Influence of LRP5 polymorphisms on normal variation in BMD

Genetic studies based on cohorts with rare and extreme bone phenotypes have shown that the LRP5 gene is an important genetic modulator of BMD. Using family-based and case-control approaches, this study examines the role of the LRP5 gene in determining normal population variation of BMD and describes significant association and suggestive linkage between LRP5 gene polymorphisms and BMD in >900 individuals with a broad range of BMD. Introduction: Osteoporosis is a common, highly heritable condition determined by complex interactions of genetic and environmental etiologies. Genetic factors alone can account for 50-80% of the interindividual variation in BMD. Mutations in the LRP5 gene on chromosome 11q12-13 have been associated with rare syndromes characterized by extremely low or high BMD, but little is known about the contribution of this gene to the development of osteoporosis and determination of BMD in a normal population. Materials and Methods: To examine the entire spectrum of low to high BMD, 152 osteoporotic probands, their families (597 individuals), and 160 women with elevated BMD (T score > 2.5) were recruited. BMD at the lumbar spine, femoral neck, and hip were measured in each subject using DXA. Results: PAGE sequencing of the LRP5 gene revealed 10 single nucleotide polymorphisms (SNPs), 8 of which had allele frequencies of >5%, in exons 8, 9, 10, 15, and 18 and in introns 6, 7, and 21. Within families, a strong association was observed between an SNP at nucleotide C171346A in intron 21 and total hip BMD (p < 1 × 10-5 in men only, p = 0.0019 in both men and women). This association was also observed in comparisons of osteoporotic probands and unrelated elevated BMD in women (p = 0.03), along with associations with markers in exons 8 (C135242T, p = 0.007) and 9 (C141759T, p = 0.02). Haplotypes composed of two to three of the SNPs G121513A, C135242T, G138351A, and C141759T were strongly associated with BMD when comparing osteoporotic probands and high BMD cases (p < 0.003). An SNP at nucleotide C165215T in exon 18 was linked to BMD at the lumbar spine, femoral neck, and total hip (parametric LOD scores = 2.8, 2.5, and 2.2 and nonparametric LOD scores = 0.3, 1.1, and 2.2, respectively) but was not genetically associated with BMD variation. Conclusion: These results show that common LRP5 polymorphisms contribute to the determination of BMD in the general population.

Site and gender specificity of inheritance of bone mineral density

Differences in genetic control of BMD by skeletal sites and genders were examined by complex segregation analysis in 816 members of 147 families with probands with extreme low BMD. Spine BMD correlated more strongly in male-male comparisons and hip BMD in female-female comparisons, consistent with gender- and site-specificity of BMD heritability. Introduction: Evidence from studies in animals and humans suggests that the genetic control of bone mineral density (BMD) may differ at different skeletal sites and between genders. This question has important implications for the design and interpretation of genetic studies of osteoporosis. Methods: We examined the genetic profile of 147 families with 816 individuals recruited through probands with extreme low BMD (T-score < −2.5, Z-score < −2.0). Complex segregation analysis was performed using the Pedigree Analysis Package. BMD was measured by DXA at both lumbar spine (L1-L4) and femoral neck. Results: Complex segregation analysis excluded purely monogenic and environmental models of segregation of lumbar spine and femoral neck BMD in these families. Pure polygenic models were excluded at the lumbar spine when menopausal status was considered as a covariate, but not at the femoral neck. Mendelian models with a residual polygenic component were not excluded. These models were consistent with the presence of a rare Mendelian genotype of prevalence 3–19 %, causing high BMD at the hip and spine in these families, with additional polygenic effects. Total heritability range at the lumbar spine was 61–67 % and at the femoral neck was 44–67 %. Significant differences in correlation of femoral neck and lumbar spine BMD were observed between male and female relative pairs, with male-male comparisons exhibiting stronger lumbar spine BMD correlation than femoral neck, and female-female comparisons having greater femoral neck BMD correlation than lumbar spine. These findings remained true for parent-offspring correlations when menopausal status was taken into account. The recurrence risk ratio for siblings of probands of a Z-score < −2.0 was 5.4 at the lumbar spine and 5.9 at the femoral neck. Conclusions: These findings support gender- and site-specificity of the inheritance of BMD. These results should be considered in the design and interpretation of genetic studies of osteoporosis.

