Detection and Typing of Highly Pathogenic Porcine Reproductive and Respiratory Syndrome Virus by Multiplex Real-Time RT-PCR

Porcine reproductive and respiratory syndrome (PRRS) causes economic losses in the pig industry worldwide, and PRRS viruses (PRRSV) are classified into the two distinct genotypes “North American (NA, type 2)” and “European (EU, type 1)”. In 2006, a highly pathogenic NA strain of PRRSV (HP-PRRSV), characterized by high fever as well as high morbidity and mortality, emerged in swine farms in China. Therefore, a real-time reverse transcription polymerase chain reaction (RT-qPCR) assay specific for HP-PRRSV was developed and combined with type 1- and type 2-specific RT-qPCR systems. Furthermore, an internal control, based on a heterologous RNA, was successfully introduced. This final multiplex PRRSV RT-qPCR, detecting and typing PRRSV, had an analytical sensitivity of less than 200 copies per µl for the type 1-assay and 20 copies per µl for the type 2- and HP assays and a high diagnostic sensitivity. A panel of reference strains and field isolates was reliably detected and samples from an animal trial with a Chinese HP-PRRS strain were used for test validation. The new multiplex PRRSV RT-qPCR system allows for the first time the highly sensitive detection and rapid differentiation of PRRSV of both genotypes as well as the direct detection of HP-PRRSV

Properties of permutation-based gene tests and controlling type 1 error using a summary statistic based gene test

Background: The advent of genome-wide association studies has led to many novel disease-SNP associations, opening the door to focused study on their biological underpinnings. Because of the importance of analyzing these associations, numerous statistical methods have been devoted to them. However, fewer methods have attempted to associate entire genes or genomic regions with outcomes, which is potentially more useful knowledge from a biological perspective and those methods currently implemented are often permutation-based. Results: One property of some permutation-based tests is that their power varies as a function of whether significant markers are in regions of linkage disequilibrium (LD) or not, which we show from a theoretical perspective. We therefore develop two methods for quantifying the degree of association between a genomic region and outcome, both of whose power does not vary as a function of LD structure. One method uses dimension reduction to “filter” redundant information when significant LD exists in the region, while the other, called the summary-statistic test, controls for LD by scaling marker Z-statistics using knowledge of the correlation matrix of markers. An advantage of this latter test is that it does not require the original data, but only their Z-statistics from univariate regressions and an estimate of the correlation structure of markers, and we show how to modify the test to protect the type 1 error rate when the correlation structure of markers is misspecified. We apply these methods to sequence data of oral cleft and compare our results to previously proposed gene tests, in particular permutation-based ones. We evaluate the versatility of the modification of the summary-statistic test since the specification of correlation structure between markers can be inaccurate. Conclusion: We find a significant association in the sequence data between the 8q24 region and oral cleft using our dimension reduction approach and a borderline significant association using the summary-statistic based approach. We also implement the summary-statistic test using Z-statistics from an already-published GWAS of Chronic Obstructive Pulmonary Disorder (COPD) and correlation structure obtained from HapMap. We experiment with the modification of this test because the correlation structure is assumed imperfectly known

Case Report: Pediatric Renal Sarcoidosis and Prognostic Factors in Reviewed Cases

Background: Pediatric sarcoidosis is a complex inflammatory disorder with multisystemic manifestations. Kidney involvement in children is rare, and prognostic factors are unknown. Case Report and Methods: We report the case of a 16-year-old girl with multiorgan sarcoidosis and renal involvement. The patient presented with tubulointerstitial nephritis, acute kidney injury (AKI), chest CT disseminated noduli, granulomatous iridocyclitis, giant-cell sialadenitis, and arthralgia. The kidney biopsy revealed non-granulomatous interstitial nephritis. Treatment consisted of initial high-dose methylprednisolone pulse followed by oral prednisolone and methotrexate. Full remission was achieved. In addition, we performed a literature review using PubMed and analyzed data on pediatric renal sarcoidosis cases. Results: We identified 36 cases of pediatric sarcoidosis with renal involvement on presentation and data on the end-of-follow-up glomerular filtration rate (GFR). The data from the literature review showed that renal involvement was slightly more prevalent in males (60%). AKI was present in most of the described patients (84%). Oral prednisolone was used in 35 of 36 cases; in more severe cases, other immunosuppressants were used. We newly identified renal concentration impairment and granulomatous interstitial nephritis as factors with a clear trend toward GFR loss at the end of follow-up, emphasizing the importance of kidney biopsy in symptomatic patients. In contrast, higher GFR at presentation and hypercalcemia were rather favorable factors. According to the identified predictive factors, our patient has a good prognosis and is in remission. Conclusion: The factors indicating a trend toward an unfavorable renal outcome in pediatric sarcoidosis are renal concentration impairment and granulomatous interstitial nephritis at presentation, while a higher GFR is beneficial

