Testing M2T/T2M Transformations

Presentado en: 16th International Conference on Model Driven Engineering Languages and Systems (MODELS 2013). Del 29 de septiembre al 4 de octubre. Miami, EEUU.Testing model-to-model (M2M) transformations is becoming a prominent topic in the current Model-driven Engineering landscape. Current approaches for transformation testing, however, assume having explicit model representations for the input domain and for the output domain of the transformation. This excludes other important transformation kinds, such as model-to-text (M2T) and text-to-model (T2M) transformations, from being properly tested since adequate model representations are missing either for the input domain or for the output domain. The contribution of this paper to overcome this gap is extending Tracts, a M2M transformation testing approach, for M2T/T2M transformation testing. The main mechanism we employ for reusing Tracts is to represent text within a generic metamodel. By this, we transform the M2T/T2M transformation specification problems into equivalent M2M transformation specification problems. We demonstrate the applicability of the approach by two examples and present how the approach is implemented for the Eclipse Modeling Framework (EMF). Finally, we apply the approach to evaluate code generation capabilities of several existing UML tools.Universidad de Málaga. Campus de Excelencia Internacional Andalucía Tech. Proyecto TIN2011-2379

Dipeptidyl-peptidase-4 inhibitors and pancreatic cancer: a cohort study

Aims—Dipeptidyl-peptidase-4 inhibitors (DPP-4i) have been implicated with an increased pancreatic cancer risk. We therefore compared pancreatic cancer incidence and diagnostic work-up among initiators of DPP-4i versus sulfonylureas (SU) and thiazolidinediones (TZD). Methods—Medicare claims data were examined in a new-user active-comparator cohort study. Patients >65 years with no prescriptions for DPP-4i, SU or TZD at baseline were included if they had at least two claims for the same drug within 180 days. Using an as-treated approach and propensity score-adjusted Cox models, we estimated hazard ratios (HR) and 95% confidence intervals (CI) for pancreatic cancer. Diagnostic work-up was compared using risk ratios (RR). RESULTS—In the DPP-4i vs SU comparison, there were 18,179 DPP4i initiators of which 26 developed pancreatic cancer (follow-up time interquartile range 5–18 months). In the DPP-4i vs TZD comparison there were 29,366 DPP-4i initiators and 52 developed pancreatic cancer. The hazard of pancreatic cancer with DPP-4i was lower relative to SU (HR=0.6, CI 0.4–0.9) and similar to TZD (HR=1.0, CI 0.7–1.4). Excluding first 6 months of follow-up to reduce the potential for reverse causality did not alter results. Probability of diagnostic work-up post-initiation among DPP-4i initiators (79.3%) was similar to TZD (74.1%) (RR=1.06, CI 1.05–1.07) and SU (74.6%) (RR=1.06, CI1.05–1.07). The probability of diagnostic workup pre-index was ~80% for all cohorts. Conclusion—Though limited by sample size and the observed duration of treatment in the US, our well-controlled population based study suggests no increased short-term pancreatic cancer risk with DPP-4i relative to SU or TZD

Effect of glucagon-like peptide-1 receptor agonists and dipeptidyl peptidase-4 inhibitors on colorectal cancer incidence and its precursors

Incretin-based antihyperglycemic therapies increase intestinal mucosal expansion and polyp growth in mouse models. We aimed to evaluate the effect of dipeptidyl peptidase-4 inhibitors (DPP-4i) or glucagon-like peptide-1 receptor agonists (GLP-1ra) initiation on colorectal cancer incidence

Bend it like Beckham: embodying the motor skills of famous athletes.

Observing an action activates the same representations as does the actual performance of the action. Here we show for the first time that the action system can also be activated in the complete absence of action perception. When the participants had to identify the faces of famous athletes, the responses were influenced by their similarity to the motor skills of the athletes. Thus, the motor skills of the viewed athletes were retrieved automatically during person identification and had a direct influence on the action system of the observer. However, our results also indicated that motor behaviours that are implicit characteristics of other people are represented differently from when actions are directly observed. That is, unlike the facilitatory effects reported when actions were seen, the embodiment of the motor behaviour that is not concurrently perceived gave rise to contrast effects where responses similar to the behaviour of the athletes were inhibited

Electronic Medical Record Cancer Incidence over Six Years Comparing New Users of Glargine with New Users of NPH Insulin

