The genetic basis of human height : the role of estrogen

Height is a complex physical trait that displays strong heritability. Adult height is related to length of the long bones, which is determined by growth at the epiphyseal growth plate. Longitudinal bone growth occurs via the process of endochondral ossification, where bone forms over the differentiating cartilage template at the growth plate. Estrogen plays a major role in regulating longitudinal bone growth and is responsible for inducing the pubertal growth spurt and fusion of the epiphyseal growth plate. However, the mechanism by which estrogen promotes epiphyseal fusion is poorly understood. It has been hypothesised that estrogen functions to regulate growth plate fusion by stimulating chondrocyte apoptosis, angiogenesis and bone cell invasion in the growth plate. Another theory has suggested that estrogen exposure exhausts the proliferative capacity of growth plate chondrocytes, which accelerates the process of chondrocyte senescence, leading to growth plate fusion. The overall objective of this study was to gain a greater understanding of the molecular mechanisms behind estrogen-mediated growth and height attainment by examining gene regulation in chondrocytes and the role of some of these genes in normal height inheritance. With the heritability of height so well established, the initial hypothesis was that genetic variation in candidate genes associated with longitudinal bone growth would be involved in normal adult height variation. The height-related genes FGFR3, CBFA1, ER and CBFA1 were screened for novel polymorphisms using denaturing HPLC and RFLP analysis. In total, 24 polymorphisms were identified. Two SNPs in ER (rs3757323 C>T and rs1801132 G>C) were strongly associated with adult male height and displayed an 8 cm and 9 cm height difference between homozygous genotypes, respectively. The TC haplotype of these SNPs was associated with a 6 cm decrease in height and remarkably, no homozygous carriers of the TC haplotype were identified in tall subjects. No significant associations with height were found for polymorphisms in the FGFR3, CBFA1 or VDR genes. In the epiphyseal growth plate, chondrocyte proliferation, matrix synthesis and chondrocyte hypertrophy are all major contributors to long bone growth. As estrogen plays such a significant role in both growth and final height attainment, another hypothesis of this study was that estrogen exerted its effects in the growth plate by influencing chondrocyte proliferation and mediating the expression of chondrocyte marker genes. The examination of genes regulated by estrogen in chondrocyte-like cells aimed to identify potential regulators of growth plate fusion, which may further elucidate mechanisms involved in the cessation of linear growth. While estrogen did not dramatically alter the proliferation of the SW1353 cell line, gene expression experiments identified several estrogen regulated genes. Sixteen chondrocyte marker genes were examined in response to estrogen concentrations ranging from 10-12 M to 10-8 M over varying time points. Of the genes analysed, IHH, FGFR3, collagen II and collagen X were not readily detectable and PTHrP, GHR, ER, BMP6, SOX9 and TGF1 mRNAs showed no significant response to estrogen treatments. However, the expression of MMP13, CBFA1, BCL-2 and BAX genes were significantly decreased. Interestingly, the majority of estrogen regulated genes in SW1353 cells are expressed in the hypertrophic zone of the growth plate. Estrogen is also known to regulate systemic GH secretion and local GH action. At the molecular level, estrogen functions to inhibit GH action by negatively regulating GH signalling. GH treated SW1353 cells displayed increases in MMP9 mRNA expression (4.4-fold) and MMP13 mRNA expression (64-fold) in SW1353 cells. Increases were also detected in their respective proteins. Treatment with AG490, an established JAK2 inhibitor, blocked the GH mediated stimulation of both MMP9 and MMP13 mRNA expression. The application of estrogen and GH to SW1353 cells attenuated GH-stimulated MMP13 levels, but did not affect MMP9 levels. Investigation of GH signalling revealed that SW1353 cells have high levels of activated JAK2 and exposure to GH, estrogen, AG490 and other signalling inhibitors did not affect JAK2 phosphorylation. Interestingly, AG490 treatment dramatically decreased ERK2 signalling, although GH did stimulate ERK2 phosphorylation above control levels. AG490 also decreased CBFA1 expression, a transcription factor known to activate MMP9 and MMP13. Finally, GH and estrogen treatment increased expression of SOCS3 mRNA, suggesting that SOCS3 may regulate JAK/STAT signalling in SW1353 cells. The modulation of GH-mediated MMP expression by estrogen in SW1353 cells represents a potentially novel mechanism by which estrogen may regulate longitudinal bone growth. However, further investigation is required in order to elucidate the precise mechanisms behind estrogen and GH regulation of MMP13 expression in SW1353 cells. This study has provided additional evidence that estrogen and the ER gene are major factors in the regulation of growth and the determination of adult height. Newly identified polymorphisms in the ER gene not only contribute to our understanding of the genetic basis of human height, but may also be useful in association studies examining other complex traits. This study also identified several estrogen regulated genes and indicated that estrogen modifies the expression of genes which are primarily expressed in the hypertrophic region of the epiphyseal growth plate. Furthermore, synergistic studies incorporating GH and estrogen have revealed the ability of estrogen to attenuate the effects of GH on MMP13 expression, revealing potential pathways by which estrogen may modulate growth plate fusion, longitudinal bone growth and even arthritis.

