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.

Event-related potential (ERP) correlates of impaired visuospatial memory in schizophrenia

Previous studies have reported that patients with schizophrenia demonstrate impaired performance during working memory (WM) tasks. The current study aimed to determine whether WM impairments in schizophrenia are accompanied by reduced slow wave (SW) activity during on-line maintenance of mnemonic information. Event-related potentials were obtained from patients with schizophrenia and well controls as they performed a visuospatial delayed response task. On 50% of trials, a distractor stimulus was introduced during the delay. Compared with controls, patients with schizophrenia produced less SW memory negativity, particularly over the right hemisphere, together with reduced frontal enhancement of SW memory negativity in response to distraction. The results indicate that patients with schizophrenia generate less maintenance phase neuronal activity during WM performance, especially under conditions of distraction.

Working memory correlates of three symptom clusters in schizophrenia

Examined whether discrete working memory deficits underlie positive, negative and disorganised symptoms of schizophrenia. 52 outpatients (mean age 37.5 yrs) with schizophrenia were studied using items drawn from the Positive and Negative Syndrome Scale (PANSS). Linear regression and correlational analyses were conducted to examine whether symptom dimension scores were related to performance on several tests of working memory function. Severity of negative symptoms correlated with reduced production of words during a verbal fluency task, impaired ability to hold letter and number sequences on-line and manipulate them simultaneously, reduced performance during a dual task, and compromised visuospatial working memory under distraction-free conditions. Severity of disorganisation symptoms correlated with impaired visuospatial working memory under conditions of distraction, failure of inhibition during a verbal fluency task, perseverative responding on a test of set-shifting ability, and impaired ability to judge the veracity of simple declarative statements. The present study provides evidence that the positive, negative and disorganised symptom dimensions of the PANSS constitute independent clusters, associated with unique patterns of working memory impairment.

The politics of literacy in David Almond and Dave McKean’s "The Savage" (2008)

Competency in language and literacy are central to contemporary debates about education in Anglophone nations around the world. This paper suggests that such debates are informing not just educational policy but children’s literature itself as can be seen in Almond and McKean’s The Savage. This hybrid text combines prose and graphic narrative and narration in order to tell the story of Blue, a young British boy negotiating his identity in the aftermath of his father's death. While foregrounding a narrative of ideal masculinity, The Savage enacts and privileges a formal and thematic ideal of literacy as index of individual agency and development. Almond and McKean produce a politicised understanding of language and literacy that simultaneously positions The Savage in a textual tradition of socio-culturally disenfranchised youth, and intervenes in that tradition to (perhaps ironically) affirm the very conditions previously critiqued by that very tradition. Where earlier authors such as Barry Hines sought to challenge normative accounts of language and literacy in order to indict educational policy and praxes, Almond and McKean work to naturalise the very logics of education and agency by which their protagonist has been disenfranchised. In doing so, The Savage exemplifies current approaches to education which claim to value social and cultural diversity while imposing national standardised testing predicated on assumptions about the legitimacy of uniform standards and definitions of literacy.

David Hicks and Cathie Holden (eds.) (2007). Teaching The Global Dimension. London: Routledge, Taylor & Francis Group, 212 pages.

Teaching The Global Dimension (2007) is intended for primary and secondary teachers, pre-service teachers and educators interested in fostering global concerns in the education system. It aims at linking theory and practice and is structured as follows. Part 1, the global dimension, proposes an educational framework for understanding global concerns. Individual chapters in this section deal with some educational responses to global issues and the ways in which young people might become, in Hick’s terms, more “world-minded”. In the first two chapters, Hicks presents first, some educational responses to global issues that have emerged in recent decades, and second, an outline of the evolution of global education as a specific field. As with all the chapters in this book, most of the examples are drawn from the United Kingdom. Young people’s concerns, student teachers’ views and the teaching of controversial issues, comprise the other chapters in this section. Taken collectively, the chapters in Part 2 articulate the conceptual framework for developing, teaching and evaluating a global dimension across the curriculum. Individual chapters in this section, written by a range of authors, explore eight key concepts considered necessary to underpin appropriate learning experiences in the classroom. These are conflict, social justice, values and perceptions, sustainability, interdependence, human rights, diversity and citizenship. These chapters are engaging and well structured. Their common format consists of a succinct introduction, reference to positive action for change, and examples of recent effective classroom practice. Two chapters comprise the final section of this book and suggest different ways in which the global dimension can be achieved in the primary and the secondary classroom.

