Elevated circulating sclerostin concentrations in individuals with high bone mass, with and without LRP5 mutations

CONTEXT: The role and importance of circulating sclerostin is poorly understood. High bone mass (HBM) caused by activating LRP5 mutations has been reported to be associated with increased plasma sclerostin concentrations; whether the same applies to HBM due to other causes is unknown. OBJECTIVE: Our objective was to determine circulating sclerostin concentrations in HBM. DESIGN AND PARTICIPANTS: In this case-control study, 406 HBM index cases were identified by screening dual-energy x-ray absorptiometry (DXA) databases from 4 United Kingdom centers (n = 219 088), excluding significant osteoarthritis/artifact. Controls comprised unaffected relatives and spouses. MAIN MEASURES: Plasma sclerostin; lumbar spine L1, total hip, and total body DXA; and radial and tibial peripheral quantitative computed tomography (subgroup only) were evaluated. RESULTS: Sclerostin concentrations were significantly higher in both LRP5 HBM and non-LRP5 HBM cases compared with controls: mean (SD) 130.1 (61.7) and 88.0 (39.3) vs 66.4 (32.3) pmol/L (both P < .001, which persisted after adjustment for a priori confounders). In combined adjusted analyses of cases and controls, sclerostin concentrations were positively related to all bone parameters found to be increased in HBM cases (ie, L1, total hip, and total body DXA bone mineral density and radial/tibial cortical area, cortical bone mineral density, and trabecular density). Although these relationships were broadly equivalent in HBM cases and controls, there was some evidence that associations between sclerostin and trabecular phenotypes were stronger in HBM cases, particularly for radial trabecular density (interaction P < .01). CONCLUSIONS: Circulating plasma sclerostin concentrations are increased in both LRP5 and non-LRP5 HBM compared with controls. In addition to the general positive relationship between sclerostin and DXA/peripheral quantitative computed tomography parameters, genetic factors predisposing to HBM may contribute to increased sclerostin levels.

The reproducibility of acquiring three dimensional gait and plantar pressure data using established protocols in participants with and without type 2 diabetes and foot ulcers

Background Several prospective studies have suggested that gait and plantar pressure abnormalities secondary to diabetic peripheral neuropathy contributes to foot ulceration. There are many different methods by which gait and plantar pressures are assessed and currently there is no agreed standardised approach. This study aimed to describe the methods and reproducibility of three-dimensional gait and plantar pressure assessments in a small subset of participants using pre-existing protocols. Methods Fourteen participants were conveniently sampled prior to a planned longitudinal study; four patients with diabetes and plantar foot ulcers, five patients with diabetes but no foot ulcers and five healthy controls. The repeatability of measuring key biomechanical data was assessed including the identification of 16 key anatomical landmarks, the measurement of seven leg dimensions, the processing of 22 three-dimensional gait parameters and the analysis of four different plantar pressures measures at 20 foot regions. Results The mean inter-observer differences were within the pre-defined acceptable level (<7 mm) for 100 % (16 of 16) of key anatomical landmarks measured for gait analysis. The intra-observer assessment concordance correlation coefficients were > 0.9 for 100 % (7 of 7) of leg dimensions. The coefficients of variations (CVs) were within the pre-defined acceptable level (<10 %) for 100 % (22 of 22) of gait parameters. The CVs were within the pre-defined acceptable level (<30 %) for 95 % (19 of 20) of the contact area measures, 85 % (17 of 20) of mean plantar pressures, 70 % (14 of 20) of pressure time integrals and 55 % (11 of 20) of maximum sensor plantar pressure measures. Conclusion Overall, the findings of this study suggest that important gait and plantar pressure measurements can be reliably acquired. Nearly all measures contributing to three-dimensional gait parameter assessments were within predefined acceptable limits. Most plantar pressure measurements were also within predefined acceptable limits; however, reproducibility was not as good for assessment of the maximum sensor pressure. To our knowledge, this is the first study to investigate the reproducibility of several biomechanical methods in a heterogeneous cohort.

Middle aged wasps mate through most of the year, without regard to body size, ovarian development and nestmateship: a laboratory study of the primitively eusocial wasp Ropalidia marginata

We studied the mating behaviour of the primi-tively eusocial wasp Ropalidia marginata and the factors that may influence sperm transfer. By introducing a male and a female R. marginata into ventilated transparent plastic boxes, we were able to observe mating behaviour, and it involved mounting and short or long conjugation of the wasps. Dissection of female wasps after the observation indicated that long conjugation is a good behavioural predictor of sperm transfer. This finding makes it possible to obtain mated females without dissecting them every time. We tested the effect of age, season, relatedness, body size and female's ovarian status on mating. Under laboratory conditions, mating success declined rapidly below and above the ages 5-20 days. Within this age range mating success was significantly low in December compared to other months tested. There was no nestmate discrimination, and there was no influence of male and female body size or of the ovarian state of the female on the probability of sperm transfer.

