1,650 research outputs found
Perceptions about the elisa test of people diagnosed at the aids stage
Indexación: Web of Science; Scopus; Scielo.Background: The delay in the diagnosis of AIDS results in higher treatment costs. Aim: To reveal the experiences of people who were diagnosed in the AIDS stage about the access to the ELISA test. Material and Methods: In depth interviews were carried out to 15 participants from public hospitals who were in the AIDS stage at the moment of the diagnosis. The main questions asked were about the motivations to take the test, the barriers found and the help received from the health care personnel. All interviews were recorded and analyzed according to Kripperdorff. Results: The three categories that emerged were the motivations to take the test, the facilitators found and the difficulties to access to the test. The main motivation was a condition of vulnerability due to the suspicion or certainty of being infected. The main facilitator was the sensation of being accepted and not discriminated. The main difficulties were the fear of having a positive test and of being discriminated and the lack of information. Conclusions: Knowing these experiences will help to improve the early detection of HIV infections.http://ref.scielo.org/m53w8
Expansive actions on uniform spaces and surjunctive maps
We present a uniform version of a result of M. Gromov on the surjunctivity of
maps commuting with expansive group actions and discuss several applications.
We prove in particular that for any group and any field \K, the
space of -marked groups such that the group algebra \K[G] is
stably finite is compact.Comment: 21 page
Predictions from Lattice QCD
In the past year, we calculated with lattice QCD three quantities that were
unknown or poorly known. They are the dependence of the form factor in
semileptonic decay, the decay constant of the meson, and the
mass of the meson. In this talk, we summarize these calculations, with
emphasis on their (subsequent) confirmation by experiments.Comment: v1: talk given at the International Conference on QCD and Hadronic
Physics, Beijing, June 16-20, 2005; v2: poster presented at the XXIIIrd
International Symposium on Lattice Field Theory, Dublin, July 25-3
A transient helix in the disordered region of dynein light intermediate chain links the motor to structurally diverse adaptors for cargo transport
All animal cells use the motor cytoplasmic dynein 1 (dynein) to transport diverse cargo toward microtubule minus ends and to organize and position microtubule arrays such as the mitotic spindle. Cargo-specific adaptors engage with dynein to recruit and activate the motor, but the molecular mechanisms remain incompletely understood. Here, we use structural and dynamic nuclear magnetic resonance (NMR) analysis to demonstrate that the C-terminal region of human dynein light intermediate chain 1 (LIC1) is intrinsically disordered and contains two short conserved segments with helical propensity. NMR titration experiments reveal that the first helical segment (helix 1) constitutes the main interaction site for the adaptors Spindly (SPDL1), bicaudal D homolog 2 (BICD2), and Hook homolog 3 (HOOK3). In vitro binding assays show that helix 1, but not helix 2, is essential in both LIC1 and LIC2 for binding to SPDL1, BICD2, HOOK3, RAB-interacting lysosomal protein (RILP), RAB11 family-interacting protein 3 (RAB11FIP3), ninein (NIN), and trafficking kinesin-bind-ing protein 1 (TRAK1). Helix 1 is sufficient to bind RILP, whereas other adaptors require additional segments preceding helix 1 for efficient binding. Point mutations in the C-terminal helix 1 of Caenorhabditis elegans LIC, introduced by genome editing, severely affect development, locomotion, and life span of the animal and disrupt the distribution and transport kinetics of membrane cargo in axons of mechanosensory neurons, identical to what is observed when the entire LIC C-terminal region is deleted. Deletion of the C-terminal helix 2 delays dynein-dependent spindle positioning in the one-cell embryo but overall does not significantly perturb dynein function. We conclude that helix 1 in the intrinsically disordered region of LIC provides a conserved link between dynein and structurally diverse cargo adaptor families that is critical for dynein function in vivo.This work was financed by the Fundo Europeu de Desenvolvimento Regional (FEDER) through the Norte Portugal Regional Operational Programme (NORTE 2020), Portugal 2020 (RG); by the Fundação para a Ciência e a Tecnologia (FCT)/Ministério da Ciência, Tecnologia e Ensino Superior in the framework of the project NORTE-01-0145-FEDER-030507 (RG); by FCT fellowships IF/01015/2013/CP1157/CT0006 (RG) and SFRH/ BPD/101898/2014 (DJB); by the European Research Council under the European Union’s Seventh Framework Programme, ERC grant agreement no. ERC-2013-StG-338410-DYNEINOME (RG), and by a start-up package of the University of Colorado (BV). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript
