Inference of the genetic architecture underlying BMI and height with the use of 20,240 sibling pairs

Evidence that complex traits are highly polygenic has been presented by population-based genome-wide association studies (GWASs) through the identification of many significant variants, as well as by family-based de novo sequencing studies indicating that several traits have a large mutational target size. Here, using a third study design, we show results consistent with extreme polygenicity for body mass index (BMI) and height. On a sample of 20,240 siblings (from 9,570 nuclear families), we used a within-family method to obtain narrow-sense heritability estimates of 0.42 (SE = 0.17, p = 0.01) and 0.69 (SE = 0.14, p = 6 x 10(-)(7)) for BMI and height, respectively, after adjusting for covariates. The genomic inflation factors from locus-specific linkage analysis were 1.69 (SE = 0.21, p = 0.04) for BMI and 2.18 (SE = 0.21, p = 2 x 10(-10)) for height. This inflation is free of confounding and congruent with polygenicity, consistent with observations of ever-increasing genomic-inflation factors from GWASs with large sample sizes, implying that those signals are due to true genetic signals across the genome rather than population stratification. We also demonstrate that the distribution of the observed test statistics is consistent with both rare and common variants underlying a polygenic architecture and that previous reports of linkage signals in complex traits are probably a consequence of polygenic architecture rather than the segregation of variants with large effects. The convergent empirical evidence from GWASs, de novo studies, and within-family segregation implies that family-based sequencing studies for complex traits require very large sample sizes because the effects of causal variants are small on average.

Tombstone of Sophie Molling nee Benjamin; Strangriede Cemetery (R 20.09); Hannover Cemeteries Tombs

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Effects of dietary phosphorus and calcium-to-phosphorus ratio on calcium and bone metabolism in healthy 20- to 43-year-old Finnish women

Dietary habits have changed during the past decades towards an increasing consumption of processed foods, which has notably increased not only total dietary phosphorus (P) intake, but also intake of P from phosphate additives. While the intake of calcium (Ca) in many Western countries remains below recommended levels (800 mg/d), the usual daily P intake in a typical Western diet exceeds by 2- to 3-fold the dietary guidelines (600 mg/d). The effects of high P intake in healthy humans have been investigated seldom. In this thesis healthy 20- to 43-year-old women were studied. In the first controlled study (n = 14), we examined the effects of P doses, and in a cross-sectional study (n = 147) the associations of habitual P intakes with Ca and bone metabolism. In this same cross-sectional study, we also investigated whether differences exist between dietary P originating from natural P sources and phosphate additives. The second controlled study (n = 12) investigated whether by increasing the Ca intake, the effects of a high P intake could be reduced. The associations of habitual dietary calcium-to-phosphorus ratios (Ca:P ratio) with Ca and bone metabolism were determined in a cross-sectional study design (n = 147). In the controlled study, the oral intake of P doses (495, 745, 1245 and 1995 mg/d) with a low Ca intake (250 mg/d) increased serum parathyroid hormone (S-PTH) concentration in a dose-dependent manner. In addition, the highest P dose decreased serum ionized calcium (S-iCa) concentration and bone formation and increased bone resorption. In the second controlled study with a dietary P intake of 1850 mg/d, by increasing the Ca intake from 480 mg/d to 1080 mg/d and then to 1680 mg/d, the S-PTH concentration decreased, the S-iCa concentration increased and bone resorption decreased dose-dependently. However, not even the highest Ca intake could counteract the effect of high dietary P on bone formation, as indicated by unchanged bone formation activity. In the cross-sectional studies, a higher habitual dietary P intake (>1650 mg/d) was associated with lower S-iCa and higher S-PTH concentrations. The consumption of phosphate additive-containing foods was associated with a higher S-PTH concentration. Moreover, habitual low dietary Ca:P ratios (≤0.50, molar ratio) were associated with higher S-PTH concentrations and 24-h urinary Ca excretions, suggesting that low dietary Ca:P ratios may interfere with homeostasis of Ca metabolism and increase bone resorption. In summary, excessive dietary P intake in healthy Finnish women seems to be detrimental to Ca and bone metabolism, especially when dietary Ca intake is low. The results indicate that by increasing dietary Ca intake to the recommended level, the negative effects of high P intake could be diminished, but not totally prevented. These findings imply that phosphate additives may be more harmful than natural P. Thus, reduction of an excessively high dietary P intake is also beneficial for healthy individuals.

