Allelic variation investigation of the estrogen receptor within an Australian multiple sclerosis population

Multiple Sclerosis (MS) is a central nervous system (CNS) chronic inflammatory demyelinating disease leading to various neurological disabilities. The disorder is more prevalent for women with a ratio of 3:2 female to male. Objectives: To investigate variation within the estrogen receptor 1 (ESR1) polymorphism gene in an Australian MS case-control population using two intragenic restriction fragment length polymorphisms; the G594A located in exon 8 detected with the BtgI restriction enzyme and T938C located in intron 1, detected with PvuII. One hundred and ten Australian MS patients were studied, with patients classified clinically as Relapsing Remitting MS (RR-MS), Secondary Progressive MS (SP-MS) or Primary Progressive MS (PP-MS). Also, 110 age, sex and ethnicity matched controls were investigated as a comparative group. No significant difference in the allelic distribution frequency was found between the case and control groups for the ESR1 PvuII (P = 0.50) and Btg1 (P = 0.45) marker. Our results do not support a role for these two ESR1 markers in multiple sclerosis susceptibility, however other markers within ESR1 should not be excluded for potential involvement in the disorder.

Investigation of the low-density lipoprotein receptor gene and cholesterol as a risk factor for migraine

The Low-Density Lipoprotein Receptor (LDLR) gene is a cell surface receptor that plays an important role in cholesterol homeostasis. We investigated the (TA)n polymorphism in exon 18 of the LDLR gene on chromosome 19p13.2 performing an association analysis in 244 typical migraine-affected patients, 151 suffering from migraine with aura (MA), 96 with migraine without aura (MO) and 244 unaffected controls. The populations consisted of Caucasians only, and controls were age- and sex-matched. The results showed no significant difference between groups for allele frequency distributions of the (TA)n polymorphism even after separation of the migraine-affected individuals into subgroups of MA and MO affected patients. This is in contradiction to Mochi et al. who found a positive association of this variant with MO. Our study discusses possible differences between the two studies and extends this research by investigating circulating cholesterol levels in a migraine-affected population.

Association of a polymorphism of the angiotensin I-converting enzyme gene with essential hypertension

A polymorphism of the angiotensin I converting enzyme (ACE) gene has recently been reported and analysis of this polymorphism has indicated that it is associated with several cardiovascular diseases. However, the results are still controversial and such association has not yet been established conclusively. To determine whether the ACE gene may be responsible for essential hypertension in a Japanese population, we also compared the distribution of genotypes and the allele frequency of this polymorphism in our findings of a Japanese population with these features in other countries. Eighty-seven hypertensive patients with a family history of essential hypertension and 95 normotensive patients whose parents had no such history were enrolled in the study. Polymorphism of the ACE gene was determined by using the polymerase chain reaction. Homozygotes for this polymorphism had either a 490-bp band (II) or a 190-bp band (DD) and heterozygotes had both bands (ID). In hypertensive subjects, the numbers and frequency of the ACE genotypes were: II, 44 (0.51); ID, 26 (0.30); DD, 17 (0.19). In normotensive subjects these were: II, 35 (0.37); ID, 43 (0.45); DD, 17 (0.18). There were no significant differences between the two groups in derived allele frequencies (chi 2 = 1.41). The difference between the overall allelic frequency in Japan and that reported in several other countries was significant. We did not find any association between ACE gene polymorphism and essential hypertension in Japan. However, there were significant differences in derived allele frequencies between our findings in a Japanese population and those reported from Europe and Australia.

An investigation of the 5-HT2C receptor gene as a migraine candidate gene

Migraine is a common complex disorder, currently classified into two main subtypes, migraine with aura (MA) and migraine without aura (MO). The strong preponderance of females to males suggests an X-linked genetic component. Recent studies have identified an X chromosomal susceptibility region (Xq24-q28) in two typical migraine pedigrees. This region harbours a potential candidate gene for the disorder, the serotonin receptor 2C (5-HT2C) gene. This study involved a linkage and association approach to investigate two single nucleotide variants in the 5-HT2C gene. In addition, exonic coding regions of the 5-HT2C gene were also sequenced for mutations in X-linked migraine pedigrees. Results of this study did not detect any linkage or association, and no disease causing mutations were identified. Hence, results for this study do not support a significant role of the 5-HT 2C gene in migraine predisposition. © 2003 Wiley-Liss, Inc.

