953 resultados para All My Sons
Resumo:
The leading Australian High Court case of Cameron v Hogan (1934) 51 CLR 358 confirmed that associations which are 'social, sporting, political, scientific, religious, artistic or humanitarian in character’, and not formed ‘for private gain or material advantage’, are usually formed on a basis of mutual consent. Unless there is some clear, positive indication that the members wish to relate to each other in a legal fashion, the rules of the association will not be treated as an enforceable contract in contrast to the rules of incorporated bodies. Australian unincorporated associations experiencing internal disputes, like those in most other common law jurisdictions, have found courts reluctant to provide a remedy unless there is a proprietary interest or trust to protect. This is further compounded by the judicial view that an unincorporated association has no legal recognition as a ‘juristic person’. The right to hold property and the ability to sue and be sued are incidences of this recognition. By contrast, the law recognises ‘artificial’ legal persons such as corporations, who are given rights to hold property and to sue and be sued. However, when a number of individuals associate together for a non-commercial, lawful purpose, but not by way of a corporate structure, legal recognition ‘as a group’ is denied. Since 1934, a significant number of cases have distinguished or otherwise declined to follow this precedent of the High Court. A trenchant criticism is found in McKinnon v Grogan [1974] 1 NSWLR 295, 298 where Wootten J said that ‘citizens are entitled to look to the courts for the same assistance in resolving disputes about the conduct of sporting, political and social organisations as they can expect in relation to commercial institutions’. According to Wootten J at 298, if disputes are not settled by the courts, this would create a ‘legal-no-man's land, in which disputes are settled not in accordance with justice and the fulfilment of deliberately undertaken obligations, but by deceit, craftiness, and an arrogant disregard of rights’. Cameron v Hogan was decided in 1934. There is an increasing volume of first instance cases which distinguish or, in the words of Palmer J, ‘just pay lip service’ to this High Court decision. (Coleman v Liberal Party of Australia (2007) 212 FLR 271, 278). The dissenting cases seem to call for a judicial policy initiative. This would require recognition by judges that voluntary associations play a significant role in society and that members have a legitimate, enforceable expectation that the rules of the association will be observed by members and in the last resort, enforced by the courts without the need to prove contractual intention, the existence of a trust or the existence of a right of a proprietary nature. This thesis asks: what legal, as distinct from political, redress does an ordinary member have, when a rule is made or a process followed which is contrary to the underlying doctrines and philosophies embodied in the constitutional documents of an unincorporated religious association? When, if at all, will a court intervene to ensure doctrinal purity or to supervise the daily life of a large unincorporated religious association? My research objective is to examine and analyse leading cases and relevant legislation on the enforceability of the constitutions of large, unincorporated, religious associations with particular reference to the Anglican Church in New South Wales. Given its numerical size, wide geographical spread and presence since the foundation of New South Wales, the Anglican Church in New South Wales, contains a sufficient variety of ‘real life’ situations to be representative of the legal issues posed by Cameron v Hogan which may be faced by other large, unincorporated, religious associations in New South Wales. In contemporary society, large, unincorporated, religious associations play an important community role. The resolution of internal disputes in such associations should not remain captive to legal doctrines of an earlier age.
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Increasingly, schools are being asked to meet the challenges of providing inclusive classrooms for all children. Inclusion is no longer about special education for a special group of students. It is about school improvement in order to bring about the changes that are needed to classroom practices to ensure the improvement of student learning outcomes. Inclusion is no longer a policy initiative. Rather it has been transformed to become a process that moves a school towards inclusive practices that will result in school improvement, heightened student learning outcomes and greater opportunities for all students to gain equal access to education. This study focuses on the challenge of diversity as it translates into implementing inclusive practices across two secondary school contexts. I have undertaken this research in my role as a Learning Support Teacher over a period of five years. Central to my research is a constructivist ontology and a practice epistemology that aligns with a practitioner research methodology of action research. Seven generalisable propositions have emerged from this research that inform the strategies I am using to more easily accommodate legislated inclusivitiy. These propositions include: 1. School communities need to share a common understanding of equity. 2. The school principal must provide overt leadership in moving towards an inclusive school culture. 3. A whole-school approach is needed to narrow the gap between inclusion rhetoric and classroom practice. 4. Pedagogical reform is the most effective strategy for catering for diverse student learning needs. 5. Differentiating curriculum is achieved when collaborative planning teams develop appropriate units of work. 6. School communities need to make a commitment to gather, share and manage relevant information concerning students. 7. The Learning Support Teacher needs to be repositioned within a curriculum planning team.
