Harmony: Towards automated self-adaptive consistency in cloud storage

In just a few years cloud computing has become a very popular paradigm and a business success story, with storage being one of the key features. To achieve high data availability, cloud storage services rely on replication. In this context, one major challenge is data consistency. In contrast to traditional approaches that are mostly based on strong consistency, many cloud storage services opt for weaker consistency models in order to achieve better availability and performance. This comes at the cost of a high probability of stale data being read, as the replicas involved in the reads may not always have the most recent write. In this paper, we propose a novel approach, named Harmony, which adaptively tunes the consistency level at run-time according to the application requirements. The key idea behind Harmony is an intelligent estimation model of stale reads, allowing to elastically scale up or down the number of replicas involved in read operations to maintain a low (possibly zero) tolerable fraction of stale reads. As a result, Harmony can meet the desired consistency of the applications while achieving good performance. We have implemented Harmony and performed extensive evaluations with the Cassandra cloud storage on Grid?5000 testbed and on Amazon EC2. The results show that Harmony can achieve good performance without exceeding the tolerated number of stale reads. For instance, in contrast to the static eventual consistency used in Cassandra, Harmony reduces the stale data being read by almost 80% while adding only minimal latency. Meanwhile, it improves the throughput of the system by 45% while maintaining the desired consistency requirements of the applications when compared to the strong consistency model in Cassandra.

Analysis of the suitability of existing medical ontologies for building a scalable semantic interoperability solution supporting multi-site collaboration in oncology

Semantic interoperability is essential to facilitate efficient collaboration in heterogeneous multi-site healthcare environments. The deployment of a semantic interoperability solution has the potential to enable a wide range of informatics supported applications in clinical care and research both within as ingle healthcare organization and in a network of organizations. At the same time, building and deploying a semantic interoperability solution may require significant effort to carryout data transformation and to harmonize the semantics of the information in the different systems. Our approach to semantic interoperability leverages existing healthcare standards and ontologies, focusing first on specific clinical domains and key applications, and gradually expanding the solution when needed. An important objective of this work is to create a semantic link between clinical research and care environments to enable applications such as streamlining the execution of multi-centric clinical trials, including the identification of eligible patients for the trials. This paper presents an analysis of the suitability of several widely-used medical ontologies in the clinical domain: SNOMED-CT, LOINC, MedDRA, to capture the semantics of the clinical trial eligibility criteria, of the clinical trial data (e.g., Clinical Report Forms), and of the corresponding patient record data that would enable the automatic identification of eligible patients. Next to the coverage provided by the ontologies we evaluate and compare the sizes of the sets of relevant concepts and their relative frequency to estimate the cost of data transformation, of building the necessary semantic mappings, and of extending the solution to new domains. This analysis shows that our approach is both feasible and scalable.

A T cell receptor antagonist peptide induces T cells that mediate bystander suppression and prevent autoimmune encephalomyelitis induced with multiple myelin antigens

Experimental autoimmune encephalomyelitis (EAE) induced with myelin proteolipid protein (PLP) residues 139–151 (HSLGKWLGHPDKF) can be prevented by treatment with a T cell receptor (TCR) antagonist peptide (L144/R147) generated by substituting at the two principal TCR contact residues in the encephalitogenic peptide. The TCR antagonist peptide blocks activation of encephalitogenic Th1 helper cells in vitro, but the mechanisms by which the antagonist peptide blocks EAE in vivo are not clear. Immunization with L144/R147 did not inhibit generation of PLP-(139–151)-specific T cells in vivo. Furthermore, preimmunization with L144/R147 protected mice from EAE induced with the encephalitogenic peptides PLP-(178–191) and myelin oligodendrocyte protein (MOG) residues 92–106 and with mouse myelin basic protein (MBP). These data suggest that the L144/R147 peptide does not act as an antagonist in vivo but mediates bystander suppression, probably by the generation of regulatory T cells. To confirm this we generated T cell lines and clones from animals immunized with PLP-(139–151) plus L144/R147. T cells specific for L144/R147 peptide were crossreactive with the native PLP-(139–151) peptide, produced Th2/Th0 cytokines, and suppressed EAE upon adoptive transfer. These studies demonstrate that TCR antagonist peptides may have multiple biological effects in vivo. One of the principal mechanisms by which these peptides inhibit autoimmunity is by the induction of regulatory T cells, leading to bystander suppression of EAE. These results have important implications for the treatment of autoimmune diseases where there are autopathogenic responses to multiple antigens in the target organ.