Independent, marked associations of alleles of the insulin receptor and dipeptidyl carboxypeptidase-I genes with essential hypertension

1. There is evidence to suggest that essential hypertension is a polygenic disorder and that it arises from yet-to-be-identified predisposing variants of certain genes that influence blood pressure. The cloning of various hormone, enzyme, adrenoceptor and hormone receptor genes whose products are involved in blood pressure control and the identification of polymorphisms of these has permitted us to test their genetic association with hypertension. 2. Cross-sectional analyses of a number of candidate gene markers were performed in hypertensive and normotensive subjects who were selected on the basis of both parents being either hypertensive or normotensive, respectively, and the difference in total alleles on all chromosomes for each polymorphism between the hypertensive and normotensive groups was test by χ analysis with one degree of freedom. 3. A marked association was observed between hypertension and insertion alleles of polymorphisms of the insulin receptor gene (INSR) (P<0.0040) and the dipeptidyl carboxypeptidase-1 (angiotensin I-converting enzyme; kininase II) gene (DCP1) (P<0.0018). No association with hypertension was evident, however, for polymorphisms of the growth hormone, low-density lipoprotein receptor, renal kallikrein, α2- and β1-adrenoreceptor, atrial natriuretic factor and insulin genes. 4. All but one of the hypertensive subjects had at least one of the hypertension-associated alleles, and although subjects homozygous for both were three times more frequent in the hypertensive group, examination of the nine possible genotypes suggested that the INSR and DCP1 alleles are independent markers for hypertension. 5. The present results suggest that genetic variant(s) in close linkage disequilibrium with polymorphisms at INSR and DCP1 may be involved in part in the aetiology of essential hypertension.

In the shadow of the enlightenment : Le Corbusier, Le Faisceau and Georges Valois

On 9 January 1927 Le Corbusier materialised on the front cover of the Faisceau journal edited by Georges Valois Le Nouveau Siècle which printed the single-point perspective of Le Corbusier’s Plan Voisin and an extract from the architect’s discourse in Urbanisme. In May Le Corbusier presented slides of his urban designs at a fascist rally. These facts have been known ever since the late 1980s when studies emerged in art history that situated Le Corbusier’s philosophy in relation to the birth of twentieth-century fascism in France—an elision in the dominant reading of Le Corbusier’s philosophy, as a project of social utopianism, whose received genealogy is Saint-Simon and Charles Fourier. Le Corbusier participated with the first group in France to call itself fascist, Valois’s militant Faisceau des Combattants et Producteurs, the “Blue Shirts,” inspired by the Italian “Fasci” of Mussolini. Thanks to Mark Antliff, we know the Faisceau did not misappropriate Le Corbusier’s plans, in some remote quasi-symbolic sense, rather Valois’s organisation was premised on the redesign of Paris based on Le Corbusier’s schematic designs. Le Corbusier’s Urbanisme was considered the “prodigious” model for the fascist state Valois called La Cité Française – after his mentor the anarcho-syndicalist Georges Sorel. Valois stated that Le Corbusier’s architectural concepts were “an expression of our profoundest thoughts,” the Faisceau, who “saw their own thought materialized” on the pages of Le Corbusier’s plans. The question I pose is, In what sense is Le Corbusier’s plan a complete representation of La Cité? For Valois, the fascist city “represents the collective will of La Cité” invoking Enlightenment philosophy, operative in Sorel, namely Rousseau, for whom the notion of “collective will” is linked to the idea of political representation: to ‘stand in’ for someone or a group of subjects i.e. the majority vote. The figures in Voisin are not empty abstractions but the result of “the will” of the “combatant-producers” who build the town. Yet, the paradox in anarcho-syndicalist anti-enlightenment thought – and one that became a problem for Le Corbusier – is precisely that of authority and representation. In Le Corbusier’s plan, the “morality of the producers” and “the master” (the transcendent authority that hovers above La Cité) is lattened into a single picture plane, thereby abolishing representation. I argue that La Cité pushed to the limits of formal abstraction by Le Corbusier thereby reverts to the Enlightenment myth it first opposed, what Theodor Adorno would call the dialectic of enlightenment.

