243 research outputs found
Reading on Grade Level in Third Grade: How Is It Related to High School Performance and College Enrollment?
Illustrates how third-grade reading level correlates with eighth-grade reading level, which, along with ninth-grade school traits, correlates with ninth-grade performance, which in turn correlates with high school graduation and college attendance rates
Genome-wide screen for temperature-regulated genes of the obligate intracellular bacterium, Rickettsia typhi
<p>Abstract</p> <p>Background</p> <p>The ability of rickettsiae to survive in multiple eukaryotic host environments provides a good model for studying pathogen-host molecular interactions. <it>Rickettsia typhi</it>, the etiologic agent of murine typhus, is a strictly intracellular gram negative α-proteobacterium, which is transmitted to humans by its arthropod vector, the oriental rat flea, <it>Xenopsylla cheopis</it>. Thus, <it>R. typhi </it>must cycle between mammalian and flea hosts, two drastically different environments. We hypothesize that temperature plays a role in regulating host-specific gene expression, allowing <it>R. typhi </it>to survive in mammalian and arthropod hosts. In this study, we used Affymetrix microarrays to screen for temperature-induced genes upon a temperature shift from 37°C to 25°C, mimicking the two different host temperatures <it>in vitro</it>.</p> <p>Results</p> <p>Temperature-responsive genes belonged to multiple functional categories including among others, transcription, translation, posttranslational modification/protein turnover/chaperones and intracellular trafficking and secretion. A large number of differentially expressed genes are still poorly characterized, and either have no known function or are not in the COG database. The microarray results were validated with quantitative real time RT-PCR.</p> <p>Conclusion</p> <p>This microarray screen identified various genes that were differentially expressed upon a shift in temperature from 37°C to 25°C. Further characterization of the identified genes may provide new insights into the ability of <it>R. typhi </it>to successfully transition between its mammalian and arthropod hosts.</p
Resident-Led Physical Wellness Initiative Linked to Less Burnout for Emergency Physicians during COVID-19 Pandemic
Introduction: The COVID-19 pandemic has taken a significant toll on societal, physical, and psychological health. Emergency physicians (EPs) are susceptible to burnout under ordinary circumstances and may be particularly vulnerable during the pandemic. To reduce pandemic-related burnout, we implemented a residency-led physical wellness initiative and evaluated the effect on burnout among EPs.
Methods: In the spring of 2020, we invited all resident and attending EPs in our department to participate in a four-week physical wellness initiative as part of a prospective study. After completing or opting out of this wellness initiative, EPs responded to an online survey comprised of five sections: demographics, participation, opinion on wellness initiative, opinion on the impact of COVID-19, and the Maslach Burnout Index (MBI-HSS). We stratified respondents by initiative participation, described the characteristics of each group, and then compared the perceived impact of COVID-19 and the MBI-HSS results between the two groups.
Results: Out of 110 eligible participants, 57 EPs completed the survey (51.8%). Thirty-five respondents completed the wellness initiative. Few (37.1%) documented their progress, though most worked with accountability partners (85.7%). Most enrollees enjoyed participation (Likert Score 3.2-5, CI 2.9-3.5) and would participate again (3.3, CI 3.0-3.6). The reported effect of the COVID-19 pandemic on mental wellbeing was lower for participants, although this was not significant (2.1, CI 1.5-2.1 vs 2.4, CI 2.0-2.7, p=0.312). On the MBI-HSS, participants had a lower emotional exhaustion score (1.4, 95% CI 0.9-1.8) than non-participants (2.2, 95%CI 1.8-2.6, p=0.005).
Conclusion: Participation in a residency-led, physical wellness initiative was linked to lower emotional exhaustion for EPs during the COVID-19 pandemic
The Theory of the Interleaving Distance on Multidimensional Persistence Modules
In 2009, Chazal et al. introduced -interleavings of persistence
modules. -interleavings induce a pseudometric on (isomorphism
classes of) persistence modules, the interleaving distance. The definitions of
-interleavings and generalize readily to multidimensional
persistence modules. In this paper, we develop the theory of multidimensional
interleavings, with a view towards applications to topological data analysis.
