Bioequivalence of two tablet formulations of capecitabine and exploration of age, gender, body surface area, and creatinine clearance as factors influencing systemic exposure in cancer patients

Purpose: The objective of the study was to assess the bioequivalence of two tablet formulations of capecitabine and to explore the effect of age, gender, body surface area and creatinine clearance on the systemic exposure to capecitabine and its metabolites. Methods: The study was designed as an open, randomized two-way crossover trial. A single oral dose of 2000 mg capecitabine was administered on two separate days to 25 patients with solid tumors. On one day, the patients received four 500-mg tablets of formulation B (test formulation) and on the other day, four 500-mg tablets of formulation A (reference formulation). The washout period between the two administrations was between 2 and 8 days. After each administration, serial blood and urine samples were collected for up to 12 and 24 h, respectively. Unchanged capecitabine and its metabolites were determined in plasma using LC/MS-MS and in urine by NMRS. Results: Based on the primary pharmacokinetic parameter, AUC(0-∞) of 5'-DFUR, equivalence was concluded for the two formulations, since the 90% confidence interval of the estimate of formulation B relative to formulation A of 97% to 107% was within the acceptance region 80% to 125%. There was no clinically significant difference between the t(max) for the two formulations (median 2.1 versus 2.0 h). The estimate for C(max) was 111% for formulation B compared to formulation A and the 90% confidence interval of 95% to 136% was within the reference region 70% to 143%. Overall, these results suggest no relevant difference between the two formulations regarding the extent to which 5'-DFUR reached the systemic circulation and the rate at which 5'-DFUR appeared in the systemic circulation. The overall urinary excretions were 86.0% and 86.5% of the dose, respectively, and the proportion recovered as each metabolite was similar for the two formulations. The majority of the dose was excreted as FBAL (61.5% and 60.3%), all other chemical species making a minor contribution. Univariate and multivariate regression analysis to explore the influence of age, gender, body surface area and creatinine clearance on the log-transformed pharmacokinetic parameters AUC(0-∞) and C(max) of capecitabine and its metabolites revealed no clinically significant effects. The only statistically significant results were obtained for AUC(0-∞) and C(max) of intact drug and for C(max) of FBAL, which were higher in females than in males. Conclusion: The bioavailability of 5'-DFUR in the systemic circulation was practically identical after administration of the two tablet formulations. Therefore, the two formulations can be regarded as bioequivalent. The variables investigated (age, gender, body surface area, and creatinine clearance) had no clinically significant effect on the pharmacokinetics of capecitabine or its metabolites.

A novel method for purification of low grade diatomite powders in centrifugal fields

This study presented a novel method for purification of three different grades of diatomite from China by scrubbing technique using sodiumhexametaphosphate (SHMP) as dispersant combinedwith centrifugation. Effects of pH value and dispersant amount on the grade of purified diatomitewere studied and the optimumexperimental conditions were obtained. The characterizations of original diatomite and derived products after purification were determined by scanning electron microscopy (SEM), X-ray diffraction (XRD), infrared spectroscopy (IR) and specific surface area analyzer (BET). The results indicated that the pore size distribution, impurity content and bulk density of purified diatomite were improved significantly. The dispersive effect of pH and SHMP on the separation of diatomite from clay minerals was discussed systematically through zeta potential test. Additionally, a possible purification mechanism was proposed in the light of the obtained experimental results.