Suggestive linkage of the parathyroid receptor type 1 to osteoporosis

We have investigated the role of 23 candidate genes in the control of bone mineral density (BMD) by linkage studies in families of probands with osteoporosis (lumbar spine [LS] or femoral neck [FN] BMD T score < -2.5) and low BMD relative to an age- and gender-matched cohort (Z score < -2.0). One hundred and fifteen probands (35 male, 80 female) and 499 of their first- or second-degree relatives (223 males and 276 females) were recruited for the study. BMD was measured at the LS and FN using dual-energy X-ray absorptiometry and expressed as age- and gender-matched Z scores corrected for body mass index. The candidate genes studied were the androgen receptor, type I collagen A1 (COLIA1), COLIA2, COLIIA1, vitamin D receptor (VDR), colony-stimulating factor 1, calcium-sensing receptor, epidermal growth factor (EGF), estrogen receptor 1 (ESR1), fibrillin type 1, insulin-like growth factor 1, interleukin-1 alpha (IL-1α), interleukin-4 (IL-4), interleukin-6 (IL-6), interleukin-11 (IL-11), osteopontin, parathyroid hormone (PTH), PTH-related peptide, PTH receptor type 1 (PTHR1), transforming growth factor-beta 1, and tumor necrosis factors alpha and beta. Sixty-four microsatellites lying close to or within these genes were investigated for linkage with BMD. Using the program MapMaker/Sibs there was suggestive evidence of linkage between BMD and PTHR1 (maximum LOD score obtained [MLS] 2.7-3.5). Moderate evidence of linkage was also observed with EGF (MLS 1.8), COLIA1 (MLS 1.7), COLIIA1/VDR (MLS 1.7), ESR1 (MLS 1.4), IL-1α (MLS 1.4), IL-4 (MLS 1.2), and IL-6 (MLS 1.2). Variance components analysis using the program ACT, correcting for proband-wise ascertainment, also showed evidence of linkage (p ≤0.05) at markers close to or within the candidate genes IL- 1α, PTHR1, IL-6, and COLIIA1/VDR. Further studies will be required to confirm these findings, to refine the location of gene responsible for the observed linkage, and to screen the candidate genes targeted at these loci for mutations.

Widening participation creatively: Creative arts education for social inclusion

University participation among students from low socio-economic backgrounds in Australia is low and nationwide strategies are in place to help bridge the gap. This article presents a preliminary evaluation of a creative arts-based outreach program to raise awareness and aspiration for university study among students from low-income backgrounds. The program is part of a national Australian federally funded initiative, the Higher Education Participation and Partnerships Program. It reviews an outreach advertising program facilitated by a Brisbane university. We argue that arts education has a particular role in provoking attitudinal change, due to the self-reflective, meaning-making and expressive characteristics of arts-based disciplines. In evaluating the advertising program, the value of creativity and trust as techniques of student engagement is considered. Evaluation occurred in two outer suburban high schools in Brisbane (a State capital city), using surveys and ethnographic fieldwork. The findings support an engagement model that employs creativity and uses student facilitators (undergraduate and postgraduate) to deliver the program, to meet the program's aims.

Risk analysis of prostate cancer in PRACTICAL, a multinational consortium, using 25 known prostate cancer susceptibility loci

Background Genome-wide association studies have identified multiple genetic variants associated with prostate cancer risk which explain a substantial proportion of familial relative risk. These variants can be used to stratify individuals by their risk of prostate cancer. Methods We genotyped 25 prostate cancer susceptibility loci in 40,414 individuals and derived a polygenic risk score (PRS).We estimated empirical odds ratios (OR) for prostate cancer associated with different risk strata defined by PRS and derived agespecific absolute risks of developing prostate cancer by PRS stratum and family history. Results The prostate cancer risk for men in the top 1% of the PRS distribution was 30.6 (95% CI, 16.4-57.3) fold compared with men in the bottom 1%, and 4.2 (95% CI, 3.2-5.5) fold compared with the median risk. The absolute risk of prostate cancer by age of 85 years was 65.8% for a man with family history in the top 1% of the PRS distribution, compared with 3.7% for a man in the bottom 1%. The PRS was only weakly correlated with serum PSA level (correlation = 0.09). Conclusions Risk profiling can identify men at substantially increased or reduced risk of prostate cancer. The effect size, measured by OR per unit PRS, was higher in men at younger ages and in men with family history of prostate cancer. Incorporating additional newly identified loci into a PRS should improve the predictive value of risk profiles. Impact:We demonstrate that the risk profiling based on SNPs can identify men at substantially increased or reduced risk that could have useful implications for targeted prevention and screening programs.