We present four main results. First, we show that on 1-D persistence modules,
is equal to the bottleneck distance . This result, which first
appeared in an earlier preprint of this paper, has since appeared in several
other places, and is now known as the isometry theorem. Second, we present a
characterization of the -interleaving relation on multidimensional
persistence modules. This expresses transparently the sense in which two
-interleaved modules are algebraically similar. Third, using this
characterization, we show that when we define our persistence modules over a
prime field, satisfies a universality property. This universality result
is the central result of the paper. It says that satisfies a stability
property generalizing one which is known to satisfy, and that in
addition, if is any other pseudometric on multidimensional persistence
modules satisfying the same stability property, then . We also show
that a variant of this universality result holds for , over arbitrary
fields. Finally, we show that restricts to a metric on isomorphism
classes of finitely presented multidimensional persistence modules.Comment: Major revision; exposition improved throughout. To appear in
Foundations of Computational Mathematics. 36 page
The persistence landscape and some of its properties
Persistence landscapes map persistence diagrams into a function space, which
may often be taken to be a Banach space or even a Hilbert space. In the latter
case, it is a feature map and there is an associated kernel. The main advantage
of this summary is that it allows one to apply tools from statistics and
machine learning. Furthermore, the mapping from persistence diagrams to
persistence landscapes is stable and invertible. We introduce a weighted
version of the persistence landscape and define a one-parameter family of
Poisson-weighted persistence landscape kernels that may be useful for learning.
We also demonstrate some additional properties of the persistence landscape.
First, the persistence landscape may be viewed as a tropical rational function.
Second, in many cases it is possible to exactly reconstruct all of the
component persistence diagrams from an average persistence landscape. It
follows that the persistence landscape kernel is characteristic for certain
generic empirical measures. Finally, the persistence landscape distance may be
arbitrarily small compared to the interleaving distance.Comment: 18 pages, to appear in the Proceedings of the 2018 Abel Symposiu
A Genomic Pathway Approach to a Complex Disease: Axon Guidance and Parkinson Disease
While major inroads have been made in identifying the genetic causes of rare Mendelian disorders, little progress has been made in the discovery of common gene variations that predispose to complex diseases. The single gene variants that have been shown to associate reproducibly with complex diseases typically have small effect sizes or attributable risks. However, the joint actions of common gene variants within pathways may play a major role in predisposing to complex diseases (the paradigm of complex genetics). The goal of this study was to determine whether polymorphism in a candidate pathway (axon guidance) predisposed to a complex disease (Parkinson disease [PD]). We mined a whole-genome association dataset and identified single nucleotide polymorphisms (SNPs) that were within axon-guidance pathway genes. We then constructed models of axon-guidance pathway SNPs that predicted three outcomes: PD susceptibility (odds ratio = 90.8, p = 4.64 × 10−38), survival free of PD (hazards ratio = 19.0, p = 5.43 × 10−48), and PD age at onset (R2 = 0.68, p = 1.68 × 10−51). By contrast, models constructed from thousands of random selections of genomic SNPs predicted the three PD outcomes poorly. Mining of a second whole-genome association dataset and mining of an expression profiling dataset also supported a role for many axon-guidance pathway genes in PD. These findings could have important implications regarding the pathogenesis of PD. This genomic pathway approach may also offer insights into other complex diseases such as Alzheimer disease, diabetes mellitus, nicotine and alcohol dependence, and several cancers
Topological Methods for Exploring Low-density States in Biomolecular Folding Pathways
Characterization of transient intermediate or transition states is crucial
for the description of biomolecular folding pathways, which is however
difficult in both experiments and computer simulations. Such transient states
are typically of low population in simulation samples. Even for simple systems
such as RNA hairpins, recently there are mounting debates over the existence of
multiple intermediate states. In this paper, we develop a computational
approach to explore the relatively low populated transition or intermediate