Ghrelin gene-related peptides : multifunctional endocrine/autocrine modulators in health and disease

Ghrelin is a multi-functional peptide hormone which affects various processes including growth hormone and insulin release, appetite regulation, gut motility, metabolism and cancer cell proliferation. Ghrelin is produced in the stomach and in other normal and pathological cell types. It may act as an endocrine or autocrine/paracrine factor. The ghrelin gene encodes a precursor protein, preproghrelin, from which ghrelin and other potentially active peptides are derived by alternative mRNA splicing and/or proteolytic processing. The metabolic role of the peptide obestatin, derived from the preproghrelin C-terminal region, is controversial. However, it has direct effects on cancer cell proliferation. The regulation of ghrelin expression and the mechanisms through which the peptide products arise are unclear. We have recently re-examined the organisation of the ghrelin gene and identified several novel exons and transcripts. One transcript, which lacks the ghrelin-coding region of preproghrelin, contains the coding sequence of obestatin. Furthermore, we have identified an overlapping gene on the antisense strand of ghrelin, GHRLOS, which generates transcripts that may function as non-coding regulatory RNAs or code for novel, short bioactive peptides. The identification of these novel ghrelin-gene related transcripts and peptides raises critical questions regarding their physiological function and their role in obesity, diabetes and cancer.

Crossing boundaries: Implications of advances in basic sciences for the management of addiction.

This set of papers in this issue of "Addictive Behaviors" was presented at the 2004 'Addictions' conference, which, for the first time, was held in the Southern Hemisphere, on the Sunshine Coast of Queensland, Australia. The theme of the conference, Crossing Boundaries: Implications of Advances in Basic Sciences for the Management of Addiction, speaks for itself. The papers derive from a wide range of empirical paradigms and cover issues with relevance to the development of addiction, to the maintenance of problematic use, and to assessment, treatment, and relapse. Research from Europe and the United States is represented, as well as work from Australia. An international perspective is strongly emphasized from the initial paper by Obot, Poznyak, and Moneiro, (see record 2004-19599-015) which describes the WHO Report on the Neuroscience of Psychoactive Substance Use and Dependence, and summarises some of the report's implications for policy and practice. Hall, Carter, and Morley (see record 2004-19599-014) close the issue with a paper on the wide-ranging ethical implications of advances in neuroscience research, including issues arising from the identification of high risk for addiction, the potential for coercive pharmacotherapy, use of medications to enhance function, and risks to privacy.