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Objective: To examine current knowledge and practice of occupational health and safety (OH&S) regarding hepatitis C in beauty therapy practice. Methods: A questionnaire was sent to all beauty therapy practices identified through the Telstra Yellow Pages and distributed via beauty therapy product agencies. Results: 119 questionnaires were completed by employers and employees in 99 beauty therapy practices in metropolitan Adelaide. Beauty therapists reported carrying out many practices that had exposed them to blood in the past. More than 80% of the procedures carried out by beauty therapists in the previous week were reported to have led to exposure to blood. 39.5% of respondents had not received information about OH&S practices related to blood spills and 77.5% of respondents had received no OH&S information about hepatitis C. Knowledge of hepatitis C and its transmission was poor, with 62% of respondents incorrectly identifying the prevalence of hepatitis C and respondents incorrectly identifying sneezing (28%), kissing (46%) and sharing coffee cups (42%) as a modes of transmission. 80% of beauty therapy practices had no OH&S representative. Conclusion: Beauty therapy practice can expose both operator and client to blood and is therefore a potential site for the transmission of blood-borne diseases including hepatitis C. OH&S information is inadequate in this industry and knowledge of hepatitis C is poor.
Resumo:
Previous research employing indirect measures of arch structure, such as those derived from footprints, have indicated that obesity results in a “flatter” foot type. In the absence of radiographic measures, however, definitive conclusions regarding the osseous alignment of the foot cannot be made. We determined the effect of body mass index (BMI) on radiographic and footprint‐based measures of arch structure. The research was a cross‐sectional study in which radiographic and footprint‐based measures of foot structure were made in 30 subjects (10 males, 20 female) in addition to standard anthropometric measures of height, weight, and BMI. Multiple (univariate) regression analysis demonstrated that both BMI ( β = 0.39, t 26 = 2.12, p = 0.04) and radiographic arch alignment ( β = 0.51, t 26 = 3.32, p < 0.01) were significant predictors of footprint‐based measures of arch height after controlling for all variables in the model ( R 2 = 0.59, F 3,26 = 12.3, p < 0.01). In contrast, radiographic arch alignment was not significantly associated with BMI ( β = −0.03, t 26 = −0.13, p = 0.89) when Arch Index and age were held constant ( R 2 = 0.52, F 3,26 = 9.3, p < 0.01). Adult obesity does not influence osseous alignment of the medial longitudinal arch, but selectively distorts footprint‐based measures of arch structure. Footprint‐based measures of arch structure should be interpreted with caution when comparing groups of varying body composition.
Resumo:
Serial killers are among the most popular and enduring character types in contemporary culture. In this exegesis I investigate one of the reasons for this popularity by examining the representational relationships between serial killers and serial consumers. I initially establish that all monsters, whether they are vampires, werewolves or serial killers, emerge from cultural anxieties and signify the anxiety which gave them birth. I go on to identify that the cultural anxiety at play with serial killers is consumerism and in doing so, I identify two key parallels between the serial killer and the consumer, namely a sense of lack and a desire for transformation. I then examine the ways in which the serial killer is representative of the consumer in three exemplar texts, The Silence of the Lambs by Thomas Harris, American Psycho by Bret Easton Ellis and Darkly Dreaming Dexter by Jeff Lindsay. I go on to self-reflexively examine the creation of my novel Carnivore, the accompanying draft of which has been influenced by both the exemplar texts and the findings of the exegesis.
