1,446 research outputs found
Preclinical correction of human Fanconi anemia complementation group A bone marrow cells using a safety-modified lentiviral vector.
One of the major hurdles for the development of gene therapy for Fanconi anemia (FA) is the increased sensitivity of FA stem cells to free radical-induced DNA damage during ex vivo culture and manipulation. To minimize this damage, we have developed a brief transduction procedure for lentivirus vector-mediated transduction of hematopoietic progenitor cells from patients with Fanconi anemia complementation group A (FANCA). The lentiviral vector FancA-sW contains the phosphoglycerate kinase promoter, the FANCA cDNA, and a synthetic, safety-modified woodchuck post transcriptional regulatory element (sW). Bone marrow mononuclear cells or purified CD34(+) cells from patients with FANCA were transduced in an overnight culture on recombinant fibronectin peptide CH-296, in low (5%) oxygen, with the reducing agent, N-acetyl-L-cysteine (NAC), and a combination of growth factors, granulocyte colony-stimulating factor (G-CSF), Flt3 ligand, stem cell factor, and thrombopoietin. Transduced cells plated in methylcellulose in hypoxia with NAC showed increased colony formation compared with 21% oxygen without NAC (P<0.03), showed increased resistance to mitomycin C compared with green fluorescent protein (GFP) vector-transduced controls (P<0.007), and increased survival. Thus, combining short transduction and reducing oxidative stress may enhance the viability and engraftment of gene-corrected cells in patients with FANCA
Multiclass Semi-Supervised Learning on Graphs using Ginzburg-Landau Functional Minimization
We present a graph-based variational algorithm for classification of
high-dimensional data, generalizing the binary diffuse interface model to the
case of multiple classes. Motivated by total variation techniques, the method
involves minimizing an energy functional made up of three terms. The first two
terms promote a stepwise continuous classification function with sharp
transitions between classes, while preserving symmetry among the class labels.
The third term is a data fidelity term, allowing us to incorporate prior
information into the model in a semi-supervised framework. The performance of
the algorithm on synthetic data, as well as on the COIL and MNIST benchmark
datasets, is competitive with state-of-the-art graph-based multiclass
segmentation methods.Comment: 16 pages, to appear in Springer's Lecture Notes in Computer Science
volume "Pattern Recognition Applications and Methods 2013", part of series on
Advances in Intelligent and Soft Computin
Leukocyte adhesion deficiency-I: A comprehensive review of all published cases
Leukocyte adhesion deficiency-I (LAD-I) is a rare, serious disorder with severity determined by defective CD18 expression. LAD-I is characterized by umbilical complications, granulocytosis, and diverse infections. Severe LAD-I is frequently fatal before the age of 2 years without allogeneic transplant. We identified 323 cases published between 1975 and 2017
Korn's second inequality and geometric rigidity with mixed growth conditions
Geometric rigidity states that a gradient field which is -close to the
set of proper rotations is necessarily -close to a fixed rotation, and is
one key estimate in nonlinear elasticity. In several applications, as for
example in the theory of plasticity, energy densities with mixed growth appear.
We show here that geometric rigidity holds also in and in
interpolation spaces. As a first step we prove the corresponding linear
inequality, which generalizes Korn's inequality to these spaces
The WHO checklist: a global tool to prevent errors in surgery
In this article, we welcome the adoption of the WHO surgical checklist to prevent errors in surgical practice. We highlight the scale of the problem and discuss the adoption of this tool in the UK
Dynamic screening of a localized hole during photoemission from a metal cluster
Recent advances in attosecond spectroscopy techniques have fueled the
interest in the theoretical description of electronic processes taking place in
the subfemtosecond time scale. Here we study the coupled dynamic screening of a
localized hole and a photoelectron emitted from a metal cluster using a
semi-classical model. Electron density dynamics in the cluster is calculated
with Time-Dependent Density Functional Theory and the motion of the
photoemitted electron is described classically. We show that the dynamic
screening of the hole by the cluster electrons affects the motion of the
photoemitted electron. At the very beginning of its trajectory, the
photoemitted electron interacts with the cluster electrons that pile up to
screen the hole. Within our model, this gives rise to a significant reduction
of the energy lost by the photoelectron. Thus, this is a velocity dependent
effect that should be accounted for when calculating the average losses
suffered by photoemitted electrons in metals.Comment: 15 pages, 5 figure
The implausibility of ‘usual care’ in an open system: sedation and weaning practices in Paediatric Intensive Care Units (PICUs) in the United Kingdom (UK)
Background: The power of the randomised controlled trial depends upon its capacity to operate in a closed
system whereby the intervention is the only causal force acting upon the experimental group and absent in the
control group, permitting a valid assessment of intervention efficacy. Conversely, clinical arenas are open systems
where factors relating to context, resources, interpretation and actions of individuals will affect implementation and
effectiveness of interventions. Consequently, the comparator (usual care) can be difficult to define and variable in
multi-centre trials. Hence outcomes cannot be understood without considering usual care and factors that may
affect implementation and impact on the intervention.
