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.

The impact of changes to the graduated driver licensing program in Queensland, Australia on the experiences of learner drivers

Purpose: Graduated driver licensing (GDL) has been introduced in numerous jurisdictions in Australia and internationally in an attempt to ameliorate the significantly greater risk of death and injury for young novice drivers arising from road crashes. The GDL program in Queensland, Australia, was extensively modified in July 2007. This paper reports the driving and licensing experiences of Learner drivers progressing through the current-GDL program, and compares them to the experiences of Learners who progressed through the former-GDL program. ----- ----- Method: Young drivers (n = 1032, 609 females, 423 males) aged 17 to 19 years (M = 17.43, SD = 0.67) were recruited as they progressed from a Learner to a Provisional driver’s licence. They completed a survey exploring their sociodemographic characteristics, driving and licensing experiences as a Learner. Key measures for a subsample (n = 183) of the current-GDL drivers were compared with the former-GDL drivers (n = 149) via t-tests and chi-square analyses. ----- ----- Results: As expected, Learner drivers progressing through the current-GDL program gained significantly more driving practice than those in the former program, which was more likely to be provided by mothers than in the past. Female learners in the current-GDL program reported less difficulty obtaining supervision than those in the former program. The number of attempts needed to pass the practical driving assessment did not change, nor did the amount of professional supervision. The current-GDL Learners held their licence for a significantly longer duration than those in the former program, with the majority reporting that their Logbook entries were accurate on the whole. Compared to those in the former program, a significantly smaller proportion of male current-GDL Learners reported being detected for a driving offence while the females reported significantly lower crash involvement. Most current-GDL drivers reported undertaking their supervised practice at the end of the Learner period. ----- ----- Conclusions: The enhancements to the GDL program in Queensland appear to have achieved many of their intended results. The current-GDL learners participating in the study reported obtaining a significantly greater amount of supervised driving experience compared to former-GDL learners. Encouragingly, the current-GDL Learners did not report any greater difficulty in obtaining supervised driving practice, and there was a decline in the proportion of current-GDL Learners engaging in unsupervised driving. In addition, the majority of Learners do not appear to be attempting to subvert logbook recording requirements, as evidenced by high rates of self-reported logbook accuracy. The results have implications for the development and the evaluation of GDL programs in Australia and around the world.

Alcohol expectancy changes over a 12-week cognitive–behavioral therapy program are predictive of treatment success

This study examines if outcome expectancies (perceived consequences of engaging in certain behavior) and self- efficacy expectancies (confidence in personal capacity to regulate behavior) contribute to treatment outcome for alcohol dependence. Few clinical studies have examined these constructs. The Drinking Expectancy Profile (DEP), a psychometric measure of alcohol expectancy and drinking refusal selfefficacy, was administered to 298 alcohol-dependent patients (207 males) at assessment and on completion of a 12-week cognitive–behavioral therapy alcohol abstinence program. Baseline measures of expectancy and self-efficacy were not strong predictors of outcome. However, for the 164 patients who completed treatment, all alcohol expectancy and self-efficacy factors of the DEP showed change over time. The DEP scores approximated community norms at the end of treatment. Discriminant analysis indicated that change in social pressure drinking refusal self-efficacy, sexual enhancement expectancies, and assertion expectancies successfully discriminated those who successfully completed treatment from those who did not. Future research should examine the basis of expectancies related to social functioning as a possible mechanism of treatment response and a means to enhance treatment outcome.

The patella morphology in trochlear dysplasia : a comparative MRI study

BACKGROUND: Trochlear dysplasia is suspected to have a genetic basis and causes recurrent patellar instability due to insufficient anatomical geometry. Numerous studies about trochlear morphology and the optimal surgical treatment have been carried out, but no attention has been paid to the corresponding patellar morphology.----- ----- PURPOSE: The aim of this study was the evaluation of the patellar morphology in normal and trochlear dysplastic knees. ----- ----- STUDY DESIGN: Biometric analysis. ----- ----- METHODS: Twenty two patellae with underlying trochlear dysplasia (study group--SG) were compared with 22 matched knees with normal trochlear shape (control group--CG) on transverse and sagittal MRI slices. We compared transverse diameter, cartilaginous thickness, Wiberg-index and -angle, length and radius of lateral and medial facet, patellar shape and angle, retropatellar length, and type of trochlear dysplasia. For statistical analysis we used the Wilcoxon signed ranks test. ----- ----- RESULTS: The transverse and sagittal diameter, mean length of medial patellar facet, and mean cartilaginous and subchondral Wiberg-index showed statistical differences between the two groups. ----- ----- CONCLUSIONS: Although the insufficient trochlear depth and decreased lateral trochlear slope are responsible for patellofemoral instability, the patella shows morphological changes in trochlear dysplastic knees. Its overall size and the medial facet are smaller. Although the femoral sulcus angle is larger, the Wiberg-angle and -index are equal to the control group. This may indicate that the patellar morphology may not be a result of missing medial patellofemoral pressure in trochlear dysplastic knees, but a decreased medial patellofemoral traction. This seems to be caused by hypotrophic medial patellofemoral restraints in combination with an increased lateral patellar tilt, both resulting in a decreased tension onto the medial patella facet. Whether there is a genetic component to the patellar morphology remains open.

