Indirect likelihood inference

Given a sample from a fully specified parametric model, let Zn be a given finite-dimensional statistic - for example, an initial estimator or a set of sample moments. We propose to (re-)estimate the parameters of the model by maximizing the likelihood of Zn. We call this the maximum indirect likelihood (MIL) estimator. We also propose a computationally tractable Bayesian version of the estimator which we refer to as a Bayesian Indirect Likelihood (BIL) estimator. In most cases, the density of the statistic will be of unknown form, and we develop simulated versions of the MIL and BIL estimators. We show that the indirect likelihood estimators are consistent and asymptotically normally distributed, with the same asymptotic variance as that of the corresponding efficient two-step GMM estimator based on the same statistic. However, our likelihood-based estimators, by taking into account the full finite-sample distribution of the statistic, are higher order efficient relative to GMM-type estimators. Furthermore, in many cases they enjoy a bias reduction property similar to that of the indirect inference estimator. Monte Carlo results for a number of applications including dynamic and nonlinear panel data models, a structural auction model and two DSGE models show that the proposed estimators indeed have attractive finite sample properties.

Age effects, unobserved characteristics and hedonic price indexes: The Spanish car market in the 1990s

This paper computes and compares alternative quality-adjusted price indexes for new cars in Spain in the period 1990-2000. The proposed hedonic approach simultaneously controls for time-invariant unobserved product e¤ects and time-variant unobserved quality changes, that are assumed to be captured by model age effects. The results show that the non-adjusted price index largely overstates the increase in the cost of living induced by changes in car prices and that previous evidence for this market have not measured the real extent of that bias, probably due to the omission of controls for unobservables. It is also shown that omitting age effects can also lead to misleading conclusions. The estimated price indexes give also some insights on what could have been the determinants of price evolution in the Spanish car market.

Age effects, unobserved characteristics and hedonic price indexes: The Spanish car market in the 1990's

This paper computes and compares alternative quality-adjusted price indexes for new cars in Spain in the period 1990-2000. The proposed hedonic approach simultaneously controls for time-invariant unobserved product effects and time-variant unobserved quality changes, that are assumed to be captured by model age effects. The results show that the non-adjusted price index largely overstates the increase in the cost of living induced by changes in car prices and that previous evidence for this market have not measured the real extent of that bias, probably due to the omission of controls for unobservables. It is also shown that omitting age effects can also lead to misleading conclusions. The estimated price indexes give also some insights on what could have been the determinants of price evolution in the Spanish car market. JEL classi…fication numbers: C43, E31, L11, L13, Keywords: Hedonic price indexes, Spanish car market, car prices, CPI, Cost of living

Amplification efficiency: linking baseline and bias in the analysis of quantitative PCR data.

Despite the central role of quantitative PCR (qPCR) in the quantification of mRNA transcripts, most analyses of qPCR data are still delegated to the software that comes with the qPCR apparatus. This is especially true for the handling of the fluorescence baseline. This article shows that baseline estimation errors are directly reflected in the observed PCR efficiency values and are thus propagated exponentially in the estimated starting concentrations as well as 'fold-difference' results. Because of the unknown origin and kinetics of the baseline fluorescence, the fluorescence values monitored in the initial cycles of the PCR reaction cannot be used to estimate a useful baseline value. An algorithm that estimates the baseline by reconstructing the log-linear phase downward from the early plateau phase of the PCR reaction was developed and shown to lead to very reproducible PCR efficiency values. PCR efficiency values were determined per sample by fitting a regression line to a subset of data points in the log-linear phase. The variability, as well as the bias, in qPCR results was significantly reduced when the mean of these PCR efficiencies per amplicon was used in the calculation of an estimate of the starting concentration per sample.

Neurally adjusted ventilatory assist (NAVA) improves patient-ventilator interaction during non-invasive ventilation delivered by face mask.

