Deprivation is an independent predictor of 1-year mortality in outpatients with chronic obstructive pulmonary disease

Deprivation is linked to increased incidence in a number of chronic diseases but its relationship to chronic obstructive pulmonary disease (COPD) is uncertain despite suggestions that the socioeconomic gradient seen in COPD is as great, if not greater, than any other disease (Prescott and Vestbo).1 There is also a need to take into account the confounding effects of malnutrition which have been shown to be independently linked to increased mortality (Collins et al).2 The current study investigated the influence of social deprivation on 1-year survival rates in COPD outpatients, independently of malnutrition. 424 outpatients with COPD were routinely screened for malnutrition risk using the ‘Malnutrition Universal Screening Tool’; ‘MUST’ (Elia),3 between July and May 2009; 222 males and 202 females; mean age 73 (SD 9.9) years; body mass index 25.8 (SD 6.3) kg/m2. Each individual's deprivation was calculated using the index of multiple deprivation (IMD) which was established according to the geographical location of each patient's address (postcode). IMD includes a number of indicators covering economic, housing and social issues (eg, health, education and employment) into a single deprivation score (Nobel et al).4 The lower the IMD score, the lower an individual's deprivation. The IMD was assigned to each outpatient at the time of screening and related to1-year mortality from the date screened. Outpatients who died within 1-year of screening were significantly more likely to reside within a deprived postcode (IMD 19.7±SD 13.1 vs 15.4±SD 10.7; p=0.023, OR 1.03, 95% CI 1.00 to 1.06) than those that did not die. Deprivation remained a significant independent risk factor for 1-year mortality even when adjusted for malnutrition as well as age, gender and disease severity (binary logistic regression; p=0.008, OR 1.04, 95% CI 1.04 to 1.07). Deprivation was not associated with disease-severity (p=0.906) or body mass index, kg/m2 (p=0.921) using ANOVA. This is the first study to show that deprivation, assessed using IMD, is associated with increased 1-year mortality in outpatients with COPD independently of malnutrition, age and disease severity. Deprivation should be considered in the targeted management of these patients.

PARP inhibition induces BAX/BAK-independent synthetic lethality of BRCA1-deficient non-small cell lung cancer

Evasion of apoptosis contributes to both tumourigenesis and drug resistance in non-small cell lung carcinoma (NSCLC). The pro-apoptotic BCL-2 family proteins BAX and BAK are critical regulators of mitochondrial apoptosis. New strategies for targeting NSCLC in a mitochondria-independent manner should bypass this common mechanism of apoptosis block. BRCA1 mutation frequency in lung cancer is low; however, decreased BRCA1 mRNA and protein expression levels have been reported in a significant proportion of lung adenocarcinomas. BRCA1 mutation/deficiency confers a defect in homologous recombination DNA repair that has been exploited by synthetic lethality through inhibition of PARP (PARPi) in breast and ovarian cells; however, it is not known whether this same synthetic lethal mechanism exists in NSCLC cells. Additionally, it is unknown whether the mitochondrial apoptotic pathway is required for BRCA1/PARPi-mediated synthetic lethality. Here we demonstrate that silencing of BRCA1 expression by RNA interference sensitizes NSCLC cells to PARP inhibition. Importantly, this sensitivity was not attenuated in cells harbouring mitochondrial apoptosis block induced by co-depletion of BAX and BAK. Furthermore, we demonstrate that BRCA1 inhibition cannot override platinum resistance, which is often mediated by loss of mitochondrial apoptosis signalling, but can still sensitize to PARP inhibition. Finally we demonstrate the existence of a BRCA1-deficient subgroup (11–19%) of NSCLC patients by analysing BRCA1 protein levels using immunohistochemistry in two independent primary NSCLC cohorts. Taken together, the existence of BRCA1-immunodeficient NSCLC suggests that this molecular subgroup could be effectively targeted by PARP inhibitors in the clinic and that PARP inhibitors could be used for the treatment of BRCA1-immunodeficient, platinum-resistant tumours.

