A strategy to ensure safety of stem cell-derived retinal pigment epithelium cells

Cell replacement and regenerative therapy using embryonic stem cell-derived material holds promise for the treatment of several pathologies. However, the safety of this approach is of prime importance given the teratogenic potential of residual stem cells, if present in the differentiated cell product. Using the example of embryonic stem cell-derived retinal pigment epithelium (RPE) for the treatment of age-related macular degeneration, we present a novel strategy for ensuring the absence of stem cells in the RPE population. Based on an unbiased screening approach, we identify and validate the expression of CD59, a cell surface marker expressed on RPE but absent on stem cells. We further demonstrate that flow sorting on the basis of CD59 expression can effectively purify RPE and deplete stem cells, resulting in a population free from stem cell impurity. This purification helps to ensure removal of stem cells and hence increases the safety of cells that may be used for clinical transplantation. This strategy can potentially be applied to other pluripotent stem cell-derived material and help mitigate concerns of using such cells for therapy

Theoretical Description of the Role of Halides, Silver, and Surfactants on the Structure of Gold Nanorods

Density functional theory simulations including dispersion provide an atomistic description of the role of different compounds in the synthesis of gold-nanorods. Anisotropy is caused by the formation of a complex between the surfactant, bromine, and silver that preferentially adsorbs on some facets of the seeds, blocking them from further growth. In turn, the nanorod structure is driven by the perferential adsorption of the surfactant, which induces the appearance of open {520} lateral facets

Universality of Load Balancing Schemes on Diffusion Scale

We consider a system of $N$ parallel queues with identical exponential service rates and a single dispatcher where tasks arrive as a Poisson process. When a task arrives, the dispatcher always assigns it to an idle server, if there is any, and to a server with the shortest queue among $d$ randomly selected servers otherwise $(1 \leq d \leq N)$. This load balancing scheme subsumes the so-called Join-the-Idle Queue (JIQ) policy $(d = 1)$ and the celebrated Join-the-Shortest Queue (JSQ) policy $(d = N)$ as two crucial special cases. We develop a stochastic coupling construction to obtain the diffusion limit of the queue process in the Halfin-Whitt heavy-traffic regime, and establish that it does not depend on the value of $d$, implying that assigning tasks to idle servers is sufficient for diffusion level optimality

Acceptance and commitment therapy delivered in a dyad after a severe traumatic brain injury: a feasibility study

Objective: There is a high prevalence of complex psychological distress after a traumatic brain injury but limited evidence of effective interventions. We examined the feasibility of Acceptance and Commitment Therapy after a severe traumatic brain injury using the criteria, investigating a therapeutic effect, and reviewing the acceptability of measures, treatment protocol, and delivery method (in a dyad of two clients and a therapist). Method: Two male outpatients with severe traumatic brain injury and associated psychological distress jointly engaged in a seven session treatment program based on Acceptance and Commitment Therapy principles. Pre- and post-treatment measures of mood, psychological flexibility, and participation were taken in addition to weekly measures. Results: The intervention showed a therapeutic effect with one participant, and appeared to be acceptable for both participants with regard to program content, measures, and delivery mode by in a dyad. One participant showed both significant clinical and reliable change across several outcome measures including measures of mood and psychological flexibility. The second participant did not show a reduction in psychological inflexibility, but did show a significant drop in negative affect. Significant changes pre- to post-treatment for measures of participation were not indicated. Qualitatively, both participants engaged in committed action set in accordance with their values. Conclusions: This study suggests that Acceptance and Commitment Therapy may be feasible to be delivered in a dyad with individuals who have a severe traumatic brain injury. A further test of its potential efficacy in a phase II clinical trial is recommended

