The eradication of compulsory retirement and age discrimination in the Australian workplace : A cause for celebration and concern

Earlier this year the Age Discrimination Act 2004 was passed by the Commonwealth government. This paper provides an overview of the Age Discrimination Act 2004 and critically examines whether it is likely to be successful in eradicating compulsory retirement and age discrimination within the workforce. Empirical studies suggesting that law reform alone is insufficient to eliminate ageist employer behaviour are discussed as is the need for public awareness campaigns. Given that compliance with the law is closely linked with normative belief, this paper also considers whether a moral duty to refrain from age discrimination can be grounded within the natural law ethic.

Vascular attack by 5,6-dimethylxanthenone-4-acetic acid combined with B7.1 (CD80)-mediated immunotherapy overcomes immune resistance and leads to the eradication of large tumors and multiple tumor foci

The promise of cancer immunotherapy is that it will not only eradicate primary tumors but will generate systemic antitumor immunity capable of destroying distant metastases. A major problem that must first be surmounted relates to the immune resistance of large tumors. Here we reveal that immune resistance can be overcome by combining immunotherapy with a concerted attack on the tumor vasculature. The functionally related antitumor drugs 5,6-dimethylxanthenone-4-acetic acid (DMXAA) and flavone acetic acid (FAA), which cause tumor vasculature collapse and tumor necrosis, were used to attack the tumor vasculature, whereas the T-cell costimulator B7.1 (CD80), which costimulates T-cell proliferation via the CD28 pathway, was used to stimulate antitumor immunity. The injection of cDNA (60–180 µg) encoding B7.1 into large EL-4 tumors (0.8 cm in diameter) established in C57BL/6 mice, followed 24 h later by i.p. administration of either DMXAA (25 mg/kg) or FAA (300 mg/kg), resulted in complete tumor eradication within 2–6 weeks. In contrast, monotherapies were ineffective. Both vascular attack and B7.1 immunotherapy led to up-regulation of heat shock protein 70 on stressed and dying tumor cells, potentially augmenting immunotherapy. Remarkably, large tumors took on the appearance of a wound that rapidly ameliorated, leaving perfectly healed skin. Combined therapy was mediated by CD8+ T cells and natural killer cells, accompanied by heightened and prolonged antitumor cytolytic activity (P < 0.001), and by a marked increase in tumor cell apoptosis. Cured animals completely rejected a challenge of 1 x 107 parental EL-4 tumor cells but not a challenge of 1 x 104 Lewis lung carcinoma cells, demonstrating that antitumor immunity was tumor specific. Adoptive transfer of 2 x 108 splenocytes from treated mice into recipients bearing established (0.8 cm in diameter) tumors resulted in rapid and complete tumor rejection within 3 weeks. Although DMXAA and B7.1 monotherapies are complicated by a narrow range of effective doses, combined therapy was less dosage dependent. Thus, a broad range of amounts of B7.1 cDNA were effective in combination with 25 mg/kg DMXAA. In contrast, DMXAA, which has a very narrow range of high active doses, was effective at a low dose (18 mg/kg) when administered with a large amount (180 µg) of B7.1 cDNA. Importantly, combinational therapy generated heightened antitumor immunity, such that gene transfer of B7.1 into one tumor, followed by systemic DMXAA treatment, led to the complete rejection of multiple untreated tumor nodules established in the opposing flank. These findings have important implications for the future direction and utility of cancer immunotherapies aimed at harnessing patients’ immune responses to their own tumors.

A randomized comparison of quadruple and triple therapies for helicobacter pylori eradication: The QUADRATE study.

