cycles of cisplatin 120 mg/m2, doxorubicin 75 mg/m2, methotrexate 12 g/m2 × 2 (MAP) and post-operatively two further cycles of MAP and two cycles of just MA. Patients were randomised after surgery. Those with ≥10% viable tumour in the resected specimen received MAP or MAP with ifosfamide and etoposide. Those with <10% viable tumour were allocated to MAP or MAP followed by pegylated interferon. Longitudinal evaluation of quality of life was undertaken.
Recruitment was completed to the largest osteosarcoma study to date in 75 months. Commencing March 2005, 2260 patients were registered from 326 centres across 17 countries. About 1334 of 2260 registered patients (59%) were randomised. Pre-operative chemotherapy was completed according to protocol in 94%. Grade 3–4 neutropenia affected 83% of cycles and 59% were complicated by infection. There were three (0.13%) deaths related to pre-operative chemotherapy. At definitive surgery, 50% of patients had at least 90% necrosis in the resected specimen.
New models of collaboration are required to successfully conduct trials to improve outcomes of patients with rare cancers; EURAMOS-1 demonstrates achievability. Considerable regulatory, financial and operational challenges must be overcome to develop similar studies in the future.
The trial is registered as NCT00134030 and ISRCTN 67613327.
There is a consensus that type Ia supernovae (SNe Ia) arise from the thermonuclear explosion of white dwarf stars that accrete matter from a binary companion. However, direct observation of SN Ia ...progenitors is lacking, and the precise nature of the binary companion remains uncertain. A temporal series of high-resolution optical spectra of the SN Ia PTF 11kx reveals a complex circumstellar environment that provides an unprecedentedly detailed view of the progenitor system. Multiple shells of circumstellar material are detected, and the SN ejecta are seen to interact with circumstellar material starting 59 days after the explosion. These features are best described by a symbiotic nova progenitor, similar to RS Ophiuchi.
We present observational constraints on the nature of dark energy using the Supernova Legacy Survey three-year sample (SNLS3) of Guy et al. and Conley et al. We use the 472 Type Ia supernovae (SNe ...Ia) in this sample, accounting for recently discovered correlations between SN Ia luminosity and host galaxy properties, and include the effects of all identified systematic uncertainties directly in the cosmological fits. Combining the SNLS3 data with the full WMAP7 power spectrum, the Sloan Digital Sky Survey luminous red galaxy power spectrum, and a prior on the Hubble constant H 0 from SHOES, in a flat universe we find Delta *W m = 0.269 ? 0.015 and w = --1.061+0.069 -- 0.068 (where the uncertainties include all statistical and SN Ia systematic errors)--a 6.5% measure of the dark energy equation-of-state parameter w. The statistical and systematic uncertainties are approximately equal, with the systematic uncertainties dominated by the photometric calibration of the SN Ia fluxes--without these calibration effects, systematics contribute only a ~2% error in w. When relaxing the assumption of flatness, we find Delta *W m = 0.271 ? 0.015, Delta *W k = --0.002 ? 0.006, and w = --1.069+0.091 -- 0.092. Parameterizing the time evolution of w as w(a) = w 0 + wa (1 -- a) gives w 0 = --0.905 ? 0.196, wa = --0.984+1.094 -- 1.097 in a flat universe. All of our results are consistent with a flat, w = --1 universe. The size of the SNLS3 sample allows various tests to be performed with the SNe segregated according to their light curve and host galaxy properties. We find that the cosmological constraints derived from these different subsamples are consistent. There is evidence that the coefficient, Delta *b, relating SN Ia luminosity and color, varies with host parameters at >4 Delta *s significance (in addition to the known SN luminosity-host relation); however, this has only a small effect on the cosmological results and is currently a subdominant systematic.
We combine high-redshift Type Ia supernovae from the first three years of the Supernova Legacy Survey (SNLS) with other supernova (SN) samples, primarily at lower redshifts, to form a high-quality ...joint sample of 472 SNe (123 low-z, 93 SDSS, 242 SNLS, and 14 Hubble Space Telescope). SN data alone require cosmic acceleration at >99.999% confidence, including systematic effects. For the dark energy equation of state parameter (assumed constant out to at least z = 1.4) in a flat universe, we find w = --0.91+0.16 --0.20(stat)+0.07 --0.14(sys) from SNe only, consistent with a cosmological constant. Our fits include a correction for the recently discovered relationship between host-galaxy mass and SN absolute brightness. We pay particular attention to systematic uncertainties, characterizing them using a systematic covariance matrix that incorporates the redshift dependence of these effects, as well as the shape-luminosity and color-luminosity relationships. Unlike previous work, we include the effects of systematic terms on the empirical light-curve models. The total systematic uncertainty is dominated by calibration terms. We describe how the systematic uncertainties can be reduced with soon to be available improved nearby and intermediate-redshift samples, particularly those calibrated onto USNO/SDSS-like systems.
