Genetic analyses in a sample of individuals with high or low BMD shows association with multiple Wnt pathway genes

INTRODUCTION Although the high heritability of BMD variation has long been established, few genes have been conclusively shown to affect the variation of BMD in the general population. Extreme truncate selection has been proposed as a more powerful alternative to unselected cohort designs in quantitative trait association studies. We sought to test these theoretical predictions in studies of the bone densitometry measures BMD, BMC, and femoral neck area, by investigating their association with members of the Wnt pathway, some of which have previously been shown to be associated with BMD in much larger cohorts, in a moderate-sized extreme truncate selected cohort (absolute value BMD Z-scores = 1.5-4.0; n = 344). MATERIALS AND METHODS Ninety-six tag-single nucleotide polymorphism (SNPs) lying in 13 Wnt signaling pathway genes were selected to tag common genetic variation (minor allele frequency [MAF] > 5% with an r(2) > 0.8) within 5 kb of all exons of 13 Wnt signaling pathway genes. The genes studied included LRP1, LRP5, LRP6, Wnt3a, Wnt7b, Wnt10b, SFRP1, SFRP2, DKK1, DKK2, FZD7, WISP3, and SOST. Three hundred forty-four cases with either high or low BMD were genotyped by Illumina Goldengate microarray SNP genotyping methods. Association was tested either by Cochrane-Armitage test for dichotomous variables or by linear regression for quantitative traits. RESULTS Strong association was shown with LRP5, polymorphisms of which have previously been shown to influence total hip BMD (minimum p = 0.0006). In addition, polymorphisms of the Wnt antagonist, SFRP1, were significantly associated with BMD and BMC (minimum p = 0.00042). Previously reported associations of LRP1, LRP6, and SOST with BMD were confirmed. Two other Wnt pathway genes, Wnt3a and DKK2, also showed nominal association with BMD. CONCLUSIONS This study shows that polymorphisms of multiple members of the Wnt pathway are associated with BMD variation. Furthermore, this study shows in a practical trial that study designs involving extreme truncate selection and moderate sample sizes can robustly identify genes of relevant effect sizes involved in BMD variation in the general population. This has implications for the design of future genome-wide studies of quantitative bone phenotypes relevant to osteoporosis.

Criminal histories of crash and non-crash involved Queensland speeding offenders: Evidence supporting the idea that we drive as we live

Evidence increasingly suggests that our behaviour on the road mirrors our behaviour across other aspects of our life. The idea that we drive as we live, described by Tillman and Hobbs more than 65 years ago when examining off-road behaviours of taxi drivers (1949), is the focus of the current paper. As part of a larger study examining the impact of penalty changes on a large cohort of Queensland speeding offenders, criminal (lifetime) and crash history (10 year period) data for a sub-sample of 1000 offenders were obtained. Based on the ‘drive as we live’ maxim, it was hypothesised that crash-involved speeding offenders would be more likely to have a criminal history than non-crash involved offenders. Overall, only 30% of speeding offenders had a criminal history. However, crash-involved offenders were significantly more likely to have a criminal history (49.4%) than non-crash involved offenders (28.6%), supporting the hypothesis. Furthermore, those deemed ‘most at fault’ in a crash were the group most likely to have at least one criminal offence (52.2%). When compared to the non-crash involved offenders, those deemed ‘not most at fault’ in a crash were also more likely to have had at least one criminal offence (46.5%). Therefore, when compared to non-crash involved speeding offenders, those offenders involved in a crash were more likely to have been convicted of at least one criminal offence, irrespective of whether they were deemed ‘most at fault’ in that crash. Implications for traffic offender management and policing are discussed.