Background & Aims: Direct comparisons of bismuth and proton pump inhibitor (PPI)-based triple and quadruple therapies for Helicobacter pylori eradication are lacking. To address this, a randomized study was conducted.Methods: Infected dyspeptic patients received pantoprazole 40 mg, amoxicillin 1000 mg, and clarithromycin 500 mg, all twice daily, for 7 days (PAC7); or pantoprazole 40 mg twice daily, bismuth subcitrate 108 mg, and tetracycline 500 mg, both 4 times daily, and metronidazole 200 mg 3 times daily and 400 mg at night for 7 days (PBTM7); bismuth subcitrate 108 mg and tetracycline 500 mg, both 4 times daily, and metronidazole 200 mg 3 times daily and 400 mg at night for 14 days (BTM14). Outcome was assessed with ¹³C-urea breath test.Results: Eradication rates (intention to treat [n = 405]/per protocol [n = 320]) were similar for PAC7 (78%/82%) and PBTM7 (82%/88%); the latter significantly superior to BTM14 (69%/74%; P < 0.01). Pretreatment metronidazole resistance (MR) was 53% and clarithromycin resistance was 8%. Eradication rates for primary metronidazole sensitive/resistant isolates were 74%/87% with PAC7 and 80%/81% for PBTM7, compared with 76%/55% (P < 0.02) for BTM14. Noncompliance was greater with BTM14 (15%; P < 0.001) than PAC7 (3%) or PBTM7 (6%). Moderate-severe adverse events were more common with BTM14 (45%; P < 0.001), than PAC7 (23%) or PBTM7 (25%) with more discontinuations (9%, 2%, 3%, respectively).Conclusions: One-week PPI triple therapy is well tolerated and effective. The addition of PPI to bismuth triple therapy allows reduction of treatment duration with improved efficacy and tolerability, despite a high rate of MR. Quadruple therapy appears to overcome pretreatment MR in most cases. Two-week bismuth triple therapy is significantly inferior to quadruple therapy and less well tolerated than both 1-week therapies.

The climate change and development nexus

The rapid economic success achieved by the developing countries in general, and India and China in particular, has brought the issue of climate change, which is a spin-off of development, to the fore. Economic growth is essential for the eradication of poverty and generation of wealth. However, it drives energy consumption and demand for energy which, in turn, produces toxic gases like carbon dioxide (CO2 ). Thus, the price of economic growth is climate change. The paradox lies in the fact that when economic growth is the only solution to poverty, the resultant climate change (characterized by emission of greenhouse gases) also affects the poor greatly. In this context, it is observed that while traditionally the developed countries were charged with polluting the environment globally, now the developing countries have overtaken their counterparts as polluters. The developing countries have emerged, over the years, as the agents responsible for growing pollution in the world, though they are also the victims, as most of the poor people belong to the developing countries. The author explores the nexus between climate change and development in the context of the economic growth of the developing countries and its impact on them.

The health equity dimensions of urban food systems

There is increasing recognition that the nutrition transition sweeping the world’s cities is multifaceted. Urban food and nutrition systems are beginning to share similar features, including an increase in dietary diversity, a convergence toward “Western-style” diets rich in fat and refined carbohydrate and within-country bifurcation of food supplies and dietary conventions. Unequal access to the available dietary diversity, calories, and gastronomically satisfying eating experience leads to nutritional inequalities and diet-related health inequities in rich and poor cities alike. Understanding the determinants of inequalities in food security and nutritional quality is a precondition for developing preventive policy responses. Finding common solutions to under- and overnutrition is required, the first step of which is poverty eradication through creating livelihood strategies. In many cities, thousands of positions of paid employment could be created through the establishment of sustainable and self-sufficient local food systems, including urban agriculture and food processing initiatives, food distribution centers, healthy food market services, and urban planning that provides for multiple modes of transport to food outlets. Greater engagement with the food supply may dispel many of the food anxieties affluent consumers are experiencing.

'Iron-saturated' lactoferrin is a potent natural adjuvant for augmenting cancer chemotherapy

