4,209 research outputs found
Effects of chelators (desferal, deferiprone & deferaairox) on the growth of klebsiella and aeromonas isolated from transfusion dependent thalassemia patients
Poster Presentation (Doctor’s Session)Infection is among the leading causes of death for
thalassemia major patients. The known predisposing factors
of infection include prior splenectomy, iron overload and
use of iron chelator such as desferal (desferrioxamine).
While encapsulated organisms frequently found in
splenectomized patients were readily controlled by
prophylactic vaccination and vigilant antibiotic treatment,
ferrophilic organisms such as Yersinia and Klebsiella
remains common among Thalassemic patients. The
inductive iron overloaded environment favours the growth
of these organisms but their growth is also affected by the
environment temperature. For example, Yersinia infection
is more prevalent in temperate regions and Klebsiella
infection is commonly found in subtropical areas.
Furthermore, the use of iron chelator in the form of desferal
further aggravates the risk of Yersinia infection. It is because
the iron membrane transport protein siderophore found in
desferal can be adopted by the bacteria for iron acquisition. However, oral chelators such as deferiprone do not enhance
growth of Yersinia in vitro or in vivo. In order to find out
whether such observation can be extended to Klebsiella and
Aeromona infection, in vitro culture assay using Klebsiella
pneumoniae and Aeromonas hydrophila obtained directly
from our transfusion dependent thalassaemic patients were
performed. The growth rates of the bacteria under iron rich,
iron poor with or without different chelators were assessed.
The growth rates were analyzed by both: (1) optic density
of bacterial broth; and (2) colony count by bacterial agar
plate. We found that the growth of Klebsiella was marginally
enhanced by desferal in vitro when compared to Yersinia.
Such unfavourable effect was not found in either deferiprone
or deferasirox in vitro. On the other hand, the growth of
Aeromonas was not affected by the presence of any of the 3
chelators. Therefore, we suggested that factors other than
desferal may account for the increase prevalence of
Klebsiella and Aeromonas infection among Asian
thalassemic patients. It also suggests that oral chelators are
safe for thalassemic patients during febrile illness. Unlike
desferal, withholding iron chelator during infectious period
may not be mandatory. But care has to be exercised
especially for patients on deferiprone, since neutropenia has
to be ruled out during febrile illness.
This project was supported by the Children's Thalassaemia
Foundationspublished_or_final_versio
Personalisation and recommender systems in digital libraries
Widespread use of the Internet has resulted in digital libraries that are increasingly used by diverse communities of users for diverse purposes and in which sharing and collaboration have become important social elements. As such libraries become commonplace, as their contents and services become more varied, and as their patrons become more experienced with computer technology, users will expect more sophisticated services from these libraries. A simple search function, normally an integral part of any digital library, increasingly leads to user frustration as user needs become more complex and as the volume of managed information increases. Proactive digital libraries, where the library evolves from being passive and untailored, are seen as offering great potential for addressing and overcoming these issues and include techniques such as personalisation and recommender systems. In this paper, following on from the DELOS/NSF Working Group on Personalisation and Recommender Systems for Digital Libraries, which met and reported during 2003, we present some background material on the scope of personalisation and recommender systems in digital libraries. We then outline the working group’s vision for the evolution of digital libraries and the role that personalisation and recommender systems will play, and we present a series of research challenges and specific recommendations and research priorities for the field
Extrapontine myelinolysis presenting as acute parkinsonism
BACKGROUND: Extrapontine myelinolysis presenting with extra pyramidal features suggestive of parkinsonism may be a challenging clinical syndrome. Clinicians should maintain their vigilance while correcting electrolyte imbalances, especially with associated co-morbidity. CASE PRESENTATION: A 41-year-old woman presented with acute parkinsonism like features while on a holiday. This followed slow correction of hyponatraemia after repeated vomiting. MRI changes were suggestive of Extrapontine myelinolysis(EPM). This case is at variance with four previous cases reported in the medical literature in that the patient made a full clinical recovery and the MR changes resolved with symptomatic support alone. CONCLUSION: Extrapontine myelinolysis could make a complete recovery with symptomatic support alone. During hyponatraemia correction, rapid osmotic shifts of fluid that cause hypernatremia, causes myelinolysis rather than absolute serum sodium level. Even gradual correction of hyponatraemia can produce myelinolysis, especially with pre-existing malnourishment, alcoholism, drug misuse, Addison's disease and immuno-suppression. Pallidial sparing is typical of EPM in MRI scans
A parabolic approach to the control of opinion spreading
We analyze the problem of controlling to consensus a nonlinear system
modeling opinion spreading. We derive explicit exponential estimates on the
cost of approximately controlling these systems to consensus, as a function of
the number of agents N and the control time-horizon T. Our strategy makes use
of known results on the controllability of spatially discretized semilinear
parabolic equations. Both systems can be linked through time-rescalin
Exosomes from Human Adipose Tissue-Derived Mesenchymal Stem Cells Promote Epidermal Barrier Repair by Inducing de Novo Synthesis of Ceramides in Atopic Dermatitis.
