Arsenic, mode of action at biologically plausible low doses : what are the implications for low dose cancer risk?

Arsenic is an established human carcinogen. However, there has been much controversy about the shape of the arsenic response curve, particularly at low doses. This controversy has been exacerbated by the fact that the  mechanism(s) of arsenic carcinogenesis are still unclear and because there are few satisfactory animal models for arsenic-induced carcinogenesis. Recent epidemiological studies have shown that the relative risk for cancer among populations exposed to ≤60 ppb As in their drinking water is often lower than the risk for the unexposed control population. We have found that treatment of human keratinocyte and fibroblast cells with 0.1 to 1 μM arsenite (As^III) also produces a low dose protective effect against oxidative stress and DNA damage. This response includes increased transcription, protein levels and enzyme activity of several base excision repair genes, including DNA polymerase β and DNA ligase I. At higher concentrations (> 10 μM), As induces down-regulation of DNA repair, oxidative DNA damage and apoptosis. This low dose adaptive (protective) response by a toxic agent is known as hormesis and is characteristic of many agents that induce oxidative stress. A mechanistic model for arsenic carcinogenesis based on these data would predict that the low dose risk for carcinogenesis should be sub-linear. The threshold dose where toxicity outweighs protection is hard to predict based on in vitro dose response data, but might be estimated if one could determine the form (metabolite) and concentration of arsenic responsible for changes in gene regulation in the target tissues.

The roles of prior experience and the timing of misinformation presentation on young children's event memories

The current study addressed how the timing of interviews affected children's memories of unique and repeated events. Five- to six-year-olds (N= 125) participated in activities 1 or 4 times and were misinformed either 3 or 21 days after the only or last event. Although single-experience children were subsequently less accurate in the 21- versus 3-day condition, the timing of the misinformation session did not affect memories of repeated-experience children regarding invariant details. Children were more suggestible in the 21- versus 3-day condition for variable details when the test occurred soon after misinformation presentation. Thus, timing differentially affected memories of single and repeated events and depended on the combination of event-misinformation and misinformation-test delays rather than the overall retention interval.

G-CSF: function and modes of action (Review)

Since the observations in the 1960s that granulocyte-colony stimulating factor (G-CSF) stimulated the proliferation of granulocytic cells in semisolid cultures of bone marrow cells, G-CSF has established itself as a useful clinical agent for increasing levels of neutrophilic granulocytes. However, these early findings did not firmly establish whether G-CSF is a genuine regulator of granulocyte formation under normal physiological conditions or rather acts as an emergency regulator, playing an important role only under stress conditions. The advent of <gene-knockout technology> has allowed us to evaluate these questions in a physiological setting through analysis of mice with a targeted mutation of G-CSF or its receptor, while the development of relevant cell models has enabled us to dissect the molecular basis of G-CSF action. This review discusses our current state of knowledge regarding the role of G-CSF in granulopoiesis.

A qualitative examination of the experience of 'depression' in hospitalized medically ill patients

Background: Research into depression in the medically ill has progressed without sufficient attention being given to the validity, in this group, of the taxonomic categories. We aimed to describe, using qualitative interviews, the experience of 'being depressed', separating experiences that are unique to depression from experiences that are common to being ill and in hospital.
Method: Forty-nine patients hospitalized for medical illness underwent a 30-min interview in which they were asked to 'Describe how you have been unwell and, in particular, how that has made you feel.' From the transcripts, a 'folk' taxonomy was constructed using a phenomenological framework involving four steps: frame elicitation to identify the important themes, componential analysis to systematically cluster the attributes into domains, a comparison of the experiences of patients screening depressed and  not-depressed, and a theoretical analysis comparing the resulting taxonomy with currently used theoretical constructs.
Results: Experiences common to all patients were being in hospital, being ill or in pain, adjusting to not being able to do things, and having time to think. In addition, all participants described being depressed, down or sad. Patients who were identified by screening as being depressed described unique experiences of depression, which included 'having to think about things' (a forceful intrusive thinking), 'not being able to sleep', 'having to rely on others', 'being a burden' to others (with associated shame and guilt), feelings of 'not getting better' and 'feeling like giving up'. Theoretical analysis suggested that this experience of depression fitted well with the concept of demoralization described by Jerome Frank.
Conclusions: Demoralization, which involves feelings of being unable to cope, helplessness, hopelessness and diminished personal esteem, characterizes much of the depression seen in hospitalized medically ill patients

