Two-finger selection theory in the Saffman-Taylor problem

We find that solvability theory selects a set of stationary solutions of the Saffman-Taylor problem with coexistence of two \it unequal \rm fingers advancing with the same velocity but with different relative widths $\lambda_1$ and $\lambda_2$ and different tip positions. For vanishingly small dimensionless surface tension $d_0$, an infinite discrete set of values of the total filling fraction $\lambda = \lambda_1 + \lambda_2$ and of the relative individual finger width $p=\lambda_1/\lambda_2$ are selected out of a two-parameter continuous degeneracy. They scale as $\lambda-1/2 \sim d_0^{2/3}$ and $|p-1/2| \sim d_0^{1/3}$. The selected values of $\lambda$ differ from those of the single finger case. Explicit approximate expressions for both spectra are given.Comment: 4 pages, 3 figure

Parent-worker relationships in child & family social work: a Belgian case study

The involvement of parents within child and family social work has become an important research topic during the past few decades. Within this research, a lot of attention is paid to partnership, which is recognised as a dominant concept in current thinking about the parent-worker relationship in present-day practice. The debate on parent-worker relationships, however, seems to be mainly focussed on the individual relationship between the parent and the social worker. Based on a historical analysis of policy documents on a Belgian child and family welfare service, this article offers a historical and sociopolitical contextualisation of the current debate on the parent-worker relationship. The analysis reveals that sociopolitical ideas about the responsibilities of the state, the community and the private family have induced a continuous reflection on which children and parents should be seen as the most appropriate clients for a particular service, as well as an ongoing development of diagnostic instruments to legitimise inclusion and exclusion of families within child and family social work. Consequences for parent-worker relationships in child and family social work are discussed, as well as some implications for future research on child and family social work practices

Democratic experimentation in early childhood education

Qualifications of the early years workforce are a salient predictors of quality and therefore of children’s outcomes. International reports advise that a majority of staff is trained at Bachelor’s levels and rank countries according to this criterion. There is fewer consensus on what this professionalism should be. In a majority of countries, large numbers of professionals are untrained, unqualified and sometimes invisible in the official reports. Many of these unqualified “assistants” take up crucial “care” tasks, while the teacher’s tasks are defined as “education”. The separation between care and education occurs in split systems as well as in systems where education and care are supposed to be integrated. In addition, the growing diversity of families challenges our preconceived ideas about “the good life” for children. These observations urge us to rethink professionalism in terms of reflexivity and the capacity of co-constructing pedagogy with parents and children. A case study in Ghent shows how low qualified professionals develop research capacities. The analysis of their experience suggests that “learning” may be less a quality of the individual than a quality of the systemic relationships that are build in the teams as well as in the interaction between teams and their social contexts

Framework, principles and recommendations for utilising participatory methodologies in the co-creation and evaluation of public health interventions

Background: Due to the chronic disease burden on society, there is a need for preventive public health interventions to stimulate society towards a healthier lifestyle. To deal with the complex variability between individual lifestyles and settings, collaborating with end-users to develop interventions tailored to their unique circumstances has been suggested as a potential way to improve effectiveness and adherence. Co-creation of public health interventions using participatory methodologies has shown promise but lacks a framework to make this process systematic. The aim of this paper was to identify and set key principles and recommendations for systematically applying participatory methodologies to co-create and evaluate public health interventions. Methods: These principles and recommendations were derived using an iterative reflection process, combining key learning from published literature in addition to critical reflection on three case studies conducted by research groups in three European institutions, all of whom have expertise in co-creating public health interventions using different participatory methodologies. Results: Key principles and recommendations for using participatory methodologies in public health intervention co-creation are presented for the stages of: Planning (framing the aim of the study and identifying the appropriate sampling strategy); Conducting (defining the procedure, in addition to manifesting ownership); Evaluating (the process and the effectiveness) and Reporting (providing guidelines to report the findings). Three scaling models are proposed to demonstrate how to scale locally developed interventions to a population level. Conclusions: These recommendations aim to facilitate public health intervention co-creation and evaluation utilising participatory methodologies by ensuring the process is systematic and reproducible

Rivaroxaban:Xarelto® - Recommendations for pharmacists

Rivaroxaban is one of the new oral anticoagulants (NOACs) (recommended as reference treatments when a long-term anticoagulation is needed). It has many potential advantages in comparison with Vitamin K Antagonists (VKA). It has a predictable anticoagulant effect and does not theoretically require biological monitoring. It is also characterized by less food and drug interactions. However, due to major risks associated with over- and under-dosage, its optimal use in patients should be carefully followed by health care professionals. The aim of this article is to provide recommendations for pharmacists on the practical use of Xarelto® in its different approved indications. This document is adapted from the practical user guide of rivaroxaban which was developed by an independent group of Belgian experts in the field of thrombosis and haemostasis