Support Frameworks for the Use of Social Media by Emergency Management Organisations

Social media platforms such as Facebook and Twitter are now widely recognised as playing an increasingly important role in the dissemination of information during crisis events. They are used by emergency management organisations as well as by the public to share information and advice. However, the official use of social media for crisis communication within emergency management organisations is still relatively new and ad hoc, rather than being systematically embedded within or effectively coordinated across agencies. This policy report suggests a more effectively coordinated approach to leverage social media use, involving stronger networking between social media staff within emergency management organisations. This could be realised by establishing a national network of social media practitioners managed by the Australia-New Zealand Emergency Management Committee (ANZEMC), reinforced by a Federal government task force that promotes further policy initiatives in this space.

Die Großstadt als Gegner? : Zur Wahrnehmung Berlins in Literatur, Film und Hörspiel der späten Weimarer Republik

Tässä tutkielmassa tarkastellaan, miten Berliinin suurkaupunki vaikutti Weimarin tasavallan loppuaikoina yksilöön. Tutkimusaineistona on Alfred Döblinin romaani Berlin Alexanderplatz sekä Walter Ruttmannin elokuva Berlin. Die Sinfonie der Großstadt ja kuunnelma Weekend. Teoreettisena taustana hyödynnetään kulttuuri- ja mediahistorian mentaliteetti- ja sosiaalihistoriaa. Aihetta käsitellään myös historiallis-temaattisesta lähtökohdasta, eli työssä tutkitaan todellisen Berliinin asemaa kyseisenä aikana, modernin metropolin olemusta, modernin ajan murrosvaihetta sekä uusasiallisen taidesuuntauksen vaikutusta teoksiin. Weimarin tasavallan aikana Saksassa elettiin murroksen keskellä. Toisaalta yhteiskunta oli poliittisesti pirstoutunut ja taloudellisesti epävakaa, mutta toisaalta kulttuurielämä oli lyhyen aikaa rikasta. Suurkaupungin asukkailla oli enemmän vapaa-aikaa ja mahdollisuuksia toteuttaa itseään omassa ympäristössään. Toisaalta ajan ristiriitaisuus kuitenkin vaikeutti yksilöllisen elämäntavan toteutumista; ihmiset odottivat murroskauden päättymiseltä materiaalista tyydytystä, jolloin henkiselle kehitykselle jäi vähän tilaa. Tärkein kysymyksenasettelu koskee suurkaupungin roolia oman aikansa tuotteena: missä määrin kaupunki oli ihmisen todellinen vastustaja ja missä määrin sen asema oli kuviteltua? Todellisen Berliinin suhdetta reflektoidaan fiktiiviseen suurkaupunkiympäristöön. Ensin tarkastellaan Berliiniä toimijana murroskaudella ja sitten käsitellään ajan ja tilan havainnointia. Koska teokset ovat fiktiivisiä, erityisen tarkastelun kohteena on todellisuuden, fiktion ja simulaation suhde. Tässä yhteydessä tarkastellaan myös kaupungin ja maaseudun välistä problematiikkaa. Kolmannessa osassa esille nousee yksilön ja massan välinen suhde, joka sekin vaikuttaa ihmisen ja suurkaupungin väliseen vastakkainasetteluun. Ilmensikö koneiden ja liikenteen dominoiva asema futuristista asetelmaa? Lisäksi käsitellään alamaailman ja kultaisen 20-luvun välistä kuilua. Kaikkia kolmea teosta yhdistää 24 tunnin aikakäsite; ajalla on selkeästi rajattu alku ja loppu, ja myös tilan käsite on tarkastelussa tärkeä. Kaikissa teoksissa on hyödynnetty montaasitekniikkaa. Kohtaukset vaihtuvat hyvinkin nopeasti, jolloin lukija, katsoja tai kuulija vieraantuu varsinaisesta kohteestaan. Montaasi vaikuttaa ratkaisevasti myös kaupungin ja yksilön suhteen kuvaukseen. Suurkaupungista muotoutuu lähes hirviömäinen, personifioitu subjekti, joka konemaisella olemuksellaan pyrkii nujertamaan pienen ihmisen. Döblinin romaanissa kertoja toimii ikään kuin yksilöä vastaan liittämällä kerronnan väliin uutisaiheita, säätiedotuksia ja kohtalokertomuksia. Elokuvassa ja kuunnelmassa teknologisen kehityksen ihannointi on noussut etualalle: ihmiset muistuttavat sekä yksilöinä että massana koneita, jotka liikkuvat hektisen mekaanisesti eteenpäin kuin liikennevälineet. He eivät kyseenalaista ympäristöään eivätkä koe olevansa oravanpyörässä. Romaanin päähenkilö on heijastanut omat pelkonsa konkreettisesti suurkaupungin infrastruktuuriin, kerrostaloihin, jotka tuntuvat kaatuvan hänen päälleen. Yksilöllinen kehitys on vaarassa pysähtyä, sillä koneistuminen tekee yksilöistä massaa. Elokuvassa ja kuunnelmassa kamppailu suurkaupunkiorganismin ja ihmisten välillä jatkuu, mutta romaanissa kamppailu päättyy päähenkilön parantumiseen. Hänestä tulee mallikansalainen - vaiennettu ja kuuliainen. Kaikkien kolmen teoksen hahmoja kuvataan modernin ajan uhreina. Heiltä puuttuu mekanismi, jolla he voisivat käsitellä kokonaisuuksia. Modernin ajan hahmojen elämä on lopulta kuin tanssia tulivuoren päällä - epävarmaa ja riskialtista.