Students' academic stress and welfare as perceived by the teachers

The objective of the present study was to understand the teachers' perception about students' academic stress and other welfare related issues. A group of 125 secondary and higher secondary school teachers (43 male and 82 female) from five schools located in Kolkata were covered in the study following convenience sampling technique. Data were collected by using a semi-structured questionnaire developed by the first author. Findings revealed that more than half of the teachers (55.8% male and 54.9% female) felt that today's students are not brought up in child friendly environment while an overwhelming number of teachers stated that students face some social problems (88.4% male and 96.3% female) which affects their mental health and causes stress (90.7% male and 92.7% female). However, majority of them (79.1% male and 78% female teachers), irrespective of gender, denied the fact that teaching method followed in schools could cause academic stress. Vast majority of the teachers felt that New Education System in India i.e., making Grade X examination (popularly known as secondary examination) optional will not be beneficial for students. So far as motivation of the students is concerned, introducing innovative teaching methods like project work, field visit, using audio-visual aids in the schools has been suggested by more than 95% of the teachers. This apart, most of the teachers suggested reward system in the schools in addition to taking classes seriously by the teachers and punctuality. Reduction of load of home work was also suggested by more than two-fifth teachers. Although corporal punishment has gone down, it is still practiced by some of the teachers' especially male teachers in Kolkata. Male and female teachers differed significantly with respect to two issues only (p < .05) i.e., applying corporal punishment and impact of sexual health education. Male teachers apply more corporal punishment compared to female teachers and secondly, male teachers do not forsee any negative influence of sexual health education.

Real-time video event detection in crowded scenes using MPEG derived features : a multiple instance learning approach

This paper presents an investigation into event detection in crowded scenes, where the event of interest co-occurs with other activities and only binary labels at the clip level are available. The proposed approach incorporates a fast feature descriptor from the MPEG domain, and a novel multiple instance learning (MIL) algorithm using sparse approximation and random sensing. MPEG motion vectors are used to build particle trajectories that represent the motion of objects in uniform video clips, and the MPEG DCT coefficients are used to compute a foreground map to remove background particles. Trajectories are transformed into the Fourier domain, and the Fourier representations are quantized into visual words using the K-Means algorithm. The proposed MIL algorithm models the scene as a linear combination of independent events, where each event is a distribution of visual words. Experimental results show that the proposed approaches achieve promising results for event detection compared to the state-of-the-art.

Bail and remand for young people in Australia : a national research project

Funded and endorsed by the Australasian Juvenile Justice Administrators, this is one of the first national scale research reports into the bail and remand practices for young Australians. A young person can be placed in custody on remand (ie refused bail) after being arrested by police in relation to a suspected criminal offence, before entering a plea, while awaiting trial, during trial or awaiting sentence. Although custodial remand plays an important role in Western criminal justice systems, minimising the unnecessary use of remand is important given the obligations Australia has under several UN instruments to use, as a last resort, youth detention of any kind. This research identifies trends in the use of custodial remand and explores the factors that influence its use for young people nationally and in each of Australia’s jurisdictions.

The effectiveness of non-pharmacological interventions in improving psychological outcomes for heart transplant recipients : a systematic review

Background Post-heart transplant psychological distress may both directly hinder physiological health as well as indirectly impact on clinical outcomes by increasing unhealthy behaviours, such as immunosuppression non-adherence. Reducing psychological distress for heart transplant recipients is therefore vitally important, in order to improve patients’ overall health and well-being but also clinical outcomes, such as morbidity and mortality. Evidence from other populations suggests that non-pharmacological interventions may be an effective strategy. Aim To appraise the efficacy of non-pharmacological interventions on psychological outcomes after heart transplant. Method A systematic review was conducted using the Joanna Briggs Institute methodology. Experimental and quasi-experimental studies that involved any non-pharmacological intervention for heart transplant recipients were included, provided that data on psychological outcomes were reported. Multiple electronic databases were searched for published and unpublished studies and reference lists of retrieved studies were scrutinized for further primary research. Data were extracted using a standardised data extraction tool. Included studies were assessed by two independent reviewers using standardised critical appraisal instruments. Results Three studies fulfilled the inclusion and exclusion criteria, which involved only 125 heart transplant recipients. Two studies reported on exercise programs. One study reported a web-based psychosocial intervention. While psychological outcomes significantly improved from baseline to follow-up for the recipients who received the interventions, between-group comparisons were not reported. The methodological quality of the studies was judged to be poor. Conclusions Further research is required, as we found there is insufficient evidence available to draw conclusions for or against the use of non-pharmacological interventions after heart transplant.

