The Effectiveness of Alexander Technique on Music Performance and Musicians' Health and Well-being – a Systematic Review

Purpose Musicians often suffer injuries related to their music playing. Therefore, some use the Alexander Technique (AT), a psycho-physical method that helps to release unnecessary muscle tension and re-educates non-beneficial movement patterns through enhanced kinaesthetic awareness. According to a recent review AT may be effective for chronic back pain. This review aimed to evaluate the evidence for the effectiveness of AT lessons on music performance and musicians’ health and well-being. Methods The following electronic databases were searched up to July 2012 for relevant literature: PUBMED, Google Scholar, CINAHL and EMBASE. The search criteria were "Alexander technique" AND "music*" [all fields]. References were searched, and experts and societies of AT or musicians' medicine contacted for further publications. Results 100 studies were identified. 35 studies were included for further analysis, 5 of which were randomised controlled trials (RCTs), 5 controlled but not randomised, 5 not controlled, 5 qualitative case studies, 2 mixed-models (RCT and case studies), 7 surveys, 4 qualitative case reports and 2 unpublished pilot studies. 13 to 72 musicians participated per RCT. In 5 RCTs AT groups received between 12 and 20 one-to-one lessons. In 4 RCTs control groups received no interventions. Primary outcomes were performance anxiety, performance, "use" as well as respiratory function and pain. Performance anxiety decreased by AT in 3 of 4 RCTs. Music performance was improved by AT in 1 RCT, yet in 2 RCTs comparing neurofeedback (NF) to AT, only NF showed improvements. Conclusions To investigate the effectiveness of AT in musicians a variety of study designs and outcome measures have been used. Evidence from RCTs suggests that AT may improve performance anxiety in musicians. Effects on music performance, body use and respiratory function yet remain inconsistent. Future trials with well-established study designs are warranted to further and more reliably explore the potential of AT as a relatively low cost and low risk method in the interest of musicians.

A coalescent analysis for modeling the mutation process in colorectal cancer

Colorectal cancer is the forth most common diagnosed cancer in the United States. Every year about a hundred forty-seven thousand people will be diagnosed with colorectal cancer and fifty-six thousand people lose their lives due to this disease. Most of the hereditary nonpolyposis colorectal cancer (HNPCC) and 12% of the sporadic colorectal cancer show microsatellite instability. Colorectal cancer is a multistep progressive disease. It starts from a mutation in a normal colorectal cell and grows into a clone of cells that further accumulates mutations and finally develops into a malignant tumor. In terms of molecular evolution, the process of colorectal tumor progression represents the acquisition of sequential mutations. ^ Clinical studies use biomarkers such as microsatellite or single nucleotide polymorphisms (SNPs) to study mutation frequencies in colorectal cancer. Microsatellite data obtained from single genome equivalent PCR or small pool PCR can be used to infer tumor progression. Since tumor progression is similar to population evolution, we used an approach known as coalescent, which is well established in population genetics, to analyze this type of data. Coalescent theory has been known to infer the sample's evolutionary path through the analysis of microsatellite data. ^ The simulation results indicate that the constant population size pattern and the rapid tumor growth pattern have different genetic polymorphic patterns. The simulation results were compared with experimental data collected from HNPCC patients. The preliminary result shows the mutation rate in 6 HNPCC patients range from 0.001 to 0.01. The patients' polymorphic patterns are similar to the constant population size pattern which implies the tumor progression is through multilineage persistence instead of clonal sequential evolution. The results should be further verified using a larger dataset. ^

Redistribution of Soil Organic Matter by Permafrost Disturbance in the Canadian High Arctic

With increased warming in the Arctic, permafrost thaw may induce localized physical disturbance of slopes. These disturbances, referred to as active layer detachments (ALDs), redistribute soil across the landscape, potentially releasing previously unavailable carbon (C). In 2007–2008, widespread ALD activity was reported at the Cape Bounty Arctic Watershed Observatory in Nunavut, Canada. Our study investigated organic matter (OM) composition in soil profiles from ALD-impacted and undisturbed areas. Solid-state 13C nuclear magnetic resonance (NMR) and solvent-extractable biomarkers were used to characterize soil OM. Throughout the disturbed upslope profile, where surface soils and vegetation had been removed, NMR revealed low O-alkyl C content and biomarker analysis revealed low concentrations of solvent-extractable compounds suggesting enhanced erosion of labile-rich OM by the ALD. In the disturbed downslope region, vegetation remained intact but displaced material from upslope produced lateral compression ridges at the surface. High O-alkyl content in the surface horizon was consistent with enrichment of carbohydrates and peptides, but low concentrations of labile biomarkers (i.e., sugars) suggested the presence of relatively unaltered labile-rich OM. Decreased O-alkyl content and biomarker concentrations below the surface contrasted with the undisturbed profile and may indicate the loss of well-established pre-ALD surface drainage with compression ridge formation. However, pre-ALD profile composition remains unknown and the observed decreases may result from nominal pre-ALD OM inputs. These results are the first to establish OM composition in ALD-impacted soil profiles, suggesting reallocation of permafrost-derived soil C to areas where degradation or erosion may contribute to increased C losses from disturbed Arctic soils.