Resumo:
The giant freshwater prawn (Macrobrachium rosenbergii) or GFP is one of the most important freshwater crustacean species in the inland aquaculture sector of many tropical and subtropical countries. Since the 1990’s, there has been rapid global expansion of freshwater prawn farming, especially in Asian countries, with an average annual rate of increase of 48% between 1999 and 2001 (New, 2005). In Vietnam, GFP is cultured in a variety of culture systems, typically in integrated or rotational rice-prawn culture (Phuong et al., 2006) and has become one of the most common farmed aquatic species in the country, due to its ability to grow rapidly and to attract high market price and high demand. Despite potential for expanded production, sustainability of freshwater prawn farming in the region is currently threatened by low production efficiency and vulnerability of farmed stocks to disease. Commercial large scale and small scale GFP farms in Vietnam have experienced relatively low stock productivity, large size and weight variation, a low proportion of edible meat (large head to body ratio), scarcity of good quality seed stock. The current situation highlights the need for a systematic stock improvement program for GFP in Vietnam aimed at improving economically important traits in this species. This study reports on the breeding program for fast growth employing combined (between and within) family selection in giant freshwater prawn in Vietnam. The base population was synthesized using a complete diallel cross including 9 crosses from two local stocks (DN and MK strains) and a third exotic stock (Malaysian strain - MY). In the next three selection generations, matings were conducted between genetically unrelated brood stock to produce full-sib and (paternal) half-sib families. All families were produced and reared separately until juveniles in each family were tagged as a batch using visible implant elastomer (VIE) at a body size of approximately 2 g. After tags were verified, 60 to 120 juveniles chosen randomly from each family were released into two common earthen ponds of 3,500 m2 pond for a grow-out period of 16 to 18 weeks. Selection applied at harvest on body weight was a combined (between and within) family selection approach. 81, 89, 96 and 114 families were produced for the Selection line in the F0, F1, F2 and F3 generations, respectively. In addition to the Selection line, 17 to 42 families were produced for the Control group in each generation. Results reported here are based on a data set consisting of 18,387 body and 1,730 carcass records, as well as full pedigree information collected over four generations. Variance and covariance components were estimated by restricted maximum likelihood fitting a multi-trait animal model. Experiments assessed performance of VIE tags in juvenile GFP of different size classes and individuals tagged with different numbers of tags showed that juvenile GFP at 2 g were of suitable size for VIE tags with no negative effects evident on growth or survival. Tag retention rates were above 97.8% and tag readability rates were 100% with a correct assignment rate of 95% through to mature animal size of up to 170 g. Across generations, estimates of heritability for body traits (body weight, body length, cephalothorax length, abdominal length, cephalothorax width and abdominal width) and carcass weight traits (abdominal weight, skeleton-off weight and telson-off weight) were moderate and ranged from 0.14 to 0.19 and 0.17 to 0.21, respectively. Body trait heritabilities estimated for females were significantly higher than for males whereas carcass weight trait heritabilities estimated for females and males were not significantly different (P > 0.05). Maternal and common environmental effects for body traits accounted for 4 to 5% of the total variance and were greater in females (7 to 10%) than in males (4 to 5%). Genetic correlations among body traits were generally high in both sexes. Genetic correlations between body and carcass weight traits were also high in the mixed sexes. Average selection response (% per generation) for body weight (transformed to square root) estimated as the difference between the Selection and the Control group was 7.4% calculated from least squares means (LSMs), 7.0% from estimated breeding values (EBVs) and 4.4% calculated from EBVs between two consecutive generations. Favourable correlated selection responses (estimated from LSMs) were detected for other body traits (12.1%, 14.5%, 10.4%, 15.5% and 13.3% for body length, cephalothorax length, abdominal length, cephalothorax width and abdominal width, respectively) over three selection generations. Data in the second selection generation showed positive correlated responses for carcass weight traits (8.8%, 8.6% and 8.8% for abdominal weight, skeleton-off weight and telson-off weight, respectively). Data in the third selection generation showed that heritability for body traits were moderate and ranged from 0.06 to 0.11 and 0.11 to 0.22 at weeks 10 and 18, respectively. Body trait heritabilities estimated at week 10 were not significantly lower than at week 18. Genetic correlations between body traits within age and genetic correlations for body traits between ages were generally high. Overall our results suggest that growth rate responds well to the application of family selection and carcass weight traits can also be improved in parallel, using this approach. Moreover, selection for high growth rate in GFP can be undertaken successfully before full market size has been reached. The outcome of this study was production of an improved culture strain of GFP for the Vietnamese culture industry that will be trialed in real farm production environments to confirm the genetic gains identified in the experimental stock improvement program.
