181 research outputs found
Criminal Law—Statutory Definition of Knowledge—State v. Shipp, 93 Wn. 2d 510, 610 P.2d 1322 (1980)
In State v. Shipp the Washington Supreme Court interpreted the meaning of knowledge as used in Washington\u27s criminal culpability statute. Defendants in three different trials were convicted of crimes requiring proof of knowledge. In each case the trial court gave jury instructions directing the jury to find that a person has knowledge if it finds that \u27he has information which would lead a reasonable person in the same situation to believe that [the relevant] facts exist.\u27 The issue in Shipp was whether these instructions, which were taken almost verbatim from the statute, were correct. This note argues that, contrary to the view expressed by the Shipp majority, the statutory definition of criminal knowledge, RCW § 9A.08.010(l)(b), can be interpreted reasonably in only one way: The jury must find that a defendant had knowledge of the fact in question if it finds that a reasonable person in the same situation possessing the same information would have had such knowledge. In other words, for the purposes of the Washington criminal code, this note argues that the term knowledge has been redefined by the Washington Legislature to embrace not only actual knowledge, but constructive knowledge as well. This interpretation of the statute can withstand an attack on constitutional grounds. Further, although it does yield a substantial inconsistency within the statute, this interpretation is directed by well-established rules of statutory construction
The effects of velocities and lensing on moments of the Hubble diagram
We consider the dispersion on the supernova distance-redshift relation due to
peculiar velocities and gravitational lensing, and the sensitivity of these
effects to the amplitude of the matter power spectrum. We use the MeMo lensing
likelihood developed by Quartin, Marra & Amendola (2014), which accounts for
the characteristic non-Gaussian distribution caused by lensing magnification
with measurements of the first four central moments of the distribution of
magnitudes. We build on the MeMo likelihood by including the effects of
peculiar velocities directly into the model for the moments. In order to
measure the moments from sparse numbers of supernovae, we take a new approach
using Kernel Density Estimation to estimate the underlying probability density
function of the magnitude residuals. We also describe a bootstrap re-sampling
approach to estimate the data covariance matrix. We then apply the method to
the Joint Light-curve Analysis (JLA) supernova catalogue. When we impose only
that the intrinsic dispersion in magnitudes is independent of redshift, we find
at the one standard deviation level, although
we note that in tests on simulations, this model tends to overestimate the
magnitude of the intrinsic dispersion, and underestimate . We note
that the degeneracy between intrinsic dispersion and the effects of
is more pronounced when lensing and velocity effects are considered
simultaneously, due to a cancellation of redshift dependence when both effects
are included. Keeping the model of the intrinsic dispersion fixed as a Gaussian
distribution of width 0.14 mag, we find .Comment: 16 pages, updated to match version accepted in MNRA
Stroke in Patients With Acute Coronary Syndromes: Incidence and Outcomes in the Platelet Glycoprotein IIb/IIIa in Unstable Angina: Receptor Suppression Using Integrilin Therapy (PURSUIT) Trial
BACKGROUND: The incidence of stroke in patients with acute coronary
syndromes has not been clearly defined because few trials in this patient
population have been large enough to provide stable estimates of stroke
rates. METHODS AND RESULTS: We studied the 10 948 patients with acute
coronary syndromes without persistent ST-segment elevation who were
randomly assigned to placebo or the platelet glycoprotein IIb/IIIa
receptor inhibitor eptifibatide in the Platelet Glycoprotein IIb/IIIa in
Unstable Angina: Receptor Suppression Using Integrilin Therapy (PURSUIT)
trial to determine stroke rates, stroke types, clinical outcomes in
patients with stroke, and independent baseline clinical predictors for
nonhemorrhagic stroke. Stroke occurred in 79 (0.7%) patients, with 66
(0.6%) nonhemorrhagic, 6 intracranial hemorrhages, 3 cerebral infarctions
with hemorrhagic conversion, and 4 of uncertain cause. There were no
differences in stroke rates between patients who received placebo and
those assigned high-dose eptifibatide (odds ratios and 95% confidence
intervals 0.82 [0.59, 1.14] and 0.70 [0.49, 0.99], respectively). Of the
79 patients with stroke, 17 (22%) died within 30 days, and another 26
(32%) were disabled by hospital discharge or 30 days, whichever came
first. Higher heart rate was the most important baseline clinical
predictor of nonhemorrhagic stroke, followed by older age, prior anterior
myocardial infarction, prior stroke or transient ischemic attack, and
diabetes mellitus. These factors were used to develop a simple scoring
nomogram that can predict the risk of nonhemorrhagic stroke. CONCLUSIONS:
Stro
Single-cell genomics reveals population structures from in vitro evolutionary studies of Salmonella
