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Although autism spectrum disorders (ASDs) have a substantial genetic basis, most of the known genetic risk has been traced to rare variants, principally copy number variants (CNVs). To identify common risk variation, the Autism Genome Project (AGP) Consortium genotyped 1558 rigorously defined ASD families for 1 million single-nucleotide polymorphisms (SNPs) and analyzed these SNP genotypes for association with ASD. In one of four primary association analyses, the association signal for marker rs4141463, located within MACROD2, crossed the genome-wide association significance threshold of P < 5 × 10−8. When a smaller replication sample was analyzed, the risk allele at rs4141463 was again over-transmitted; yet, consistent with the winner's curse, its effect size in the replication sample was much smaller; and, for the combined samples, the association signal barely fell below the P < 5 × 10−8 threshold. Exploratory analyses of phenotypic subtypes yielded no significant associations after correction for multiple testing. They did, however, yield strong signals within several genes, KIAA0564, PLD5, POU6F2, ST8SIA2 and TAF1C.
We report measurements of Xi and Xi-bar hyperon absolute yields as a function of rapidity in 158 GeV/c Pb+Pb collisions. At midrapidity, dN/dy = 2.29 +/- 0.12 for Xi, and 0.52 +/- 0.05 for Xi-bar, leading to the ratio of Xi-bar/Xi = 0.23 +/- 0.03. Inverse slope parameters fitted to the measured transverse mass spectra are of the order of 300 MeV near mid-rapidity. The estimated total yield of Xi particles in Pb+Pb central interactions amounts to 7.4 +/- 1.0 per collision. Comparison to Xi production in properly scaled p+p reactions at the same energy reveals a dramatic enhancement (about one order of magnitude) of Xi production in Pb+Pb central collisions over elementary hadron interactions.
The large acceptance TPCs of the NA49 spectrometer allow for a systematic multidimensional study of two-particle correlations in different part of phase space. Results from Bertsch-Pratt and Yano-Koonin-Podgoretskii parametrizations are presented differentially in transverse pair momentum and pair rapidity. These studies give an insight into the dynamical space-time evolution of relativistic Pb+Pb collisions, which is dominated by longitudinal expansion.
Two-particle correlation functions of negative hadrons over wide phase space, and transverse mass spectra of negative hadrons and deuterons near mid-rapidity have been measured in central Pb+Pb collisions at 158 GeV per nucleon by the NA49 experiment at the CERN SPS. A novel Coulomb correction procedure for the negative two-particle correlations is employed making use of the measured oppositely charged particle correlation. Within an expanding source scenario these results are used to extract the dynamic characteristics of the hadronic source, resolving the ambiguities between the temperature and transverse expansion velocity of the source, that are unavoidable when single and two particle spectra are analysed separately. The source shape, the total duration of the source expansion, the duration of particle emission, the freeze-out temperature and the longitudinal and transverse expansion velocities are deduced.
The directed and elliptic flow of protons and charged pions has been observed from the semi-central collisions of a 158 GeV/nucleon Pb beam with a Pb target. The rapidity and transverse momentum dependence of the flow has been measured. The directed flow of the pions is opposite to that of the protons but both exhibit negative flow at low pt. The elliptic flow of both is fairly independent of rapidity but rises with pt. PACS numbers: 25.75.-q, 25.75.Ld
Using the NA49 main TPC, the central production of hyperons has been measured in CERN SPS Pb - Pb collisions at 158 GeV c-1. The preliminary ratio, studied at 2.0 < y < 2.6 and 1 < pT < 3 GeV c-1, equals ~ (13 ± 4)% (systematic error only). It is compatible, within errors, with the previously obtained ratios for central S + S [1], S + W [2], and S + Au [3] collisions. The fit to the transverse momentum distribution resulted in an inverse slope parameter T of 297 MeV. At this level of statistics we do not see any noticeable enhancement of hyperon production with the increased volume (and, possibly, degree of equilibration) of the system from S + S to Pb + Pb. This result is unexpected and counterintuitive, and should be further investigated. If confirmed, it will have a significant impact on our understanding of mechanisms leading to the enhanced strangeness production in heavy-ion collisions.
Preliminary data on phi production in central Pb + Pb collisions at 158 GeV per nucleon are presented, measured by the NA49 experiment in the hadronic decay channel phi - K+K-. At mid-rapidity, the kaons were separated from pions and protons by combining dE/dx and time-of-flight information; in the forward rapidity range only dE/dx identification was used to obtain the rapidity distribution and a rapidity-integrated mt-spectrum. The mid-rapidity yield obtained was dN/dy = 1.85 ± 0.3 per event; the total phi multiplicity was estimated to be 5.0 ± 0.7 per event. Comparison with published pp data shows a slight, but not very significant strangeness enhancement.
