Sporadic bloody diarrhoea-associated thrombotic thrombocytopenic purpura-haemolytic uraemic syndrome: an adult and paediatric comparison

Although diarrhoea-associated haemolytic uremic syndrome (HUS) in children is well described, the clinical features of bloody diarrhoea-associated thrombotic thrombocytopenic purpura (TTP)-HUS in adults are not documented. Twenty-one adults, 6.5% of the 322 adults in The Oklahoma TTP-HUS Registry, 1989-2006, have presented with bloody diarrhoea. There were no case clusters. Escherichia coli O157:H7 was identified in five patients, but many patients did not have appropriate studies. The annual incidence was 0.68/10(6), 10-fold less than the incidence of diarrhoea-associated HUS in children in Oklahoma. Two (13%) of 16 patients in whom ADAMTS13 (A Disintegrin And Metalloproteinase with a ThromboSpondin type 1 motif, member 13) was measured had <10% activity. Severe neurological abnormalities (67%) and renal failure (62%) were common; seven patients (33%) died; no survivors have relapsed. Compared to the 38 other Oklahoma Registry patients with ADAMTS13 <10%, frequency of severe neurological abnormalities and death was not different; frequency of renal failure was greater; frequency of relapse was less. Compared to 5999 children with sporadic diarrhoea-associated HUS in published reports, frequency of renal failure and relapse was not different; frequency of severe neurological abnormalities and death was greater (P < 0.05 for all differences). Awareness of the continuous occurrence of sporadic bloody diarrhoea-associated TTP-HUS in adults is important for prompt diagnosis and appropriate management.

A case-control study of sporadic Creutzfeldt-Jakob disease in Switzerland: analysis of potential risk factors with regard to an increased CJD incidence in the years 2001-2004

BACKGROUND: In 2001, the observed annual mortality from Creutzfeldt-Jakob disease (CJD) in Switzerland increased from less than 1.5 to 2.6 per million inhabitants. An underlying cause could not be identified. METHODS: To analyse potential risk factors for sCJD in Switzerland, close relatives of 69 sCJD-patients and 224 frequency age-matched controls were interviewed in a case-control study using a standardised questionnaire. 135 potential risk factors including socio-demographics, medical history, occupation and diet were analysed by logistic regression adjusting for age, sex and education. RESULTS: sCJD patients were more likely to have travelled abroad, worked at an animal laboratory, undergone invasive dental treatment, orthopaedic surgery, ophthalmologic surgery after 1980, regular GP visits, taken medication regularly, and consumed kidney. No differences between patients and controls were found for residency, family history, and exposure to environmental and other dietary factors. CONCLUSION: Although some factors were significantly more frequent among sCJD-cases, this study did not reveal specific explanations for the increased incidence of deaths due to sporadic CJD observed in Switzerland since 2001. Results have to be interpreted with caution due to multiple testing and possible recall bias in association with a long incubation period. The most plausible reason for the increase in Swiss sCJD cases after 2000 is an improved case ascertainment. Therefore, underreporting of cases might well have occurred before the year 2001, and the "real" yearly incidence of sCJD might not be lower than, but rather above 2 per million inhabitants.

VHL inactivation is an important pathway for the development of malignant sporadic pancreatic endocrine tumors

A small subset of familial pancreatic endocrine tumors (PET) arises in patients with von Hippel-Lindau syndrome and these tumors may have an adverse outcome compared to other familial PET. Sporadic PET rarely harbors somatic VHL mutations, but the chromosomal location of the VHL gene is frequently deleted in sporadic PET. A subset of sporadic PET shows active hypoxia signals on mRNA and protein level. To identify the frequency of functionally relevant VHL inactivation in sporadic PET and to examine a possible prognostic significance we correlated epigenetic and genetic VHL alterations with hypoxia signals. VHL mutations were absent in all 37 PETs examined. In 2 out of 35 informative PET (6%) methylation of the VHL promoter region was detected and VHL deletion by fluorescence in situ hybridization was found in 14 out of 79 PET (18%). Hypoxia inducible factor 1alpha (HIF1-alpha), carbonic anhydrase 9 (CA-9), and glucose transporter 1 (GLUT-1) protein was expressed in 19, 27, and 30% of the 152 PETs examined. Protein expression of the HIF1-alpha downstream target CA-9 correlated significantly with the expression of CA-9 RNA (P<0.001), VHL RNA (P<0.05), and VHL deletion (P<0.001) as well as with HIF1-alpha (P<0.005) and GLUT-1 immunohistochemistry (P<0.001). These PET with VHL alterations and signs of hypoxia signalling were characterized by a significantly shortened disease-free survival. We conclude that VHL gene impairment by promoter methylation and VHL deletion in nearly 25% of PET leads to the activation of the HIF-pathway. Our data suggest that VHL inactivation and consecutive hypoxia signals may be a mechanism for the development of sporadic PET with an adverse outcome.

