Stereotyping and the treatment of missing data for drug and alcohol clinical trials

Stigma and stereotyping of marginalized groups often is insidious and shows up in unlikely places, for instance in how clinical trials consider dropouts in treatment research. A surprising number of studies presume that people who do not complete the study protocol relapse and code their data as if they had been observed. There is no good statistical rationale for this treatment of missing data and numerous and more defensible alternative methods are available. We need to be mindful about our attitudes and preconceptions about the people we are intending to help. There is no good reason to continue to support science built on this scientifically indefensible stereotyping, however unintentional

A record-linkage study of the development of hepatocellular carcinoma in persons with hepatitis C infection in Scotland

We investigated trends in first time hospital admissions and deaths attributable to hepatocellular carcinoma (HCC) in a large population based cohort of 22 073 individuals diagnosed with hepatitis C viral (HCV) infection through laboratory testing in Scotland in 1991 2006. We identified new cases of HCC through record linkage to the national inpatient hospital discharge database and deaths registry. A total of 172 persons diagnosed with HCV were admitted to hospital or died with first time mention of HCC. Hepatocellular carcinoma incidence increased between 1996 and 2006 (average annual change of 6.1, 95% confidence interval (CI):0.9 11.6%, P¼0.021). The adjusted relative risk of HCC was greater for males (hazard ratio¼2.7, 95% CI: 1.7 4.2), for those aged 60 years or older (hazard ratio ¼2.7, 95% CI: 1.9 4.1) compared with 50 59 years, and for those with a previous alcohol related hospital admission (hazard ratio¼2.5, 95% CI: 1.7 3.7). The risk of individuals diagnosed with HCV developing HCC was greatlyincreased compared with the general Scottish population (standardised incidence ratio¼127, 95% CI: 102 156). Owing to the advancing age of the Scottish HCV diagnosed population, the annual number of HCC cases is projected to increase, with a consequent increasing burden on the public healthcare system

Universality of Phases in QCD and QCD-like Theories

We argue that the whole or the part of the phase diagrams of QCD and QCD-like theories should be universal in the large-N_c limit through the orbifold equivalence. The whole phase diagrams, including the chiral phase transitions and the BEC-BCS crossover regions, are identical between SU(N_c) QCD at finite isospin chemical potential and SO(2N_c) and Sp(2N_c) gauge theories at finite baryon chemical potential. Outside the BEC-BCS crossover region in these theories, the phase diagrams are also identical to that of SU(N_c) QCD at finite baryon chemical potential. We give examples of the universality in some solvable cases: (i) QCD and QCD-like theories at asymptotically high density where the controlled weak-coupling calculations are possible, (ii) chiral random matrix theories of different universality classes, which are solvable large-N (large volume) matrix models of QCD. Our results strongly suggest that the chiral phase transition and the QCD critical point at finite baryon chemical potential can be studied using sign-free theories, such as QCD at finite isospin chemical potential, in lattice simulations.Comment: v1: 35 pages, 6 figures; v2: 37 pages, 6 figures, minor improvements, conclusion unchanged; v3: version published in JHE