Trapped lipopolysaccharide and LptD intermediates reveal lipopolysaccharide translocation steps across the Escherichia coli outer membrane
Lipopolysaccharide (LPS) is a main component of the outer membrane of Gram-negative bacteria, which is essential for the vitality of most Gram-negative bacteria and plays a critical role for drug resistance. LptD/E complex forms a N-terminal LPS transport slide, a hydrophobic intramembrane hole and the hydrophilic channel of the barrel, for LPS transport, lipid A insertion and core oligosaccharide and O-antigen polysaccharide translocation, respectively. However, there is no direct evidence to confirm that LptD/E transports LPS from the periplasm to the external leaflet of the outer membrane. By replacing LptD residues with an unnatural amino acid p-benzoyl-L-phenyalanine (pBPA) and UV-photo-cross-linking in E.coli, the translocon and LPS intermediates were obtained at the N-terminal domain, the intramembrane hole, the lumenal gate, the lumen of LptD channel, and the extracellular loop 1 and 4, providing the first direct evidence and “snapshots” to reveal LPS translocation steps across the outer membrane
A novel PKC activating molecule promotes neuroblast differentiation and delivery of newborn neurons in brain injuries
Neural stem cells are activated within neurogenic niches in response to brain injuries. This results in the production of neuroblasts, which unsuccessfully attempt to migrate toward the damaged tissue. Injuries constitute a gliogenic/non-neurogenic niche generated by the presence of anti-neurogenic signals, which impair neuronal differentiation and migration. Kinases of the protein kinase C (PKC) family mediate the release of growth factors that participate in different steps of the neurogenic process, particularly, novel PKC isozymes facilitate the release of the neurogenic growth factor neuregulin. We have demonstrated herein that a plant derived diterpene, (EOF2; CAS number 2230806-06-9), with the capacity to activate PKC facilitates the release of neuregulin 1, and promotes neuroblasts differentiation and survival in cultures of subventricular zone (SVZ) isolated cells in a novel PKC dependent manner. Local infusion of this compound in mechanical cortical injuries induces neuroblast enrichment within the perilesional area, and noninvasive intranasal administration of EOF2 promotes migration of neuroblasts from the SVZ towards the injury, allowing their survival and differentiation into mature neurons, being some of them cholinergic and GABAergic. Our results elucidate the mechanism of EOF2 promoting neurogenesis in injuries and highlight the role of novel PKC isozymes as targets in brain injury regeneration
Cosmic Flows on 100 Mpc/h Scales: Standardized Minimum Variance Bulk Flow, Shear and Octupole Moments
The low order moments, such as the bulk flow and shear, of the large scale
peculiar velocity field are sensitive probes of the matter density fluctuations
on very large scales. In practice, however, peculiar velocity surveys are
usually sparse and noisy, which can lead to the aliasing of small scale power
into what is meant to be a probe of the largest scales. Previously, we
developed an optimal ``minimum variance'' (MV) weighting scheme, designed to
overcome this problem by minimizing the difference between the measured bulk
flow (BF) and that which would be measured by an ideal survey. Here we extend
this MV analysis to include the shear and octupole moments, which are designed
to have almost no correlations between them so that they are virtually
orthogonal. We apply this MV analysis to a compilation of all major peculiar
velocity surveys, consisting of 4536 measurements. Our estimate of the BF on
scales of ~ 100 Mpc/h has a magnitude of |v|= 416 +/- 78 km/s towards Galactic
l = 282 degree +/- 11 degree and b = 6 degree +/- 6 degree. This result is in
disagreement with LCDM with WMAP5 cosmological parameters at a high confidence
level, but is in good agreement with our previous MV result without an
orthogonality constraint, showing that the shear and octupole moments did not
