785 research outputs found
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P10. Concomitant gemcitabine therapy negatively affects DC vaccine-induced CD8+ T cell and B cell responses but improves clinical efficacy in a murine pancreatic carcinoma model
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Rhythm in the speech of a person with right hemisphere damage: Applying the pairwise variability index
Although several aspects of prosody have been studied in speakers with right hemisphere damage (RHD), rhythm remains largely uninvestigated. This study compares the rhythm of an Australian English speaker with right hemisphere damage (due to a stroke, but with no concomitant dysarthria) to that of a neurologically unimpaired individual. The speakers' rhythm is compared using the pairwise variability index (PVI) which allows for an acoustic characterization of rhythm by comparing the duration of successive vocalic and intervocalic intervals. A sample of speech from a structured interview between a speech and language therapist and each participant was analysed. Previous research has shown that speakers with RHD may have difficulties with intonation production, and therefore it was hypothesized that there may also be rhythmic disturbance. Results show that the neurologically normal control uses a similar rhythm to that reported for British English (there are no previous studies available for Australian English), whilst the speaker with RHD produces speech with a less strongly stress-timed rhythm. This finding was statistically significant for the intervocalic intervals measured (t(8) = 4.7, p < .01), and suggests that some aspects of prosody may be right lateralized for this speaker. The findings are discussed in relation to previous findings of dysprosody in RHD populations, and in relation to syllable-timed speech of people with other neurological conditions
Assessing the Health of Richibucto Estuary with the Latent Health Factor Index
The ability to quantitatively assess the health of an ecosystem is often of
great interest to those tasked with monitoring and conserving ecosystems. For
decades, research in this area has relied upon multimetric indices of various
forms. Although indices may be numbers, many are constructed based on
procedures that are highly qualitative in nature, thus limiting the
quantitative rigour of the practical interpretations made from these indices.
The statistical modelling approach to construct the latent health factor index
(LHFI) was recently developed to express ecological data, collected to
construct conventional multimetric health indices, in a rigorous quantitative
model that integrates qualitative features of ecosystem health and preconceived
ecological relationships among such features. This hierarchical modelling
approach allows (a) statistical inference of health for observed sites and (b)
prediction of health for unobserved sites, all accompanied by formal
uncertainty statements. Thus far, the LHFI approach has been demonstrated and
validated on freshwater ecosystems. The goal of this paper is to adapt this
approach to modelling estuarine ecosystem health, particularly that of the
previously unassessed system in Richibucto in New Brunswick, Canada. Field data
correspond to biotic health metrics that constitute the AZTI marine biotic
index (AMBI) and abiotic predictors preconceived to influence biota. We also
briefly discuss related LHFI research involving additional metrics that form
the infaunal trophic index (ITI). Our paper is the first to construct a
scientifically sensible model to rigorously identify the collective explanatory
capacity of salinity, distance downstream, channel depth, and silt-clay content
--- all regarded a priori as qualitatively important abiotic drivers ---
towards site health in the Richibucto ecosystem.Comment: On 2013-05-01, a revised version of this article was accepted for
publication in PLoS One. See Journal reference and DOI belo
Speech-in-noise perception is linked to rhythm production skills in adult percussionists and non-musicians
Speech rhythms guide perception, especially in noise. We recently revealed that percussionists outperform non-musicians in speech-in-noise perception, with better speech-in-noise perception associated with better rhythm discrimination across a range of rhythmic expertise. Here, we consider rhythm production skills, specifically drumming to a beat (metronome or music) and to sequences (metrical or jittered patterns), as well as speech-in-noise perception in adult percussionists and non-musicians. Given the absence of a regular beat in speech, we hypothesise that processing of sequences is more important for speech-in-noise perception than the ability to entrain to a regular beat. Consistent with our hypothesis, we find that the sequence-based drumming measures predict speech-in-noise perception, above and beyond hearing thresholds and IQ, whereas the beat-based measures do not. Outcomes suggest temporal patterns may help disambiguate speech under degraded listening conditions, extending theoretical considerations about speech rhythm to the everyday challenge of listening in noise
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A cell autonomous torsinA requirement for cholinergic neuron survival and motor control
Cholinergic dysfunction is strongly implicated in dystonia pathophysiology. Previously (Pappas et al., 2015;4:e08352), we reported that Dlx5/6-Cre mediated forebrain deletion of the DYT1 dystonia protein torsinA (Dlx-CKO) causes abnormal twisting and selective degeneration of dorsal striatal cholinergic interneurons (ChI) (Pappas et al., 2015). A central question raised by that work is whether the ChI loss is cell autonomous or requires torsinA loss from neurons synaptically connected to ChIs. Here, we addressed this question by using ChAT-Cre mice to conditionally delete torsinA from cholinergic neurons (‘ChAT-CKO’). ChAT-CKO mice phenocopy the Dlx-CKO phenotype of selective dorsal striatal ChI loss and identify an essential requirement for torsinA in brainstem and spinal cholinergic neurons. ChAT-CKO mice are tremulous, weak, and exhibit trunk twisting and postural abnormalities. These findings are the first to demonstrate a cell autonomous requirement for torsinA in specific populations of cholinergic neurons, strengthening the connection between torsinA, cholinergic dysfunction and dystonia pathophysiology
The Role of Native Language and the Fundamental Design of the Auditory System in Detecting Rhythm Changes
Accepted December 13, 2018Purpose: We investigated whether rhythm discrimination
is mainly driven by the native language of the listener or
by the fundamental design of the human auditory system
and universal cognitive mechanisms shared by all people
irrespective of rhythmic patterns in their native language.