Wie aufgeklärt sind unsere Grundschüler? Befragung von 111 Kindern der 4. Jahrgangsstufe zum Thema Sexualität

Die Untersuchung fand 2006 in 5 Klassen der vierten Jahrgangsstufe in ländlicher Umgebung statt. Von den befragten 111 Schülern waren 45 Jungen und 66 Mädchen. 70 der 111 Schüler hatten bereits Sexualkundeunterricht. Dieser führte nach dem Ergebnis dieser Untersuchung nicht zu einem umfassenden Wissensstand. Im Rahmen der Lehrerausbildung in Niedersachsen ist eine Vorbereitung auf den Sexualkundeunterricht nicht verpflichtend und das, obwohl die Pubertät im Vergleich zu den vorhergehenden Generationen früher einsetzt. Eine qualitativ hochwertige sexuelle Aufklärung scheint daher für alle Kinder vor Einsetzen der Pubertät sinnvoll

Barriers and Strategies in Guideline Implementation—A Scoping Review

Fischer F, Lange K, Klose K, Greiner W, Krämer A. Barriers and Strategies in Guideline Implementation—A Scoping Review. Healthcare. 2016;4(3): 36.Research indicates that clinical guidelines are often not applied. The success of their implementation depends on the consideration of a variety of barriers and the use of adequate strategies to overcome them. Therefore, this scoping review aims to describe and categorize the most important barriers to guideline implementation. Furthermore, it provides an overview of different kinds of suitable strategies that are tailored to overcome these barriers. The search algorithm led to the identification of 1659 articles in PubMed. Overall, 69 articles were included in the data synthesis. The content of these articles was analysed by using a qualitative synthesis approach, to extract the most important information on barriers and strategies. The barriers to guideline implementation can be differentiated into personal factors, guideline-related factors, and external factors. The scoping review revealed the following aspects as central elements of successful strategies for guideline implementation: dissemination, education and training, social interaction, decision support systems and standing orders. Available evidence indicates that a structured implementation can improve adherence to guidelines. Therefore, the barriers to guideline implementation and adherence need to be analysed in advance so that strategies that are tailored to the specific setting and target groups can be developed

Nanoproteomic analysis of ischemia-dependent changes in signaling protein phosphorylation in colorectal normal and cancer tissue

Additional file 1: Table S1. Clinical data for the 20 patients analyzed in the study. Presents patient clinical data including tumor stage and grade

‘Location, Location, Location’: a spatial approach for rare variant analysis and an application to a study on non-syndromic cleft lip with or without cleft palate

Motivation: For the analysis of rare variants in sequence data, numerous approaches have been suggested. Fixed and flexible threshold approaches collapse the rare variant information of a genomic region into a test statistic with reduced dimensionality. Alternatively, the rare variant information can be combined in statistical frameworks that are based on suitable regression models, machine learning, etc. Although the existing approaches provide powerful tests that can incorporate information on allele frequencies and prior biological knowledge, differences in the spatial clustering of rare variants between cases and controls cannot be incorporated. Based on the assumption that deleterious variants and protective variants cluster or occur in different parts of the genomic region of interest, we propose a testing strategy for rare variants that builds on spatial cluster methodology and that guides the identification of the biological relevant segments of the region. Our approach does not require any assumption about the directions of the genetic effects. Results: In simulation studies, we assess the power of the clustering approach and compare it with existing methodology. Our simulation results suggest that the clustering approach for rare variants is well powered, even in situations that are ideal for standard methods. The efficiency of our spatial clustering approach is not affected by the presence of rare variants that have opposite effect size directions. An application to a sequencing study for non-syndromic cleft lip with or without cleft palate (NSCL/P) demonstrates its practical relevance. The proposed testing strategy is applied to a genomic region on chromosome 15q13.3 that was implicated in NSCL/P etiology in a previous genome-wide association study, and its results are compared with standard approaches. Availability: Source code and documentation for the implementation in R will be provided online. Currently, the R-implementation only supports genotype data. We currently are working on an extension for VCF files. Contact: [email protected]

Resilience management processes in the offshore wind industry: Schematization and application to an export cable attack

Offshore wind energy (OWE) production is a crucial element for increasing the amount of renewable energy. Consequently, one can observe a strong and constant rise of the OWE industry, turning it to an important contributor of national energy provision. This trend, however, is accompanied by increasing pressure on the reliability, safety, and security of the OWE infrastructure. Related security threats are characterized by high uncertainty regarding impact and probability leading to considerable complication of the risk assessment. On the other hand, the resilience concept emphasizes the consideration of the system’s response to such threats, and thus, offers a solution for dealing with the high uncertainty. In this work, we present an approach for combining the strengths of risk and resilience management to provide a solution for handling security threats in OWE infrastructures. Within this context, we introduce a quality assessment enabling the quantification of the trustworthiness of obtained results