Evaluation of sample size effect on the identification of haplotype blocks

<p>Abstract</p> <p>Background</p> <p>Genome-wide maps of linkage disequilibrium (LD) and haplotypes have been created for different populations. Substantial sharing of the boundaries and haplotypes among populations was observed, but haplotype variations have also been reported across populations. Conflicting observations on the extent and distribution of haplotypes require careful examination. The mechanisms that shape haplotypes have not been fully explored, although the effect of sample size has been implicated. We present a close examination of the effect of sample size on haplotype blocks using an original computational simulation.</p> <p>Results</p> <p>A region spanning 19.31 Mb on chromosome 20q was genotyped for 1,147 SNPs in 725 Japanese subjects. One region of 445 kb exhibiting a single strong LD value (average |D'|; 0.94) was selected for the analysis of sample size effect on haplotype structure. Three different block definitions (recombination-based, LD-based, and diversity-based) were exploited to create simulations for block identification with <it>θ </it>value from real genotyping data. As a result, it was quite difficult to estimate a haplotype block for data with less than 200 samples. Attainment of a reliable haplotype structure with 50 samples was not possible, although the simulation was repeated 10,000 times.</p> <p>Conclusion</p> <p>These analyses underscored the difficulties of estimating haplotype blocks. To acquire a reliable result, it would be necessary to increase sample size more than 725 and to repeat the simulation 3,000 times. Even in one genomic region showing a high LD value, the haplotype block might be fragile. We emphasize the importance of applying careful confidence measures when using the estimated haplotype structure in biomedical research.</p

Evaluation of sample size effect on the identification of haplotype blocks

Background: Genome-wide maps of linkage disequilibrium (LD) and haplotypes have been created for different populations. Substantial sharing of the boundaries and haplotypes among populations was observed, but haplotype variations have also been reported across populations. Conflicting observations on the extent and distribution of haplotypes require careful examination. The mechanisms that shape haplotypes have not been fully explored, although the effect of sample size has been implicated. We present a close examination of the effect of sample size on haplotype blocks using an original computational simulation. Results: A region spanning 19.31 Mb on chromosome 20q was genotyped for 1,147 SNPs in 725 Japanese subjects. One region of 445 kb exhibiting a single strong LD value (average |D'|; 0.94) was selected for the analysis of sample size effect on haplotype structure. Three different block definitions (recombination-based, LD-based, and diversity-based) were exploited to create simulations for block identification with θ value from real genotyping data. As a result, it was quite difficult to estimate a haplotype block for data with less than 200 samples. Attainment of a reliable haplotype structure with 50 samples was not possible, although the simulation was repeated 10,000 times. Conclusion: These analyses underscored the difficulties of estimating haplotype blocks. To acquire a reliable result, it would be necessary to increase sample size more than 725 and to repeat the simulation 3,000 times. Even in one genomic region showing a high LD value, the haplotype block might be fragile. We emphasize the importance of applying careful confidence measures when using the estimated haplotype structure in biomedical research

Anti-fibrotic efficacy of nintedanib in pulmonary fibrosis via the inhibition of fibrocyte activity

Background: Nintedanib, a tyrosine kinase inhibitor that is specific for platelet-derived growth factor receptors (PDGFR), fibroblast growth factor receptors (FGFR), and vascular endothelial growth factor receptors (VEGFR), has recently been approved for idiopathic pulmonary fibrosis. Fibrocytes are bone marrow-derived progenitor cells that produce growth factors and contribute to fibrogenesis in the lungs. However, the effects of nintedanib on the functions of fibrocytes remain unclear. Methods: Human monocytes were isolated from the peripheral blood of healthy volunteers. The expression of growth factors and their receptors in fibrocytes was analyzed using ELISA and Western blotting. The effects of nintedanib on the ability of fibrocytes to stimulate lung fibroblasts were examined in terms of their proliferation. The direct effects of nintedanib on the differentiation and migration of fibrocytes were also assessed. We investigated whether nintedanib affected the accumulation of fibrocytes in mouse lungs treated with bleomycin. Results: Human fibrocytes produced PDGF, FGF2, and VEGF-A. Nintedanib and specific inhibitors for each growth factor receptor significantly inhibited the proliferation of lung fibroblasts stimulated by the supernatant of fibrocytes. Nintedanib inhibited the migration and differentiation of fibrocytes induced by growth factors in vitro. The number of fibrocytes in the bleomycin-induced lung fibrosis model was reduced by the administration of nintedanib, and this was associated with anti-fibrotic effects. Conclusions: These results support the role of fibrocytes as producers of and responders to growth factors, and suggest that the anti-fibrotic effects of nintedanib are at least partly mediated by suppression of fibrocyte function