Writing the oriental woman : an examination of the representation of Japanese women in contemporary Australian crime fiction

This study considers the challenges in representing women from other cultures in the crime fiction genre. The study is presented in two parts; an exegesis and a creative practice component consisting of a full length crime fiction novel, Batafurai. The exegesis examines the historical period of a section of the novel—post-war Japan—and how the area of research known as Occupation Studies provides an insight into the conditions of women during this period. The exegesis also examines selected postcolonial theory and its exposition of representations of the 'other' as a western construct designed to serve Eurocentric ends. The genre of crime fiction is reviewed, also, to determine how characters purportedly representing Oriental cultures are constricted by established stereotypes. Two case studies are examined to investigate whether these stereotypes are still apparent in contemporary Australian crime fiction. Finally, I discuss my own novel, Batafurai, to review how I represented people of Asian background, and whether my attempts to resist stereotype were successful. My conclusion illustrates how novels written in the crime fiction genre are reliant on strategies that are action-focused, rather than character-based, and thus often use easily recognizable types to quickly establish frameworks for their stories. As a sub-set of popular fiction, crime fiction has a tendency to replicate rather than challenge established stereotypes. Where it does challenge stereotypes, it reflects a territory that popular culture has already visited, such as the 'female', 'black' or 'gay' detective. Crime fiction also has, as one of its central concerns, an interest in examining and reinforcing the notion of societal order. It repeatedly demonstrates that crime either does not pay or should not pay. One of the ways it does this is to contrast what is 'good', known and understood with what is 'bad', unknown, foreign or beyond our normal comprehension. In western culture, the east has traditionally been employed as the site of difference, and has been constantly used as a setting of contrast, excitement or fear. Crime fiction conforms to this pattern, using the east to add a richness and depth to what otherwise might become a 'dry' tale. However, when used in such a way, what is variously eastern, 'other' or Oriental can never be paramount, always falling to secondary side of the binary opposites (good/evil, known/unknown, redeemed/doomed) at work. In an age of globalisation, the challenge for contemporary writers of popular fiction is to be responsive to an audience that demands respect for all cultures. Writers must demonstrate that they are sensitive to such concerns and can skillfully manage the tensions caused by the need to deliver work that operates within the parameters of the genre, and the desire to avoid offence to any cultural or ethnic group. In my work, my strategy to manage these tensions has been to create a back-story for my characters of Asian background, developing them above mere genre types, and to situate them with credibility in time and place through appropriate historical research.

The ISR and ESR scales : measures of the project manager-stakeholder relationship

In this paper, we develop two stakeholder relationships scales. These scales assess project managers’ perceived competence in establishing and maintaining high quality, effective relationships with people internal to the project as well as those stakeholders who are external to the project. We developed the scales using an online survey study of three hundred and seventy three complex project managers from a sub-set of the Australian Defence Industry. Both the internal stakeholder relationships’ scale and the external stakeholder relationships’ scale demonstrated validity and reliability. This research has implications for the interpersonal work relationships’ literature and the stakeholder management literature. We recommend future research tests these scales with multiple samples, across different project types and project industries. The stakeholder relationships’ scales should be versatile enough to be applied to project management generally but are best suited to large-scale complex project environments.

Overexpression of the mammalian target of rapamycin (mTOR) and angioinvasion are poor prognostic factors in early stage NSCLC: A verification study

Background: A recent study by Dhillon et al. [12], identified both angioinvasion and mTOR as prognostic biomarkers for poor survival in early stage NSCLC. The aim of this study was to verify the above study by examining the angioinvasion and mTOR expression profile in a cohort of early stage NSCLC patients and correlate the results to patient clinico-pathological data and survival. Methods: Angioinvasion was routinely recorded by the pathologist at the initial assessment of the tumor following resection. mTOR was evaluated in 141 early stage (IA-IIB) NSCLC patients (67 - squamous; 60 - adenocarcinoma; 14 - others) using immunohistochemistry (IHC) analysis with an immunohistochemical score (IHS) calculated (% positive cells × staining intensity). Intensity was scored as follows: 0 (negative); 1+ (weak); 2+ (moderate); 3+ (strong). The range of scores was 0-300. Based on the previous study a cut-off score of 30 was used to define positive versus negative patients. The impact of angioinvasion and mTOR expression on prognosis was then evaluated. Results: 101 of the 141 tumors studied expressed mTOR. There was no difference in mTOR expression between squamous cell carcinoma and adenocarcinoma. Angioinvasion (p= 0.024) and mTOR staining (p= 0.048) were significant univariate predictors of poor survival. Both remained significant after multivariate analysis (p= 0.037 and p= 0.020, respectively). Conclusions: Our findings verify angioinvasion and mTOR expression as new biomarkers for poor outcome in patients with early stage NSCLC. mTOR expressing patients may benefit from novel therapies targeting the mTOR survival pathway. © 2011 Elsevier Ireland Ltd.