Atopic dermatitis (AD) is a multifactorial, heterogeneous disease associated with epidermal barrier disruption and intense systemic inflammation. Previously, we showed that exosomes derived from human adipose tissue-derived mesenchymal stem cells (ASC-exosomes) attenuate AD-like symptoms by reducing multiple inflammatory cytokine levels. Here, we investigated ASC-exosomes' effects on skin barrier restoration by analyzing protein and lipid contents. We found that subcutaneous injection of ASC-exosomes in an oxazolone-induced dermatitis model remarkably reduced trans-epidermal water loss, while enhancing stratum corneum (SC) hydration and markedly decreasing the levels of inflammatory cytokines such as IL-4, IL-5, IL-13, TNF-α, IFN-γ, IL-17, and TSLP, all in a dose-dependent manner. Interestingly, ASC-exosomes induced the production of ceramides and dihydroceramides. Electron microscopic analysis revealed enhanced epidermal lamellar bodies and formation of lamellar layer at the interface of the SC and stratum granulosum with ASC-exosomes treatment. Deep RNA sequencing analysis of skin lesions demonstrated that ASC-exosomes restores the expression of genes involved in skin barrier, lipid metabolism, cell cycle, and inflammatory response in the diseased area. Collectively, our results suggest that ASC-exosomes effectively restore epidermal barrier functions in AD by facilitating the de novo synthesis of ceramides, resulting in a promising cell-free therapeutic option for treating AD
Nonequilibrium Dynamics in Noncommutative Spacetime
We study the effects of spacetime noncommutativity on the nonequilibrium
dynamics of particles in a thermal bath. We show that the noncommutative
thermal bath does not suffer from any further IR/UV mixing problem in the sense
that all the finite-temperature non-planar quantities are free from infrared
singularities. We also point out that the combined effect of finite temperature
and noncommutative geometry has a distinct effect on the nonequilibrium
dynamics of particles propagating in a thermal bath: depending on the momentum
of the mode of concern, noncommutative geometry may switch on or switch off
their decay and thermalization. This momentum dependent alternation of the
decay and thermalization rates could have significant impacts on the
nonequilibrium phenomena in the early universe at which spacetime
noncommutativity may be present. Our results suggest a re-examination of some
of the important processes in the early universe such as reheating after
inflation, baryogenesis and the freeze-out of superheavy dark matter
candidates.Comment: 24 pages, 2 figure
Population Genetics of Franciscana Dolphins (Pontoporia blainvillei): Introducing a New Population from the Southern Edge of Their Distribution
Due to anthropogenic factors, the franciscana dolphin, Pontoporia blainvillei, is the most threatened small cetacean on the Atlantic coast of South America. Four Franciscana Management Areas have been proposed: Espiritu Santo to Rio de Janeiro (FMA I), São Paulo to Santa Catarina (FMA II), Rio Grande do Sul to Uruguay (FMA III), and Argentina (FMA IV). Further genetic studies distinguished additional populations within these FMAs. We analyzed the population structure, phylogeography, and demographic history in the southernmost portion of the species range. From the analysis of mitochondrial DNA control region sequences, 5 novel haplotypes were found, totalizing 60 haplotypes for the entire distribution range. The haplotype network did not show an apparent phylogeographical signal for the southern FMAs. Two populations were identified: Monte Hermoso (MH) and Necochea (NC)+Claromecó (CL)+Río Negro (RN). The low levels of genetic variability, the relative constant size over time, and the low levels of gene flow may indicate that MH has been colonized by a few maternal lineages and became isolated from geographically close populations. The apparent increase in NC+CL+RN size would be consistent with the higher genetic variability found, since genetic diversity is generally higher in older and expanding populations. Additionally, RN may have experienced a recent split from CL and NC; current high levels of gene flow may be occurring between the latter ones. FMA IV would comprise four franciscana dolphin populations: Samborombón West+Samborombón South, Cabo San Antonio+Buenos Aires East, NC+CL+Buenos Aires Southwest+RN and MH. Results achieved in this study need to be taken into account in order to ensure the long-term survival of the species.Fil: Gariboldi, María Constanza. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Maimónides. Área de Investigaciones Biomédicas y Biotecnológicas. Centro de Estudios Biomédicos, Biotecnológicos, Ambientales y de Diagnóstico; ArgentinaFil: Tunez, Juan Ignacio. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional de Luján; ArgentinaFil: Dejean, Cristina Beatriz. Universidad Maimónides. Área de Investigaciones Biomédicas y Biotecnológicas. Centro de Estudios Biomédicos, Biotecnológicos, Ambientales y de Diagnóstico; Argentina. Universidad de Buenos Aires. Facultad de Filosofía y Letras. Instituto de Ciencias Antropológicas. Sección Antropología Biológica; ArgentinaFil: Failla, Mauricio. Fundación Cethus; ArgentinaFil: Vitullo, Alfredo Daniel. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Maimónides. Área de Investigaciones Biomédicas y Biotecnológicas. Centro de Estudios Biomédicos, Biotecnológicos, Ambientales y de Diagnóstico; ArgentinaFil: Negri, Maria Fernanda. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Museo Argentino de Ciencias Naturales ; ArgentinaFil: Cappozzo, Humberto Luis. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Maimónides. Área de Investigaciones Biomédicas y Biotecnológicas. Centro de Estudios Biomédicos, Biotecnológicos, Ambientales y de Diagnóstico; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Museo Argentino de Ciencias Naturales ; Argentin
Bistability in Apoptosis by Receptor Clustering
Apoptosis is a highly regulated cell death mechanism involved in many
physiological processes. A key component of extrinsically activated apoptosis
is the death receptor Fas, which, on binding to its cognate ligand FasL,
oligomerize to form the death-inducing signaling complex. Motivated by recent
experimental data, we propose a mathematical model of death ligand-receptor
dynamics where FasL acts as a clustering agent for Fas, which form locally
stable signaling platforms through proximity-induced receptor interactions.