Clinical significance of Mycobacterium asiaticum isolates in Queensland, Australia

Mycobacterium asiaticum was first reported as a cause of human disease in 1982, with only a few cases in the literature to date. This study aims to review the clinical significance of M. asiaticum isolates in Queensland, Australia. A retrospective review (1989 to 2008) of patients with M. asiaticum isolates was conducted. Data were collected through the Queensland TB Control Centre database. Disease was defined in accordance with the American Thoracic Society criteria. Twenty-four patients (13 female) had a positive culture of M. asiaticum, many residing around the Tropic of Capricorn. M. asiaticum was responsible for pulmonary disease (n = 2), childhood lymphadenitis (n = 1), olecranon bursitis (n = 1), 6 cases of possible pulmonary disease, and 2 possible wound infections. Chronic lung disease was a risk factor for pulmonary infection, and wounds/lacerations were a risk factor for extrapulmonary disease. Extrapulmonary disease responded to local measures. Pulmonary disease responded to ethambutol-isoniazid-rifampin plus pyrazinamide for the first 2 months in one patient, and amikacin-azithromycin-minocycline in another patient. While M. asiaticum is rare in Queensland, there appears to be an environmental niche. Although often a colonizer, it can be a cause of pulmonary and extrapulmonary disease. Treatment of pulmonary disease remains challenging. Extrapulmonary disease does not mandate specific nontuberculous mycobacterium (NTM) treatment.

Comparison of methods for processing drinking water samples for the isolation of Myocbacterium avium and intracellulare

Several protocols for isolation of mycobacteria from water exist, but there is no established standard method. This study compared methods of processing potable water samples for the isolation of Mycobacterium avium and Mycobacterium intracellulare using spiked sterilized water and tap water decontaminated using 0.005% cetylpyridinium chloride (CPC). Samples were concentrated by centrifugation or filtration and inoculated onto Middlebrook 7H10 and 7H11 plates and Lowenstein-Jensen slants and into mycobacterial growth indicator tubes with or without polymyxin, azlocillin, nalidixic acid, trimethoprim, and amphotericin B. The solid media were incubated at 32°C, at 35°C, and at 35°C with CO2 and read weekly. The results suggest that filtration of water for the isolation of mycobacteria is a more sensitive method for concentration than centrifugation. The addition of sodium thiosulfate may not be necessary and may reduce the yield. Middlebrook M7H10 and 7H11 were equally sensitive culture media. CPC decontamination, while effective for reducing growth of contaminants, also significantly reduces mycobacterial numbers. There was no difference at 3 weeks between the different incubation temperatures.

Two Thai teachers' perceptions of cooperative learning

Over the past decade, the need for educational reform in Thailand has become increasingly apparent. The strong tradition of teacher-directed instruction has been the major teaching and learning style in Thai education. Recent policy changes have focused on expanding education opportunities, the implementation of compulsory education and also on more student-centered pedagogies (Carter, 2006). A suggested way of bringing about the changes necessary to improve the standard of education in primary schools and retention rates is to incorporate cooperative learning into Thai primary school classrooms. The action research in this study proceeded in four stages. There were pre-implementation interviews of teachers, teacher preparation, implementation of program, and post-implementation evaluation. This study focused on the two Thai teachers' perceptions about the benefits of cooperative learning and the roles of the teachers in cooperative learning classroom. The study found that the two teachers had constructed different levels of perceptions about the benefits of cooperative learning and the roles of the teacher. These findings indicated that Thai teachers who are relatively inexperienced, lacking in confidence and with little or no experience with group work strategies such as peer tutoring need alternative, less intense professional development programs conducted over a period of a semester than the professional development program implemented in this study. In addition to being conducted over a longer period of time, the findings also indicate that alternative teacher professional programs need to provide additional workshops to improve their understanding of cooperative learning and the teachers' roles.