Methods: Using a fieldwork approach, we describe PICU context, ‘usual’ practice in sedation and weaning from
mechanical ventilation, and factors affecting implementation prior to designing a trial involving a sedation and
ventilation weaning intervention. We collected data from 23 UK PICUs between June and November 2014 using
observation, individual and multi-disciplinary group interviews with staff.
Results: Pain and sedation practices were broadly similar in terms of drug usage and assessment tools. Sedation
protocols linking assessment to appropriate titration of sedatives and sedation holds were rarely used (9 % and 4 %
of PICUs respectively). Ventilator weaning was primarily a medical-led process with 39 % of PICUs engaging senior
nurses in the process: weaning protocols were rarely used (9 % of PICUs). Weaning methods were variably based
on clinician preference. No formal criteria or use of spontaneous breathing trials were used to test weaning
readiness. Seventeen PICUs (74 %) had prior engagement in multi-centre trials, but limited research nurse
availability. Barriers to previous trial implementation were intervention complexity, lack of belief in the evidence and
inadequate training. Facilitating factors were senior staff buy-in and dedicated research nurse provision.
Conclusions: We examined and identified contextual and organisational factors that may impact on the
implementation of our intervention. We found usual practice relating to sedation, analgesia and ventilator weaning
broadly similar, yet distinctively different from our proposed intervention, providing assurance in our ability to
evaluate intervention effects. The data will enable us to develop an implementation plan; considering these factors
we can more fully understand their impact on study outcomes
Assessing Adverse Events in Madeira Primary
In last three decades, several epidemiological studies have been developed in order to assess the magnitude, nature and type of adverse events (AEs). Most of these studies focus on hospital settings, where the activities are more standardised, but imultaneously more complex and involving higher risks. However, in the last years, there is a growing movement and strong evidence that point out the importance of studying other healthcare contexts, such as primary care and long-term care. In Portugal, studies on primary care setting are scarce and still in the early stages.
In this article, the authors describe the AEs assessment in Portuguese Primary
Health Care (PHC) units in Madeira Island/Portugal. This study was quantitative,
cross-sectional, observational and analytical, with probability sampling. We quantify and analyse the AEs registered by healthcare providers using the APEAS-PT formulary.
A link to the APEAS–PT form was sent to 520 healthcare professionals (111 specialist in Family Medicine, 27 medical students, 382 nurses) who worked in 32 PHC centres. These professionals identified and analysed 85 AEs and 42 incidents, which corresponds to a prevalence of 3.9 AEs per 10,000 visits,with a 95% confidence interval (CI) between 3.7 and 4 AE. Most of the AEs were preventable (96%). The most frequent causal factors of AEs were associated with medication (69%), health care provided to users (54%), communication (41%) and diagnosis (22%). This analysis of AEs in Madeira island PHC contributed to reinforce patient safety culture and to better understand quaternary prevention.info:eu-repo/semantics/publishedVersio
Selective scattering between Floquet-Bloch and Volkov states in a topological insulator
The coherent optical manipulation of solids is emerging as a promising way to
engineer novel quantum states of matter. The strong time periodic potential of
intense laser light can be used to generate hybrid photon-electron states.
Interaction of light with Bloch states leads to Floquet-Bloch states which are
essential in realizing new photo-induced quantum phases. Similarly, dressing of
free electron states near the surface of a solid generates Volkov states which
are used to study non-linear optics in atoms and semiconductors. The
interaction of these two dynamic states with each other remains an open
experimental problem. Here we use Time and Angle Resolved Photoemission
Spectroscopy (Tr-ARPES) to selectively study the transition between these two
states on the surface of the topological insulator Bi2Se3. We find that the
coupling between the two strongly depends on the electron momentum, providing a
route to enhance or inhibit it. Moreover, by controlling the light polarization
we can negate Volkov states in order to generate pure Floquet-Bloch states.
This work establishes a systematic path for the coherent manipulation of solids
via light-matter interaction.Comment: 21 pages, 6 figures, final version to appear in Nature Physic
- …