An exercise intervention during chemotherapy for women with recurrent ovarian cancer: A feasibility study

Objective: The aim of this study was to determine the feasibility of a combined supervised and home-based exercise intervention during chemotherapy for women with recurrent ovarian cancer. Secondary aims were to determine the impact of physical activity on physical and psychological outcomes and on chemotherapy completion rates. Methods: Women with recurrent ovarian cancer were recruited from 3 oncology outpatient clinics in Sydney and Canberra, Australia. All participants received an individualized exercise program that consisted of 90 minutes or more of low to moderate aerobic, resistance, core stability, and balance exercise per week, for 12 weeks. Feasibility was determined by recruitment rate, retention rate, intervention adherence, and adverse events. Aerobic capacity, muscular strength, fatigue, sleep quality, quality of life, depression, and chemotherapy completion rates were assessed at weeks 0, 12, and 24. Results: Thirty participants were recruited (recruitment rate, 63%), with a retention rate of 70%. Participants averaged 196 ± 138 min · wk of low to moderate physical activity throughout the intervention, with adherence to the program at 81%. There were no adverse events resulting from the exercise intervention. Participants who completed the study displayed significant improvements in quality of life (P = 0.017), fatigue (P = 0.004), mental health (P = 0.007), muscular strength (P = 0.001), and balance (P = 0.003) after the intervention. Participants completing the intervention had a higher relative dose intensity than noncompleters (P = 0.03). Conclusions: A program consisting of low to moderate exercise of 90 min · wk was achieved by two-thirds of women with recurrent ovarian cancer in this study, with no adverse events reported. Randomized control studies are required to confirm the benefits of exercise reported in this study.

Telomere length in circulating leukocytes is associated with lung function and disease

Several clinical studies suggest the involvement of premature ageing processes in chronic obstructive pulmonary disease (COPD). Using an epidemiological approach, we studied whether accelerated ageing indicated by telomere length, a marker of biological age, is associated with COPD and asthma, and whether intrinsic age-related processes contribute to the interindividual variability of lung function. Our meta-analysis of 14 studies included 934 COPD cases with 15 846 controls defined according to the Global Lungs Initiative (GLI) criteria (or 1189 COPD cases according to the Global Initiative for Chronic Obstructive Lung Disease (GOLD) criteria), 2834 asthma cases with 28 195 controls, and spirometric parameters (forced expiratory volume in 1 s (FEV1), forced vital capacity (FVC) and FEV1/FVC) of 12 595 individuals. Associations with telomere length were tested by linear regression, adjusting for age, sex and smoking status. We observed negative associations between telomere length and asthma (β= −0.0452, p=0.024) as well as COPD (β= −0.0982, p=0.001), with associations being stronger and more significant when using GLI criteria than those of GOLD. In both diseases, effects were stronger in females than males. The investigation of spirometric indices showed positive associations between telomere length and FEV1 (p=1.07×10−7), FVC (p=2.07×10−5), and FEV1/FVC (p=5.27×10−3). The effect was somewhat weaker in apparently healthy subjects than in COPD or asthma patients. Our results provide indirect evidence for the hypothesis that cellular senescence may contribute to the pathogenesis of COPD and asthma, and that lung function may reflect biological ageing primarily due to intrinsic processes, which are likely to be aggravated in lung diseases.

Reliability and criterion-related validity with a smartphone used in timed-up-and-go test

Background The capacity to diagnosys, quantify and evaluate movement beyond the general confines of a clinical environment under effectiveness conditions may alleviate rampant strain on limited, expensive and highly specialized medical resources. An iPhone 4® mounted a three dimensional accelerometer subsystem with highly robust software applications. The present study aimed to evaluate the reliability and concurrent criterion-related validity of the accelerations with an iPhone 4® in an Extended Timed Get Up and Go test. Extended Timed Get Up and Go is a clinical test with that the patient get up from the chair and walking ten meters, turn and coming back to the chair. Methods A repeated measure, cross-sectional, analytical study. Test-retest reliability of the kinematic measurements of the iPhone 4® compared with a standard validated laboratory device. We calculated the Coefficient of Multiple Correlation between the two sensors acceleration signal of each subject, in each sub-stage, in each of the three Extended Timed Get Up and Go test trials. To investigate statistical agreement between the two sensors we used the Bland-Altman method. Results With respect to the analysis of the correlation data in the present work, the Coefficient of Multiple Correlation of the five subjects in their triplicated trials were as follows: in sub-phase Sit to Stand the ranged between r = 0.991 to 0.842; in Gait Go, r = 0.967 to 0.852; in Turn, 0.979 to 0.798; in Gait Come, 0.964 to 0.887; and in Turn to Stand to Sit, 0.992 to 0.877. All the correlations between the sensors were significant (p < 0.001). The Bland-Altman plots obtained showed a solid tendency to stay at close to zero, especially on the y and x-axes, during the five phases of the Extended Timed Get Up and Go test. Conclusions The inertial sensor mounted in the iPhone 4® is sufficiently reliable and accurate to evaluate and identify the kinematic patterns in an Extended Timed Get and Go test. While analysis and interpretation of 3D kinematics data continue to be dauntingly complex, the iPhone 4® makes the task of acquiring the data relatively inexpensive and easy to use.

