Phase III study of matrix metalloproteinase inhibitor prinomastat in non-small-cell lung cancer

Purpose: Matrix metalloproteinases (MMPs) degrade extracellular proteins and facilitate tumor growth, invasion, metastasis, and angiogenesis. This trial was undertaken to determine the effect of prinomastat, an inhibitor of selected MMPs, on the survival of patients with advanced non-small-cell lung cancer (NSCLC), when given in combination with gemcitabine-cisplatin chemotherapy. Patients and Methods: Chemotherapy-naive patients were randomly assigned to receive prinomastat 15 mg or placebo twice daily orally continuously, in combination with gemcitabine 1,250 mg/m2 days 1 and 8 plus cisplatin 75 mg/m2 day 1, every 21 days for up to six cycles. The planned sample size was 420 patients. Results: Study results at an interim analysis and lack of efficacy in another phase III trial prompted early closure of this study. There were 362 patients randomized (181 on prinomastat and 181 on placebo). One hundred thirty-four patients had stage IIIB disease with T4 primary tumor, 193 had stage IV disease, and 34 had recurrent disease (one enrolled patient was ineligible with stage IIIA disease). Overall response rates for the two treatment arms were similar (27% for prinomastat v 26% for placebo; P = .81). There was no difference in overall survival or time to progression; for prinomastat versus placebo patients, the median overall survival times were 11.5 versus 10.8 months (P = .82), 1-year survival rates were 43% v 38% (P = .45), and progression-free survival times were 6.1 v 5.5 months (P = .11), respectively. The toxicities of prinomastat were arthralgia, stiffness, and joint swelling. Treatment interruption was required in 38% of prinomastat patients and 12% of placebo patients. Conclusion: Prinomastat does not improve the outcome of chemotherapy in advanced NSCLC. © 2005 by American Society of Clinical Oncology.

Welfare surveillance, income management and new paternalism in Australia

This article discusses the situation of income support claimants in Australia, constructed as faulty citizens and flawed welfare subjects. Many are on the receiving end of complex, multi-layered forms of surveillance aimed at securing socially responsible and compliant behaviours. In Australia, as in other Western countries, neoliberal economic regimes with their harsh and often repressive treatment of welfare recipients operate in tandem with a burgeoning and costly arsenal of CCTV and other surveillance and governance assemblages. Through a program of ‘Income Management’, initially targeting (mainly) Indigenous welfare recipients in Australia’s Northern Territory, the BasicsCard (administered by Centrelink, on behalf of the Australian Federal Government’s Department of Human Services) is one example of this welfare surveillance. The scheme operates by ‘quarantining’ a percentage of a claimant’s welfare entitlements to be spent by way of the BasicsCard on ‘approved’ items only. The BasicsCard scheme raises significant questions about whether it is possible to encourage people to take responsibility for themselves if they no longer have real control over the most important aspects of their lives. Some Indigenous communities have resisted the BasicsCard, criticising it because the imposition of income management leads to a loss of trust, dignity, and individual agency. Further, income management of individuals by the welfare state contradicts the purported aim that they become less ‘welfare dependent’ and more ‘self-reliant’. In highlighting issues around compulsory income management this paper makes a contribution to the largely under discussed area of income management and welfare surveillance, with its propensity for function creep, garnering large volumes of data on BasicsCard user’s approved (and declined) purchasing decisions, complete with dates, amounts, times and locations.

Predicting invasion in grassland ecosystems: is exotic dominance the real embarrassment of richness?

Invasions have increased the size of regional species pools, but are typically assumed to reduce native diversity. However, global-scale tests of this assumption have been elusive because of the focus on exotic species richness, rather than relative abundance. This is problematic because low invader richness can indicate invasion resistance by the native community or, alternatively, dominance by a single exotic species. Here, we used a globally replicated study to quantify relationships between exotic richness and abundance in grass-dominated ecosystems in 13 countries on six continents, ranging from salt marshes to alpine tundra. We tested effects of human land use, native community diversity, herbivore pressure, and nutrient limitation on exotic plant dominance. Despite its widespread use, exotic richness was a poor proxy for exotic dominance at low exotic richness, because sites that contained few exotic species ranged from relatively pristine (low exotic richness and cover) to almost completely exotic-dominated ones (low exotic richness but high exotic cover). Both exotic cover and richness were predicted by native plant diversity (native grass richness) and land use (distance to cultivation). Although climate was important for predicting both exotic cover and richness, climatic factors predicting cover (precipitation variability) differed from those predicting richness (maximum temperature and mean temperature in the wettest quarter). Herbivory and nutrient limitation did not predict exotic richness or cover. Exotic dominance was greatest in areas with low native grass richness at the site- or regional-scale. Although this could reflect native grass displacement, a lack of biotic resistance is a more likely explanation, given that grasses comprise the most aggressive invaders. These findings underscore the need to move beyond richness as a surrogate for the extent of invasion, because this metric confounds monodominance with invasion resistance. Monitoring species' relative abundance will more rapidly advance our understanding of invasions.