An interview with Professor David Held : exploring the concepts of cosmopolitanism and democracy

David Held is the Graham Wallace Chair in Political Science, and co-director of LSE Global Governance, at the London School of Economics. He is the author of many works, such as Cosmopolitanism: Ideals and Realities (2010); The Cosmopolitanism Reader (2010), with Garrett Brown; Globalisation/AntiGlobalisation (2007), Models of Democracy (2006), Global Covenant (2004) and Global Transformations: Politics, Economics and Culture (1999). Professor Held is also the co-founder, alongside Lord Professor Anthony Giddens, of Polity Press. Professor Held is widely known for his work concerning cosmopolitan theory, democracy, and social, political and economic global improvement. His Global Policy Journal endeavours to marry academic developments with practitioner realities, and contributes to the understanding and improvement of our governing systems.

Influence of preexercise muscle glycogen content on transcriptional activity of metabolic and myogenic genes in well-trained humans

To determine whether pre-exercise muscle glycogen content influences the transcription of several early-response genes involved in the regulation of muscle growth, seven male strength-trained subjects performed one-legged cycling exercise to exhaustion to lower muscle glycogen levels (Low) in one leg compared with the leg with normal muscle glycogen (Norm) and then the following day completed a unilateral bout of resistance training (RT). Muscle biopsies from both legs were taken at rest, immediately after RT, and after 3 h of recovery. Resting glycogen content was higher in the control leg (Norm leg) than in the Low leg (435 ± 87 vs. 193 ± 29 mmol/kg dry wt; P < 0.01). RT decreased glycogen content in both legs (P < 0.05), but postexercise values remained significantly higher in the Norm than the Low leg (312 ± 129 vs. 102 ± 34 mmol/kg dry wt; P < 0.01). GLUT4 (3-fold; P < 0.01) and glycogenin mRNA abundance (2.5-fold; not significant) were elevated at rest in the Norm leg, but such differences were abolished after exercise. Preexercise mRNA abundance of atrogenes was also higher in the Norm compared with the Low leg [atrogin: ?14-fold, P < 0.01; RING (really interesting novel gene) finger: ?3-fold, P < 0.05] but decreased for atrogin in Norm following RT (P < 0.05). There were no differences in the mRNA abundance of myogenic regulatory factors and IGF-I in the Norm compared with the Low leg. Our results demonstrate that 1) low muscle glycogen content has variable effects on the basal transcription of select metabolic and myogenic genes at rest, and 2) any differences in basal transcription are completely abolished after a single bout of heavy resistance training. We conclude that commencing resistance exercise with low muscle glycogen does not enhance the activity of genes implicated in promoting hypertrophy.

Interaction of contractile activity and training history on mRNA abundance in skeletal muscle from trained athletes

Skeletal muscle displays enormous plasticity to respond to contractile activity with muscle from strength- (ST) and endurance-trained (ET) athletes representing diverse states of the adaptation continuum. Training adaptation can be viewed as the accumulation of specific proteins. Hence, the altered gene expression that allows for changes in protein concentration is of major importance for any training adaptation. Accordingly, the aim of the present study was to quantify acute subcellular responses in muscle to habitual and unfamiliar exercise. After 24-h diet/exercise control, 13 male subjects (7 ST and 6 ET) performed a random order of either resistance (8 × 5 maximal leg extensions) or endurance exercise (1 h of cycling at 70% peak O2 uptake). Muscle biopsies were taken from vastus lateralis at rest and 3 h after exercise. Gene expression was analyzed using real-time PCR with changes normalized relative to preexercise values. After cycling exercise, peroxisome proliferator-activated receptor-γ coactivator-1α (ET ∼8.5-fold, ST ∼10-fold, P < 0.001), pyruvate dehydrogenase kinase-4 (PDK-4; ET ∼26-fold, ST ∼39-fold), vascular endothelial growth factor (VEGF; ET ∼4.5-fold, ST ∼4-fold), and muscle atrophy F-box protein (MAFbx) (ET ∼2-fold, ST ∼0.4-fold) mRNA increased in both groups, whereas MyoD (∼3-fold), myogenin (∼0.9-fold), and myostatin (∼2-fold) mRNA increased in ET but not in ST (P < 0.05). After resistance exercise PDK-4 (∼7-fold, P < 0.01) and MyoD (∼0.7-fold) increased, whereas MAFbx (∼0.7-fold) and myostatin (∼0.6-fold) decreased in ET but not in ST. We conclude that prior training history can modify the acute gene responses in skeletal muscle to subsequent exercise.

Do Australian public and nonprofit nurses cope with administrative stressors?

