Diagnostic delay in Crohn's disease is associated with a complicated disease course and increased operation rate.

OBJECTIVES: The impact of diagnostic delay (a period from appearance of first symptoms to diagnosis) on the clinical course of Crohn's disease (CD) is unknown. We examined whether length of diagnostic delay affects disease outcomes. METHODS: Data from the Swiss IBD cohort study were analyzed. Patients were recruited from university centers (68%), regional hospitals (14%), and private practices (18%). The frequencies of occurrence of bowel stenoses, internal fistulas, perianal fistulas, and CD-related surgery (intestinal and perianal) were analyzed. RESULTS: A total of 905 CD patients (53.4% female, median age at diagnosis 26 (20-36) years) were stratified into four groups according to the quartiles of diagnostic delay (0-3, 4-9, 10-24, and ≥25 months, respectively). Median diagnostic delay was 9 (3-24) months. The frequency of immunomodulator and/or antitumor necrosis factor drug use did not differ among the four groups. The length of diagnostic delay was positively correlated with the occurrence of bowel stenosis (odds ratio (OR) 1.76, P=0.011 for delay of ≥25 months) and intestinal surgery (OR 1.76, P=0.014 for delay of 10-24 months and OR 2.03, P=0.003 for delay of ≥25 months). Disease duration was positively associated and non-ileal disease location was negatively associated with bowel stenosis (OR 1.07, P<0.001, and OR 0.41, P=0.005, respectively) and intestinal surgery (OR 1.14, P<0.001, and OR 0.23, P<0.001, respectively). CONCLUSIONS: The length of diagnostic delay is correlated with an increased risk of bowel stenosis and CD-related intestinal surgery. Efforts should be undertaken to shorten the diagnostic delay.

Bioassay for detection of transgenic soybean seeds tolerant to glyphosate

Glyphosate is a systemic, nonselective, postemergence herbicide that inhibits growth of both weeds and crop plants. Once inside the plant, glyphosate interferes with biosynthesis of aromatic amino acids phenylalanine, tyrosine, and tryptophan, by inhibiting the activity of 5enolpyruvylshikimate-3-phosphate synthase (EPSPS), a key enzyme of the shikimate pathway. The objective of this work was to develop a simple, effective and inexpensible method for identification of transgenic soybean tolerant to glyphosate. This technique consisted in germinating soybean seeds in filter paper moistened with 100 to 200 muM of glyphosate. Transgenic soybean seeds tolerant to glyphosate germinated normally in this solution and, between 7 and 10 days, started to develop a primary root system. However non-transgenic seeds stopped primary root growth and emission of secondary roots.

Long diagnostic delay in Crohn's disease is associated with complicated disease course and increased operation rate

Background and Aims: The impact of d iagnostic delay ( a period from appearance of f irst s ymptoms t o diagnosis) o n the clinical c ourse o f Crohn's disease (CD) i s unknown. W e examined whether length of d iagnostic delay a ffects d isease outcome. Methods: Data from the Swiss IBD cohort study were analyzed. T he frequencies of o ccurrence of b owel s tenoses, internal fistulas, perianal f istulas, and CD-related surgery at distinct i ntervals a fter C D diagnosis (0 - < 2 , 2 - < 6,  6 years) were c ompared f or g roups o f patients w ith different length of d iagnostic delay. Results: T he data from a g roup o f 200 CD patients with long diagnostic delay (> 24 months, 76th - 100th p ercentile) were c ompared to t hose from a group of 4 61 patients with a short diagnostic delay ( within 9 months, 1st - 50th p ercentile). T reatment r egimens d id n ot d iffer between t he two groups. Two years following diagnosis, p atients with long diagnostic delay presented more frequently with bowel stenoses (25% vs. 13.1%, p = 0.044), internal fistulas (10% vs. 2%, p = 0.018), perianal f istulas ( 20% vs. 8 .1%, p = 0.023) a nd more frequently underwent intestinal surgery (15% vs. 5 .1%, p = 0.024) t han patients with short diagnostic delay. Intestinal surgery was a lso m ore frequently p erformed  6 y ears after diagnosis in t he group with long d iagnostic delay ( 56.2% vs. 42.3%, p = 0.005) w hen compared to t he g roup with short diagnostic delay. Conclusions: L ong diagnostic delay i s associated with worse o utcome c haracterized by t he development o f increased bowel damage, n ecessitating more frequently operations in t he years following CD d iagnosis. Efforts should be undertaken to shorten the diagnostic delay.