Resumo:
This research is an autoethnographic investigation of consumption experiences, public and quasi-public spaces, and their relationship to community within an inner city neighbourhood. The research specifically focuses on the gentrifying inner city, where class-based processes of change can have implications for people’s abilities to remain within, or feel connected to place. However, the thesis draws on broader theories of the throwntogetherness of the contemporary city (e.g., Amin and Thrift, 2002; Massey 2005) to argue that the city is a space where place-based meanings cannot be seen to be fixed, and are instead better understood as events of place – based on ever shifting interrelations between the trajectories of people and things. This perspective argues the experience of belonging to community is not just born of a social encounter, but also draws on the physical and symbolic elements of the context in which it is situated. The thesis particularly explores the ways people construct identifications within this shifting urban environment. As such, consumption practices and spaces offer one important lens through which to explore the interplay of the physical, social and symbolic. Consumer research tells us that consumption practices can facilitate experiences in which identity-defining meaning can be generated and shared. Consumption spaces can also support different kinds of collective identification – as anchoring realms for specific cultural groups or exposure realms that enable individuals to share in the identification practices of others with limited risk (Aubert-Gamet & Cova, 1999). Furthermore, the consumption-based lifestyles that gentrifying inner city neighbourhoods both support and encourage can also mean that consumption practices may be a key reason that people are moving through public space. That is, consumption practices and spaces may provide a purpose for which – and spatial frame against which – our everyday interactions and connections with people and objects are undertaken within such neighbourhoods. The purpose of this investigation then was to delve into the subjectivities at the heart of identifying with places, using the lens of our consumption-based experiences within them. The enquiry describes individual and collective identifications and emotional connections, and explores how these arise within and through our experiences within public and quasi-public spaces. It then theorises these ‘imaginings’ as representative of an experience of community. To do so, it draws on theories of imagination and its relation to community. Theories of imagined community remind us that both the values and identities of community are held together by projections that create relational links out of objects and shared practices (e.g., Benedict Anderson, 2006; Urry, 2000). Drawing on broader theories of the processes of the imagination, this thesis suggests that an interplay between reflexivity and fantasy – which are products of the critical and the fascinated consciousness – plays a role in this imagining of community (e.g., Brann, 1991; Ricoeur, 1994). This thesis therefore seeks to explore how these processes of imagining are implicated within the construction of an experience of belonging to neighbourhood-based community through consumption practices and the public and quasi-public spaces that frame them. The key question of this thesis is how do an individual’s consumption practices work to construct an imagined presence of neighbourhood-based community? Given the focus on public and quasi-public spaces and our experiences within them, the research also asked how do experiences in the public and quasi-public spaces that frame these practices contribute to the construction of this imagined presence? This investigation of imagining community through consumption practices is based on my own experiences of moving to, and attempting to construct community connections within, an inner city neighbourhood in Melbourne, Australia. To do so, I adopted autoethnographic methodology. This is because autoethnography provides the methodological tools through which one can explore and make visible the subjectivities inherent within the lived experiences of interest to the thesis (Ellis, 2004). I describe imagining community through consumption as an extension of a placebased self. This self is manifest through personal identification in consumption spaces that operate as anchoring realms for specific cultural groups, as well as through a broader imagining of spaces, people, and practices as connected through experiences within realms of exposure. However, this is a process that oscillates through cycles of identification; these anchor one within place personally, but also disrupt those attachments. This instability can force one to question the orientation and motives of these imaginings, and reframe them according to different spaces and reference groups in ways that can also work to construct a more anonymous and, conversely, more achievable collective identification. All the while, the ‘I’ at the heart of this identification is in an ongoing process of negotiation, and similarly, the imagined community is never complete. That is, imagining