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.

Is there something quantum-like about the human mental lexicon?

Following an early claim by Nelson & McEvoy suggesting that word associations can display `spooky action at a distance behaviour', a serious investigation of the potentially quantum nature of such associations is currently underway. In this paper quantum theory is proposed as a framework suitable for modelling the mental lexicon, specifically the results obtained from both intralist and extralist word association experiments. Some initial models exploring this hypothesis are discussed, and they appear to be capable of substantial agreement with pre-existing experimental data. The paper concludes with a discussion of some experiments that will be performed in order to test these models.

CSI Lincoln : an investigation into a declining housing market

The residential property market in New Zealand has been experiencing a boom and bubble period from 2001 through to mid 2007. Following a number of increases in the Official Cash Rate by the Reserve Bank and a decline in net migration numbers the housing market was perceived to be over inflated and due for a major correction. Numerous media, Government Departments, property experts and economists have been predicting significant reductions in the median price of residential property throughout New Zealand. This paper will analyse house prices in specific socio-economic locations within Christchurch over the past 12 months to determine how significant the current housing decline is. This study will review the change in residential property prices, variations in property listings since April 2008, sale volumes and days on the market across a range of housing sectors to determine the extent and range of any residential property downturn in the NZ recession.

Does occupational stress really matter? A study of psychological climate and stress on job satisfaction in Thailand

This study explored the prediction of psychological climate and stresses on job satisfaction in non U.S. setting. A total of 450 surveys were sent to 11 organisations in Thailand and employees were asked to fill out the survey. The first hypothesis that positive psychological climate dimensions predicted lower level of stresses among Thai employees was partially accepted. Further regression analysis tested second hypothesis that positive psychological climate dimensions and low level of stresses predict job satisfaction among Thai employees. Contrary to expectation, only stress variables predicted job satisfaction. Thai culture influence was discussed.

Psychological treatment dropout among pathological gamblers

Premature dropout from treatments for pathological gambling is potentially of significant importance, if it occurs before substantial progress has been made in addressing the problem. A systematic review of current research on dropout from psychological treatments for pathological gambling identified 12 studies from five countries. Dropout ranged from 14% to 50%, with a median of dropout 26%. Overall, 31% of the participants dropped out of treatment. Few studies distinguish between dropouts at different stages of participation. The evidence on specific variables that predict dropout is limited or inconsistent, and is characterised by a lack of a coherent, gambling-specific model and by methodological problems. Two studies that attempted to apply motivational and compliance-enhancing techniques were found. Both showed promising effects on reduction of dropout and improvement of short-term impact of treatment, but inconsistent results on longer-term outcomes were obtained. The review highlighted a need for more rigorous investigation of the extent of dropout and of variables associated with dropout from pathological gambling treatment programs. Further research on interventions to enhance retention and reduce dropout from psychological treatment is also required.

The stimulation of healing within a rat calvarial defect by mPCL–TCP/collagen scaffolds loaded with rhBMP-2

Bone morphogenetic proteins (BMPs) have been widely investigated for their clinical use in bone repair and it is known that a suitable carrier matrix to deliver them is essential for optimal bone regeneration within a specific defect site. Fused deposited modeling (FDM) allows for the fabrication of medical grade poly 3-caprolactone/tricalcium phosphate (mPCL–TCP) scaffolds with high reproducibility and tailor designed dimensions. Here we loaded FDM fabricated mPCL–TCP/collagen scaffolds with 5 mg recombinant human (rh)BMP-2 and evaluated bone healing within a rat calvarial critical-sized defect. Using a comprehensive approach, this study assessed the newly regenerated bone employing microcomputed tomography (mCT), histology/histomorphometry, and mechanical assessments. By 15 weeks, mPCL–TCP/collagen/rhBMP-2 defects exhibited complete healing of the calvarium whereas the non- BMP-2-loaded scaffolds showed significant less bone ingrowth, as confirmed by mCT. Histomorphometry revealed significantly increased bone healing amongst the rhBMP-2 groups compared to non-treated scaffolds at 4 and 15 weeks, although the % BV/TV did not indicate complete mineralisation of the entire defect site. Hence, our study confirms that it is important to combine microCt and histomorphometry to be able to study bone regeneration comprehensively in 3D. A significant up-regulation of the osteogenic proteins, type I collagen and osteocalcin, was evident at both time points in rhBMP-2 groups. Although mineral apposition rates at 15 weeks were statistically equivalent amongst treatment groups, microcompression and push-out strengths indicated superior bone quality at 15 weeks for defects treated with mPCL–TCP/collagen/rhBMP-2. Consistently over all modalities, the progression of healing was from empty defect < mPCL–TCP/collagen < mPCL–TCP/collagen/rhBMP-2, providing substantiating data to support the hypothesis that the release of rhBMP-2 from FDM-created mPCL–TCP/collagen scaffolds is a clinically relevant approach to repair and regenerate critically-sized craniofacial bone defects. Crown Copyright 2008 Published by Elsevier Ltd. All rights reserved.