A Ca2+-dependent early functional heterogeneity in amoebae of Dictyostelium discoideum, revealed by flow cytometry

When freshly starved amoebae of Dictyostelium discoideum are loaded with the Ca2+-specific dye indo-1/AM and analyzed in a fluorescence-activated cell sorter, they exhibit a quasi-bimodal distribution of fluorescence. This permits a separation of the population into two classes: H, or ''high Ca2+-indo-1 fluorescence,'' and L, or ''low Ca2+-indo-1 fluorescence.'' Simultaneous monitoring of Ca2+-indo-1 and Ca2+-chlortetracycline fluorescence shows that by and large the same cells tend to have high (or low) levels of both cytoplasmic and sequestered Ca2+. Next we label H cells with tetramethylrhodamine isothiocyanate (TRITC) and mix them in a 1:4 ratio with L cells, In the slugs that result, TRITC fluorescence is confined mainly to the anterior prestalk region. This implies that amoebae with relatively high Ca2+ at the vegetative stage tend to develop into prestalk cells and those with low Ca2+ into prespores. Polysphondylium violaceum, a cellular slime mold that does not possess prestalk and prespore cells, also does not display a Ca2+-dependent heterogeneity at the vegetative stage or in slugs. Finally, confirming earlier findings with the fluorophore fura-2 (Azhar ef al., Curr. Sci. 68, 337-342 (1995)), a prestalk-prespore difference in cellular Ca2+ is present in the cells of the slug in vivo. These findings are discussed in light of the possible roles of Ca2+ for cell differentiation in D. discoideum.

Traffic behaviour and compliance with the law in low and middle income countries: are we observing "pragmatic driving"?

A common theme in many accounts of road safety and road use in low and middle income countries is a widespread lack of compliance with traffic laws and related legislation. A key element of the success of road crash prevention strategies in high income countries has been the achievement of safer road user behaviour through compliance with traffic laws. Deterrence-based approaches such as speed cameras and random breath testing, which rely on drivers making an assessment that they are likely to be caught if they offend, have been very effective in this regard. However, the long term success of (for example) drink driving legislation has been supported by drivers adopting a moral approach to compliance rather than relying solely on the intensity of police operations. For low and middle income countries such morally based compliance is important, since levels of police resourcing are typically much lower than in Western countries. In the absence of morally based compliance, it is arguable that the patterns of behaviours observed in low and middle income countries can be described as "pragmatic driving": compliance only when there is a high chance of being detected and fined, or where a crash might occur. The potential characteristics of pragmatic driving in the macro-, meso- and micro-context of driving and the enforcement approach that could address it are outlined, with reference to the limited existing information available.

Examining novice education: What can we learn from a compulsory program delivered to both mature-age and young pre-learner licence drivers?

This paper reports results from a qualitative evaluation of a compulsory pre-Learner driver education program within the Australian Capital Territory(ACT), Australia. Two methods were used to obtain feedback from those involved in the delivery of the program as well as those who participated in programs. The first, semi-structured interviews, was undertaken with class room teachers who run the program in their schools, group facilitators running the program with more mature-age students at private facilities (n = 15 in total), and former participants in both school-based and private-based versions of the program (n = 19). The second method used an on-line survey for students (n = 79). Results from both methods were consistent with each other, indicating that strengths of the program were perceived as being its interactive components and the high level of engagement of the target audience. There was strong support from young and mature-age students for the program to remain compulsory. However, consistent with other findings on novice driver education, mature-age participants identified that the program was less relevant to them. It may be that to have greater relevance to mature-age learners, content could address and challenge perceptions about behaviours other than intentional high-risk behaviours (e.g. low level speeding, fatigue) as well as encourage planning/strategies to avoid them. While a longer term, outcome focussed, evaluation of the pre-learner education program is needed, this study suggests that the program is well received by pre-licence drivers and that teachers and facilitators perceive it as both effective and beneficial.

We need to fund more than just science priorities for Australia’s future

Australia's Science and Research Priorities focus on activating STEM researchers (science, technology, engineering, maths). In this article in The Conversation, Professor Marcus Foth argues that we need to fund more than just science priorities for Australia’s future.

Study of Pinna nobilis growth from inner record: How biased are posterior adductor muscle scars estimates?

