Comprehensive Cell Surface Antigen Analysis Identifies Transferrin Receptor Protein-1 (CD71) as a Negative Selection Marker for Human Neuronal Cells.

Cell state-, developmental stage-, and lineage-specific combinatorial expression of cluster of differentiation (CD) molecules enables the identification of cellular subsets via multicolor flow cytometry. We describe an exhaustive characterization of neural cell types by surface antigens, exploiting human pluripotent stem cell-derived neural cell systems. Using multiwell screening approaches followed by detailed validation of expression patterns and dynamics, we exemplify a strategy for resolving cellular heterogeneity in stem cell paradigms. In addition to providing a catalog of surface antigens expressed in the neural lineage, we identified the transferrin receptor-1 (CD71) to be differentially expressed in neural stem cells and differentiated neurons. In this context, we describe a role for N-Myc proto-oncogene (MYCN) in maintaining CD71 expression in proliferating neural cells. We report that in vitro human stem cell-derived neurons lack CD71 surface expression and that the observed differential expression can be used to identify and enrich CD71- neuronal derivatives from heterogeneous cultures. Stem Cells 2019;37:1293-1306

Reticulocyte hemoglobin equivalent (Ret He) and assessment of iron-deficient states

Direct measurement of the reticulocyte hemoglobin content provides useful information for the diagnosis and treatment of iron-deficient states. We have examined direct measurements of reticulocyte and red cell hemoglobin content on the Sysmex XE 2100 (Ret He and RBC He respectively) and the Bayer ADVIA 2120 (CHr and CH respectively) analyzers. Good agreement was found between Ret He and CHr (Y = 1.04X − 1.06; r(2) = 0.88) and between the RBC He and CH parameters (Y = 0.93X + 1; r(2) = 0.84 n = 200) in pediatric patients and in normal adults (Ret He and CHr; Y = 1.06X − 0.43; r(2) = 0.83; n = 126; RBC He and CH; Y = 0.94X + 1; r(2) = 0.87; n = 126). In 1500 blood samples from patients on chronic dialysis, Ret He was compared with traditional parameters for iron deficiency (serum iron <40 μg/dl, Tsat <20%, ferritin <100 ng/ml, hemoglobin <11 g/dl) for identifying iron-deficient states. Receiver operator characteristic (ROC) curve analysis revealed values of the area under the curve for Ret He of 0.913 (P < 0.0001). With a Ret He cutoff level of 27.2 pg, iron deficiency could be diagnosed with a sensitivity of 93.3%, and a specificity of 83.2%. Ret He is a reliable marker of cellular hemoglobin content and can be used to identify the presence of iron-deficient states

Formalizing (web) standards: an application of test and proof

Most popular technologies are based on informal or semiformal standards that lack a rigid formal semantics. Typical examples include web technologies such as the DOM or HTML, which are defined by the Web Hypertext Application Technology Working Group (WHATWG) and the World Wide Web Consortium (W3C). While there might be API specifications and test cases meant to assert the compliance of a certain implementation, the actual standard is rarely accompanied by a formal model that would lend itself for, e.g., verifying the security or safety properties of real systems. Even when such a formalization of a standard exists, two important questions arise: first, to what extend does the formal model comply to the standard and, second, to what extend does the implementation comply to the formal model and the assumptions made during the verification? In this paper, we present an approach that brings all three involved artifacts - the (semi-)formal standard, the formalization of the standard, and the implementations - closer together by combining verification, symbolic execution, and specification based testing

Effect of increased convective clearance by on-line hemodiafiltration on all cause and cardiovascular mortality in chronic hemodialysis patients – the Dutch CONvective TRAnsport STudy (CONTRAST): rationale and design of a randomised controlled trial [ISRCTN38365125]

BACKGROUND: The high incidence of cardiovascular disease in patients with end stage renal disease (ESRD) is related to the accumulation of uremic toxins in the middle and large-middle molecular weight range. As online hemodiafiltration (HDF) removes these molecules more effectively than standard hemodialysis (HD), it has been suggested that online HDF improves survival and cardiovascular outcome. Thus far, no conclusive data of HDF on target organ damage and cardiovascular morbidity and mortality are available. Therefore, the CONvective TRAnsport STudy (CONTRAST) has been initiated. METHODS: CONTRAST is a Dutch multi-center randomised controlled trial. In this trial, approximately 800 chronic hemodialysis patients will be randomised between online HDF and low-flux HD, and followed for three years. The primary endpoint is all cause mortality. The main secondary outcome variables are fatal and non-fatal cardiovascular events. CONCLUSION: The study is designed to provide conclusive evidence whether online HDF leads to a lower mortality and less cardiovascular events as compared to standard HD

Bismarck or Beveridge: a beauty contest between dinosaurs

<p>Abstract</p> <p>Background</p> <p>Health systems delivery systems can be divided into two broad categories: National Health Services (NHS) on the one hand and Social Security (based) Health care systems (SSH) on the other hand. Existing literature is inconclusive about which system performs best. In this paper we would like to improve the evidence-base for discussion about pros and cons of NHS-systems versus SSH-system for health outcomes, expenditure and population satisfaction.</p> <p>Methods</p> <p>In this study we used time series data for 17 European countries, that were characterized as either NHS or SSH country. We used the following performance indicators: For health outcome: overall mortality rate, infant mortality rate and life expectancy at birth. For health care costs: health care expenditure per capita in pppUS$ and health expenditure as percentage of GDP. Time series dated from 1970 until 2003 or 2004, depending on availability. Sources were OECD health data base 2006 and WHO health for all database 2006. For satisfaction we used the Eurobarometer studies from 1996, 1998 and 1999.</p> <p>Results</p> <p>SSH systems perform slightly better on overall mortality rates and life expectancy (after 1980). For infant mortality the rates converged between the two types of systems and since 1980 no differences ceased to exist.</p> <p>SSH systems are more expensive and NHS systems have a better cost containment. Inhabitants of countries with SSH-systems are on average substantially more satisfied than those in NHS countries.</p> <p>Conclusion</p> <p>We concluded that the question 'which type of system performs best' can be answered empirically as far as health outcomes, health care expenditures and patient satisfaction are concerned. Whether this selection of indicators covers all or even most relevant aspects of health system comparison remains to be seen. Perhaps further and more conclusive research into health system related differences in, for instance, equity should be completed before the leading question of this paper can be answered. We do think, however, that this study can form a base for a policy debate on the pros and cons of the existing health care systems in Europe.</p