Novel formulations for antigen delivery using biodegradable polymers: new approaches for the use of new and established adjuvants

The use of immunological adjuvants has been established since 1924 and ever since many candidates have been extensively researched in vaccine development. The controlled release of vaccine is another area of biotechnology research, which is advancing rapidly with great potential and success. Encapsulation of peptide and protein drugs within biodegradable microspheres has been amongst the most successful of approaches within the past decade. The present studies have focused on combining the advantages of microsphere delivery systems composed of biodegradable polylactide (PLLA) and polylactide-co-glycolide (PLGA) polymers with that of safe and effective adjuvants. The research efforts were directed to the development of single-dose delivery vehicles which, can be manufactured easily, safely, under mild and favourable conditions to the encapsulated antigens. In pursuing this objective non ionic block copolymers (NIBCs) (Pluronics@ LI01 and L121) were incorporated within poly-dl-lactide (PDLA) micorospheres prepared with emulsification-diffusion method. LI0I and L121 served both as adjuvants and stabilising agents within these vaccine delivery vehicles. These formulations encapsulating the model antigens lysozyme, ovalbumin (OVA) and diphtheria toxoid (DT) resulted in high entrapment efficiency (99%), yield (96.7%) and elicited high and sustained immune response (IgG titres up to 9427) after one single administration over nine months. The structural integrity of the antigens was preserved within these formulations. In evaluating new approaches for the use of well-established adjuvants such as alum, these particles were incorporated within PLLA and PLGA microspheres at much lesser quantities (5-10 times lower) than those contained within conventional alum-adsorbed vaccines. These studies focused on the incorporation of the clinically relevant tetanus toxoid (TT) antigen within biodegradable microspheres. The encapsulation of both alum particles and TT antigen within these micropheres resulted in preparations with high encapsulation efficiency (95%) and yield (91.2%). The immune response to these particles was also investigated to evaluate the secretion of serum IgG, IgG1, IgG2a and IgG2b after a single administration of these vaccines. The Splenic cells proliferation was also investigated as an indication for the induction of cell mediated immunity. These particles resulted in high and sustained immune response over a period of 14 months. The stability of TT within particles was also investigated under dry storage over a period of several months. NIBC microspheres were also investigated as potential DNA vaccine delivery systems using hepatitis B plasmid. These particles resulted in micro spheres of 3-5 μm diameter and were shown to preserve the integrity of the encapsulated (27.7% entrapment efficiency) hepatitis B plasmid.

Lys9 for Glu9 substitution in glucagon-like peptide-1(7-36)amide confers dipeptidylpeptidase IV resistance with cellular and metabolic actions similar to those of established antagonists glucagon-like peptide-1(9-36)amide and exendin (9-39)

The incretin hormone glucagon-like peptide-1(7-36)amide (GLP-1) has been deemed of considerable importance in the regulation of blood glucose. Its effects, mediated through the regulation of insulin, glucagon, and somatostatin, are glucose-dependent and contribute to the tight control of glucose levels. Much enthusiasm has been assigned to a possible role of GLP-1 in the treatment of type 2 diabetes. GLIP-l's action unfortunately is limited through enzymatic inactivation caused by dipeptidylpeptidase IV (DPP IV). It is now well established that modifying GLP-1 at the N-terminal amino acids, His7 and Ala8, can greatly improve resistance to this enzyme. Little research has assessed what effect Glu9-substitution has on GLP-1 activity and its degradation by DPP IV. Here, we report that the replacement of Glu9 of GLP-1 with Lys dramatically increased resistance to DPP IV. This analogue (Lys9)GLP-1, exhibited a preserved GLP-1 receptor affinity, but the usual stimulatory effects of GLP-1 were completely eliminated, a trait duplicated by the other established GLP-1-antagonists, exendin (9-39) and GLP-1 (9-36)amide. We investigated the in vivo antagonistic actions of (Lys9)GLP-1 in comparison with GLP-1(9-36)amide and exendin (9-39) and revealed that this novel analogue may serve as a functional antagonist of the GLP-1 receptor.

