Low gravity rotational culture and the integration of immunomodulatory stem cells reduce human islet allo-reactivity

Modification of human islets prior to transplantation may improve long-term clinical outcome in terms of diabetes management, by supporting graft function and reducing the potential for allo-rejection. Intragraft incorporation of stem cells secreting beta (β)-cell trophic and immunomodulatory factors represents a credible approach, but requires suitable culture methods to facilitate islet alteration without compromising integrity. This study employed a three-dimensional rotational cell culture system (RCCS) to achieve modification, preserve function, and ultimately influence immune cell responsiveness to human islets. Islets underwent intentional dispersal and rotational culture-assisted aggregation with amniotic epithelial cells (AEC) exhibiting intrinsic immunomodulatory potential. Reassembled islet constructs were assessed for functional integrity, and their ability to induce an allo-response in discrete T-cell subsets determined using mixed islet:lymphocyte reaction assays. RCCS supported the formation of islet:AEC aggregates with improved insulin secretory capacity compared to unmodified islets. Further, the allo-response of peripheral blood mononuclear cell (PBMC) and purified CD4+ and CD8+ T-cell subsets to AEC-bearing grafts was significantly (p < 0.05) attenuated. Rotational culture enables pre-transplant islet modification involving their integration with immunomodulatory stem cells capable of subduing the allo-reactivity of T cells relevant to islet rejection. The approach may play a role in achieving acute and long-term graft survival in islet transplantation.

Linking design and manufacturing domains via web-based and enterprise integration technologies

The manufacturing industry faces many challenges such as reducing time-to-market and cutting costs. In order to meet these increasing demands, effective methods are need to support the early product development stages by bridging the gap of communicating early design ideas and the evaluation of manufacturing performance. This paper introduces methods of linking design and manufacturing domains using disparate technologies. The combined technologies include knowledge management supporting for product lifecycle management systems, Enterprise Resource Planning (ERP) systems, aggregate process planning systems, workflow management and data exchange formats. A case study has been used to demonstrate the use of these technologies, illustrated by adding manufacturing knowledge to generate alternative early process plan which are in turn used by an ERP system to obtain and optimise a rough-cut capacity plan. Copyright © 2010 Inderscience Enterprises Ltd.

Leader-member exchange and attitudes:a theoretical and empirical integration

The central proposition of this thesis is that there are key benefits to examining leadership perceptions as an attitude towards the leader. In particular, it is argued that doing so can provide an enhanced understanding of leadership perceptions and therefore advance theory in this area. To provide empirical support for this theoretcial integration, the current research focused on one of the most popular leadership theories, leader-member exchange (LMX), and demonstrated how the concept of attitude strength could advance understanding of how and when LMX influenced employee job performance. Although the measurement of LMX requires employees to provide a cognitive evaluation of their relationship with their leader, previous research has, to date, not considered this evaluation to be an attitude. This thesis provides a justification for doing so and develops two novel constructs: LMX importance and LMX ambivalence. Both of these variables are argued to represent previously unconsidered facets of the LMX relationship, which, according to attitude theory, provide a more multifaceted understanding of leadership perceptions than previously envisaged. Such an understanding can provide a more detailed understanding of how such perceptions influence outcomes. Two studies provided an empirical test of the above reasoning. Study 1, a longitudinal field study, demonstrated initial support for many of the hypotheses. LMX amivalence was shown to lead to poorer task performance and organisational citizenship behaviour, mediated by the experience of negative affect. Evidence was also found for the moderating effect of LMX importance, although felt obligations was not found to mediate this moderated effect. While Study 1 used project groups as its participants, Study 2 provided a first test of the construct in an organisational setting; with three companies proving data. Again, strong support was found for the negative effects of LMX ambivalence on employee outcomes, with evidence also found for the role of perceived organisational support in mitigating these negative effects. Support was also found for the moderated mediation hypothesis related to LMX importance, although this was only found in the largest organisation sample. Some of the main theoretical and methodological implications of viewing leadership perceptions as attitudes to the wider leadership area were discussed. The cross-fertilisation of research from the attitudes literature to understanding leadership perceptions provides new insights into leadership processes and potential avenues for further research.

Editorial : which weight loss diet?

Full editorial: A recent study evaluating the long-term (2 yr) weight reducing efficacy of different types of diets – high or low in carbohydrates (CHOs), protein or fat - confirmed that it is calorie deficit not dietary composition that determines the loss and maintenance of body weight.1 Is there any advantage in following a specific weight loss diet? Short-term use of nutritionally complete commercially available (very) low calorie diets has benefited people with diabetes when  supported by education programmes.2 Initial weight loss has been encouraging with some fad diets eg the Atkins and the South Beach diets, but these diets are difficult to maintain and there are safety issues regarding their short- and long-term use – especially in people with diabetes.3 The types of macronutrients consumed can have a considerable impact on glycaemic control and energy metabolism. Although a low CHO diet additionally enhances initial weight loss by reducing cellular water content, if fat is not proportionally reduced the diet may not benefit the lipid profile for vascular disease risk. High fat and high protein diets – which are simultaneously low in CHOs – increase vulnerability to hypoglycaemia in people taking insulin secretagogues or on insulin therapy, and may promote excess fat metabolism and ketogenesis, particularly in people vulnerable to lack of insulin. Very low protein diets are not recommended as lean body mass tends to be reduced in diabetes. Altering the macronutrient balance has implications for the micronutrient mix: deficiencies are higher if more foods are excluded and conversely specific micronutrient excess can occur with some fad diets. The altered nutrient mix affects intestinal fauna and flora, and gut motility and glycaemic control are influenced by the quantity and type of fibre consumed. Support programmes help individuals achieve long term weight loss and there is mounting evidence that community schemes which educate and promote lifestyle changes may stem the rising tide of obesity and consequent type 2 diabetes.4 Consuming smaller portions of a balanced diet (and adjusting antidiabetic medications accordingly) will create an energy deficit to promote healthy weight loss. Increased movement/exercise will enhance this energy deficit. Knowledge (eg 1g fat has 2.25 times more energy than 1g CHO) allows sensible food choices and compensation for inclusion of small volumes of  ‘naughty but nice’ foods. Ultimately weight control requires self control. References 1. Sacks FM, Bray GA, Carey VJ et al. Comparison of weight-loss diets with different compositions of fat, protein, and carbohydrates. N Engl J Med 2009;360:859–73. 2. Bennett P. Obesity, diabetes and VLCD. Br J Diabetes Vasc Dis 2004;4:328–30. 3. Baldwin EJ. Fad diets in diabetes. Br J Diabetes Vasc DIs 2004;4:333–7. 4. Romon M, Lommoz A, Tafflet M et al. Downward trends in the prevalence of childhood overweight in the setting of 12-year school- and community-based programmes. Public Health Nutr 2008; Dec 28, 1–8 [Epub ahead of print].