The Optical Emission from Gamma-ray Quasars

We present photometric observations of six radio-loud quasars that were detected by the COMPTEL gamma-ray telescope. The data encompasses seven wavebands in the optical and near-infrared. After correction for Galactic extinction, we find a wide range in optical slopes. Two sources are as blue as optically-selected quasars, and are likely to be dominated by the accretion disc emission, while three others show colours consistent with a red synchrotron component. We discuss the properties of the COMPTEL sample of quasars, as well as the implications our observations have for multi-wavelength modelling of gamma-ray quasars.Comment: 12 pages, 3 figures, accepted for publication in P.A.S.A; minor typos correcte

The development of QUADAS : a tool for the quality assessment of studies of diagnostic accuracy included in systematic reviews

BACKGROUND: In the era of evidence based medicine, with systematic reviews as its cornerstone, adequate quality assessment tools should be available. There is currently a lack of a systematically developed and evaluated tool for the assessment of diagnostic accuracy studies. The aim of this project was to combine empirical evidence and expert opinion in a formal consensus method to develop a tool to be used in systematic reviews to assess the quality of primary studies of diagnostic accuracy. METHODS: We conducted a Delphi procedure to develop the quality assessment tool by refining an initial list of items. Members of the Delphi panel were experts in the area of diagnostic research. The results of three previously conducted reviews of the diagnostic literature were used to generate a list of potential items for inclusion in the tool and to provide an evidence base upon which to develop the tool. RESULTS: A total of nine experts in the field of diagnostics took part in the Delphi procedure. The Delphi procedure consisted of four rounds, after which agreement was reached on the items to be included in the tool which we have called QUADAS. The initial list of 28 items was reduced to fourteen items in the final tool. Items included covered patient spectrum, reference standard, disease progression bias, verification bias, review bias, clinical review bias, incorporation bias, test execution, study withdrawals, and indeterminate results. The QUADAS tool is presented together with guidelines for scoring each of the items included in the tool. CONCLUSIONS: This project has produced an evidence based quality assessment tool to be used in systematic reviews of diagnostic accuracy studies. Further work to determine the usability and validity of the tool continue

Unravelling Active Galactic Nuclei

A complete flat-spectrum radio-loud sample of AGN includes a significant fraction of Seyfert-like AGN including a NLS1. Analysis of their optical spectra suggests that the reddest continuum colours are either associated with AGN in nearby resolved galaxies, or distant quasars showing relatively narrow permitted emission lines.Comment: Poster contribution presented at the Joint MPE,AIP,ESO workshop on NLS1s, Bad Honnef, Dec. 1999, to appear in New Astronomy Reviews; also available at http://wave.xray.mpe.mpg.de/conferences/nls1-worksho

Greenhouse gas balance over thaw-freeze cycles in discontinuous zone permafrost

Peat in the discontinuous permafrost zone contains a globally significant reservoir of carbon that has undergone multiple permafrost-thaw cycles since the end of the mid-Holocene (~3700 years before present). Periods of thaw increase C decomposition rates which leads to the release of CO2 and CH4 to the atmosphere creating potential climate feedback. To determine the magnitude and direction of such feedback, we measured CO2 and CH4 emissions and modeled C accumulation rates and radiative fluxes from measurements of two radioactive tracers with differing lifetimes to describe the C balance of the peatland over multiple permafrost-thaw cycles since the initiation of permafrost at the site. At thaw features, the balance between increased primary production and higher CH4 emission stimulated by warmer temperatures and wetter conditions favors C sequestration and enhanced peat accumulation. Flux measurements suggest that frozen plateaus may intermittently (order of years to decades) act as CO2 sources depending on temperature and net ecosystem respiration rates, but modeling results suggest that—despite brief periods of net C loss to the atmosphere at the initiation of thaw—integrated over millennia, these sites have acted as net C sinks via peat accumulation. In greenhouse gas terms, the transition from frozen permafrost to thawed wetland is accompanied by increasing CO2 uptake that is partially offset by increasing CH4 emissions. In the short-term (decadal time scale) the net effect of this transition is likely enhanced warming via increased radiative C emissions, while in the long-term (centuries) net C deposition provides a negative feedback to climate warming