‘We wrapped him in cotton wool’: a qualitative study examining the healthcare experience of parents following the burn or scald of their child; and the effect of the injury on the family.

Childhood injury affects many families in the United Kingdom. In particular, burn injury can have a devastating effect, and disproportionately affects preschool children. In 2005, 158 children under five in Scotland were burned or scalded severely enough to require treatment as inpatients (ISD Scotland 2006).The aim of this thesis is to examine the impact of childhood burn injury on the family, and the parents’ view of its effect on the long-term parent-child relationship, whilst gaining an understanding of the views, opinions and feelings about the healthcare experience of parents after serious burn injury to their child. From an area in the central belt of Scotland, a group of nine families of children who had been burn injured while less than five years of age were recruited. Thirteen parents were interviewed using a semi-structured interviewing technique. The study utilised a qualitative research method, interpretive description, to obtain and analyse rich descriptions of the reality of caring for a burn injured child. Parents’ feelings and opinions about the impact of the injury on long term family relationships were analysed to reveal that parents go through a process of adjustment and adaptation to parenting a burn injured child. This process has 3 stages, the first, ‘holding’ was recognised when parents described an overwhelming obligation to hold and be close to their child. The second, ‘guarding’ was identified as the parents’ imperative to keep their child away from further danger and to regain their feeling of competence lost when the child was injured. The third stage, ‘defending’ has two elements; parental efforts to defend the child and family from shame at the appearance of the burn injury, and defending the child from becoming a burn injury victim. This study contributes to the research on childhood burn injury by identifying a process for parental adaptation, especially in view of the long term physical and psychological effects of burn injury scarring. The implication of the parental adaptation process is that health professionals need to be able to support and facilitate parents at each stage of adaptation; helping parents to be close to their child in particular at the time of treatment, regain their feelings of lost competence by keeping the child safe, and come to terms with the reality of their child’s burn injury scarring and the effects of this on their future. As the treatment and outcomes for burn injury survivors continues to improve, understanding the needs of the family in adjusting to living with a burn injured child becomes ever more important in the development of effective professional practice

CD8+ T Cell Priming by Dendritic Cell Vaccines Requires Antigen Transfer to Endogenous Antigen Presenting Cells

Immunotherapeutic strategies to stimulate anti-tumor immunity are promising approaches for cancer treatment. A major barrier to their success is the immunosuppressive microenvironment of tumors, which inhibits the functions of endogenous dendritic cells (DCs) that are necessary for the generation of anti-tumor CD8+ T cells. To overcome this problem, autologous DCs are generated ex vivo, loaded with tumor antigens, and activated in this non-suppressive environment before administration to patients. However, DC-based vaccines rarely induce tumor regression.We examined the fate and function of these DCs following their injection using murine models, in order to better understand their interaction with the host immune system. Contrary to previous assumptions, we show that DC vaccines have an insignificant role in directly priming CD8+ T cells, but instead function primarily as vehicles for transferring antigens to endogenous antigen presenting cells, which are responsible for the subsequent activation of T cells.This reliance on endogenous immune cells may explain the limited success of current DC vaccines to treat cancer and offers new insight into how these therapies can be improved. Future approaches should focus on creating DC vaccines that are more effective at directly priming T cells, or abrogating the tumor induced suppression of endogenous DCs

Evidence that a salt bridge in the light chain contributes to the physical stability difference between heavy and light human ferritins.

Human ferritin, a multimeric iron storage protein, is composed by various proportions of two subunit types: the H- and L-chains. The biological functions of these two genic products have not been clarified, although differences in reactivity with iron have been shown. Starting from the hypothesis that the high stability typical of ferritin is an important property which may be relevant for its iron storage function, we studied ferritin homopolymers of H- and L-chains in different denaturing conditions. In addition we analyzed 13 H-chain variants with alterations in regions conserved within mammalian H-chains. In all the denaturation experiments H-chain ferritin showed lower stability than L-chain ferritin. The difference was greater in guanidine HCl denaturation experiments, where the end products are fully unfolded peptides, than in acidic denaturation experiments, where the end products are peptides with properties analogous to "molten globule." The study on H-chain variants showed: (i) ferritin stability was not affected by alterations of regions exposed to the inner or outer surface of the shell and not involved in intra- or inter-chain interactions; (ii) stability was reduced by alterations of sequences involved in inter-subunit interactions such as the deletion of the N-terminal extension or substitutions along the hydrophobic and hydrophilic channels; (iii) stability was increased by the substitution of 2 amino acids inside the four-helix bundle with those of the homologous L-chain. One of the residues is involved in a salt bridge in the L-chain, and we concluded that the stability difference between H- and L-ferritins is to a large extent due to the stabilizing effect of this salt bridge on the L-subunit fold

