The relationship between anti-mullerian hormone in women receiving fertility assessments and age at menopause in subfertile women : evidence from large population studies

Context: Anti-Müllerian hormone (AMH) concentration reflects ovarian aging and is argued to be a useful predictor of age at menopause (AMP). It is hypothesized that AMH falling below a critical threshold corresponds to follicle depletion, which results in menopause. With this threshold, theoretical predictions of AMP can be made. Comparisons of such predictions with observed AMP from population studies support the role for AMH as a forecaster of menopause. Objective: The objective of the study was to investigate whether previous relationships between AMH and AMP are valid using a much larger data set. Setting: AMH was measured in 27 563 women attending fertility clinics. Study Design: From these data a model of age-related AMH change was constructed using a robust regression analysis. Data on AMP from subfertile women were obtained from the population-based Prospect-European Prospective Investigation into Cancer and Nutrition (Prospect- EPIC) cohort (n � 2249). By constructing a probability distribution of age at which AMH falls below a critical threshold and fitting this to Prospect-EPIC menopausal age data using maximum likelihood, such a threshold was estimated. Main Outcome: The main outcome was conformity between observed and predicted AMP. Results: To get a distribution of AMH-predicted AMP that fit the Prospect-EPIC data, we found the critical AMH threshold should vary among women in such a way that women with low age-specific AMH would have lower thresholds, whereas women with high age-specific AMH would have higher thresholds (mean 0.075 ng/mL; interquartile range 0.038–0.15 ng/mL). Such a varying AMH threshold for menopause is a novel and biologically plausible finding. AMH became undetectable (�0.2 ng/mL) approximately 5 years before the occurrence of menopause, in line with a previous report. Conclusions: The conformity of the observed and predicted distributions of AMP supports the hypothesis that declining population averages of AMH are associated with menopause, making AMH an excellent candidate biomarker for AMP prediction. Further research will help establish the accuracy of AMH levels to predict AMP within individuals.

Emptiness and fullness : Pinter, anti-architecture and politics

Classical architecture has a long history of representing the idealized proportions of the human body, derived from the Vitruvian man. This association with the idealized human form has also associated architecture as symbiotic with prevailing power structures. Meaning that architecture is always loaded with some signification, it creates a highly inscribed space. In the absence of architecture space is not necessarily without inscription, for within the void there can exist an anti-architecture. Like the black box theatre, it is both empty and full at the same time, in the absence of the architecture, the void of space and how it is occupied becomes much more profound. As Dorita Hannah writes, ‘In denying a purely visual apprehension of built space, and suggesting a profound interiority, the black-box posits a new way of regarding the body in space.’ This paper analyses the work of Harold Pinter and his use of the body to create an anti-architecture to subvert oppressors and power structures. Pinter’s works are an important case study in this research due to their political nature. His works are also heavily tied to territory, which bound the works in a dependent relationship with a simulated ‘place’. In the citation accompanying the playwright’s Nobel Laureate it states, '...in his plays [he] uncovers the precipice under everyday prattle and forces entry into oppression's closed rooms.' In Pinter’s work oppression manifests itself in the representation of a room, the architecture, which is the cause of a power struggle when objectified and defeated when subjectified. The following work examines how Pinter uses the body to subjectify and represent architecture as authority in his earlier works, which relied on detailed mimetic sets of domestic rooms, and then in his later political works, that were freed of representational scenography. This paper will also look at the adaption of Pinter’s work by the Belarus Free Theatre in their 2008 production of ‘Being Harold Pinter.’ The work of Pinter and the Belarus Free Theatre are concerned with authoritarian political structures. That is, political structures that works against ideas of individualism, ascribing to a mass-produced body as an artifact of dictatorship and conservatism. The focus on the body in space on an empty stage draws attention to the individual – the body amongst scenography can become merely another prop, lost in the borders and boundaries the scenery dictates. Through an analysis of selected works by Harold Pinter and their interpretations, this paper examines this paradox of emptiness and fullness through the body as anti-architecture in performance.