Networking of differentially expressed genes in human cancer cells resistant to methotrexate

BACKGROUND: The need for an integrated view of data obtained from high-throughput technologies gave rise to network analyses. These are especially useful to rationalize how external perturbations propagate through the expression of genes. To address this issue in the case of drug resistance, we constructed biological association networks of genes differentially expressed in cell lines resistant to methotrexate (MTX). METHODS: Seven cell lines representative of different types of cancer, including colon cancer (HT29 and Caco2), breast cancer (MCF-7 and MDA-MB-468), pancreatic cancer (MIA PaCa-2), erythroblastic leukemia (K562) and osteosarcoma (Saos-2), were used. The differential expression pattern between sensitive and MTX-resistant cells was determined by whole human genome microarrays and analyzed with the GeneSpring GX software package. Genes deregulated in common between the different cancer cell lines served to generate biological association networks using the Pathway Architect software. RESULTS: Dikkopf homolog-1 (DKK1) is a highly interconnected node in the network generated with genes in common between the two colon cancer cell lines, and functional validations of this target using small interfering RNAs (siRNAs) showed a chemosensitization toward MTX. Members of the UDP-glucuronosyltransferase 1A (UGT1A) family formed a network of genes differentially expressed in the two breast cancer cell lines. siRNA treatment against UGT1A also showed an increase in MTX sensitivity. Eukaryotic translation elongation factor 1 alpha 1 (EEF1A1) was overexpressed among the pancreatic cancer, leukemia and osteosarcoma cell lines, and siRNA treatment against EEF1A1 produced a chemosensitization toward MTX. CONCLUSIONS: Biological association networks identified DKK1, UGT1As and EEF1A1 as important gene nodes in MTX-resistance. Treatments using siRNA technology against these three genes showed chemosensitization toward MTX.

Effect of Delay in Testing Asphalt Concrete Specimens for Marshall Stability, MLR-86-08, Draft, 1986

The Central Laboratory has been delaying the mix design testing of 2 1/2" X 4" Marshall specimens for stability, until the next day after molding. For example, if the mixes are made and samples molded on Friday a man would have to come in and work on Saturday to test these specimens. The reason for this is that the ASTM-01559 "Resistance to Plastic Flow of Bituminous Mixes Using Marshall Apparatus," states that "the specimens after being molded shall be carefully transferred to a smooth, flat surface and allowed to stand overnight at room temperature, before being weighed, measured and tested." The AASHTO procedure, AASHTO Designation T-245-82 "Resistance to Plastic Flow of Bituminous Mixtures using Marshall Apparatus," does not say when the specimens shall be tested for stability. The IDOT Lab. Specifications, Test Method No. Iowa 502-8 and test method No. Iowa 506-C "compacting asphaltic concrete by the Marshall Method" and "Resistance to Plastic Flow of Bituminous Mixtures Using the Marshall Apparatus," respectively, only state that the specimens shall be cooled before testing. Due to the above conflict in specifications, a number of mix samples were tested, in the Central Lab, for stability on different days. This should furnish enough information to allow us to change the procedure and to test for stability the same day molded, or be able to delay the testing for 3 days or more.

Reduction in the use of diagnostic tests in infants with risk factors for early-onset neonatal sepsis does not delay antibiotic treatment.