Bovine lactoferrin (bLf), an iron-containing natural defence protein found in bodily secretions, has been reported to inhibit carcinogenesis and the growth of tumours. Here, we investigated whether natural bLf and iron-saturated forms of bLf differ in their ability to augment cancer chemotherapy. bLf was supplemented into the diet of C57BL/6 mice that were subsequently challenged subcutaneously with tumour cells, and treated by chemotherapy. Chemotherapy eradicated large (0.6 cm diameter) EL-4 lymphomas in mice that had been fed iron-saturated bLf (here designated Lf(+)) for 6 weeks prior to chemotherapy, but surprisingly not in mice that were fed lesser iron-saturated forms of bLf, including apo-bLf (4% iron saturated), natural bLf (approximately 15% iron saturated) and 50% iron-saturated bLf. Lf(+)-fed mice bearing either EL-4, Lewis lung carcinoma or B16 melanoma tumours completely rejected their tumours within 3 weeks following a single injection of either paclitaxel, doxorubicin, epirubicin or fluorouracil, whereas mice fed the control diet were resistant to chemotherapy. Lf(+) had to be fed to mice for more than 2 weeks prior to chemotherapy to be wholly effective in eradicating tumours from all mice, suggesting that it acts as a competence factor. It significantly reduced tumour vascularity and blood flow, and increased antitumour cytotoxicity, tumour apoptosis and the infiltration of tumours by leukocytes. Lf(+) bound to the intestinal epithelium and was preferentially taken up within Peyer's patches. It increased the production of Th1 and Th2 cytokines within the intestine and tumour, including TNF, IFN-gamma, as well as nitric oxide that have been reported to sensitize tumours to chemotherapy. Importantly, it restored both red and white peripheral blood cell numbers depleted by chemotherapy, potentially fortifying the mice against cancer. In summary, bLf is a potent natural adjuvant and fortifying agent for augmenting cancer chemotherapy, but needs to be saturated with iron to be effective.

Cidadania mediada : processos de democratização da política municipal no Brasil

This article discusses the notion that the persistence of “traditional” political practices weakens Brazil’s democracy.Drawing on the cases of three Brazilian municipalities administered by the Workers’ Party (PT), the author examines the space between “traditional” and “modern” and argues that successful democratization does not eradicate practices such as clientelism and patronage, but it tends to incorporate and build on these traditional political elements. Moreover, the article maintains that the democratization of municipal politics is inextricably bound up with the eradication of poverty and the construction of a responsive, state-based social safety net.

Syphilis and AIDS : historical and social comparisons

Drawing on the literatures of history, sociology, epidemiology, and microbiology, this thesis compares syphillis with human immunodeficiency virus, with special reference to the social and historical factors likely to be relevant to the control or eradication of acquired imune dificiency syndrom (AIDS). The sudden appearance of a new disease causing suffering and death in a community, engenders apprehension and fear which is often manifested as hysteria against, and vilification of, those who have the disease. This fear is greatly increased should the disease be sexually-transmitted. Syphilis in a venereal form, occured in Europe toward the end of the 15th Century. Initially it was an acute, fulminating disease which rapidly spread through Europe and Asia. Attempts to control the disease have gone through periods of either partial successes or massive failures and have ended in frustration for the authorities. When the syndrome of acquired immune deficiency (AIDS) was first reported, it was seen in Western countries in homosexual men. However, as non-homosexual community members and children became infected, it became apparent to authorities that a pandemic was accurring. Within a few years, the disease was identified worldwide. Isolation of the virus (HIV-1), and development of test for detection of carriers, plus restoration of clean blood and blood-product supplies, have reassured the community to some extent. The history of syphilis shows that neither the epidemiological medical, nor the economic political approaches to disease control work, although there are positive aspects resulting from both. It is social responses that will offer the most hope in the long term for the control of AIDS and other sexually-transmitted diseases.

Requirements for ICAM-1 immunogene therapy of lymphoma.

