Test Based on Independent,but Non-identically Distributed Random Variables

The binomial test is applied for the problem of testing a hypothesis based on a sample of independent, but non-identically distributed random variables. The used basic idea is that each random variable indicates the presence of the hypothesis. Hence each random variable is transformed such that the binomial test can be used as a simple procedure.     

FISH in der Diagnostik hämatologischer Neoplasien

All hematological malignancies are characterized by considerable clinical heterogeneity. The diverse entities can be subdivided into a variety of prognosis-defining subtypes on the basis of cytogenetic aberrations and molecular mutations. To adapt the intensity of treatment to the patient’s individual risk profile, an exact classification of the subtypes on the basis of genetic markers is essential. Diverse fluorescent in situ hybridization (FISH) techniques thereby play a central role in interaction with classic chromosome banding analyses for clarifying findings of chromosome analyses, such as in the acute leukemias, or for classifying the diverse subtypes, as in the non-Hodgkin’s lymphomas. Depending on the disease, the clinical impact of FISH varies. It is used as the method of choice for genetic characterization (e.g., in multiple myeloma) or is used in combination with chromosome banding analysis. Furthermore, interphase FISH is essential when rapid confirmation of the diagnosis is needed, as in acute promyelocytic leukemia with the t(15;17)/PML-RARA rearrangement, for which therapy with all-trans retinoic acid (ATRA) should be immediately started.     

Pränatale Detektion fetaler chromosomaler Aberrationen im 1. und 2. Trimenon

Modern noninvasive methods of prenatal medicine, in particular first-trimester-screening, enable early risk evaluation of the most common forms of aneuploidy. With over 4000 certified gynecologists in Germany, this method nowadays represents the standard in prenatal risk evaluation. The importance of classic genetic sonography during the second trimester by detection of soft markers for aneuploidy has declined. However, detailed sonography during the second trimester remains the gold standard for the detection of congenital anomalies. Therefore, the specialist in prenatal medicine must be able to recognize soft markers during this examination in order to re-evaluate the maternal risk for aneuploidy.     

Beckwith-Wiedemann-Syndrom

The Beckwith-Wiedemann syndrome (BWS) is a pediatric overgrowth syndrome with a variable clinical appearance. The phenotype normalizes with age but the diagnosis of BWS is important as syndrome-specific complications may develop, in particular as a result of a 400-fold increased risk of patients developing certain tumor entities, predominantly nephroblastomas (Wilms’ tumors) and hepatoblastomas, within the first years of life. BWS displays a clinical overlap with other syndromes so that an unambiguous molecular diagnostic is required for risk assessment and appropriate therapy. At the molecular level BWS is associated with the chromosomal region 11p15.5, where two clusters with imprinted genes are located. In patients both genetic mutations and in most cases aberrant DNA methylation can be observed, which pathogenically affect the gene dosage of functionally available monoallelically expressed 11p15.5 genes. Currently only a very incomplete genotype-phenotype correlation exists for BWS. Current research projects provide insights in the molecular etiopathogenesis of the syndrome by identifying interacting partners which modify the epigenetic regulation of imprinted 11p15.5-genes.     

Mathematical Modelling of the Transmission Dynamics of Contagious Bovine Pleuropneumonia Reveals Minimal Target Profiles for Improved Vaccines and Diagnostic Assays

Contagious bovine pleuropneumonia (CBPP) is a cattle disease that has hampered the development of the livestock sector in sub-Saharan Africa. Currently, vaccination with a live vaccine strain is its recommended control measure although unofficial antimicrobial use is widely practiced. Here, modelling techniques are used to assess the potential impact of early elimination of infected cattle via accurate diagnosis on CBPP dynamics. A herd-level stochastic epidemiological model explicitly incorporating test sensitivity and specificity is developed. Interventions by annual vaccination, annual testing and elimination and a combination of both are implemented in a stepwise manner and their effectiveness compared by running 1000 simulations per intervention over ten years. The model predicts that among the simulated interventions, the ones likely to eliminate the disease from an isolated herd all involved annual vaccination of more than 75% of the animals with a vaccine that protects for at least 18 months combined with annual testing (and elimination of positive reactors) of 75% of the animals every six months after vaccination. The highest probability of disease elimination was 97.5% and this could occur within a median of 2.3 years. Generally, our model predicts that regular testing and elimination of positive reactors using improved tests will play a significant role in minimizing CBPP burden especially in the current situation where improved vaccines are yet to be developed.     