Summary
Background
Recessive dystrophic epidermolysis bullosa (RDEB) is a severe systemic genodermatosis lacking therapies beyond supportive care for its extensive, life‐limiting manifestations.
...Objectives
To report the safety and preliminary responses of 10 patients with RDEB to bone marrow transplant (BMT) with post‐transplant cyclophosphamide (PTCy BMT) after reduced‐intensity conditioning with infusions of immunomodulatory donor‐derived mesenchymal stromal cells (median follow‐up 16 months).
Methods
BMT toxicities, donor blood and skin engraftment, skin biopsies, photographic and dynamic assessments of RDEB disease activity were obtained at intervals from pre‐BMT to 1 year post‐BMT.
Results
Related donors varied from haploidentical (n = 6) to human leucocyte antigen (HLA)‐matched (n = 3), with one HLA‐matched unrelated donor. Transplant complications included graft failure (n = 3; two pursued a second PTCy BMT), veno‐occlusive disease (n = 2), posterior reversible encephalopathy (n = 1) and chronic graft‐versus‐host disease (n = 1; this patient died). In the nine ultimately engrafted patients, median donor chimerism at 180 days after transplant was 100% in peripheral blood and 27% in skin. Skin biopsies showed stable (n = 7) to improved (n = 2) type VII collagen protein expression by immunofluorescence and gain of anchoring fibril components (n = 3) by transmission electron microscopy. Early signs of clinical response include trends toward reduced body surface area of blisters/erosions from a median of 49·5% to 27·5% at 100 days after BMT (P = 0·05), with parental measures indicating stable quality of life.
Conclusions
PTCy BMT in RDEB provides a means of attaining immunotolerance for future donor‐derived cellular grafts (ClinicalTrials.gov identifier NCT02582775).
What's already known about this topic?
Severe, generalized recessive dystrophic epidermolysis bullosa (RDEB) is marked by great morbidity and early death.
No cure currently exists for RDEB.
Bone marrow transplant (BMT) is the only described systemic therapy for RDEB.
What does this study add?
The first description of post‐transplant cyclophosphamide (PTCy) BMT for RDEB.
PTCy was well tolerated and provided excellent graft‐versus‐host disease prophylaxis, replacing long courses of calcineurin inhibitors in patients receiving human leucocyte antigen‐matched sibling BMT.
What is the translational message?
The PTCy BMT platform permits identification of a suitable related donor for most patients and for subsequent adoptive transfer of donor nonhaematopoietic cells after establishment of immunological tolerance.
Respond to this article
Plain language summary available online
Context.
AT 2019abn was discovered in the nearby M51 galaxy by the Zwicky Transient Facility at more than two magnitudes and around three weeks prior to its optical peak.
Aims.
We aim to conduct a ...detailed photometric and spectroscopic follow-up campaign for AT 2019abn, with early discovery allowing for significant pre-maximum observations of an intermediate luminosity red transient (ILRT) for the first time.
Methods.
This work is based on the analysis of
u
′
B
V
r
′
i
′
z
′
H
photometry and low-resolution spectroscopy using the Liverpool Telescope, medium-resolution spectroscopy with the Gran Telescopio Canarias (GTC), and near-infrared imaging with the GTC and the Nordic Optical Telescope.
Results.
We present the most detailed optical light curve of an ILRT to date, with multi-band photometry starting around three weeks before peak brightness. The transient peaked at an observed absolute magnitude of
M
r
′
= −13.1, although it is subject to significant reddening from dust in M51, implying an intrinsic
M
r
′
∼ −15.2. The initial light curve showed a linear, achromatic rise in magnitude before becoming bluer at peak. After peak brightness, the transient gradually cooled. This is reflected in our spectra, which at later times show absorption from such species as Fe
I
, Ni
I
and Li
I
. A spectrum taken around peak brightness shows narrow, low-velocity absorption lines, which we interpret as likely to originate from pre-existing circumstellar material.
Conclusions.
