F8 haplotype and inhibitor risk: results from the Hemophilia Inhibitor Genetics Study (HIGS) Combined Cohort.

To access publisher's full text version of this article. Please click on the hyperlink in Additional Links field.Ancestral background, specifically African descent, confers higher risk for development of inhibitory antibodies to factor VIII (FVIII) in haemophilia A. It has been suggested that differences in the distribution of FVIII gene (F8) haplotypes, and mismatch between endogenous F8 haplotypes and those comprising products used for treatment could contribute to risk. Data from the Hemophilia Inhibitor Genetics Study (HIGS) Combined Cohort were used to determine the association between F8 haplotype 3 (H3) vs. haplotypes 1 and 2 (H1 + H2) and inhibitor risk among individuals of genetically determined African descent. Other variables known to affect inhibitor risk including type of F8 mutation and human leucocyte antigen (HLA) were included in the analysis. A second research question regarding risk related to mismatch in endogenous F8 haplotype and recombinant FVIII products used for treatment was addressed. Haplotype 3 was associated with higher inhibitor risk among those genetically identified (N = 49) as of African ancestry, but the association did not remain significant after adjustment for F8 mutation type and the HLA variables. Among subjects of all racial ancestries enrolled in HIGS who reported early use of recombinant products (N = 223), mismatch in endogenous haplotype and the FVIII proteins constituting the products used did not confer greater risk for inhibitor development. Haplotype 3 was not an independent predictor of inhibitor risk. Furthermore, our findings did not support a higher risk of inhibitors in the presence of a haplotype mismatch between the FVIII molecule infused and that of the individual.Baxter BioScience Frederick National Laboratory for Cancer Research, National Institutes of Health (NIH) HHSN261200800001E Wyeth Research Fund at Malmo University Hospital NIH, National Institute of Child Health and Human Development R01-HD-41224 Bayer Inspiration Biopharmaceuticals, Inc. Grifols, Inc. Baxter Biogen Idec Biotest CSL Behring Grifols Inspiration Biopharmaceuticals NovoNordisk Octapharma Swedish Orphan Biovitrum Wyeth/Pfize

DNA Evidence: Examining Police Officers' Knowledge of Handling Procedures in a Mid-Size Department

Studies of policing dominate the criminal justice literature but very few studies report empirical data regarding police handling of evidence, specifically including DNA evidence. Given that evidence handling is crucial in the investigation and prosecution of criminal offenders, this gap in the literature is surprising. The present paper addresses the quality of evidence handling in a mid-size police department in the northwest United States. Three surveys - two of officers within the department and one of state crime lab managers who test and examine evidence samples provided to them by local police departments - suggest that police offers in this mid-size city are only modestly familiar with proper evidence handling procedures, including those procedures regarding the collection, packaging, transportation and submission of possible DNA evidence

Mixture models for gene expression experiments with two species

Cross-species research in drug development is novel and challenging. A bivariate mixture model utilizing information across two species was proposed to solve the fundamental problem of identifying differentially expressed genes in microarray experiments in order to potentially improve the understanding of translation between preclinical and clinical studies for drug development. The proposed approach models the joint distribution of treatment effects estimated from independent linear models. The mixture model posits up to nine components, four of which include groups in which genes are differentially expressed in both species. A comprehensive simulation to evaluate the model performance and one application on a real world data set, a mouse and human type II diabetes experiment, suggest that the proposed model, though highly structured, can handle various configurations of differential gene expression and is practically useful on identifying differentially expressed genes, especially when the magnitude of differential expression due to different treatment intervention is weak. In the mouse and human application, the proposed mixture model was able to eliminate unimportant genes and identify a list of genes that were differentially expressed in both species and could be potential gene targets for drug development

SOSIALISASI PENCEGAHAN BULLYING DIKALANGAN SISWA

Cases of bullying are no strangers to the ears of mass media observers. Newsreaders read it through electronic television media, announcers explain it through electronic radio media, and journalists write about it in various newspapers. This socialization activity aims to provide an explanation of material about bullying to all students. The method used in this service is by direct observation and presentation of material. The results of all the contents of the questionnaire show that acts of bullying often occur in high school students compared to students of Ullath Public Middle School and Elementary School. This is due to several factors both in the social environment, family and from social media. To overcome this, we, as Ullath State Community Service students, appeal to all students not to bull

Good practice guidelines for biomarker discovery from array data: a case study for breast cancer prognosis

