We present the discovery of ASASSN-18ey (MAXI J1820+070), a new black hole low-mass X-ray binary (LMXB) discovered by the All-Sky Automated Survey for SuperNovae (ASAS-SN). A week after ASAS-SN ...discovered ASASSN-18ey as an optical transient, it was detected as an X-ray transient by MAXI/GCS. Here, we analyze ASAS-SN and Asteroid Terrestrial-impact Last Alert System pre-outburst optical light curves, finding evidence of intrinsic variability for several years prior to the outburst. While there was no long-term rise leading to the outburst, as has been seen in several other systems, the start of the outburst in the optical preceded that in the X-rays by 7.20 0.97 days. We analyze the spectroscopic evolution of ASASSN-18ey from pre-maximum to >100 days post-maximum. The spectra of ASASSN-18ey exhibit broad, asymmetric, double-peaked H emission. The Bowen blend (λ 4650 ) in the post-maximum spectra shows highly variable double-peaked profiles, likely arising from irradiation of the companion by the accretion disk, typical of low-mass X-ray binaries. The optical and X-ray luminosities of ASASSN-18ey are consistent with black hole low-mass X-ray binaries, both in outburst and quiescence.
Microgastrine wasps are among the most species‐rich and numerous parasitoids of caterpillars (Lepidoptera). They are often host‐specific and thus are extensively used in biological control efforts ...and figure prominently in trophic webs. However, their extraordinary diversity coupled with the occurrence of many cryptic species produces a significant taxonomic impediment. We present and release the results of 8 years (2004–2011) of DNA barcoding microgastrine wasps. Currently they are the best represented group of parasitoid Hymenoptera in the Barcode of Life Data System (BOLD), a massive barcode storage and analysis data management site for the International Barcoding of Life (iBOL) program. There are records from more than 20 000 specimens from 75 countries, including 50 genera (90% of the known total) and more than 1700 species (as indicated by Barcode Index Numbers and 2% MOTU). We briefly discuss the importance of this DNA data set and its collateral information for future research in: (1) discovery of cryptic species and description of new taxa; (2) estimating species numbers in biodiversity inventories; (3) clarification of generic boundaries; (4) biological control programmes; (5) molecular studies of host‐parasitoid biology and ecology; (6) evaluation of shifts in species distribution and phenology; and (7) fostering collaboration at national, regional and world levels. The integration of DNA barcoding with traditional morphology‐based taxonomy, host records, and other data has substantially improved the accuracy of microgastrine wasp identifications and will significantly accelerate further studies on this group of parasitoids.
Since the year 2000, a concerted campaign against malaria has led to unprecedented levels of intervention coverage across sub-Saharan Africa. Understanding the effect of this control effort is vital ...to inform future control planning. However, the effect of malaria interventions across the varied epidemiological settings of Africa remains poorly understood owing to the absence of reliable surveillance data and the simplistic approaches underlying current disease estimates. Here we link a large database of malaria field surveys with detailed reconstructions of changing intervention coverage to directly evaluate trends from 2000 to 2015, and quantify the attributable effect of malaria disease control efforts. We found that Plasmodium falciparum infection prevalence in endemic Africa halved and the incidence of clinical disease fell by 40% between 2000 and 2015. We estimate that interventions have averted 663 (542-753 credible interval) million clinical cases since 2000. Insecticide-treated nets, the most widespread intervention, were by far the largest contributor (68% of cases averted). Although still below target levels, current malaria interventions have substantially reduced malaria disease incidence across the continent. Increasing access to these interventions, and maintaining their effectiveness in the face of insecticide and drug resistance, should form a cornerstone of post-2015 control strategies.