The prognostic significance of quality of life following breast cancer [Conference Abstract]

Introduction: Evidence suggests a positive association between quality of life (QOL). and overall survival(OS). among metastatic breast cancer (BC). patients, although the relationship in early-stage BC is unclear. This work examines the association between QOL and OS following a diagnosis of early-stage BC. ----- Methods: A population-based sample of Queensland women (n=287). with early-stage, invasive, unilateral BC, were prospectively observed for a median of 6.6 years. QOL was assessed at six and 18 months post-diagnosis using the Functional Assessment of Cancer Therapy, Breast FACT-B+4. questionnaire. Raw scores for the FACT-B+4 scales were computed and individuals were categorised according to whether QOL declined, remained stable or improved over time. OS was measured from the date of diagnosis to the date of death or was censored at the date of last follow-up. Risk ratios (RR) and 95% confidence intervals (CI). for the association between QOL and OS were obtained using Cox proportional hazards survival models adjusted for confounding characteristics. ----- Results: A total of 27 (9.4%). women died during the follow-up period. Three baseline QOL scales (emotional, general and overall QOL) were significantly associated with OS, with RRs ranging between 0.89 95% CI: 0.81, 0.98; P=0.01. and 0.98 (95% CI: 0.96, 0.99; P=0.03),indicating a 2%-11% reduced risk of death for every one unit increase in QOL. When QOL was categorised according to changes between six and 18 months post-diagnosis, analyses showed that for those who experienced declines in functional and physical QOL, risk of death increased by two- (95% CI: 1.43, 12.52; P<0.01) and four-fold (95% CI: 1.15, 7.19; P=0.02), respectively. Conclusions: This work indicates that specific QOL scales at six months post-diagnosis, and changes in certain QOL scales over the subsequent 12-month period (as measured by the FACT-B+4), are associated with overall survival in women with early-stage breast cancer.

Longitudinal patterns of weight in women diagnosed with breast cancer [Conference Abstract]

Introduction: Weight gain is a common concern following breast cancer and has been associated with negative health outcomes. As such, prevention of weight gain is of clinical interest. This work describes weight change between 6- and 18-months following a breast cancer diagnosis and explores the personal, treatment and behavioural characteristics associated with gains in weight. Methods: Body mass index was objectively assessed, at three-monthly intervals, on a population-based sample of women newly diagnosed with unilateral breast cancer (n=185). Changes in BMI between 6- and 18-months post-diagnosis were calculated, with gains of one or more being considered clinically detrimental to future health. Results: Approximately 60% of participants were overweight or obese at 6-months post-diagnosis. While BMI remained relatively stable across the testing period (range=27.3-27.8), 24% of participants experienced clinically relevant gains in BMI (median gains=1.9). Following adjustment for potential confounders, younger age (<45 years; Odds ratio, OR=9.8), being morbidly obese at baseline (OR=4.6) and receiving hormone therapy (OR=4.8) were characteristics associated with an increased odds (p<0.05) of gaining BMI. Other characteristics associated with gains in BMI were more extensive surgery and having a history of smoking, although these relationships were not supported statistically. In contrast, caring for younger children was associated with reduced risk of gaining BMI (OR=0.3, p=0.20). Conclusions: Clinically relevant weight gain between 6- and 18-months post-breast cancer diagnosis is an issue for one in four women, with certain subgroups being particularly susceptible. However, the majority of women diagnosed with breast cancer are overweight or obese and gains in body weight are common. Thus, interventions that address the importance of achieving and sustaining a healthy body weight, delivered to all women with breast cancer, may have greater public health impact than interventions targeting any specific breast cancer subgroup.