Despite a low positive predictive value, diagnostic tests such as complete blood count (CBC) and C-reactive protein (CRP) are commonly used to evaluate whether infants with risk factors for early-onset neonatal sepsis (EOS) should be treated with antibiotics. We investigated the impact of implementing a protocol aiming at reducing the number of diagnostic tests in infants with risk factors for EOS in order to compare the diagnostic performance of repeated clinical examination with CBC and CRP measurement. The primary outcome was the time between birth and the first dose of antibiotics in infants treated for suspected EOS. Among the 11,503 infants born at ≥35 weeks during the study period, 222 were treated with antibiotics for suspected EOS. The proportion of infants receiving antibiotics for suspected EOS was 2.1% and 1.7% before and after the change of protocol (p = 0.09). Reduction of diagnostic tests was associated with earlier antibiotic treatment in infants treated for suspected EOS (hazard ratio 1.58; 95% confidence interval [CI] 1.20-2.07; p <0.001), and in infants with neonatal infection (hazard ratio 2.20; 95% CI 1.19-4.06; p = 0.01). There was no difference in the duration of hospital stay nor in the proportion of infants requiring respiratory or cardiovascular support before and after the change of protocol. Reduction of diagnostic tests such as CBC and CRP does not delay initiation of antibiotic treatment in infants with suspected EOS. The importance of clinical examination in infants with risk factors for EOS should be emphasised.

Development of herbicide-tolerant irrigated rice cultivars

The objective of this work was to develop new irrigated rice lines tolerant to imidazolinone herbicides. The backcross breeding procedure was used to transfer the imidazolinone tolerance allele from mutant 93AS3510 to the recurrent parents 'BRS 7 Taim' and 'BRS Pelota'. Individual herbicide-tolerant plants were selected in each generation, for three backcrossings (RC1 to RC3), followed by three selfing generations (RC3F1 to RC3F3). The best four RC3F3 lines for agronomic traits were genotyped with 44 microsatellite markers. The observed conversion index of the new imidazolinone-tolerant lines varied from 91.86 to 97.67%. Pairwise genetic distance analysis between these lines and 22 accessions from the Embrapa's Rice Germplasm Bank clustered the new lines with their respective recurrent parents, but not with 'IRGA 417', which was originally used as recurrent parent to derive IRGA 422 CL, the only imidazolinone-tolerant irrigated rice cultivar recommended for cultivation in Brazil. Therefore, these lines represent new options of genetically diverse imidazolinone-tolerant rice accessions. Lines CNA10756 ('BRS Sinuelo CL') and CNA10757 will be released for cultivation in the Clearfield irrigated rice production system in Rio Grande do Sul, Brazil.

Tannin-tolerant bacteria from crossbred Holstein x Zebu cows

The objective of this work was to isolate and characterize tannin-tolerant ruminal bacteria from crossbred Holstein x Zebu cows fed a chopped mixture of elephant grass (Pennisetum purpureum), young stems of "angico-vermelho" (Parapiptadenia rigida), and banana tree (Musa sp.) leaves. A total of 117 bacteria strains were isolated from enrichment cultures of rumen microflora in medium containing tannin extracts. Of these, 11 isolates were able to tolerate up to 3 g L-1 of tannins. Classical characterization procedures indicated that different morphological and physiological groups were represented. Restriction fragments profiles using Alu1 and Taq1 of 1,450 bp PCR products from the 16S rRNA gene grouped the 11 isolates into types I to VI. Sequencing of 16S rRNA PCR products was used for identification. From the 11 strains studied, seven were not identifiable by the methods used in this work, two were strains of Butyrivibrio fibrisolvens, and two of Streptococcus bovis.

Long diagnostic delay in Crohn's disease is associated with complicated disease course and increased operation rate