contaminate the previous BF measurement. The shear and octupole moments are
consistent with WMAP5 power spectrum, although the measurement noise is larger
for these moments than for the BF. The relatively low shear moments suggest
that the sources responsible for the BF are at large distances.Comment: 13 Pages, 7 figures, 4 tables. Some changes to reflect the published
versio
Human-computer collaboration for skin cancer recognition
The rapid increase in telemedicine coupled with recent advances in diagnostic artificial intelligence (AI) create the imperative to consider the opportunities and risks of inserting AI-based support into new paradigms of care. Here we build on recent achievements in the accuracy of image-based AI for skin cancer diagnosis to address the effects of varied representations of AI-based support across different levels of clinical expertise and multiple clinical workflows. We find that good quality AI-based support of clinical decision-making improves diagnostic accuracy over that of either AI or physicians alone, and that the least experienced clinicians gain the most from AI-based support. We further find that AI-based multiclass probabilities outperformed content-based image retrieval (CBIR) representations of AI in the mobile technology environment, and AI-based support had utility in simulations of second opinions and of telemedicine triage. In addition to demonstrating the potential benefits associated with good quality AI in the hands of non-expert clinicians, we find that faulty AI can mislead the entire spectrum of clinicians, including experts. Lastly, we show that insights derived from AI class-activation maps can inform improvements in human diagnosis. Together, our approach and findings offer a framework for future studies across the spectrum of image-based diagnostics to improve human-computer collaboration in clinical practice
Designing an automated clinical decision support system to match clinical practice guidelines for opioid therapy for chronic pain
Abstract Background Opioid prescribing for chronic pain is common and controversial, but recommended clinical practices are followed inconsistently in many clinical settings. Strategies for increasing adherence to clinical practice guideline recommendations are needed to increase effectiveness and reduce negative consequences of opioid prescribing in chronic pain patients. Methods Here we describe the process and outcomes of a project to operationalize the 2003 VA/DOD Clinical Practice Guideline for Opioid Therapy for Chronic Non-Cancer Pain into a computerized decision support system (DSS) to encourage good opioid prescribing practices during primary care visits. We based the DSS on the existing ATHENA-DSS. We used an iterative process of design, testing, and revision of the DSS by a diverse team including guideline authors, medical informatics experts, clinical content experts, and end-users to convert the written clinical practice guideline into a computable algorithm to generate patient-specific recommendations for care based upon existing information in the electronic medical record (EMR), and a set of clinical tools. Results The iterative revision process identified numerous and varied problems with the initially designed system despite diverse expert participation in the design process. The process of operationalizing the guideline identified areas in which the guideline was vague, left decisions to clinical judgment, or required clarification of detail to insure safe clinical implementation. The revisions led to workable solutions to problems, defined the limits of the DSS and its utility in clinical practice, improved integration into clinical workflow, and improved the clarity and accuracy of system recommendations and tools. Conclusions Use of this iterative process led to development of a multifunctional DSS that met the approval of the clinical practice guideline authors, content experts, and clinicians involved in testing. The process and experiences described provide a model for development of other DSSs that translate written guidelines into actionable, real-time clinical recommendations.http://deepblue.lib.umich.edu/bitstream/2027.42/78267/1/1748-5908-5-26.xmlhttp://deepblue.lib.umich.edu/bitstream/2027.42/78267/2/1748-5908-5-26.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/78267/3/1748-5908-5-26-S3.TIFFhttp://deepblue.lib.umich.edu/bitstream/2027.42/78267/4/1748-5908-5-26-S2.TIFFhttp://deepblue.lib.umich.edu/bitstream/2027.42/78267/5/1748-5908-5-26-S1.TIFFPeer Reviewe
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