Regulations on E-Commerce Consumer Protection Rules in China and Europe Compared – Same Same but Different?

This article provides a comprehensive overview of the regulations on e-commerce protection rules in China and the European Union. It starts by giving a general overview of different approaches towards consumer protection in e-commerce. This article then scrutinizes the current legal system in China by mainly focusing on SAIC’s “Interim Measures for the Administration of Online Commodity Trading and Relevant Service Activities”. The subsequent chapter covers the supervision of consumer protection in e-commerce in China, which covers both the regulatory objects of online commodity trading and the applied regulatory mechanisms. While the regulatory objects include operating agents, operating objects, operating behavior, electronic contracts, intellectual property and consumer protection, the regulatory mechanisms for e-commerce in China combines market mechanism and industry self-discipline under the government’s administrative regulation. Further, this article examines the current European legal system in online commodity trading. It outlines the aim and the scope of EU legislation in the respective field. Subsequently, the paper describes the European approach towards the supervision of consumer protection in e-commerce. As there is no central EU agency for consumer protection in e-commerce transactions, the EU stipulates a framework for Member States’ institutions, thereby creating a European supervisory network of Member States’ institutions and empowers private consumer organisations to supervise the market on their behalf. Moreover, the EU encourages the industry to self- or co-regulate e-commerce by providing incentives. Consequently, this article concludes that consumer protection may be achieved by different means and different systems. However, even though at first glance the Chinese and the European system appear to differ substantially, a closer look reveals tendencies of convergence between the two systems.

Dreidimensionale Bewegungserfassung mit Consumer-Highspeedkameras: Eine Systementwicklung unter besonderer Berücksichtigung der Messunsicherheit

Schwerpunkt dieser Arbeit ist die Entwicklung und der Test eines auf Consumer-Highspeedkameras basierenden Bewegungserfassungssystems. Consumer-Kameras sind flexibler einsetzbar als kommerzielle Bewegungserfassungssysteme, zugleich kostengünstiger und werden daher oft in der sportwissenschaftlichen Forschung verwendet. Durch ihren Einsatz entstehen jedoch prinzipbedingt höhere Messunsicherheiten, deren Bestimmung in der vorliegenden Arbeit ein besonderer Stellenwert eingeräumt wird. Nach einem Überblick über aktuelle Bewegungserfassungssysteme und deren Genauigkeiten folgt eine Betrachtung der Messunsicherheit aus metrologischer Perspektive. Anschließend werden die Prozesse der Bilderfassung bei digitalen Consumer-Kameras sowie die zur Modellierung des Kameraabbildungsverhaltens notwendigen Parameteridentifikationsmethoden dargestellt. Diese reichen vom häufig genutzten DLT-Verfahren über Methoden mit Verzeichnungskorrektur bis zu Bündelausgleichsverfahren. Im Anschluss werden die für die verwendeten Kameras geeigneten Methoden auf Basis funktionaler Hardwaretests ausgewählt und weitere für das Bewegungserfassungssystem notwendige Softwarekomponenten diskutiert. Dazu gehören neben der automatisierten Video- und Bildverarbeitung, spezielle Verfahren zur Korrektur von Consumer-Kamera-spezifischen Abweichungen, z.B. die Korrektur von Rolling-Shutter-Verzerrungen. Im zweiten Teil der Arbeit richtet sich der Fokus auf die Simulation der Effekte von Parameterungenauigkeiten auf die Systemgenauigkeit sowie auf die Validierung und den Test des implementierten Systems. Dabei konnte die Rekonstruktionsgenauigkeit von 11.86mm bei einer Referenzrahmenkalibration durch den Einsatz der Kalibrationsmethode mit Bündelausgleichsverfahren von Svoboda u. a. (2005) auf maximal 4.126mm (M=0.073 mm; SD=1.486 mm) reduziert werden. Diese Methode erlaubt zudem eine einfachere Kalibration größerer Messvolumen ohne aufwändige Referenzrahmen und ist daher ideal für den sportwissenschaftlichen Einsatz geeignet. Ein weiteres Ergebnis der Arbeit ist die theoretische Ableitung der Fehlerfortpflanzung für die Prozessschritte der Bewegungserfassung. In Kombination mit der entwickelten Simulationsumgebung wird damit die Grundlage für eine Prädiktion der erreichbaren Messunsicherheit bereits vor der eigentlichen Messung gelegt.