The roles and importance of formal and informal sources of business support in young firms : evidence from the UK’s 2008 Federation of Small Business Survey

Objectives This research explores the relationship between young firms, their growth orientation-intention and a range of relationships which can be seen to provide business support. Prior-work Research indicates that networks impact the firm’s ability to secure resources (Sirmon and Hitt 2003; Liao and Welsch. 2004; Hanlon and Saunders 2007). Networks have been evaluated in a number of ways ranging from simple counts to characteristics of their composition (Davidsson and Honig 2003), strength of relationships (Granovetter 1973) and network diversity (Carter et al 2003). By providing access to resources and knowledge (from start-up assistance and raising capital, (e.g. Smallbone et al, 2003), networks may assist in enabling continued persistence during those times where firms may experience resource constraints owing to firm growth (Baker and Nelson 2005). Approach The data used in this research was generated in the 2008 UK Federation of Small Businesses (FSB) survey. Over 1,000 of the firms responding were found to fall into the category of “young”, ((defined as firms under 4 years old). Firms were considered the unit of analysis with the entrepreneur being the chief spokesperson for the firm. Preliminary data analysis considered key demographic characteristics and industry classifications, comparing the FSB data with that of the UK government’s own (BERR) Small Business Surveys of 2007 and 2008, to establish some degree of representativeness of the respondents. The analysis then examined networks with varying potential ability to provide support for young firms, the networks measured in terms of number, diversity, characteristic and strength in its relationship to young firm growth orientation. The diversity of business-support-related relationships ranged from friends and family, through professional services, customers and suppliers, and government business services, to trade associations and informal business networks. The characteristics of these formal and informal sources of support for new businesses are examined across a range of business support-type activities for new firms. The number of relationships and types of business support are also explored. Finally, the strength of these relationships is examined by analysis of the source of business support, type of business support, and links to the growth orientation-intention of the firm, after controlling for a number of key variables related to firm and industry status and owner characteristics. Results Preliminary analysis of the data by means of univariate analysis showed that average number of sources of advice was around 2.5 (from a potential total of 6). In terms of the diversity of relationships, universities had by far the smallest percentage of firms receiving beneficial advice from them. Government business services were beneficially used by 40% of young firms, the other relationship types being around the 50-55% mark. In terms of characteristics of the advice, the average number of areas in which benefit was achieved was around 5.5 of a maximum of 15. Start-up advice has by far the highest percentage of firms obtaining beneficial advice, with increasing sales, improving contacts and improving confidence being the other categories at or around the 50% mark. Other market-focused areas where benefits were also received were in the areas of new markets, existing product improvements and new product improvements, where around 40% of the young responding firms obtained benefit. Regression techniques evaluating the strength of these relationships in terms of the links between business support (by source of support, type of support, and range of support) and firm growth orientation-intention focus highlighted a number of significant relationships, even after controlling for a range of other explanatory variables identified in the literature. Specifically, there was found to be a positive relationship between receiving business advice generally (regardless of type or source) and growth orientation. This relationship was seen to be stronger, however, when looking at the number of types of beneficial advice received, and stronger again for the number of sources of this advice. In terms of individual sources of advice, customers and suppliers had the strongest relationship with growth, with Government business services also found to be significant. Combining these two sources was also seen to increase the strength of the relationship between these two sources of advice and growth orientation. In considering areas of support, growth was most strongly positively related to advice that benefited the development of new products and services, and also business confidence, but was negatively related to advice linked to business recovery. Finally, amalgamating the 4 key types and sources of advice to examine the impact of combinations of these types and sources of advice also improved the strength of the relationship. Implications The findings will assist in the understanding of young firms in general and growth more specifically, particularly the role and importance of specific sources, types and combinations of business support used more extensively by new young growth-oriented firms. Value This research may assist in processes designed to allow entrepreneurs to make better decisions; educators and support organizations to develop better advice and assistance, and Governments design better conditions for the creation of new growth-oriented businesses.