Is the unigram relevance model term independent? Classifying term dependencies in query expansion

This paper develops a framework for classifying term dependencies in query expansion with respect to the role terms play in structural linguistic associations. The framework is used to classify and compare the query expansion terms produced by the unigram and positional relevance models. As the unigram relevance model does not explicitly model term dependencies in its estimation process it is often thought to ignore dependencies that exist between words in natural language. The framework presented in this paper is underpinned by two types of linguistic association, namely syntagmatic and paradigmatic associations. It was found that syntagmatic associations were a more prevalent form of linguistic association used in query expansion. Paradoxically, it was the unigram model that exhibited this association more than the positional relevance model. This surprising finding has two potential implications for information retrieval models: (1) if linguistic associations underpin query expansion, then a probabilistic term dependence assumption based on position is inadequate for capturing them; (2) the unigram relevance model captures more term dependency information than its underlying theoretical model suggests, so its normative position as a baseline that ignores term dependencies should perhaps be reviewed.

Clines in cuticular hydrocarbons in two Drosophila species with independent population histories

We took a comparative approach utilizing clines to investigate the extent to which natural selection may have shaped population divergence in cuticular hydrocarbons (CHCs) that are also under sexual selection in Drosophila. We detected the presence of CHC clines along a latitudinal gradient on the east coast of Australia in two fly species with independent phylogenetic and population histories, suggesting adaptation to shared abiotic factors. For both species, significant associations were detected between clinal variation in CHCs and temperature variation along the gradient, suggesting temperature maxima as a candidate abiotic factor shaping CHC variation among populations. However, rainfall and humidity correlated with CHC variation to differing extents in the two species, suggesting that response to these abiotic factors may vary in a species-specific manner. Our results suggest that natural selection, in addition to sexual selection, plays a significant role in structuring among-population variation in sexually selected traits in Drosophila.

Lessons on sin and forgiveness : a crisis in the Roman Catholic Church

One of the greatest challenges facing the Roman Catholic Church (the Church) across the world continues to be found in addressing complaints of child sexual abuse (csa) by clergy. The list of Catholic clergy in Australia who have been criminally processed for sexual offences against children is disturbingly long. As disturbing as this list is, more disturbing are the accounts of clergy who have not been criminally prosecuted, but protected within the cloister of the Church. It is increasingly recognised that the significant difficulty with child sexual abuse in Catholic Churches, in particular, has not been the presence of perpetrators but the response of Church leadership to allegations of csa by clergy. Those who have faced criminal charges have often done so due to the resilience of victim/survivors and not because of the support of Church structures or culture. The Church has been slow to come to terms with the realities of the perpetration of csa by its clergy and even slower to recognise the need to prioritise victims in any effective, just response. The church has been slowest of all recognising that there are significant cultural and discursive challenges to confront in addressing the management of csa by clergy. There is, however, progressive recognition of the role that discursive constructs of forgiveness have played in perpetuating the crises and ultimately in perpetuating abuse. The institutional praxis of forgiveness can be demonstrated not only in the Church, but in lessons learned from use of forgiveness as an institutional response to mass violations of human rights. This paper explores the juncture between criminality, church culture and forgiveness in responding to csa by clergy.

Independent people

A 3,000-word essay about Iceland

Integrated configuration of enterprise systems for interoperability : towards process model and business document specification alignment

Enterprise Systems (ES) can be understood as the de facto standard for holistic operational and managerial support within an organization. Most commonly ES are offered as commercial off-the-shelf packages, requiring customization in the user organization. This process is a complex and resource-intensive task, which often prevents small and midsize enterprises (SME) from undertaking configuration projects. Especially in the SME market independent software vendors provide pre-configured ES for a small customer base. The problem of ES configuration is shifted from the customer to the vendor, but remains critical. We argue that the yet unexplored link between process configuration and business document configuration must be closer examined as both types of configuration are closely tied to one another.