Consumer Behavior in Moral Markets. On the Relevance of Identity, Justice Beliefs, Social Norms, Status and Trust in Ethical Consumption

This article addresses ethical consumer behavior and uses the purchase of Fair Trade (FT) coffee to gain insights into determinants of ‘moral behavior’ in the marketplace. Our primary concern is to clarify which theoretical concepts and determinants are more useful than others in explaining FT consumption. We compare the explanatory power of consumer budget restrictions, consumer identity, social and personal norms, social status, justice beliefs, and trust. Our second aim is methodological; we contrast data on self-reported consumption of FT coffee with experimental data on hypothetical choices of different coffee products. To gain insights into the robustness of our measurement and findings, we test our propositions using two samples of undergraduate students from Germany and the United States. Our data show that consumer identity and personal norms are the major determinants of FT consumption in both samples, the results from survey-based data and from our experimental data are similar in this regard. Further, we demonstrate that studies based on a limited number of determinants might overestimate effects; the effect of justice beliefs for instance vanishes if other determinants are taken into account.

"Deal of the day” platforms: what drives consumer loyalty?

Maintaining a loyal customer base is challenging for “Deal of the Day” (DoD) platforms. DoD providers market and sell deals on products and services, yet it is the merchants who ultimately deliver those to consumers. Low entry and switching costs drive competition in this market. However, research on the determinants of user loyalty in the DoD context is limited. This study uses Grounded Theory and Structural Equation Modeling to explore the phenomenon of DoD platform loyalty. Particularly, monetary benefits, signal-to-noise ratio, perceived risk, and service friendliness during a merchant encounter emerge as powerful determinants of loyalty in this novel context.

Consumer Health Information for Asians (CHIA): a collaborative project.

According to the 2000 United States Census, the Asian population in Houston, Texas, has increased more than 67% in the last ten years. To supplement an already active consumer health information program, the staff of the Houston Academy of Medicine-Texas Medical Center Library worked with community partners to bring health information to predominantly Asian neighborhoods. Brochures on health topics of concern to the Asian community were translated and placed in eight informational kiosks in Asian centers such as temples and an Asian grocery store. A press conference and a ribbon cutting ceremony were held to debut the kiosks and to introduce the Consumer Health Information for Asians (CHIA) program. Project goals for the future include digitizing the translated brochures, mounting them on the Houston HealthWays Website, and developing touch-screen kiosks. The CHIA group is investigating adding health resources in other Asian languages, as well as Spanish. Funding for this project has come from outside sources rather than from the regular library budget.