The African naked mole-rat’s (Heterocephalus glaber) social and subterranean lifestyle generates a hypoxic niche. Under experimental conditions, naked mole-rats tolerate hours of extreme hypoxia and ...survive 18 minutes of total oxygen deprivation (anoxia) without apparent injury. During anoxia, the naked mole-rat switches to anaerobic metabolism fueled by fructose, which is actively accumulated and metabolized to lactate in the brain. Global expression of the GLUT5 fructose transporter and high levels of ketohexokinase were identified as molecular signatures of fructose metabolism. Fructose-driven glycolytic respiration in naked mole-rat tissues avoids feedback inhibition of glycolysis via phosphofructokinase, supporting viability. The metabolic rewiring of glycolysis can circumvent the normally lethal effects of oxygen deprivation, a mechanism that could be harnessed to minimize hypoxic damage in human disease.
Fusarium head blight (FHB),is a devastating disease of barley (Hordeum vulgare L.), causing reductions in yield and quality. Marker-based selection for resistance to FHB and lowered deoxynivalenol ...(DON) grain concentration would save considerable costs and time associated with phenotyping. A marker-based selection approach called genomic selection (GS) uses genomewide marker information to predict genetic value. We used a cross-validation approach that separated training sets from validation sets by both entry and environment. We used this framework to test the potential of GS for genetic improvement of FHB and DON as well as test the effect of different factors on prediction accuracy. Prediction accuracy for FHB was found to be as high as 0.72 and that for DON was found to be as high as 0.68. Little difference was found between marker effect estimation methods in terms of prediction of entry genetic value. The extensive linkage disequilibrium (LD) present in this population allowed the marker set to be reduced to 384 markers and training population (TP) size to be reduced 200 with little effect on prediction accuracy. We found little to no advantage to combining subpopulations that correspond to neighboring breeding programs to increase TP size. Apparently, little genetic information is shared between subpopulations, either because of different marker–quantitative trait loci (QTL) linkage phases, different segregating QTL, or nonadditive gene action.
We performed a genome-wide association study of 6447 bipolar disorder (BD) cases and 12 639 controls from the International Cohort Collection for Bipolar Disorder (ICCBD). Meta-analysis was performed ...with prior results from the Psychiatric Genomics Consortium Bipolar Disorder Working Group for a combined sample of 13 902 cases and 19 279 controls. We identified eight genome-wide significant, associated regions, including a novel associated region on chromosome 10 (rs10884920; P=3.28 × 10
) that includes the brain-enriched cytoskeleton protein adducin 3 (ADD3), a non-coding RNA, and a neuropeptide-specific aminopeptidase P (XPNPEP1). Our large sample size allowed us to test the heritability and genetic correlation of BD subtypes and investigate their genetic overlap with schizophrenia and major depressive disorder. We found a significant difference in heritability of the two most common forms of BD (BD I SNP-h
=0.35; BD II SNP-h
=0.25; P=0.02). The genetic correlation between BD I and BD II was 0.78, whereas the genetic correlation was 0.97 when BD cohorts containing both types were compared. In addition, we demonstrated a significantly greater load of polygenic risk alleles for schizophrenia and BD in patients with BD I compared with patients with BD II, and a greater load of schizophrenia risk alleles in patients with the bipolar type of schizoaffective disorder compared with patients with either BD I or BD II. These results point to a partial difference in the genetic architecture of BD subtypes as currently defined.
The Asteroid Terrestrial-impact Last Alert System (ATLAS) carries out its primary planetary defense mission by surveying about 13,000 deg2 at least four times per night. The resulting data set is ...useful for the discovery of variable stars to a magnitude limit fainter than r ∼ 18, with amplitudes down to 0.02 mag for bright objects. Here, we present a Data Release One catalog of variable stars based on analyzing the light curves of 142 million stars that were measured at least 100 times in the first two years of ATLAS operations. Using a Lomb-Scargle periodogram and other variability metrics, we identify 4.7 million candidate variables. Through the Space Telescope Science Institute, we publicly release light curves for all of them, together with a vector of 169 classification features for each star. We do this at the level of unconfirmed candidate variables in order to provide the community with a large set of homogeneously analyzed photometry and to avoid pre-judging which types of objects others may find most interesting. We use machine learning to classify the candidates into 15 different broad categories based on light-curve morphology. About 10% (427,000 stars) pass extensive tests designed to screen out spurious variability detections: we label these as "probable" variables. Of these, 214,000 receive specific classifications as eclipsing binaries, pulsating, Mira-type, or sinusoidal variables: these are the "classified" variables. New discoveries among the probable variables number 315,000, while 141,000 of the classified variables are new, including about 10,400 pulsating variables, 2060 Mira stars, and 74,700 eclipsing binaries.