Changes in cannabis use among psychotic clients without specialised substance use treatment

The need to address substance use among people with psychosis has been well established. However, treatment studies targeting substance use in this population have reported mixed results. Substance users with psychosis in no or minimal treatment control groups achieve similar reductions in substance use compared to those in more active substance use treatment, suggesting a role for natural recovery from substance use. This meta-analysis aims to quantify the amount of natural recovery from substance use within control groups of treatment studies containing samples of psychotic substance users, with a particular focus on changes in cannabis use. A systematic search was conducted to identify substance use treatment studies. Meta-analyses were performed to quantify reductions in the frequency of substance use in the past 30 days. Significant but modest reductions (mean reduction of 0.3–0.4 SD across the time points) in the frequency of substance use were found at 6 to 24 months follow up. The current study is the first to quantify changes in substance use in samples enrolled in no treatment or minimal treatment control conditions. These findings highlight the potential role of natural recovery from substance use among individuals with psychosis, although they do not rule out effects of regression to the mean. Additionally, the results provide a baseline from which to estimate likely changes or needed effects sizes in intervention studies. Future research is required to identify the processes underpinning these changes, in order to identify strategies that may better support self-management of substance use in people with psychosis.

A multi-centre open-label randomised non-inferiority trial comparing watchful waiting to antibiotic treatment for acute otitis media without perforation in low-risk urban Aboriginal and Torres Strait Islander children (the WATCH trial): study protocol for a randomised controlled trial

Background Treatment guidelines recommend watchful waiting for children older than 2 years with acute otitis media (AOM) without perforation, unless they are at high risk of complications. The high prevalence of chronic suppurative otitis media (CSOM) in remote Aboriginal and Torres Strait Islander communities leads these children to be classified as high risk. Urban Aboriginal and Torres Strait Islander children are at lower risk of complications, but evidence to support the subsequent recommendation for watchful waiting in this population is lacking. Methods/Design This non-inferiority multi-centre randomised controlled trial will determine whether watchful waiting is non-inferior to immediate antibiotics for urban Aboriginal and Torres Strait Islander children with AOM without perforation. Children aged 2 − 16 years with AOM who are considered at low risk for complications will be recruited from six participating urban primary health care services across Australia. We will obtain informed consent from each participant or their guardian. The primary outcome is clinical resolution on day 7 (no pain, no fever of at least 38 °C, no bulging eardrum and no complications of AOM such as perforation or mastoiditis) as assessed by general practitioners or nurse practitioners. Participants and outcome assessors will not be blinded to treatment. With a sample size of 198 children in each arm, we have 80 % power to detect a non-inferiority margin of up to 10 % at a significance level of 5 %, assuming clinical improvement of at least 80 % in both groups. Allowing for a 20 % dropout rate, we aim to recruit 495 children. We will analyse both by intention-to-treat and per protocol. We will assess the cost- effectiveness of watchful waiting compared to immediate antibiotic prescription. We will also report on the implementation of the trial from the perspectives of parents/carers, health professionals and researchers. Discussion The trial will provide evidence for the safety and effectiveness of watchful waiting for the management of AOM in Aboriginal and Torres Strait Islander children living in urban settings who are considered to be at low risk of complications.

Tuning the Conductance of Dirac Fermions on the Surface of a Topological Insulator

We study the transport properties of the Dirac fermions with a Fermi velocity v(F) on the surface of a topological insulator across a ferromagnetic strip providing an exchange field J over a region of width d. We show that the conductance of such a junction, in the clean limit and at low temperature, changes from oscillatory to a monotonically decreasing function of d beyond a critical J. This leads to the possible realization of a magnetic switch using these junctions. We also study the conductance of these Dirac fermions across a potential barrier of width d and potential V-0 in the presence of such a ferromagnetic strip and show that beyond a critical J, the criteria of conductance maxima changes from chi = eV(0)d/(h) over barv(F) = n pi to chi = (n + 1/2)pi for integer n. We point out that these novel phenomena have no analogs in graphene and suggest experiments which can probe them.

Wigner distributions for finite-state systems without redundant phase-point operators

We set up Wigner distributions for N-state quantum systems following a Dirac-inspired approach. In contrast to much of the work in this study, requiring a 2N x 2N phase space, particularly when N is even, our approach is uniformly based on an N x N phase-space grid and thereby avoids the necessity of having to invoke a `quadrupled' phase space and hence the attendant redundance. Both N odd and even cases are analysed in detail and it is found that there are striking differences between the two. While the N odd case permits full implementation of the marginal property, the even case does so only in a restricted sense. This has the consequence that in the even case one is led to several equally good definitions of the Wigner distributions as opposed to the odd case where the choice turns out to be unique.