Climate and infectious disease: Use of remote sensing for detection of Vibrio cholerae by indirect measurement

It has long been known that cholera outbreaks can be initiated when Vibrio cholerae, the bacterium that causes cholera, is present in drinking water in sufficient numbers to constitute an infective dose, if ingested by humans. Outbreaks associated with drinking or bathing in unpurified river or brackish water may directly or indirectly depend on such conditions as water temperature, nutrient concentration, and plankton production that may be favorable for growth and reproduction of the bacterium. Although these environmental parameters have routinely been measured by using water samples collected aboard research ships, the available data sets are sparse and infrequent. Furthermore, shipboard data acquisition is both expensive and time-consuming. Interpolation to regional scales can also be problematic. Although the bacterium, V. cholerae, cannot be sensed directly, remotely sensed data can be used to infer its presence. In the study reported here, satellite data were used to monitor the timing and spread of cholera. Public domain remote sensing data for the Bay of Bengal were compared directly with cholera case data collected in Bangladesh from 1992–1995. The remote sensing data included sea surface temperature and sea surface height. It was discovered that sea surface temperature shows an annual cycle similar to the cholera case data. Sea surface height may be an indicator of incursion of plankton-laden water inland, e.g., tidal rivers, because it was also found to be correlated with cholera outbreaks. The extensive studies accomplished during the past 25 years, confirming the hypothesis that V. cholerae is autochthonous to the aquatic environment and is a commensal of zooplankton, i.e., copepods, when combined with the findings of the satellite data analyses, provide strong evidence that cholera epidemics are climate-linked.

Spontaneous rupture of malarial spleen: two case reports and review of literature

Malaria has long been among the most common diseases in the southeast Anatolia region of Turkey. In 1992, 18676 cases were diagnosed in Turkey, and Diyarbakir city had the highest incidence (4168 cases), followed by SanliUrfa city (3578 cases). Malaria was especially common during 1994 and 1995, with 84 345 and 82 094 cases being diagnosed in these years, respectively. Spontaneous rupture of malarial spleen is rare. We saw two cases during 1998, which are reported herein. Both patients were male, and were receiving chloroquine treatment for an acute attack of malaria. One of the patients had developed abdominal pain and palpitations, followed by fainting. The other patient had abdominal pain and fever. Explorative laparotomy revealed an enlarged spleen in both patients. Splenectomy was performed in both patients. We have identified 15 episodes of spontaneous rupture of the spleen in the English language literature published since 1961. Because of increased travel to endemic areas and resistance to antimalarial drugs, malaria is a major medical problem that is becoming increasingly important to surgeons worldwide. Malaria is a particularly important problem in the southeast Anatolia region of Turkey. Prophylactic precautions should be taken by tourists who travel to this region, especially during the summer.

Targeted inactivation of sister of P-glycoprotein gene (spgp) in mice results in nonprogressive but persistent intrahepatic cholestasis

