63 research outputs found

    Statistical strategies for avoiding false discoveries in metabolomics and related experiments

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    Search for gravitational-wave transients associated with magnetar bursts in advanced LIGO and advanced Virgo data from the third observing run

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    Gravitational waves are expected to be produced from neutron star oscillations associated with magnetar giant f lares and short bursts. We present the results of a search for short-duration (milliseconds to seconds) and longduration (∼100 s) transient gravitational waves from 13 magnetar short bursts observed during Advanced LIGO, Advanced Virgo, and KAGRA’s third observation run. These 13 bursts come from two magnetars, SGR1935 +2154 and SwiftJ1818.0−1607. We also include three other electromagnetic burst events detected by FermiGBM which were identified as likely coming from one or more magnetars, but they have no association with a known magnetar. No magnetar giant flares were detected during the analysis period. We find no evidence of gravitational waves associated with any of these 16 bursts. We place upper limits on the rms of the integrated incident gravitational-wave strain that reach 3.6 × 10−²³ Hz at 100 Hz for the short-duration search and 1.1 ×10−²² Hz at 450 Hz for the long-duration search. For a ringdown signal at 1590 Hz targeted by the short-duration search the limit is set to 2.3 × 10−²² Hz. Using the estimated distance to each magnetar, we derive upper limits upper limits on the emitted gravitational-wave energy of 1.5 × 1044 erg (1.0 × 1044 erg) for SGR 1935+2154 and 9.4 × 10^43 erg (1.3 × 1044 erg) for Swift J1818.0−1607, for the short-duration (long-duration) search. Assuming isotropic emission of electromagnetic radiation of the burst fluences, we constrain the ratio of gravitational-wave energy to electromagnetic energy for bursts from SGR 1935+2154 with the available fluence information. The lowest of these ratios is 4.5 × 103

    A joint Fermi-GBM and Swift-BAT analysis of gravitational-wave candidates from the third gravitational-wave observing run

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    We present Fermi Gamma-ray Burst Monitor (Fermi-GBM) and Swift Burst Alert Telescope (Swift-BAT) searches for gamma-ray/X-ray counterparts to gravitational-wave (GW) candidate events identified during the third observing run of the Advanced LIGO and Advanced Virgo detectors. Using Fermi-GBM onboard triggers and subthreshold gamma-ray burst (GRB) candidates found in the Fermi-GBM ground analyses, the Targeted Search and the Untargeted Search, we investigate whether there are any coincident GRBs associated with the GWs. We also search the Swift-BAT rate data around the GW times to determine whether a GRB counterpart is present. No counterparts are found. Using both the Fermi-GBM Targeted Search and the Swift-BAT search, we calculate flux upper limits and present joint upper limits on the gamma-ray luminosity of each GW. Given these limits, we constrain theoretical models for the emission of gamma rays from binary black hole mergers

    Constraints on the cosmic expansion history from GWTC–3

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    We use 47 gravitational wave sources from the Third LIGO–Virgo–Kamioka Gravitational Wave Detector Gravitational Wave Transient Catalog (GWTC–3) to estimate the Hubble parameter H(z), including its current value, the Hubble constant H0. Each gravitational wave (GW) signal provides the luminosity distance to the source, and we estimate the corresponding redshift using two methods: the redshifted masses and a galaxy catalog. Using the binary black hole (BBH) redshifted masses, we simultaneously infer the source mass distribution and H(z). The source mass distribution displays a peak around 34 M⊙, followed by a drop-off. Assuming this mass scale does not evolve with the redshift results in a H(z) measurement, yielding H0=688+12km  s1Mpc1{H}_{0}={68}_{-8}^{+12}\,\mathrm{km}\ \,\ {{\rm{s}}}^{-1}\,{\mathrm{Mpc}}^{-1} (68% credible interval) when combined with the H0 measurement from GW170817 and its electromagnetic counterpart. This represents an improvement of 17% with respect to the H0 estimate from GWTC–1. The second method associates each GW event with its probable host galaxy in the catalog GLADE+, statistically marginalizing over the redshifts of each event's potential hosts. Assuming a fixed BBH population, we estimate a value of H0=686+8km  s1Mpc1{H}_{0}={68}_{-6}^{+8}\,\mathrm{km}\ \,\ {{\rm{s}}}^{-1}\,{\mathrm{Mpc}}^{-1} with the galaxy catalog method, an improvement of 42% with respect to our GWTC–1 result and 20% with respect to recent H0 studies using GWTC–2 events. However, we show that this result is strongly impacted by assumptions about the BBH source mass distribution; the only event which is not strongly impacted by such assumptions (and is thus informative about H0) is the well-localized event GW190814

    Volunteers' experiences of providing telephone-based breast-feeding peer support in the RUBY randomised controlled trial

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    Objective: The Ringing Up About Breastfeeding earlY (RUBY) randomised controlled trial (RCT) found that a telephone-based peer volunteer support intervention increased breast-feeding duration in a setting with high breast-feeding initiation. This sub-study of the RUBY RCT describes the motivation, preparation and experiences of volunteers who provided the peer support intervention. Design: An online survey was completed by 154 (67 %) volunteers after ceasing volunteering. Setting: Volunteers provided peer support to primiparous women (n 574) who birthed at one of three public hospitals in Melbourne, Australia, between February 2013 and December 2015. Participants: Volunteers (n 230) had themselves breastfed for at least 6 months and received 4 h of training for the role. Results: The median number of mothers supported was two (range 1–11), and two-thirds of respondents supported at least one mother for 6 months. Volunteers were motivated by a strong desire to support new mothers to establish and continue breast-feeding. Most (93 %) considered the training session adequate. The majority (60 %) reported following the call schedule ‘most of the time’, but many commented that ‘it depends on the mother’. Overall, 84 % of volunteers were satisfied with the role and reported that the experience was enjoyable (85 %) and worthwhile (90 %). Volunteers agreed that telephone support for breast-feeding was valued by women (88 %) and that the programme would be effective in helping women to breastfeed (93 %). Conclusions: These findings are important for those developing similar peer support programmes in which recruiting volunteers and developing training requirements are an integral and recurrent part of volunteer management