Randomized phase II trial of the efficacy and safety of trastuzumab combined with docetaxel in patients with human epidermal growth factor receptor 2-positive metastatic breast cancer administered as first-line treatment : the M77001 study group

Purpose: This randomized, multicenter trial compared first-line trastuzumab plus docetaxel versus docetaxel alone in patients with human epidermal growth factor receptor 2 (HER2)-positive metastatic breast cancer (MBC). Patients and Methods: Patients were randomly assigned to six cycles of docetaxel 100 mg/m 2 every 3 weeks, with or without trastuzumab 4 mg/kg loading dose followed by 2 mg/kg weekly until disease progression. Results: A total of 186 patients received at least one dose of the study drug. Trastuzumab plus docetaxel was significantly superior to docetaxel alone in terms of overall response rate (61% v 34%; P = .0002), overall survival (median, 31.2 v 22.7 months; P = .0325), time to disease progression (median, 11.7 v 6.1 months; P = .0001), time to treatment failure (median, 9.8 v 5.3 months; P = .0001), and duration of response (median, 11.7 v 5.7 months; P = .009). There was little difference in the number and severity of adverse events between the arms. Grade 3 to 4 neutropenia was seen more commonly with the combination (32%) than with docetaxel alone (22%), and there was a slightly higher incidence of febrile neutropenia in the combination arm (23% v 17%). One patient in the combination arm experienced symptomatic heart failure (1%). Another patient experienced symptomatic heart failure 5 months after discontinuation of trastuzumab because of disease progression, while being treated with an investigational anthracycline for 4 months. Conclusion: Trastuzumab combined with docetaxel is superior to docetaxel alone as first-line treatment of patients with HER2-positive MBC in terms of overall survival, response rate, response duration, time to progression, and time to treatment failure, with little additional toxicity. © 2005 by American Society of Clinical Oncology.

Dynamic contrast-enhanced magnetic resonance imaging as a biomarker for the pharmacological response of PTK787/ZK 222584, an inhibitor of the vascular endothelial growth factor receptor tyrosine kinases, in patients with advanced colorectal cancer and liver metastases: Results from two phase I studies

Purpose: PTK787/ZK 222584 (PTK/ZK), an orally active inhibitor of vascular endothelial growth factor (VEGF) receptor tyrosine kinases, inhibits VEGF-mediated angiogenesis. The pharmacodynamic effects of PTK/ZK were evaluated by assessing changes in contrast-enhancement parameters of metastatic liver lesions using dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) in patients with advanced colorectal cancer treated in two ongoing, dose-escalating phase I studies. Patients and Methods: Twenty-six patients had DCE-MRI performed at baseline, day 2, and at the end of each 28-day cycle. Doses of oral PTK/ZK ranged from 50 to 2000 mg once daily. Tumor permeability and vascularity were assessed by calculating the bidirectional transfer constant (Ki). The percentage of baseline Ki (% of baseline Ki) at each time point was compared with pharmacokinetic and clinical end points. Results: A significant negative correlation exists between the % of baseline Ki and increase in PTK/ZK oral dose and plasma levels (P = .01 for oral dose; P = .0001 for area under the plasma concentration curve at day 2). Patients with a best response of stable disease had a significantly greater reduction in Ki at both day 2 and at the end of cycle 1 compared with progressors (mean difference in % of baseline Ki, 47%, P = .004%; and 51%, P = .006; respectively). The difference in % of baseline Ki remained statistically significant after adjusting for baseline WHO performance status. Conclusion: These findings should help to define a biologically active dose of PTK/ZK. These results suggest that DCE-MRI may be a useful biomarker for defining the pharmacological response and dose of angiogenesis inhibitiors, such as PTK/ZK, for further clinical development. © 2003 by American Society of Clinical Oncology.

On the beach : exploring the complex egalitarianism of the Australian beach

Australia, internationally, is known as a beach loving country, particularly in popular culture. The beach did not figure significantly in academic discussion before the 1980s when Fiske, Hodge, and Turner (1987, 54) researched the beach as a space of myth, seeing it as an integral part of the modern Australian identity. One common myth in Australia is that the beach is an equaliser, a place of multiple ethnicities, shapes, sizes, and genders (Dutton, 1985). I agree that the beach remains a significant aspect of Australian identity; however, limiting its meaning to a mythic space contributing to a homogenous national identity is not adequate. This paper will explore how Australian texts comment on or challenge the myth of the beach as an egalitarian space. I argue that recent Australian texts show a more complex, layered representation of this concept; and that the beach also in this respect can no longer be understood as a myth transcending difference.