community is a negotiation, with people and spaces – but mostly with the different identifications of the self. This thesis has been undertaken by publication, and thus the process of imagining community is explored and described through four papers. Of these, the first two focus on specific types of consumption spaces – a bar and a shopping centre – and consider the ways that anchoring and exposure within these spaces support the process of imagining community. The third paper examines the ways that the public and quasi-public spaces that make up the broader neighbourhood context are themselves throwntogether as a realm of exposure, and considers the ways this shapes my imaginings of this neighbourhood as community. The final paper develops a theory of imagined community, as a process of comparison and contrast with imagined others, to provide a summative conceptualisation of the first three papers. The first paper, chapter five, explores this process of comparison and contrast in relation to authenticity, which in itself is a subjective assessment of identity. This chapter was written as a direct response to the recent work of Zukin (2010), and draws on theories of authenticity as applied to personal and collective identification practices by consumer researchers Arnould and Price (2000). In this chapter, I describe how my assessments of the authenticity of my anchoring experiences within one specific consumption space, a neighbourhood bar, are evaluated in comparison to my observations of and affective reactions to the social practices of another group of residents in a different consumption space, the local shopping centre. Chapter five also provides an overview of the key sites and experiences that are considered in more detail in the following two chapters. In chapter six, I again draw on my experiences within the bar introduced in chapter five, this time to explore the process of developing a regular identity within a specific consumption space. Addressing the popular theory of the cafe or bar as third place (Oldenburg, 1999), this paper considers the purpose of developing anchored relationships with people within specific consumption spaces, and explores the different ways this may be achieved in an urban context where the mobilities and lifestyle practices of residents complicate the idea of a consumption space as an anchoring or third place. In doing so, this chapter also considers the manner in which this type of regular identification may be seen to be the beginning of the process of imagining community. In chapter seven, I consider the ways the broader public spaces of the neighbourhood work cumulatively to expose different aspects of its identity by following my everyday movements through the neighbourhood’s shopping centre and main street. Drawing on the theories of Urry (2000), Massey (2005), and Amin (2007, 2008), this chapter describes how these spaces operate as exposure realms, enabling the expression of different senses of the neighbourhood’s spaces, times, cultures, and identities through their physical, social, and symbolic elements. Yet they also enable them to be united: through habitual pathways, group practices of appropriation of space, and memory traces that construct connections between objects and experiences. This chapter describes this as a process of exposure to these different elements. Our imagination begins to expand the scope of the frames onto which it projects an imagined presence; it searches for patterns within the physical, social, and symbolic environment and draws connections between people and practices across spaces. As the final paper, chapter eight, deduces, it is in making these connections that one constructs the objects and shared practices of imagined community. This chapter describes this as an imagining of neighbourhood as a place-based extension of the self, and then explores the ways in which I drew on physical, social, and symbolic elements in an attempt to construct a fit between the neighbourhood’s offerings and my desires for place-based identity definition. This was as a cumulative but fragmented process, in which positive and negative experiences of interaction and identification with people and things were searched for their potential to operate as the objects and shared practices of imagined community. This chapter describes these connections as constructed through interplay between reflexivity and fantasy, as the imagination seeks balance between desires for experiences of belonging, and the complexities of constructing them within the throwntogether context of the contemporary city. The conclusion of the thesis describes the process of imagining community as a reflexive fantasy, that is, as a product of both the critical and fascinated consciousness (Ricoeur, 1994). It suggests that the fascinated consciousness imbues experiences with hope and desire, which the reflexive imagining can turn to disappointment and shame as it critically reflects on the reality of those fascinated projections. At the same time, the reflexive imagination also searches the practices of others for affirmation of those projections, effectively seeking to prove the reality of the fantasy of the imagined community.
