375 research outputs found
Assessing Google Flu Trends Performance in the United States during the 2009 Influenza Virus A (H1N1) Pandemic
Google Flu Trends (GFT) uses anonymized, aggregated internet search activity to provide near-real time estimates of influenza activity. GFT estimates have shown a strong correlation with official influenza surveillance data. The 2009 influenza virus A (H1N1) pandemic [pH1N1] provided the first opportunity to evaluate GFT during a non-seasonal influenza outbreak. In September 2009, an updated United States GFT model was developed using data from the beginning of pH1N1.We evaluated the accuracy of each U.S. GFT model by comparing weekly estimates of ILI (influenza-like illness) activity with the U.S. Outpatient Influenza-like Illness Surveillance Network (ILINet). For each GFT model we calculated the correlation and RMSE (root mean square error) between model estimates and ILINet for four time periods: pre-H1N1, Summer H1N1, Winter H1N1, and H1N1 overall (Mar 2009βDec 2009). We also compared the number of queries, query volume, and types of queries (e.g., influenza symptoms, influenza complications) in each model. Both models' estimates were highly correlated with ILINet pre-H1N1 and over the entire surveillance period, although the original model underestimated the magnitude of ILI activity during pH1N1. The updated model was more correlated with ILINet than the original model during Summer H1N1 (rβ=β0.95 and 0.29, respectively). The updated model included more search query terms than the original model, with more queries directly related to influenza infection, whereas the original model contained more queries related to influenza complications.Internet search behavior changed during pH1N1, particularly in the categories βinfluenza complicationsβ and βterm for influenza.β The complications associated with pH1N1, the fact that pH1N1 began in the summer rather than winter, and changes in health-seeking behavior each may have played a part. Both GFT models performed well prior to and during pH1N1, although the updated model performed better during pH1N1, especially during the summer months
Outcomes from a 12-Week, Open-Label, Multicenter Clinical Trial of Teduglutide in Pediatric Short Bowel Syndrome
Objective
To determine safety and pharmacodynamics/efficacy of teduglutide in children with intestinal failure associated with short bowel syndrome (SBS-IF).
Study design
This 12-week, open-label study enrolled patients aged 1-17 years with SBS-IF who required parenteral nutrition (PN) and showed minimal or no advance in enteral nutrition (EN) feeds. Patients enrolled sequentially into 3 teduglutide cohorts (0.0125βmg/kg/d [nβ=β8], 0.025βmg/kg/d [nβ=β14], 0.05βmg/kg/d [nβ=β15]) or received standard of care (SOC, nβ=β5). Descriptive summary statistics were used.
Results
All patients experienced β₯1 treatment-emergent adverse event; most were mild or moderate. No serious teduglutide-related treatment-emergent adverse events occurred. Between baseline and week 12, prescribed PN volume and calories (kcal/kg/d) changed by a median of β41% and β45%, respectively, with 0.025βmg/kg/d teduglutide and by β25% and β52% with 0.05βmg/kg/d teduglutide. In contrast, PN volume and calories changed by 0% and β6%, respectively, with 0.0125βmg/kg/d teduglutide and by 0% and β1% with SOC. Per patient diary data, EN volume increased by a median of 22%, 32%, and 40% in the 0.0125, 0.025, and 0.05 mg/kg/d cohorts, respectively, and by 11% with SOC. Four patients achieved independence from PN, 3 in the 0.05 mg/kg/d cohort and 1 in the 0.025 mg/kg/d cohort. Study limitations included its short-term, open-label design, and small sample size.