Lambda and Antilambda reconstruction in central Pb+Pb collisions using a time projection chamber
(1997)
The large acceptance time projection chambers of the NA49 experiment are used to record the trajectory of charged particles from Pb + Pb collisions at 158 GeV per nucleon. Neutral strange hadrons have been reconstructed from their charged decay products. To obtain distributions of Λ, and Ks0 in discrete bins of rapidity, y, and transverse momentum, pT, calculations have been performed to determine the acceptance of the detector and the efficiency of the reconstruction software as a function of both variables. The lifetime distributions obtained give values of cτ = 7.8 ± 0.6 cm for Λ and cτ = 2.5 ± 0.3 cm for Ks0, consistent with data book values.
Iberia has one of the richest bee faunas in the world, and the genus Andrena is no exception with around 200 species known from the Peninsula. The fauna of Andrena was largely revised in the 1970s, but since then, it has received little attention. Molecular investigation of the taxonomically challenging subgenus Taeniandrena has revealed that the situation is more complicated than previously thought with several cryptic and overlooked species. From the species allied to Andrena (T. ) gelriae van der Vecht, 1927, Andrena (T. ) gredana Warncke, 1975 stat. nov. from Spain and Portugal is raised to species status, and Andrena (T. ) levante Wood & Praz sp. nov. from southeastern Spain is newly described. Furthermore, Andrena (T. ) benoisti Wood & Praz sp. nov. is described, having previously been referred to as Andrena (T. ) wilkella beaumonti Benoist, 1961. Andrena (T. ) beaumonti stat. rev. is itself distinct and restricted to the High Atlas Mountains of Morocco. Outside of the subgenus Taeniandrena, Andrena (Euandrena) fortipunctata Wood sp. nov. and Andrena (Charitandrena) hattorfiana nigricauda Wood subsp. nov. are described from Spain, and Andrena (Notandrena) juliana Wood sp. nov. is described from Spain and Portugal. The male of Andrena (Lepidandrena) baetica Wood, 2020 is also described. Andrena (Euandrena) impressa Warncke, 1967 stat. nov. is raised to species status, displaying a West Mediterranean distribution. Finally, a further two species of Andrena are newly recorded for Spain, Andrena laurivora Warncke, 1974 and Andrena confinis Stoeckhert, 1930. Altogether, these findings reinforce the fact that our understanding of the taxonomy and distribution of Andrena in southern Europe remains incomplete.
Background: Tisagenlecleucel, an anti-CD19 chimeric antigen receptor T cell therapy, has demonstrated efficacy in children and young adults with relapsed/refractory B cell acute lymphoblastic leukemia (B-ALL) in two multicenter phase 2 trials (ClinicalTrials.gov, NCT02435849 (ELIANA) and NCT02228096 (ENSIGN)), leading to commercialization of tisagenlecleucel for the treatment of patients up to age 25 years with B-ALL that is refractory or in second or greater relapse.
Methods: A pooled analysis of 137 patients from these trials (ELIANA: n=79; ENSIGN: n=58) was performed to provide a comprehensive safety profile for tisagenlecleucel.
Results: Grade 3/4 tisagenlecleucel-related adverse events (AEs) were reported in 77% of patients. Specific AEs of interest that occurred ≤8 weeks postinfusion included cytokine-release syndrome (CRS; 79% (grade 4: 22%)), infections (42%; grade 3/4: 19%), prolonged (not resolved by day 28) cytopenias (40%; grade 3/4: 34%), neurologic events (36%; grade 3: 10%; no grade 4 events), and tumor lysis syndrome (4%; all grade 3). Treatment for CRS included tocilizumab (40%) and corticosteroids (23%). The frequency of neurologic events increased with CRS severity (p<0.001). Median time to resolution of grade 3/4 cytopenias to grade ≤2 was 2.0 (95% CI 1.87 to 2.23) months for neutropenia, 2.4 (95% CI 1.97 to 3.68) months for lymphopenia, 2.0 (95% CI 1.87 to 2.27) months for leukopenia, 1.9 (95% CI 1.74 to 2.10) months for thrombocytopenia, and 1.0 (95% CI 0.95 to 1.87) month for anemia. All patients who achieved complete remission (CR)/CR with incomplete hematologic recovery experienced B cell aplasia; however, as nearly all responders also received immunoglobulin replacement, few grade 3/4 infections occurred >1 year postinfusion.