Children as change agents for sustainability : an action research case study in a kindergarten

At a time when global consumption and production levels are 25 percent higher than the Earth’s sustainable carrying capacity, there are worldwide calls to find ways to sustain the Earth for this and future generations. A central premise of this study is that education systems have an obligation to participate in this move towards sustainability and can respond by embedding education for sustainability into curricula. This study took early childhood education as its focus due to the teacherresearcher’s own concerns about the state of the planet, coupled with early childhood education’s established traditions of nature-based and child-centred pedagogy. The study explored the experiences of a class of kindergarten children as they undertook a Project Approach to learning about environmental sustainability. The Project Approach is an adaptation of Chard’s work which is situated within a constructivist theoretical framework (Chard, 2011). The Project Approach involves in-depth investigations around an identified topic of interest. It has three phases: introductory, synthesising and culminating phase. The study also investigated the learning journey of the classroom teacher/researcher who broadened her long-held co-constructivist teaching approaches to include transformative practices in order to facilitate curriculum which embedded education for sustainability. While coconstructivist approaches focus on the co-construction of knowledge, transformative practices are concerned with creating change. An action research case study was conducted. This involved twenty-two children who attended an Australian kindergarten. Data were collected and analysed over a seven week period. The study found that young children can be change agents for sustainability when a Project Approach is broadened to include transformative practices. The study also found that the child participants were able to think critically about environmental and sustainability issues, were able to create change in their local contexts, and took on the role of educators to influence others’ environmental behaviours. Another finding was that the teacher-researcher’s participation in the study caused a transformation of both her teaching philosophy and the culture at the kindergarten. An important outcome of the study was the development of a new curriculum model that integrates and has applicability for curriculum development and teacher practice.

The beliefs which influence young males to speed and strategies to slow them down : informing the content of anti-speeding messages

Young male drivers are over-represented in road-related fatalities. Speeding represents a pervasive and significant contributor to road trauma. Anti-speeding messages represent a long-standing strategy aimed at discouraging drivers from speeding. These messages, however, have not always achieved their persuasive objectives which may be due, in part, to them not always targeting the most salient beliefs underpinning the speeding behavior of particular driver groups. The current study elicited key beliefs underpinning speeding behavior as well as strategies used to avoid speeding, using a well-validated belief-based model, the Theory of Planned Behavior and in-depth qualitative methods. To obtain the most comprehensive understanding about the salient beliefs and strategies of young male drivers, how such beliefs and strategies compared with those of drivers of varying ages and gender, was also explored. Overall, 75 males and females (aged 17-25 or 30-55 years) participated in group discussions. The findings revealed beliefs that were particularly relevant to young males and that would likely represent key foci for developing message content. For instance, the need to feel in control and the desire to experience positive affect when driving were salient advantages; while infringements were a salient disadvantage and, in particular, the loss of points and the implications associated with potential licence loss as opposed to the monetary (fine) loss (behavioral beliefs). For normative influences, young males appeared to hold notable misperceptions (compared with other drivers, such as young females); for instance, young males believed that females/girlfriends were impressed by their speeding. In the case of control beliefs, the findings revealed low perceptions of control with respect to being able to not speed and a belief that something “extraordinary” would need to happen for a young male driver to lose control of their vehicle while speeding. The practical implications of the findings, in terms of providing suggestions for devising the content of anti-speeding messages, are discussed.

Inclusion, schools and anti-discrimination law : parents' experiences and inclusion

With the increasing enrolment of students with disabilities in primary schools and the enactment of legislative protections for students with disabilities in Disability Discrimination legislation and the Disability Standards for Education, this study examines the experiences of parents of students with disabilities in Queensland State schools. This study is concerned with the experiences that parents of children with disabilities have in relation to the concept and processes of inclusive classroom practice within the primary school. The experiences of parents in large metropolitan schools in Queensland, Australia are analysed in light of current anti-discrimination legislation operating within Australia. Data were collected using a mixed methodology in which 50 parents from nine large metropolitan Queensland State schools responded to a Parent Questionnaire about their experiences in their child’s school. This was followed by two focus groups with a total of six parents who described their experiences in their child’s school. Together the qualitative and quantitative information complemented the other to provide a unique perspective on the impact of anti-discrimination legislation. The findings from the study suggest that parents and their children continue to be discriminated against and that the legislation and associated standards have not eliminated this discrimination. Recommendations are made in the final chapter that propose an inclusive schooling framework for students with disabilities. This intends to ensure not only compliance with the ‘spirit’ of Anti-Discrimination legislation and the Disability Standards, but also a means by which schools may evolve to become inclusive and embracing of difference as part of overall richness of schools as opposed to deficiency.