Mediastinal Tracheostoma for Treatment of Tracheostenosis after Tracheostomy in a Patient with Mucopolysaccharidosis-Induced Tracheomalacia

Background. Treatment of tracheostenosis after tracheostomy in pediatric patients is often difficult. Mucopolysaccharidosis is a lysosomal storage disease that may induce obstruction of the airways. Case Presentation. A 16-year-old male patient underwent long-term follow-up after postnatal diagnosis of type II mucopolysaccharidosis. At 11 years of age, tracheostomy was performed for mucopolysaccharidosis-induced laryngeal stenosis. One week prior to presentation, he was admitted to another hospital on an emergency basis for major dyspnea. He was diagnosed with tracheostenosis caused by granulation. The patient was then referred to our institution. The peripheral view of his airway was difficult because of mucopolysaccharidosis-induced tracheomalacia. For airway management, a mediastinal tracheostoma was created with extracorporeal membrane oxygenation. To maintain the blood flow, the skin incision for the mediastinal tracheal hole was sharply cut without an electrotome. The postoperative course was uneventful, and the patient was weaned from the ventilator on postoperative day 19. He was discharged 1.5 months postoperatively. Although he was referred to another institution because of respiratory failure caused by his primary disease 6 months postoperatively, his airway management remained successful for 1.5 years postoperatively. Conclusion. Mediastinal tracheostomy was useful for treatment of tracheostenosis caused by granulation tissue formation after a tracheostomy

昭和南海地震震源域-四国沖～紀伊半島沖-の構造変化

BE12-54講演要旨 / ブルーアース2012（2012年3月22日～23日, 東京海洋大学品川キャンパス

Structural variation from off Shikoku to the Kii Peninsula related to various earhthquake phenomena

南海トラフで繰り返し発生する巨大地震の中には、東海・東南海・南海地震が連動して発生する超巨大地震のケースがあることが指摘されている。このような超巨大地震について、どのような場合に連動し、あるいは非連動性巨大地震となるのかを明らかにすることが必要である。連動型地震の滑り域の範囲がどこまで広がるかを見積もることが重要な課題であり、そのためには南海トラフから沈み込むフィリピン海プレートの形状およびプレート境界周辺の構造、地震活動に関する詳細かつ高精度な情報が必要である。また、南海地震単独で発生した場合についても、深部および浅部低周波地震発生域まで含めた正確な破壊の広がりの把握、複雑な破壊分布の原因を明らかにするために南海地震破壊域とその縁辺での地殻構造や地震活動は重要な情報となる。平成20年度は日向灘、平成21年度は四国沖で調査を実施し、平成22年度は調査海域を東方の紀伊半島沖まで拡大し、沈み込み帯の地殻構造、巨大地震の発生、地震活動の相互関係の解明を目的として、南海・地震破壊域における沈み込みに関する詳細な構造のイメージングおよび地震のアスペリティに関する構造を明らかにするためのデータの取得、および西南日本の付加体先端部付近で発生している低周波地震や微動を含む自然地震観測を実施した。 　本講演では、四国沖?紀伊半島沖の平成21~22年度の調査結果について述べる。平成21年10月、および平成22年10~11月、（独）海洋研究開発機構の海洋調査船「かいれい」によって短周期海底地震計各々180台と大容量チューンドエアガン（7800cu. in.)を用いた屈折法・広角反射法探査を実施した（図１）。海底地震計設置期間中に自然地震観測も実施した。四国沖では21観測点、紀伊半島沖では20観測点による約9ヶ月間の長期地震観測も実施した（一部実施中）。なお、本調査は文部科学省からの受託研究「東海・東南海・南海地震の連動性評価のための 調査観測・研究」の個別研究テーマ「南海トラフ域海域地震探査・地震観測」（平成20年度から受託）の一環として実施した。 　一部の調査測線の解析の結果、足摺岬沖から日向灘に向かって約6km/sの古い付加体を示す岩体の分布が海側に張り出していること、また、SK05の構造モデルによると、SK03とSK02の中間付近からSK01付近までの付加堆積物が極端に薄いことなど、トラフ平行方向に構造変化があることがわかり、破壊様式の違いに関係する構造ではないかと考えられる。また、測線延長上のHi-net陸上観測点のデータを加えた海陸統合解析を実施しており、これにより深部低周波地震現象と構造との関連性が明らかになると期待されるC11-10発表要旨, 日本地震学会2011年度秋季大会（2011年10月12日～15日, 静岡県静岡市