PURPOSE: To determine if, compared to pressure support (PS), neurally adjusted ventilatory assist (NAVA) reduces patient-ventilator asynchrony in intensive care patients undergoing noninvasive ventilation with an oronasal face mask. METHODS: In this prospective interventional study we compared patient-ventilator synchrony between PS (with ventilator settings determined by the clinician) and NAVA (with the level set so as to obtain the same maximal airway pressure as in PS). Two 20-min recordings of airway pressure, flow and electrical activity of the diaphragm during PS and NAVA were acquired in a randomized order. Trigger delay (T(d)), the patient's neural inspiratory time (T(in)), ventilator pressurization duration (T(iv)), inspiratory time in excess (T(iex)), number of asynchrony events per minute and asynchrony index (AI) were determined. RESULTS: The study included 13 patients, six with COPD, and two with mixed pulmonary disease. T(d) was reduced with NAVA: median 35 ms (IQR 31-53 ms) versus 181 ms (122-208 ms); p = 0.0002. NAVA reduced both premature and delayed cyclings in the majority of patients, but not the median T(iex) value. The total number of asynchrony events tended to be reduced with NAVA: 1.0 events/min (0.5-3.1 events/min) versus 4.4 events/min (0.9-12.1 events/min); p = 0.08. AI was lower with NAVA: 4.9 % (2.5-10.5 %) versus 15.8 % (5.5-49.6 %); p = 0.03. During NAVA, there were no ineffective efforts, or late or premature cyclings. PaO(2) and PaCO(2) were not different between ventilatory modes. CONCLUSION: Compared to PS, NAVA improved patient ventilator synchrony during noninvasive ventilation by reducing T(d) and AI. Moreover, with NAVA, ineffective efforts, and late and premature cyclings were absent.

Aplicación de un score semiquantitativo de tac-ar para el control y evaluación del pronóstico de pacientes con fibrosis pulmonar idiopática

Estudi prospectiu amb 36 pacients, on definírem un score semiquantitatiu per a diferents patrons de FPI a la TCAR, i la suma resultant (Score Total). Estudiàrem la relació amb paràmetres funcionals i cel.lularitat del RBA, analitzant-se’n les diferències amb els pacients morts. Trobàrem correlació entre el score de bresca (honeycomb) i total amb alguns paràmetres funcionals, prova de marxa de 6 minuts i la gasometria arterial. Els morts hi tenien major score total i tendència a la neutrofília. Concluírem que un score semiquantitatiu de TCAR és útil per a valorar la gravetat inicial i preveure l’evolució de la FPI. Paraules clau: TCAR, FPI, Score semiquantitatiu, gravetat, evolució.

MP2RAGE, a self bias-field corrected sequence for improved segmentation and T-1-mapping at high field

The large spatial inhomogeneity in transmit B, field (B-1(+)) observable in human MR images at hi h static magnetic fields (B-0) severely impairs image quality. To overcome this effect in brain T-1-weighted images the, MPRAGE sequence was modified to generate two different images at different inversion times MP2RAGE By combining the two images in a novel fashion, it was possible to create T-1-weigthed images where the result image was free of proton density contrast, T-2* contrast, reception bias field, and, to first order transmit field inhomogeneity. MP2RAGE sequence parameters were optimized using Bloch equations to maximize contrast-to-noise ratio per unit of time between brain tissues and minimize the effect of B-1(+) variations through space. Images of high anatomical quality and excellent brain tissue differentiation suitable for applications such as segmentation and voxel-based morphometry were obtained at 3 and 7 T. From such T-1-weighted images, acquired within 12 min, high-resolution 3D T-1 maps were routinely calculated at 7 T with sub-millimeter voxel resolution (0.65-0.85 mm isotropic). T-1 maps were validated in phantom experiments. In humans, the T, values obtained at 7 T were 1.15 +/- 0.06 s for white matter (WM) and 1.92 +/- 0.16 s for grey matter (GM), in good agreement with literature values obtained at lower spatial resolution. At 3 T, where whole-brain acquisitions with 1 mm isotropic voxels were acquired in 8 min the T-1 values obtained (0.81 +/- 0.03 S for WM and 1.35 +/- 0.05 for GM) were once again found to be in very good agreement with values in the literature. (C) 2009 Elsevier Inc. All rights reserved.