Protective effects of sweroside on human MG-63 cells and rat osteoblasts

Herbal Fructus Corni is a folk medicine with a long history of safe use for treating osteoporosis in postmenopausal women or elderly men in Asia. Sweroside is a bioactive herbal ingredient isolated from Fructus Corni, which has been widely used for the treatment of osteoporosis in traditional Chinese medicine (TCM). Unfortunately, the working mechanisms of this compound are difficult to determine and thus remain unclear. The aim of the study was performed to determine the potential molecular mechanism of the anti-osteoporotic effect of sweroside on the human MG-63 cells and rat osteoblasts. 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) test was used to observe the effect of sweroside on cell proliferation. The activity of alkaline phosphatase (ALP) and the amount of osteocalcin were also assayed the cell differentiation. Sweroside significantly increased the proliferation of human MG-63 cells and rat osteoblasts (P<0.01). It increased the activity of ALP, and osteocalcin was also elevated in response to sweroside (P<0.05). Of note, flowcytometer assay showed that sweroside can attenuate and inhibit apoptosis. Sweroside has a direct osteogenic effect on the proliferation and differentiation of cultured human MG-63 cells and rat osteoblasts in vitro. These data will help in understanding the molecular mechanisms of therapeutic efficacy of sweroside, and highlight insights into drug discovery. In the current study, sweroside has been suggested to be a promising osteoporosis therapeutic natural product.

Isolation of bioactive compounds that relate to the anti-platelet activity of Cymbopogon ambiguus

Infusions and decoctions of Cymbopogon ambiguus have been used traditionally in Australia for the treatment of headache, chest infections and muscle cramps. The aim of the present study was to screen and identify bioactive compounds from C. ambiguus that could explain this plant's anti-headache activity. A dichloromethane extract of C. ambiguus was identified as having activity in adenosine-diphosphate-induced human platelet aggregation and serotonin-release inhibition bioassays. Subsequent fractionation of this extract led to the isolation of four phenylpropenoids, eugenol, elemicin, Eugenol methylether and trans-isoelemicin. While both Eugenol and elemicin exhibited dose-dependent inhibition of ADP-induced human platelet serotonin release, only eugenol displayed potent inhibitory activity with an IC(50) value of 46.6 microM, in comparison to aspirin, with an IC(50) value of 46.1 microM. These findings provide evidence to support the therapeutic efficacy of C. ambiguus in the non-conventional treatment of Headache and Inflammatory conditions.

Results of a phase IIa clinical trial of an anti-inflammatory molecule, chaperonin 10, in multiple sclerosis

Background Chaperonin 10 (Cpn10) is a mitochondrial molecule involved in protein folding. The aim of this study was to determine the safety profile of Cpn10 in patients with multiple sclerosis (MS). Methods A total of 50 patients with relapse-remitting or secondary progressive MS were intravenously administered 5 mg or 10 mg of Cpn10 weekly for 12 weeks in a double-blind, randomized, placebo controlled, phase II trial. Clinical reviews, including Expanded Disability Status Scale and magnetic resonance imaging (MRI) with Gadolinium, were undertaken every 4 weeks. Stimulation of patient peripheral blood mononuclear cells with lipopolysaccharide ex vivo was used to measure the in vivo activity of Cpn10. Results No significant differences in the frequency of adverse events were seen between treatment and placebo arms. Leukocytes from both groups of Cpn10-treated patients produced significantly lower levels of critical proinflammatory cytokines. A trend toward improvement in new Gadolinium enhancing lesions on MRI was observed, but this difference was not statistically significant. No differences in clinical outcome measures were seen. Conclusions Cpn10 is safe and well tolerated when administered to patients with MS for 3 months, however, a further extended phase II study primarily focused on efficacy is warranted.

