Comparing principal stratification and selection models in parametric causal inference with nonignorable missingness

Two approaches for dealing with “endogenous selection” problems when estimating causal effects are considered. They are principal stratification and selection models. The main goal is to highlight similarities and differences between the two approaches, by investigating the different nature of their parametric hypotheses. The principal stratification approach focuses on information contained in specific subgroups of units. The aim is to produce valid inference conditional on such subgroups, without an a priori extension of the results to the whole population. Selection models, on the contrary, aim at estimating parameters that should be valid for the whole population, as if the data come from random sampling. A simulation study is conducted to show their different performances, with data generating processes coming from either approach. It is also argued that principal stratification is able to suggest alternative identification strategies not always easily translatable into assumptions of a selection model.     

Endothelin-1 infusion inhibits plasma insulin responsiveness in normal men

OBJECTIVES: Elevated plasma endothelin (ET)-1 levels have been described in insulin-resistant states such as syndrome X, obesity, non-insulin-dependent diabetes mellitus, and in some studies in essential hypertension. To investigate whether increases in circulating ET-1 to levels observed in insulin-resistant states can modulate insulin levels and/or insulin sensitivity in humans, we assessed these variables during low, non-pressor-dose ET-1 compared with placebo infusion. DESIGN: In a randomized, single blind, crossover design, 10 lean normotensive male subjects received either an intravenous infusion of subpressor doses of ET-1 dissolved in polygeline or a control infusion of polygeline only (placebo). Using dynamic assessment by the minimal model approach with the modified frequent sampling intravenous glucose tolerance test (FSIGT) the following and other parameters were measured: insulin sensitivity; acute insulin response to glucose (AIR(G)) calculated as the average of the three peak values between 2 and 5 min after injection of glucose from which the basal insulin levels were subtracted; the initial area under the curve (AUC(1-19)) from insulin values between time 0 and 19 min and the first-phase insulin secretion (phi1) from insulin kinetics parameters. RESULTS: ET-1 infusion reduced AIR(G) (to 34.85 +/- 4.27 compared with 49.3 +/- 6.9 microU/ml during placebo, P=0.017) and the acute C-peptide response to glucose (to 2.33 +/- 0.41 compared with 3.1 +/- 0.44 ng/ml, P=0.018), decreased plasma insulin levels during the FSIGT compared with placebo (analysis of variance P<0.0001) and decreased the AUC(1-19) (to 2.1 +/- 0.2 compared with 2.9 +/- 0.3 U/l per 20 min, P<0.01) while phi1 tended to be lower. S1 measured during ET-1 infusion was unaltered (11.11 +/- 1.91 x 10(-4) versus 10.88 +/- 2.11 10(-4)/min per mU per l, NS). CONCLUSIONS: These findings demonstrate that an increase in circulating ET-1 to levels observed in insulin-resistant states acutely diminishes the insulin secretory response but does not significantly modify insulin sensitivity.     

Multi-objective Swarm Intelligence schedulers for online scientific Clouds

Cloud Computing is a promising paradigm for parallel computing. However, as Cloud-based services become more dynamic, resource provisioning in Clouds becomes more challenging. The paradigm, with its promise of virtually infinite resources, seems to suit well in solving resource greedy scientific computing problems. In a Cloud, an appropriate number of Virtual Machines (VM) is created and allocated in physical resources for executing jobs. This work focuses on the Infrastructure as a Service (IaaS) model where custom VMs are launched in appropriate hosts available in a Cloud to execute scientific experiments coming from multiple users. Finding optimal solutions to allocate VMs to physical resources is an NP-complete problem, and therefore many heuristics have been developed. In this work, we describe and evaluate two Cloud schedulers based on Swarm Intelligence (SI) techniques, particularly Ant Colony Optimization (ACO) and Particle Swarm Optimization (PSO). The main performance metrics to study are the number of serviced users by the Cloud and the total number of created VMs in online (non-batch) scheduling scenarios. We also perform a sensitivity analysis by varying the specific-parameter values of each algorithm to evaluate the impact on the performance of the two objective metrics. The intra-Cloud network traffic is also measured. Simulated experiments performed using CloudSim and job data from real scientific problems show that the use of SI-based techniques succeeds in balancing the studied metrics compared to Genetic Algorithms.     

Oncostatic-Cytoprotective Effect of Melatonin and Other Bioactive Molecules: A Common Target in Mitochondrial Respiration

For several years, oncostatic and antiproliferative properties, as well as thoses of cell death induction through 5-methoxy-N-acetiltryptamine or melatonin treatment, have been known. Paradoxically, its remarkable scavenger, cytoprotective and anti-apoptotic characteristics in neurodegeneration models, such as Alzheimer’s disease and Parkinson’s disease are known too. Analogous results have been confirmed by a large literature to be associated to the use of many other bioactive molecules such as resveratrol, tocopherol derivatives or vitamin E and others. It is interesting to note that the two opposite situations, namely the neoplastic pathology and the neurodegeneration, are characterized by deep alterations of the metabolome, of mitochondrial function and of oxygen consumption, so that the oncostatic and cytoprotective action can find a potential rationalization because of the different metabolic and mitochondrial situations, and in the effect that these molecules exercise on the mitochondrial function. In this review we discuss historical and general aspects of melatonin, relations between cancers and the metabolome and between neurodegeneration and the metabolome, and the possible effects of melatonin and of other bioactive molecules on metabolic and mitochondrial dynamics. Finally, we suggest a common general mechanism as responsible for the oncostatic/cytoprotective effect of melatonin and of other molecules examined.     