Background: Recent studies suggested that insulin glargine use could be associated with increased risk of cancer. We compared the incidence of cancer in new users of glargine versus new users of NPH in a longitudinal clinical cohort with diabetes for up to 6 years. Methods and Findings: From all patients who had been regularly followed at Massachusetts General Hospital from 1/01/2005 to 12/31/2010, 3,680 patients who had a medication record for glargine or NPH usage were obtained from the electronic medical record (EMR). From those we selected 539 new glargine users (age: 60.1±13.6 years, BMI: 32.7±7.5 kg/m2) and 343 new NPH users (61.5±14.1 years, 32.7±8.3 kg/m2) who had no prevalent cancer during 19 months prior to glargine or NPH initiation. All incident cancer cases were ascertained from the EMR requiring at least 2 ICD-9 codes within a 2 month period. Insulin exposure time and cumulative dose were validated. The statistical analysis compared the rates of cancer in new glargine vs. new NPH users while on treatment, adjusted for the propensity to receive one or the other insulin. There were 26 and 28 new cancer cases in new glargine and new NPH users for 1559 and 1126 person-years follow-up, respectively. There were no differences in the propensity-adjusted clinical characteristics between groups. The adjusted hazard ratio for the cancer incidence comparing glargine vs. NPH use was 0.65 (95% CI: 0.36–1.19). Conclusions: Insulin glargine is not associated with development of cancers when compared with NPH in this longitudinal and carefully retrieved EMR data

Propensity Score Estimation to Address Calendar Time-Specific Channeling in Comparative Effectiveness Research of Second Generation Antipsychotics

BackgroundChanneling occurs when a medication and its potential comparators are selectively prescribed based on differences in underlying patient characteristics. Drug safety advisories can provide new information regarding the relative safety or effectiveness of a drug product which might increase selective prescribing. In particular, when reported adverse effects vary among drugs within a therapeutic class, clinicians may channel patients toward or away from a drug based on the patient's underlying risk for an adverse outcome. If channeling is not identified and appropriately managed it might lead to confounding in observational comparative effectiveness studies.ObjectiveTo demonstrate channeling among new users of second generation antipsychotics following a Food and Drug Administration safety advisory and to evaluate the impact of channeling on cardiovascular risk estimates over time.Data SourceFlorida Medicaid data from 2001–2006.Study DesignRetrospective cohort of adults initiating second generation antipsychotics. We used propensity scores to match olanzapine initiators with other second generation antipsychotic initiators. To evaluate channeling away from olanzapine following an FDA safety advisory, we estimated calendar time-specific propensity scores. We compare the performance of these calendar time-specific propensity scores with conventionally-estimated propensity scores on estimates of cardiovascular risk.Principal FindingsIncreased channeling away from olanzapine was evident for some, but not all, cardiovascular risk factors and corresponded with the timing of the FDA advisory. Covariate balance was optimized within period and across all periods when using the calendar time-specific propensity score. Hazard ratio estimates for cardiovascular outcomes did not differ across models (Conventional PS: 0.97, 95%CI: 0.81–3.18 versus calendar time-specific PS: 0.93, 95%CI: 0.77–3.04).ConclusionsChanges in channeling over time was evident for several covariates but had limited impact on cardiovascular risk estimates, possibly due to unmeasured confounding. Although calendar time-specific propensity scores appear to improve covariate balance, the impact on comparative effectiveness results is limited in this setting

Lumbar spine radiographic features and demographic, clinical, and radiographic knee, hip and hand osteoarthritis: The Johnston County Osteoarthritis Project

