In vitro frequency analysis of spleen colony-forming and marrow-repopulating hemopoietic stem cells in the mouse

An assay is described for Day-12 spleen colony-forming cells (CFU-S-12) and hemopoietic stem cells with marrow-repopulating ability (MRA) in the mouse using a miniaturized stroma-dependent bone marrow culture assay in vitro. Bone marrow cells are grown in liquid culture in microtiter wells, and the resulting adherent stromal layers are depleted of all hemopoietic activity by 20 Gy gamma irradiation. Subsequently, single cell suspensions containing stem cells are overlaid in a range of concentrations, and the presence of one or more emerging phase nonrefractive cell clones (cobblestone areas) in a single well scored as positive. The frequencies of cobblestone area-forming cells (CAFC) are then calculated by employing Poisson statistics. It is shown that the CAFC Day-10 and CAFC Day-28 frequencies closely correlate with those of CFU-S-12 and MRA cells, respectively

Key findings from the 2006 Scottish Health Behaviour in School-aged Children study

The HBSC study in Scotland is funded by NHS Health Scotland.Publisher PD

Tool catalogue frame-based information tools

In the perception, knowledge production and policymaking on complex issues (‘wicked problems’), such as climate change, frames and framing play an important but often hidden role. Frames relate to one’s ‘schemas of interpretation’; the conceptual images, values, starting points, and mental models that one may have of an issue. This can include, for instance, one’s problem definition, perceptions of the cause-effect relationships in an issue, one’s primary goals, perception of one’s and others’ roles and responsibilities relating to the issue, and views on suitable strategies and interaction with (other) stakeholders (cf. Dewulf et al., 2005)

A dynamical system approach to higher order gravity

The dynamical system approach has recently acquired great importance in the investigation on higher order theories of gravity. In this talk I review the main results and I give brief comments on the perspectives for further developments.Comment: 6 pages, 1 figure, 2 tables, talk given at IRGAC 2006, July 200

Investigation of amphibian mortality events in wildlife reveals an on-going ranavirus epidemic in the North of the Netherlands

In the four years following the first detection of ranavirus (genus Ranavirus, family Iridoviridae) infection in Dutch wildlife in 2010, amphibian mortality events were investigated nationwide to detect, characterize and map ranaviruses in amphibians over time, and to establish the affected host species and the clinico-pathological presentation of the disease in these hosts. The ultimate goal was to obtain more insight into ranavirus disease emergence and ecological risk. In total 155 dead amphibians from 52 sites were submitted between 2011 and 2014, and examined using histopathology, immunohistochemistry, virus isolation and molecular genetic characterization. Ranavirus-associated amphibian mortality events occurred at 18 sites (35%), initially only in proximity of the 2010 index site. Specimens belonging to approximately half of the native amphibian species were infected, including the threatened Pelobates fuscus (spadefoot toad). Clustered massive outbreaks involving dead adult specimens and ranavirus genomic identity indicated that one common midwife toad virus (CMTV)-like ranavirus strain is emerging in provinces in the north of the Netherlands. Modelling based on the spatiotemporal pattern of spread showed a high probability that this emerging virus will continue to be detected at new sites (the discrete reproductive power of this outbreak is 0.35). Phylogenetically distinct CMTV-like ranaviruses were found in the south of the Netherlands more recently. In addition to showing that CMTV-like ranaviruses threaten wild amphibian populations not only in Spain but also in the Netherlands, the current spread and risk of establishment reiterate that understanding the underlying causes of CMTV-like ranavirus emergence requires international attention

Mental health care use in medically unexplained and explained physical symptoms: findings from a general population study

Objective: The aim of this study was to explore mental health care utilization patterns in primary and specialized mental health care of people with unexplained or explained physicalnsymptoms. Methods: Data were derived from the first wave of the Netherlands Mental Health Surveyband Incidence Study-2, a nationally representative face-to-face cohort study among the general population aged 18–64 years. We selected subjects with medically unexplained symptoms (MUS) only (MUSonly; n=177), explained physical symptoms only (PHYonly, n=1,952), combined MUS and explained physical symptoms (MUS + PHY, n=209), and controls without physical symptoms (NONE, n=4,168). We studied entry into mental health care and the number of treatment contacts for mental problems, in both primary care and specialized mental health care. Analyses were adjusted for sociodemographic characteristics and presence of any 12-month mental disorder assessed with the Composite International Diagnostic Interview 3.0. Results: At the primary care level, all three groups of subjects with physical symptoms showed entry into care for mental health problems significantly more often than controls. The adjusted odds ratios were 2.29 (1.33, 3.95) for MUSonly, 1.55 (1.13, 2.12) for PHYonly, and 2.25 (1.41, 3.57) for MUS + PHY. At the specialized mental health care level, this was the case only for MUSonly subjects (adjusted odds ratio 1.65 [1.04, 2.61]). In both the primary and specialized mental health care, there were no significant differences between the four groups in the number of treatment contacts once they entered into treatment. Conclusion: All sorts of physical symptoms, unexplained as well as explained, were associated with significant higher entry into primary care for mental problems. In specialized mental health care, this was true only for MUSonly. No differences were found in the number of treatment contacts. This warrants further research aimed at the content of the treatment contacts