Resumo:
Remote monitoring for heart failure has been evaluated in numerous systematic reviews. The aim of this meta-review was to appraise their quality and synthesise results. We electronically searched online databases, performed a forward citation search and hand-searched bibliographies. Systematic reviews of remote monitoring interventions that were used for surveillance of heart failure patients were included. Seven (41%) systematic reviews pooled results for meta-analysis. Eight (47%) considered all non-invasive remote monitoring strategies. Five (29%) focused on telemonitoring. Four (24%) included both non-invasive and invasive technologies. According to AMSTAR criteria, ten (58%) systematic reviews were of poor methodological quality. In high quality reviews, the relative risk of mortality in patients who received remote monitoring ranged from 0.53 (95% CI=0.29-0.96) to 0.88 (95% CI=0.76-1.01). High quality reviews also reported that remote monitoring reduced the relative risk of all-cause (0.52; 95% CI=0.28-0.96 to 0.96; 95% CI=0.90–1.03) and heart failure-related hospitalizations (0.72; 95% CI=0.64–0.81 to RR 0.79; 95% CI=0.67-0.94) and, as a consequence, healthcare costs. As the high quality reviews reported that remote monitoring reduced hospitalizations, mortality and healthcare costs, research efforts should now be directed towards optimising these interventions in preparation for more widespread implementation.
Resumo:
Background/aims: Remote monitoring for heart failure has not only been evaluated in a large number of randomised controlled trials, but also in many systematic reviews and meta-analyses. The aim of this meta-review was to identify, appraise and synthesise existing systematic reviews that have evaluated the effects of remote monitoring in heart failure. Methods: Using a Cochrane methodology, we electronically searched all relevant online databases and search engines, performed a forward citation search as well as hand-searched bibliographies. Only fully published systematic reviews of invasive and/or non-invasive remote monitoring interventions were included. Two reviewers independently extracted data. Results: Sixty-five publications from 3333 citations were identified. Seventeen fulfilled the inclusion and exclusion criteria. Quality varied with A Measurement Tool to Assess Systematic Reviews (AMSTAR scores) ranging from 2 to 11 (mean 5.88). Seven reviews (41%) pooled results from individual studies for meta-analysis. Eight (47%) considered all non-invasive remote monitoring strategies. Four (24%) focused specifically on telemonitoring. Four (24%) included studies investigating both non-invasive and invasive technologies. Population characteristics of the included studies were not reported consistently. Mortality and hospitalisations were the most frequently reported outcomes 12 (70%). Only five reviews (29%) reported healthcare costs and compliance. A high degree of heterogeneity was reported in many of the meta-analyses. Conclusions: These results should be considered in context of two negative RCTs of remote monitoring for heart failure that have been published since the meta-analyses (TIM-HF and Tele-HF). However, high quality reviews demonstrated improved mortality, quality of life, reduction in hospitalisations and healthcare costs.
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Whether to keep products segregated (e.g., unbundled) or integrate some or all of them (e.g., bundle) has been a problem of profound interest in areas such as portfolio theory in finance, risk capital allocations in insurance and marketing of consumer products. Such decisions are inherently complex and depend on factors such as the underlying product values and consumer preferences, the latter being frequently described using value functions, also known as utility functions in economics. In this paper, we develop decision rules for multiple products, which we generally call ‘exposure units’ to naturally cover manifold scenarios spanning well beyond ‘products’. Our findings show, e.g. that the celebrated Thaler's principles of mental accounting hold as originally postulated when the values of all exposure units are positive (i.e. all are gains) or all negative (i.e. all are losses). In the case of exposure units with mixed-sign values, decision rules are much more complex and rely on cataloging the Bell number of cases that grow very fast depending on the number of exposure units. Consequently, in the present paper, we provide detailed rules for the integration and segregation decisions in the case up to three exposure units, and partial rules for the arbitrary number of units.
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Socially just, intergenerational urban spaces should not only accommodate children and adolescents, but engage them as participants in the planning and design of welcoming spaces. With this goal, city agencies in Boulder, Colorado, the Boulder Valley School District, the Children, Youth and Environments Center at the University of Colorado, and a number of community organizations have been working in partnership to integrate young people’s ideas and concerns into the redesign of parks and civic areas and the identification of issues for city planning. Underlying their work is a commitment to the Convention on the Rights of the Child and children’s rights to active citizenship from a young age. This paper describes approaches used to engage with young people and methods of participation, and reflects on lessons learned about how to most effectively involve youth from underrepresented populations and embed diverse youth voices into the culture of city planning.
