2,515 research outputs found
Learning to Build Police-Community Trust Implementation Assessment Findings from the Evaluation of the National Initiative for Building Community Trust and Justice
This research report documents the training, policy development, and reconciliation activities of the six cities that took part in the National Initiative for Building Community Trust and Justice, an effort to promote more equitable, just, and respectful policing practices and improve relationships and trust between law enforcement and community members. We found that the training component of the Initiative, which exposed officers to concepts of procedural justice and implicit bias, was implemented as intended and was well received by officers. In addition, the reconciliation framework used to improve relationships between police and communities was powerful and impactful, leading police departments to make changes to their policies to build trust and institutionalize improvements to practices. We also observed that local contexts affected the implementation process, with factors such as police leadership stability and the dynamics underlying relations between police, political leadership, and the community facilitating or impeding progress
Evaluation of Embrace WetBond and Helioseal-F sealant retention with and without a Self-etch adhesive : a 12 month follow-up
Pit and fissures on the young permanent tooth are ideal in harbouring dental plaque and calculus. Hence it is important to provide a preventive agent to protect against dental caries. Aim: To evaluate the retention of two different pit and fissure sealan
A new strategy for enhancing imputation quality of rare variants from next-generation sequencing data via combining SNP and exome chip data
Background: Rare variants have gathered increasing attention as a possible alternative source of missing heritability. Since next generation sequencing technology is not yet cost-effective for large-scale genomic studies, a widely used alternative approach is imputation. However, the imputation approach may be limited by the low accuracy of the imputed rare variants. To improve imputation accuracy of rare variants, various approaches have been suggested, including increasing the sample size of the reference panel, using sequencing data from study-specific samples (i.e., specific populations), and using local reference panels by genotyping or sequencing a subset of study samples. While these approaches mainly utilize reference panels, imputation accuracy of rare variants can also be increased by using exome chips containing rare variants. The exome chip contains 250 K rare variants selected from the discovered variants of about 12,000 sequenced samples. If exome chip data are available for previously genotyped samples, the combined approach using a genotype panel of merged data, including exome chips and SNP chips, should increase the imputation accuracy of rare variants. Results: In this study, we describe a combined imputation which uses both exome chip and SNP chip data simultaneously as a genotype panel. The effectiveness and performance of the combined approach was demonstrated using a reference panel of 848 samples constructed using exome sequencing data from the T2D-GENES consortium and 5,349 sample genotype panels consisting of an exome chip and SNP chip. As a result, the combined approach increased imputation quality up to 11 %, and genomic coverage for rare variants up to 117.7 % (MAF < 1 %), compared to imputation using the SNP chip alone. Also, we investigated the systematic effect of reference panels on imputation quality using five reference panels and three genotype panels. The best performing approach was the combination of the study specific reference panel and the genotype panel of combined data. Conclusions: Our study demonstrates that combined datasets, including SNP chips and exome chips, enhances both the imputation quality and genomic coverage of rare variants
2016 International Land Model Benchmarking (ILAMB) Workshop Report
As earth system models (ESMs) become increasingly complex, there is a growing need for comprehensive and multi-faceted evaluation of model projections. To advance understanding of terrestrial biogeochemical processes and their interactions with hydrology and climate under conditions of increasing atmospheric carbon dioxide, new analysis methods are required that use observations to constrain model predictions, inform model development, and identify needed measurements and field experiments. Better representations of biogeochemistryclimate feedbacks and ecosystem processes in these models are essential for reducing the acknowledged substantial uncertainties in 21st century climate change projections
Measurements of the pp → ZZ production cross section and the Z → 4ℓ branching fraction, and constraints on anomalous triple gauge couplings at √s = 13 TeV
Four-lepton production in proton-proton collisions, pp -> (Z/gamma*)(Z/gamma*) -> 4l, where l = e or mu, is studied at a center-of-mass energy of 13 TeV with the CMS detector at the LHC. The data sample corresponds to an integrated luminosity of 35.9 fb(-1). The ZZ production cross section, sigma(pp -> ZZ) = 17.2 +/- 0.5 (stat) +/- 0.7 (syst) +/- 0.4 (theo) +/- 0.4 (lumi) pb, measured using events with two opposite-sign, same-flavor lepton pairs produced in the mass region 60 4l) = 4.83(-0.22)(+0.23) (stat)(-0.29)(+0.32) (syst) +/- 0.08 (theo) +/- 0.12(lumi) x 10(-6) for events with a four-lepton invariant mass in the range 80 4GeV for all opposite-sign, same-flavor lepton pairs. The results agree with standard model predictions. The invariant mass distribution of the four-lepton system is used to set limits on anomalous ZZZ and ZZ. couplings at 95% confidence level: -0.0012 < f(4)(Z) < 0.0010, -0.0010 < f(5)(Z) < 0.0013, -0.0012 < f(4)(gamma) < 0.0013, -0.0012 < f(5)(gamma) < 0.0013