Background: We have recently shown that the median diagnostic delay to establish Crohn's disease (CD) diagnosis in the Swiss IBD Cohort (SIBDC) was 9 months. Seventy five percent of all CD patients were diagnosed within 24 months. The clinical impact of a long diagnostic delay on the natural history of CD is unknown. Aim: To compare the frequency and type of CD-related complications in the patient groups with long diagnostic delay (>24 months) vs. the ones diagnosed within 24 months. Methods: Retrospective analysis of data from the SIBDCS, comprising a large sample of CD patients followed in hospitals and private practices across Switzerland. Results: Two hundred CD patients (121 female, mean age 44.9 ± 15.0 years, 38% smokers, 71% ever treated with immunomodulators and 35% with anti-TNF) with long diagnostic delay were compared to 697 CD patients (358 female, mean age 39.1 ± 14.9 years, 33% smokers, 74% ever treated with immunomodulators and 33% with anti-TNF) diagnosed within 24 months. No differences in the outcomes were observed between the two patient groups within year one after CD diagnosis. Among those diagnosed 2-5 years ago, CD patients with long diagnostic delay (n = 45) presented more frequently with internal fistulas (11.1% vs. 3.1%, p = 0.03) and bowel stenoses (28.9% vs. 15.7%, p = 0.05), and they more frequently underwent CD-related operations (15.6% vs. 5.0%, p = 0.02) compared to the patients diagnosed within 24 months (n = 159). Among those diagnosed 6-10 years ago, CD patients with long diagnostic delay (n = 48) presented more frequently with extraintestinal manifestations (60.4% vs. 34.6%, p = 0.001) than those diagnosed within 24 months (n = 182). For the patients diagnosed 11-15 years ago, no differences in outcomes were found between the long diagnostic delay group (n = 106) and the one diagnosed within 24 months (n = 32). Among those diagnosed >= 16 years ago, the group with long diagnostic delay (n = 71) more frequently underwent CD-related operations (63.4% vs. 46.5%, p = 0.01) compared to the group diagnosed with CD within 24 months (n = 241). Conclusions: A long diagnostic delay in CD patients is associated with a more complicated disease course and higher number of CD-related operations in the years following the diagnosis. Our results indicate that efforts should be undertaken to shorten the diagnostic delay in CD patients in order to reduce the risk for progression towards a complicated disease phenotype.

Science 2.0 : The use of social networking in research.

REBIUN study on Science 2.0 and social web applications for research. There are three categories: share research, share resources and share results. Describes the applications and selected resources of interest: scientific social networks, scientific databases, research platforms, surveys, concept maps, file sharing, bibliographic management, social bookmarking, citation indexes, blogs and wikis, science news, open access. The services are evaluated and the report describes his interest to libraries.

Extending Learning Objects by Means of Social Networking

Learning objects have been the promise of providing people with high quality learning resources. Initiatives such as MIT Open-CourseWare, MERLOT and others have shown the real possibilities of creating and sharing knowledge through Internet. Thousands of educational resources are available through learning object repositories. We indeed live in an age of content abundance, and content can be considered as infrastructure for building adaptive and personalized learning paths, promoting both formal and informal learning. Nevertheless, although most educational institutions are adopting a more open approach, publishing huge amounts of educational resources, the reality is that these resources are barely used in other educational contexts. This paradox can be partly explained by the dificulties in adapting such resources with respect to language, e-learning standards and specifications and, finally, granularity. Furthermore, if we want our learners to use and take advantage of learning object repositories, we need to provide them with additional services than just browsing and searching for resources. Social networks can be a first step towards creating an open social community of learning around a topic or a subject. In this paper we discuss and analyze the process of using a learning object repository and building a social network on the top of it, with respect to the information architecture needed to capture and store the interaction between learners and resources in form of learning object metadata.

Reconstruction of the join time-delay Doppler-scale reflectivity density in the wide-band regime. A frame theory based approach

The inverse scattering problem concerning the determination of the joint time-delayDoppler-scale reflectivity density characterizing continuous target environments is addressed by recourse to the generalized frame theory. A reconstruction formula,involving the echoes of a frame of outgoing signals and its corresponding reciprocalframe, is developed. A ‘‘realistic’’ situation with respect to the transmission ofa finite number of signals is further considered. In such a case, our reconstruction formula is shown to yield the orthogonal projection of the reflectivity density onto a subspace generated by the transmitted signals.