Thai students' engagement with cooperative learning in mathematics classrooms

Over the past decade, Thai schools have been encouraged by the Thai Ministry of Education to introduce more student-centred pedagogies such as cooperative learning into their classrooms (Carter, 2006). However, prior research has indicated that the implementation of cooperative learning into Thai schools has been confounded by cultural traditions endemic within Thai schools (Deveney, 2005). The purpose of the study was to investigate how 32 Grade 3 and 32 Grade 4 students enrolled in a Thai school engaged with cooperative learning in mathematics classrooms after they had been taught cooperative learning strategies and skills. These strategies and skills were derived from a conceptual framework that was the outcome of an analysis and synthesis of social learning, behaviourist and socio-cognitive theories found in the research literature. The intervention began with a two week program during which the students were introduced to and engaged in practicing a set of cooperative learning strategies and skills (3 times a week). Then during the next four weeks (3 times a week), these cooperative learning strategies and skills were applied in the contexts of two units of mathematics lessons. A survey of student attitudes with respect to their engagement in cooperative learning was conducted at the conclusion of the six-week intervention. The results from the analysis of the survey data were triangulated with the results derived from the analysis of data from classroom observations and teacher interviews. The analysis of data identified four complementary processes that need to be considered by Thai teachers attempting to implement cooperative learning into their mathematics classrooms. The paper concludes with a set of criteria derived from the results of the study to guide Thai teachers intending to implement cooperative learning strategies and skills in their classrooms.

The effect of monocular and binocular cataract blur on postural stability among older adults

Purpose: First-eye cataract surgery can reduce the rate of falls among older adults, yet the effect of second-eye surgery on the rate of falling remains unclear. The present study investigated the effect of monocular and binocular simulated cataract blur on postural stability among older adults. Methods: Postural stability was assessed on 34 healthy older adults (mean 68.2 years, SD 3.5) with normal vision, using a portable force platform (BT4, HUR Labs, Finland) which collected data on centre of pressure (COP) displacement. Stability was assessed on firm and foam surfaces under four binocular viewing conditions using Vistech filters to simulate cataract blur: [1] best-corrected vision both eyes; [2] blur over non-dominant eye, [3] blur over dominant eye and [4] blur over both eyes. Binocular logMAR visual acuity, Pelli-Robson contrast sensitivity and stereoacuity were also measured under these viewing conditions and ocular dominance measured using the hole-in-card test. Generalized estimating equations with an exchangeable correlation structure examined the effect of the surface and vision conditions on postural stability. Results: Visual acuity and contrast sensitivity were significantly reduced under monocular and binocular cataract blur compared to normal viewing. All blur conditions resulted in loss of stereoacuity. Binocular cataract blur significantly reduced postural stability compared to normal vision on the firm (COP path length; p=0.013) and foam surface (anterior-posterior COP RMS, COP path length and COP area; p<0.01). However, no significant differences in postural stability were found between the monocular blur conditions compared to normal vision, or between the dominant and non-dominant monocular blur conditions on either the firm or foam surfaces. Conclusions: Findings indicate that binocular blur significantly impairs postural stability, and suggests that improvements in postural stability may justify first-eye cataract surgery, particularly during somatosensory disruption. Postural stability was not significantly impaired in the monocular cataract blur conditions compared to the normal vision condition, nor was there any effect of ocular dominance on postural stability in the presence of monocular cataract blur.

Do strategy choices matter for nascent firms? A study on effectuation and causation impacts on new ventures outcomes