Identifying belief targets to increase bone marrow registry participation among students who have never donated blood

New members on bone marrow registries worldwide are needed to allow sufficient diversity in the donor pool to meet patient needs. We used the theory of planned behaviour belief-basis and surveyed students who had not donated blood previously (i.e. non-donors) (N = 150) about the behavioural, normative, and control beliefs informing their intentions to join the Australian Bone Marrow Donor Registry. Key beliefs predicting non-donors’ intentions included: viewing bone marrow donation as an invasion of the body (β = −.35), normative support from parents (β = .40), anticipating pain/side effects from giving blood (β = −.27), and lack of knowledge about how to register (β  = −.30). Few non-donors endorsed these beliefs, suggesting they are ideal targets for change in strategies encouraging bone marrow donor registration.

Phase II trial of Oxaliplatin and 5-Fluorouracil/Leucovorin combination in epithelial ovarian carcinoma relapsing within 2 years of platinum-based therapy

Objective To evaluate the efficacy and toxicity of Oxaliplatin and 5-Fluorouracil (5-FU)/Leucovorin (LV) combination in ovarian cancer relapsing within 2 years of prior platinum-based chemotherapy in a phase II trial. Methods Eligible patients had at least one prior platinum-based chemotherapy regimen, elevated CA-125 ≥ 60 IU/l, radiological evidence of disease progression and adequate hepatic, renal and bone marrow function. Patients with raised CA-125 levels alone as marker of disease relapse were not eligible. Oxaliplatin (85 mg/m 2) was given on day 1, and 5-Fluorouracil (370 mg/m 2) and Leucovorin (30 mg) was given on days 1 and 8 of a 14-day cycle. Results Twenty-seven patients were enrolled. The median age was 57 years (range 42-74 years). The median platinum-free interval (PFI) was 5 months (range 0-17 months) with only 30% of patients being platinum sensitive (PFI > 6 months). Six patients (22%) had two prior regimens of chemotherapy. A total of 191 cycles were administered (median 7; range 2-12). All patients were evaluable for toxicity. The following grade 3/4 toxicities were noted: anemia 4%; neutropenia 15%; thrombocytopenia 11%; neurotoxicity 8%; lethargy 4%; diarrhea 4%; hypokalemia 11%; hypomagnesemia 11%. Among 27 enrolled patients, 20 patients were evaluable for response by WHO criteria and 25 patients were evaluable by Rustin's CA-125 criteria. The overall response rate (RR) by WHO criteria was 30% (95% CI: 15- 52) [three complete responses (CRs) and three partial responses (PRs)]. The CA-125 response rate was 56% (95% CI: 37-73). Significantly, a 25% (95% CI: 9-53) radiological and a 50% (95% CI: 28-72) CA-125 response rate were noted in platinum resistant patients (PFI < 6 months). The median response duration was 4 months (range 3-12) and the median overall survival was 10 months. Conclusion Oxaliplatin and 5-Fluorouracil/ Leucovorin combination has a good safety profile and is active in platinum-pretreated advanced epithelial ovarian cancer. © 2004 Elsevier Inc. All rights reserved.

The Yd2 resistance to barley yellow dwarf virus is effective in barley plants but not in their leaf protoplasts

The Yd2 gene for “resistance” to barley yellow dwarf virus (BYDV) has been widely used in barley (Hordeum vulgare). We have tested Australian isolates of BYDV of varying severity against barley genotypes with and without the Yd2 gene and report here a positive relationship between symptoms and virus levels determined by ELISA. Cultivar Shannon is the result of backcrossing the resistant line CI 3208 to cultivar Proctor, a susceptible line. It appears to be intermediate in reaction to BYDV between Proctor and CI 3208, although it carries the major gene, Yd2. Unlike the whole plant studies, no significant differences were observed with regard to the ability of protoplasts derived from these various genotypes to support BYDV replication. It is therefore demonstrated for the first time that the Yd2 gene is not among the small number of resistance genes which are effective against virus replication in isolated protoplasts.