How well do women adapt to changes in their body size and shape across the course of pregnancy

This study examined body image across pregnancy. Pregnant women ( N = 158) completed measures of general attractiveness, feeling fat, fitness and strength, salience of weight and shape, and ideal and current body size at pre-pregnancy (retrospective), and in early, middle and late pregnancy. Body image was found to be fairly stable across pregnancy such that women who started with greater body concerns maintained them over time. Although women were least satisfied with their stomach size at late pregnancy, women's ideal body shape increased in parallel with increases in body size. Women with the most body concerns reported more depressive symptoms, tendency towards dieting, and smoking during pregnancy suggesting they were at greater risk in terms of health and well-being during pregnancy.

The role of the surveying profession in reducing carbon emissions of existing office stock in the Melbourne CBD

As professionals, surveyors and property professionals are in the front line and have a moral and ethical duty to take a lead when advising clients appropriately on measures to reduce greenhouse gas emissions from their buildings. As such, surveying professionals and the profession must increase their knowledge base and enhance their skills in respect of built environment sustainability. This research conducted a detailed analysis of energy efficiency in the Melbourne CBD office stock and examined all office buildings to identify what was likely to happen between 2005 and 2020 in respect of carbon emissions. The research profiled a business-as-usual or no change approach, a minor change approach, an intermediate approach, and a major change approach. The study examined variables such as building size, number of employees, occupancy levels, visual appearance and age. After modelling all CBD office buildings, it was recommended that an intermediate change scenario should be adopted. This course of action incorporates a transition period and includes increasing ‘green power’, increasing the number of employees per buildings, as well as reducing electricity and gas consumption. It was concluded that the surveying profession should adopt a proactive stance towards office buildings and climate change, which is currently being stifled by barriers such as a lack of education and perception concerning the long-term benefits of energy efficient office buildings. To date there has been much debate and promotion of policies to encourage the uptake of sustainability practices within the property sector; however, this research concludes that action is needed if targets are to be met.

Critical analysis of action research-based inservice teacher education : four case histories

Changing the nature of institutionalised education is the central theme of the thesis. The potential for radical changes to classroom teaching and to inservice teacher education is considered through four curriculum and teaching reform projects structured by action -research. The problems explored through the thesis are at the levels of teaching, institutional and research practices. It is argued that the professional activity of teachers, administrators, consultants, teacher educators and researchers can be understood to be tightly bound and determined by rules for acceptable professional ways of acting which are often unquestioned and unexamined by educators themselves. It is further argued that institutionalised education is dominated by ways of thinking and acting that are inherently individualistic. The thesis analyses the ideological character of this 'individualistic1 structuring of educational practice, identifying belief systems that hold the lived reality of educators and students in place. The thesis endeavours to show that the bureaucratic character of institutionalised education primarily serves and maintains the interests of dominant groups. The thesis examines the possibilities for radical reform in classroom teaching, the support teachers need when embarking on curriculum and teaching change processes, and the possible outcomes of such reform. The thesis also examines the interaction between the institutional practices of schools, universities and regional offices in the Ministry of Education in Victoria, Australia on these reform processes in classrooms. Finally, the thesis examines the potential of action research as a research and educative process in the professional development of educators who are both critically aware of the ideological nature of institutionalised education and committed to collective social action. From the analyses of the four action research projects the thesis concludes that action research has the potential to transform institutionalised education when its own practice is firstly, developed as a liberating pedagogy and not as research projects structured by individualistic and paternalistic interests; secondly, is driven by a commitment to the political struggle for equity and social justice; and thirdly, is itself an expression of communitarian work. The thesis concludes that the transformative processes associated with action research under these conditions hold the promise of democratising the 'individualistic' character of institutional education.