Deregulated MHC class II transactivator expression leads to a strong Th2 bias in CD4+ T lymphocytes.

The MHC class II (MHC-II) transactivator (CIITA) is the master transcriptional regulator of genes involved in MHC-II-restricted Ag presentation. Fine tuning of CIITA gene expression determines the cell type-specific expression of MHC-II genes. This regulation is achieved by the selective usage of multiple CIITA promoters. It has recently been suggested that CIITA also contributes to Th cell differentiation by suppressing IL-4 expression in Th1 cells. In this study, we show that endogenous CIITA is expressed at low levels in activated mouse T cells. Importantly CIITA is not regulated differentially in murine and human Th1 and Th2 cells. Ectopic expression of a CIITA transgene in multiple mouse cell types including T cells, does not interfere with normal development of CD4(+) T cells. However, upon TCR activation the CIITA transgenic CD4(+) T cells preferentially differentiate into IL-4-secreting Th2-type cells. These results imply that CIITA is not a direct Th1-specific repressor of the IL-4 gene and that tight control over the expression of CIITA and MHC-II is required to maintain the normal balance between Th1 and Th2 responses.

U-Pb and Ar-Ar geochronological data from the Pelagonian basement in Evia (Greece): geodynamic implications for the evolution of Paleotethys

High precision U-Pb zircon and Ar-40/Ar-39 mica geochronological data on metagranodiorites, metagranites and mica schists from north and central Evia island (Greece) are presented in this study. U-Pb zircon ages range from 308 to 1912 Ma, and indicate a prolonged magmatic activity in Late Carboniferous. Proterozoic ages represent inherited cores within younger crystals. Muscovite Ar-40/Ar-39 plateau ages of 288 to 297 Ma are interpreted as cooling ages of the magmatic bodies and metamorphic host rocks in upper greenschist to epidote-amphibolite metamorphic conditions. The multistage magmatism had a duration between 308 and 319 hla but some older intrusions, as well as metamorphic events, cannot be excluded. Geochemical analyses and zircon typology indicate calc-alkaline affinities for the granites of central Evia and alkaline to calc-alkaline characteristics for the metagranodiorites from the northern part of the island. The new data point towards the SE continuation, in Evia and the Cyclades, of a Variscan continental crust already recognised in northern Greece (Pelagonian basement). The Late Carboniferous magmatism is viewed as a result of northward subduction of the Paleotethys under the Eurasian margin.

The relationship between forensic science and judicial error: a study covering error sources, bias, and remedies