Workplace belongingness, psychological distress and resilience in emergency service workers

- Objective Ambulance personnel provide emergency medical services to the community, often attending to highly challenging and traumatic scenes in complex and chaotic circumstances. Currently the assessment of predictors of psychological well-being remains limited. The current study investigated whether workplace belongingness was significant in predicting psychological distress as well as the presence of resilience in ambulance personnel whilst controlling for more routinely examined factors. - Method Australian ambulance officers (N = 740) completed a survey battery including the Kessler 10 (Kessler & Mroczek, 1994), Brief Resilience Scale (Smith et al., 2008) and Psychological Sense of Organisational Membership (Cockshaw & Shochet, 2010) scale. - Results Controlling for more commonly examined factors such as severity of trauma exposure and length of service, hierarchical multiple regression analyses demonstrated that workplace belongingness was significantly associated with reduced distress levels and enhanced resilience levels. - Conclusions Results suggest that strategies to enhance a sense of workplace belongingness in emergency service organisations could promote the well-being of emergency workers despite routine exposure to potentially traumatic events.

Breastmilk-saliva interactions boost innate immunity by regulating the oral microbiome in early infancy

Introduction Xanthine oxidase (XO) is distributed in mammals largely in the liver and small intestine, but also is highly active in milk where it generates hydrogen peroxide (H2O2). Adult human saliva is low in hypoxanthine and xanthine, the substrates of XO, and high in the lactoperoxidase substrate thiocyanate, but saliva of neonates has not been examined. Results Median concentrations of hypoxanthine and xanthine in neonatal saliva (27 and 19 μM respectively) were ten-fold higher than in adult saliva (2.1 and 1.7 μM). Fresh breastmilk contained 27.3±12.2 μM H2O2 but mixing baby saliva with breastmilk additionally generated >40 μM H2O2, sufficient to inhibit growth of the opportunistic pathogens Staphylococcus aureus and Salmonella spp. Oral peroxidase activity in neonatal saliva was variable but low (median 7 U/L, range 2–449) compared to adults (620 U/L, 48–1348), while peroxidase substrate thiocyanate in neonatal saliva was surprisingly high. Baby but not adult saliva also contained nucleosides and nucleobases that encouraged growth of the commensal bacteria Lactobacillus, but inhibited opportunistic pathogens; these nucleosides/bases may also promote growth of immature gut cells. Transition from neonatal to adult saliva pattern occurred during the weaning period. A survey of saliva from domesticated mammals revealed wide variation in nucleoside/base patterns. Discussion and Conclusion During breast-feeding, baby saliva reacts with breastmilk to produce reactive oxygen species, while simultaneously providing growth-promoting nucleotide precursors. Milk thus plays more than a simply nutritional role in mammals, interacting with infant saliva to produce a potent combination of stimulatory and inhibitory metabolites that regulate early oral–and hence gut–microbiota. Consequently, milk-saliva mixing appears to represent unique biochemical synergism which boosts early innate immunity.