Method: In multiple experiments, we asked participants to
listen to 2 continuous acoustic sequences and to determine
whether their rhythms were the same or different (AX
discrimination). Participants were native speakers of
4 languages with different rhythmic properties (Spanish,
French, English, and German) to understand whether the
predominant rhythmic patterns of a native language affect
sensitivity, bias, and reaction time in detecting rhythmic
changes in linguistic (Experiment 2) and in nonlinguistic
(Experiments 1 and 2) acoustic sequences. We examined
sensitivity and bias measures, as well as reaction times.
We also computed Bayes factors in order to assess the
effect of native language.
Results: All listeners performed better (i.e., responded
faster and manifested higher sensitivity and accuracy)
when detecting the presence or absence of a rhythm
change when the 1st stimulus in an AX test pair exhibited
regular rhythm (i.e., a syllable-timed rhythmic pattern)
than when the 1st stimulus exhibited irregular rhythm (i.e.,
stress-timed rhythmic pattern). This result pattern was
observed both on linguistic and nonlinguistic stimuli
and was not modulated by the native language of the
participant.
Conclusion: We conclude that rhythm change detection is
a fundamental function of a processing system that relies
on general auditory mechanisms and is not modulated by
linguistic experience.The authors acknowledge support from Spanish Ministry of Economy and Competitiveness Grant PSI2017-82563-P (awarded to A. G. S.), the “Severo Ochoa” Programme for Centres/Units of Excellence in R&D Grant SEV-2015-490 (BCBL), and the Basque Foundation for Science Grant IKERBASQUE (awarded to A. G. S. and M. O.). D. M. G. was supported by Grant PIA/Basal FB0003 from the Chilean Research Council. L. P. was supported by the Spanish Ministry of Economy and Competitiveness via Juan de la Cierva fellowship
TOM40 Mediates Mitochondrial Dysfunction Induced by α-Synuclein Accumulation in Parkinson's Disease.
Alpha-synuclein (α-Syn) accumulation/aggregation and mitochondrial dysfunction play prominent roles in the pathology of Parkinson's disease. We have previously shown that postmortem human dopaminergic neurons from PD brains accumulate high levels of mitochondrial DNA (mtDNA) deletions. We now addressed the question, whether alterations in a component of the mitochondrial import machinery -TOM40- might contribute to the mitochondrial dysfunction and damage in PD. For this purpose, we studied levels of TOM40, mtDNA deletions, oxidative damage, energy production, and complexes of the respiratory chain in brain homogenates as well as in single neurons, using laser-capture-microdissection in transgenic mice overexpressing human wildtype α-Syn. Additionally, we used lentivirus-mediated stereotactic delivery of a component of this import machinery into mouse brain as a novel therapeutic strategy. We report here that TOM40 is significantly reduced in the brain of PD patients and in α-Syn transgenic mice. TOM40 deficits were associated with increased mtDNA deletions and oxidative DNA damage, and with decreased energy production and altered levels of complex I proteins in α-Syn transgenic mice. Lentiviral-mediated overexpression of Tom40 in α-Syn-transgenic mice brains ameliorated energy deficits as well as oxidative burden. Our results suggest that alterations in the mitochondrial protein transport machinery might contribute to mitochondrial impairment in α-Synucleinopathies
Radiation Safety in the Treatment of Patients with Thyroid Diseases by Radioiodine 131I: Practice Recommendations of the American Thyroid Association
Background: Radiation safety is an essential component in the treatment of patients with thyroid diseases by 131I. The American Thyroid Association created a task force to develop recommendations that would inform medical professionals about attainment of radiation safety for patients, family members, and the public. The task force was constituted so as to obtain advice, experience, and methods from relevant medical specialties and disciplines. Methods: Reviews of Nuclear Regulatory Commission regulations and International Commission on Radiological Protection recommendations formed the basic structure of recommendations. Members of the task force contributed both ideas and methods that are used at their respective institutions to aid groups responsible for treatments and that instruct patients and caregivers in the attainment of radiation safety. There are insufficient data on long-term outcomes to create evidence-based guidelines. Results: The information was used to compile delineations of radiation safety. Factors and situations that govern implementation of safety practices are cited and discussed. Examples of the development of tables to ascertain the number of hours or days (24-hour cycles) of radiation precaution appropriate for individual patients treated with 131I for hyperthyroidism and thyroid cancer have been provided. Reminders in the form of a checklist are presented to assist in assessing patients while taking into account individual circumstances that would bear on radiation safety. Information is presented to supplement the treating physician's advice to patients and caregivers on precautions to be adopted within and outside the home. Conclusion: Recommendations, complying with Nuclear Regulatory Commission regulations and consistent with guidelines promulgated by the National Council on Radiation Protection and Measurement (NCRP-155), can help physicians and patients maintain radiation safety after treatment with 131I of patients with thyroid diseases. Both treating physicians and patients must be informed if radiation safety, an integral part of therapy with 131I, is to be attained. Based on current regulations and understanding of radiation exposures, recommendations have been made to guide physicians and patients in safe practices after treatment with radioactive iodine.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/90492/1/thy-2E2010-2E0403.pd
Set optimization - a rather short introduction
Recent developments in set optimization are surveyed and extended including
various set relations as well as fundamental constructions of a convex analysis
for set- and vector-valued functions, and duality for set optimization
problems. Extensive sections with bibliographical comments summarize the state
of the art. Applications to vector optimization and financial risk measures are
discussed along with algorithmic approaches to set optimization problems
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