Driver licensing experience of Korean Australians

Graduated licensing has been identified as the most promising approach to reducing the crash risk of novice drivers. However, research suggests that the effectiveness of graduated licensing appears to differ between urban and rural novice drivers and according to race or ethnicity. Extensive supervised driving practice as a learner driver is an important component of graduated licensing systems in Australia and many other countries. Earlier CARRS-Q research identified that falsification of logbooks was more common among particular demographic groups. The factors underlying this are not well understood. It is unclear whether this reflects a lack of understanding of the importance of supervised practice (given that it is not a licensing requirement in many countries of origin), or it reflects lack of access to vehicles and supervising drivers, or whether there is less respect for driver licensing requirements among some groups. It is possible that the importance of these factors may differ across ethnic groups, depending on socioeconomic factors and cultural attitudes to road safety. In an attempt to better understand these issues, this study presents some preliminary results of focus groups examining the experience of the Queensland Graduated Driver Licensing System by Korean-Australian novice drivers and their parents.

Knowledge and behaviours of drunk driving offenders in Guangzhou, China

Background Alcohol is a major contributor to road crashes in China (Li, Xie, Nie, & Zhang, 2012; Cochrane, & Chen, 2003). Two levels of offence are defined in legislation: the lower level is driving under the influence (DUI, also translated as “drink driving”) and the higher level is driving while intoxicated (DWI, also translated as “drunk driving”, where the driver has BAC>0.08mg/100ml). This study focuses on a 2011 legislative amendment that made drunk driving (DWI) a criminal offence. However, it is not known whether drivers are aware of the law, and whether this knowledge, their exposure to enforcement and the existence of alcohol use disorders relate to their drink driving behaviour. This study explored these relationships in a sample of convicted drunk drivers. Method A survey collected information about offenders’ knowledge and practices related to drunk driving in Guangzhou. The Alcohol Use Disorders Identification Test (AUDIT) (Babor, & Grant, 1989; Chen, & Cheng, 2005) assessed hazardous drinking levels. In total, 101 drunk driving offenders were recruited while in detention. Results Males represented 90% of the sample; the average age was 33.6 years (SD=8.7; range 17-59 years). The average age at which offenders reported starting to drink alcohol was 19.5 years (SD=4.1; range 8-30 years). Driver’s licences had been held for a median of 7 years. Knowledge about legal limits for DUI and DWI offences was surprisingly low, at 27.7% and 40.6% respectively. On average, offenders had experienced 1.5 police alcohol breath tests in the previous year (SD=1.3; range 1-10). AUDIT scores indicated that a substantial proportion of the offenders had high levels of alcohol use disorders. Higher AUDIT scores were found among the least experienced drivers, those with lack of knowledge about the legal limits, and recidivist drunk drivers. Discussion and conclusions Limited awareness of legal alcohol limits might contribute to offending; high levels of alcohol consumption by many offenders suggest that hazardous drinking levels may also contribute. Novice drivers are a concern and their higher AUDIT scores merit some followup. Overall, this study provides important information to assist in refining community education and prevention efforts to align with China’s new regulations.

Consequences of introducing mandatory reporting legislation for child sexual abuse

To improve detection of child sexual abuse, many jurisdictions have enacted mandatory reporting laws requiring selected persons to report known and suspected cases. In Ireland, the Child First approach previously incorporated only a policy-based approach to reporting. Due to a perceived lack of efficacy, the Children First Bill was drafted in 2012 to shift this policy guidance to a legislative approach. What effects will the new legislative reporting duties have on numbers of reports, and outcomes of reports, of suspected child sexual abuse? This paper will shed light on these important questions by presenting results of analyses of the introduction of legislative reporting obligations in two Australian States. Three questions will be explored: 1. Does introducing reporting legislation result in enhanced detection of child sexual abuse? 2. Do different reporter groups have different patterns of reporting? 3. What do the patterns of report numbers and outcomes indicate for child protection systems and communities?

Data requirements of hedonic models in determining the impact of infrastructure charges on new housing costs

The use of hedonic models to estimate the effects of various factors on house prices is well established. This paper examines a number of international hedonic house price models that seek to quantify the effect of infrastructure charges on new house prices. This work is an important factor in the housing affordability debate, with many governments in high growth areas having user-pays infrastructure charging policies operating in tandem with housing affordability objectives, with no empirical evidence on the impact of one on the other. This research finds there is little consistency between existing models and the data sets utilised. Specification appears dependent upon data availability rather than sound theoretical grounding. This may lead to a lack of external validity with model specification dependent upon data availability rather than sound theoretical grounding.