We conclude that while there are some peculiarities, such as the radius evolution, AT 2019abn fits in well overall with the ILRT class of objects and is the most luminous member of the class seen to date.
In addition to vesicle release at synaptic ribbons, rod photoreceptors are capable of substantial slow release at non-ribbon release sites triggered by Ca(2+)-induced Ca(2+) release (CICR) from ...intracellular stores. To maintain CICR as rods remain depolarized in darkness, we hypothesized that Ca(2+) released into the cytoplasm from terminal endoplasmic reticulum (ER) can be replenished continuously by ions diffusing within the ER from the soma. We measured Ca(2+) changes in cytoplasm and ER of rods from Ambystoma tigrinum retina using various dyes. ER Ca(2+) changes were measured by loading ER with fluo-5N and then washing dye from the cytoplasm with a dye-free patch pipette solution. Small dye molecules diffused within ER between soma and terminal showing a single continuous ER compartment. Depolarization of rods to -40 mV depleted Ca(2+) from terminal ER, followed by a decline in somatic ER Ca(2+). Local activation of ryanodine receptors in terminals with a spatially confined puff of ryanodine caused a decline in terminal ER Ca(2+), followed by a secondary decrease in somatic ER. Localized photolytic uncaging of Ca(2+) from o-nitrophenyl-EGTA in somatic ER caused an abrupt Ca(2+) increase in somatic ER, followed by a slower Ca(2+) increase in terminal ER. These data suggest that, during maintained depolarization, a soma-to-terminal Ca(2+) gradient develops within the ER that promotes diffusion of Ca(2+) ions to resupply intraterminal ER Ca(2+) stores and thus sustain CICR-mediated synaptic release. The ability of Ca(2+) to move freely through the ER may also promote bidirectional communication of Ca(2+) changes between soma and terminal.
Vertebrate rod and cone photoreceptors both release vesicles at synaptic ribbons, but rods also exhibit substantial slow release at non-ribbon sites triggered by Ca(2+)-induced Ca(2+) release (CICR). Blocking CICR inhibits >50% of release from rods in darkness. How do rods maintain sufficiently high Ca(2+) in terminal endoplasmic reticulum (ER) to support sustained CICR-driven synaptic transmission? We show that maintained depolarization creates a Ca(2+) gradient within the rod ER lumen that promotes soma-to-terminal diffusion of Ca(2+) to replenish intraterminal ER stores. This mechanism allows CICR-triggered synaptic release to be sustained indefinitely while rods remain depolarized in darkness. Free diffusion of Ca(2+) within the ER may also communicate synaptic Ca(2+) changes back to the soma to influence other critical cell processes.
Spatial estimates of crop evapotranspiration with high accuracy from the field to watershed scale have become increasingly important for water management, particularly over irrigated agriculture in ...semiarid regions. Here, we provide a comprehensive assessment on patterns of annual agricultural water use over California's Central Valley, using 30‐m daily evapotranspiration estimates based on Landsat satellite data. A semiempirical Priestley‐Taylor approach was locally optimized and cross‐validated with available field measurements for major crops including alfalfa, almond, citrus, corn, pasture, and rice. The evapotranspiration estimates explained >70% variance in daily measurements from independent sites with an RMSE of 0.88 mm day−1. When aggregated over the Valley, we estimated an average evapotranspiration of 820 ± 290 mm yr−1 in 2014. Agricultural water use varied significantly across and within crop types, with a coefficient of variation ranging from 8% for Rice (1,110 ± 85 mm yr−1) to 59% for Pistachio (592 ± 352 mm yr−1). Total water uses in 2016 increased by 9.6%, as compared to 2014, mostly because of land‐use conversion from fallow/idle land to cropland. Analysis across 134 Groundwater Sustainability Agencies (GSAs) further showed a large variation of agricultural evapotranspiration among and within GSAs, especially for tree crops, e.g., almond evapotranspiration ranging from 339 ± 80 mm yr−1 in Tracy to 1,240 ± 136 mm yr−1 in Tri‐County Water Authority. Continuous monitoring and assessment of the dynamics and spatial heterogeneity of agricultural evapotranspiration provide data‐driven guidance for more effective land use and water planning across scales.
Key Points
A 30‐m daily evapotranspiration product estimated using regionally optimized approach and Landsat Analysis Ready Data Collection 1
Assessment of agricultural consumptive water use over Central Valley provides critical guidance for sustainable groundwater management
Large variation of water use was found, mostly due to crop diversity, age structure, and physiological factors
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