Keittiömaailman matkassa 20 vuotta : Tutkimus erään keittiökalustevalmistajan johtavan markkina-aseman rakentamisesta ja säilyttämisestä

A View into the World of Kitchen: Development and retention of a leading position in the market of kitchen interiors - a case study of 20 years. This study focuses on the development of a kitchen interiors company, presently called Novart Inc., into the leading company of the industry from 1980´s to the present. The objective of the study is to describe the effects of strategic choices, the decisions of the management and the owner´s direction and control to the build up and the retaining of the leading position in the market. From theory point of view, strategic choices refer to com-pany purchases as corporate-level strategies, and business and marketing strategies. The empirical research was carried out in two phases and it is based on various company documents and records, and on the intensive interviews of seven key executives in the company. An abductive research design was utilized. The company gained the leading position in the kitchen market in Finland by company purchases, and the company has been able to retain the position. Firstly the goal was to expand to retail market and, secondly, the company has maintained the balance of supply and demand by closing the purchased production units when needed. The simultaneous use of these two strategic goals is a kind of a new observation, and the strategy may be suitable only for market leaders. During the latter part of the research period the strategy of com-pany purchases has been abandoned and the leading position in the market has been main-tained by developing systematically business and marketing capability. In the business and marketing strategies the distribution channels and the brands have been emphasized. During the research period the company has almost totally abandoned the long distribution channels and started to use its own channels built and named after the main brands. These are A la Carte, Parma and Petra. At the moment, in the beginning of the 21st century, a new distribution channel, the concept of the Kitchen World, is being built in addition to the channels mentioned above. The management´s decision making and the implementation the decisions have been well-considered. The executives emphasized the valuing of the importance of the decisions dif-ferently except the two decisions named the most important ones, i.e., the decisions to start own production of the raw material and to concentrate the business only to one company. The executive staff has also succeeded in managing crisis and threats of bankruptcy, and the company has been managed profitable. During all the four terms of ownership: Puolimatka Corporation, the Hankkija/Novera Corporation, the ownership period of the "bank", and the Nobia Corporate the ownership direction and control has been somewhat different. All the owners have paid attention to economic issues. The direction of cash flows and investments was at its strongest during the Hankkija/Novera term. For the last owner Nobia the production and marketing of the kitchen interiors has been the core business, which thus has strengthened the business and marketing capabilities of the target company of this research. A common denominator during all the four terms of ownership has been owners' trust gained by the professional skills of the management of the target company. This has lead to greater independence of the management of the company and less owners´ direction. Keywords: leading position, marketing strategy, management decisions, acquisition, corporate governance

Familienerinnerungen. Ein Fragment 1790-1913

History of the family of Isak Mirabeau (born 1840); his maternal grandfather Isak Henle was the first Jew to receive civic rights in Hall (Wuerttemberg); his paternal grandfather came from Olnhausen (Wuerttemberg); he was a hops and wool merchant; he became wealthy as a supplier for the French army, and entered the banking business; notes on Jewish history in 19th century Wuerttemberg; contains also instructions to his son for the case of his death (does not have to say kaddish).

Phytochemicals in Japanese plums: impact of maturity and bioaccessibility

In recent years there has been increasing consumer interest in the potential health benefits of dietary derived phytochemicals such as polyphenols (including anthocyanins and flavonols) and carotenoids. A new variety of Japanese plum (Prunus salicina Lindl.), named Queen Garnet (QG), was developed as a high anthocyanin plum in a Queensland (Australia) Government breeding program and may be attractive to consumers, but knowledge of other phytochemical content, and bioaccessibility, is currently limited. As a result, the present study examined (1) the impact of harvest date on anthocyanins, quercetin glycosides and carotenoids in Queen Garnet and another red fleshed commercial Japanese plum variety, Black Diamond (BD), (2) the content of bound phenolics in plum fruit and (3) the in vitro bioaccessibility and release of these phytochemicals as an initial measure to predict their potential bioavailability. For both QG and BD, the last harvest resulted in the highest anthocyanin content in peel, flesh and whole fruit, whereas no significant effects could be observed for quercetin glycosides, and total carotenoids decreased over time. The highest content of bound phenolics (30% of total amount) could be found in BD flesh. Between 53% and 59% of quercetin glycosides and anthocyanins were released from QG after the gastric and small intestinal digestion procedure, whereas the release of carotenoids ranged between 4–6%. A relative high release of anthocyanins and quercetin glycosides could be observed from QG which may result in a higher gastro-intestinal absorption rate of these compounds. However, follow-up studies (clinical trials) are warranted to investigate the in vivo bioavailability and subsequently biological activity of QG.