Three of a kind? The special case of Australia's Island Councils

In common with many other countries, Australian local government policymakers have focussed heavily on improving financial sustainability and operational efficiency through structural change and other modes of systemic reform. However, this system-wide approach cannot adequately deal with small island councils due to their sui generis characteristics. In an effort to fill this gap in the literature, this article examines the financial sustainability of Australia’s three island councils – Flinders, Kangaroo and King – over the period 2008–2013 in order to determine whether alternative organisational arrangements may be better suited to their unique circumstances. In so doing, our study contributes to the literature by providing the first empirical analysis of the financial viability of Australia’s island councils while considering the need for an alternative organisation entity in an effort to enhance their long-term financial sustainability.

The tumour-promoting receptor tyrosine kinase, EphB4, regulates expression of Integrin-β8 in prostate cancer cells

Background The EphB4 receptor tyrosine kinase is overexpressed in many cancers including prostate cancer. The molecular mechanisms by which this ephrin receptor influences cancer progression are complex as there are tumor-promoting ligand-independent mechanisms in place as well as ligand-dependent tumor suppressive pathways. Methods We employed transient knockdown of EPHB4 in prostate cancer cells, coupled with gene microarray analysis, to identify genes that were regulated by EPHB4 and may represent linked tumor-promoting factors. We validated target genes using qRT-PCR and employed functional assays to determine their role in prostate cancer migration and invasion. Results We discovered that over 500 genes were deregulated upon EPHB4 siRNA knockdown, with integrin β8 (ITGB8) being the top hit (29-fold down-regulated compared to negative non-silencing siRNA). Gene ontology analysis found that the process of cell adhesion was highly deregulated and two other integrin genes, ITGA3 and ITGA10, were also differentially expressed. In parallel, we also discovered that over-expression of EPHB4 led to a concomitant increase in ITGB8 expression. In silico analysis of a prostate cancer progression microarray publically available in the Oncomine database showed that both EPHB4 and ITGB8 are highly expressed in prostatic intraepithelial neoplasia, the precursor to prostate cancer. Knockdown of ITGB8 in PC-3 and 22Rv1 prostate cancer cells in vitro resulted in significant reduction of cell migration and invasion. Conclusions These results reveal that EphB4 regulates integrin β8 expression and that integrin β8 plays a hitherto unrecognized role in the motility of prostate cancer cells and thus targeting integrin β8 may be a new treatment strategy for prostate cancer.

23andMe Inc.: Patent law and lifestyle genetics

The venture, 23andMe Inc., raises a host of issues in respect of patent law, policy, and practice in respect of lifestyle genetics and personalised medicine. The company observes: ‘We recognize that the availability of personal genetic information raises important issues at the nexus of ethics, law, and public policy’. 23andMe Inc. has tested the boundaries of patent law, with its patent applications, which cut across information technology, medicine, and biotechnology. The company’s research raises fundamental issues about patentability, especially in light of the litigation in Bilski v. Kappos, Mayo Collaborative Services v. Prometheus Laboratories Inc. and Association for Molecular Pathology v. United States Patent and Trademark Office and Myriad Genetics Inc. There has been much debate and controversy over 23andMe Inc. filing patent applications – particularly in respect of its granted patent on ‘Polymorphisms associated with Parkinson’s Disease’. The direct-to-consumer marketing of genetic testing by 23andMe Inc. has also raised important questions of bioethics and human rights. It is queried whether the terms of service for 23andMe Inc. provide adequate recognition of the concepts of informed consent and benefit-sharing, especially in light of litigation in this area in the United States. Given the patent thickets surrounding genetic testing, the case study of 23andMe Inc. also highlights questions about patent infringement and patent exceptions. The future reform of patent law, policy, and practice needs to take into account new developments in lifestyle genetics and personalised medicine – as exemplified by 23andMe Inc.