Immunohistochemical analysis of structural changes in collagen for the assessment of osteoarthritis

Collagen fibrillation within articular cartilage (AC) plays a key role in joint osteoarthritis (OA) progression and, therefore, studying collagen synthesis changes could be an indicator for use in the assessment of OA. Various staining techniques have been developed and used to determine the collagen network transformation under microscopy. However, because collagen and proteoglycan coexist and have the same index of refraction, conventional methods for specific visualization of collagen tissue is difficult. This study aimed to develop an advanced staining technique to distinguish collagen from proteoglycan and to determine its evolution in relation to OA progression using optical and laser scanning confocal microscopy (LSCM). A number of AC samples were obtained from sheep joints, including both healthy and abnormal joints with OA grades 1 to 3. The samples were stained using two different trichrome methods and immunohistochemistry (IHC) to stain both colourimetrically and with fluorescence. Using optical microscopy and LSCM, the present authors demonstrated that the IHC technique stains collagens only, allowing the collagen network to be separated and directly investigated. Fluorescently-stained IHC samples were also subjected to LSCM to obtain three-dimensional images of the collagen fibres. Changes in the collagen fibres were then correlated with the grade of OA in tissue. This study is the first to successfully utilize the IHC staining technique in conjunction with laser scanning confocal microscopy. This is a valuable tool for assessing changes to articular cartilage in OA.

For the better or the worse? The impact of business idea changes on new venture performance and novelty

Should new ventures stick to their knitting once they start commercialising or should they engage in frequent changes of their business idea? In this paper we argue that new ventures still need to learn their way in the early phases of commercialisation and that changes are good, but subject to two important contingencies. First is that changes should be aimed at enhancing uniqueness, which in turn enhances new venture performance. Second is that our results show that changes have limited affect on uniqueness and performance for entrepreneurs aiming at maximising opportunities, but that changing the business idea has a significant positive impact for entrepreneurs focusing on minimising losses. Our findings indicate that entrepreneurs aiming at minimising losses may offset their initial disadvantages by engaging in a series of adaptations of the business idea to gain higher performance and a more unique product offering.

Motivational Interviewing changes the treatment trajectory of group Cognitive-Behavioural Therapy for anxiety

Anxiety disorders have been viewed as manifestations of broad underlying predisposing personality constructs such as neuroticism combined with more specific individual differences of unhelpful information processing styles. Given the high prevalence of anxiety and the significant impairment that it causes, there is an important need to continue to explore successful treatments for this disorder. Research indicates that there is still room for significantly improving attrition rates and treatment adherence. Traditionally Motivational Interviewing (MI) has been used to facilitate health behaviour change. Recently MI has been applied to psychotherapy and has been shown to improve the outcome of CBT. However, these studies have been limited to only considering pre- and post-treatment measures and neglected to consider when changes occur along the course of therapy. This leaves the unanswered question of what is the impact of pre-treatment MI on the treatment trajectory of therapy. This study provides preliminary research into answering this question by tracking changes on a weekly basis along the course of group CBT. Prior to group CBT, 40 individuals with a principal anxiety disorder diagnosis were randomly assigned to receive either 3 individual sessions of MI or placed on a waitlist control group. All participants then received the same dosage of 10 weekly 2 hour sessions of group CBT. Tracking treatment outcome trajectory over the course of CBT, the pre-treatment MI group, compared to the control group, experienced a greater improvement early on in the course of therapy in their symptom distress, interpersonal relationships and quality of life. This early advantage over the control group was then maintained throughout therapy. These results not only demonstrate the value of adding MI to CBT, but also highlight the immediacy of MI effects. Further research is needed to determine the robustness of these effects to inform clinical implications of how to best apply MI to improve treatment adherence to CBT for anxiety disorders.