Conclusions: This pooled analysis provides a detailed safety profile for tisagenlecleucel during the course of clinical trials, and AE management guidance, with a longer follow-up duration compared with previous reports.
India is a large country in Asia, and covers the transition zone between the Palaearctic and Indomalayan biogeographic realms, with influences from both. Present in India are members of the genus Andrena, an enormous bee genus distributed predominantly throughout the Holarctic, with the greatest Indian diversity in the Himalayan region due to its Palaearctic influences. Despite early studies in the late 19th and early 20th centuries, there has been almost no work on this group in India during the past century. A revision of type and non-type museum material combined with new collections has produced a revised total of 36 species of Andrena for India, including 11 species reported for the first time as well as the newly described Andrena (Melandrena) kedarnatha Wood & Gautam sp. nov. (northern India and Nepal) and Andrena (Simandrena) tungnatha Wood & Gautam sp. nov. (northern India). The true holotype of A. (Euandrena) communis Smith, 1879 is definitively located. Andrena burkelii Bingham, 1908 is synonymised with A. (Pallandrena) morosa Cameron, 1897. Lectotypes are designated for A. (Euandrena) murreensis Cockerell, 1923 and A. (incertae sedis) comberima beharica Cockerell, 1920. Further comments are made on the status of Andrena taxa described from India for which type material is and is not currently available. Thirty additional Andrena taxa suggested as present in the Indian fauna are excluded as either erroneous or lacking supporting data. These results illustrate the extent to which study of the Indian Andrena fauna has been confused, and provide a more stable taxonomic base for future studies in this country.
Iran is a huge but understudied Middle Eastern country with a rich but chronically understudied bee fauna, including for the highly-speciose bee genus Andrena. Examination of unidentified museum material combined with recent field collections and a critical review of the literature has revealed a total of 197 species of Andrena in the Iranian fauna, of which 65 are newly reported for the country, with an additional 16 species new for science. Andrena (Aciandrena) deminuta Wood sp. nov., Andrena (Euandrena) boustaniae Wood sp. nov., Andrena (Euandrena) oblata sp. nov., Andrena (Euandrena) sani sp. nov., Andrena (Micrandrena) elam Wood sp. nov., Andrena (Micrandrena) subviridula Wood sp. nov., Andrena (Notandrena) idigna Wood sp. nov., Andrena (Planiandrena) flagrans Wood sp. nov., Andrena (Planiandrena) sella Wood sp. nov., Andrena (Ulandrena) bulbosa Wood sp. nov., Andrena (incertae sedis) hosseiniiae Wood & Monfared sp. nov., and Andrena (incertae sedis) rostamiae sp. nov. are described from Iran, Andrena (Micrandrena) extenuata sp. nov. is described from Iran and Syria, Andrena (Micrandrena) tabula Wood sp. nov. and Andrena (Micrandrena) obsidiana Wood sp. nov. are described from Iran and Turkey, and Andrena (Planiandrena) huma sp. nov. is described from Iran, Syria, and the Golan Heights. Eight taxa are synonymised (valid name first): Andrena (Melandrena) assimilis Radoszkowski, 1876 = Andrena (Melandrena) gallica Schmiedeknecht, 1883 syn. nov.; Andrena (Notandrena) emesiana Pérez, 1911 stat. resurr. = Andrena (Notandrena) recurvirostra Warncke, 1975 syn. nov.; Andrena (Plastandrena) eversmanni Radoszkowski, 1867 = Andrena (Plastandrena) peshinica Nurse, 1904 syn. nov.; Andrena (incertae sedis) hieroglyphica Morawitz, 1876 = Andrena (Carandrena) cara Nurse, 1904 syn. nov. and Andrena (Carandrena) halictoides Nurse, 1904 syn. nov.; Andrena (Melandrena) induta Morawitz, 1894 = Andrena (Melandrena) patella Nurse, 1903 syn. nov.; Andrena (incertae sedis) minor Warncke, 1975 stat. nov. = Andrena (Carandrena) splendula Osytshnjuk, 1984 syn. nov.; Andrena (Notandrena) zostera Warncke, 1975 = Andrena (Carandrena) subsmaragdina Osytshnjuk, 1984 syn. nov. Overall, these results considerably improve our understanding of the Iranian Andrena fauna, and suggest that overall bee diversity in this country is substantially more than 1000 species.