Ureaplasma parvum undergoes selection in utero resulting in genetically diverse isolates colonising the chorioamnion of fetal sheep

Ureaplasmas are the microorganisms most frequently isolated from the amniotic fluid of pregnant women and can cause chronic intrauterine infections. These tiny bacteria are thought to undergo rapid evolution and exhibit a hypermutatable phenotype; however, little is known about how ureaplasmas respond to selective pressures in utero. Using an ovine model of chronic intra-amniotic infection, we investigated if exposure of ureaplasmas to sub-inhibitory concentrations of erythromycin could induce phenotypic or genetic indicators of macrolide resistance. At 55 days gestation, 12 pregnant ewes received an intra-amniotic injection of a non-clonal, clinical U. parvum strain, followed by: (i) erythromycin treatment (IM, 30 mg/kg/day, n=6); or (ii) saline (IM, n=6) at 100 days gestation. Fetuses were then delivered surgically at 125 days gestation. Despite injecting the same inoculum into all ewes, significant differences between amniotic fluid and chorioamnion ureaplasmas were detected following chronic intra-amniotic infection. Numerous polymorphisms were observed in domain V of the 23S rRNA gene of ureaplasmas isolated from the chorioamnion (but not the amniotic fluid), resulting in a mosaic-like sequence. Chorioamnion isolates also harboured the macrolide resistance genes erm(B) and msr(D) and were associated with variable roxithromycin minimum inhibitory concentrations. Remarkably, this variability occurred independently of exposure of ureaplasmas to erythromycin, suggesting that low-level erythromycin exposure does not induce ureaplasmal macrolide resistance in utero. Rather, the significant differences observed between amniotic fluid and chorioamnion ureaplasmas suggest that different anatomical sites may select for ureaplasma sub-types within non-clonal, clinical strains. This may have implications for the treatment of intrauterine ureaplasma infections.

Facilitating local stories in post-disaster regional communities : evaluation in narrative-driven oral history projects

Cyclone Yasi struck the Cassowary Coast of Northern Queensland, Australia, in the early hours of February 3, 2011, destroying many homes and property, including the destruction of the Cardwell and district historical society’s premises. With their own homes flattened, many residents were forced to live in mobile accommodation, with extended family, or leave the area altogether. The historical society members seemed, however, particularly devastated by their flattened foreshore museum and loss of their precious collection of material. A call for assistance was made through the Oral History Association of Australia’s Queensland branch (OHAA Qld), which along with a Queensland University of Technology (QUT) research team sponsored a trip to best plan how they could start to pick up the pieces to rebuild the museum. This chapter highlights the need for communities to gather, preserve and present their own stories, in a way that is sustainable and meaningful to them – whether that be because of a disaster, or as they go about life in their contemporary communities – the key being that good advice, professional support and embedded evaluation practices at crucial moments along the way can be critically important.

The Australian screen producer in transition

The role of the screen producer is ramifying. Not only are there numerous producer categories, but the screen producer function is also found on a continuum across film, television, advertising, corporate video, and the burgeoning digital media sector. In recent years, fundamental changes to distribution and consumption practices and technologies should have had a correlate impact on screen production practices and on the role of existing screen producers. At the same time, new and recent producers are learning and practicing their craft in a field that has already been transformed by digitisation and media convergence. Our analysis of the work, experience and outlook of screen producers in this chapter is based on data collected in the Australian Screen Producer Survey (ASPS), a nation-wide survey conducted by the ARC Centre of Excellence for Creative Industries and Innovation, the media marketing firm Bergent Research, and the Centre for Screen Business at the Australian Film, Television and Radio School (AFTRS) in 2008/09 and 2011. We analyse the results to better understand the practice of screen production in a period of industry transition, and to recognise the persistence of established production cultures that serve to distinguish different industry sectors.