Changes in resting and walking energy expenditure and walking speed during pregnancy in obese women

Background Energy conserving processes reported in undernourished women during pregnancy are a recognised strategy to provide energy required to support fetal development. Women who are obese before conceiving arguably have sufficient fat stores to support the energy demands of pregnancy without the need to provoke energy conserving mechanisms. Objective We tested the hypothesis that obese women would demonstrate behavioural adaptation (i.e. decrease in self-selected walking (SSW) speed) but not metabolic compensation (i.e. decrease in resting metabolic rate (RMR) or metabolic cost of walking) during gestation. Design RMR, SSW speed, metabolic cost of walking, and anthropometry were measured in 23 women (BMI: 33.6 ± 2.5 kg/m2; 31 ± 4 years) at approximately weeks 15 (wk 15) and 30 (wk 30) of gestation. RMR was also measured in two cohorts of non-pregnant controls matched for age, weight and height of the pregnant cohort at wk 15 (N=23) and wk 30 (N=23). Results GWG varied widely (11.3 ± 5.4 kg) and 52% of women gained more weight than is recommended. RMR increased significantly by an average 177 ± 176 kcal/d (11±12%; P<0.0001); however the within-group variability was large. Both the metabolic cost of walking and SSW speed decreased significantly (P<0.01). While RMR increased in >80% of the cohort, the net oxygen cost of walking decreased in the same proportion of women. Conclusions While the increase in RMR was greater than was explained by weight gain, there was evidence of both behavioural and biological compensation in the metabolic cost of walking in obese women during gestation.

Analysis of micro-structural changes and measurement of their parameters of a food material

Food microstructure represents the way their elements arrangement and their interaction. Researchers in this field benefit from identifying new methods of examination of the microstructure and analysing the images. Experiments were undertaken to study micro-structural changes of food material during drying. Micro-structural images were obtained for potato samples of cubical shape at different moisture contents during drying using scanning electron microscopy. Physical parameters such as cell wall perimeter, and area were calculated using an image identification algorithm, based on edge detection and morphological operators. The algorithm was developed using Matlab.

Changes to conveyancing in Queensland

Significant amendments to the Property Agents and Motor Dealers Act 2000 (Qld) (‘PAMDA’) and the Body Corporate and Community Management Act 1997 (Qld) (‘BCCMA’) were made by the Liquor and Other Acts Amendment Act 2005 (Qld). These amendments commenced on 1 December 2005. The purpose of this article is to briefly describe the amendments and to indicate certain issues that may arise in practice.

Changes to the REIQ contract and conveyancing case law update

The Reference Schedule to the REIQ houses and land contract and the lots in a Community Titles Scheme (“CTS”) contract has been amended to contain provision for disclosure concerning the installation of an approved safety switch. This section will not be required to be completed if the land is vacant (in the case of the houses and land contract) or if the present use is a commercial use (in the case of the lots in a CTS contract).

Lateral distortional buckling tests of a new hollow flange channel beam

The LiteSteel beam (LSB) is a new hollow flange channel section developed by OneSteel Australian Tube Mills using their patented dual electric resistance welding and automated continuous roll-forming process. It has a unique geometry consisting of torsionally rigid rectangular hollow flanges and a relatively slender web. The LSBs are commonly used as flexural members in buildings. However, the LSB flexural members are subjected to lateral distortional buckling, which reduces their member moment capacities. Unlike the commonly observed lateral torsional buckling of steel beams, the lateral distortional buckling of LSBs is characterised by simultaneous lateral deflection, twist, and cross sectional change due to web distortion. An experimental study including more than 50 lateral buckling tests was therefore conducted to investigate the behaviour and strength of LSB flexural members. It included the available 13 LSB sections with spans ranging from 1200 to 4000 mm. Lateral buckling tests based on a quarter point loading were conducted using a special test rig designed to simulate the required simply supported and loading conditions accurately. Experimental moment capacities were compared with the predictions from the design rules in the Australian cold-formed steel structures standard. The new design rules in the standard were able to predict the moment capacities more accurately than previous design rules. This paper presents the details of lateral distortional buckling tests, in particular the features of the lateral buckling test rig, the results and the comparisons. It also includes the results of detailed studies into the mechanical properties and residual stresses of LSBs.