Intercellular cell adhesion molecule-1 (ICAM-1) is a cell-surface glycoprotein capable of eliciting bidirectional signals that activate signalling pathways in leukocytes, endothelial, and smooth muscle cells. Gene transfer of xenogeneic ICAM-1 into EL-4 lymphomas causes complete tumor rejection; however, it is unknown whether the mechanism responsible involves the "foreignness" of the ICAM-1 transgene, bidirectional signalling events, ICAM-1-receptor interaction, or a combination of the latter. To begin to address this question, we constructed four different therapeutic expression vectors encoding full-length ICAM-1, and forms in which the N-terminal ligand-binding domains and cytoplasmic tail had been deleted. Mouse EL-4 tumors (0.5 cm in diameter), which actively suppress the immune response, were significantly inhibited in their growth following injection of expression plasmids encoding either full-length xenogenic (human) ICAM-1, or a functional cytoplasmic domain-deficient form that retains ligand-binding activity. Efficacy of ICAM-1-mediated antitumor immunity was significantly augmented by administration of the antivascular drug 5,6-dimethylxanthenone-4-acetic acid (DMXAA), which suppressed blood supply to the tumor, leading to enhanced leukocyte infiltration, and complete tumor eradication in a gene dosage and CD8(+) T cell and NK cell-dependent fashion. Generation of potent cytotoxic T cell (CTL)-mediated antitumor immunity was reflected by ICAM-1-facilitated apoptosis of tumor cells in situ. In contrast, nonfunctional ICAM-1 lacking the N-terminal ligand-binding Ig domain failed to generate antitumor immunity, even in the presence of DMXAA. These studies demonstrate that ICAM-1-stimulated antitumor immunity can overcome tumor-mediated immunosuppression, particularly when employed in combination with an attack on the tumor vasculature. The ligand-binding domain of ICAM-1 is essential for generating antitumor immunity, whereas the cytoplasmic domain and bidirectional activation of tumor signalling pathways are not essential.

Nurses' role in medication safety

Aim To explore the nurses role in the process of medication management and identify the challenges associated with safe medication management in contemporary clinical practice.
Background Medication errors have been a long-standing factor affecting consumer safety. The nursing profession has been identified as essential to the promotion of patient safety.
Evaluation A review of literature on medication errors and the use of electronic prescribing in medication errors.
Key issues Medication management requires a multidisciplinary approach and interdisciplinary communication is essential to reduce medication errors. Information technologies can help to reduce some medication errors through eradication of transcription and dosing errors. Nurses must play a major role in the design of computerized medication systems to ensure a smooth transition to such as system.
Conclusion The nurses roles in medication management cannot be over-emphasized. This is particularly true when designing a computerized medication system.
Implication for nursing management The adoption of safety measures during decision making that parallel those of the aviation industry safety procedures can provide some strategies to prevent medication error. Innovations in information technology offer potential mechanisms to avert adverse events in medication management for nurses.

Remedying discrimination : the limits of the law and the need for a systemic approach

Very few discrimination complaints reach the courts each year. As with other civil litigation, the reasons for this include the cost of pursuing litigation and, particularly for complainants, the risk of losing or receiving less than the complainant could have negotiated prior.

Drawing on interviews with lawyers and non-legal advocates in Victoria and an analysis of successful cases in three jurisdictions, this article examines the remedy the court is likely to award in a successful discrimination complaint and considers the effect of this on the eradication of discrimination in society. A comprehensive examination of the remedies awarded in successful discrimination complaints in Victoria over a three year period shows that courts are most likely to order compensation at modest amounts and complainants are not regularly awarded their costs. A comparison with Queensland and the federal system reveals a similar experience. Even in those jurisdictions where wider remedies are available, courts rarely take the opportunity to make broad orders which could affect other similarly situated individuals or deter would-be respondents.

While it is necessary to remedy the complainant’s experience, it is also necessary to address broader, systemic discrimination and a compensation award cannot do this. Remedying discrimination with compensation is primarily a problem because it is reactive. Compensation does not address other instances of discrimination in society or achieve systemic change nor does it encourage compliance because the respondent is not required to take anticipatory action to prevent another complaint.

Based on the interpretive principles and extensive remedies provided in South Africa’s recent anti-discrimination and a study of remedies ordered by the South African Equality Courts and the Irish Equality Tribunal, the article proposes reforms to Australia’s anti-discrimination legislation to enable courts to make wider orders which target other instances of discrimination in addition to remedying the complainant’s experience.

Effect of bronchoalveolar lavage-directed therapy on pseudomonas aeruginosa infection and structural lung injury in children with cystic fibrosis

Context Early pulmonary infection in children with cystic fibrosis leads to increased morbidity and mortality. Despite wide use of oropharyngeal cultures to identify pulmonary infection, concerns remain over their diagnostic accuracy. While bronchoalveolar lavage (BAL) is an alternative diagnostic tool, evidence for its clinical benefit is lacking.