Significant Digits: Responsible use of quantitative information

We live in an age when good policies are assumed to be evidence-based. And that evidential base is assumed to be at its best when expressed in numbers. The digital information may be derived from quantitative data organised in statistics, or from qualitative data organised in indicators. Either way, evidence in digital form provides the accepted foundation of policy arguments over a very broad range of issues. In the policy realm there are frequent debates over particular policy issues and their associated evidence. But only rarely is the nature of the evidence called into question. Such a faith in numbers can be dangerous. Policies in economic and financial policy, based on numbers whose significance was less than assumed, recently turned out to be quite disastrously wrong. Other examples can easily be cited. The decades-long period of blaming dietary fats for heart disease, rather than sugar, is a notable recent case. We are concerned here with the systemic problem: whether we are regularly placing too much of an evidentiary burden on quantitative sciences whose strength and maturity are inherently inadequate. The harm that has been done to those sciences, as well as to the policy process, should be recognised. Only in that way can future errors be avoided.JRC.DDG.01-Econometrics and applied statistic

Vps3 and Vps8 control integrin trafficking from early to recycling endosomes and regulate integrin-dependent functions

Recycling endosomes maintain plasma membrane homeostasis and are important for cell polarity, migration, and cytokinesis. Yet, the molecular machineries that drive endocytic recycling remain largely unclear. The CORVET complex is a multi-subunit tether required for fusion between early endosomes. Here we show that the CORVET-specific subunits Vps3 and Vps8 also regulate vesicular transport from early to recycling endosomes. Vps3 and Vps8 localise to Rab4-positive recycling vesicles and co-localise with the CHEVI complex on Rab11-positive recycling endosomes. Depletion of Vps3 or Vps8 does not affect transferrin recycling, but delays the delivery of internalised integrins to recycling endosomes and their subsequent return to the plasma membrane. Consequently, Vps3/8 depletion results in defects in integrin-dependent cell adhesion and spreading, focal adhesion formation, and cell migration. These data reveal a role for Vps3 and Vps8 in a specialised recycling pathway important for integrin trafficking

Nebulized heparin in burn patients with inhalation trauma : safety and feasibility

Background: Pulmonary hypercoagulopathy is intrinsic to inhalation trauma. Nebulized heparin could theoretically be beneficial in patients with inhalation injury, but current data are conflicting. We aimed to investigate the safety, feasibility, and effectiveness of nebulized heparin. Methods: International multicenter, double-blind, placebo-controlled randomized clinical trial in specialized burn care centers. Adult patients with inhalation trauma received nebulizations of unfractionated heparin (25,000 international unit (IU), 5 mL) or placebo (0.9% NaCl, 5 mL) every four hours for 14 days or until extubation. The primary outcome was the number of ventilator-free days at day 28 post-admission. Here, we report on the secondary outcomes related to safety and feasibility. Results: The study was prematurely stopped after inclusion of 13 patients (heparin N = 7, placebo N = 6) due to low recruitment and high costs associated with the trial medication. Therefore, no analyses on effectiveness were performed. In the heparin group, serious respiratory problems occurred due to saturation of the expiratory filter following nebulizations. In total, 129 out of 427 scheduled nebulizations were withheld in the heparin group (in 3 patients) and 45 out of 299 scheduled nebulizations were withheld in the placebo group (in 2 patients). Blood-stained sputum or expected increased bleeding risks were the most frequent reasons to withhold nebulizations. Conclusion: In this prematurely stopped trial, we encountered important safety and feasibility issues related to frequent heparin nebulizations in burn patients with inhalation trauma. This should be taken into account when heparin nebulizations are considered in these patients