Analysis of androgen and anti-androgen regulation of KLK-related peptidase 2, 3, and 4 alternative transcripts in prostate cancer

We assessed whether alternative transcripts (using KLK2, KLK3 and KLK4 as models) are differentially regulated by androgens and anti-androgens as an indicator of prostate cancers as they acquire treatment resistance. Using RNAseq of LNCaP cells treated with dihydrotestosterone, bicalutamide and enzalutamide, we show that the expression of variant KLK transcripts is markedly different to other variant transcripts at those loci. We also reveal that KLK variants are also over 2-fold more highly expressed in prostate cancers compared to their corresponding normal prostate. We propose that androgens and anti-androgens can activate specific variant transcripts of critical prostate cancer genes during treatment resistance

Pten and Ndufb8 aberrations in cervical cancer tissue

Cervical cancer is one of the world's major health issues. Despite many studies in this field, the carcinogenetic events of malignant conversion in cervical tumours have not been significantly characterised. The first aim of this project was to investigate the mutation status of the tumour suppressor gene- Phosphatase and Tension Homolog (PTEN)- in cervical cancer tissue. The second aim of this study was the analysis in the same cervical cancer tissue for aberrations in the mitochondrial electron transport chain subunit gene NDUFB8, which is localised to the same chromosomal contig as PTEN. The third aim was the evaluation of the potential therapeutic anti-cancer drug 2,4-Thiazolidinediones (TZDs) and its affect in regulating the PTEN protein in a cervical cancer cell line (HeLa). To approach the aims, paraffin-embedded cancerous cervical tissue and non-cancerous cervical tissue were obtained. DNA recovered from those tissues was then used to investigate the putative genomic changes regarding the NDUFB8 gene utilising SYBR Green I Real-Time PCR. The PTEN gene was studied via Dual-Labelled probe Real-Time PCR. To investigate the protein expression change of the PTEN protein, HeLa cells were firstly treated with different concentrations of 2,4-Thiazolidinediones and the level of PTEN protein expression was then observed utilising standard protein assays. Results indicated that there were putative copy-number changes between the cancerous cervical tissue and non-cancerous cervical tissue, with regard to the PTEN locus. This implies a potential gain of the PTEN gene in cancerous cervical tissue. With regards to normal cervical tissue versus cancerous cervical tissue no significant melting temperature differences were observed with the SYBR Green I Real-Time PCR in respect to the NDUFB8 gene. A putative up-regulation of PTEN protein was observed in TZD treated HeLa cells. © 2008 Springer Science+Business Media, LLC.

Identification of a serine protease inhibitor which causes inclusion vacuole reduction and is lethal to Chlamydia trachomatis

The mechanistic details of the pathogenesis of Chlamydia, an obligate intracellular pathogen of global importance, have eluded scientists due to the scarcity of traditional molecular genetic tools to investigate this organism. Here we report a chemical biology strategy that has uncovered the first essential protease for this organism. Identification and application of a unique CtHtrA inhibitor (JO146) to cultures of Chlamydia resulted in a complete loss of viable elementary body formation. JO146 treatment during the replicative phase of development resulted in a loss of Chlamydia cell morphology, diminishing inclusion size, and ultimate loss of inclusions from the host cells. This completely prevented the formation of viable Chlamydia elementary bodies. In addition to its effect on the human C. trachomatis strain, JO146 inhibited the viability of the mouse strain, Chlamydia muridarum, both in vitro and in vivo. Thus, we report a chemical biology approach to establish an essential role for Chlamydia CtHtrA. The function of CtHtrA for Chlamydia appears to be essential for maintenance of cell morphology during replicative the phase and these findings provide proof of concept that proteases can be targetted for anti-microbial therapy for intracellular pathogens.

A new method for quantifying the contribution of different critical agents on railway bridge deterioration

Railway Bridges deteriorate over time due to different critical factors including, flood, wind, earthquake, collision, and environment factors, such as corrosion, wear, termite attack, etc. In current practice, the contributions of the critical factors, towards the deterioration of railway bridges, which show their criticalities, are not appropriately taken into account. In this paper, a new method for quantifying the criticality of these factors will be introduced. The available knowledge as well as risk analyses conducted in different Australian standards and developed for bridge-design will be adopted. The analytic hierarchy process (AHP) is utilized for prioritising the factors. The method is used for synthetic rating of railway bridges developed by the authors of this paper. Enhancing the reliability of predicting the vulnerability of railway bridges to the critical factors, will be the significant achievement of this research.

