Repeatability and validity of lens densitometry measured with Scheimpflug imaging

Purpose To assess the repeatability and validity of lens densitometry derived from the Pentacam Scheimpflug imaging system. Setting Eye Clinic, Queensland University of Technology, Brisbane, Australia. Methods This prospective cross-sectional study evaluated 1 eye of subjects with or without cataract. Scheimpflug measurements and slitlamp and retroillumination photographs were taken through a dilated pupil. Lenses were graded with the Lens Opacities Classification System III. Intraobserver and interobserver reliability of 3 observers performing 3 repeated Scheimpflug lens densitometry measurements each was assessed. Three lens densitometry metrics were evaluated: linear, for which a line was drawn through the visual axis and a mean lens densitometry value given; peak, which is the point at which lens densitometry is greatest on the densitogram; 3-dimensional (3D), in which a fixed, circular 3.0 mm area of the lens is selected and a mean lens densitometry value given. Bland and Altman analysis of repeatability for multiple measures was applied; results were reported as the repeatability coefficient and relative repeatability (RR). Results Twenty eyes were evaluated. Repeatability was high. Overall, interobserver repeatability was marginally lower than intraobserver repeatability. The peak was the least reliable metric (RR 37.31%) and 3D, the most reliable (RR 5.88%). Intraobserver and interobserver lens densitometry values in the cataract group were slightly less repeatable than in the noncataract group. Conclusion The intraobserver and interobserver repeatability of Scheimpflug lens densitometry was high in eyes with cataract and eyes without cataract, which supports the use of automated lens density scoring using the Scheimpflug system evaluated in the study

The contribution of different androgen receptor domains to receptor dimerization and signaling

The androgen receptor (AR) is a ligand-activated transcription factor of the nuclear receptor superfamily that plays a critical role in male physiology and pathology. Activated by binding of the native androgens testosterone and 5-dihydrotestosterone, the AR regulates transcription of genes involved in the development and maintenance of male phenotype and male reproductive function as well as other tissues such as bone and muscle. Deregulation of AR signaling can cause a diverse range of clinical conditions, including the X-linked androgen insensitivity syndrome, a form of motor neuron disease known as Kennedy’s disease, and male infertility. In addition, there is now compelling evidence that the AR is involved in all stages of prostate tumorigenesis including initiation, progression, and treatment resistance. To better understand the role of AR signaling in the pathogenesis of these conditions, it is important to have a comprehensive understanding of the key determinants of AR structure and function. Binding of androgens to the AR induces receptor dimerization, facilitating DNA binding and the recruitment of cofactors and transcriptional machinery to regulate expression of target genes. Various models of dimerization have been described for the AR, the most well characterized interaction being DNA-binding domain- mediated dimerization, which is essential for the AR to bind DNA and regulate transcription. Additional AR interactions with potential to contribute to receptor dimerization include the intermolecular interaction between the AR amino terminal domain and ligand-binding domain known as the N-terminal/C-terminal interaction, and ligand-binding domain dimerization. In this review, we discuss each form of dimerization utilized by the AR to achieve transcriptional competence and highlight that dimerization through multiple domains is necessary for optimal AR signaling.

The effects of exercise-induced weight loss on appetite-related peptides and motivation to eat

Context: The magnitude of exercise-induced weight loss depends on the extent of compensatory responses. An increase in energy intake is likely to result from changes in the appetite control system toward an orexigenic environment; however, few studies have measured how exercise impacts on both orexigenic and anorexigenic peptides. ---------- Objective: The aim of the study was to investigate the effects of medium-term exercise on fasting/postprandial levels of appetite-related hormones and subjective appetite sensations in overweight/obese individuals. ---------- Design and Setting: We conducted a longitudinal study in a university research center. ---------- Participants and Intervention: Twenty-two sedentary overweight/obese individuals (age, 36.9 ± 8.3 yr; body mass index, 31.3 ± 3.3 kg/m2) took part in a 12-wk supervised exercise programme (five times per week, 75% maximal heart rate) and were requested not to change their food intake during the study. ---------- Main Outcome Measures: We measured changes in body weight and fasting/postprandial plasma levels of glucose, insulin, total ghrelin, acylated ghrelin (AG), peptide YY, and glucagon-like peptide-1 and feelings of appetite. ---------- Results: Exercise resulted in a significant reduction in body weight and fasting insulin and an increase in AG plasma levels and fasting hunger sensations. A significant reduction in postprandial insulin plasma levels and a tendency toward an increase in the delayed release of glucagon-like peptide-1 (90–180 min) were also observed after exercise, as well as a significant increase (127%) in the suppression of AG postprandially. ---------- Conclusions: Exercise-induced weight loss is associated with physiological and biopsychological changes toward an increased drive to eat in the fasting state. However, this seems to be balanced by an improved satiety response to a meal and improved sensitivity of the appetite control system.