Culture as a driver of entrepreneurship : contrasting independent entrepreneurship versus employee entrepreneurship

Principal Topic Counties in Northern Europe, such as Sweden, Finland and Denmark, have comparatively low per capita rates of entrepreneurship as measured by independent new venture start-up rates – as for example measured by the Global Entrepreneurship Monitor (GEM) Total entrepreneurial activity (TEA) rate. However, the latest 2011 GEM data reveals that these same countries have comparatively very high Employee Entrepreneurship Activity (EEA) rates – that is a high rate per capita of employees involved in new product development or new enterprise activities. This observation has prompted us to investigate the role of national culture in driving independent versus employee entrepreneurial activities. Prior research has established that national (and regional) culture plays an important role in forming an “entrepreneurial culture” that encourages (or discourages) independent business start-ups and TEA (e.g. Davidsson, 1995; Beugelsdijk, 2007). However, the relationship of culture and EEA has not received research attention. Moreover, empirical relationships between elements of national culture and independent entrepreneurship have revealed some surprising results. For example, Wildeman et al. (1999) report an unexpected higher share of individual business ownership in countries that have higher uncertainty avoidance, higher power distance and lower individualism according to Hofstede’s dimensions of culture. They speculate that dissatisfaction can be a source of entrepreneurship: in countries with a high power distance, a high uncertainty avoidance and low individualism, there may be relatively more business owners since enterprising individuals cannot satisfy their needs within existing organizations. Yet it remains a rather open question whether entrepreneurial behaviour in existing organisations provides a satisfactory explanation for these empirical findings. Methods We will conduct a cross sectional study of the influence of national culture according to the five / six dimensions of Hofstede (1980; 2001) on both TEA and EEA for the 54 countries that participated in GEM 2011. Since it is well established that the opportunities for entrepreneurship vary substantially with a country’s level of economic development, we intend to conduct separate analyses for the three categories of development – innovation driven economies, efficient driven economies and factor driven economies. We also intend to restrict our assessment of TEA to opportunity driven entrepreneurship, as necessity driven entrepreneurship has a different relationship to the “entrepreneurial culture” that is the focus of our study. We will control for a range of factors such as GDP growth, ease of doing business index and unemployment. Results and Implications Descriptive analyses of the GEM TEA and EEA data reveal clusters of countries that appear to be have similar national culture. We are yet to conduct regression analyses.

Vitamin D status and skin cancer risk independent of time outdoors : 11-year prospective study in and Australian community

Vitamin D may have anti-skin cancer effects, but population-based evidence is lacking. We therefore assessed associations between vitamin D status and skin cancer risk in an Australian subtropical community. We analyzed prospective skin cancer incidence for 11 years following baseline assessment of serum 25(OH)-vitamin D in 1,191 adults (average age 54 years) and used multivariable logistic regression analysis to adjust risk estimates for age, sex, detailed assessments of usual time spent outdoors, phenotypic characteristics, and other possible confounders. Participants with serum 25(OH)-vitamin D concentrations above 75 nmol  l(-1) versus those below 75 nmol  l(-1) more often developed basal cell carcinoma (odds ratio (OR)=1.51 (95% confidence interval (CI): 1.10-2.07, P=0.01) and melanoma (OR=2.71 (95% CI: 0.98-7.48, P=0.05)). Squamous cell carcinoma incidence tended to be lower in persons with serum 25(OH)-vitamin D concentrations above 75 nmol  l(-1) compared with those below 75 nmol  l(-1) (OR=0.67 (95% CI: 0.44-1.03, P=0.07)). Vitamin D status was not associated with skin cancer incidence when participants were classified as above or below 50 nmol  l(-1) 25(OH)-vitamin D. Our findings do not indicate that the carcinogenicity of high sun exposure can be counteracted by high vitamin D status. High sun exposure is to be avoided as a means to achieve high vitamin D status.