Discussions in space

In-place digital augmentation enhances the experience of physical spaces through digital technologies that are directly accessible within that space. This can take place in many forms and ways, e.g., through location-aware applications running on the individuals’ portable devices, such as smart phones, or through large static devices, such as public displays, which are located within the augmented space and accessible by everyone. The hypothesis of this study is that in-place digital augmentation, in the context of civic participation, where citizens collaboratively aim at making their community or city a better place, offers significant new benefits, because it allows access to services or information that are currently inaccessible to urban dwellers where and when they are needed: in place. This paper describes our work in progress deploying a public screen to promote civic issues in public, urban spaces, and to encourage public feedback and discourse via mobile phones.

Novel educational training program for community pharmacists

There is little evidence that workshops alone have a lasting impact on the day-to-day practice of participants. The current paper examined a strategy to increase generalization and maintenance of skills in the natural environment using pseudo-patients and immediate performance feedback to reinforce skills acquisition. A random half of pharmacies (N=30) took part in workshop training aimed at optimizing consumers' use of nonprescription analgesic products. Pharmacies in the training group also received performance feedback on their adherence to the recommended protocol. Feedback occurred immediately after a pseudo-patient visit in which confederates posed as purchasers of analgesics, and combined positive and corrective elements. Trained pharmacists were significantly more accurate at identifying people who misused the medication (P<0.001). The trained pharmacists were more likely than controls to use open-ended questions (P<0.001), assess readiness to change problematic use (P <0.001), and to deliver a brief intervention that was tailored to the person's commitment to alter his/her usage (P <0.001). Participants responded to the feedback positively. Results were consistent with the hypothesis that when workshop is combined with on-site performance feedback, it enhances practitioners' adherence to protocols in the natural setting.

Eye-movements and visual imagery : a working memory approach to the treatment of post-traumatic stress disorder

It has been claimed that the symptoms of post-traumatic stress disorder (PTSD) can be ameliorated by eye-movement desensitization-reprocessing therapy (EMD-R), a procedure that involves the individual making saccadic eye-movements while imagining the traumatic event. We hypothesized that these eye-movements reduce the vividness of distressing images by disrupting the function of the visuospatial sketchpad (VSSP) of working memory, and that by doing so they reduce the intensity of the emotion associated with the image. This hypothesis was tested by asking non-PTSD participants to form images of neutral and negative pictures under dual task conditions. Their images were less vivid with concurrent eye-movements and with a concurrent spatial tapping task that did not involve eye-movements. In the first three experiments, these secondary tasks did not consistently affect participants' emotional responses to the images. However, Expt 4 used personal recollections as stimuli for the imagery task, and demonstrated a significant reduction in emotional response under the same dual task conditions. These results suggest that, if EMD-R works, it does so by reducing the vividness and emotiveness of traumatic images via the VSSP of working memory. Other visuospatial tasks may also be of therapeutic value.