The Economic Impact of Eradicating Peste des Petits Ruminants: A Benefit-Cost Analysis

Peste des petits ruminants (PPR) is an important cause of mortality and production loss among sheep and goats in the developing world. Despite control efforts in a number of countries, it has continued to spread across Africa and Asia, placing an increasing burden on the livelihoods of livestock keepers and on veterinary resources in affected countries. Given the similarities between PPR and rinderpest, and the lessons learned from the successful global eradication of rinderpest, the eradication of PPR seems appealing, both eliminating an important disease and improving the livelihoods of the poor in developing countries. We conducted a benefit-cost analysis to examine the economic returns from a proposed programme for the global eradication of PPR. Based on our knowledge and experience, we developed the eradication strategy and estimated its costs. The benefits of the programme were determined from (i) the averted mortality costs, based on an analysis of the literature, (ii) the downstream impact of reduced mortality using a social accounting matrix, and (iii) the avoided control costs based on current levels of vaccination. The results of the benefit-cost analysis suggest strong economic returns from PPR eradication. Based on a 15-year programme with total discounted costs of US$2.26 billion, we estimate discounted benefits of US$76.5 billion, yielding a net benefit of US$74.2 billion. This suggests a benefit cost ratio of 33.8, and an internal rate of return (IRR) of 199%. As PPR mortality rates are highly variable in different populations, we conducted a sensitivity analysis based on lower and higher mortality scenarios. All the scenarios examined indicate that investment in PPR eradication would be highly beneficial economically. Furthermore, removing one of the major constraints to small ruminant production would be of considerable benefit to many of the most vulnerable communities in Africa and Asia.     

Structural changes and relaxations monitored by luminescence

Luminescence data have often been used to study imperfections and to characterize lattice distortions because the signals are sensitive to changes of structure and composition. Previous studies have included intentionally added probe ions such as rare earth ions to sense distortions in local crystal fields caused by modified structural environments. An under‐exploited extension of this approach was to use luminescence to monitor crystalline phase changes. A current overview of this new and powerful technique shows that continuous scanning of the sample temperatures immediately offered at least three types of signatures for phase transitions. Because of high sensitivity, luminescence signals were equally responsive to structural changes from inclusions and nanoparticles. These coupled to the host material via long‐range interactions and modified the host signals. Two frequently observed examples that are normally overlooked are from nanoparticle inclusions of water and CO_2. Examples also indicated that phase transitions were detected in more diverse materials such as superconductors and fullerenes. Finally, luminescence studies have shown that in some crystalline examples, high dose ion implantation of surface layers could induce relaxations and/or structural changes of the entire underlying bulk material. This was an unexpected result and therefore such a possibility has not previously been explored. However, the implications for ion implication are significant and could be far more general than the examples mentioned here. Copyright © 2012 John Wiley & Sons, Ltd.     

Osteogenesis imperfecta

Osteogenesis imperfecta (OI) is the most frequently occurring congenital disorder with an increased fracture rate and systemic skeletal involvement. The vast majority of patients have an autosomal dominant form of OI resulting from a mutation in one of the two type I collagen genes COL1A1 or COL1A2. Since 2006, eight genes for autosomal recessive forms of the disorder have been identified, as well as one additional gene for autosomal dominant OI. Our knowledge concerning molecular pathophysiology has been substantially broadened, such that the paradigm of OI as a pure ??collagenopathy?? no longer applies and the clinical classification system will have to be revised. Standard therapy for the more severe forms of OI comprises intravenous administration of bisphosphonates. Additional elements of a multimodal therapeutic concept include surgical intervention for bone deformities or fractures and physiotherapy.