Closed-loop regulation of arterial pressure after acute brain death

The purpose of this concept study was to investigate the possibility of automatic mean arterial pressure (MAP) regulation in a porcine heart-beating brain death (BD) model. Hemodynamic stability of BD donors is necessary for maintaining acceptable quality of donated organs for transplantation. Manual stabilization is challenging, due to the lack of vasomotor function in BD donors. Closed-loop stabilization therefore has the potential of increasing availability of acceptable donor organs, and serves to indicate feasibility within less demanding patient groups. A dynamic model of nitroglycerine pharmacology, suitable for controller synthesis, was identified from an experiment involving an anesthetized pig, using a gradient-based output error method. The model was used to synthesize a robust PID controller for hypertension prevention, evaluated in a second experiment, on a second, brain dead, pig. Hypotension was simultaneously prevented using closed-loop controlled infusion of noradrenaline, by means of a previously published controller. A linear model of low order, with variable (uncertain) gain, was sufficient to describe the dynamics to be controlled. The robustly tuned PID controller utilized in the second experiment kept the MAP within a user-defined range. The system was able to prevent hypertension, exceeding a reference of 100 mmHg by more than 10%, during 98% of a 12 h experiment. This early work demonstrates feasibility of the investigated modelling and control synthesis approach, for the purpose of maintaining normotension in a porcine BD model. There remains a need to characterize individual variability, in order to ensure robust performance over the expected population.     

Surface‐expressed insulin receptors as well as IGF‐I receptors both contribute to the mitogenic effects of human insulin and its analogues

There is a medical need for new insulin analogues. Yet, molecular alterations to the insulin molecule can theoretically result in analogues with carcinogenic effects. Preclinical carcinogenicity risk assessment for insulin analogues rests to a large extent on mitogenicity assays in cell lines. We therefore optimized mitogenicity assay conditions for a panel of five cell lines. All cell lines expressed insulin receptors (IR), IGF‐I receptors (IGF‐IR) and hybrid receptors, and in all cell lines, insulin as well as the comparator compounds X10 and IGF‐I caused phosphorylation of the IR as well as IGF‐IR. Insulin exhibited mitogenicity EC₅₀ values in the single‐digit nanomolar to picomolar range. We observed correlations across cell types between (i) mitogenic potency of insulin and IGF‐IR/IR ratio, (ii) Akt phosphorylation and mitogenic potency and (iii) Akt phosphorylation and IR phosphorylation. Using siRNA‐mediated knockdown of IR and IGF‐IR, we observed that in HCT 116 cells the IR appeared dominant in driving the mitogenic response to insulin, whereas in MCF7 cells the IGF‐IR appeared dominant in driving the mitogenic response to insulin. Together, our results show that the IR as well as IGF‐IR may contribute to the mitogenic potency of insulin. While insulin was a more potent mitogen than IGF‐I in cells expressing more IR than IGF‐IR, the hyper‐mitogenic insulin analogue X10 was a more potent mitogen than insulin across all cell types, supporting that the hyper‐mitogenic effect of X10 involves the IR as well as the IGF‐IR. These results are relevant for preclinical safety assessment of developmental insulin analogues. Copyright © 2014 John Wiley & Sons, Ltd.     

Empowerment in healthcare policy making: three domains of substantive controversy

This paper distinguishes between the uses of empowerment across different contexts in healthcare policy and health promotion, providing a model for the ethical and political scrutiny of those uses. We argue that the controversies currently engendered by empowerment are better understood by means of a historical distinction between two concepts of empowerment, namely, what we call the radical empowerment approach and the new wave of empowerment. Building on this distinction, we present a research agenda for ethicists and policy makers, highlighting three domains of controversy raised by the new wave of empowerment, namely: (1) the relationship between empowerment and paternalistic interferences on the part of professionals; (2) the evaluative commitment of empowerment strategies to the achievement of health‐related goals; and (3) the problems arising from the emphasis on responsibility for health in recent uses of empowerment. Finally, we encourage the explicit theorisation of these moral controversies as a necessary step for the development and implementation of ethically legitimate empowerment processes.     

Teaching minority children hygiene: investigating hygiene education in kindergartens and homes of ethnic minority children in northern Vietnam

Objectives. Ethnic minority children in Vietnam experience high levels of hygiene- and sanitation-related diseases. Improving hygiene for minority children is therefore vital for improving child health. The study objective was to investigate how kindergarten and home environments influence the learning of hygiene of pre-school ethnic minority children in rural Vietnam.

Design. Eight months of ethnographic field studies were conducted among four ethnic minority groups living in highland and lowland communities in northern Vietnam. Data included participant observation in four kindergartens and 20 homes of pre-school children, together with 67 semi-structured interviews with caregivers and five kindergarten staff. Thematic analysis was applied and concepts of social learning provided inputs to the analysis.

Findings. This study showed that poor living conditions with lack of basic sanitation infrastructures were important barriers for the implementation of safe home child hygiene. Furthermore, the everyday life of highland villages, with parents working away from the households resulted in little daily adult supervision of safe child hygiene practices. While kindergartens were identified as potentially important institutions for improving child hygiene education, essential and well-functioning hygiene infrastructures were lacking. Also, hygiene teaching relied on theoretical and non-practice-based learning styles, which did not facilitate hygiene behaviour change in small children. Minority children were further disadvantaged as teaching was only provided in non-minority language.

Conclusions. Kindergartens can be important institutions for the promotion of safe hygiene practices among children, but they must invest in the maintenance of hygiene and sanitation infrastructures and adopt a strong practice-based teaching approach in daily work and in teacher's education. To support highland minority children in particular, teaching styles must take local living conditions and caregiver structures into account and teach in local languages. Creating stronger links between home and institutional learning environments can be vital to support disadvantaged highland families in improving child health.