Gene-modified T cells for adoptive immunotherapy of renal cell cancer maintain transgene-specific immune functions in vivo

Abstract BACKGROUND: We have treated three patients with carboxy-anhydrase-IX (CAIX) positive metastatic renal cell cancer (RCC) by adoptive transfer of autologous T-cells that had been gene-transduced to express a single-chain antibody-G250 chimeric receptor [scFv(G250)], and encountered liver toxicity necessitating adaptation of the treatment protocol. Here, we investigate whether or not the in vivo activity of the infused scFv(G250)(+) T cells is reflected by changes of selected immune parameters measured in peripheral blood. METHODS: ScFv(G250)-chimeric receptor-mediated functions of peripheral blood mononuclear cells (PBMC) obtained from three patients during and after treatment were compared to the same functions of scFv(G250)(+) T lymphocytes prior to infusion, and were correlated with plasma cytokine levels. RESULTS: Prior to infusion, scFv(G250)(+) T lymphocytes showed in vitro high levels of scFv(G250)-chimeric receptor-mediated functions such as killing of CAIX(+) RCC cell lines and cytokine production upon exposure to these cells. High levels of IFN-gamma were produced, whilst production of TNF-alpha, interleukin-4 (IL-4), IL-5 and IL-10 was variable and to lower levels, and that of IL-2 virtually absent. PBMC taken from patients during therapy showed lower levels of in vitro scFv(G250)-receptor-mediated functions as compared to pre-infusion, whilst IFN-gamma was the only detectable cytokine upon in vitro PBMC exposure to CAIX. During treatment, plasma levels of IFN-gamma increased only in the patient with the most prominent liver toxicity. IL-5 plasma levels increased transiently during treatment in all patients, which may have been triggered by the co-administration of IL-2. CONCLUSION: ScFv(G250)-receptor-mediated functions of the scFv(G250)(+) T lymphocytes are, by and large, preserved in vivo upon administration, and may be reflected by fluctuations in plasma IFN-gamma levels

Oxidative stress and proinflammatory cytokines contribute to demyelination and axonal damage in a cerebellar culture model of neuroinflammation

Background: Demyelination and axonal damage are critical processes in the pathogenesis of multiple sclerosis (MS). Oxidative stress and pro-inflammatory cytokines elicited by inflammation mediates tissue damage. Methods/Principal Findings: To monitor the demyelination and axonal injury associated with microglia activation we employed a model using cerebellar organotypic cultures stimulated with lipopolysaccharide (LPS). Microglia activated by LPS released pro-inflammatory cytokines (IL-1β, IL-6 and TNFα), and increased the expression of inducible nitric oxide synthase (iNOS) and production of reactive oxygen species (ROS). This activation was associated with demyelination and axonal damage in cerebellar cultures. Axonal damage, as revealed by the presence of non-phosphorylated neurofilaments, mitochondrial accumulation in axonal spheroids, and axonal transection, was associated with stronger iNOS expression and concomitant increases in ROS. Moreover, we analyzed the contribution of pro-inflammatory cytokines and oxidative stress in demyelination and axonal degeneration using the iNOS inhibitor ethyl pyruvate, a free-scavenger and xanthine oxidase inhibitor allopurinol, as well as via blockage of pro-inflammatory cytokines using a Fc-TNFR1 construct. We found that blocking microglia activation with ethyl pyruvate or allopurinol significantly decreased axonal damage, and to a lesser extent, demyelination. Blocking TNFα significantly decreased demyelination but did not prevented axonal damage. Moreover, the most common therapy for MS, interferon-beta, was used as an example of an immunomodulator compound that can be tested in this model. In vitro, interferon-beta treatment decreased oxidative stress (iNOS and ROS levels) and the release of pro-inflammatory cytokines after LPS stimulation, reducing axonal damage. Conclusion: The model of neuroinflammation using cerebellar culture stimulated with endotoxin mimicked myelin and axonal damage mediated by the combination of oxidative stress and pro-inflammatory cytokines. This model may both facilitate understanding of the events involved in neuroinflammation and aid in the development of neuroprotective therapies for the treatment of MS and other neurodegenerative diseases