Embodying multiplicity : the independent dancer's moving identity

In this article, I argue for an acknowledgement of the significance of the dancer’s role in the creation of independent contemporary dance. I propose the term ‘moving identity’ to outline the independent contemporary dancer’s ‘way of moving’ which could be perceived as the accumulation of various factors including training approaches, choreographic movement traces and anatomical structures. The concept of the moving identity allows us to appreciate the dancer’s unique signature movement style as the collation of embodied experiences into a unique way of moving. However, the moving identity is also open to change when the dancer encounters new choreography and the choreographer. Professional dance training produces particular types of dancers, depending on the techniques with which they engage. I demonstrate how the independent contemporary dancer troubles this distinctiveness by engaging with a multitude of movement styles and approaches throughout a career. This leads me to a fresh description of the dancer’s activity through the lens of Deleuzean concepts of multiplicity and de-stratification. Finally, I propose a definition of the dancer as a fluid and mutable body-in-flux with the creative potential to significantly influence the outcome of the choreographic process.

Habituated objects : everyday tangibles that foster the independent living of an elderly woman

The boundaries between 'the digital' and our everyday physical world are dissolving as we develop more physical ways of interacting with computing. This forum presents some of the topics discussed in the colorful multidisciplinary field of tangible and embodied interaction

CD4+ tumor infiltrating lymphocytes are prognostic and independent of R-IPI in patients with DLBCL receiving R-CHOP chemo-immunotherapy

Despite the Revised International Prognostic Index's (R-IPI) undoubted utility in diffuse large B-cell lymphoma (DLBCL), significant clinical heterogeneity within R-IPI categories persists. Emerging evidence indicates that circulating host immunity is a robust and R-IPI independent prognosticator, most likely reflecting the immune status of the intratumoral microenvironment. We hypothesized that direct quantification of immunity within lymphomatous tissue would better permit stratification within R-IPI categories. We analyzed 122 newly diagnosed consecutive DLBCL patients treated with rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) chemo-immunotherapy. Median follow-up was 4 years. As expected, the R-IPI was a significant predictor of outcome with 5-year overall survival (OS) 87% for very good, 87% for good, and 51% for poor-risk R-IPI scores (P < 0.001). Consistent with previous reports, systemic immunity also predicted outcome (86% OS for high lymphocyte to monocyte ratio [LMR], versus 63% with low LMR, P = 0.01). Multivariate analysis confirmed LMR as independently prognostic. Flow cytometry on fresh diagnostic lymphoma tissue, identified CD4+ T-cell infiltration as the most significant predictor of outcome with ≥23% infiltration dividing the cohort into high and low risk groups with regard to event-free survival (EFS, P = 0.007) and OS (P = 0.003). EFS and OS were independent of the R-IPI and LMR. Importantly, within very good/good R-IPI patients, CD4+ T-cells still distinguished patients with different 5 year OS (high 96% versus low 63%, P = 0.02). These results illustrate the importance of circulating and local intratumoral immunity in DLBCL treated with R-CHOP.

Confirmation that Xq27 and Xq28 are susceptibility loci for migraine in independent pedigrees and a case-control cohort

Investigations into migraine genetics have suggested that susceptibility loci exist on the X chromosome. These reports are supported by evidence that demonstrates male probands as having a higher proportion of affected first-degree relatives as well as the female preponderance of 3:1 that the disorder displays. We have previously implicated the Xq24-28 locus in migraine using two independent multigenerational Australian pedigrees that demonstrated excess allele sharing at the Xq24, Xq27 and Xq28 loci. Here, we expand this work to investigate a further six independent migraine pedigrees using 11 microsatellite markers spanning the Xq27–28 region. Furthermore, 11 candidate genes are investigated in an Australian case-control cohort consisting of 500 cases and 500 controls. Microsatellite analysis showed evidence of excess allele sharing to the Xq27 marker DXS8043 (LOD* 1.38 P = 0.005) in MF879 whilst a second independent pedigree showed excess allele sharing to DXS8061 at Xq28 (LOD* 1.5 P = 0.004). Furthermore, analysis of these key markers in a case control cohort showed significant association to migraine in females at the DXS8043 marker (T1 P = 0.009) and association with MO at DXS8061 (T1 P = 0.05). Further analysis of 11 key genes across these regions showed significant association of a three-marker risk haplotype in the NSDHL gene at Xq28 (P = 0.0082). The results of this study add further support to the presence of migraine susceptibility loci on chromosome Xq27 and Xq28 as well as point to potential candidate genes in the regions that warrant further investigation.