states in biomolecular folding pathways, based on a topological data analysis
tool, Mapper, with simulation data from large-scale distributed computing. The
method is inspired by the classical Morse theory in mathematics which
characterizes the topology of high dimensional shapes via some functional level
sets. In this paper we exploit a conditional density filter which enables us to
focus on the structures on pathways, followed by clustering analysis on its
level sets, which helps separate low populated intermediates from high
populated uninteresting structures. A successful application of this method is
given on a motivating example, a RNA hairpin with GCAA tetraloop, where we are
able to provide structural evidence from computer simulations on the multiple
intermediate states and exhibit different pictures about unfolding and
refolding pathways. The method is effective in dealing with high degree of
heterogeneity in distribution, capturing structural features in multiple
pathways, and being less sensitive to the distance metric than nonlinear
dimensionality reduction or geometric embedding methods. It provides us a
systematic tool to explore the low density intermediate states in complex
biomolecular folding systems.Comment: 23 pages, 6 figure
'Education, education, education' : legal, moral and clinical
This article brings together Professor Donald Nicolson's intellectual interest in professional legal ethics and his long-standing involvement with law clinics both as an advisor at the University of Cape Town and Director of the University of Bristol Law Clinic and the University of Strathclyde Law Clinic. In this article he looks at how legal education may help start this process of character development, arguing that the best means is through student involvement in voluntary law clinics. And here he builds upon his recent article which argues for voluntary, community service oriented law clinics over those which emphasise the education of students
Frequency and topography of cerebral microbleeds in dementia with Lewy bodies compared to Alzheimer's disease
AbstractAimTo determine the frequency and topographic distribution of cerebral microbleeds (CMBs) in dementia with Lewy bodies (DLB) in comparison to CMBs in Alzheimer disease dementia (AD).MethodsConsecutive probable DLB (n = 23) patients who underwent 3-T T2* weighted gradient-recalled-echo MRI, and age and gender matched probable Alzheimer's disease patients (n = 46) were compared for the frequency and location of CMBs.ResultsThe frequency of one or more CMBs was similar among patients with DLB (30%) and AD (24%). Highest densities of CMBs were found in the occipital lobes of patients with both DLB and AD. Patients with AD had greater densities of CMBs in the parietal, temporal lobes and infratentorial regions compared to DLB (p < 0.05).ConclusionCMBs are as common in patients with DLB as in patients with AD, with highest densities observed in the occipital lobes, suggesting common pathophysiologic mechanisms underlying CMBs in both diseases
Neither Replication nor Simulation Supports a Role for the Axon Guidance Pathway in the Genetics of Parkinson's Disease
Susceptibility to sporadic Parkinson's disease (PD) is thought to be influenced by both genetic and environmental factors and their interaction with each other. Statistical models including multiple variants in axon guidance pathway genes have recently been purported to be capable of predicting PD risk, survival free of the disease and age at disease onset; however the specific models have not undergone independent validation. Here we tested the best proposed risk panel of 23 single nucleotide polymorphisms (SNPs) in two PD sample sets, with a total of 525 cases and 518 controls. By single marker analysis, only one marker was significantly associated with PD risk in one of our sample sets (rs6692804: P = 0.03). Multi-marker analysis using the reported model found a mild association in one sample set (two sided P = 0.049, odds ratio for each score change = 1.07) but no significance in the other (two sided P = 0.98, odds ratio = 1), a stark contrast to the reported strong association with PD risk (P = 4.64×10−38, odds ratio as high as 90.8). Following a procedure similar to that used to build the reported model, simulated multi-marker models containing SNPs from randomly chosen genes in a genome wide PD dataset produced P-values that were highly significant and indistinguishable from similar models where disease status was permuted (3.13×10−23 to 4.90×10−64), demonstrating the potential for overfitting in the model building process. Together, these results challenge the robustness of the reported panel of genetic markers to predict PD risk in particular and a role of the axon guidance pathway in PD genetics in general
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