2,415 research outputs found
A sufficient condition related to mistaken intuition about adjusted sums-of-squares in linear regression
We consider a misconception common among students of statistics involving "adjusted" and "unadjusted" sums-of-squares. While the presence of misconception has been noted before (e.g. Hamilton (1986)), we argue that it may be related to the language we use in describing the meaning of sums-of-squares. For linear regression with two independent variables, we then present a sufficient condition for SSR( X1 | X2 ) > SSR( X1 ) in terms of the signs of the sample correlations between pairs of predictor and response variables, and note how this sufficient condition may also be related to misconceptions held by some students of statistics. --
A sufficient condition related to mistaken intuition about adjusted sums-of-squares in linear regression
We consider a misconception common among students of statistics involving "adjusted" and "unadjusted" sums-of-squares. While the presence of misconception has been noted before (e.g. Hamilton (1986)), we argue that it may be related to the language we use in describing the meaning of sums-of-squares. For linear regression with two independent variables, we then present a sufficient condition for SSR( X1 | X2 ) > SSR( X1 ) in terms of the signs of the sample correlations between pairs of predictor and response variables, and note how this sufficient condition may also be related to misconceptions held by some students of statistics
A Sufficient Condition Related to Mistaken Intuition about "Adjusted" Sums-of-Squares in Linear Regression
We consider a misconception common among students of statistics involving "adjusted" and "unadjusted" sums-of-squares. While the presence of misconception has been noted before (e.g. Hamilton (1986)), we argue that it may be related to the language we use in describing the meaning of sums-of-squares. For linear regression with two independent variables, we then present a sufficient condition for SSR( X1 | X2 ) > SSR( X1 ) in terms of the signs of the sample correlations between pairs of predictor and response variables, and note how this sufficient condition may also be related to misconceptions held by some students of statistics
Phenotypic insights into ADCY5-associated disease
BACKGROUND: Adenylyl cyclase 5 (ADCY5) mutations is associated with heterogenous syndromes: familial dyskinesia and facial myokymia; paroxysmal chorea and dystonia; autosomal-dominant chorea and dystonia; and benign hereditary chorea. We provide detailed clinical data on 7 patients from six new kindreds with mutations in the ADCY5 gene, in order to expand and define the phenotypic spectrum of ADCY5 mutations. METHODS: In 5 of the 7 patients, followed over a period of 9 to 32 years, ADCY5 was sequenced by Sanger sequencing. The other 2 unrelated patients participated in studies for undiagnosed pediatric hyperkinetic movement disorders and underwent whole-exome sequencing. RESULTS: Five patients had the previously reported p.R418W ADCY5 mutation; we also identified two novel mutations at p.R418G and p.R418Q. All patients presented with motor milestone delay, infantile-onset action-induced generalized choreoathetosis, dystonia, or myoclonus, with episodic exacerbations during drowsiness being a characteristic feature. Axial hypotonia, impaired upward saccades, and intellectual disability were variable features. The p.R418G and p.R418Q mutation patients had a milder phenotype. Six of seven patients had mild functional gain with clonazepam or clobazam. One patient had bilateral globus pallidal DBS at the age of 33 with marked reduction in dyskinesia, which resulted in mild functional improvement. CONCLUSION: We further delineate the clinical features of ADCY5 gene mutations and illustrate its wide phenotypic expression. We describe mild improvement after treatment with clonazepam, clobazam, and bilateral pallidal DBS. ADCY5-associated dyskinesia may be under-recognized, and its diagnosis has important prognostic, genetic, and therapeutic implications. © 2016 The Authors. Movement Disorders published by Wiley Periodicals, Inc. on behalf of International Parkinson and Movement Disorder Society
High-Redshift Starbursting Dwarf Galaxies Revealed by GRB Afterglows
We present a study of 15 long-duration gamma-ray burst (GRB) host galaxies at
z>2. The GRBs are selected with available early-time afterglow spectra in order
to compare interstellar medium (ISM) absorption-line properties with stellar
properties of the host galaxies. In addition to five previously studied hosts,
we consider new detections for the host galaxies of GRB050820 and GRB060206 and
place 2-sigma upper limits to the luminosities of the remaining unidentified
hosts. We examine the nature of the host galaxy population and find that (1)
the UV luminosity distribution of GRB host galaxies is consistent with
expectations from a UV luminosity weighted random galaxy population with a
median luminosity of =0.1 L*; (2) there exists a moderate correlation
between UV luminosity and SiII 1526 absorption width, which together with the
observed large line widths of W(1526)>1.5 Ang for a large fraction of the
objects suggests a galactic outflow driven velocity field in the host galaxies;
(3) there is tentative evidence for a trend of declining ISM metallicity with
decreasing galaxy luminosity in the star-forming galaxy population at z=2-4;
(4) the interstellar UV radiation field is found ~ 35-350 times higher in GRB
hosts than the Galactic mean value; and (5) additional galaxies are found at <
2" from the GRB host in all fields with known presence of strong MgII
absorbers, but no additional faint galaxies are found at < 2" in fields without
strong MgII absorbers. Our study confirms that the GRB host galaxies (with
known optical afterglows) are representative of unobscured star-forming
galaxies at z>2, and demonstrates that high spatial resolution images are
necessary for an accurate identification of GRB host galaxies in the presence
of strong intervening absorbers.Comment: 24 emulateapj pages, 24 figures, ApJ in press; full-resolution
version available at http://lambda.uchicago.edu/public/tmp/ghost.pd
Statistical Confirmation of Empirical Observations Concerning Tool Mark Striae
Toolmarks produced by 44 sequentially manufactured screwdriver tips have been characterized for surface roughness using a profilometer. Toolmarks were produced in lead at angles of 30°, 60°, and 85°. A computer program developed to compare and match the profilometer data has been used to show that marks from a single tip produced at similar angles yield much higher correlation values than marks produced from the same tip but at different angles. This analysis provides statistical support for the widely-accepted empirical observation that toolmark striae must be reproduced at similar angles in order to be unambiguously identified as being made by a particular tool
Cytoscape Web: an interactive web-based network browser
Summary: Cytoscape Web is a web-based network visualization tool–modeled after Cytoscape–which is open source, interactive, customizable and easily integrated into web sites. Multiple file exchange formats can be used to load data into Cytoscape Web, including GraphML, XGMML and SIF
A dual-center cohort study on the association between early deep sedation and clinical outcomes in mechanically ventilated patients during the COVID-19 pandemic: The COVID-SED study
BACKGROUND: Mechanically ventilated patients have experienced greater periods of prolonged deep sedation during the coronavirus disease (COVID-19) pandemic. Multiple studies from the pre-COVID era demonstrate that early deep sedation is associated with worse outcome. Despite this, there is a lack of data on sedation depth and its impact on outcome for mechanically ventilated patients during the COVID-19 pandemic. We sought to characterize the emergency department (ED) and intensive care unit (ICU) sedation practices during the COVID-19 pandemic, and to determine if early deep sedation was associated with worse clinical outcomes.