Impacts of newly established non-indigenous green crab (Carcinus maenas) on native fauna in Placentia Bay, Newfoundland

The recent invasion of the European green crab (Carcinus maenas) populations in Placentia Bay, Newfoundland and Labrador (NL) raises great concern about potential impacts on local fisheries and native biodiversity. Green crab are highly adaptable and in both native and invaded areas, green crab are well established predators that can outcompete other similarly sized decapods. The main objectives of this thesis were to: 1) identify the native species that green crab compete with for resources; 2) determine the depths and substrate types in which these interactions likely occur; 3) assess the indirect effects of green crab on native crustaceans and their changes in behavior; 4) assess the impacts of green crab on benthic community structure; 5) compare the NL population with other Atlantic Canadian populations in terms of competitive abilities; and 6) compare morphological features of the NL population with other Atlantic Canadian populations. I found that green crab overlap in space and diet with both rock crab (Cancer irroratus) and American lobster (Homarus americanus), potentially leading to a shift in habitat. Laboratory studies on naïve juvenile lobster also suggested shifts in behavior related to green crab, in that lobster decreased foraging activity and increased shelter use in the presence of green crab. Benthic community analyses showed fewer species in mud, sand, and eelgrass sites heavily populated by green crab compared to sites without green crab, although results depended on the taxa involved and I could not eliminate environmental differences through a short term caging study. Foraging ability of green crab varied in intraspecific competition experiments, with populations from NL and Prince Edward Island dominating longer-established populations from Nova Scotia and New Brunswick. Additional studies excluded claw size as a factor driving these results and behavioral differences likely reflected differences in invasion time and population genetics. Overall, green crab in Placentia Bay appear to be altering community structure of benthic invertebrates through predation and they also appear to indirectly impact native crustaceans through competition.

Sea ice and wind variability during the Holocene in East Antarctica

A high-resolution continuous record of diatom census counts and diatom specific biomarkers in sediment core NBP0101-JPC24 allows assessment of oceanographic and environmental conditions in eastern Prydz Bay during the deglaciation (11 100-9000 cal yr BP) at decadal timescale. Our study improves previous snapshots investigations based on resin-embedded thin sections and presents a new proxy that compliments the diatom census counts. Our results suggest that the ice sheet retreat over the core site is dated at ~11 100 cal yr BP, setting the onset of local deglaciation and subsequent open marine conditions. The glacial retreat in Prydz Bay is due to global warming initiated at 18 cal ka BP and the regional development of the Prydz Bay cyclonic gyre. Our results further demonstrate that the deglaciation in eastern Prydz Bay can be separated in four phases: the first between 11 100 and 10 900 cal yr BP when the ice shelf was proximal and sea ice was almost perennial; the second and the third phases between 10 900-10 400 cal yr BP and 10 400-9900 cal yr BP, respectively, when the ice shelf retreated and seasonal sea ice cycle consequently developed promoting warmer water to pump into the bay within the gyre, which in turn forced the ice shelf recession and the yearly sea ice cycle establishment; and the fourth between 9900 and 9000 cal yr BP when Holocene condition were set with a recurrent seasonal sea ice cycle and a well established Prydz Bay gyre.

Redistribution of Soil Organic Matter by Permafrost Disturbance in the Canadian High Arctic

With increased warming in the Arctic, permafrost thaw may induce localized physical disturbance of slopes. These disturbances, referred to as active layer detachments (ALDs), redistribute soil across the landscape, potentially releasing previously unavailable carbon (C). In 2007–2008, widespread ALD activity was reported at the Cape Bounty Arctic Watershed Observatory in Nunavut, Canada. Our study investigated organic matter (OM) composition in soil profiles from ALD-impacted and undisturbed areas. Solid-state 13C nuclear magnetic resonance (NMR) and solvent-extractable biomarkers were used to characterize soil OM. Throughout the disturbed upslope profile, where surface soils and vegetation had been removed, NMR revealed low O-alkyl C content and biomarker analysis revealed low concentrations of solvent-extractable compounds suggesting enhanced erosion of labile-rich OM by the ALD. In the disturbed downslope region, vegetation remained intact but displaced material from upslope produced lateral compression ridges at the surface. High O-alkyl content in the surface horizon was consistent with enrichment of carbohydrates and peptides, but low concentrations of labile biomarkers (i.e., sugars) suggested the presence of relatively unaltered labile-rich OM. Decreased O-alkyl content and biomarker concentrations below the surface contrasted with the undisturbed profile and may indicate the loss of well-established pre-ALD surface drainage with compression ridge formation. However, pre-ALD profile composition remains unknown and the observed decreases may result from nominal pre-ALD OM inputs. These results are the first to establish OM composition in ALD-impacted soil profiles, suggesting reallocation of permafrost-derived soil C to areas where degradation or erosion may contribute to increased C losses from disturbed Arctic soils.