Summary : Forensic science - both as a source of and as a remedy for error potentially leading to judicial error - has been studied empirically in this research. A comprehensive literature review, experimental tests on the influence of observational biases in fingermark comparison, and semistructured interviews with heads of forensic science laboratories/units in Switzerland and abroad were the tools used. For the literature review, some of the areas studied are: the quality of forensic science work in general, the complex interaction between science and law, and specific propositions as to error sources not directly related to the interaction between law and science. A list of potential error sources all the way from the crime scene to the writing of the report has been established as well. For the empirical tests, the ACE-V (Analysis, Comparison, Evaluation, and Verification) process of fingermark comparison was selected as an area of special interest for the study of observational biases, due to its heavy reliance on visual observation and recent cases of misidentifications. Results of the tests performed with forensic science students tend to show that decision-making stages are the most vulnerable to stimuli inducing observational biases. For the semi-structured interviews, eleven senior forensic scientists answered questions on several subjects, for example on potential and existing error sources in their work, of the limitations of what can be done with forensic science, and of the possibilities and tools to minimise errors. Training and education to augment the quality of forensic science have been discussed together with possible solutions to minimise the risk of errors in forensic science. In addition, the time that samples of physical evidence are kept has been determined as well. Results tend to show considerable agreement on most subjects among the international participants. Their opinions on possible explanations for the occurrence of such problems and the relative weight of such errors in the three stages of crime scene, laboratory, and report writing, disagree, however, with opinions widely represented in existing literature. Through the present research it was therefore possible to obtain a better view of the interaction of forensic science and judicial error to propose practical recommendations to minimise their occurrence. Résumé : Les sciences forensiques - considérés aussi bien comme source de que comme remède à l'erreur judiciaire - ont été étudiées empiriquement dans cette recherche. Une revue complète de littérature, des tests expérimentaux sur l'influence du biais de l'observation dans l'individualisation de traces digitales et des entretiens semi-directifs avec des responsables de laboratoires et unités de sciences forensiques en Suisse et à l'étranger étaient les outils utilisés. Pour la revue de littérature, quelques éléments étudies comprennent: la qualité du travail en sciences forensiques en général, l'interaction complexe entre la science et le droit, et des propositions spécifiques quant aux sources d'erreur pas directement liées à l'interaction entre droit et science. Une liste des sources potentielles d'erreur tout le long du processus de la scène de crime à la rédaction du rapport a également été établie. Pour les tests empiriques, le processus d'ACE-V (analyse, comparaison, évaluation et vérification) de l'individualisation de traces digitales a été choisi comme un sujet d'intérêt spécial pour l'étude des effets d'observation, due à son fort recours à l'observation visuelle et dû à des cas récents d'identification erronée. Les résultats des tests avec des étudiants tendent à prouver que les étapes de prise de décision sont les plus vulnérables aux stimuli induisant des biais d'observation. Pour les entretiens semi-structurés, onze forensiciens ont répondu à des questions sur des sujets variés, par exemple sur des sources potentielles et existantes d'erreur dans leur travail, des limitations de ce qui peut être fait en sciences forensiques, et des possibilités et des outils pour réduire au minimum ses erreurs. La formation et l'éducation pour augmenter la qualité des sciences forensiques ont été discutées ainsi que les solutions possibles pour réduire au minimum le risque d'erreurs en sciences forensiques. Le temps que des échantillons sont gardés a été également déterminé. En général, les résultats tendent à montrer un grand accord sur la plupart des sujets abordés pour les divers participants internationaux. Leur avis sur des explications possibles pour l'occurrence de tels problèmes et sur le poids relatif de telles erreurs dans les trois étapes scène de crime;', laboratoire et rédaction de rapports est cependant en désaccord avec les avis largement représentés dans la littérature existante. Par cette recherche il était donc possible d'obtenir une meilleure vue de l'interaction des sciences forensiques et de l'erreur judiciaire afin de proposer des recommandations pratiques pour réduire au minimum leur occurrence. Zusammenfassung : Forensische Wissenschaften - als Ursache und als Hilfsmittel gegen Fehler, die möglicherweise zu Justizirrtümern führen könnten - sind hier empirisch erforscht worden. Die eingestzten Methoden waren eine Literaturübersicht, experimentelle Tests über den Einfluss von Beobachtungseffekten (observer bias) in der Individualisierung von Fingerabdrücken und halbstandardisierte Interviews mit Verantwortlichen von kriminalistischen Labors/Diensten in der Schweiz und im Ausland. Der Literaturüberblick