Current status of pharmacogenomics testing for anti-tumor drug therapies : approaches to non-melanoma skin cancer

Skin cancer is one of the most commonly occurring cancer types, with substantial social, physical, and financial burdens on both individuals and societies. Although the role of UV light in initiating skin cancer development has been well characterized, genetic studies continue to show that predisposing factors can influence an individual's susceptibility to skin cancer and response to treatment. In the future, it is hoped that genetic profiles, comprising a number of genetic markers collectively involved in skin cancer susceptibility and response to treatment or prognosis, will aid in more accurately informing practitioners' choices of treatment. Individualized treatment based on these profiles has the potential to increase the efficacy of treatments, saving both time and money for the patient by avoiding the need for extensive or repeated treatment. Increased treatment responses may in turn prevent recurrence of skin cancers, reducing the burden of this disease on society. Currently existing pharmacogenomic tests, such as those that assess variation in the metabolism of the anticancer drug fluorouracil, have the potential to reduce the toxic effects of anti-tumor drugs used in the treatment of non-melanoma skin cancer (NMSC) by determining individualized appropriate dosage. If the savings generated by reducing adverse events negate the costs of developing these tests, pharmacogenomic testing may increasingly inform personalized NMSC treatment.

Baseline study of alcohol dependence among general drivers and drunk driving offenders in Guangzhou, China

This study aimed to investigate drink driving in a sample of general drivers and convicted drunk driving offenders in Guangzhou, China. The study also aimed to explore some potential factors that impact on alcohol-related driving behaviour. Samples of 406 general drivers and 101 drunk driving offenders were recruited between May and October 2012. A survey was used to collect information about demographic characteristics, knowledge, attitudes and practices related to drink driving. The Alcohol Use Disorders Identification Test (AUDIT) was used to assess possible drinking problems. The average age reported for starting to drink alcohol for both groups of participants was around 19 years old. The mean AUDIT score of general drivers was 7.4 (SD = 5.4) representing a low level of alcohol problems, and for convicted drunk driving offenders was 11.1 (SD = 5.9) representing a medium level of alcohol problems (significant difference between means, t = 5.75, p < 0.001). AUDIT scores indicated that a substantial proportion (65%) of the offenders had medium to high levels of alcohol use disorders, compared with 38.5% among general drivers. Offenders who knew the drunk driving legal limit had a lower AUDIT score (M = 9.8, SD = 5.16) than those who did not know it (M = 12.2, SD = 6.257, t = -1.987. p = 0.05). In addition, offenders who were novice drivers (licensed less than 2 years) had a higher AUDIT score (M = 16.4, SD = 7.6) than the other three driver experience categories used.

Accelerating the Mathematics Learning of Low Socio-Economic Status Junior Secondary Students : an early report

The Accelerating the Mathematics Learning of Low Socio-Economic Status Junior Secondary Students project aims to address the issues faced by very underperforming mathematics students as they enter high school. Its aim is to accelerate learning of mathematics through a vertical curriculum to enable students to access Year 10 mathematics subjects, thus improving life chances. This paper reports upon the theory underpinning this project and illustrates it with examples of the curriculum that has been designed to achieve acceleration.

Platinum-based chemotherapy in metastatic breast cancer : current status

Cisplatin and carboplatin are active in previously untreated patients with metastatic breast cancer (MBC) with mean response rates (RRs) of 50 and 32%, respectively. In pretreated patients the RR to cisplatin/carboplatin monotherapy declines markedly to <10%. Cisplatin and carboplatin have been combined with many other cytotoxics. In first-line setting high activity has been observed in combination with taxanes or vinorelbine (RRs consistently ∼60%). It appears that these newer combinations are superior to older regimens with etoposide (RRs 30 to 50%) or 5-fluorouracil (RRs 40 to 60%). Cisplatin-/carboplatin-based regimens with infusional 5-FU and epirubicin/paclitaxel/vinorelbine achieve high RRs of around 60 to 80%. However these regimens are difficult to administer in all patients because they require central venous access for continuous 5-FU infusion. In pretreated MBC the combinations of cisplatin-taxane/vinorelbine/gemcitabine or carboplatin-docetaxel/vinorelbine yield RRs of 40 to 50%, which are higher than those achieved with platinum-etoposide/5-FU. In locally advanced disease cisplatin-based regimens achieve very high RRs (>80%). This would suggest that in chemotherapy-naïve patients platinum-based therapy might have an important role to play. Additionally the synergy demonstrated between platinum compounds, taxanes and herceptin, in preclinical and clinical studies is of immense importance and the results of the two ongoing Breast Cancer International Research Group randomized phase III studies are eagerly awaited. These studies may help clarify the role of platinum compounds in the treatment of metastatic and possibly early breast cancer. © 2003 Elsevier Ltd. All rights reserved.