A preliminary study of the effects of Tai Chi and Qigong medical exercise on indicators of metabolic syndrome, glycaemic control, health-related quality of life, and psychological health in adults with elevated blood glucose

Objectives To evaluate the feasibility, acceptability and effects of a Tai Chi and Qigong exercise programme in adults with elevated blood glucose. Design, Setting, and Participants A single group pre–post feasibility trial with 11 participants (3 male and 8 female; aged 42–65 years) with elevated blood glucose. Intervention Participants attended Tai Chi and Qigong exercise training for 1 to 1.5 h, 3 times per week for 12 weeks, and were encouraged to practise the exercises at home. Main Outcome Measures Indicators of metabolic syndrome (body mass index (BMI), waist circumference, blood pressure, fasting blood glucose, triglycerides, HDL-cholesterol); glucose control (HbA1c, fasting insulin and insulin resistance (HOMA)); health-related quality of life; stress and depressive symptoms. Results There was good adherence and high acceptability. There were significant improvements in four of the seven indicators of metabolic syndrome including BMI (mean difference −1.05, p<0.001), waist circumference (−2.80 cm, p<0.05), and systolic (−11.64 mm Hg, p<0.01) and diastolic blood pressure (−9.73 mm Hg, p<0.001), as well as in HbA1c (−0.32%, p<0.01), insulin resistance (−0.53, p<0.05), stress (−2.27, p<0.05), depressive symptoms (−3.60, p<0.05), and the SF-36 mental health summary score (5.13, p<0.05) and subscales for general health (19.00, p<0.01), mental health (10.55, p<0.01) and vitality (23.18, p<0.05). Conclusions The programme was feasible and acceptable and participants showed improvements in metabolic and psychological variables. A larger controlled trial is now needed to confirm these promising preliminary results.

Social and traditional entrepreneurial intention : what is the difference?

The concept of entrepreneurship has developed during the past decades and has a long history in the business sector. Miller et al. (2009) refer that entrepreneurship is an important part of the economic scenery, providing opportunities and jobs for substantial numbers of people. Audresch et al. (2002) clarify how the positive and statistically robust link between entrepreneurship and economic growth has been indisputably verified across a wide spectrum of units and observation, spanning the establishment, the enterprise, the industry, the region and the country. In the literature there has been an evolution and intense debate about the role of entrepreneurship as a field of research and about the creation of a conceptual framework for the entrepreneurship field as a whole. Shane and Venkataraman (2000) define the field of entrepreneurship as the scholarly examination of how, by whom, and with what effects opportunities to create future goods and services are discovered, evaluated, and exploited. For this reason the field involves the study of sources of opportunities; the processes of discovery, evaluation, and exploitation of opportunities; and the set of individuals who discover, evaluate, and exploit them.

Perioperative medication management: expanding the role of the preadmission clinic pharmacist in a single centre, randomised controlled trial of collaborative prescribing

Objectives Current evidence to support non-medical prescribing is predominantly qualitative, with little evaluation of accuracy, safety and appropriateness. Our aim was to evaluate a new model of service for the Australia healthcare system, of inpatient medication prescribing by a pharmacist in an elective surgery preadmission clinic (PAC) against usual care, using an endorsed performance framework. Design Single centre, randomised controlled, two-arm trial. Setting Elective surgery PAC in a Brisbane-based tertiary hospital. Participants 400 adults scheduled for elective surgery were randomised to intervention or control. Intervention A pharmacist generated the inpatient medication chart to reflect the patient's regular medication, made a plan for medication perioperatively and prescribed venous thromboembolism (VTE) prophylaxis. In the control arm, the medication chart was generated by the Resident Medical Officers. Outcome measures Primary outcome was frequency of omissions and prescribing errors when compared against the medication history. The clinical significance of omissions was also analysed. Secondary outcome was appropriateness of VTE prophylaxis prescribing. Results There were significantly less unintended omissions of medications: 11 of 887 (1.2%) intervention orders compared with 383 of 1217 (31.5%) control (p<0.001). There were significantly less prescribing errors involving selection of drug, dose or frequency: 2 in 857 (0.2%) intervention orders compared with 51 in 807 (6.3%) control (p<0.001). Orders with at least one component of the prescription missing, incorrect or unclear occurred in 208 of 904 (23%) intervention orders and 445 of 1034 (43%) controls (p<0.001). VTE prophylaxis on admission to the ward was appropriate in 93% of intervention patients and 90% controls (p=0.29). Conclusions Medication charts in the intervention arm contained fewer clinically significant omissions, and prescribing errors, when compared with controls. There was no difference in appropriateness of VTE prophylaxis on admission between the two groups.