3,610 research outputs found
Children's traditional ecological knowledge of wild food resources: a case study in a rural village in Northeast Thailand
Consuming wild foods is part of the food ways of people in many societies, including farming populations throughout the world. Knowledge of non-domesticated food resources is part of traditional and tacit ecological knowledge, and is largely transmitted through socialization within cultural and household contexts. The context of this study, a small village in Northeast Thailand, is one where the community has experienced changes due to the migration of the parental generation, with the children being left behind in the village to be raised by their grandparents
The attitude of patients with progressive ataxias towards clinical trials
Background
The development of new therapies may rely on the conduct of human experimentation as well as later clinical trials of therapeutic interventions. Ethical considerations seek to protect the patient from risk but few have sought to ascertain the attitude to such risk of patients with progressive debilitating or terminal conditions, for which no mitigating or curative therapies exist. Such understanding is also important if recruitment is to be maximized. We therefore sought to define the motivations for and barriers to trial participation amongst patients with progressive ataxias, as well as their condition-specific trial preferences.
Methods
We conducted an online survey consisting of 29 questions covering four key domains (demographics, personal motivation, drug therapy and study design) relating to the design of clinical trials. Two major ataxia charities, Ataxia UK and the Friedreich’s Ataxia Research Alliance (FARA) sent the survey to their members. Responses were analysed by disease and by ambulatory status.
Results
Of 342 respondents, 204 reported a diagnosis of Friedreich’s ataxia (FRDA), 55 inherited cerebellar ataxia (CA) and 70 idiopathic CA. The most important symptoms to be addressed by a trial were considered to be balance problems and ambulation, although these were superseded by speech problems in wheelchair users. Common motivations for participation were potential benefits to self and others. Reasons for non-participation included concerns about side effects, and the burden and cost of travel. Financial reimbursement for expenses was reported to be likely to increase trial engagement, Phase two trials were the most popular to participate in, and the use of a placebo arm was seen as a disincentive. Across all disease subgroups, drug repurposing trials proved popular and just under 70% of participants would be prepared to undergo intrathecal drug administration.
Conclusions
Knowledge of motivations for and barriers to trial participation as well as the acceptability of investigations, time commitments and routes of drug administration should inform better, more patient focused trial design. This in turn may improve recruitment and retention of participants to future trials
Plasma Markers of Neurodegeneration Are Raised in Friedreich's Ataxia
Background: Friedreich’s ataxia (FRDA) is the most common autosomal recessive ataxia. Disease-modifying treatments are not available yet; however, several compounds are currently under investigation. As a result, there is a growing need for the identification of robust and easily accessible biomarkers for the monitoring of disease activity and therapeutic efficacy. The simultaneous measurement of multiple brain-derived proteins could represent a time- and cost-efficient approach for biomarker investigation in pathologically complex neurodegenerative diseases like FRDA.
Objectives: To investigate the role of plasma neurofilament-light chain (NfL), glial fibrillary acidic protein (GFAP), total tau (t-tau) and ubiquitin C-terminal hydrolase L1(UCHL1) as biomarkers in FRDA. Additionally, NfL measurements derived from the novel multiplex assay were compared to those from an established NfL singleplex assay.
Methods: In this study, an ultrasensitive Single molecule array (Simoa) 4-plex assay was used for the measurement of plasma NfL, GFAP, t-tau, and UCHL1 in 33 FRDA patients and 13 age-matched controls. Differences in biomarker concentrations between these groups were computed and associations with genetic and disease related parameters investigated. Additionally, the agreement between NfL measurements derived from the 4-Plex and an established Simoa NfL singleplex assay was assessed.
Results: Mean plasma NfL, GFAP and UCHL1 levels were significantly higher in FRDA patients than in controls (NfL: p < 0.001; GFAP: p = 0.006, and UCHL1: p = 0.020). Conversely, there was no significant difference in concentrations of t-tau in the patient and control group (p = 0.236). None of the proteins correlated with the GAA repeat length or the employed measures of disease severity. The individual NfL values derived from the two assays showed a strong concordance (rc = 0.93). Although the mean difference of 1.29 pg/mL differed significantly from 0 (p = 0.006), regression analysis did not indicate the presence of a proportional bias.