Satiety responsiveness in toddlerhood predicts energy intake and weight status at four years of age

The aim of this study was to examine whether maternal-report of child eating behaviour at two years predicted self-regulation of energy intake and weight status at four years. Using an ‘eating in the absence of hunger’ paradigm, children’s energy intake (kJ) from a semi-standardized lunch meal and a standardized selection of snacks were measured. Participants were 37 mother-child dyads (16 boys, Median child age = 4.4 years, Inter-quartile range = 3.7-4.5 years) recruited from an existing longitudinal study (NOURISH randomised controlled trial). All participants were tested in their own home. Details of maternal characteristics, child eating behaviours (at age two years) reported by mothers on a validated questionnaire, and measured child height and weight (at age 3.5-4 years) were sourced from existing NOURISH trial data. Correlation and partial correlation analyses were used to examine longitudinal relationships. Satiety responsiveness and Slowness in eating were inversely associated with energy intake of the lunch meal (partial r = -.40, p =.023, and partial r = -.40, p = .023) and the former was also negatively associated with BMI-for-age Z score (partial r = -.42, p = .015). Food responsiveness and Enjoyment of food were not related to energy intake or BMI Z score. None of the eating behaviours were significantly associated with energy intake of the snacks (i.e., eating in the absence of hunger). The small and predominantly ‘healthy weight’ sample of children may have limited the ability to detect some hypothesized effects. Nevertheless, the study provides evidence for the predictive validity of two eating behaviours and future research with a larger and more diverse sample should be able to better evaluate the predictive validity of other children’s early eating behaviour styles.

What makes juvenile offenders different from adult offenders?

Historically, children in criminal justice proceedings were treated much the same as adults and subject to the same criminal justice processes as adults. Until the early twentieth century, children in Australia were even subjected to the same penalties as adults, including hard labour and corporal and capital punishment (Carrington & Pereira 2009). Until the mid-nineteenth century, there was no separate category of ’juvenile offender’ in Western legal systems and children as young as six years of age were incarcerated in Australian prisons (Cunneen & White 2007). It is widely acknowledged today, however, both in Australia and internationally, that juveniles should be subject to a system of criminal justice that is separate from the adult system and that recognises their inexperience and immaturity. As such, juveniles are typically dealt with separately from adults and treated less harshly than their adult counterparts. The United Nations’ (1985: 2) Standard Minimum Rules for the Administration of Juvenile Justice (the ‘Beijing Rules’) stress the importance of nations establishing a set of laws, rules and provisions specifically applicable to juvenile offenders and institutions and bodies entrusted with the functions of the administration of juvenile justice and designed to meet the varying needs of juvenile offenders, while protecting their basic rights. In each Australian jurisdiction, except Queensland, a juvenile is defined as a person aged between 10 and 17 years of age, inclusive. In Queensland, a juvenile is defined as a person aged between 10 and 16 years, inclusive. In all jurisdictions, the minimum age of criminal responsibility is 10 years. That is, children under 10 years of age cannot be held legally responsible for their actions.

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.

Single-agent versus combination chemotherapy in patients with advanced non-small cell lung cancer and a performance status of 2 : prognostic factors and treatment selection based on two large randomized clinical trials

Purpose: Data from two randomized phase III trials were analyzed to evaluate prognostic factors and treatment selection in the first-line management of advanced non-small cell lung cancer patients with performance status (PS) 2. Patients and Methods: Patients randomized to combination chemotherapy (carboplatin and paclitaxel) in one trial and single-agent therapy (gemcitabine or vinorelbine) in the second were included in these analyses. Both studies had identical eligibility criteria and were conducted simultaneously. Comparison of efficacy and safety was performed between the two cohorts. A regression analysis identified prognostic factors and subgroups of patients that may benefit from combination or single-agent therapy. Results: Two hundred one patients were treated with combination and 190 with single-agent therapy. Objective responses were 37 and 15%, respectively. Median time to progression was 4.6 months in the combination arm and 3.5 months in the single-agent arm (p < 0.001). Median survival imes were 8.0 and 6.6 months, and 1-year survival rates were 31 and 26%, respectively. Albumin <3.5 g, extrathoracic metastases, lactate dehydrogenase ≥200 IU, and 2 comorbid conditions predicted outcome. Patients with 0-2 risk factors had similar outcomes independent of treatment, whereas patients with 3-4 factors had a nonsignificant improvement in median survival with combination chemotherapy. Conclusion: Our results show that PS2 non-small cell lung cancer patients are a heterogeneous group who have significantly different outcomes. Patients treated with first-line combination chemotherapy had a higher response and longer time to progression, whereas overall survival did not appear significantly different. A prognostic model may be helpful in selecting PS 2 patients for either treatment strategy. © 2009 by the International Association for the Study of Lung Cancer.