Economic Aspects of the Missing Data Problem - the Case of the Patient Registry

Registries are indispensable in medical studies and provide the basis for reliable study results for research questions. Depending on the purpose of use, a high quality of data is a prerequisite. However, with increasing registry quality, costs also increase accordingly. Considering these time and cost factors, this work is an attempt to estimate the cost advantages of applying statistical tools to existing registry data, including quality evaluation. Results for quality analysis showed that there are unquestionable savings of millions in study costs by reducing the time horizon and saving on average EUR 523,126 for every reduced year. Replacing additionally the over 25 % missing data in some variables, data quality was immensely improved. To conclude, our findings showed dearly the importance of data quality and statistical input in avoiding biased conclusions due to incomplete data.O

Engineering transient dynamics of artificial cells by stochastic distribution of enzymes

Here the authors develop a coacervate micromotor that can display autonomous motion as a result of stochastic distribution of propelling units. This stochastic-induced mobility is validated and explained through experiments and theory. Random fluctuations are inherent to all complex molecular systems. Although nature has evolved mechanisms to control stochastic events to achieve the desired biological output, reproducing this in synthetic systems represents a significant challenge. Here we present an artificial platform that enables us to exploit stochasticity to direct motile behavior. We found that enzymes, when confined to the fluidic polymer membrane of a core-shell coacervate, were distributed stochastically in time and space. This resulted in a transient, asymmetric configuration of propulsive units, which imparted motility to such coacervates in presence of substrate. This mechanism was confirmed by stochastic modelling and simulations in silico. Furthermore, we showed that a deeper understanding of the mechanism of stochasticity could be utilized to modulate the motion output. Conceptually, this work represents a leap in design philosophy in the construction of synthetic systems with life-like behaviors

A SynBio community comes of age: political, academical, industrial, and societal developments in the Netherlands

Synthetic biology (SynBio) is a rapidly growing scientific discipline. In the Netherlands, various universities and companies are tackling a variety of opportunities and challenges within this field. In this perspective article, we review the current synthetic biology landscape in the Netherlands across academia, industry, politics, and society. Especially within Dutch academia there is an active, though only partially connected, research community involved in various domains of SynBio. Mostly supported by governmental funding, academic research is focusing on top-down synthetic biology, involving the engineering of for example bacteria and yeast for bioproduction, as well as bottom-up and cell-free synthetic biology aiming to understand life and build synthetic cells. There is also a large number of talented and motivated students interested in the field, exemplified by the participation and success of Dutch teams in the international iGEM synthetic biology competition. Commercial synthetic biology activities are taking place in various large industrial companies, as well as in start-ups and spin-offs, mostly divided over several ‘SynBio hubs’ in the Netherlands. However, the investment, regulatory and public-perception landscape is not yet optimal to stimulate entrepreneurial activities in SynBio. The Dutch and global society can further benefit from the large promise of SynBio through better integration of people active in the Dutch SynBio field, frequent political and public dialogue, and more attention towards regulatory issues. The recently founded Dutch synthetic biology association SynBioNL aims to contribute to realizing a positive impact on society by stimulating advances of the field in the Netherlands and beyond.Microbial Biotechnolog

Mimicking Cellular Compartmentalization in a Hierarchical Protocell through Spontaneous Spatial Organization

A systemic feature of eukaryotic cells is the spatial organization of functional components through compartmentalization. Developing protocells with compartmentalized synthetic organelles is, therefore, a critical milestone toward emulating one of the core characteristics of cellular life. Here we demonstrate the bottom-up, multistep, noncovalent, assembly of rudimentary subcompartmentalized protocells through the spontaneous encapsulation of semipermeable, polymersome proto-organelles inside cell-sized coacervates. The coacervate microdroplets are membranized using tailor-made terpolymers, to complete the hierarchical self-assembly of protocells, a system that mimics both the condensed cytosol and the structure of a cell membrane. In this way, the spatial organization of enzymes can be finely tuned, leading to an enhancement of functionality. Moreover, incompatible components can be sequestered in the same microenvironments without detrimental effect. The robust stability of the subcompartmentalized coacervate protocells in biocompatible milieu, such as in PBS or cell culture media, makes it a versatile platform to be extended toward studies in vitro, and perhaps, in vivo