Policing LGBTIQ people in rural spaces: Emerging issues and future concerns

This article argues identifying as lesbian, gay, bisexual, transgender, intersex, queer and/or questioning (LGBTIQ) in rural spaces can produce specific types of policing experiences. While some literature examines the experiences of LGBTIQ people with police, very little has focused on how rurality explicitly shapes these experiences. This is significant considering research highlights how rurality can be connected to pronounced experiences of homophobia and trans-phobia. The article highlights examples from three research projects that explored: LGBTIQ young people's interactions with police; LGBTI people's interactions with police liaison services; and LGBTIQ-identifying police officers. The examples demonstrate the need for further research to examine how policing “happens” with rural LGBTIQ people to ensure more accountable policing policies and practice, and to highlight the complexities of localized, rural policing contexts that can both support and marginalize LGBTIQ people.

Roy Kenzie Kiyooka

Roy Kenzie Kiyooka Canadian, born 1926 Roy Kiyooka was born in Moose Jaw, Saskatchewan in 1926. Throughout his career, he was known as a painter, photographer, sculptor, poet, musician, filmmaker and teacher. He studied at the Provincial Institute of Technology and Art in Calgary from 1946-49, and then at the Instituto Allende in Mexico in 1955. During the summers of 1958 - 1960 he attended the Emma Lake Workshops in Saskatchewan, where he worked closely with Barnett Newman and Clement Greenberg. In 1959 he executed his first series of abstract paintings, The Hoarfrost Series, which assume a disciplined minimal quality. In the late 1960's Kiyooka began to push beyond painting and created mixed media works, including collage, photography, film and poetry. Kiyooka’s art is born out of personal experience and through it he records his relationship to the surrounding landscape; a night in a motel, a trip to the coast, or hoarfrost on the trees. Through the unfolding of Kiyooka’s interior/exterior landscapes he shares his personal journeys with us all. The Art Gallery of Ontario's collection of Roy Kiyooka's work began with the purchase of two paintings; Barometer No. 2, in 1964 and Surya, in 1987.

Retoriset keinot ja kirjoittajaroolit virolaisen Postimees-lehden ja suomalaisen Helsingin Sanomien verkkosivujen mielipidekeskusteluissa