Prominent reflector beneath around the segmentation boundary between Tonankai-Nankai earthquake area

In the Nankai Trough subduction seismogenic zone, the Nankai and Tonankai earthquakes had often occurred simultaneously, and caused a great event. In most cases, first break of such large events of Nankai Trough usually begins from southwest off the Kii Peninsula so far. The idea of split Philippine Sea plate between the Kii Peninsula and the Shikoku Island, which explains seismicity, tectonic background, receiver function image and historical plate motion, was previously suggested. Moreover, between the Kii Peninsula and the Shikoku Island, there is a gap of deep low-frequency events observed in the belt-like zone along the strike of the subducting Philippine Sea plate. In 2010 and 2011, we conducted the large-scale high-resolution wide-angle and reflection (MCS) seismic study, and long-term observation from off Shikoku and Kii Peninsula. Marine active source seismic data have been acquired along grid two-dimensional profiles having the total length of ~800km/year. A three-dimensional seismic tomography using active and passive seismic data observed both land and ocean bottom stations have been also performed. From those data, we found a possible prominent reflector imaged in the offshore side in the Kii channel at the depth of ~18km. The velocity just beneath the reflector cannot be determined due to the lack of ray paths. Based of the amplitude information, we interpret the reflector as the forearc Moho based on the velocity gap (from ~6.4km/s to ~7.4km/s). However, the reflector is shallower than the forearc Moho of other area along the Nankai Trough. Similar reflectors are recognized along other seismic profiles around the Kii channel. In this presentation, we will show the result of structure analysis to understand the peculiar structure including the prominent reflector around the Kii channel. Relation between the structure and the existence of the segmentation of the Nankai megathrust earthquake or seismic gap of the deep low-frequency events will be also discussed. This study is part of 'Research concerning Interaction Between the Tokai, Tonankai and Nankai Earthquakes' funded by Ministry of Education, Culture, Sports, Science and Technology, Japan.Poster abstract T43C-2670 presented at 2013 Fall Meeting, AGU, San Francisco, Calif., 9-13 Dec

ガクセイ アンケート チョウサ ニヨル コウギ ヒョウカ ト ソノ モンダイテン

近年,医学教育改革が目まぐるしく行われている.その中で,学生による講義評価が行われはじめているが,まだその報告は少ない.獨協医科大学では学年委員会が主体となって,講義・実習に対するアンケート調査を第1学年から第4学年まで行った.その結果,講義に対して「十分に満足している」という学生は,どの学年においても多くはなかった.さらに,「わかりやすい講義」をしている教員の共通点は,板書・プリント・シラパスを活用しているという点であった.実習に関しては,「基礎医学」に関わる実習に対しての評価が高かった.今後の医学教育において,学生の意見の反映がよりよい講義につながるものと考えられる.Extensive innovations in medical education have been carried out in recent years in our country. Although student evaluations of lectures have been conducted, there have been few reports on this issue. Thus, our committee consisting of representatives of every grade played a leading role in making and evaluating a questionnaire investigation of the lectures and the experiments. The investigation covered students from freshmen to seniors. We found that there were few students in each grade who were satisfied with the lectures. Students gave high marks to lecturers who wrote in detail on the blackboard, distributed well-organized documents, and made practical use of the syllabus. Experiments concerning the preclinical course were also well accepted. We consider that this sort of investigation will be influential in improving the quality of lectures