STUDY DESIGN AND METHODS: Dual-center, retrospective cohort study conducted over 6 months (March-August, 2020), involving consecutive, mechanically ventilated adults. All sedation-related data during the first 48 h were collected. Deep sedation was defined as Richmond Agitation-Sedation Scale of - 3 to - 5 or Riker Sedation-Agitation Scale of 1-3. To examine impact of early sedation depth on hospital mortality (primary outcome), we used a multivariable logistic regression model. Secondary outcomes included ventilator-, ICU-, and hospital-free days.
RESULTS: 391 patients were studied, and 283 (72.4%) experienced early deep sedation. Deeply sedated patients received higher cumulative doses of fentanyl, propofol, midazolam, and ketamine when compared to light sedation. Deep sedation patients experienced fewer ventilator-, ICU-, and hospital-free days, and greater mortality (30.4% versus 11.1%) when compared to light sedation (p \u3c 0.01 for all). After adjusting for confounders, early deep sedation remained significantly associated with higher mortality (adjusted OR 3.44; 95% CI 1.65-7.17; p \u3c 0.01). These results were stable in the subgroup of patients with COVID-19.
CONCLUSIONS: The management of sedation for mechanically ventilated patients in the ICU has changed during the COVID pandemic. Early deep sedation is common and independently associated with worse clinical outcomes. A protocol-driven approach to sedation, targeting light sedation as early as possible, should continue to remain the default approach
Basic science232. Certolizumab pegol prevents pro-inflammatory alterations in endothelial cell function
Background: Cardiovascular disease is a major comorbidity of rheumatoid arthritis (RA) and a leading cause of death. Chronic systemic inflammation involving tumour necrosis factor alpha (TNF) could contribute to endothelial activation and atherogenesis. A number of anti-TNF therapies are in current use for the treatment of RA, including certolizumab pegol (CZP), (Cimzia ®; UCB, Belgium). Anti-TNF therapy has been associated with reduced clinical cardiovascular disease risk and ameliorated vascular function in RA patients. However, the specific effects of TNF inhibitors on endothelial cell function are largely unknown. Our aim was to investigate the mechanisms underpinning CZP effects on TNF-activated human endothelial cells. Methods: Human aortic endothelial cells (HAoECs) were cultured in vitro and exposed to a) TNF alone, b) TNF plus CZP, or c) neither agent. Microarray analysis was used to examine the transcriptional profile of cells treated for 6 hrs and quantitative polymerase chain reaction (qPCR) analysed gene expression at 1, 3, 6 and 24 hrs. NF-κB localization and IκB degradation were investigated using immunocytochemistry, high content analysis and western blotting. Flow cytometry was conducted to detect microparticle release from HAoECs. Results: Transcriptional profiling revealed that while TNF alone had strong effects on endothelial gene expression, TNF and CZP in combination produced a global gene expression pattern similar to untreated control. The two most highly up-regulated genes in response to TNF treatment were adhesion molecules E-selectin and VCAM-1 (q 0.2 compared to control; p > 0.05 compared to TNF alone). The NF-κB pathway was confirmed as a downstream target of TNF-induced HAoEC activation, via nuclear translocation of NF-κB and degradation of IκB, effects which were abolished by treatment with CZP. In addition, flow cytometry detected an increased production of endothelial microparticles in TNF-activated HAoECs, which was prevented by treatment with CZP. Conclusions: We have found at a cellular level that a clinically available TNF inhibitor, CZP reduces the expression of adhesion molecule expression, and prevents TNF-induced activation of the NF-κB pathway. Furthermore, CZP prevents the production of microparticles by activated endothelial cells. This could be central to the prevention of inflammatory environments underlying these conditions and measurement of microparticles has potential as a novel prognostic marker for future cardiovascular events in this patient group. Disclosure statement: Y.A. received a research grant from UCB. I.B. received a research grant from UCB. S.H. received a research grant from UCB. All other authors have declared no conflicts of interes
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