Imputation strategies for missing binary outcomes in cluster randomized trials

<p>Abstract</p> <p>Background</p> <p>Attrition, which leads to missing data, is a common problem in cluster randomized trials (CRTs), where groups of patients rather than individuals are randomized. Standard multiple imputation (MI) strategies may not be appropriate to impute missing data from CRTs since they assume independent data. In this paper, under the assumption of missing completely at random and covariate dependent missing, we compared six MI strategies which account for the intra-cluster correlation for missing binary outcomes in CRTs with the standard imputation strategies and complete case analysis approach using a simulation study.</p> <p>Method</p> <p>We considered three within-cluster and three across-cluster MI strategies for missing binary outcomes in CRTs. The three within-cluster MI strategies are logistic regression method, propensity score method, and Markov chain Monte Carlo (MCMC) method, which apply standard MI strategies within each cluster. The three across-cluster MI strategies are propensity score method, random-effects (RE) logistic regression approach, and logistic regression with cluster as a fixed effect. Based on the community hypertension assessment trial (CHAT) which has complete data, we designed a simulation study to investigate the performance of above MI strategies.</p> <p>Results</p> <p>The estimated treatment effect and its 95% confidence interval (CI) from generalized estimating equations (GEE) model based on the CHAT complete dataset are 1.14 (0.76 1.70). When 30% of binary outcome are missing completely at random, a simulation study shows that the estimated treatment effects and the corresponding 95% CIs from GEE model are 1.15 (0.76 1.75) if complete case analysis is used, 1.12 (0.72 1.73) if within-cluster MCMC method is used, 1.21 (0.80 1.81) if across-cluster RE logistic regression is used, and 1.16 (0.82 1.64) if standard logistic regression which does not account for clustering is used.</p> <p>Conclusion</p> <p>When the percentage of missing data is low or intra-cluster correlation coefficient is small, different approaches for handling missing binary outcome data generate quite similar results. When the percentage of missing data is large, standard MI strategies, which do not take into account the intra-cluster correlation, underestimate the variance of the treatment effect. Within-cluster and across-cluster MI strategies (except for random-effects logistic regression MI strategy), which take the intra-cluster correlation into account, seem to be more appropriate to handle the missing outcome from CRTs. Under the same imputation strategy and percentage of missingness, the estimates of the treatment effect from GEE and RE logistic regression models are similar.</p

Science that "knows" and science that "asks"

Clinician-researchers and experimental scientists do not speak the same language; they have different professional environments and different end-points in their research. This creates considerable problems of comprehension and communication, which constitute a major drawback in multidisciplinary work such as translational medicine. A stereotypic representation of both these worlds is presented as a starting point to encourage debate on this issue