A model for assessing and correcting construction project health

Abstract Maintaining the health of a construction project can help to achieve the desired outcomes of the project. An analogy is drawn to the medical process of a human health check where it is possible to broadly diagnose health in terms of a number of key areas such as blood pressure or cholesterol level. Similarly it appears possible to diagnose the current health of a construction project in terms of a number of Critical Success Factors (CSFs) and key performance indicators (KPIs). The medical analogy continues into the detailed investigation phase where a number of contributing factors are evaluated to identify possible causes of ill health and through the identification of potential remedies to return the project to the desired level of health. This paper presents the development of a model that diagnoses the immediate health of a construction project, investigates the factors which appear to be causing the ill health and proposes a remedy to return the project to good health. The proposed model uses the well-established continuous improvement management model (Deming, 1986) to adapt the process of human physical health checking to construction project health.

Business and software service lifecycle management

Although the service-oriented paradigm has been well established in the technical domain for quite some time now, service governance is still considered a research gap. To ensure adequate governance, there is a necessity to manage services as first-class assets throughout the lifecycle. Now that the concept of ser-vice-orientation is also increasingly applied on the business level to structure an organisation’s capabili-ties, the problem has become an even bigger chal-lenge. This paper presents a generic business and software service lifecycle and aligns it with the com-mon management layers in organisations. Using ser-vice analysis as an example, it moreover illustrates how activities in the service lifecycle may vary on lower levels of granularity depending on the focus on business or software services.

Open Specification for BIM : Sydney Opera House Case Study

Executive Summary The objective of this report was to use the Sydney Opera House as a case study of the application of Building Information Modelling (BIM). The Sydney opera House is a complex, large building with very irregular building configuration, that makes it a challenging test. A number of key concerns are evident at SOH: • the building structure is complex, and building service systems - already the major cost of ongoing maintenance - are undergoing technology change, with new computer based services becoming increasingly important. • the current “documentation” of the facility is comprised of several independent systems, some overlapping and is inadequate to service current and future services required • the building has reached a milestone age in terms of the condition and maintainability of key public areas and service systems, functionality of spaces and longer term strategic management. • many business functions such as space or event management require up-to-date information of the facility that are currently inadequately delivered, expensive and time consuming to update and deliver to customers. • major building upgrades are being planned that will put considerable strain on existing Facilities Portfolio services, and their capacity to manage them effectively While some of these concerns are unique to the House, many will be common to larger commercial and institutional portfolios. The work described here supported a complementary task which sought to identify if a building information model – an integrated building database – could be created, that would support asset & facility management functions (see Sydney Opera House – FM Exemplar Project, Report Number: 2005-001-C-4 Building Information Modelling for FM at Sydney Opera House), a business strategy that has been well demonstrated. The development of the BIMSS - Open Specification for BIM has been surprisingly straightforward. The lack of technical difficulties in converting the House’s existing conventions and standards to the new model based environment can be related to three key factors: • SOH Facilities Portfolio – the internal group responsible for asset and facility management - have already well established building and documentation policies in place. The setting and adherence to well thought out operational standards has been based on the need to create an environment that is understood by all users and that addresses the major business needs of the House. • The second factor is the nature of the IFC Model Specification used to define the BIM protocol. The IFC standard is based on building practice and nomenclature, widely used in the construction industries across the globe. For example the nomenclature of building parts – eg ifcWall, corresponds to our normal terminology, but extends the traditional drawing environment currently used for design and documentation. This demonstrates that the international IFC model accurately represents local practice for building data representation and management. • a BIM environment sets up opportunities for innovative processes that can exploit the rich data in the model and improve services and functions for the House: for example several high-level processes have been identified that could benefit from standardized Building Information Models such as maintenance processes using engineering data, business processes using scheduling, venue access, security data and benchmarking processes using building performance data. The new technology matches business needs for current and new services. The adoption of IFC compliant applications opens the way forward for shared building model collaboration and new processes, a significant new focus of the BIM standards. In summary, SOH current building standards have been successfully drafted for a BIM environment and are confidently expected to be fully developed when BIM is adopted operationally by SOH. These BIM standards and their application to the Opera House are intended as a template for other organisations to adopt for the own procurement and facility management activities. Appendices provide an overview of the IFC Integrated Object Model and an understanding IFC Model Data.

