Long-term effects of pre-and postnatal glucocorticoid treatment in congenital adrenal hyperplasia

Congenital adrenal hyperplasia (CAH) is an autosomal recessive disorder mostly caused by mutations in the CYP21A2 gene leading to impaired production of cortisol and aldosterone. Precursors in the steroidogenic pathway are shunted to pathways of androgen production and elevated levels of androgens may cause virilization of the external genitalia in females with CAH already in utero. Prenatal treatment with the synthetic glucocorticoid (GC) dexamethasone (DEX) can ameliorate virilization of the female fetus but because of the recessive mode of the inheritance of CAH and that treatment has to be initiated before the genotype of the fetus can be determined, the majority of the treated cases will be unnecessarily exposed to DEX during fetal life. Moreover, patients with CAH require GC replacement therapy after birth and during their life span there may be episodes of over- or under-treatment with a risk of developing adverse effects. Side effects of pre-and postnatal GC exposure may develop into chronic conditions with permanent effects on growth, metabolism, cognition, behavior and normal immune functioning. In this study, the effects of prenatal DEX treatment and postnatal GC treatment in the context of CAH were evaluated in a cohort of 265 individuals. The cohort comprised DEX-treated individuals with and without CAH, patients with CAH not prenatally treated with DEX and controls from the general population. The long-term impact on cognition, behavior, brain morphology, metabolism and DNA methylation was studied. Prenatal treatment with DEX was associated with cognitive impairments, particularly working memory. The effects seem to normalize by adult age in individuals without CAH who were treated with DEX during the first trimester of fetal life. In patients with CAH, prenatal DEX therapy was associated with reduced thickness and surface area bilaterally of a large area encompassing the parietal and superior occipital cortex. Moreover, the effects of DEX treatment on DNA methylation were associated with alterations in the DNA methylation profile, denoting an altered epigenetic programming of the immune system and, in particular, inflammation in individuals without CAH treated in the first trimester. This finding may confer altered risks for immune-related disorders later in life. When looking at the long-term outcome in patients with CAH, patients showed deficits in tests measuring executive functioning. Deficits in spatial working memory were associated with decreased white matter integrity that, in turn, was associated with lower dosages of GCs. Patients also showed structural alterations in the prefrontal regions involved in executive functioning and in areas of the parietal and superior occipital cortex involved in sensory integration. In addition, patients exhibited reduced cerebellar volume. In our analysis of DNA methylation in patients with CAH, we identified hypermethylation in two CpGs in two genes (FAIM2 and SFI1). Methylation was associated with the severity of CAH and brain structure, but we could not identify any association between methylation in these two genes and metabolic or cognitive outcome. In conclusion, this study extends our knowledge about the effects of pre-and postnatal GC treatment in CAH. The results have implications for the use of prenatal DEX treatment

Maatalouden rakenteen kehitysennusteet eri menetelmillä

vokKirjasto Aj-

A Study Program for Doctoral Supervisors – a Vehicle for Development

A study program for doctoral supervisors is currently being implemented at two higher education institutions: One large and traditional research university and one university college. The overall aim of the program is to improve supervision as well as local practices for doctoral education and doctoral research in departments and research groups but also at the institutional level. In planning the program three important considerations were made. The program should:- be aligned with existing qualification frameworks for tenure and promotion; - serve as a platform and source for knowledge building and organisational learning on doctoral supervision and doctoral student learning; - serve as an arena for supervisors, educational developers, and educational researchers to collaborate on doctoral student learning and doctoral supervision.These considerations will be discussed in relation to enhancement of supervision and doctoral student learning, the scholarship of teaching and learning movement, and compulsory higher education teacher training. The study program of Lund and Kristianstad will be used as a case. The presentation will be made against a contextual backdrop in which doctoral education is claimed to be under increasing tensions. On one hand doctoral education has become increasingly important for research production and research funding. On the other hand there is a strong push for doctoral education to focus learning and employability and to serve a wider purpose than the re-growth of the academy. In Europe this is most visible through the Bologna process

En modell för simulering av lantbruksföretagets ekonomiska utveckling

vokKirjasto Aj-

Implementation of a Plastically Dissipated Energy Criterion for Three Dimensional Modeling of Fatigue Crack Growth

Fatigue crack growth is simulated using three dimensional elastic-plastic finite element analysis. The crack extension per load cycle, da/dN, as well as crack front profile changes (crack tunneling) under cyclic loading is not specified as an input but evaluated based on a condition that relates plastically dissipated energy to a critical value. Simulation of cyclic crack propagation in a middle-crack tension M(T) specimen using this implementation captures the well established, experimentally obtained crack growth rate reduction accompanying a single overload event. The analysis predicts that the single overload also affects the crack front profile, where a tunneling crack propagates with a flatter crack front in the overload affected zone