Previous studies have shown that the external growth records of the posterior adductor muscle scar (PAMS) of the bivalve Pinna nobilis are incomplete and do not produce accurate age estimations. We have developed a new methodology to study age and growth using the inner record of the PAMS, which avoids the necessity of costly in situ shell measurements or isotopic studies. Using the inner record we identified the positions of PAMS previously obscured by nacre and estimated the number of missing records in adult specimens with strong abrasion of the calcite layer in the anterior portion of the shell. The study of the PAMS and inner record of two shells that were 6 years old when collected showed that only 2 and 3 PAMS were observed, while 6 inner records could be counted, thus confirming our working methodology. Growth parameters of a P. nobilis population located in Moraira, Spain (western Mediterranean) were estimated with the new methodology and compared to those obtained using PAMS data and in situ measurements. For the comparisons, we applied different models considering the data alternatively as length-at-age (LA) and tag-recapture (TR). Among every method we tested to fit the Von Bertalanffy growth model, we observed that LA data from inner record fitted to the model using non-linear mixed effects and the estimation of missing records using the calcite width was the most appropriate. The equation obtained with this method, L = 573*(1 - e(-0.16(t-0.02))), is very similar to that calculated previously from in situ measurements for the same population.

Copper-doped mesoporous silica nanospheres, a promising immunomodulatory agent for inducing osteogenesis

The application of mesoporous silica nanospheres (MSNs) loaded with drugs/growth factors to induce osteogenic differentiation of stem cells has been trialed by a number of researchers recently. However, limitations such as high cost, complex fabrication and unintended side effects from supraphysiological concentrations of the drugs/growth factors represent major obstacles to any potential clinical application in the near term. In this study we reported an in situ one-pot synthesis strategy of MSNs doped with hypoxia-inducing copper ions and systematically evaluated the nanospheres by in vitro biological assessments. The Cu-containing mesoporous silica nanospheres (Cu-MSNs) had uniform spherical morphology (∼100 nm), ordered mesoporous channels (∼2 nm) and homogeneous Cu distribution. Cu-MSNs demonstrated sustained release of both silicon (Si) and Cu ions and controlled degradability. The Cu-MSNs were phagocytized by immune cells and appeared to modulate a favorable immune environment by initiating proper pro-inflammatory cytokines, inducing osteogenic/angiogenic factors and suppressing osteoclastogenic factors by the immune cells. The immune microenvironment induced by the Cu-MSNs led to robust osteogenic differentiation of bone mesenchymal stem cells (BMSCs) via the activation of Oncostation M (OSM) pathway. These results suggest that the novel Cu-MSNs could be used as an immunomodulatory agent with osteostimulatory capacity for bone regeneration/therapy application. Statement of significance In order to stimulate both osteogenesis and angiogenesis of stem cells for further bone regeneration, a new kind of hypoxia-inducing copper doped mesoporous silica nanospheres (Cu-MSNs) were prepared via one-pot synthesis. Biological assessments under immune environment which better reflect the in vivo response revealed that the nanospheres possessed osteostimulatory capacity and had potential as immunomodulatory agent for bone regeneration/therapy application. The strategy of introducing controllable amount of therapeutic ions instead of loading expensive drugs/growth factors in mesoporous silica nanosphere provides new options for bioactive nanomaterial functionalization.

“We live in in a house of blo- in a block of flats.” – Self-repair in EFL Spoken Language