A model for assessing and correcting project Health

Maintaining the health of a construction project can help to achieve the desired outcomes of the project. An analogy is drawn to the medical process of a human health check where it is possible to broadly diagnose health in terms of a number of key areas such as blood pressure or cholesterol level. Similarly it appears possible to diagnose the current health of a construction project in terms of a number of Critical Success Factors (CSFs) and key performance indicators (KPIs). The medical analogy continues into the detailed investigation phase where a number of contributing factors are evaluated to identify possible causes of ill health and through the identification of potential remedies to return the project to the desired level of health. This paper presents the development of a model that diagnoses the immediate health of a construction project, investigates the factors which appear to be causing the ill health and proposes a remedy to return the project to good health. The proposed model uses the well-established continuous improvement management model (Deming, 1986) to adapt the process of human physical health checking to construction project health.

Knowing a donor and identifying as one : determinants of people's willingness for related and anonymous living donation in Australia

While LRD (living donation to a genetically/emotionally related recipient) is well established in Australia, LAD (living anonymous donation to a stranger) is rare. Given the increasing use of LAD overseas, Australia may likely follow suit. Understanding the determinants of people’s willingness for LAD is essential but infrequently studied in Australia. Consequently, we compared the determinants of people’s LRD and LAD willingness, and assessed whether these determinants differed according to type of living donation. We surveyed 487 health students about their LRD and LAD willingness, attitudes, identity, prior experience with blood and organ donation, deceased donation preference, and demographics. We used Structural Equation Modelling (SEM) to identify the determinants of willingness for LRD and LAD and paired sample t-tests to examine differences in LRD and LAD attitudes, identity, and willingness. Mean differences in willingness (LRD 5.93, LAD 3.92), attitudes (LRD 6.43, LAD 5.53), and identity (LRD 5.69, LAD 3.58) were statistically significant. Revised SEM models provided a good fit to the data (LRD: x2 (41) = 67.67, p = 0.005, CFI = 0.96, RMSEA = 0.04; LAD: x2 (40) = 79.64, p < 0.001, CFI = 0.95, RMSEA = 0.05) and explained 45% and 54% of the variation in LRD and LAD willingness, respectively. Four common determinants of LRD and LAD willingness emerged: identity, attitude, past blood donation, and knowing a deceased donor. Religious affiliation and deceased donation preference predicted LAD willingness also. Identifying similarities and differences in these determinants can inform future efforts aimed at understanding people’s LRD and LAD willingness and the evaluation of potential living donor motives. Notably, this study highlights the importance of people’s identification as a living donor as a motive underlying their willingness to donate their organs while living.

Establishment of a preclinical ovine model for tibial segmental bone defect repair by applying bone tissue engineering strategies

Currently, well-established clinical therapeutic approaches for bone reconstruction are restricted to the transplantation of autografts and allografts, and the implantation of metal devices or ceramic-based implants to assist bone regeneration. Bone grafts possess osteoconductive and osteoinductive properties, however they are limited in access and availability and associated with donor site morbidity, haemorrhage, risk of infection, insufficient transplant integration, graft devitalisation, and subsequent resorption resulting in decreased mechanical stability. As a result, recent research focuses on the development of alternative therapeutic concepts. The field of tissue engineering has emerged as an important approach to bone regeneration. However, bench to bedside translations are still infrequent as the process towards approval by regulatory bodies is protracted and costly, requiring both comprehensive in vitro and in vivo studies. The subsequent gap between research and clinical translation, hence commercialization, is referred to as the ‘Valley of Death’ and describes a large number of projects and/or ventures that are ceased due to a lack of funding during the transition from product/technology development to regulatory approval and subsequently commercialization. One of the greatest difficulties in bridging the Valley of Death is to develop good manufacturing processes (GMP) and scalable designs and to apply these in pre-clinical studies. In this article, we describe part of the rationale and road map of how our multidisciplinary research team has approached the first steps to translate orthopaedic bone engineering from bench to bedside byestablishing a pre-clinical ovine critical-sized tibial segmental bone defect model and discuss our preliminary data relating to this decisive step.

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.