Conclusion: This is the first study demonstrating that NfL, GFAP, and UCHL1 levels are raised in FRDA, potentially reflecting ongoing neuronal degeneration and glial activation. Further studies are required to determine their role as marker for disease activity and progression. Furthermore, the novel 4-plex assay appears to be a valid tool to simultaneously measure brain-derived proteins at extremely low concentrations in the peripheral circulation
Validation of the SCID-hu Thy/Liv mouse model with four classes of licensed antiretrovirals.
BackgroundThe SCID-hu Thy/Liv mouse model of HIV-1 infection is a useful platform for the preclinical evaluation of antiviral efficacy in vivo. We performed this study to validate the model with representatives of all four classes of licensed antiretrovirals.Methodology/principal findingsEndpoint analyses for quantification of Thy/Liv implant viral load included ELISA for cell-associated p24, branched DNA assay for HIV-1 RNA, and detection of infected thymocytes by intracellular staining for Gag-p24. Antiviral protection from HIV-1-mediated thymocyte depletion was assessed by multicolor flow cytometric analysis of thymocyte subpopulations based on surface expression of CD3, CD4, and CD8. These mice can be productively infected with molecular clones of HIV-1 (e.g., the X4 clone NL4-3) as well as with primary R5 and R5X4 isolates. To determine whether results in this model are concordant with those found in humans, we performed direct comparisons of two drugs in the same class, each of which has known potency and dosing levels in humans. Here we show that second-generation antiretrovirals were, as expected, more potent than their first-generation predecessors: emtricitabine was more potent than lamivudine, efavirenz was more potent than nevirapine, and atazanavir was more potent than indinavir. After interspecies pharmacodynamic scaling, the dose ranges found to inhibit viral replication in the SCID-hu Thy/Liv mouse were similar to those used in humans. Moreover, HIV-1 replication in these mice was genetically stable; treatment of the mice with lamivudine did not result in the M184V substitution in reverse transcriptase, and the multidrug-resistant NY index case HIV-1 retained its drug-resistance substitutions.ConclusionGiven the fidelity of such comparisons, we conclude that this highly reproducible mouse model is likely to predict clinical antiviral efficacy in humans
Astrophysically Triggered Searches for Gravitational Waves: Status and Prospects
In gravitational-wave detection, special emphasis is put onto searches that
focus on cosmic events detected by other types of astrophysical observatories.
The astrophysical triggers, e.g. from gamma-ray and X-ray satellites, optical
telescopes and neutrino observatories, provide a trigger time for analyzing
gravitational wave data coincident with the event. In certain cases the
expected frequency range, source energetics, directional and progenitor
information is also available. Beyond allowing the recognition of gravitational
waveforms with amplitudes closer to the noise floor of the detector, these
triggered searches should also lead to rich science results even before the
onset of Advanced LIGO. In this paper we provide a broad review of LIGO's
astrophysically triggered searches and the sources they target
Search for Gravitational Wave Bursts from Soft Gamma Repeaters
We present the results of a LIGO search for short-duration gravitational
waves (GWs) associated with Soft Gamma Repeater (SGR) bursts. This is the first
search sensitive to neutron star f-modes, usually considered the most efficient
GW emitting modes. We find no evidence of GWs associated with any SGR burst in
a sample consisting of the 27 Dec. 2004 giant flare from SGR 1806-20 and 190
lesser events from SGR 1806-20 and SGR 1900+14 which occurred during the first
year of LIGO's fifth science run. GW strain upper limits and model-dependent GW
emission energy upper limits are estimated for individual bursts using a
variety of simulated waveforms. The unprecedented sensitivity of the detectors
allows us to set the most stringent limits on transient GW amplitudes published
to date. We find upper limit estimates on the model-dependent isotropic GW
emission energies (at a nominal distance of 10 kpc) between 3x10^45 and 9x10^52
erg depending on waveform type, detector antenna factors and noise
characteristics at the time of the burst. These upper limits are within the
theoretically predicted range of some SGR models.Comment: 6 pages, 1 Postscript figur
A Joint Search for Gravitational Wave Bursts with AURIGA and LIGO
The first simultaneous operation of the AURIGA detector and the LIGO
observatory was an opportunity to explore real data, joint analysis methods
between two very different types of gravitational wave detectors: resonant bars
and interferometers. This paper describes a coincident gravitational wave burst
search, where data from the LIGO interferometers are cross-correlated at the
time of AURIGA candidate events to identify coherent transients. The analysis
pipeline is tuned with two thresholds, on the signal-to-noise ratio of AURIGA
candidate events and on the significance of the cross-correlation test in LIGO.