MODELING SPORADIC TUMOR FORMATION DRIVEN BY TELOMERE DYSFUNCTION IN THE GASTROINTESTINAL TRACT

Colorectal cancer is a complex disease that is thought to arise when cells accumulate mutations that allow for uncontrolled growth. There are several recognized mechanisms for generating such mutations in sporadic colon cancer; one of which is chromosomal instability (CIN). One hypothesized driver of CIN in cancer is the improper repair of dysfunctional telomeres. Telomeres comprise the linear ends of chromosomes and play a dual role in cancer. Its length is maintained by the ribonucleoprotein, telomerase, which is not a normally expressed in somatic cells and as cells divide, telomeres continuously shorten. Critically shortened telomeres are considered dysfunctional as they are recognized as sites of DNA damage and cells respond by entering into replicative senescence or apoptosis, a process that is p53-dependent and the mechanism for telomere-induced tumor suppression. Loss of this checkpoint and improper repair of dysfunctional telomeres can initiate a cycle of fusion, bridge and breakage that can lead to chromosomal changes and genomic instability, a process that can lead to transformation of normal cells to cancer cells. Mouse models of telomere dysfunction are currently based on knocking out the telomerase protein or RNA component; however, the naturally long telomeres of mice require multiple generational crosses of telomerase null mice to achieve critically short telomeres. Shelterin is a complex of six core proteins that bind to telomeres specifically. Pot1a is a highly conserved member of this complex that specifically binds to the telomeric single-stranded 3’ G-rich overhang. Previous work in our lab has shown that Pot1a is essential for chromosomal end protection as deletion of Pot1a in murine embryonic fibroblasts (MEFs) leads to open telomere ends that initiate a DNA damage response mediated by ATR, resulting in p53-dependent cellular senescence. Loss of Pot1a in the background of p53 deficiency results in increased aberrant homologous recombination at telomeres and elevated genomic instability, which allows Pot1a-/-, p53-/- MEFs to form tumors when injected into SCID mice. These phenotypes are similar to those seen in cells with critically shortened telomeres. In this work, we created a mouse model of telomere ysfunction in the gastrointestinal tract through the conditional deletion of Pot1a that recapitulates the microscopic features seen in severe telomere attrition. Combined intestinal loss of Pot1a and p53 lead to formation of invasive adenocarcinomas in the small and large intestines. The tumors formed with long latency, low multiplicity and had complex genomes due to chromosomal instability, features similar to those seen in sporadic human colorectal cancers. Taken together, we have developed a novel mouse model of intestinal tumorigenesis based on genomic instability driven by telomere dysfunction.

Characterization of the inflammatory cells in ascending thoracic aortic aneurysms in patients with Marfan syndrome, familial thoracic aortic aneurysms, and sporadic aneurysms.

OBJECTIVE: This study sought to characterize the inflammatory infiltrate in ascending thoracic aortic aneurysm in patients with Marfan syndrome, familial thoracic aortic aneurysm, or nonfamilial thoracic aortic aneurysm. BACKGROUND: Thoracic aortic aneurysms are associated with a pathologic lesion termed "medial degeneration," which is described as a noninflammatory lesion. Thoracic aortic aneurysms are a complication of Marfan syndrome and can be inherited in an autosomal dominant manner of familial thoracic aortic aneurysm. METHODS: Full aortic segments were collected from patients undergoing elective repair with Marfan syndrome (n = 5), familial thoracic aortic aneurysm (n = 6), and thoracic aortic aneurysms (n = 9), along with control aortas (n = 5). Immunohistochemistry staining was performed using antibodies directed against markers of lymphocytes and macrophages. Real-time polymerase chain reaction analysis was performed to quantify the expression level of the T-cell receptor beta-chain variable region gene. RESULTS: Immunohistochemistry of thoracic aortic aneurysm aortas demonstrated that the media and adventitia from Marfan syndrome, familial thoracic aortic aneurysm, and sporadic cases had increased numbers of T lymphocytes and macrophages when compared with control aortas. The number of T cells and macrophages in the aortic media of the aneurysm correlated inversely with the patient's age at the time of prophylactic surgical repair of the aorta. T-cell receptor profiling indicated a similar clonal nature of the T cells in the aortic wall in a majority of aneurysms, whether the patient had Marfan syndrome, familial thoracic aortic aneurysm, or sporadic disease. CONCLUSION: These results indicate that the infiltration of inflammatory cells contributes to the pathogenesis of thoracic aortic aneurysms. Superantigen-driven stimulation of T lymphocytes in the aortic tissues of patients with thoracic aortic aneurysms may contribute to the initial immune response.