Conclusions
Teduglutide was well tolerated in pediatric patients with SBS-IF. Teduglutide 0.025 or 0.05βmg/kg/d was associated with trends toward reductions in PN requirements and advancements in EN feeding in children with SBS-IF
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Modular mixing in plasmonic metal oxide nanocrystal gels with thermoreversible links
Gelation offers a powerful strategy to assemble plasmonic nanocrystal networks incorporating both the distinctive optical properties of con-
stituent building blocks and customizable collective properties. Beyond what a single-component assembly can offer, the characteristics of
nanocrystal networks can be tuned in a broader range when two or more components are intimately combined. Here, we demonstrate
mixed nanocrystal gel networks using thermoresponsive metalβterpyridine links that enable rapid gel assembly and disassembly with ther-
mal cycling. Plasmonic indium oxide nanocrystals with different sizes, doping concentrations, and shapes are reliably intermixed in linked
gel assemblies, exhibiting collective infrared absorption that reflects the contributions of each component while also deviating systematically
from a linear combination of the spectra for single-component gels. We extend a many-bodied, mutual polarization method to simulate the
optical response of mixed nanocrystal gels, reproducing the experimental trends with no free parameters and revealing that spectral devia-
tions originate from cross-coupling between nanocrystals with distinct plasmonic properties. Our thermoreversible linking strategy directs
the assembly of mixed nanocrystal gels with continuously tunable far- and near-field optical properties that are distinct from those of the
building blocks or mixed close-packed structures.This research was primarily supported by the National Science
Foundation through the Center for Dynamics and Control of Mate-
rials: an NSF MRSEC under Cooperative Agreement No. DMR-
1720595, with additional support from an Arnold O. Beckman
Postdoctoral Fellowship (Z.M.S.) and the Welch Foundation (Grant
Nos. F-1696 and F-1848). E.V.A. acknowledges support from the
Welch Regents Chair (No. F-0046). We acknowledge the Texas
Advanced Computing Center (TACC) at the University of Texas at
Austin for providing HPC resources.Center for Dynamics and Control of Material
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Plasmonic response of complex nanoparticle assemblies
Optical properties of nanoparticle assemblies reflect distinctive characteristics of their building blocks and spatial organization, giving rise to emergent phenomena. Integrated experimental and computational studies have established design principles connecting the structure to properties for assembled clusters and superlattices. However, conventional electromagnetic simulations are too computationally expensive to treat more complex assemblies. Here we establish a fast, materials agnostic method to simulate the optical response of large nanoparticle assemblies incorporating both structural and compositional complexity. This many-bodied, mutual polarization method resolves limitations of established approaches, achieving rapid, accurate convergence for configurations including thousands of nanoparticles, with some overlapping. We demonstrate these capabilities by reproducing experimental trends and uncovering far- and near-field mechanisms governing the optical response of plasmonic semiconductor nanocrystal assemblies including structurally complex gel networks and compositionally complex mixed binary superlattices. This broadly applicable framework will facilitate the design of complex, hierarchically structured, and dynamic assemblies for desired optical characteristics.This research was primarily supported by the National Science Foundation through the Center for Dynamics and Control of Materials: an NSF Materials Research Science and Engineering Center (NSF MRSEC) under Cooperative Agreement DMR-1720595. E.V.A. acknowledges support from the Welch Regents Chair (F-0046). D.J.M. and T.M.T. acknowledge support from the Welch Foundation (F-1696 and F-1848) and NSF (CHE-1905263). This work was supported by an NSF Graduate Research Fellowship (DGE-1610403) to S.A.V. and Arnold O. Beckman Postdoctoral Fellowship to Z.M.S. We acknowledge the Texas Materials Institute for use of the SAXSLAB Ganesha, acquired using an NSF MRI grant CBET-1624659.Center for Dynamics and Control of Material
Differential limit on the extremely-high-energy cosmic neutrino flux in the presence of astrophysical background from nine years of IceCube data
We report a quasi-differential upper limit on the extremely-high-energy (EHE)
neutrino flux above GeV based on an analysis of nine years of
IceCube data. The astrophysical neutrino flux measured by IceCube extends to
PeV energies, and it is a background flux when searching for an independent
signal flux at higher energies, such as the cosmogenic neutrino signal. We have
developed a new method to place robust limits on the EHE neutrino flux in the
presence of an astrophysical background, whose spectrum has yet to be
understood with high precision at PeV energies. A distinct event with a
deposited energy above GeV was found in the new two-year sample, in
addition to the one event previously found in the seven-year EHE neutrino
search. These two events represent a neutrino flux that is incompatible with
predictions for a cosmogenic neutrino flux and are considered to be an
astrophysical background in the current study. The obtained limit is the most
stringent to date in the energy range between and GeV. This result constrains neutrino models predicting a three-flavor
neutrino flux of $E_\nu^2\phi_{\nu_e+\nu_\mu+\nu_\tau}\simeq2\times 10^{-8}\
{\rm GeV}/{\rm cm}^2\ \sec\ {\rm sr}10^9\ {\rm GeV}$. A significant part
of the parameter-space for EHE neutrino production scenarios assuming a
proton-dominated composition of ultra-high-energy cosmic rays is excluded.Comment: The version accepted for publication in Physical Review
Is the superior verbal memory span of Mandarin speakers due to faster rehearsal?
It is well established that digit span in native Chinese speakers is atypically high. This is commonly attributed to a capacity for more rapid subvocal rehearsal for that group. We explored this hypothesis by testing a group of English-speaking native Mandarin speakers on digit span and word span in both Mandarin and English, together with a measure of speed of articulation for each. When compared to the performance of native English speakers, the Mandarin group proved to be superior on both digit and word spans while predictably having lower spans in English. This suggests that the Mandarin advantage is not limited to digits. Speed of rehearsal correlated with span performance across materials. However, this correlation was more pronounced for English speakers than for any of the Chinese measures. Further analysis suggested that speed of rehearsal did not provide an adequate account of differences between Mandarin and English spans or for the advantage of digits over words. Possible alternative explanations are discussed
Finding needles in haystacks:Linking scientific names, reference specimens and molecular data for Fungi
DNA phylogenetic comparisons have shown that morphology-based species recognition
often underestimates fungal diversity. Therefore, the need for accurate DNA sequence
data, tied to both correct taxonomic names and clearly annotated specimen data, has
never been greater. Furthermore, the growing number of molecular ecology and microbiome
projects using high-throughput sequencing require fast and effective methods for
en masse species assignments. In this article, we focus on selecting and re-annotating a
set of marker reference sequences that represent each currently accepted order of Fungi.