Single-cell DNA sequencing has the potential to reveal detailed hierarchical structures in evolving populations of cells. Single cell approaches are increasingly used to study clonal evolution in human ageing and cancer but have not yet been deployed to study evolving clonal microbial populations. Here, we present an approach for single bacterial genomic analysis for in vitro evolution experiments using FACS isolation of individual bacteria followed by whole-genome amplification and sequencing. We apply this to the experimental evolution of a hypermutator strain of Salmonella in response to antibiotic stress (ciprofloxacin). By analysing sequence polymorphisms in individual cells from populations we identified the presence and prevalence of sub-populations which have acquired polymorphisms in genes previously demonstrated to be associated with ciprofloxacin susceptibility. We were also able to identify that the population exposed to antibiotic stress was able to develop resistance whilst maintaining diversity. This population structure could not be resolved from bulk sequence data, and our results show how high-throughput single-cell sequencing can enhance experimental studies of bacterial evolution
En Attendant Centiloid
Aims: Test the robustness of a linear regression transformation of semiquantitative values from different Aβ tracers into a single continuous scale. Study Design: Retrospective analysis. Place and Duration of Study: PET imaging data acquired in Melbourne and Perth, Australia, between August 2006 and May 2014. Methodology: Aβ imaging in 633 participants was performed with four different radiotracers: flutemetamol (n=267), florbetapir (n=195), florbetaben (n=126) and NAV4694 (n=45). SUVR were generated with the methods recommended for each tracer, and classified as high (Aβ+) or low (Aβ-) based on their respective thresholds. Linear regression transformation based on reported head-to-head comparisons of each tracer with PiB was applied to each tracer result. Each tracer native classification was compared with the classification derived from the transformed data into PiB-like SUVR units (or BeCKeT: Before the Centiloid Kernel Transformation) using 1.50 as a cut-off. Results: Misclassification after transformation to PiB-like SUVR compared to native classification was extremely low with only 3/267 (1.1%) of flutemetamol, 1/195 (0.5%) of florbetapir, 1/45 (2.2%) of NAV4694, and 1/126 (0.8%) of florbetaben cases assigned into the wrong category. When misclassification occurred (Conclusion: While a definitive transformation into centesimal units is being established, application of linear regression transformations provide an interim, albeit robust, way of converting results from different Aβ imaging tracers into more familiar PiB-like SUVR units
Skeletal muscle munc18c and syntaxin 4 in human obesity
<p>Abstract</p> <p>Background</p> <p>Animal and cell culture data suggest a critical role for Munc18c and Syntaxin 4 proteins in insulin mediated glucose transport in skeletal muscle, but no studies have been published in humans.</p> <p>Methods</p> <p>We investigated the effect of a 12 vs. 48 hr fast on insulin action and skeletal muscle Munc18c and Syntaxin 4 protein in lean and obese subjects. Healthy lean (n = 14; age = 28.0 +/- 1.4 yr; BMI = 22.8 +/- 0.42 kg/m<sup>2</sup>) and obese subjects (n = 11; age = 34.6 +/- 2.3 yr; BMI = 36.1 +/- 1.5 kg/m<sup>2</sup>) were studied twice following a 12 and 48 hr fast. Skeletal muscle biopsies were obtained before a 3 hr 40 mU/m<sup>2</sup>/min hyperinsulinemic-euglycemic clamp with [6,6-<sup>2</sup>H<sub>2</sub>]glucose infusion.</p> <p>Results</p> <p>Glucose rate of disappearance (Rd) during the clamp was lower in obese vs. lean subjects after the 12 hr fast (obese: 6.25 +/- 0.67 vs. lean: 9.42 +/- 1.1 mg/kgFFM/min, p = 0.007), and decreased significantly in both groups after the 48 hr fast (obese 3.49 +/- 0.31 vs. lean: 3.91 +/- 0.42 mg/kgFFM/min, p = 0.002). Munc18c content was not significantly different between lean and obese subjects after the 12 hour fast, and decreased after the 48 hr fast in both groups (p = 0.013). Syntaxin 4 content was not altered by obesity or fasting duration. There was a strong positive relationship between plasma glucose concentration and Munc18c content in lean and obese subjects during both 12 and 48 hr fasts (R<sup>2 </sup>= 0.447, p = 0.0015). Significant negative relationships were also found between Munc18c and FFA (p = 0.041), beta-hydroxybutyrate (p = 0.039), and skeletal muscle AKT content (p = 0.035) in lean and obese subjects.</p> <p>Conclusion</p> <p>These data indicate Munc18c and Syntaxin 4 are present in human skeletal muscle. Munc18c content was not significantly different between lean and obese subjects, and is therefore unlikely to explain obesity-induced insulin resistance. Munc18c content decreased after prolonged fasting in lean and obese subjects concurrently with reduced insulin action. These data suggest changes in Munc18c content in skeletal muscle are associated with short-term changes in insulin action in humans.</p
Eliciting health state utilities for Dupuytren's contracture using a discrete choice experiment
Background and purpose An internet-based discrete choice
experiment (DCE) was conducted to elicit preferences for a wide
range of Dupuytren’s contracture (DC)-related health states. An
algorithm was subsequently developed to convert these preferences
into health state utilities that can be used to assess DC’s
impact on quality of life and the value of its treatments.
