Buccal mucosa graft for laryngotracheal reconstruction in severe laryngeal stenosis.

OBJECTIVE: An operative technique is described as a salvage treatment for severe subglottic and supraglottic laryngeal stenosis. In addition to expansion of the laryngeal framework with an anterior cartilage graft, as used in a classical laryngotracheal reconstruction, the scar tissue obliterating the airway lumen is excised and a mucosal graft is placed to reconstruct the inner lining of the airway. The graft is harvested from buccal mucosa. METHODS: The operative technique is outlined. Three cases, 2 paediatric and one adult, with complete or near complete laryngeal stenosis are presented where this operative technique was employed. In all patients several surgeries had been performed previously which were unsuccessful. RESULTS: In all 3 patients a patent airway was achieved with decannulation of the tracheostomy in the 2 paediatric patients. CONCLUSIONS: In patients with severe subglottic or supraglottic airway stenosis where other surgeries have failed, excision of endoluminal scar tissue and placement of a buccal mucosal graft, in addition to conventional laryngotracheal reconstruction, is a promising technique. In revision cases of subglottic stenosis cricotracheal resection might not be an option because of scarring from previous surgeries. This operation is an alternative, which allows an increase in the airway lumen by excising the scar tissue then re-lining the exposed internal lumen. The buccal mucosa reduces granulation formation and re-stenosis.

Directional dominance on stature and cognition in diverse human populations.

Homozygosity has long been associated with rare, often devastating, Mendelian disorders, and Darwin was one of the first to recognize that inbreeding reduces evolutionary fitness. However, the effect of the more distant parental relatedness that is common in modern human populations is less well understood. Genomic data now allow us to investigate the effects of homozygosity on traits of public health importance by observing contiguous homozygous segments (runs of homozygosity), which are inferred to be homozygous along their complete length. Given the low levels of genome-wide homozygosity prevalent in most human populations, information is required on very large numbers of people to provide sufficient power. Here we use runs of homozygosity to study 16 health-related quantitative traits in 354,224 individuals from 102 cohorts, and find statistically significant associations between summed runs of homozygosity and four complex traits: height, forced expiratory lung volume in one second, general cognitive ability and educational attainment (P < 1 × 10(-300), 2.1 × 10(-6), 2.5 × 10(-10) and 1.8 × 10(-10), respectively). In each case, increased homozygosity was associated with decreased trait value, equivalent to the offspring of first cousins being 1.2 cm shorter and having 10 months' less education. Similar effect sizes were found across four continental groups and populations with different degrees of genome-wide homozygosity, providing evidence that homozygosity, rather than confounding, directly contributes to phenotypic variance. Contrary to earlier reports in substantially smaller samples, no evidence was seen of an influence of genome-wide homozygosity on blood pressure and low density lipoprotein cholesterol, or ten other cardio-metabolic traits. Since directional dominance is predicted for traits under directional evolutionary selection, this study provides evidence that increased stature and cognitive function have been positively selected in human evolution, whereas many important risk factors for late-onset complex diseases may not have been.

Large-scale genomic analyses link reproductive aging to hypothalamic signaling, breast cancer susceptibility and BRCA1-mediated DNA repair.

Menopause timing has a substantial impact on infertility and risk of disease, including breast cancer, but the underlying mechanisms are poorly understood. We report a dual strategy in ∼70,000 women to identify common and low-frequency protein-coding variation associated with age at natural menopause (ANM). We identified 44 regions with common variants, including two regions harboring additional rare missense alleles of large effect. We found enrichment of signals in or near genes involved in delayed puberty, highlighting the first molecular links between the onset and end of reproductive lifespan. Pathway analyses identified major association with DNA damage response (DDR) genes, including the first common coding variant in BRCA1 associated with any complex trait. Mendelian randomization analyses supported a causal effect of later ANM on breast cancer risk (∼6% increase in risk per year; P = 3 × 10(-14)), likely mediated by prolonged sex hormone exposure rather than DDR mechanisms.

Genetic associations at 53 loci highlight cell types and biological pathways relevant for kidney function.

Reduced glomerular filtration rate defines chronic kidney disease and is associated with cardiovascular and all-cause mortality. We conducted a meta-analysis of genome-wide association studies for estimated glomerular filtration rate (eGFR), combining data across 133,413 individuals with replication in up to 42,166 individuals. We identify 24 new and confirm 29 previously identified loci. Of these 53 loci, 19 associate with eGFR among individuals with diabetes. Using bioinformatics, we show that identified genes at eGFR loci are enriched for expression in kidney tissues and in pathways relevant for kidney development and transmembrane transporter activity, kidney structure, and regulation of glucose metabolism. Chromatin state mapping and DNase I hypersensitivity analyses across adult tissues demonstrate preferential mapping of associated variants to regulatory regions in kidney but not extra-renal tissues. These findings suggest that genetic determinants of eGFR are mediated largely through direct effects within the kidney and highlight important cell types and biological pathways.