Research opportunities for argumentation in social networks

Nowadays, many websites allow social networking between their users in an explicit or implicit way. In this work, we show how argumentation schemes theory can provide a valuable help to formalize and structure on-line discussions and user opinions in decision support and business oriented websites that held social networks between their users. Two real case studies are studied and analysed. Then, guidelines to enhance social decision support and recommendations with argumentation are provided.This work summarises results of the authors joint research, funded by an STMS of the Agreement Technologies COST Action 0801, by the Spanish government grants [CONSOLIDER-INGENIO 2010 CSD2007-00022, and TIN2012-36586-C03-01] and by the GVA project [PROMETEO 2008/051].Heras Barberá, SM.; Atkinson, KM.; Botti Navarro, VJ.; Grasso, F.; Julian Inglada, VJ.; Mcburney, PJ. (2013). Research opportunities for argumentation in social networks. Artificial Intelligence Review. 39(1):39-62. doi:10.1007/s10462-012-9389-0S3962391Amgoud L (2009) Argumentation for decision making. Argumentation in artificial intelligence. Springer, BerlinAnderson P (2007) What is Web 2.0? Ideas, technologies and implications for education. JISC Iechnology and Standards Watch reportBentahar J, Meyer CJJ, Moulin B (2007) Securing agent-oriented systems: an argumentation and reputation-based approach. In: Proceedings of the 4th international conference on information technology: new generations (ITNG 2007), IEEE Computer Society, pp 507–515Buckingham Shum S (2008) Cohere: towards Web 2.0 argumentation. In: Proceedings of the 2nd international conference on computational models of argument, COMMA, pp 28–30Burke R (2002) Hybrid recommender systems: survey and experiments. User Model User-Adapt Interact 12:331–370Cartwright D, Atkinson K (2008) Political engagement through tools for argumentation. In: Proceedings of the second international conference on computational models of argument (COMMA 2008), pp 116–127Chesñevar C, McGinnis J, Modgil S, Rahwan I, Reed C, Simari G, South M, Vreeswijk G, Willmott S (2006) Towards an argument interchange format. Knowl Eng Rev 21(4):293–316Chesñevar CI, Maguitman AG, Gonzàlez MP (2009) Empowering recommendation technologies through argumentation. Argumentation in artificial intelligence. Springer, Berlin, pp 403–422García AJ, Dix J, Simari GR (2009) Argument-based logic programming. Argumentation in artificial intelligence. Springer, BerlinGolbeck J (2006) Generating predictive movie recommendations from trust in social networks. In: Proceedings of the fourth international conference on trust management, LNCS, vol 3986, 93–104Gordon T, Prakken H, Walton D (2007) The Carneades model of argument and burden of proof. Artif Intell 171(10–15):875–896Guha R, Kumar R, Raghavan P, Tomkins A (2004) Propagating trust and distrust. In: Proceedings of the 13th international conference on, World Wide Web, pp 403–412Heras S, Navarro M, Botti V, Julián V (2009) Applying dialogue games to manage recommendation in social networks. In: Proceedings of the 6th international workshop on argumentation in multi-agent aystems, ArgMASHeras S, Atkinson K, Botti V, Grasso F, Julián V, McBurney P (2010a) How argumentation can enhance dialogues in social networks. In: Proceedings of the 3rd international conference on computational models of argument, COMMA, vol 216, pp 267–274Heras S, Atkinson K, Botti V, Grasso F, Julián V, McBurney P (2010b) Applying argumentation to enhance dialogues in social networks. In: ECAI 2010 workshop on computational models of natural argument, CMNA, pp 10–17Karacapilidis N, Tzagarakis M (2007) Web-based collaboration and decision making support: a multi-disciplinary approach. Web-Based Learn Teach Technol 2(4):12–23Kim D, Benbasat I (2003) Trust-related arguments in internet stores: a framework for evaluation. J Electron Commer Res 4(2):49–64Kim D, Benbasat I (2006) The effects of trust-assuring arguments on consumer trust in internet stores: application of Toulmin’s model of argumentation. Inf Syst Rese 17(3):286–300Laera L, Tamma V, Euzenat J, Bench-Capon T, Payne T (2006) Reaching agreement over ontology alignments. In: Proceedings of the 5th international semantic web conference (ISWC 2006)Lange C, Bojãrs U, Groza T, Breslin J, Handschuh S (2008) Expressing argumentative discussions in social media sites. In: Social data on the web (SDoW2008) workshop at the 7th international semantic web conferenceLinden G, Smith B, York J (2003) Amazon.com recommendations: item-to-item collaborative filtering. IEEE Internet Comput 7(1):76–80Linden G, Hong J, Stonebraker M, Guzdial M (2009) Recommendation algorithms, online privacy and more. 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In: Dissensus and the search for common ground, OSSA-07, volume CD-ROM, pp 1–11Sabater J, Sierra C (2002) Reputation and social network analysis in multi-agent systems. In: Proceedings of the 1st international joint conference on autonomous agents and multiagent systems, vol 1, pp 475–482Schafer JB, Konstan JA, Riedl J (2001) E-commerce recommendation applications. Data Min Knowl Discov 5:115–153Schafer JB, Frankowski D, Herlocker J, Sen S (2007) Collaborative filtering recommender systems. In: The adaptive web, LNCS, vol 4321, pp 291–324Schneider J, Groza T, Passant A (2012) A review of argumentation for the aocial semantic web. Semantic web-interoperability, usability, applicability. IOS Press, Washington, DCTempich C, Pinto HS, Sure Y, Staab S (2005) An argumentation ontology for distributed, loosely-controlled and evolvInG Engineering processes of oNTologies (DILIGENT). 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Src Dependent Pancreatic Acinar Injury Can Be Initiated Independent of an Increase in Cytosolic Calcium