Significantly, the model exhibits hysteresis, providing an upstream mechanism
for bistability and robustness. At low receptor concentrations, the bistability
is contingent on the trimerism of FasL. Moreover, irreversible bistability,
representing a committed cell death decision, emerges at high concentrations,
which may be achieved through receptor pre-association or localization onto
membrane lipid rafts. Thus, our model provides a novel theory for these
observed biological phenomena within the unified context of bistability.
Importantly, as Fas interactions initiate the extrinsic apoptotic pathway, our
model also suggests a mechanism by which cells may function as bistable
life/death switches independently of any such dynamics in their downstream
components. Our results highlight the role of death receptors in deciding cell
fate and add to the signal processing capabilities attributed to receptor
clustering.Comment: Accepted by PLoS Comput Bio
Cost effectiveness of stapled haemorrhoidopexy and traditional excisional surgery for the treatment of haemorrhoidal disease
Objective
Our objective was to compare the cost effectiveness of stapled haemorrhoidopexy (SH) and traditional haemorrhoidectomy (TH) in the treatment of grade II–IV haemorrhoidal disease from the perspective of the UK national health service.
Methods
An economic evaluation was conducted alongside an open, two-arm, parallel-group, pragmatic, multicentre, randomised controlled trial conducted in several hospitals in the UK. Patients were randomised into either SH or TH surgery between January 2011 and August 2014 and were followed up for 24 months. Intervention and subsequent resource use data were collected using case review forms and questionnaires. Benefits were collected using the EQ-5D-3L (EuroQoL—five dimensions—three levels) instrument. The primary economic outcome was incremental cost measured in pounds (£), year 2016 values, relative to the incremental benefit, which was estimated using quality-adjusted life-years (QALYs). Cost and benefits accrued in the second year were discounted at 3.5%. The base-case analysis was based on imputed data. Uncertainty was explored using univariate sensitivity analyses.
Results
Participants (n = 777) were randomised to SH (n = 389) or TH (n = 388). The mean cost of SH was £337 (95% confidence interval [CI] 251–423) higher than that of TH and the mean QALYs were −0.070 (95% CI −0.127 to −0.011) lower than for TH. The base-case cost-utility analysis indicated that SH has zero probability of being cost effective at both the £20,000 and the £30,000 threshold. Results from the sensitivity analyses were similar to those from the base-case analysis.
Conclusions
The evidence suggests that, on average, the total mean costs over the 24-month follow-up period were significantly higher for the SH arm than for the TH arm. The QALYs were also, on average, significantly lower for the SH arm. These results were supported by the sensitivity analyses. Therefore, in terms of cost effectiveness, TH is a superior surgical treatment for the management of grade II–IV haemorrhoids when compared with SH
Probing scrambling using statistical correlations between randomized measurements
We propose and analyze a protocol to study quantum information scrambling
using statistical correlations between measurements, which are performed after
evolving a quantum system from randomized initial states. We prove that the
resulting correlations precisely capture the so-called out-of-time-ordered
correlators and can be used to probe chaos in strongly-interacting, many-body
systems. Our protocol requires neither reversing time evolution nor auxiliary
degrees of freedom, and can be realized in state-of-the-art quantum simulation
experiments.Comment: This version v2 (8 pages, 7 figures) includes important new results
compared to our original submission. (1) We present a protocol and
corresponding mathematical proof to access OTOCs with local operations, and
which can be realized in quantum simulation experiments with available
technology. (2) We illustrate the realization of the protocols with different
examples for Hubbard and spin model
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