MINMOD: a computer program to calculate insulin sensitivity and pancreatic responsivity from the frequently sampled intravenous glucose tolerance test

Insulin sensitivity and pancreatic responsivity are the two main factors controlling glucose tolerance. We have proposed a method for measuring these two factors, using computer analysis of a frequently-sampled intravenous glucose tolerance test (FSIGT). This 'minimal modelling approach' fits two mathematical models with FSIGT glucose and insulin data: one of glucose disappearance and one of insulin kinetics. MINMOD is the computer program which identifies the model parameters for each individual. A nonlinear least squares estimation technique is used, employing a gradient-type of estimation algorithm, and the first derivatives (not known analytically) are computed according to the 'sensitivity approach'. The program yields the parameter estimates and the precision of their estimation. From the model parameters, it is possible to extract four indices: SG, the ability of glucose per se to enhance its own disappearance at basal insulin, SI, the tissue insulin sensitivity index, phi 1, first phase pancreatic responsivity, and phi 2, second phase pancreatic responsivity. These four characteristic parameters have been shown to represent an integrated metabolic portrait of a single individual.     

The relation of rational and experiential information processing styles to personality, basic beliefs, and the ratio-bias phenomenon.

A new version of the Rational-Experiential Inventory (REI), which measures rational and experiential thinking styles and includes subscales of self-reported ability and engagement, was examined in two studies. In Study 1, the two main scales were independent, and they and their subscales exhibited discriminant validity and contributed to the prediction of a variety of measures beyond the contribution of the Big Five scales. A rational thinking style was most strongly and directly related to ego strength, openness, conscientiousness, and favorable basic beliefs about the self and the world, and it was most strongly inversely related to Neuroticism and Conservatism. An experiential thinking style was most strongly directly related to Extraversion, Agreeableness, Favorable Relationships Beliefs, and Emotional Expressivity, and it was most strongly inversely related to Categorical Thinking, Distrust of Others, and Intolerance. In Study 2, a rational thinking style was inversely related and an experiential thinking style was unrelated to nonoptimal responses in a game of chance. It was concluded that the new REI is a significant improvement over the previous version and measures unique aspects of personality. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Outcome of 309 patients with metastatic differentiated thyroid carcinoma treated with radioiodine

From 1969 to 1990 there were 309 patients with differentiated thyroid carcinoma (241 papillary and 68 follicular) treated with radioactive iodine for functioning node metastases alone (n = 191) or distant metastases (n = 118) with or without node metastases. These patients represented 32.7% of 945 patients treated in our institution during the same period. Initial treatment included near-total thyroidectomy and 131I ablation of postsurgical thyroid residue, followed by L-thyroxine suppressive therapy. At the end of follow-up (mean 5.8 years), 146 patients (76.4%) in the group with nodal metastases were considered cured, as assessed by clinical and laboratory evaluation including whole body scan (WBS) and serum thyroglobulin (Tg) levels; 32 patients (16.7%) had persistent disease. Loss of 131I uptake in persistent metastatic lesions occurred in five patients (2.6%), and newly developed distant metastases occurred in eight patients (4.2%). Of the patients with distant metastases, 36.4% were cured by 131I. Distant metastases from papillary carcinomas had a higher cure rate than follicular carcinomas (p < 0.01). The metastases of four patients (5.2%) lost the property to take up radioiodine. Lung and bone metastases detectable by WBS but not by radiography were most likely to be cured by 131I. The overall survival at the end of follow-up was 95.8% in patients with only lymph node metastases and 76.0% in those with distant metastases. Tumor-related deaths were 3.6% and 23.7%, respectively. Our data indicate that 131I therapy is highly effective in the treatment of lymph node metastases from differentiated thyroid carcinoma.(ABSTRACT TRUNCATED AT 250 WORDS)     

Somatic mutations of the ret protooncogene in sporadic medullary thyroid carcinoma are not restricted to exon 16 and are associated with tumor recurrence

Germline point mutations in exons 10, 11, and 16 of the ret protooncogene have been identified as causative in multiple endocrine neoplasia type 2 and in familial medullary thyroid carcinoma (MTC). Somatic point mutations of the same gene, exclusively associated with codon 918 of exon 16, have also been reported in few cases of sporadic medullary thyroid carcinoma. We analyzed the blood and tumor DNA of 19 patients with sporadic MTC and 6 patients with primary parathyroid adenoma for point mutations at exons 10, 11, and 16 of the ret protooncogene by restriction analysis of the PCR-amplified product and by sequence analysis of exons 10 and 11. A Cys634-->Tyr mutation was found in both the tumoral and blood DNA of one patient, indicating that he was affected by an hereditary form of MTC, erroneously considered sporadic. In the other 18 patients with MTC, somatic point mutations of ret were found in 8 cases (44.4%). In 5 cases the mutation affected exon 16 (Met918-->Thr), and in 3 cases it affected exon 11 (Cys634-->Arg in 1 and Cys634-->Trp in 2); these 3 mutations were confirmed by sequence analysis. The remaining 10 patients had no mutation in exon 10 by either restriction analysis or sequence analysis. Clinical data showed that 75% of the patients whose tumor carried ret mutation had tumor recurrence and/or increased serum calcitonin concentrations during the postsurgical follow-up period as opposed to 10% of the patients without mutations (P < 0.02, by chi2 analysis). No ret mutation was found in the tumoral DNA from parathyroid adenomas. Our findings indicate that the somatic ret point mutation frequently found in sporadic MTC may affect not only exon 16 but also exon 11 and is associated with less favorable clinical outcome.