Työssä tutkitaan erilaisin tekstintutkimuksen keinoin suomalaisen Helsingin Sanomat -lehden ja virolaisen Postimees-lehden internet-julkaisuissa ilmestyneisiin uutisiin liittyviä mielipidekirjoituksia. Työn tavoitteena on tarkastella eroja suomalaisten ja virolaisten kirjoittajien retoriikassa, argumentaatiossa ja roolivalinnoissa. Työn aineisto koostuu Helsingin Sanomien ja Postimees´in internet-sivuilla tammikuussa 2008 ilmestyneiden uutisten saamista mielipiteistä eli kommenteista. Molemmista lehdistä on valittu mukaan kymmenen uutista, jotka kaikki ovat saaneet keskimäärin 30 kommenttia. Uutiset ovat molemmissa maissa kotimaan uutisia ja ne on valittu satunnaisesti, joskin muutamien uutisten aiheet ovat lehdissä samankaltaisia. Työn neljännessä luvussa aineistoa analysoidaan rekisterien, tekstityyppien ja retoriikan näkökulmista. Rekistereistä puhuttaessa tarkoitetaan erilaisia tapoja kirjoittaa erilaisissa tilanteissa. Internetistä löytyvät mielipidekirjoitukset vaihtelevat virallisen kirjakielen ja arkisen puhekielen, jopa slangin, käytön välillä. Mielipidekirjoitukset kuuluvat argumentoivaan tekstityyppiin. Niiden tehtävä ei ole kertoa asioista neutraalisti, vaan kirjoittaja ilmaisee tekstissään omia arvojaan, mielipiteitään ja käsityksiään. Viidennessä luvussa aineistoa tutkitaan retorisen diskurssianalyysin keinoin, eli analysoidaan millaisia retorisia keinoja kirjoittajat käyttävät argumentaationsa vahvistamiseen. Retorisia keinoja esitellään työssä Arja Jokisen esittämän jaotuksen mukaisesti. Argumentaatiota voidaan jaotella myös sen mukaan, onko kyseessä hyökkäävä, puolustava, fakta- tai tunnepohjainen retoriikka. Kuudennessa luvussa analysoidaan mielipidekirjoitusten kohteita eli adressaatteja sekä kirjoittajien itselleen ottamia rooleja. Kirjoittajat voivat osoittaa roolivalintaansa useiden retoristen keinojen avulla. Rooleista yleisimmät ovat opettaja, asiantuntija ja kriitikko, marginaalisempia puolestaan kysyjä ja kannattaja/tukija. Aineiston analysointi on nostanut esille useita eroja suomalaisten ja virolaisten mielipidekirjoitusten välillä. Suomalaiset kirjoitukset kirjoitetaan usein yleis- tai kirjakielellä ja neutraalilla sävyllä. Virolaisissa mielipidekirjoituksissa on enemmän puhekielisyyttä ja kirjoitusvirheitä. Kirjoitusten sävy on jyrkempi ja arvoja tai arvioita välittävät sanat usein hyvin affektisia. Suomalaisissa mielipidekirjoituksissa kirjoittajat käyttävät argumentaationsa vahvistamiseen paljon oman asiantuntijuutensa korostamista tai vahvistamista konsensuksella, oma pätevyys myös perustellaan koulutuksen tai ammatin avulla. Suomalaisissa kirjoituksissa mielipiteet ovat myös pääasiassa faktoihin ja puolustavaan retoriikkaan perustuvia. Virolaisissa mielipiteissä kirjoittajat esittävät väitteensä tosiasioina ilman erityisiä perusteita. Argumentaatio rakentuu pääasiallisesti hyökkäävän ja tunnepohjaisen retoriikan päälle. Myös roolivalintojen välillä on eroja: suomalaismielipiteet esitetään useimmiten opettajan tai asiantuntijan roolista, virolaisissa mielipiteissä kirjoittaja on yleensä kriitikko tai asiantuntija.

The acceptability, usability and short-term outcomes of Get Real: A web-based program for psychotic-like experiences (PLEs)

Background Psychotic-like experiences (PLEs) are subclinical delusional ideas and perceptual disturbances that have been associated with a range of adverse mental health outcomes. This study reports a qualitative and quantitative analysis of the acceptability, usability and short term outcomes of Get Real, a web program for PLEs in young people. Methods Participants were twelve respondents to an online survey, who reported at least one PLE in the previous 3 months, and were currently distressed. Ratings of the program were collected after participants trialled it for a month. Individual semi-structured interviews then elicited qualitative feedback, which was analyzed using Consensual Qualitative Research (CQR) methodology. PLEs and distress were reassessed at 3 months post-baseline. Results User ratings supported the program's acceptability, usability and perceived utility. Significant reductions in the number, frequency and severity of PLE-related distress were found at 3 months follow-up. The CQR analysis identified four qualitative domains: initial and current understandings of PLEs, responses to the program, and context of its use. Initial understanding involved emotional reactions, avoidance or minimization, limited coping skills and non-psychotic attributions. After using the program, participants saw PLEs as normal and common, had greater self-awareness and understanding of stress, and reported increased capacity to cope and accept experiences. Positive responses to the program focused on its normalization of PLEs, usefulness of its strategies, self-monitoring of mood, and information putting PLEs into perspective. Some respondents wanted more specific and individualized information, thought the program would be more useful for other audiences, or doubted its effectiveness. The program was mostly used in low-stress situations. Conclusions The current study provided initial support for the acceptability, utility and positive short-term outcomes of Get Real. The program now requires efficacy testing in randomized controlled trials.

Inscription on the Holocaust memorial, Mahnmal am Opernplatz; Hannover, Germany.

Gottschalk family member names engraved on the memorial to the Jews of Hannover who perished in the Holocaust; Elizabeth Gottschalk nee Steinfeld, Henriette Gottschalk nee Rothschild, Jeanette Gottschalk (relationship unknown), and Karl Gottschalk.

Studio portrait of Louis Gottschalk.

Digital Image