Silver absorption on burns after the application of Acticoat : data from pediatric patients and a porcine burn model

Silver dressings have been widely used to successfully prevent burn wound infection and sepsis. However, a few case studies have reported the functional abnormality and failure of vital organs, possibly caused by silver deposits. The aim of this study was to investigate the serum silver level in the pediatric burn population and also in several internal organs in a porcine burn model after the application of Acticoat. A total of 125 blood samples were collected from 46 pediatric burn patients. Thirty-six patients with a mean of 13.4% TBSA burns had a mean peak serum silver level of 114 microg/L, whereas 10 patients with a mean of 1.85% TBSA burns had an undetectable level of silver (<5.4 microg/L). Overall, serum silver levels were closely related to burn sizes. However, the highest serum silver was 735 microg/L in a 15-month-old toddler with 10% TBSA burns and the second highest was 367 microg/L in a 3-year old with 28% TBSA burns. In a porcine model with 2% TBSA burns, the mean peak silver level was 38 microg/L at 2 to 3 weeks after application of Acticoat and was then significantly reduced to an almost undetectable level at 6 weeks. Of a total of four pigs, silver was detected in all four livers (1.413 microg/g) and all four hearts (0.342 microg/g), three of four kidneys (1.113 microg/g), and two of four brains (0.402 microg/g). This result demonstrated that although variable, the level of serum silver was positively associated with the size of burns, and significant amounts of silver were deposited in internal organs in pigs with only 2% TBSA burns, after application of Acticoat.

Management of over-the-counter insomnia complaints in Australian community pharmacies: A standardized patient study

Objective To evaluate the current management of over-the-counter (OTC) insomnia complaints in Australian community pharmacies using standardized patient methodology. Methods Trained standardized patients visited a sample of 100 randomly selected South East Queensland community pharmacies in June 2011. The standardized patients enacted two OTC insomnia scenarios: a direct product request (DPR) (n = 50) and a symptom-based request (SBR) (n = 50). Results of the interactions were documented immediately after each visit and evaluated using the Pharmaceutical Society of Australia's WHAT STOP GO protocol as a standard comparison. Key findings Of all DPRs, 30% were handled entirely by the pharmacist, 70% of staff enquired about specific symptoms and 28% investigated the cause of insomnia. No staff investigated the frequency of product use. The DPR scenario resulted in a 92% supply of the requested doxylamine product (Restavit). In the SBR scenario, 18% of requests were handled entirely by the pharmacist, 58% of staff enquired about specific symptoms and 44% investigated the cause of insomnia. Staff recommended medicated products (38%), or herbal (78%) or non-drug techniques (18%). Investigation into smoking and alcohol intake was not undertaken in DPR or SBR interactions, while questioning on caffeine intake was undertaken in 2 and 14% of cases respectively. There were no significant differences found in the handling of sleep requests by pharmacists compared to pharmacy assistants. Conclusion The standardized patient methodology was a successful way to assess the community pharmacy counselling provided with OTC sleep requests and suboptimal staff responses were found when compared with recommended practice standards.

Language and mobility : unexpected places [Book Review]

Language and Mobility is the latest monograph by Alastair Pennycook. It is part of the series, Critical Language and Literacy Studies. Co-edited by Pennycook, along with Brian Morgan and Ryuko Kubota, the series looks at relations of power in diverse worlds of language and literacy. As the title indicates, Pennycook’s own volume explores the idea of language turning up in ‘unexpected’ places, for example, Cornish in Moonta, South Australia, a century or two after it supposedly died with its last speaker. Why is it, Pennycook asks, that we expect to find a (particular form of a) language in a particular place? This question is generated by a critical project that seeks to leverage the educational potential of everyday moments of language use...