In a phase III trial in patients with advanced, well-differentiated, progressive pancreatic neuroendocrine tumors, sunitinib 37.5 mg/day improved investigator-assessed progression-free survival (PFS) ...versus placebo (11.4 versus 5.5 months; HR, 0.42; P < 0.001). Here, we present PFS using retrospective blinded independent central review (BICR) and final median overall survival (OS), including an assessment highlighting the impact of patient crossover from placebo to sunitinib.
In this randomized, double-blind, placebo-controlled study, cross-sectional imaging from patients was evaluated retrospectively by blinded third-party radiologists using a two-reader, two-time-point lock, followed by a sequential locked-read, batch-mode paradigm. OS was summarized using the Kaplan–Meier method and Cox proportional hazards model. Crossover-adjusted OS effect was derived using rank-preserving structural failure time (RPSFT) analyses.
Of 171 randomized patients (sunitinib, n = 86; placebo, n = 85), 160 (94%) had complete scan sets/time points. By BICR, median (95% confidence interval CI) PFS was 12.6 (11.1–20.6) months for sunitinib and 5.8 (3.8–7.2) months for placebo (HR, 0.32; 95% CI 0.18–0.55; P = 0.000015). Five years after study closure, median (95% CI) OS was 38.6 (25.6–56.4) months for sunitinib and 29.1 (16.4–36.8) months for placebo (HR, 0.73; 95% CI 0.50–1.06; P = 0.094), with 69% of placebo patients having crossed over to sunitinib. RPSFT analysis confirmed an OS benefit for sunitinib.
BICR confirmed the doubling of PFS with sunitinib compared with placebo. Although the observed median OS improved by nearly 10 months, the effect estimate did not reach statistical significance, potentially due to crossover from placebo to sunitinib.
NCT00428597.
Neoadjuvant anti-PD-1 may improve outcomes for patients with resectable NSCLC and provides a critical window for examining pathologic features associated with response. Resections showing major ...pathologic response to neoadjuvant therapy, defined as ≤10% residual viable tumor (RVT), may predict improved long-term patient outcome. However, %RVT calculations were developed in the context of chemotherapy (%cRVT). An immune-related %RVT (%irRVT) has yet to be developed.
The first trial of neoadjuvant anti-PD-1 (nivolumab, NCT02259621) was just reported. We analyzed hematoxylin and eosin-stained slides from the post-treatment resection specimens of the 20 patients with non-small-cell lung carcinoma who underwent definitive surgery. Pretreatment tumor biopsies and preresection radiographic ‘tumor’ measurements were also assessed.
We found that the regression bed (the area of immune-mediated tumor clearance) accounts for the previously noted discrepancy between CT imaging and pathologic assessment of residual tumor. The regression bed is characterized by (i) immune activation—dense tumor infiltrating lymphocytes with macrophages and tertiary lymphoid structures; (ii) massive tumor cell death—cholesterol clefts; and (iii) tissue repair—neovascularization and proliferative fibrosis (each feature enriched in major pathologic responders versus nonresponders, P<0.05). This distinct constellation of histologic findings was not identified in any pretreatment specimens. Histopathologic features of the regression bed were used to develop ‘Immune-Related Pathologic Response Criteria’ (irPRC), and these criteria were shown to be reproducible amongst pathologists. Specifically, %irRVT had improved interobserver consistency compared with %cRVT median per-case %RVT variability 5% (0%–29%) versus 10% (0%–58%), P=0.007 and a twofold decrease in median standard deviation across pathologists within a sample (4.6 versus 2.2, P=0.002).
irPRC may be used to standardize pathologic assessment of immunotherapeutic efficacy. Long-term follow-up is needed to determine irPRC reliability as a surrogate for recurrence-free and overall survival.