Social differences in avoidable mortality between small areas of 15 European cities: an ecological study

Health and inequalities in health among inhabitants of European cities are of major importance for European public health and there is great interest in how different health care systems in Europe perform in the reduction of health inequalities. However, evidence on the spatial distribution of cause-specific mortality across neighbourhoods of European cities is scarce. This study presents maps of avoidable mortality in European cities and analyses differences in avoidable mortality between neighbourhoods with different levels of deprivation. Methods: We determined the level of mortality from 14 avoidable causes of death for each neighbourhood of 15 large cities in different European regions. To address the problems associated with Standardised Mortality Ratios for small areas we smooth them using the Bayesian model proposed by Besag, York and Mollié. Ecological regression analysis was used to assess the association between social deprivation and mortality. Results: Mortality from avoidable causes of death is higher in deprived neighbourhoods and mortality rate ratios between areas with different levels of deprivation differ between gender and cities. In most cases rate ratios are lower among women. While Eastern and Southern European cities show higher levels of avoidable mortality, the association of mortality with social deprivation tends to be higher in Northern and lower in Southern Europe. Conclusions: There are marked differences in the level of avoidable mortality between neighbourhoods of European cities and the level of avoidable mortality is associated with social deprivation. There is no systematic difference in the magnitude of this association between European cities or regions. Spatial patterns of avoidable mortality across small city areas can point to possible local problems and specific strategies to reduce health inequality which is important for the development of urban areas and the well-being of their inhabitants

”The music the world makes has no words”: Musiikillisen tradition funktiot ja merkitys Toni Morrisonin romaanissa Jazz

Pro gradu -tutkielmassani tarkastelen niit�� merkityksiä, joita afrikkalaisamerikkalainen musiikillinen esitystraditio saa Nobel-kirjailija Toni Morrisonin romaanissa Jazz (1992).Morrison on toistuvasti löyt��nyt vertailukohdan omalle kirjoittamiselleen mustasta musiikkitraditiosta. Kuvaillessaan Jazz-romaanin luomisprosessia hän on kertonut pyrkineensä rakentamaan teoksen improvisatorisen jazz-performanssin muotoon. Tutkielmassa kysyn, millä tavalla t��mä jazz-improvisatorinen kerrontamuoto ilmenee Jazz-romaanissa ja miksi musiikki ja kerronnan musiikillisuus on saanut niin merkittävän roolin afrikkalaisamerikkalaisen kirjallisuuden traditiossa. Keskeiselle sijalle tutkielmassani nousee ajatus improvisatorisesta jazz-performanssista sekä romaania ohjaavana kerronnallisena periaatteena että mustan diasporisen kulttuurin ja identiteetin rakentamisen välineenä. Tukeutumalla muun muassa Ralph Ellisonin, James Baldwinin, Albert Murrayn, Henry Louis Gates Jr:n, Houston A. Baker Jr:n, Paul Gilroyn, Kimberly W. Benstonin ja Nathaniel Mackeyn kirjoituksiin mustasta esitystraditiosta tarkastelen, mit�� eri merkityksiä jazz- ja blues-musiikille on annettu afrikkalaisamerikkalaisessa kirjallisuudessa. Jazzissa musiikki toimii ensisijaisesti keinona työst��ä menneisyyttä: musiikillinen improvisaatio avaa tien ihmisen henkilökohtaisten muistojen ja menneisyyden konfliktien tarkastelulle. Kyse on identiteettiprosessista, joka ohjaa toistuvasti määrittelemään uudelleen ne rakenteet, joissa ihmisen minuus kehittyy. Samalla musiikillisuuden taustalta voidaan löyt��ä pyrkimys vapauttaa teos kertovuudesta ja kohdistaa lukijan huomio tekstin tuottamaan liikkeeseen, romaaniin performanssina. T��mä ohjaa kirjallisuuden kohti rituaalista: musiikillisuuden funktiona on tuoda tarina voimakkaammin osaksi lukijan kokemuksellista nykyhetkeä. Morrisonin romaanikirjoittamista ohjaa halu kehittää jatkuvasti uusia mahdollisuuksia ymmärt��ä ja lähestyä menneisyyttä sekä rakentaa kriittinen suhde afrikkalaisamerikkalaista kulttuuria määrittäneisiin historiallisiin narratiiveihin. Jazzromaanin tapahtumat sijoittuvat keskelle afrikkalaisamerikkalaisen urbaanin kulttuurin ja amerikkalaisen modernismin kehityksen keskeisint�� vuosikymment��, 1920-lukua. Romaanin sisällön analyysissa tarkastelen muun muassa romaanin kaupunkitilan kuvausta ja sen kiinnittymist�� urbaanin kulutuskulttuurin tuottamaan visuaaliseen spektaakkeliin. Jazzissa Morrisonin voidaan nähdä työst��vän suhdetta tiettyyn historialliseen aikakauteen, joka on merkittävällä tavalla muokannut sekä afrikkalaisamerikkalaista kulttuurista yhteisöllisyyttä että tiettyjä ”mustan” tai ”mustuuden” representaatioita osana amerikkalaista urbaania ympärist��ä.

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耶穌基利士督我主救者新遺詔書Ye su ji li shi du wo zhu jiu zhe xin yi zhao shu.

Le Nouveau Testament.Traduction dat��e de 1813, faite et publiée à Canton par Robert Morrison. Table des matières.8 livres.

耶穌基利士督我主救者新遺詔書Ye su ji li shi du wo zhu jiu zhe xin yi zhao shu.

Le Nouveau Testament.Traduction dat��e de 1813, faite et publiée à Canton par Robert Morrison. Table des matières.8 livres.