Several deleterious intra-acinar phenomena are simultaneously triggered on initiating acute pancreatitis. These culminate in acinar injury or inflammatory mediator generation in vitro and parenchymal damage in vivo. Supraphysiologic caerulein is one such initiator which simultaneously activates numerous signaling pathways including non-receptor tyrosine kinases such as of the Src family. It also causes a sustained increase in cytosolic calcium- a player thought to be crucial in regulating deleterious phenomena. We have shown Src to be involved in caerulein induced actin remodeling, and caerulein induced changes in the Golgi and post-Golgi trafficking to be involved in trypsinogen activation, which initiates acinar cell injury. However, it remains unclear whether an increase in cytosolic calcium is necessary to initiate acinar injury or if injury can be initiated at basal cytosolic calcium levels by an alternate pathway. To study the interplay between tyrosine kinase signaling and calcium, we treated mouse pancreatic acinar cells with the tyrosine phosphatase inhibitor pervanadate. We studied the effect of the clinically used Src inhibitor Dasatinib (BMS-354825) on pervanadate or caerulein induced changes in Src activation, trypsinogen activation, cell injury, upstream cytosolic calcium, actin and Golgi morphology. Pervanadate, like supraphysiologic caerulein, induced Src activation, redistribution of the F-actin from its normal location in the sub-apical area to the basolateral areas, and caused antegrade fragmentation of the Golgi. These changes, like those induced by supraphysiologic caerulein, were associated with trypsinogen activation and acinar injury, all of which were prevented by Dasatinib. Interestingly, however, pervanadate did not cause an increase in cytosolic calcium, and the caerulein induced increase in cytosolic calcium was not affected by Dasatinib. These findings suggest that intra-acinar deleterious phenomena may be initiated independent of an increase in cytosolic calcium. Other players resulting in acinar injury along with the Src family of tyrosine kinases remain to be explored. © 2013 Mishra et al

Skin Cornification Proteins Provide Global Link between ROS Detoxification and Cell Migration during Wound Healing

Wound healing is a complex dynamic process characterised by a uniform flow of events in nearly all types of tissue damage, from a small skin scratch to myocardial infarction. Reactive oxygen species (ROS) are essential during the healing process at multiple stages, ranging from the initial signal that instigates the immune response, to the triggering of intracellular redox-dependent signalling pathways and the defence against invading bacteria. Excessive ROS in the wound milieu nevertheless impedes new tissue formation. Here we identify small proline-rich (SPRR) proteins as essential players in this latter process, as they directly link ROS detoxification with cell migration. A literature-based meta-analysis revealed their up-regulation in various forms of tissue injury, ranging from heart infarction and commensal-induced gut responses to nerve regeneration and burn injury. Apparently, SPRR proteins have a far more widespread role in wound healing and tissue remodelling than their established function in skin cornification. It is inferred that SPRR proteins provide injured tissue with an efficient, finely tuneable antioxidant barrier specifically adapted to the tissue involved and the damage inflicted. Their recognition as novel cell protective proteins combining ROS detoxification with cell migration will provide new venues to study and manage tissue repair and wound healing at a molecular level

Gravitational Radiation from Post-Newtonian Sources and Inspiralling Compact Binaries

The article reviews the current status of a theoretical approach to the problem of the emission of gravitational waves by isolated systems in the context of general relativity. Part A of the article deals with general post-Newtonian sources. The exterior field of the source is investigated by means of a combination of analytic post-Minkowskian and multipolar approximations. The physical observables in the far-zone of the source are described by a specific set of radiative multipole moments. By matching the exterior solution to the metric of the post-Newtonian source in the near-zone we obtain the explicit expressions of the source multipole moments. The relationships between the radiative and source moments involve many non-linear multipole interactions, among them those associated with the tails (and tails-of-tails) of gravitational waves. Part B of the article is devoted to the application to compact binary systems. We present the equations of binary motion, and the associated Lagrangian and Hamiltonian, at the third post-Newtonian (3PN) order beyond the Newtonian acceleration. The gravitational-wave energy flux, taking consistently into account the relativistic corrections in the binary moments as well as the various tail effects, is derived through 3.5PN order with respect to the quadrupole formalism. The binary's orbital phase, whose prior knowledge is crucial for searching and analyzing the signals from inspiralling compact binaries, is deduced from an energy balance argument.Comment: 109 pages, 1 figure; this version is an update of the Living Review article originally published in 2002; available on-line at http://www.livingreviews.org