Comparison of performance parameters of poly(3,4 ethylenedioxythiophene) (PEDOT) based electrochromic device on glass with and without counter electrode

Conjugated polymers are promising materials for electrochromic device technology. Aqueous dispersions of poly(3,4-ethylenedioxythiophene)-(PEDOT) were spin coated onto transparent conducting oxide (TCO) coated glass substrates. A seven-layer electrochromic device was fabricated with the following configuration: glass/transparent conducting oxide (TCO)/PEDOT (main electrochromic layer)/gel electrolyte/prussian blue (counter electrode)/TCO/glass. The device fabricated with counter electrode (Prussian blue) showed a contrast of 18% and without counter electrode showed visible contrast of 5% at 632 nm at a voltage of 1.9 V. The comparison of the device is done in terms of the colouration efficiency of the devices with and without counter electrode.

Truckies and health promotion: A “hard-to-reach” group without a “proper” workplace.

This literature review was undertaken to inform a settings based health promotion research project, conducted by a public health research team at the Queensland University of Technology (QUT). The aim of this project is to identify how transport workplaces can support their truck drivers to access healthy food options and increase physical activity. Truck drivers in Australia are at increased risk of numerous chronic diseases, in part due to the restrictions placed upon them by the environment in which they work. Barriers to good health through adequate nutrition and physical activity are the result of a complex interaction between government regulations, corporate policies, the built environment and individual factors. Few interventions target this population in a meaningful and sustainable way, though evidence exists for interventions which can be translated into truck drivers working environment.

Solubilities of Hexadecanoic and Octadecanoic Acids in Supercritical CO2 With and Without Cosolvents

The solubilities of hexadecanoic acid (palmitic acid) and octadecanoic acid (stearic acid) in supercritical carbon dioxide without cosolvents and with two cosolvents, namely, ethanol and 3-methyl-1-butanol, were determined at (308 and 318) K at pressures varying from (12.8 to 22.6) MPa. The solubility data, in both the absence and presence of cosolvents, were correlated by a model proposed by Mendez-Santiago and Teja.

Characterizing Physical Properties of Wetting Paper by Air Coupled Ultrasound and Light

This thesis reports investigations into the paper wetting process and its effects on the surface roughness and the out-of-plane (ZD) stiffness of machine-made paper. The aim of this work was to test the feasibility of employing air-borne ultrasound methods to determine surface roughness (by reflection) and ZD stiffness (by through transmission) of paper during penetration of distilled water, isopropanol and their mixtures. Air-borne ultrasound provides a non-contacting way to evaluate sample structure and mechanics during the liquid penetration event. Contrary to liquid immersion techniques, an air-borne measurement allows studying partial wetting of paper. In addition, two optical methods were developed to reveal the liquid location in paper during wetting. The laser light through transmission method was developed to monitor the liquid location in partially wetted paper. The white light reflection method was primarily used to monitor the penetration of the liquid front in the thickness direction. In the latter experiment the paper was fully wetted. The main results of the thesis were: 1) Liquid penetration induced surface roughening was quantified by monitoring the ultrasound reflection from the paper surface. 2) Liquid penetration induced stiffness alteration in the ZD of paper could be followed by measuring the change in the ultrasound ZD resonance in paper. 3) Through transmitted light revealed the liquid location in the partially wetted paper. 4) Liquid movement in the ZD of the paper could be observed by light reflection. The results imply that the presented ultrasonic means can without contact measure the alteration of paper roughness and stiffness during liquid transport. These methods can help avoiding over engineering the paper which reduces raw material and energy consumption in paper manufacturing. The presented optical means can estimate paper specific wetting properties, such as liquid penetration speed, transport mechanisms and liquid location within the paper structure. In process monitoring, these methods allow process tuning and manufacturing of paper with engineered liquid transport characteristics. With such knowledge the paper behaviour during printing can be predicted. These findings provide new methods for paper printing, surface sizing, and paper coating research.