The false alarm rate is estimated by introducing time shifts between data sets
and the network detection efficiency is measured with simulated signals with
power in the narrower AURIGA band. In the absence of a detection, we discuss
how to set an upper limit on the rate of gravitational waves and to interpret
it according to different source models. Due to the short amount of analyzed
data and to the high rate of non-Gaussian transients in the detectors noise at
the time, the relevance of this study is methodological: this was the first
joint search for gravitational wave bursts among detectors with such different
spectral sensitivity and the first opportunity for the resonant and
interferometric communities to unify languages and techniques in the pursuit of
their common goal.Comment: 18 pages, IOP, 12 EPS figure
Sensitivity to Gravitational Waves from Compact Binary Coalescences Achieved during LIGO's Fifth and Virgo's First Science Run
We summarize the sensitivity achieved by the LIGO and Virgo gravitational
wave detectors for compact binary coalescence (CBC) searches during LIGO's
fifth science run and Virgo's first science run. We present noise spectral
density curves for each of the four detectors that operated during these
science runs which are representative of the typical performance achieved by
the detectors for CBC searches. These spectra are intended for release to the
public as a summary of detector performance for CBC searches during these
science runs.Comment: 12 pages, 5 figure
All-sky LIGO Search for Periodic Gravitational Waves in the Early S5 Data
We report on an all-sky search with the LIGO detectors for periodic
gravitational waves in the frequency range 50--1100 Hz and with the frequency's
time derivative in the range -5.0E-9 Hz/s to zero. Data from the first eight
months of the fifth LIGO science run (S5) have been used in this search, which
is based on a semi-coherent method (PowerFlux) of summing strain power.
Observing no evidence of periodic gravitational radiation, we report 95%
confidence-level upper limits on radiation emitted by any unknown isolated
rotating neutron stars within the search range. Strain limits below 1.E-24 are
obtained over a 200-Hz band, and the sensitivity improvement over previous
searches increases the spatial volume sampled by an average factor of about 100
over the entire search band. For a neutron star with nominal equatorial
ellipticity of 1.0E-6, the search is sensitive to distances as great as 500
pc--a range that could encompass many undiscovered neutron stars, albeit only a
tiny fraction of which would likely be rotating fast enough to be accessible to
LIGO. This ellipticity is at the upper range thought to be sustainable by
conventional neutron stars and well below the maximum sustainable by a strange
quark star.Comment: 6 pages, 1 figur
Gravitational Waves From Known Pulsars: Results From The Initial Detector Era
We present the results of searches for gravitational waves from a large selection of pulsars using data from the most recent science runs (S6, VSR2 and VSR4) of the initial generation of interferometric gravitational wave detectors LIGO (Laser Interferometric Gravitational-wave Observatory) and Virgo. We do not see evidence for gravitational wave emission from any of the targeted sources but produce upper limits on the emission amplitude. We highlight the results from seven young pulsars with large spin-down luminosities. We reach within a factor of five of the canonical spin-down limit for all seven of these, whilst for the Crab and Vela pulsars we further surpass their spin-down limits. We present new or updated limits for 172 other pulsars (including both young and millisecond pulsars). Now that the detectors are undergoing major upgrades, and, for completeness, we bring together all of the most up-to-date results from all pulsars searched for during the operations of the first-generation LIGO, Virgo and GEO600 detectors. This gives a total of 195 pulsars including the most recent results described in this paper.United States National Science FoundationScience and Technology Facilities Council of the United KingdomMax-Planck-SocietyState of Niedersachsen/GermanyAustralian Research CouncilInternational Science Linkages program of the Commonwealth of AustraliaCouncil of Scientific and Industrial Research of IndiaIstituto Nazionale di Fisica Nucleare of ItalySpanish Ministerio de Economia y CompetitividadConselleria d'Economia Hisenda i Innovacio of the Govern de les Illes BalearsNetherlands Organisation for Scientific ResearchPolish Ministry of Science and Higher EducationFOCUS Programme of Foundation for Polish ScienceRoyal SocietyScottish Funding CouncilScottish Universities Physics AllianceNational Aeronautics and Space AdministrationOTKA of HungaryLyon Institute of Origins (LIO)National Research Foundation of KoreaIndustry CanadaProvince of Ontario through the Ministry of Economic Development and InnovationNational Science and Engineering Research Council CanadaCarnegie TrustLeverhulme TrustDavid and Lucile Packard FoundationResearch CorporationAlfred P. Sloan FoundationAstronom
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