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Predicate encryption is a new primitive that supports flexible control over access to encrypted data. We study predicate encryption systems, evaluating a wide class of predicates. Our systems are more expressive than the existing attribute-hiding systems in the sense that the proposed constructions support not only all existing predicate evaluations but also arbitrary conjunctions and disjunctions of comparison and subset queries. Toward our goal, we propose encryption schemes supporting multi-inner-product predicate and provide formal security analysis. We show how to apply the proposed schemes to achieve all those predicate evaluations.
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Preservice teachers consistently report that managing student behaviour is one of their major concerns prior to and during practicum (Capel, 1997; Kyriacou & Stephens, 1999). Not surprisingly, preservice teachers are keen to gain knowledge and understanding of effective classroom management approaches that facilitate the development of positive learning environments in which students are engaged in learning. Establishing democratic teaching practices that allow student choice, communicating in a positive, helpful manner, ensuring the right to teach and the right to learn without disruptions is upheld, and promoting self-discipline are important steps in preventing misbehavior and developing a democratic community of learners.
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The goal of improving systemic treatment of breast cancers is to evolve from treating every patient with non-specific cytotoxic chemotherapy/hormonal therapy, to a more individually-tailored direct treatment. Although anatomic staging and histological grade are important prognostic factors, they often fail to predict the clinical course of this disease. This study aimed to develop a gene expression profile associated with breast cancers of differing grades. We extracted mRNA from FFPE archival breast IDC tissue samples (Grades I–III), including benign tumours. Affymetrix GeneChip� Human Genome U133 Plus 2.0 Arrays were used to determine gene expression profiles and validated by Q-PCR. IHC was used to detect the AXIN2 protein in all tissues. From the array data, an independent group t-test revealed that 178 genes were significantly (P B 0.01) differentially expressed between three grades of malignant breast tumours when compared to benign tissues. From these results, eight genes were significantly differentially expressed in more than one comparison group and are involved in processes implicated in breast cancer development and/or progression. The two most implicated candidates genes were CLD10 and ESPTI1 as their gene expression profile from the microarray analysis was replicated in Q-PCR analyses of the original tumour samples as well as in an extended population. The IHC revealed a significant association between AXIN2 protein expression and ER status. It is readily acknowledged and established that significant differences exist in gene expression between different cancer grades. Expansion of this approach may lead to an improved ability to discriminate between cancer grade and other pathological factors.
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Recent developments in genomic technologies have resulted in increased understanding of pathogenic mechanisms and emphasized the importance of central survival pathways. Here, we use a novel bioinformatic based integrative genomic profiling approach to elucidate conserved mechanisms of lymphomagenesis in the three commonest non-Hodgkin's lymphoma (NHL) entities: diffuse large B-cell lymphoma, follicular lymphoma, and B-cell chronic lymphocytic leukemia. By integrating genome-wide DNA copy number analysis and transcriptome profiling of tumor cohorts, we identified genetic lesions present in each entity and highlighted their likely target genes. This revealed a significant enrichment of components of both the apoptosis pathway and the mitogen activated protein kinase pathway, including amplification of the MAP3K12 locus in all three entities, within the set of genes targeted by genetic alterations in these diseases. Furthermore, amplification of 12p13.33 was identified in all three entities and found to target the FOXM1 oncogene. Amplification of FOXM1 was subsequently found to be associated with an increased MYC oncogenic signaling signature, and siRNA-mediated knock-down of FOXM1 resulted in decreased MYC expression and induced G2 arrest. Together, these findings underscore genetic alteration of the MAPK and apoptosis pathways, and genetic amplification of FOXM1 as conserved mechanisms of lymphomagenesis in common NHL entities. Integrative genomic profiling identifies common central survival mechanisms and highlights them as attractive targets for directed therapy.