In Situ Analysis of Fatigue Crack Propagation in Polymer Foams

This paper presents an in situ SEM experimental study on cyclic crack propagation in closed-cell polymer foams. The microscopic failure mechanisms in precracked PVC and PES specimens of 60 and 90 kg/m3 densities were examined under low-cycle fatigue loading. In the PVC foam, crack propagation occurred incrementally by successive failure of cell boundaries in front of the crack tip. The crack occasionally jumped to cell boundaries above or below the main crack resulting in non-self similar growth. Crack propagation in the PES foam occurred incrementally by extensive plastic tearing and subsequent tensile failure of the cell edge in front of the crack tip. Crack advance sometimes occurred by coalescence of the main crack with a secondary crack above or below the main crack. Such crack bridging involved extensive shear deformation of the cells bridging the two adjacent cracks. Overall, crack growth in the PES foams occurred through the center of the cells. At a given cycle load level, more loading cycles were required to extend the crack in the PES foam than for the PVC foam as a result of the higher ductility of the PES polymer

‘Co-Creation’ is On Everyone’s Lips – Designers’ Perception of Opportunities For and Barriers To Co-Creation in Product Development Organizations

Co-creation, aimed at encouraging users to become active partners throughout the development process, has been widely discussed in academia for the last 10-15 years as a strategy for sustainable design of products that fulfil users’ needs and enhance users’ experience of future products. However, despite the fact that universities have undertaken to educate future designers on methods and tools for co-creation with users, we emphasize that there is still a noticeable gap between theory and practice, as designers’ opportunities for incorporating co-creation activities in product development organizations remain limited. The aim of this study, consisting of twelve semi-structured, in-depth interviews with design practitioners from Swedish industry, was to create a deeper understanding of the extent to which designers can and do actively involve users in the design process in industrial organizations. While we found that designers were interested and willing to work in a more user-centered way, there was no evidence of co-creation with users. The companies’ marketing departments were mainly responsible for customer/user contact, identifying and communicating user/customer requirements by means of traditional marketing methods. Hence direct communication between designers and users was rarely supported. Moreover, the informants often experienced a strong reluctance from the marketing department to provide them with necessary contacts, as this might interfere with their relationship with the customer. The barriers to accessing users were even more pronounced for designers in consultancy firms, where the customer functioned as the link to the market and frequently declined to allocate resources to user studies, arguing that they already possessed the necessary knowledge or that such studies were too costly. Consequently, irrespective of intra- or inter-organizational settings, designers’ ability to access users often depended on individual motivation and initiatives rather than organizational factors

In Situ Analysis of Crack Propagation in Polymer Foams

This article presents an experimental study on the microscopic mechanisms associated with crack propagation in closed cell polymer foams. A brittle, slightly cross-linked polyvinyl chloride (PVC) foam of density 60 kg/m3 and a ductile thermoplastic polyether sulfone (PES) foam of density 90 kg/m3 were examined. The PVC and PES foams have similar cell size (≈0.7 mm) but the cell edges of the PES foam were much thicker than those in the PVC foam. Overall, it was observed that the elements of both foams fractured in an extensional mode. Crack propagation in the PVC foam was inter-cellular, where agglomerates of very small cells formed a region of weakness. Damaged cell walls were observed on both sides of the crack plane. For the PES foam, craze-like deformation bands were observed in the highly stretched region ahead of the blunted crack tip. Further ahead of the crack tip, highly stretched cells were observed. Fracture occurred predominantly through the center of the cells in the PES foam

Characterization of Fracture Toughness G (sub c) of PVC and PES Foams

The fracture behavior of polyvinyl chloride (PVC) and polyethersulfone (PES) foams has been examined using the single-edge notch bend and the double cantilever beam (DCB) tests. PVC foam densities ranging from 45 to 100 kg/m3 and PES foam densities ranging from 60 to 130 kg/m3 were examined. The PVC foams failed in a linear elastic brittle manner, whereas the PES foams displayed much more ductility and substantially larger toughness at a comparable foam density. The cell wall thickness of the PES foams was almost twice the thickness of the PVC foams which may have contributed to the high fracture toughness here defined as critical energy release rate (G c). The PES foam, further displayed low initiation toughness, due to the sharp artificial crack tip and large toughness corresponding to propagation from a natural crack. The results show that the ductile PES foams have toughness close to its solid counterpart whereas the toughness of the PVC foams falls substantially below its solid counterpart

Implementation of a Plastically Dissipated Energy Criterion for Three Dimensional Modeling of Fatigue Crack Growth

Fatigue crack growth is simulated using three dimensional elastic-plastic finite element analysis. The crack extension per load cycle, da/dN, as well as crack front profile changes (crack tunneling) under cyclic loading is not specified as an input but evaluated based on a condition that relates plastically dissipated energy to a critical value. Simulation of cyclic crack propagation in a middle-crack tension M(T) specimen using this implementation captures the well established, experimentally obtained crack growth rate reduction accompanying a single overload event. The analysis predicts that the single overload also affects the crack front profile, where a tunneling crack propagates with a flatter crack front in the overload affected zone