Differences in extrinsic tree quality and value of fibre production following alternative vegetation management treatments in Northwestern Ontario
This is the publisher’s version of a work published in The Forestry Chronicle 90:1 (2014) The version on the publisher's website can be viewed at http://pubs.cif-ifc.org/doi/abs/10.5558/tfc2011-012We examined differences in stem quality, and volume and value of fibre produced by planted white spruce 16 years after vegetation management treatments in northwestern Ontario. Forest Vegetation Simulator (FVSOntario) was used to project the total and merchantable volume to age 70 and BUCK-2 was used to optimize the resulting product mix. Projected value was based on 2009 prices for hog fuel, pulpwood and SPF (spruce–pine–fir) eastern green lumber prices. At 16 years posttreatment, gross total volumes in herbicide-treated and mechanically cut plots were significantly higher (120%–165% and 94%–98%, respectively) than that in control plots (14.73 m3 ha-1). Based on height, diameter, and taper criteria, observed tree quality did not differ among treatments. The projected value of the fibre produced was 36% to 53% higher in herbicide- treated plots and 24% to 37% higher in mechanically cut plots than in control plots ($18 486.76 per ha)
Abstracts from the 3rd Conference on Aneuploidy and Cancer: Clinical and Experimental Aspects
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Factors influencing survival in sphingosine phosphate lyase insufficiency syndrome: a retrospective cross-sectional natural history study of 76 patients
BackgroundSphingosine-1-phosphate lyase insufficiency syndrome (SPLIS) is a recently recognized inborn error of metabolism associated with steroid-resistant nephrotic syndrome as well as adrenal insufficiency and immunological, neurological, and skin manifestations. SPLIS is caused by inactivating mutations in SGPL1, encoding the pyridoxal 5'phosphate-dependent enzyme sphingosine-1-phosphate lyase, which catalyzes the final step of sphingolipid metabolism. Some SPLIS patients have undergone kidney transplantation, and others have been treated with vitamin B6 supplementation. In addition, targeted therapies including gene therapy are in preclinical development. In anticipation of clinical trials, it will be essential to characterize the full spectrum and natural history of SPLIS. We performed a retrospective analysis of 76 patients in whom the diagnosis of SPLIS was established in a proband with at least one suggestive finding and biallelic SGPL1 variants identified by molecular genetic testing. The main objective of the study was to identify factors influencing survival in SPLIS subjects.ResultsOverall survival at last report was 50%. Major influences on survival included: (1) age and organ involvement at first presentation; (2) receiving a kidney transplant, and (3) SGPL1 genotype. Among 48 SPLIS patients with nephropathy who had not received a kidney transplant, two clinical subgroups were distinguished. Of children diagnosed with SPLIS nephropathy before age one (n = 30), less than 30% were alive 2 years after diagnosis, and 17% were living at last report. Among those diagnosed at or after age one (n = 18), ~ 70% were alive 2 years after diagnosis, and 72% were living at time of last report. SPLIS patients homozygous for the SPL R222Q variant survived longer compared to patients with other genotypes. Kidney transplantation significantly extended survival outcomes.ConclusionOur results demonstrate that SPLIS is a phenotypically heterogeneous condition. We find that patients diagnosed with SPLIS nephropathy in the first year of life and patients presenting with prenatal findings represent two high-risk subgroups, whereas patients harboring the R222Q SGPL1 variant fare better than the rest. Time to progression from onset of proteinuria to end stage kidney disease varies from less than one month to five years, and kidney transplantation may be lifesaving
The Anti-Inflammatory Drug Leflunomide Is an Agonist of the Aryl Hydrocarbon Receptor
The aryl hydrocarbon receptor (AhR) is a ligand-activated transcription factor that mediates the toxicity and biological activity of dioxins and related chemicals. The AhR influences a variety of processes involved in cellular growth and differentiation, and recent studies have suggested that the AhR is a potential target for immune-mediated diseases.During a screen for molecules that activate the AhR, leflunomide, an immunomodulatory drug presently used in the clinic for the treatment of rheumatoid arthritis, was identified as an AhR agonist. We aimed to determine whether any biological activity of leflunomide could be attributed to a previously unappreciated interaction with the AhR. The currently established mechanism of action of leflunomide involves its metabolism to A771726, possibly by cytochrome P450 enzymes, followed by inhibition of de novo pyrimidine biosynthesis by A771726. Our results demonstrate that leflunomide, but not its metabolite A771726, caused nuclear translocation of AhR into the nucleus and increased expression of AhR-responsive reporter genes and endogenous AhR target genes in an AhR-dependent manner. In silico Molecular Docking studies employing AhR ligand binding domain revealed favorable binding energy for leflunomide, but not for A771726. Further, leflunomide, but not A771726, inhibited in vivo epimorphic regeneration in a zebrafish model of tissue regeneration in an AhR-dependent manner. However, suppression of lymphocyte proliferation by leflunomide or A771726 was not dependent on AhR.These data reveal that leflunomide, an anti-inflammatory drug, is an agonist of the AhR. Our findings link AhR activation by leflunomide to inhibition of fin regeneration in zebrafish. Identification of alternative AhR agonists is a critical step in evaluating the AhR as a therapeutic target for the treatment of immune disorders
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