Plan uchastka no 20 poluostrov Chongor Genicheskogo raiona

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Juden, Juden, Juden : juedische Chronik zu Juden, Judentum, juedischer Geschichte und Geschichte des Heiligen Landes, der Heiligen Schrift(en) sowie zur Geschichte Israels, des Antijudaismus, Antisemitismus, der Shoah und des Zionismus von den Anfaengen bis in die Gegenwart, vermehrt um allerlei Wissenswertes und Kurioses aus der juedischen (und nichtjuedischen) Welt - teilweise ergaenzt um Angaben zu geschichtlichen Ereignissen von allgemeiner Bedeutung /

Bd. 1. Bis 7. November 1862. - 2008. - 556 p. -- Bd. 2. 26. November 1862-11. Februar 1909. - 2008. - 560 p. -- Bd. 3. Ab 5. Maerz 1909 [until November 20, 2006]. - 2008. - 560 p.

Tipovai︠a︡ usadʻba s posazhenymi plodovymi derevʻi︠a︡mi tirinoi︠u︡ 20 sazhenʻ

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Plan zemelʻnogo uchastka Nº 20

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Jeremia 20:7-13 psykoanalyysissa : Nimettömän valituslaulun syntyprosessi tekstin objektimielikuvien muutosten valossa

Tämän pro gradu -työn tarkoituksena on selvittää tekstin Jer 20:7-13 jumalakuvaa ja muita ”tekstin puhujan” ilmaisemia vuorovaikutussuhteita ja vaihtelevia tunteita. On kuitenkin epäselvää, missä määrin Jeremian kirja tai sen yksittäiset jaksot kuvaavat profeetan persoonaa ja historiallista taustaa. Tekstit voivat kuvata myös muita myöhempiä tilanteita ja asenteita. Tämän tutkimuksen pääasiallinen eksegeettinen metodi on syvyyspsykologinen. Se saattaa pystyä kertomaan jotakin siitä, miten tutkittava teksti peilaa menneisyyden kokemuksellisia kaavoja. Samaan tapaan kuten psykohistoriassa, tutkimus ei yritä tutkia, tulkita tai rekonstruoida tradition tai historian Jeremiaa. Syvyyspsykologinen eksegeesi on tunnistettu jo aiemmin, mutta suomalaisessa tutkimuksessa sitä ei vielä ole sovellettu yksittäisiin teksteihin. Tämän tutkimuksen tutkimusasetelma avaa tekstin sisäisiä ja vaihtelevia vuorovaikutussuhteita eli objektisuhteita. Tutkimus nimittää tätä vuorovaikutussuhteiden analyysiä objektisuhdeanalyysiksi. Se perustuu teologian tohtori, psykoanalyytikko Matti Hyrckin psykoanalyyttiseen suhteessaolon perusmielikuvien teoriaan (SPT), jonka hän esittelee väitöskirjassaan Mielen kuvat Jumalasta (1995). Tekstin Jahve-kuvat on nähtävä objektirepresentaatioina. Nämä vahvasti värittyneet representaatiot ja kuvat kertovat enemmän kokijasta itsestään kuin niistä objekteista, joiden kuviksi ne ovat syntyneet. Käsitys objektien sisäsyntyisyydestä mahdollistaa Hyrckillä objektisuhteiden systematisoinnin ja SPT:n luomisen. Siten emotionaaliset silmälasit on tämän tutkimuksen tekijän mielestä mahdollista valjastaa myös tutkijan käyttöön. Tutkimuksen laaja näkökulmia hakeva teoriaosuus varmistaa tämän. Hermeneuttinen ”kolmen maailman malli” on lukijakeskeisyyteen ja kulttuurihyppyyn arvokas työväline. Jeremian kirja sisältää useita osin runomuotoisia valituksia, joista tutkittava teksti on viimeinen. Valituslaulujen sarja päättyy tutkittavaa tekstiä seuraavaan syntymäpäivän kiroamiseen jakeissa 14-18. Valituksen edellä kontekstina on joitakin kertomuksia Jeremiasta, mutta vasta jakeessa 20:2 Jeremia nimetään profeetaksi. Muuten valittaja on nimetön. Jeremia-kertomusten kehys on tässä toimituksellinen ja valituksen jälkeen seuraa deuteronomistista saarnaa Juudaa ja Jerusalemia vastaan. Tutkimus selvittää jakeiden 7-13 rakennetta, sisältöä ja tulkintaa ensin lähinnä laji- ja kirjallisuus- kriittisesti. Tutkimus osoittaa, että Jeremian valitus noudattaa yksilön valituslaulun kaavaa, mutta ei kuitenkaan yksiselitteisesti taivu lajin usein stereotyyppisiin tarkoituksiin. Suurin syy tähän on tekstin proosa- ja runomuodon vaihtelu ja sisällön hajanaisuus. Edes valituksen ydintä ei voi varmistaa, vaikka valituslaulun nuorimpina osina on tyypillisesti helppo pitää loppupuolen kollektiivisia lisiä. Varsinainen valitus on jakeissa 7-9 ja jakeet 10-13 ovat todennäköisimmin monivaiheinen päätössarja. Tutkimuksen keskeiset objektisuhdeteoreettiset peruskäsitteet sisäinen subjekti ja sisäinen objekti ovat ihmisen tiedostamattoman tason mielikuvia. Varhaisen tilan vuorovaikutusmielikuvien sisäisinä subjekteina ovat Riippuvainen ja Itseriittoinen. Ne ovat vaihtelevissa suhteissa Houkuttajan ja Hallitsijan muotoisia sisäisiä objekteja kohtaan. Myöhäisessä tilassa objekteille on syytä antaa uudet nimet: Vetäytyjä, Vaatija ja Parantaja. Tutkimus etenee osoittamalla tekstin ja SPT:n mukaisen mallin samankaltaisuuksia. Samalla on ollut mahdollista ottaa kantaa myös tekstin saumoihin ja tekstin syntyprosessiin. Tekstin objekti osoittautuu pääosin Hallitsijaksi, sillä Houkuttajan muotoisista jumaluuksista on kollektiivisesti pyritty tekemään pesäeroa Jerusalemin temppelin hävityksestä lähtien. Silti muistoista ja Houkuttajaksikin värittyneistä kaipuun ja pelon muodoista ei päästä eroon. Valituksen alkujakeita 7-9 leimaa Riippuvaisen masennus ja Itseriittoisen häpeä. Jakeissa 11-13 Hallitsijan muotoinen Jahve Sebaot tarjoaa hierarkkista symbioosia. Myöhäistä Vaatijaa ei tutkittavassa tekstissä ole kuin vanhurskaan käsitteenä, joka deuteronomistisessa teologiassa perustuu Jahven sanan kuulemiseen ja lain noudattamiseen. Tutkimus pyrkii osoittamaan, että kaikilla kokemuksilla on jollakin tavalla sekä yhteisöä että yksilöä eheyttäviä tarkoituksia. Kun valitus päättyy sarjaan vakuutuksia ja huipentuu kollektiiviseen ylistyskehotukseen, myös niillä on tarkoitus. Yksi osa tutkimustehtävää on ollut testata psykoanalyyttisen objektisuhdeteoreettisen metodin toimivuutta eksegeettisessä tutkimuksessa. Vaikka tulokset ovat suuntaa antavia, metodi on osoittautunut toimivaksi.