The particular focus is on sequences from the internal transcribed spacer region in the
nuclear ribosomal cistron, derived from type specimens and/or ex-type cultures. Reannotated
and verified sequences were deposited in a curated public database at the
National Center for Biotechnology Information (NCBI), namely the RefSeq Targeted Loci
(RTL) database, and will be visible during routine sequence similarity searches with
NR_prefixed accession numbers. A set of standards and protocols is proposed to improve
the data quality of new sequences, and we suggest how type and other reference
sequences can be used to improve identification of Fungi.The Intramural Research Programs
of the National Center for Biotechnology Information, National
Library of Medicine and the National Human Genome Research
Institute, both at the National Institutes of Health.http://www.ncbi.nlm.nih.gov/bioproject/PRJNA177353am201
Modulation of the Ξ²-Catenin Signaling Pathway by the Dishevelled-Associated Protein Hipk1
BACKGROUND:Wnts are evolutionarily conserved ligands that signal through beta-catenin-dependent and beta-catenin-independent pathways to regulate cell fate, proliferation, polarity, and movements during vertebrate development. Dishevelled (Dsh/Dvl) is a multi-domain scaffold protein required for virtually all known Wnt signaling activities, raising interest in the identification and functions of Dsh-associated proteins. METHODOLOGY:We conducted a yeast-2-hybrid screen using an N-terminal fragment of Dsh, resulting in isolation of the Xenopus laevis ortholog of Hipk1. Interaction between the Dsh and Hipk1 proteins was confirmed by co-immunoprecipitation assays and mass spectrometry, and further experiments suggest that Hipk1 also complexes with the transcription factor Tcf3. Supporting a nuclear function during X. laevis development, Myc-tagged Hipk1 localizes primarily to the nucleus in animal cap explants, and the endogenous transcript is strongly expressed during gastrula and neurula stages. Experimental manipulations of Hipk1 levels indicate that Hipk1 can repress Wnt/beta-catenin target gene activation, as demonstrated by beta-catenin reporter assays in human embryonic kidney cells and by indicators of dorsal specification in X. laevis embryos at the late blastula stage. In addition, a subset of Wnt-responsive genes subsequently requires Hipk1 for activation in the involuting mesoderm during gastrulation. Moreover, either over-expression or knock-down of Hipk1 leads to perturbed convergent extension cell movements involved in both gastrulation and neural tube closure. CONCLUSIONS:These results suggest that Hipk1 contributes in a complex fashion to Dsh-dependent signaling activities during early vertebrate development. This includes regulating the transcription of Wnt/beta-catenin target genes in the nucleus, possibly in both repressive and activating ways under changing developmental contexts. This regulation is required to modulate gene expression and cell movements that are essential for gastrulation
Identification of unique neoantigen qualities in long-term survivors of pancreatic cancer
Pancreatic ductal adenocarcinoma is a lethal cancer with fewer than 7% of patients surviving past 5 years. T-cell immunity has been linked to the exceptional outcome of the few long-term survivors1,2, yet the relevant antigens remain unknown. Here we use genetic, immunohistochemical and transcriptional immunoprofiling, computational biophysics, and functional assays to identify T-cell antigens in long-term survivors of pancreatic cancer. Using whole-exome sequencing and in silico neoantigen prediction, we found that tumours with both the highest neoantigen number and the most abundant CD8+ T-cell infiltrates, but neither alone, stratified patients with the longest survival. Investigating the specific neoantigen qualities promoting T-cell activation in long-term survivors, we discovered that these individuals were enriched in neoantigen qualities defined by a fitness model, and neoantigens in the tumour antigen MUC16 (also known as CA125). A neoantigen quality fitness model conferring greater immunogenicity to neoantigens with differential presentation and homology to infectious disease-derived peptides identified long-term survivors in two independent datasets, whereas a neoantigen quantity model ascribing greater immunogenicity to increasing neoantigen number alone did not. We detected intratumoural and lasting circulating T-cell reactivity to both high-quality and MUC16 neoantigens in long-term survivors of pancreatic cancer, including clones with specificity to both high-quality neoantigens and predicted cross-reactive microbial epitopes, consistent with neoantigen molecular mimicry. Notably, we observed selective loss of high-quality and MUC16 neoantigenic clones on metastatic progression, suggesting neoantigen immunoediting. Our results identify neoantigens with unique qualities as T-cell targets in pancreatic ductal adenocarcinoma. More broadly, we identify neoantigen quality as a biomarker for immunogenic tumours that may guide the application of immunotherapies
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