Methods Health state preferences for varying levels of DC
hand severity were elicited via an internet survey from a sample
of the UK adult population. Severity levels were deined using a
combination of contractures (0, 45, or 90 degrees) in 8 proximal
interphalangeal and metacarpophalangeal joints of the index,
middle, ring, and little ingers. Right-handed, left-handed, and
ambidextrous respondents indicated which hand was preferable
in each of the 10 randomly-selected hand-pairings comparing
different DC severity levels. For consistency across comparisons,
anatomically precise digital hand drawings were used. To anchor
preferences onto the traditional 0–1 utility scale used in health
economic evaluations, unaffected hands were assigned a utility
of 1.0 whereas the utility for a maximally affected hand (i.e., all
8 joints set at 90 degrees of contracture) was derived by asking
respondents to indicate what combination of attributes and levels
of the EQ-5D-5L proile most accurately relects the impact of
living with such hand. Conditional logistic models were used to
estimate indirect utilities, then rescaled to the anchor points on
the EQ-5D-5L.
Results Estimated utilities based on the responses of 1,745
qualiied respondents were 0.49, 0.57, and 0.63 for completely
affected dominant hands, non-dominant hands, or ambidextrous
hands, respectively. Utility for a dominant hand with 90-degree
contracture in t h e metacarpophalangeal joints of the ring and
little ingers was estimated to be 0.89. Separately, reducing the
contracture of metacarpophalangeal joint for a little inger from
50 to 12 degrees would improve utility by 0.02.
Interpretation DC is associated with substantial utility decrements.
The algorithms presented herein provide a robust and lexible
framework to assess utility for varying degrees of DC severity
Non-neuronal expression of SARS-CoV-2 entry genes in the olfactory system suggests mechanisms underlying COVID-19-associated anosmia
Abstract:Altered olfactory function is a common symptom of COVID-19, but its etiology is unknown. A key question is whether SARS-CoV-2 (CoV-2) – the causal agent in COVID-19 – affects olfaction directly, by infecting olfactory sensory neurons or their targets in the olfactory bulb, or indirectly, through perturbation of supporting cells. Here we identify cell types in the olfactory epithelium and olfactory bulb that express SARS-CoV-2 cell entry molecules. Bulk sequencing demonstrated that mouse, non-human primate and human olfactory mucosa expresses two key genes involved in CoV-2 entry, ACE2 and TMPRSS2. However, single cell sequencing revealed that ACE2 is expressed in support cells, stem cells, and perivascular cells, rather than in neurons. Immunostaining confirmed these results and revealed pervasive expression of ACE2 protein in dorsally-located olfactory epithelial sustentacular cells and olfactory bulb pericytes in the mouse. These findings suggest that CoV-2 infection of non-neuronal cell types leads to anosmia and related disturbances in odor perception in COVID-19 patients
Humanistic psychotherapy research 1990-2015 : from methodological innovation to evidence-supported treatment outcomes and beyond
Over the past twenty five years, humanistic psychotherapy (HP) researchers have actively contributed to the development and implementation of innovative practice-informed research measures and coding systems. Qualitative and quantitative research findings, including meta-analyses, support the identification of HP approaches as evidence-based treatments for a variety of psychological conditions. Implications for future psychotherapy research, training and practice are discussed in terms of addressing the persistent disjunction between significant HP research productivity and relatively low support for HP approaches in university-based clinical training programs, funding agencies and government-supported clinical guidelines. Finally, specific recommendations are provided to further enhance and expand the impact of humanistic psychotherapy research for clinical training programs and the development of treatment guidelines
Discovery of a z = 0.65 post-starburst BAL quasar in the DES supernova fields
We present the discovery of a z = 0.65 low-ionization broad absorption line (LoBAL) quasar in a post-starburst galaxy in data from the Dark Energy Survey (DES) and spectroscopy from the Australian Dark Energy Survey (OzDES). LoBAL quasars are a minority of all BALs, and rarer still is that this object also exhibits broad Fe II (an FeLoBAL) and Balmer absorption. This is the first BAL quasar that has signatures of recently truncated star formation, which we estimate ended about 40 Myr ago. The characteristic signatures of an FeLoBAL require high column densities, which could be explained by the emergence of a young quasar from an early, dust-enshrouded phase, or by clouds compressed by a blast wave. The age of the starburst component is comparable to estimates of the lifetime of quasars, so if we assume the quasar activity is related to the truncation of the star formation, this object is better explained by the blast wave scenario
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