Destination brand performance measurement over time: Tracking consumer perceptions of a competitive set of destinations over a 10 year period

There has been a paucity of research published in relation to the temporal aspect of destination image change over time. Given increasing investments in destination branding, research is needed to enhance understanding of how to monitor destination brand performance, of which destination image is the core construct, over time. This article reports the results of four studies tracking brand performance of a competitive set of five destinations, between 2003 and 2012. Results indicate minimal changes in perceptions held of the five destinations of interest over the 10 years, supporting the assertion of Gartner (1986) and Gartner and Hunt (1987) that destination image change will only occur slowly over time. While undertaken in Australia, the research approach provides DMOs in other parts of the world with a practical tool for evaluating brand performance over time; in terms of measures of effectiveness of past marketing communications, and indicators of future performance.

Genetic influences on brain asymmetry: A DTI study of 374 twins and siblings

Brain asymmetry, or the structural and functional specialization of each brain hemisphere, has fascinated neuroscientists for over a century. Even so, genetic and environmental factors that influence brain asymmetry are largely unknown. Diffusion tensor imaging (DTI) now allows asymmetry to be studied at a microscopic scale by examining differences in fiber characteristics across hemispheres rather than differences in structure shapes and volumes. Here we analyzed 4. Tesla DTI scans from 374 healthy adults, including 60 monozygotic twin pairs, 45 same-sex dizygotic pairs, and 164 mixed-sex DZ twins and their siblings; mean age: 24.4 years ± 1.9 SD). All DTI scans were nonlinearly aligned to a geometrically-symmetric, population-based image template. We computed voxel-wise maps of significant asymmetries (left/right differences) for common diffusion measures that reflect fiber integrity (fractional and geodesic anisotropy; FA, GA and mean diffusivity, MD). In quantitative genetic models computed from all same-sex twin pairs (N=210 subjects), genetic factors accounted for 33% of the variance in asymmetry for the inferior fronto-occipital fasciculus, 37% for the anterior thalamic radiation, and 20% for the forceps major and uncinate fasciculus (all L > R). Shared environmental factors accounted for around 15% of the variance in asymmetry for the cortico-spinal tract (R > L) and about 10% for the forceps minor (L > R). Sex differences in asymmetry (men > women) were significant, and were greatest in regions with prominent FA asymmetries. These maps identify heritable DTI-derived features, and may empower genome-wide searches for genetic polymorphisms that influence brain asymmetry.

Defective co-creation: Developing a typology of consumer dysfunction in professional services

Purpose This study aims to explore the scope of consumers’ defective co-creation behaviour in professional service encounters. One of the founding premises of service-dominant logic (Vargo and Lusch, 2004, 2008) is that consumers co-create the value they derive from service encounters. In practice, however, dysfunctional consumer behaviour can obstruct value co-creation. Extant research has not yet investigated consumers’ defective co-creation behaviour in highly relational services, such as professional services, that are heavily reliant on co-creation. Design/methodology/approach To investigate defective co-creation in professional services, 164 critical incidents were collected from 38 health-care and financial service providers using the critical incident technique within semi-structured, in-depth interviews. Thematic coding was used to identify emergent themes and patterns of consumer behaviour. Findings Thematic coding resulted in a comprehensive typology of consumers’ defective co-creation behaviour that both confirms the prevalence of previously identified dysfunctional behaviours (e.g. verbal abuse and physical aggression) and identifies two new forms of consumer misbehaviour: underparticipation and overparticipation. Further, these behaviours can vary, escalate and co-occur during service encounters. Originality/value Both underparticipation and overparticipation are newly identified forms of defective co-creation that need to be examined within the broader framework of service-dominant logic (SDL).

Axial spondyloarthritis: A new disease entity, not necessarily early ankylosing spondylitis

New classification criteria for axial spondyloarthritis have been developed with the goal of increasing sensitivity of criteria for early inflammatory spondyloarthritis. However these criteria substantially increase heterogeneity of the resulting disease group, reducing their value in both research and clinical settings. Further research to establish criteria based on better knowledge of the natural history of non-radiographic axial spondyloarthritis, its aetiopathogenesis and response to treatment is required. In the meantime the modified New York criteria for ankylosing spondylitis remain a very useful classification criteria set, defining a relatively homogenous group of cases for clinical use and research studies.