Examining gender differences in drivers' thoughts and feelings about different outcomes of speeding: Implications for future anti-speeding messages

Speeding remains a pervasive road safety problem, increasing both crash frequency and severity. Advertising countermeasures which aim to change individuals’ attitudes and behaviours are a key component in the array of countermeasures aimed at reducing this risky behaviour. Enhancing individuals’ perceptions of the personal relevance of such messages is important for increasing persuasiveness. This study examined what males and females reported as the most concerning aspects associated with (i) receiving a speeding fine, (ii) losing one’s license, and (iii) being involved in a crash. For each of these outcomes, a range of specific and appropriate aspects were assessed. For instance, in relation to receiving a fine, individuals reported the extent to which they would, for example, feel concerned about losing demerit points and paying more in insurance premiums. An online survey of 751 drivers (579 males; 16-79 years) was administered. When controlling for age, overall significant gender differences were found in relation to two of the three outcomes; receiving a fine and being in a crash. Follow-up tests of univariate effects revealed that females consistently reported being significantly more concerned than males on all aspects. Thus, for being fined, females were significantly more concerned with, for example, being caught and receiving a ticket in the mail; while, for being in a crash, specific aspects included, for example, injuring/killing oneself and seeing oneself as not a good/safe driver. The findings are discussed in terms of their implications for developing well-targeted messages aimed at discouraging drivers from speeding.

The effects and interactions of GABAergic and dopaminergic agents in the prevention of form deprivation myopia by brief periods of normal vision

Intravitreal injections of GABA antagonists, dopamine agonists and brief periods of normal vision have been shown separately to inhibit form-deprivation myopia (FDM). Our study had three aims: (i) establish whether GABAergic agents modify the myopia protective effect of normal vision, (ii) investigate the receptor sub-type specificity of any observed effect, and (iii) consider an interaction with the dopamine (DA) system. Prior to the period of normal vision GABAergic agents were applied either (i) individually, (ii) in combination with other GABAergic agents (an agonist with an antagonist), or (iii) in combination with DA agonists and antagonists. Water injections were given to groups not receiving drug treatments so that all experimental eyes received intravitreal injections. As shown previously, constant form-deprivation resulted in high myopia and when diffusers were removed for 2 h per day the period of normal vision greatly reduced the FDM that developed. GABA agonists inhibited the protective effect of normal vision whereas antagonists had the opposite effect. GABAA/C agonists and D2 DA antagonists when used in combination were additive in suppressing the protective effect of normal vision. A D2 DA agonist restored some of the protective effect of normal vision that was inhibited by a GABA agonist (muscimol). The protective effect of normal vision against form-deprivation is modifiable by both the GABAergic and DAergic pathways.

GABAergic agents modify the response of chick scleral fibroblasts to myopic and hyperopic eye cup tissues

Purpose: GABA antagonists inhibit experimental myopia in chick and GABA receptors have been localized to chick sclera and the retinal pigment epithelium (RPE). The RPE and the choroid alter scleral DNA and glycosaminoglycan (GAG) content in vitro; opposite effects have been observed for tissues from myopic and hyperopic eyes. The aim was to determine the effect of GABAergic agents on the DNA and GAG content of chick scleral fibroblasts directly and in co-culture with ocular tissues from myopic and hyperopic chick eyes. Materials and Methods: Primary cultures of fibroblastic cells expressing vimentin and α-smooth muscle actin were established. GABAergic agents were added separately (i) to the culture medium of the scleral cells and (ii) to the culture medium of the scleral cells with the addition of posterior eye cup tissue (retina, RPE, retina + RPE, choroid + RPE) to cell culture inserts. Ocular tissues were obtained from chick eyes wearing + 15D (lens-induced hyperopia, LIH) or −15D lenses (lens-induced myopia, LIM) for three days (post-hatch day 5–8) (n = 12). GAG and DNA content of scleral fibroblasts were measured. Results: GABA agents had a small direct effect on scleral cell GAG and DNA content but a larger effect was measured when GABA agents were added to the culture medium with myopic and hyperopic RPE and choroid + RPE tissues. GABA agonists increased (p = 0.002) whereas antagonists decreased (p = 0.0004) DNA content of scleral cells; effects were opposite for scleral GAG content. GABA agents significantly altered the effect of both LIM and LIH tissues (p = 0.0005) compared to control; the effects were greater for LIM tissue versus LIH tissue co-culture (p = 0.0004). Conclusion: GABAergic agents affect the DNA and GAG content of scleral fibroblasts both directly and when co-cultured with ocular tissues. GABA antagonists that prevent myopia development in chick model could act via a scleral mechanism utilizing the RPE/choroid.