    Leaf wax n-alkanes and δ13C values of CAM plants from arid southwest Africa

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    International audienceWe analysed leaves from 42 plants from the South African Succulent Karoo. Whole leaf d 13 C values clearly differentiated 3 different populations, consisting of plants operating under obligate CAM (crassulacean acid metabolism), facultative CAM and C 3 modes. In contrast, the leaf wax n-alkane d 13 C data from these metabolic groups showed a broader overlapping distribution. CAM plants operating under full CAM mode produced a wide range of apparent 13 C fractionation. Succulent/CAM plant wax yield was considerable (up to 23 mg/g in our plants), so its contribution to soil composition and sedimentary leaf wax composition should not be dismissed. The presence of CAM plant wax n-alkanes in sedimentary n-alkanes could therefore be a problem for accessing ecosystem scale C 3 –C 4 proportion

    Granulocyte-monocyte progenitors and monocyte-dendritic cell progenitors independently produce functionally distinct monocytes

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    Granulocyte-monocyte progenitors (GMPs) and monocyte-dendritic cell progenitors (MDPs) produce monocytes during homeostasis and in response to increased demand during infection. Both progenitor populations are thought to derive from common myeloid progenitors (CMPs), and a hierarchical relationship (CMP-GMP-MDP-monocyte) is presumed to underlie monocyte differentiation. Here, however, we demonstrate that mouse MDPs arose from CMPs independently of GMPs, and that GMPs and MDPs produced monocytes via similar but distinct monocyte-committed progenitors. GMPs and MDPs yielded classical (Ly6Chi) monocytes with gene expression signatures that were defined by their origins and impacted their function. GMPs produced a subset of ''neutrophil-like'' monocytes, whereas MDPs gave rise to a subset of monocytes that yielded monocyte-derived dendritic cells. GMPs and MDPs were also independentlymobilized to produce specific combinations of myeloid cell types following the injection of microbial components. Thus, the balance of GMP and MDP differentiation shapes the myeloid cell repertoire during homeostasis and following infection

    Is proactive telephone-based breastfeeding peer support a cost-effective intervention? A within-trial cost-effectiveness analysis of the 'Ringing Up about Breastfeeding earlY' (RUBY) randomised controlled trial

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    Objective: The ‘Ringing Up about Breastfeeding earlY’ (RUBY) randomised controlled trial showed increased breastfeeding at 6 months in participants who received the proactive telephone-based peer support breastfeeding intervention compared with participants allocated to receive standard care and supports. The present study aimed to evaluate if the intervention was cost-effective. Design: A within-trial cost-effectiveness analysis. Setting: Three metropolitan maternity services in Melbourne, Victoria, Australia. Participants: First time mothers intending to breastfeed their infant (1152) and peer volunteers (246). Intervention: The intervention comprised proactive telephone-based support from a peer volunteer from early postpartum up to 6 months. Participants were allocated to usual care (n=578) or the intervention (n=574). Main outcome measures: Costs during a 6-month follow-up period including individual healthcare, breastfeeding support and intervention costs in all participants, and an incremental cost-effectiveness ratio. Results: Costs per mother supported were valued at 263.75(or263.75 (or 90.33 excluding costs of donated volunteer time). There was no difference between the two arms in costs for infant and mothers in healthcare and breastfeeding support costs. These figures result in an incremental cost-effectiveness ratio of 4146(4146 (1393 if volunteer time excluded) per additional mother breast feeding at 6 months. Conclusion: Considering the significant improvement in breastfeeding outcomes, this intervention is potentially cost-effective. These findings, along with the high value placed on the intervention by women and peer volunteers provides robust evidence to upscale the implementation of this intervention

    A calcium- and calpain-dependent pathway determines the response to lenalidomide in myelodysplastic syndromes

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    Despite the high response rates of individuals with myelodysplastic syndrome (MDS) with deletion of chromosome 5q (del(5q)) to treatment with lenalidomide (LEN) and the recent identification of cereblon (CRBN) as the molecular target of LEN, the cellular mechanism by which LEN eliminates MDS clones remains elusive. Here we performed an RNA interference screen to delineate gene regulatory networks that mediate LEN responsiveness in an MDS cell line, MDSL. We identified GPR68, which encodes a G-protein-coupled receptor that has been implicated in calcium metabolism, as the top candidate gene for modulating sensitivity to LEN. LEN induced GPR68 expression via IKAROS family zinc finger 1 (IKZF1), resulting in increased cytosolic calcium levels and activation of a calcium-dependent calpain, CAPN1, which were requisite steps for induction of apoptosis in MDS cells and in acute myeloid leukemia (AML) cells. In contrast, deletion of GPR68 or inhibition of calcium and calpain activation suppressed LEN-induced cytotoxicity. Moreover, expression of calpastatin (CAST), an endogenous CAPN1 inhibitor that is encoded by a gene (CAST) deleted in del(5q) MDS, correlated with LEN responsiveness in patients with del(5q) MDS. Depletion of CAST restored responsiveness of LEN-resistant non-del(5q) MDS cells and AML cells, providing an explanation for the superior responses of patients with del(5q) MDS to LEN treatment. Our study describes a cellular mechanism by which LEN, acting through CRBN and IKZF1, has cytotoxic effects in MDS and AML that depend on a calcium- and calpain-dependent pathway
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