Ultrafine particles in indoor air of a school : possible role of secondary organic aerosols

The aim of this work was to investigate ultrafine particles (< 0.1 μm) in primary school classrooms, in relation to the classrooms activities. The investigations were conducted in three classrooms during two measuring campaigns, which together encompassed a period of 60 days. Initial investigations showed that under the normal operating conditions of the school there were many occasions in all three classrooms where indoor particle concentrations increased significantly compared to outdoor levels. By far the highest increases in the classroom resulted from art activities (painting, gluing and drawing), at times reaching over 1.4 x 105 particle cm-3. The indoor particle concentrations exceeded outdoor concentrations by approximately one order of magnitude, with a count median diameter ranging from 20-50 nm. Significant increases also occurred during cleaning activities, when detergents were used. GC-MS analysis conducted on 4 samples randomly selected from about 30 different paints and glues, as well as the detergent used in the school, showed that d-limonene was one of the main organic compounds of the detergent, however, it was not detected in the samples of the paints and the glue. Controlled experiments showed that this monoterpene, emitted from the detergent, reacted with O3 (at outdoor ambient concentrations ranging from 0.06-0.08ppm) and formed secondary organic aerosols. Further investigations to identify other liquids which may be potential sources of the precursors of secondary organic aerosols, were outside the scope of this project, however, it is expected that the problem identified by this study could be more widely spread, since most primary schools use liquid materials for art classes, and all schools use detergents for cleaning. Further studies are therefore recommended to better understand this phenomenon and also to minimize school children exposure to ultrafine particles from these indoor sources.

An effective model of using negative relevance feedback for information filtering

Over the years, people have often held the hypothesis that negative feedback should be very useful for largely improving the performance of information filtering systems; however, we have not obtained very effective models to support this hypothesis. This paper, proposes an effective model that use negative relevance feedback based on a pattern mining approach to improve extracted features. This study focuses on two main issues of using negative relevance feedback: the selection of constructive negative examples to reduce the space of negative examples; and the revision of existing features based on the selected negative examples. The former selects some offender documents, where offender documents are negative documents that are most likely to be classified in the positive group. The later groups the extracted features into three groups: the positive specific category, general category and negative specific category to easily update the weight. An iterative algorithm is also proposed to implement this approach on RCV1 data collections, and substantial experiments show that the proposed approach achieves encouraging performance.

Mood, persistence, and success

Tested the hypothesis that level of performance and persistence in completing tasks is affected by mood. 44 female and 41 male college students received tape-recorded instructions to recall vividly happy or sad experiences or to imagine a neutral situation. Results for the primary dependent variables on which a mood difference was predicted were analyzed with a multivariate analysis of variance (MANOVA). After the induction happy Ss persisted longer at an anagrams task and solved more anagrams than sad Ss. Women were also faster at reaching solutions when happy than sad. Results support the hypothesis that positive moods promote persistence and ultimate success, but they raise questions about the role of self-efficacy and the sources of gender differences.

Challenging endoscopy reprocessing guidelines: a prospective study investigating the safe shelf life of flexible endoscopes in a tertiary gastroenterology unit.

Professional prac− tice guidelines for endoscope reprocessing re− commend reprocessing endoscopes between each case and proper storage following repro− cessing after the last case of the list. There is lim− ited empirical evidence to support the efficacy of endoscope reprocessing prior to use in the first case of the day; however, internationally, many guidelines continue to recommend this practice. The aim of this study is to estimate a safe shelf life for flexible endoscopes in a high−turnover gastroenterology unit. Materials and methods: In a prospective obser− vational study, all flexible endoscopes in active service during the 3−week study period were mi− crobiologically sampled prior to reprocessing be− fore the first case of the day (n = 200). The main outcome variables were culture status, organism cultured, and shelf life. Results: Among the total number of useable samples (n = 194), the overall contamination rate was 15.5 %, with a pathogenic contamination rate of 0.5 %. Mean time between last case one day and reprocessing before the first case on the next day (that is, shelf life) was 37.62 h (SD 36.47). Median shelf life was 18.8 h (range 5.27± 165.35 h). The most frequently identified organ− ism was coagulase−negative Staphylococcus, an environmental nonpathogenic organism. Conclusions: When processed according to es− tablished guidelines, flexible endoscopes remain free from pathogenic organisms between last case and next day first case use. Significant re− ductions in the expenditure of time and resources on reprocessing endoscopes have the potential to reduce the restraints experienced by high−turnover endoscopy units and improve ser− vice delivery.