A metastatic neuroendocrine anaplastic small cell tumor in a patient with multiple endocrine neoplasia type 1 syndrome : assessment of disease status and response to doxorubicin, cyclophosphamide, etoposide chemotherapy through scintigraphic imaging with 111In-pentetreotide

Extrapulmonary small cell and small cell neuroendocrine tumors of unknown primary site are, in general, aggressive neoplasms with a short median survival. Like small cell lung cancer (SCLC), they often are responsive to chemotherapy and radiotherapy. Small cell lung cancer and well differentiated neuroendocrine carcinomas of the gastrointestinal tract and pancreas tend to express somatostatin receptors. These tumors may be localized in patients by scintigraphic imaging using radiolabeled somatostatin analogues. A patient with an anaplastic neuroendocrine small cell tumor arising on a background of multiple endocrine neoplasia type 1 syndrome is reported. The patient had a known large pancreatic gastrinoma and previously treated parathyroid adenopathy. At presentation, there was small cell cancer throughout the liver and skeleton. Imaging with a radiolabeled somatostatin analogue, 111In- pentetreotide (Mallinckrodt Medical B. V., Petten, Holland), revealed all sites of disease detected by routine biochemical and radiologic methods. After six cycles of chemotherapy with doxorubicin, cyclophosphamide, and etoposide, there was almost complete clearance of the metastatic disease. 111In-pentetreotide scintigraphy revealed uptake consistent with small areas of residual disease in the liver, the abdomen (in mesenteric lymph nodes), and posterior thorax (in a rib). The primary gastrinoma present before the onset of the anaplastic small cell cancer showed no evidence of response to the treatment. The patient remained well for 1 year and then relapsed with brain, lung, liver, and skeletal metastases. Despite an initial response to salvage radiotherapy and chemotherapy with carboplatin and dacarbazine, the patient died 6 months later.

Misperceptions about child sex offenders

Sexual offending against children is a highly emotive issue. It is nonetheless important that public policy initiatives to prevent and/or respond to child sexual abuse are based on the available evidence about child sex offenders. This paper addresses five common misperceptions about the perpetrators of sexual offences against children. Specifically, the issues addressed include whether all child sex offenders are ‘paedophiles’, who sexually abuse children, whether most child sex offenders were victims of sexual abuse themselves, rates of recidivism among child sex offenders and the number of children sex offenders typically abuse before they are detected by police. The evidence outlined in this paper highlights that there are few black and white answers to these questions. Perpetrators of sexual crimes against children are not, contrary to widespread opinion, a homogenous group. Rather, there are a number of varied offending profiles that characterise child sex offenders. Gaining an understanding of the nuances of this offender population is critical if children are to be protected from sexual abuse.

Accuracy of weight status perception in contemporary Australian children and adolescents

Aim: To explore weight status perception and its relation to actual weight status in a contemporary cohort of 5- to 17-year-old children and adolescents. Methods: Body mass index (BMI), derived from height and weight measurements, and perception of weight status (‘too thin’, ‘about right’ and ‘too fat’) were evaluated in 3043 participants from the Healthy Kids Queensland Survey. In children less than 12 years of age, weight status perception was obtained from the parents, whereas the adolescents self-reported their perceived weight status. Results: Compared with measured weight status by established BMI cut-offs, just over 20% of parents underestimated their child's weight status and only 1% overestimated. Adolescent boys were more likely to underestimate their weight status compared with girls (26.4% vs. 10.2%, P < 0.05) whereas adolescent girls were more likely to overestimate than underestimate (11.8% vs. 3.4%, P < 0.05). Underestimation was greater by parents of overweight children compared with those of obese children, but still less than 50% of parents identified their obese child as ‘too fat’. There was greater recognition of overweight status in the adolescents, with 83% of those who were obese reporting they were ‘too fat’. Conclusion: Whilst there was a high degree of accuracy of weight status perception in those of healthy weight, there was considerable underestimation of weight status, particularly by parents of children who were overweight or obese. Strategies are required that enable parents to identify what a healthy weight looks like and help them understand when intervention is needed to prevent further weight gain as the child gets older.