The story of fable : a narrative analysis of the experience of four registered nurses in their first year of practice

This research explores the transition from student to registered nurse from the perspective of the new graduate. This interpretive study uses narrative analysis as the methodology. Individual stories were collected and processed using the method of core story creation and emplotment (Emden 1998). Four newly registered nurses were invited to share stories related to how they were experiencing their role. Participants were encouraged to tell their stories in response to the open question 'what is it like to be a registered nurse?' In the final step of the analysis one honest and critical story has been crafted (Barone 1992) using a process termed emplotment thus disclosing the themes that allow the stories to be grasped together as a single story (Polkinghorne 1988, Emden 1998). The final story of 'Fable' gives insight into the ways in which newly registered nurses experience their role. Becoming a registered nurse is not easy however, Fable finds that nursing is more than just a job and describes many rewarding experiences. It is hoped that the outcomes of this research will be valuable to students, graduates, nurse academics and the profession of nursing generally by enhancing understandings of the relationship between the graduate and the actual employment experience.

Prevention of a chronic progressive form of experimental autoimmune encephalomyelitis by an antibody against mucosal addressin cell adhesion molecule-1, given early in the course of disease progression.

A role for α4 and β7 integrins in mediating leucocyte entry into the central nervous system in the multiple sclerosis (MS)-like disease experimental autoimmune encephalomyelitis (EAE) has been demonstrated. However, the individual contributions of their respective ligands mucosal addressin cell adhesion molecule-1 (MAdCAM-1), vascular cell adhesion molecule-1 (VCAM-1) and E-cadherin expressed on the blood-brain barrier has not been determined. In the present paper, it is shown that an antibody directed against MAdCAM-1, the preferential ligand for α4β7, effectively prevented the development of a progressive, non-remitting, form of EAE, actively induced by injection of myelin oligodendrocyte glycoprotein peptide (MOG(_35-55)) autoantigen. Combinational treatment with both anti-MAdCAM-1, VCAM-1, and intercellular adhesion molecule-1 (ICAM-1) (ligand for integrin lymphocyte function-associated antigen (LFA)-1) mAbs led to more rapid remission than that obtained with anti-MAdCAM-1 antibody alone. However, neither MAdCAM-1 monotherapy, nor combinational antibody blockade was preventative when administered late in the course of disease progression. In conclusion, MAdCAM-1 plays a major contributory role in the progression of chronic EAE and is a potential therapeutic target for the treatment of MS. Critically, antivascular addressin therapy must be given eaA role for alpha4 and beta7 integrins in mediating leucocyte entry into the central nervous system in the multiple sclerosis (MS)-like disease experimental autoimmune encephalomyelitis (EAE) has been demonstrated. However, the individual contributions of their respective ligands mucosal addressin cell adhesion molecule-1 (MAdCAM-1), vascular cell adhesion molecule-1 (VCAM-1) and E-cadherin expressed on the blood-brain barrier has not been determined. In the present paper, it is shown that an antibody directed against MAdCAM-1, the preferential ligand for alpha4beta7, effectively prevented the development of a progressive, non-remitting, form of EAE, actively induced by injection of myelin oligodendrocyte glycoprotein peptide (MOG(35-55)) autoantigen. Combinational treatment with both anti-MAdCAM-1, VCAM-1, and intercellular adhesion molecule-1 (ICAM-1) (ligand for integrin lymphocyte function-associated antigen (LFA)-1) mAbs led to more rapid remission than that obtained with anti-MAdCAM-1 antibody alone. However, neither MAdCAM-1 monotherapy, nor combinational antibody blockade was preventative when administered late in the course of disease progression. In conclusion, MAdCAM-1 plays a major contributory role in the progression of chronic EAE and is a potential therapeutic target for the treatment of MS. Critically, antivascular addressin therapy must be given early in the course of disease prior to the establishment of irreversible damage if it is to be effective, as a single treatment modality.