Principal Topic : Nascent entrepreneurship has drawn the attention of scholars in the last few years (Davidsson, 2006, Wagner, 2004). However, most studies have asked why firms are created focussing on questions such as what are the characteristics (Delmar and Davidsson, 2000) and motivations (Carter, Gartner, Shaver & Reynolds, 2004) of nascent entrepreneurs, or what are the success factors in venture creation (Davidsson & Honig; 2003; Delmar and Shane, 2004). In contrast, the question of how companies emerge is still in its infancy. On a theoretical side, effectuation, developed by Sarasvathy (2001) offers one view of the strategies that may be at work during the venture creation process. Causation, the theorized inverse to effectuation, may be described as a rational reasoning method to create a company. After a comprehensive market analysis to discover opportunities, the entrepreneur will select the alternative with the higher expected return and implement it through the use of a business plan. In contrast, effectuation suggests that the future entrepreneur will develop her new venture in a more iterative way by selecting possibilities through flexibility and interaction with the market, affordability of loss of resources and time invested, development of pre-commitments and alliances from stakeholders. Another contrasting point is that causation is ''goal driven'' while an effectual approach is ''mean driven'' (Sarasvathy, 2001) One of the predictions of effectuation theory is effectuation is more likely to be used by entrepreneurs early in the venture creation process (Sarasvathy, 2001). However, this temporal aspect and the impact of the effectuation strategy on the venture outcomes has so far not been systematically and empirically tested on large samples. The reason behind this research gap is twofold. Firstly, few studies collect longitudinal data on emerging ventures at an early enough stage of development to avoid severe survivor bias. Second, the studies that collect such data have not included validated measures of effectuation. The research we are conducting attempts to partially fill this gap by combining an empirical investigation on a large sample of nascent and young firms with the effectuation/causation continuum as a basis (Sarasvathy, 2001). The objectives are to understand the strategies used by the firms during the creation process and measure their impacts on the firm outcomes. Methodology/Key Propositions : This study draws its data from the first wave of the CAUSEE project where 28,383 Australian households were randomly contacted by phone using a specific methodology to capture emerging firms (Davidsson, Steffens, Gordon, Reynolds, 2008). This screening led to the identification of 594 nascent ventures (i.e., firms that are not operating yet) and 514 young firms (i.e., firms that have started operating from 2004) that were willing to participate in the study. Comprehensive phone interviews were conducted with these 1108 ventures. In a likewise comprehensive follow-up 12 months later, 80% of the eligible cases completed the interview. The questionnaire contains specific sections designed to distinguish effectual and causal processes, innovation, gestation activities, business idea changes and ventures outcomes. The effectuation questions are based on the components of effectuation strategy as described by Sarasvathy (2001) namely: flexibility, affordable loss and pre-commitment from stakeholders. Results from two rounds of pre-testing informed the design of the instrument included in the main survey. The first two waves of data have will be used to test and compare the use of effectuation in the venture creation process. To increase the robustness of the results, temporal use of effectuation will be tested both directly and indirectly. 1. By comparing the use of effectuation in nascent and young firms from wave 1 to 2, we will be able to find out how effectuation is affected by time over a 12-month duration and if the stage of venture development has an impact on its use. 2. By comparing nascent ventures early in the creation process versus nascent ventures late in the creation process. Early versus late can be determined with the help of time-stamped gestation activity questions included in the survey. This will help us to determine the change on a small time scale during the creation phase of the venture. 3. By comparing nascent firms to young (already operational) firms. 4. By comparing young firms becoming operational in 2006 with those first becoming operational in 2004. Results and Implications : Wave 1 and 2 data have been completed and wave 2 is currently being checked and 'cleaned'. Analysis work will commence in September, 2009. This paper is expected to contribute to the body of knowledge on effectuation by measuring quantitatively its use and impact on nascent and young firms activities at different stages of their development. In addition, this study will also increase the understanding of the venture creation process by comparing over time nascent and young firms from a large sample of randomly selected ventures. We acknowledge the results from this study will be preliminary and will have to be interpreted with caution as the changes identified may be due to several factors and may not only be attributed to the use/not use of effectuation. Meanwhile, we believe that this study is important to the field of entrepreneurship as it provides some much needed insights on the processes used by nascent and young firms during their creation and early operating stages.