Objective To determine if BAL-directed therapy for pulmonary exacerbations during the first 5 years of life provides better outcomes than current standard practice relying on clinical features and oropharyngeal cultures.

Design, Setting, and Participants The Australasian Cystic Fibrosis Bronchoalveolar Lavage (ACFBAL) randomized controlled trial, recruiting infants diagnosed with cystic fibrosis through newborn screening programs in 8 Australasian cystic fibrosis centers. Recruitment occurred between June 1, 1999, and April 30, 2005, with the study ending on December 31, 2009.

Interventions BAL-directed (n=84) or standard (n=86) therapy until age 5 years. The BAL-directed therapy group underwent BAL before age 6 months when well, when hospitalized for pulmonary exacerbations, if Pseudomonas aeruginosa was detected in oropharyngeal specimens, and after P aeruginosa eradication therapy. Treatment was prescribed according to BAL or oropharyngeal culture results.

Main Outcome Measures Primary outcomes at age 5 years were prevalence of P aeruginosa on BAL cultures and total cystic fibrosis computed tomography (CF-CT) score (as a percentage of the maximum score) on high-resolution chest CT scan.

Results Of 267 infants diagnosed with cystic fibrosis following newborn screening, 170 were enrolled and randomized, and 157 completed the study. At age 5 years, 8 of 79 children (10%) in the BAL-directed therapy group and 9 of 76 (12%) in the standard therapy group had P aeruginosa in final BAL cultures (risk difference, −1.7% [95% confidence interval, −11.6% to 8.1%]; P=.73). Mean total CF-CT scores for the BAL-directed therapy and standard therapy groups were 3.0% and 2.8%, respectively (mean difference, 0.19% [95% confidence interval, −0.94% to 1.33%]; P=.74).

Conclusion Among infants diagnosed with cystic fibrosis, BAL-directed therapy did not result in a lower prevalence of P aeruginosa infection or lower total CF-CT score when compared with standard therapy at age 5 years.

Trial Registration anzctr.org.au Identifier: ACTRN12605000665639

Establishment of HIV-1 latency in resting CD4+ T cells depends on chemokine-induced changes in the actin cytoskeleton

Eradication of HIV-1 with highly active antiretroviral therapy (HAART) is not possible due to the persistence of long-lived, latently infected resting memory CD4+ T cells. We now show that HIV-1 latency can be established in resting CD4+ T cells infected with HIV-1 after exposure to ligands for CCR7 (CCL19), CXCR3 (CXCL9 and CXCL10), and CCR6 (CCL20) but not in unactivated CD4+ T cells. The mechanism did not involve cell activation or significant changes in gene expression, but was associated with rapid dephosphorylation of cofilin and changes in filamentous actin. Incubation with chemokine before infection led to efficient HIV-1 nuclear localization and integration and this was inhibited by the actin stabilizer jasplakinolide. We propose a unique pathway for establishment of latency by direct HIV-1 infection of resting CD4+ T cells during normal chemokine-directed recirculation of CD4+ T cells between blood and tissue.

Anthropogenic selection enhances cancer evolution in Tasmanian devil tumours

The Tasmanian Devil Facial Tumour Disease (DFTD) provides a unique opportunity to elucidate the long-term effects of natural and anthropogenic selection on cancer evolution. Since first observed in 1996, this transmissible cancer has caused local population declines by >90%. So far, four chromosomal DFTD variants (strains) have been described and karyotypic analyses of 253 tumours showed higher levels of tetraploidy in the oldest strain. We propose that increased ploidy in the oldest strain may have evolved in response to effects of genomic decay observed in asexually reproducing organisms. In this study, we focus on the evolutionary response of DFTD to a disease suppression trial. Tumours collected from devils subjected to the removal programme showed accelerated temporal evolution of tetraploidy compared with tumours from other populations where no increase in tetraploid tumours were observed. As ploidy significantly reduces tumour growth rate, we suggest that the disease suppression trial resulted in selection favouring slower growing tumours mediated by an increased level of tetraploidy. Our study reveals that DFTD has the capacity to rapidly respond to novel selective regimes and that disease eradication may result in novel tumour adaptations, which may further imperil the long-term survival of the world's largest carnivorous marsupial.