Insulin-like growth factor-i : vitronectin complex-induced changes in gene expression effect breast cell survival and migration

Recent studies have demonstrated that IGF-I associates with VN through IGF-binding proteins (IGFBP) which in turn modulate IGF-stimulated biological functions such as cell proliferation, attachment and migration. Since IGFs play important roles in transformation and progression of breast tumours, we aimed to describe the effects of IGF-I:IGFBP:VN complexes on breast cell function and to dissect mechanisms underlying these responses. In this study we demonstrate that substrate-bound IGF-I:IGFBP:VN complexes are potent stimulators of MCF-7 breast cell survival, which is mediated by a transient activation of ERK/MAPK and sustained activation of PI3-K/AKT pathways. Furthermore, use of pharmacological inhibitors of the MAPK and PI3-K pathways confirms that both pathways are involved in IGF-I:IGFBP:VN complex-mediated increased cell survival. Microarray analysis of cells stimulated to migrate in response to IGF-I:IGFBP:VN complexes identified differential expression of genes with previously reported roles in migration, invasion and survival (Ephrin-B2, Sharp-2, Tissue-factor, Stratifin, PAI-1, IRS-1). These changes were not detected when the IGF-I analogue (\[L24]\[A31]-IGF-I), which fails to bind to the IGF-I receptor, was substituted; confirming the IGF-I-dependent differential expression of genes associated with enhanced cell migration. Taken together, these studies have established that IGF-I:IGFBP:VN complexes enhance breast cell migration and survival, processes central to facilitating metastasis. This study highlights the interdependence of ECM and growth factor interactions in biological functions critical for metastasis and identifies potential novel therapeutic targets directed at preventing breast cancer progression.

A vibrational spectroscopic study of the mixed anion mineral sanjuanite Al2(PO4)(SO4)(OH)•9H2O

The mineral sanjuanite Al2(PO4)(SO4)(OH)•9H2O has been characterised by Raman spectroscopy complimented by infrared spectroscopy. The mineral is characterised by an intense Raman band at 984 cm-1, assigned to the (PO4)3- ν1 symmetric stretching mode. A shoulder band at 1037 cm-1 is attributed to the (SO4)2- ν1 symmetric stretching mode. Two Raman bands observed at 1102 and 1148 cm-1 are assigned to (PO4)3- and (SO4)2- ν3 antisymmetric stretching modes. Multiple bands provide evidence for the reduction in symmetry of both anions. This concept is supported by the multiple sulphate and phosphate bending modes. Raman spectroscopy shows that there are more than one non-equivalent water molecules in the sanjuanite structure. There is evidence that structural disorder exists, shown by the complex set of overlapping bands in the Raman and infrared spectra. At least two types of water are identified with different hydrogen bond strengths. The involvement of water in the sanjuanite structure is essential for the mineral stability.

Pollutant concentrations within households in Lao PDR and association with housing characteristics and occupants' activities

The paper presents the results of a study conducted to investigate indoor air quality within residential dwellings in Lao PDR. Results from PM 10, CO, and NO2 measurements inside 167 dwellings in Lao PDR over a five month period (December 2005-April 2006) are discussed as a function of household characteristics and occupant activities. Extremely high PM10 and NO2 concentrations (12 h mean PM10 concentrations 1275 ± 98 μg m-3 and 1183 ± 99 μg m-3 in Vientiane and Bolikhamxay provinces, respectively; 12 h mean NO2 concentrations 1210 ± 94 μg m-3 and 561 ± 45 μg m-3 in Vientiane and Bolikhamxay, respectively) were measured within the dwellings. Correlations, ANOVA analysis (univariate and multivariate), and linear regression results suggest a substantial contribution from cookingandsmoking.The PM10 concentrations were significantly higher in houses without a chimney compared to houses in which cooking occurred on a stove with a chimney. However, no significant differences in pollutantconcentrations were observed as a function of cooking location. Furthermore, PM10 and NO2 concentrations were higher in houses in which smoking occurred, suggestive of a relationship between increased indoor concentrations and smoking (0.05 < p < 0.10). Resuspension of dust from soil floors was another significant source of PM10 inside the house (634 μg m-3, p < 0.05).

Provotypes for participatory innovation

Central to multi-stakeholder processes of participatory innovation is to generate knowledge about ‘users’ and to identify business opportunities accordingly. In these processes of collaborative analysis and synthesis, conflicting perceptions within and about a field of interest are likely to surface. Instead of the natural tendency to avoid these tensions, we demonstrate how tensions can be utilized by embodying them in provocative types (provotypes). Provotypes expose and embody tensions that surround a field of interest to support collaborative analysis and collaborative design explorations across stakeholders. In this paper we map how provotyping contributes to four related areas of contemporary Interaction Design practice. Through a case study that brings together stakeholders from the field of indoor climate, we provide characteristics of design provocations and design guidelines for provotypes for participatory innovation.