Synergistic crystal facet engineering and structural control of WO3 films exhibiting unprecedented photoelectrochemical performance

WO3 nanoplate arrays with (002) oriented facets grown on fluorine doped SnO2 (FTO) glass substrates are tailored by tuning the precursor solution via a facile hydrothermal method. A 2-step hydrothermal method leads to the preferential growth of WO3 film with enriched (002) facets, which exhibits extraordinary photoelectrochemical (PEC) performance with a remarkable photocurrent density of 3.7 mA cm–2 at 1.23 V vs. revisable hydrogen electrode (RHE) under AM 1.5 G illumination without the use of any cocatalyst, corresponding to ~93% of the theoretical photocurrent of WO3. Density functional theory (DFT) calculations together with experimental studies reveal that the enhanced photocatalytic activity and better photo-stability of the WO3 films are attributed to the synergistic effect of highly reactive (002) facet and nanoplate structure which facilitates the photo–induced charge carrier separation and suppresses the formation of peroxo-species. Without the use of oxygen evolution cocatalysts, the excellent PEC performance, demonstrated in this work, by simply tuning crystal facets and nanostructure of pristine WO3 films may open up new opportunities in designing high performance photoanodes for PEC water splitting.

Tuning the beta-turn segment in designed peptide beta-hairpins: Construction of a stable type I ' beta-turn nucleus and hairpin-helix transition promoting segments

Designed octapeptides Boc-Leu-Val-Val-Aib-(D)Xxx-Leu- Val-Val-OMe ((D)Xxx = (D)Ala, 3a; (D)Val, 3c and (D)Pro, 5a) and Boc-Leu-Phe-Val-Aib-DAla-Leu-Phe-Val-OMe (3b) have been investigated to construct models of a stable type I' beta-turn nucleated hairpin and to generate systems for investigating helix-hairpin conformational transitions. Peptide 5a, which contains a central Aib-(D)Pro segment, is shown to adopt a stable type I' beta-turn nucleated hairpin structure, stabilized by four cross-strand hydrogen bonds. The stability of the structure in diverse solvents is established by the observation of all diagnostic NOEs expected in a beta-hairpin conformation. Replacement of (D)Pro5 by (D)Ala/(D)Val (3a-c) results in sequences that form beta-hairpins in hydrogen bonding solvents like CD3OH and DMSO-d(6). However, in CDCl3 evidence for population of helical conformations is obtained. Peptide 6b (Boc-Leu-Phe-Val-Aib-Aib-Leu-Phe-Val-OMe), which contains a centrally positioned Aib-Aib segment, provides a clear example of a system, which exhibits a helical conformation in CDCl3 and a significant population of both helices and hairpins in CD3OH and DMSO-d(6). The coexistence of multiple conformations is established by the simultaneous observation of diagnostic NOEs. Control over stereochemistry of the central beta-turn permits generation of models for robust beta-hairpins and also for the construction of systems that may be used to probe helix-hairpin conformational transitions. (c) 2006 Wiley Periodicals, Inc.

Aspects of Inflationary Models at Low Energy Scales

Cosmological inflation is the dominant paradigm in explaining the origin of structure in the universe. According to the inflationary scenario, there has been a period of nearly exponential expansion in the very early universe, long before the nucleosynthesis. Inflation is commonly considered as a consequence of some scalar field or fields whose energy density starts to dominate the universe. The inflationary expansion converts the quantum fluctuations of the fields into classical perturbations on superhorizon scales and these primordial perturbations are the seeds of the structure in the universe. Moreover, inflation also naturally explains the high degree of homogeneity and spatial flatness of the early universe. The real challenge of the inflationary cosmology lies in trying to establish a connection between the fields driving inflation and theories of particle physics. In this thesis we concentrate on inflationary models at scales well below the Planck scale. The low scale allows us to seek for candidates for the inflationary matter within extensions of the Standard Model but typically also implies fine-tuning problems. We discuss a low scale model where inflation is driven by a flat direction of the Minimally Supersymmetric Standard Model. The relation between the potential along the flat direction and the underlying supergravity model is studied. The low inflationary scale requires an extremely flat potential but we find that in this particular model the associated fine-tuning problems can be solved in a rather natural fashion in a class of supergravity models. For this class of models, the flatness is a consequence of the structure of the supergravity model and is insensitive to the vacuum expectation values of the fields that break supersymmetry. Another low scale model considered in the thesis is the curvaton scenario where the primordial perturbations originate from quantum fluctuations of a curvaton field, which is different from the fields driving inflation. The curvaton gives a negligible contribution to the total energy density during inflation but its perturbations become significant in the post-inflationary epoch. The separation between the fields driving inflation and the fields giving rise to primordial perturbations opens up new possibilities to lower the inflationary scale without introducing fine-tuning problems. The curvaton model typically gives rise to relatively large level of non-gaussian features in the statistics of primordial perturbations. We find that the level of non-gaussian effects is heavily dependent on the form of the curvaton potential. Future observations that provide more accurate information of the non-gaussian statistics can therefore place constraining bounds on the curvaton interactions.