Sealed Computation: Abstract Requirements for Mechanisms to Support Trustworthy Cloud Computing

In cloud computing, data processing is delegated to a remote party for efficiency and flexibility reasons. A practical user requirement usually is that the confidentiality and integrity of data processing needs to be protected. In the common scenarios of cloud computing today, this can only be achieved by assuming that the remote party does not in any form act maliciously. In this paper, we propose an approach that avoids having to trust a single entity. Our approach is based on two concepts: (1) the technical abstraction of sealed computation, i.e., a technical mechanism to confine the processing of data within a tamper-proof hardware container, and (2) the additional role of an auditing party that itself cannot add functionality to the system but is able to check whether the system (including the mechanism for sealed computation) works as expected. We discuss the abstract technical and procedural requirements of these concepts and explain how they can be applied in practice

The melanoma-specific graded prognostic assessment does not adequately discriminate prognosis in a modern population with brain metastases from malignant melanoma

The melanoma-specific graded prognostic assessment (msGPA) assigns patients with brain metastases from malignant melanoma to 1 of 4 prognostic groups. It was largely derived using clinical data from patients treated in the era that preceded the development of newer therapies such as BRAF, MEK and immune checkpoint inhibitors. Therefore, its current relevance to patients diagnosed with brain metastases from malignant melanoma is unclear. This study is an external validation of the msGPA in two temporally distinct British populations.Performance of the msGPA was assessed in Cohort I (1997-2008, n=231) and Cohort II (2008-2013, n=162) using Kaplan-Meier methods and Harrell's c-index of concordance. Cox regression was used to explore additional factors that may have prognostic relevance.The msGPA does not perform well as a prognostic score outside of the derivation cohort, with suboptimal statistical calibration and discrimination, particularly in those patients with an intermediate prognosis. Extra-cerebral metastases, leptomeningeal disease, age and potential use of novel targeted agents after brain metastases are diagnosed, should be incorporated into future prognostic models.An improved prognostic score is required to underpin high-quality randomised controlled trials in an area with a wide disparity in clinical care

Factors Influencing Physicians’ Screening Behavior for Liver Cancer Among High-risk Patients

BACKGROUND: Little is known about physicians’ screening patterns for liver cancer despite its rising incidence. OBJECTIVE: Describe physician factors associated with liver cancer screening. DESIGN: Mailed survey. PARTICIPANTS: Physicians practicing in family practice, internal medicine, gastroenterology, or nephrology in 3 northern California counties in 2004. MEASUREMENTS: Sociodemographic and practice measures, liver cancer knowledge, attitudes, and self-reported screening behaviors. RESULTS: The response rate was 61.8% (N = 459). Gastroenterologists (100%) were more likely than Internists (88.4%), family practitioners (84.2%), or nephrologists (75.0%) to screen for liver cancer in high-risk patients (p = 0.016). In multivariate analysis, screeners were more likely than nonscreeners to think that screening for liver cancer reduced mortality (odds ratio [OR] 1.60, CI 1.09–2.34) and that not screening was a malpractice risk (OR 1.88, CI 1.29–2.75). Screeners were more likely than nonscreeners to order any screening test if it was a quality of care measure (OR 4.39, CI 1.79–10.81). CONCLUSIONS: Despite debate about screening efficacy, many physicians screen for liver cancer. Their screening behavior is influenced by malpractice and quality control concerns. More research is needed to develop better screening tests for liver cancer, to evaluate their effectiveness, and to understand how physicians behave when there is insufficient evidence

Exceptionally Preserved Jellyfishes from the Middle Cambrian

Cnidarians represent an early diverging animal group and thus insight into their origin and diversification is key to understanding metazoan evolution. Further, cnidarian jellyfish comprise an important component of modern marine planktonic ecosystems. Here we report on exceptionally preserved cnidarian jellyfish fossils from the Middle Cambrian (∼505 million years old) Marjum Formation of Utah. These are the first described Cambrian jellyfish fossils to display exquisite preservation of soft part anatomy including detailed features of structures interpreted as trailing tentacles and subumbrellar and exumbrellar surfaces. If the interpretation of these preserved characters is correct, their presence is diagnostic of modern jellyfish taxa. These new discoveries may provide insight into the scope of cnidarian diversity shortly after the Cambrian radiation, and would reinforce the notion that important taxonomic components of the modern planktonic realm were in place by the Cambrian period

The capsule polysaccharide structure and biogenesis for non-O1 Vibrio cholerae NRT36S: genes are embedded in the LPS region

BACKGROUND: In V. cholerae, the biogenesis of capsule polysaccharide is poorly understood. The elucidation of capsule structure and biogenesis is critical to understanding the evolution of surface polysaccharide and the internal relationship between the capsule and LPS in this species. V. cholerae serogroup O31 NRT36S, a human pathogen that produces a heat-stable enterotoxin (NAG-ST), is encapsulated. Here, we report the covalent structure and studies of the biogenesis of the capsule in V. cholerae NRT36S. RESULTS: The structure of the capsular (CPS) polysaccharide was determined by high resolution NMR spectroscopy and shown to be a complex structure with four residues in the repeating subunit. The gene cluster of capsule biogenesis was identified by transposon mutagenesis combined with whole genome sequencing data (GenBank accession DQ915177). The capsule gene cluster shared the same genetic locus as that of the O-antigen of lipopolysaccharide (LPS) biogenesis gene cluster. Other than V. cholerae O139, this is the first V. cholerae CPS for which a structure has been fully elucidated and the genetic locus responsible for biosynthesis identified. CONCLUSION: The co-location of CPS and LPS biosynthesis genes was unexpected, and would provide a mechanism for simultaneous emergence of new O and K antigens in a single strain. This, in turn, may be a key element for V. cholerae to evolve new strains that can escape immunologic detection by host populations

Differential gene expression profile in the small intestines of mice lacking pacemaker interstitial cells of Cajal

BACKGROUND: We previously identified eight known and novel genes differentially expressed in the small intestines of wild type and W/W(V )mice, which have greatly reduced populations of the interstitial cells of Cajal, that are responsible for the generation of electrical slow waves, by using a differential gene display method. METHODS: By using the same method we isolated additional candidate genes that were specifically down- or up-regulated in W/W(V )mice. Novel transcripts were designated as DDWMEST. RESULTS: We isolated seven candidates that were specifically down- or up-regulated in W/W(V )mice. Two novel transcripts, DDWMEST 1 and -91 were increased in both fed and fasted W/W(V )mice. Expression of another five genes was suppressed in W/W(V )mice: ARG2 (Arginase II), ONZIN (encoding leukemia inhibitory factor regulated protein), and three novel transcripts: DDWMEST62, -84, and -100. Together with the previous report, we identified fifteen differentially expressed genes in total in the small intestines of W/W(V )mice. Eight of these genes were reduced in the jejunums of W/W(V )mice compared to age matched wild type mice, whereas the other seven genes showed an increase in expression. Differential expression was the same in fasted and fed animals, suggesting that the differences were independent of the dietetic state of the animal. CONCLUSIONS: Several known and novel genes are differentially expressed in the small intestines of W/W(V )mice. Differential gene comparison might contribute to our understanding of motility disorders associated with the loss of the interstitial cells of Cajal