A novel ACVR1 mutation in the glycine/serine-rich domain found in the most benign case of a fibrodysplasia ossificans progressiva variant reported to date

Fibrodysplasia Ossificans Progressiva (FOP) is a rare, autosomal dominant condition, classically characterised by heterotopic ossification beginning in childhood and congenital great toe malformations; occurring in response to a c.617 G>A ACVR1 mutation in the functionally important glycine/serine-rich domain of exon 6. Here we describe a novel c.587 T>C mutation in the glycine/serine-rich domain of ACVR1, associated with delayed onset of heterotopic ossification and an exceptionally mild clinical course. Absence of great toe malformations, the presence of early ossification of the cervical spine facets joints, plus mild bilateral camptodactyly of the 5th fingers, together with a novel ACVR1 mutation, are consistent with the 'FOP-variant' syndrome. The c.587 T>C mutation replaces a conserved leucine with proline at residue 196. Modelling of the mutant protein reveals a steric clash with the kinase domain that will weaken interactions with FKBP12 and induce exposure of the glycine/serine-rich repeat. The mutant receptor is predicted to be hypersensitive to ligand stimulation rather than being constitutively active, consistent with the mild clinical phenotype. This case extends our understanding of the 'FOP-variant' syndrome.

Burnout and work engagement in occupational therapists

Introduction Work engagement, characterized by vigour, dedication, and absorption, is often perceived as the opposite of burnout. Occupational therapists with burnout feel exhausted and disengaged from their work. This study aims to investigate demographic and work-related psychosocial factors associated with burnout and work engagement. Method A cross-sectional postal survey of 951 occupational therapists was conducted. Findings Two models representing factors associated with burnout (F(15,871) = 28.01, p < .001) and work engagement (F(10,852) = 16.15, p < .001) accounted for 32.54% and 15.93% of the variance respectively. Burnout and work engagement were inversely associated (χ2(n = 941) = 55.16, p < .001). Conclusion Factors associated with burnout and work engagement were identified. The variables associated with burnout included: low psychological detachment from work during out-of-work hours, low income satisfaction, perceived work overload, difficulty saying ‘no’, < 10 years' experience, low frequency of having a ‘belly laugh’, and not having children. High levels of work engagement were reported by therapists with the following: low psychological detachment from work, high income satisfaction, postgraduate qualifications, > 40 hours work/week, high frequency of having a ‘belly laugh’, and having children. Understanding the factors associated with burnout and work engagement provides prerequisite information to inform strategies aimed at building healthy workforces.

Fine mapping and replication of genetic risk Loci in primary sclerosing cholangitis

Background and aims. Primary sclerosing cholangitis (PSC) is a chronic cholestatic liver disease characterized by progressive inflammation and fibrosis of the bile ducts eventually leading to biliary cirrhosis. Recent genetic studies in PSC have identified associations at 2q13, 2q35, 3p21, 4q27, 13q31 and suggestive association at 10p15. The aim of this study was to further characterize and refine the genetic architecture of PSC. Methods. We analyzed previously reported associated SNPs at four of these non-HLA loci and 59 SNPs tagging the IL-2/IL-21 (4q27) and IL2RA (10p15) loci in 992 UK PSC cases and 5162 healthy UK controls. Results. The most associated SNPs identified were rs3197999 (3p21 (MST1), p = 1.9 × 10 -6, OR A vs G = 1.28, 95% CI (1.16-1.42)); rs4147359 (10p15 (IL2RA), p = 2.6 × 10 -4, OR A vs G = 1.20, 95% CI (1.09-1.33)) and rs12511287 (4q27 (IL-2/IL-21), p = 3.0 × 10 -4, OR A vs T = 1.21, 95% CI (1.09-1.35)). In addition, we performed a meta-analysis for selected SNPs using published summary statistics from recent studies. We observed genome-wide significance for rs3197999 (3p21 (MST1), P combined = 3.8 × 10 -12) and rs4147359 (10p15 (IL2RA), P combined = 1.5 × 10 -8). Conclusion. We have for the first time confirmed the association of PSC with genetic variants at 10p15 (IL2RA) locus at genome-wide significance and replicated the associations at MST1 and IL-2/IL-21 loci in a large homogeneous UK population. These results strongly implicate the role of IL-2/IL2RA pathway in PSC and provide further confirmation of MST1 association. © Informa Healthcare.

Dark city

A synopsis and critique of an Australian/American film, Dark City, directed by Alex Proyas in the science fiction genre.