Intimate relationship status variations in violence against women : urban, suburban, and rural differences

Woman abuse varies across intimate relationship categories (e.g., marriage, divorce, separation). However, it is unclear whether relationship status variations in violence against women differ across urban, suburban, and rural areas. We test the hypothesis that rural females, regardless of their intimate partner relationship status, are at higher risk of intimate violence than their urban and suburban counterparts. Results indicate that marital status is an important aspect of the relationship between intimate victimization and geographic area and that rural divorced and separated females are victimized at rates exceeding their urban counterparts.

The association between socioeconomic status and depression in Vietnamese adults : pilot study

This study examined the prevalence of depressive symptoms and elucidated the causal pathway between socioeconomic status and depression in a community in the central region of Vietnam. The study used a combination of qualitative and quantitative research methods. Indepth interviews were applied with two local psychiatric experts and ten residents for qualitative research. A cross sectional survey with structured interview technique was implemented with 100 residents in the pilot quantitative survey. The Center for Epidemiological Studies-Depression Scale (CES-D) was applied to valuate depressive symptoms ( CES-D score over 21) and depression ( CESD core over 25). Ordinary Least Squares Regression following the three steps of Baron and Kenny’s framework was employed for testing mediation models. There was a strong social gradient with respect to depressive symptoms. People with higher education levels reported fewer depressive symptoms (lower CES-D scores). Incomes were also inversely associated with depressive symptoms, but only the ones at the bottom of the quartile income. Low level and unstable individuals in terms of occupation were associated with higher depressive symptoms compared with the highest occupation group. Employment status showed the strongest gradient with respect to its impact on the burden of depressive symptoms compared with other indicators of SES. Findings from this pilot study suggest a pattern on the negative association between socioeconomic status and depression in Vietnamese adults.

Report on a workshop to investigate the current status of environmental bio-acoustic monitoring

This workshop was supported by the Australian Centre for Ecological Analysis and Synthesis (ACEAS, http://www.aceas.org.au/), a facility of the Australian Government-funded Terrestrial Ecosystem Research Network (http://www.tern.org.au/), a research infrastructure facility established under the National Collaborative Research Infrastructure Strategy and Education Infrastructure Fund - Super Science Initiative, through the Department of Industry, Innovation, Science, Research and Tertiary Education. Hosted by: Queensland University of Technology, Brisbane, Queensland. (QUT, http://www.qut.edu.au/) Dates: 8-11 May 2012 Report Editors: Prof Stuart Parsons (Uni. Auckland, NZ) and Dr Michael Towsey (QUT). This report is a compilation of notes and discussion summaries contributed by those attending the Workshop. They have been assembled into a logical order by the editors. Another report (with photographs) can be obtained at: http://www.aceas.org.au/index.php?option=com_content&view=article&id=94&Itemid=96

French version of the Family Attitude Scale : psychometric properties and relation of attitudes to the respondent's psychiatric status

The Family Attitude Scale (FAS) is a self-report measure of critical or hostile attitudes and behaviors towards another family member, and demonstrates an ability to predict relapse in psychoses. Data are not currently available on a French version of the scale. The present study developed a French version of the FAS, using a large general population sample to test its internal structure, criterion validity and relationships with the respondents' symptoms and psychiatric diagnoses, and examined the reciprocity of FAS ratings by respondents and their partners. A total of 2072 adults from an urban population undertook a diagnostic interview and completed self-report measures, including an FAS about their partner. A subset of participants had partners who also completed the FAS. Confirmatory factor analyses revealed an excellent fit by a single-factor model, and the FAS demonstrated a strong association with dyadic adjustment. FAS scores of respondents were affected by their anxiety levels and mood, alcohol and anxiety diagnoses, and moderate reciprocity of attitudes and behaviors between the partners was seen. The French version of the FAS has similarly strong psychometric properties to the original English version. Future research should assess the ability of the French FAS to predict relapse of psychiatric disorders.