Tämä tutkielma on osa Helsingin yliopiston rahoittamaa HY-talk -tutkimusprojektia, jonka tavoite on vankentaa puheviestinnän, erityisesti vieraiden kielten suullisen taidon opetusta ja arviointia yleissivistävässä koulutuksessa ja korkeakouluasteella. Tämän tutkielman tavoite on selvittää millaisia korjauksia englantia vieraana kielenä puhuvat ihmiset tekevät puheeseensa ja tutkia itsekorjauksen ja sujuvuuden välistä suhdetta. Korjausjäsennystä ja itsekorjausta on aiemmin tutkittu sekä keskustelunanalyysin että psykolingvistiikan aloilla, ja vaikka tämä tutkielma onkin lähempänä aiempaa keskustelunanalyyttistä kuin psykolingvististä tutkimusta, siinä hyödynnetään molempia suuntauksia. Itsekorjausta on yleisesti pidetty merkkinä erityisesti ei-natiivien kielenpuhujien sujuvuuden puutteesta. Tämän tutkielman tarkoitus on selvittää, kuinka läheisesti itsekorjaus todella liittyy sujuvuuteen tai sen puutteeseen. Tutkielman materiaali koostuu HY-talk -projektia varten kerätyistä puhenäytteistä ja niiden pohjalta tehdyistä taitotasoarvioinneista. Puhenäytteet kerättiin vuonna 2007 projektia varten järjestettyjen puhekielen testaustilanteiden yhteydessä kolmessa eteläsuomalaisessa koulussa. Koska projektin tavoitteena on tutkia ja parantaa kielten suullisen taidon arviointia, projektissa mukana olleet kieliammattilaiset arvioivat puhujien taitotasot projektia varten (Eurooppalaisen Viitekehyksen taitotasokuvainten pohjalta) koottujen arviointiasteikoiden perusteella, ja nämä arvioinnit tallennettiin osaksi projektin materiaalia. Tutkielmassa analysoidaan itsekorjauksia aiemman psykolingvistisen tutkimuksen pohjalta kootun korjaustyyppiluokituksen sekä tätä tutkielmaa varten luodun korjausten oikeellisuutta vertailevan luokituksen avulla. Lisäksi siinä vertaillaan kahden korkeamman ja kahden matalamman taitotasoarvioinnin saaneen puhujan itsekorjauksia. Tulokset osoittavat, että ei-natiivien puheessa esiintyy monenlaisia eri korjaustyyppejä, ja että yleisimpiä korjauksia ovat alkuperäisen lausuman toistot. Yleisiä ovat myös korjaukset, joissa puhuja korjaa virheen tai keskeyttää puheensa ja aloittaa kokonaan uuden lausuman. Lisäksi tuloksista käy ilmi, ettei suurin osa korjauksista todennäköisesti johdu puhujien sujuvuuden puutteesta. Yleisimmät korjaustyypit voivat johtua suurimmaksi osaksi yksilön puhetyylistä, siitä, että puhuja hakee jotain tiettyä sanaa tai ilmausta mielessään tai siitä, että puhuja korjaa puheessaan huomaamansa kieliopillisen, sanastollisen tai äänteellisen virheen. Vertailu korkeammalle ja matalammalle taitotasolle arvioitujen puhujien välillä osoittaa selkeimmin, ettei suurin osa itsekorjauksista ole yhteydessä puhujan sujuvuuteen. Vertailusta käy ilmi, ettei pelkkä itsekorjausten määrä kerro kuinka sujuvasti puhuja käyttää kieltä, sillä toinen korkeammalle taitotasolle arvioiduista puhujista korjaa puhettaan lähes yhtä monesti kuin matalammalle tasolle arvioidut puhujat. Lisäksi korjausten oikeellisuutta vertailevan luokituksen tulokset viittaavat siihen, etteivät niin korkeammalle kuin matalammallekaan tasolle arvioidut puhujat useimmiten korjaa puhettaan siksi, etteivät pystyisi ilmaisemaan viestiään oikein ja ymmärrettävästi.

Are we there yet? Advancing women in Canada and Australia: Similar goals, different policies

Differences in opportunities and outcomes in the workplace are inherent in a free and competitive market. However when differences between individuals and groups are identified as resulting from particular policies, behaviours or attitudes, any resulting inequality may be identified as unfair. Increasingly, unfair disparities in societies and their workplaces are regularly challenged. Many of the unfair disparities are recognised as caused through unfair discrimination (Anker 1997). When defining discrimination, the International Labour Organization Convention (ILO) No. 111 defines it as “any distinction, exclusion or preference made on the basis of race, colour, sex, religion, political opinion, national extraction, or social origin, which has the effect of nullifying or impairing equality of opportunity or treatment in employment or occupation” (ILO, 1958). Yet, the argument for addressing this ideal of ‘equality of opportunity’ is complex. Ekmekci (2013) identifies the difficulties as the determination of whether any process should be based on equality of opportunity or equality of outcome. In addition, there is the difficulty of determining what exactly constitutes a process for addressing unfair disparity due to the haziness of what constitutes discrimination and controversy in the meaning as well as policy implications of equality (Tomei, 2003).