BACKGROUND: Biomarker discovery holds the promise for advancing personalized medicine as the biomarkers can help match patients to optimal treatment to improve patient outcomes. However, serious concerns have been raised because very few molecular biomarkers or signatures discovered from high dimensional array data can be successfully validated and applied to clinical use. We propose good practice guidelines as well as a novel tool for biomarker discovery and use breast cancer prognosis as a case study to illustrate the proposed approach. RESULTS: We applied the proposed approach to a publicly available breast cancer prognosis dataset and identified small numbers of predictive markers for patient subpopulations stratified by clinical variables. Results from an independent cross-platform validation set show that our model compares favorably to other gene signature and clinical variable based prognostic tools. About half of the discovered candidate markers can individually achieve very good performance, which further demonstrate the high quality of feature selection. These candidate markers perform extremely well for young patient with estrogen receptor-positive, lymph node-negative early stage breast cancers, suggesting a distinct subset of these patients identified by these markers is actually at high risk of recurrence and may benefit from more aggressive treatment than cur-rent practice. CONCLUSION: The results show that by following good practice guidelines, we can identify highly predictive genes in high dimensional breast cancer array data. These predictive genes have been successfully validated using an independent cross-platform dataset

Inhibition of cartilage and bone destruction in adjuvant arthritis in the rat by a matrix metalloproteinase inhibitor

Considerable evidence has associated the expression of matrix metalloproteinases (MMPs) with the degradation of cartilage and bone in chronic conditions such as arthritis. Direct evaluation of MMPs' role in vivo has awaited the development of MMP inhibitors with appropriate pharmacological properties. We have identified butanediamide, N4- hydroxy-2-(2-methylpropyl)-N1-[2-[[2-(morpholinyl)ethyl]-,[S- (R*,S*)] (GI168) as a potent MMP inhibitor with sufficient solubility and stability to permit evaluation in an experimental model of chronic destructive arthritis (adjuvant-induced arthritis) in rats. In this model, pronounced acute and chronic synovial inflammation, distal tibia and metatarsal marrow hyperplasia associated with osteoclasia, severe bone and cartilage destruction, and ectopic new bone growth are well developed by 3 wk after adjuvant injection. Rats were injected with Freund's adjuvant on day 0. GI168 was was administered systemically from days 8 to 21 by osmotic minipumps implanted subcutaneously. GI168 at 6, 12, and 25 mg/kg per d reduced ankle swelling in a dose-related fashion. Radiological and histological ankle joint evaluation on day 22 revealed a profound dose related inhibition of bone and cartilage destruction in treated rats relative to rats receiving vehicle alone. A significant reduction in edema, pannus formation, periosteal new bone growth and the numbers of adherent marrow osteoclasts was also noted. However, no significant decrease in polymorphonuclear and mononuclear leukocyte infiltration of synovium and marrow hematopoietic cellularity was seen. This unique profile of antiarthritic activity indicates that GI168 is osteo- and chondro-protective, and it supports a direct role for MMP in cartilage and bone damage and pannus formation in adjuvant- induced arthritis

PENGARUH KEPEMIMPINAN, MOTIVASI DAN LINGKUNGAN KERJA TERHADAP KINERJA GURU PADA SMA THERESIANA 1 SEMARANG

Penelitian ini dengan judul pengaruh Kepemimpinan, Motivasi dan Lingkungan Kerja terhadap Kinerja Guru pada SMA Theresiana 1 Semarang. Penelitian ini bertujuan untuk membuktikan secara empiris pengaruh secara parsial dan simultan Kepemimpinan, Motivasi dan Lingkungan Kerja terhadap Kinerja Guru. Populasi dan sampel penelitian ini adalah 40 guru SMA Theresiana 1 Semarang. Teknik pengambilan sampel yang digunakan dalam penelitian ini yaitu pengumpulan data menggunakan kuesioner. Teknik analisis yang digunakan adalah regresi berganda, dengan melakukan uji instrument (Validitas dan Reliabilitas), uji hipotesis uji t, uji F, uji Koefisien Determinasi dan uji asumsi klasik (normalitas, multikolieniritas dan heterokedastisitas). Hasil penelitian regresi berganda dapat diperoleh persamaan : Y = 4,408 + 0,428 X1 + 0,362 X2 + 0,029 X3 + e. Hasil analisis dengan menggunakan SPSS Versi 16.0 menunjukan bahwa: (1) Kepemimpinan berpengaruh terhadap kinerja guru, (2) Motivasi berpengaruh terhadap kinerja guru, (3) Lingkungan Kerja berpengaruh positif tapi tidak singnifikan terhadap kinerja guru. Angka Adjusted R Square sebesar 0,690 atau 69 % yang berarti Kinerja Guru dapat dijelaskan oleh ke empat variabel independen dalam persamaan regresi. Sedangkan sisanya sebesar 31 % dijelaskan oleh variabel lain diluar ke empat variabel yang digunakan dalam penelitian ini

Wie ein iglicher || Christ gegen allerley le=||re/ gut vnd bœse/ nach || Gottes befelh/ sich gebuer=||lich halten sol.|| Justus Menius.|| Mit einer Vorrhede || D. Mart. Luther.||

Vorlageform des Erscheinungsvermerks: Wittemberg || M D XXXVIII ||(Gedruckt ... || durch Nickel Schirlentz/||