Design of an Embedded Computer Board for Networking Applications

Tämä diplomityö tehtiin Convergens Oy:lle. Convergens on elektroniikan suunnittelutoimisto, joka on erikoistunut sulautettuihin järjestelmiin sekä tietoliikennetekniikkaan. Diplomityön tavoitteena oli suunnitella tietokonekortti tietoliikennesovelluksia varten asiakkaalle, jolta vaatimusmäärittelyt tulivat. Työ on rajattu koskemaan laitteen prototyypin suunnittelua. Työssä suunnitellaan pääasiassa WLAN-tukiaseman tietokone. Tukiasema onasennettavissa toimistoihin, varastoihin, kauppoihin sekä myös liikkuvaan ajoneuvoon. Suunnittelussa on otettu nämä asiat huomioon, ja laitteen akun pystyy lataamaan muun muassa auton akulla. Langattomat tekniikat ovat voimakkaasti yleistymässä, ja tämän työn tukiasema tarjoaakin varteenotettavan vaihtoehdon lukuisilla ominaisuuksillaan. Mukana on mm. GPS, Bluetooth sekä Ethernet-valmius. Langattomien tekniikoiden lisäksi myös sulautetut järjestelmät ovat voimakkaasti yleistymässä, ja nykyään mikroprosessoreita löytääkin lähesmistä vain. Tässä projektissa käytetty prosessori on nopeutensa puolesta kilpailukykyinen, ja siitä löytyy useita eri rajapintoja. Jatkossa tietokonekortille on myös tulossa WiMAX-tuki, joka lisää tukiaseman tulevaisuuden arvoa asiakkaalle. Projektiin valittu Freescalen MPC8321E-prosessori on PowerPC-arkkitehtuuriin perustuva ja juuri markkinoille ilmestynyt. Tämä toi mukanaan lisähaasteen, sillä kyseisestä prosessorista ei ollut vielä kaikkea tietoa saatavilla. Mekaniikka toi omat haasteensa mukanaan, sillä se rajoitti piirilevyn koonniin, että ylimääräistä piirilevytilaa ei juurikaan jäänyt. Tämän takia esimerkiksi DDR-muistit olivat haastavia reitittää, sillä muistivetojen on oltava melko samanpituisia keskenään. Käyttöjärjestelmänä projektissa käytetään Linuxia. Suunnittelu alkoi keväällä 2007 ja toimiva prototyyppi oli valmis alkusyksystä. Prototyypin testaus osoitti, että tietokonekortti kykenee täyttämään kaikki asiakkaan vaatimukset. Prototyypin testauksessa löytyneet viat ja optimoinnit on tarkoitus korjata tuotantomalliin, joten se antaa hyvän pohjan jatkosuunnittelua varten.

Networking of differentially expressed genes in human cancer cells resistant to methotrexate

BACKGROUND: The need for an integrated view of data obtained from high-throughput technologies gave rise to network analyses. These are especially useful to rationalize how external perturbations propagate through the expression of genes. To address this issue in the case of drug resistance, we constructed biological association networks of genes differentially expressed in cell lines resistant to methotrexate (MTX). METHODS: Seven cell lines representative of different types of cancer, including colon cancer (HT29 and Caco2), breast cancer (MCF-7 and MDA-MB-468), pancreatic cancer (MIA PaCa-2), erythroblastic leukemia (K562) and osteosarcoma (Saos-2), were used. The differential expression pattern between sensitive and MTX-resistant cells was determined by whole human genome microarrays and analyzed with the GeneSpring GX software package. Genes deregulated in common between the different cancer cell lines served to generate biological association networks using the Pathway Architect software. RESULTS: Dikkopf homolog-1 (DKK1) is a highly interconnected node in the network generated with genes in common between the two colon cancer cell lines, and functional validations of this target using small interfering RNAs (siRNAs) showed a chemosensitization toward MTX. Members of the UDP-glucuronosyltransferase 1A (UGT1A) family formed a network of genes differentially expressed in the two breast cancer cell lines. siRNA treatment against UGT1A also showed an increase in MTX sensitivity. Eukaryotic translation elongation factor 1 alpha 1 (EEF1A1) was overexpressed among the pancreatic cancer, leukemia and osteosarcoma cell lines, and siRNA treatment against EEF1A1 produced a chemosensitization toward MTX. CONCLUSIONS: Biological association networks identified DKK1, UGT1As and EEF1A1 as important gene nodes in MTX-resistance. Treatments using siRNA technology against these three genes showed chemosensitization toward MTX.