“We have to work within the system!”: Staff perceptions of organizational barriers to decision making for older adults with dementia in Australian aged care facilities

The current study explored the perceptions of direct care staff working in Australian residential aged care facilities (RACFs) regarding the organizational barriers that they believe prevent them from facilitating decision making for individuals with dementia. Normalization process theory (NPT) was used to interpret the findings to understand these barriers in a broader context. The qualitative study involved semi-structured interviews (N = 41) and focus groups (N = 8) with 80 direct care staff members of all levels working in Australian RACFs. Data collection and analysis were conducted in parallel and followed a systematic, inductive approach in line with grounded theory. The perceptions of participants regarding the organizational barriers to facilitating decision making for individuals with dementia can be described by the core category, Working Within the System, and three sub-themes: (a) finding time, (b) competing rights, and (c)not knowing. Examining the views of direct care staff through the lens of NPT allows possible areas for improvement to be identified at an organizational level and the perceived barriers to be understood in the context of promoting normalization of decision making for individuals with dementia.

Impaired physical function associated with childhood obesity: How should we intervene?

- Background This study examined relationships between adiposity, physical functioning and physical activity. - Methods Obese (N=107) and healthy-weight (N=132) children aged 10-13 years underwent assessments of percent body fat (%BF, dual energy X-ray absorptiometry), knee extensor strength (KE, isokinetic dynamometry), cardiorespiratory fitness (CRF, peak oxygen uptake by cycle ergometry), physical health-related quality of life (HRQOL), worst pain intensity and walking capacity [six-minute walk (6MWT)]. Structural equation modelling was used to assess relationships between variables. - Results Moderate relationships were observed between %BF and 6MWT, KE strength corrected for mass and CRF relative to mass (r -.36 to -.69, P≤.007). Weak relationships were found between: %BF and physical HRQOL (r -.27, P=.008); CRF relative to mass and physical HRQOL (r -.24, P=.003); physical activity and 6MWT (r .17, P=.004). Squared multiple correlations showed that 29.6% variance in physical HRQOL was explained by %BF, pain and CRF relative to mass, while 28% variance in 6MWT was explained by %BF and physical activity. - Conclusions It appears that children with a higher body fat percentage have poorer KE strength, CRF and overall physical functioning. Reducing percent fat appears to be the best target to improve functioning. However, a combined approach to intervention, targeting reductions in body fat percentage, pain and improvements in physical activity and CRF may assist physical functioning.

We need to support paedophiles to prevent child sex offending

The sexual abuse of children is, understandably, a key concern for the public. Child sexual abuse can cause long-lasting harms for victims, ranging from relationship difficulties to eating disorders. But misperceptions about those who perpetrate it abound in public debate. Although the terms “paedophile” and “child sex offender” are often used interchangeably, the two are distinct. Paedophiles are sexually attracted to young children. They have either acted on this attraction or fear they might. But not all paedophiles act on their attraction – and this is where support services can help reducing offending. Conversely, not everyone who offends sexually against a child is a paedophile. Some may have a sexual interest in and/or offend against both children and adults. Others do not have a sexual attraction to children but instead act opportunistically...

We'll Close! Plant Closings, Plant-Closing Threats, Union Organizing and NAFTA

This article is based on Final Report: The Effects of Plant Closing or Threat of Plant Closing on the Right of Workers to Organize. The report was commissioned by the tri-national Labor Secretariat of the Commission for Labor Cooperation (the NAFTA labor commission) "on the effects of the sudden closing of the plant on the principle of freedom of association and the right of workers to organize in the three countries."