The nursing profession in Australia and other OECD countries such as the USA and the UK, have focused on ways to recruit and retain nurses (e.g., Bartram, Joiner, & Stanton, 2004). Research has shown that the most common factors impacting negatively on retention include sources of nursing stress such as workload and work environment. While the literature has shown that nursing staff encounter these stressors, studies do not examine the effects of stress caused by an increasing degree of administrative demand placed on nurses, caused by the new public management (NPM) reform in public and nonprofit (PNP) health care organizations. At best, some studies have alluded to some aspects of administrative related stressors (vis-a-vis nursing related stressors such as death, sickness, etc), but they have not been examined in any detail. Similarly, extant research has not examined how nurses cope with these administrative stressors. These will be the main aims of the present study.

David F. Treagust : congenial soul, science educator, and international research leader

For almost a half century David F. Treafust has been an exemplary science educator who has contributed through his dedication and commitments to students, curriculum development and collaboration with teachers, and cutting edge research in science education that has impacted the field globally, nationally and locally. A hallmark of his outstanding career is his collaborative style that inspires others to produce their best work.

'In the hands of the Receivers': The Politics of Literacy in The Savage by David Almond and Dave McKean

David Almond and Dave McKean's The Savage is a hybrid prose and graphic novel which tells the story of one young man’s maturation through literacy. The protagonist learns to deal with the death of his father and his own 'savage' self by writing a graphic novel. This article reads The Savage in the context of earlier, 'Northern' literacy narrative - particularly Tony Harrison's poem "Them & [uz]" and Barry Hines' Kes — through the discourse of neoliberalism and the notion of the reluctant boy reader. It is suggested that Almond and McKean are influenced by currently dominant ideologies of gender and literacy.

Influence of field size on pupil diameter under photopic and mesopic light levels

Purpose: We investigated the interaction between adapting field size and luminance on pupil diameter when cones alone (photopic) or rods and cones (mesopic) were active. Method: Circular achromatic targets (1o to 24o diameter) were presented to eight young participants on a rectangular projector screen. The accommodative influence on pupil diameter was minimized using cycloplegia in the fixing right eye and the consensual pupil reflex was measured in the left eye. Target luminance was adjusted for each stimulus such that corneal flux density (product of field area and luminance) was constant at 3600 cd.deg2m-2 (photopic condition) and 1.49 cd.deg2m-2 (mesopic condition). Results: There were no statistically significant effects of adaptive field size on pupil diameter for either condition. Conclusion: If corneal flux density is kept constant, there will be no change in pupil diameter as the size of the stimulus field increases at either mesopic or photopic lighting levels up to at least 24°.

The complete mitochondrial genome of the gall-forming fly, Fergusonina taylori(Nelson and Yeates) (Diptera: Fergusoninidae)

The monogeneric family Fergusoninidae consists of gall-forming flies that, together with Fergusobia (Tylenchida: Neotylenchidae) nematodes, form the only known mutualistic association between insects and nematodes. In this study, the entire 16,000 bp mitochondrial genome of Fergusonina taylori Nelson and Yeates was sequenced. The circular genome contains one encoding region including 27 genes and one non-coding A þT-rich region. The arrangement of the proteincoding, ribosomal RNA (rRNA) and transfer RNA (tRNA) genes was the same as that found in the ancestral insect. Nucleotide composition is highly A þ T biased. All of the protein initiation codons are ATN, except for nad1 which begins with TTT. All 22 tRNA anticodons of F. taylori match those observed in Drosophila yakuba, and all form the typical cloverleaf structure except for tRNA-Ser (AGN) which lacks a dihydrouridine (DHU) arm. Secondary structural features of the rRNA genes of Fergusonina are similar to those proposed for other insects, with minor modifications. The mitochondrial genome of Fergusonina presented here may prove valuable for resolving the sister group to the Fergusoninidae, and expands the available mtDNA data sources for acalyptrates overall.

Sympathy for the devil [Book reviewed : "Tasmanian Devil: A Unique and Threatened Animal" by David Owen and David Pemberton]

Two representations have dominated public perceptions of the largest living marsupial carnivore, the Tasmanian devil. One is the voracious, hurricane-like innocent savage Taz of Looney Tunes cartoon fame. The other, familiar in nineteenth- and twentieth-century rural Tasmania, is the ferocious predator and scavenger that wantonly kills livestock — and perhaps even people, should they become immobilized in the wilderness at night. Devils can take prey nearly three times their size and eat more than a third of their body weight in a sitting. Even so, it is hard to imagine how this species, being only slightly larger than a fox terrier, could be so maligned in name and image...