Objective—1) To determine the prevalence of lumbar spine individual radiographic features (IRF) of disc space narrowing (DSN), osteophytes (OST) and facet joint osteoarthritis (FOA). 2) To describe the frequencies of demographic, clinic and radiographic knee, hip and hand osteoarthritis (OA) across lumbar spine IRF. 3) To determine factors associated with lumbar spine IRF. Methods—A cross-sectional study of 840 participants enrolled in the Johnston County OA Project (2003-4). Sample-based prevalence estimates were generated for each lumbar spine IRF. Associations between lumbar spine IRF and demographic, clinical and peripheral joint OA were determined with logistic regression models. Results—Sample-based prevalence estimates were similar for DSN (57.6%) and FOA (57.9%) but higher for OST (88.1%) with significant differences across race and gender. Hand and knee OA frequencies increased across IRF whereas the effect was absent for hip OA. African Americans had lower odds of FOA (adjusted odds ratio [aOR]=0.45 (95% CI 0.32, 0.62)) while there was no racial association with DSN and OST. Low back symptoms were associated with DSN (aOR=1.37 (95% CI 1.04, 1.80)) but not OST or FOA. Knee OA was associated with OST (aOR=1.62 (95% CI 1.16, 2.27)) and FOA (aOR=1.69 (95% CI 1.15, 2.49)) but not DSN. Hand OA was associated with FOA (aOR=1.67 (95% CI 1.20, 2.28)) but not with DSN or OST. No associations were found with hip OA. Conclusion—These findings underscore the importance of analyzing lumbar spine IRF separately as the associations with demographic, clinic and radiographic knee, hip and hand OA differ widely

The “Dry-Run” Analysis: A Method for Evaluating Risk Scores for Confounding Control

A propensity score (PS) model's ability to control confounding can be assessed by evaluating covariate balance across exposure groups after PS adjustment. The optimal strategy for evaluating a disease risk score (DRS) model's ability to control confounding is less clear. DRS models cannot be evaluated through balance checks within the full population, and they are usually assessed through prediction diagnostics and goodness-of-fit tests. A proposed alternative is the "dry-run" analysis, which divides the unexposed population into "pseudo-exposed" and "pseudo-unexposed" groups so that differences on observed covariates resemble differences between the actual exposed and unexposed populations. With no exposure effect separating the pseudo-exposed and pseudo-unexposed groups, a DRS model is evaluated by its ability to retrieve an unconfounded null estimate after adjustment in this pseudo-population. We used simulations and an empirical example to compare traditional DRS performance metrics with the dry-run validation. In simulations, the dry run often improved assessment of confounding control, compared with the C statistic and goodness-of-fit tests. In the empirical example, PS and DRS matching gave similar results and showed good performance in terms of covariate balance (PS matching) and controlling confounding in the dry-run analysis (DRS matching). The dry-run analysis may prove useful in evaluating confounding control through DRS models

Cancer Incidence Among Those Initiating Insulin Therapy With Glargine Versus Human NPH Insulin

OBJECTIVE To add to the evidence on comparative long-term effects of insulin analog glargine versus human NPH insulin on the risk for cancer. RESEARCH DESIGN AND METHODS We identified cohorts of initiators of glargine and human NPH without an insulin prescription during the prior 19 months among patients covered by the Inovalon Medical Outcomes Research for Effectiveness and Economics Registry (MORE2 Registry) between January 2003 and December 2010. Patients were required to have a second prescription of the same insulin within 180 days and to be free of cancer. We balanced cohorts on risk factors for cancer outcomes based on comorbidities, comedication, and health care use during the prior 12 months using inverse probability of treatment weighting. Incident cancer was defined as having two claims for cancer (any cancer) or the same cancer (breast, prostate, colon) within 2 months. We estimated adjusted hazard ratios (HRs) and their 95% CI using weighted Cox models censoring for stopping, switching, or augmenting insulin treatment, end of enrollment, and mortality. RESULTS More patients initiated glargine (43,306) than NPH (9,147). Initiators of glargine (NPH) were followed for 1.2 (1.1) years and 50,548 (10,011) person-years; 993 (178) developed cancer. The overall HR was 1.12 (95% CI 0.95–1.32). Results were consistent for breast cancer, prostate cancer, and colon cancer; various durations of treatment; and sensitivity analyses. CONCLUSIONS Patients initiating insulin glargine rather than NPH do not seem to be at an increased risk for cancer. While our study contributes significantly to our evidence base for long-term effects, this evidence is very limited mainly based on actual dynamics in insulin prescribing

Tamoxifen Initiation After Ductal Carcinoma In Situ

Endocrine therapy initiation after ductal carcinoma in situ (DCIS) is highly variable and largely unexplained. National guidelines recommend considering tamoxifen for women with estrogen receptor-positive (ER+) DCIS or who undergo excision alone. We evaluated endocrine therapy use after DCIS over a 15-year period in an integrated health care setting to identify factors related to initiation