Mutations in the sister of P-glycoprotein (Spgp) or bile salt export pump (BSEP) are associated with Progressive Familial Intrahepatic Cholestasis (PFIC2). Spgp is predominantly expressed in the canalicular membranes of liver. Consistent with in vitro evidence demonstrating the involvement of Spgp in bile salt transport, PFIC2 patients secrete less than 1% of biliary bile salts compared with normal infants. The disease rapidly progresses to hepatic failure requiring liver transplantation before adolescence. In this study, we show that the knockout of spgp gene in mice results in intrahepatic cholestasis, but with significantly less severity than PFIC2 in humans. Some unexpected characteristics are observed. Notably, although the secretion of cholic acid in mutant mice is greatly reduced (6% of wild-type), total bile salt output in mutant mice is about 30% of wild-type. Also, secretion of an unexpectedly large amount of tetra-hydroxylated bile acids (not detected in wild-type) is observed. These results suggest that hydroxylation and an alternative canalicular transport mechanism for bile acids compensate for the absence of Spgp function and protect the mutant mice from severe cholestatic damage. In addition, the spgp−/− mice display a significant increase in the secretion of cholesterol and phospholipids into the bile. This latter observation in spgp−/− mice suggests that intrahepatic, rather than intracanalicular, bile salts are the major driving force for the biliary lipid secretion. The spgp−/− mice thus provide a unique model for gaining new insights into therapeutic intervention for intrahepatic cholestasis and understanding mechanisms associated with lipid homeostasis.

Sovereignty and Intervention in the Middle East: From the Fall of the Ottoman Empire to the Arab Spring

This research provides an institutional explanation of the practices of external intervention in the Arab state system from the fall of the Ottoman Empire in 1922 to the Arab Spring. My explanation consists of two institutional variables: sovereignty and inter-state borders. I examine the changes in regional and international norms of sovereignty and their impact on the practices of external intervention in the Arab state system. I also examine the impact of the level of institutionalization of inter-state borders in the Arab World on the practices of external intervention. I argue that changes in regional and international norms of sovereignty and changes in the level of institutionalization of inter-state borders have constituted the significant variation over time in both the frequency and type of external intervention in the Arab state system from 1922 to the present. My institutional explanation and findings seriously challenge the traditional accounts of sovereignty and intervention in the Arab World, including the cultural perspectives that emphasize the conflict between sovereignty, Arabism, and Islam, the constructivist accounts that emphasize the regional norm of pan-Arabism, the comparative politics explanations that focus on the domestic material power of the Arab state, the post-colonial perspectives that emphasize the artificiality of the Arab state, and the realist accounts that focus on great powers and the regional distribution of power in the Middle East. This research also contributes to International Relations Theory. I construct a new analytical framework to study the relations between sovereignty, borders, and intervention, combining theoretical elements from the fields of Role Theory, Social Constructivism, and Institutionalization. Methodologically, this research includes both quantitative and qualitative analysis. I conduct content analysis of official documents of Arab states and the Arab League, Arabic press documents, and Arab political thought. I also utilize quantitative data sets on international intervention.

Surgical outcomes of isolated lens coloboma with or without cataract among young adults

Objective: To evaluate the visual and refractive outcomes after phacoemulsification surgery in eyes with isolated lens coloboma. Design: Prospective, consecutive case series. Participants: Eighteen eyes with isolated lens coloboma of 13 patients were included in the study. Mean patient age was 13.9 ± 6.5 years. Methods: Patients underwent phacoemulsification surgery, with combined implantation of capsular tension ring (CTR) and intraocular lens. In colobomas of less than 120°, a CTR was used, whereas in colobomas of more than 120°, a Cionni-modified single eyelet CTR was used to achieve better capsular centration. The main outcome measures were uncorrected distance visual acuity, corrected distance visual acuity, refraction, and keratometry. Results: Mean logMAR uncorrected distance visual acuity and corrected distance visual acuity improved significantly from 1.53 ± 0.35 and 1.02 ± 0.47 before surgery to 0.67 ± 0.51 and 0.52 ± 0.49 at the last visit of the follow-up (p < 0.001). Mean refractive cylinder and spherical equivalent decreased significantly from –6.73 ± 1.73 and –6.72 ± 4.07 D preoperatively to –1.40 ± 1.39 and –0.83 ± 1.31 D at the end of the follow-up (p = 0.001 and p = 0.01, respectively). Mean keratometric astigmatism at preoperative and postoperative visits were 1.58 ± 0.97 and 1.65 ± 0.94 D, respectively (p = 0.70). Conclusions: Phacoemulsification with CTR and intraocular lens implantation is an effective and safe option for providing a refractive correction and a significant visual improvement in eyes with isolated lens coloboma.

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