The Systems Theory Framework of career development: 20 years of contribution to theory and practice

The development and sustained contribution of the Systems Theory Framework to career development theory and practice is well documented in national and international literatures. In addition to its contribution to theory integration, it has added to the growing literature on connecting career theory and practice, in particular for non-Western populations. In addition, it has been the basis of the development of a broad array of constructivist approaches to career counselling, and indeed specific reflective career assessment activities. This article begins with a brief history of the Systems Theory Framework which is then followed by a rationale for its development. The contribution of the Systems Theory Framework to theory and practice is then described prior to concluding comments by the authors.

Effective 20 newsgroups dataset cleaning

The rapid increase in the number of text documents available on the Internet has created pressure to use effective cleaning techniques. Cleaning techniques are needed for converting these documents to structured documents. Text cleaning techniques are one of the key mechanisms in typical text mining application frameworks. In this paper, we explore the role of text cleaning in the 20 newsgroups dataset, and report on experimental results.

A preliminary analysis of the impact of UN MDGs and RIO+20 on corporate social accountability practices

This chapter explores the impact of UN Millennium Development Goals (MDGs) and Rio + 20 in improving Corporate Social Responsibility (CSR) practices. While MDGs and Rio + 20 have suggested additive guidelines for improving CSR practices, they do not provide a strong legislative mandate. We find both MDGs and Rio + 20 have had limited cumulative effect on CSR practices and discourses within the corporate reports. UN bodies should bring a new policy and regulatory framework that addresses limitations in the principles espoused in the MDGs and Rio + 20. An independent monitoring system (a social compliance audit mechanism) can be mandated in an attempt to make incremental substantive change.