An analysis of the RC4 family of stream ciphers against algebraic attacks

To date, most applications of algebraic analysis and attacks on stream ciphers are on those based on lin- ear feedback shift registers (LFSRs). In this paper, we extend algebraic analysis to non-LFSR based stream ciphers. Specifically, we perform an algebraic analysis on the RC4 family of stream ciphers, an example of stream ciphers based on dynamic tables, and inves- tigate its implications to potential algebraic attacks on the cipher. This is, to our knowledge, the first pa- per that evaluates the security of RC4 against alge- braic attacks through providing a full set of equations that describe the complex word manipulations in the system. For an arbitrary word size, we derive alge- braic representations for the three main operations used in RC4, namely state extraction, word addition and state permutation. Equations relating the inter- nal states and keystream of RC4 are then obtained from each component of the cipher based on these al- gebraic representations, and analysed in terms of their contributions to the security of RC4 against algebraic attacks. Interestingly, it is shown that each of the three main operations contained in the components has its own unique algebraic properties, and when their respective equations are combined, the resulting system becomes infeasible to solve. This results in a high level of security being achieved by RC4 against algebraic attacks. On the other hand, the removal of an operation from the cipher could compromise this security. Experiments on reduced versions of RC4 have been performed, which confirms the validity of our algebraic analysis and the conclusion that the full RC4 stream cipher seems to be immune to algebraic attacks at present.

Reducing high levels of communication apprehension among primary school students

This study focused on a group of primary school teachers as they implemented a variety of intervention actions within their class programs aimed towards supporting the reduction of high levels of communication apprehension (CA) among students.Six teachers and nine students, located across three primary schools, four year levels,and six classes, participated in this study. For reasons of confidentiality the schools,principals, parents, teachers, teacher assistants, and students who were involved in this study were given fictitious names. The following research question was explored in this study: What intervention actions can primary school teachers implement within their class programs that support the reduction of high CA levels among students? Throughout this study the term CA referred to "an individual's level of fear or anxiety associated with either real or anticipated (oral) communication with another person or persons" (McCroskey, 1984, p. 13). The sources of CA were explained with reference to McCroskey's state-trait continuum. The distinctions between high and appropriate levels of CA were determined conceptually and empirically. The education system within which this study was conducted promoted the philosophy of inclusion and the practices of inclusive schooling. Teachers employed in this system were encouraged to create class programs inclusive of and successful for all students. Consequently the conceptual framework within which this study was conducted was based around the notion of inclusion. Action research and case study research were the methodologies used in the study. Case studies described teachers' action research as they responded to the challenge of executing intervention actions within their class programs directed towards supporting the reduction of high CA levels among students. Consequently the teachers and not the researcher were the central characters in each of the case studies. Three principal data collection instruments were used in this study: Personal Report of Communication Fear (PRCF) scale, semistructured interviews, and dialogue journals. The PRCF scale was the screening tool used to identify a pool of students eligible for the study. Data relevant to the students involved in the study were gathered during semistructured interviews and throughout the dialogue journaling process. Dialogue journaling provided the opportunity for regular contact between teachers and the researcher, a sequence to teacher and student intervention behaviours, and a permanent record of teacher and student growth and development. The majority of teachers involved in this study endeavoured to develop class programs inclusive of all students.These teachers acknowledged the importance of modifying aspects of their class programs in response to the diverse and often multiple needs of individual students with high levels of CA. Numerous conclusions were drawn regarding practical ways that the teachers in this study supported the reduction of high CA levels among students. What this study has shown is that teachers can incorporate intervention actions within their class programs aimed towards supporting students lower their high levels of CA. Whilst no teacher developed an identical approach to intervention, similarities and differences were evident among teachers regarding their selection, interpretation, and implementation of intervention actions. Actions that teachers enacted within their class programs emerged from numerous fields of research including CA, inclusion, social skills, behaviour teaching, co-operative learning, and quality schools. Each teacher's knowledge of and familiarity with these research fields influenced their preference for and commitment to particular intervention actions. Additional factors including each teacher's paradigm of inclusion and exclusion contributed towards their choice of intervention actions. Possible implications of these conclusions were noted with reference to teachers,school administrators, support personnel, system personnel, teacher educators, parents, and researchers.