umfasst unter anderem: die Qualität der kriminalistischen Arbeit im Allgemeinen, die komplizierte Interaktion zwischen Wissenschaft und Recht und spezifische Fehlerquellen, welche nicht direkt auf der Interaktion von Recht und Wissenschaft beruhen. Eine Liste möglicher Fehlerquellen vom Tatort zum Rapportschreiben ist zudem erstellt worden. Für die empirischen Tests wurde der ACE-V (Analyse, Vergleich, Auswertung und Überprüfung) Prozess in der Fingerabdruck-Individualisierung als speziell interessantes Fachgebiet für die Studie von Beobachtungseffekten gewählt. Gründe sind die Wichtigkeit von visuellen Beobachtungen und kürzliche Fälle von Fehlidentifizierungen. Resultate der Tests, die mit Studenten durchgeführt wurden, neigen dazu Entscheidungsphasen als die anfälligsten für Stimuli aufzuzeigen, die Beobachtungseffekte anregen könnten. Für die halbstandardisierten Interviews beantworteten elf Forensiker Fragen über Themen wie zum Beispiel mögliche und vorhandene Fehlerquellen in ihrer Arbeit, Grenzen der forensischen Wissenschaften und Möglichkeiten und Mittel um Fehler zu verringern. Wie Training und Ausbildung die Qualität der forensischen Wissenschaften verbessern können ist zusammen mit möglichen Lösungen zur Fehlervermeidung im selben Bereich diskutiert worden. Wie lange Beweismitten aufbewahrt werden wurde auch festgehalten. Resultate neigen dazu, für die meisten Themen eine grosse Übereinstimmung zwischen den verschiedenen internationalen Teilnehmern zu zeigen. Ihre Meinungen über mögliche Erklärungen für das Auftreten solcher Probleme und des relativen Gewichts solcher Fehler in den drei Phasen Tatort, Labor und Rapportschreiben gehen jedoch mit den Meinungen, welche in der Literatur vertreten werden auseinander. Durch diese Forschungsarbeit war es folglich möglich, ein besseres Verständnis der Interaktion von forensischen Wissenschaften und Justizirrtümer zu erhalten, um somit praktische Empfehlungen vorzuschlagen, welche diese verringern. Resumen : Esta investigación ha analizado de manera empírica el rol de las ciencias forenses como fuente y como remedio de potenciales errores judiciales. La metodología empleada consistió en una revisión integral de la literatura, en una serie de experimentos sobre la influencia de los sesgos de observación en la individualización de huellas dactilares y en una serie de entrevistas semiestructuradas con jefes de laboratorios o unidades de ciencias forenses en Suiza y en el extranjero. En la revisión de la literatura, algunas de las áreas estudiadas fueron: la calidad del trabajo en ciencias forenses en general, la interacción compleja entre la ciencia y el derecho, así como otras fuentes de error no relacionadas directamente con la interacción entre derecho y ciencia. También se ha establecido una lista exhaustiva de las fuentes potenciales de error desde la llegada a la escena del crimen a la redacción del informe. En el marco de los tests empíricos, al analizar los sesgos de observación dedicamos especial interés al proceso de ACE-V (análisis, comparación, evaluación y verificación) para la individualización de huellas dactilares puesto que este reposa sobre la observación visual y ha originado varios casos recientes de identificaciones erróneas. Los resultados de las experimentaciones realizadas con estudiantes sugieren que las etapas en las que deben tornarse decisiones son las más vulnerables a lös factores que pueden generar sesgos de observación. En el contexto de las entrevistas semi-estructuradas, once científicos forenses de diversos países contestaron preguntas sobre varios temas, incluyendo las fuentes potenciales y existehtes de error en su trabajo, las limitaciones propias a las ciencias forenses, las posibilidades de reducir al mínimo los errores y las herramientas que podrían ser utilizadas para ello. Se han sugerido diversas soluciones para alcanzar este objetivo, incluyendo el entrenamiento y la educación para aumentar la calidad de las ciencias forenses. Además, se ha establecido el periodo de conservación de las muestras judiciales. Los resultados apuntan a un elevado grado de consenso entre los entrevistados en la mayoría de los temas. Sin embargo, sus opiniones sobre las posibles causas de estos errores y su importancia relativa en las tres etapas de la investigación -la escena del crimen, el laboratorio y la redacción de informe- discrepan con las que predominan ampliamente en la literatura actual. De este modo, esta investigación nos ha permitido obtener una mejor imagen de la interacción entre ciencias forenses y errores judiciales, y comenzar a formular una serie de recomendaciones prácticas para reducirlos al minimo.

Factors associated with improvement in disability-adjusted life years in patients with HIV/AIDS

Background The epidemic of HIV/AIDS and treatments that have emerged to alleviate, have brought about a shift in the burden of disease from death to quality of life/disability. The aim was to determine which factors are associated with improvements in the level of health of male and female patients with HIV/AIDS in Andalusia, in terms of disability-adjusted life years. Methods Descriptive study based on a sample group of 8800 people on the Andalusian AIDS register between 1983 and 2004. Dependent variables: Life lost due to premature mortality (YLL), years lost due to disability (YLD) and disability-adjusted life years (DALY). Independent variables: vital state, sex, age at the time of diagnosis, age at the time of death, transmission category, province of residence, AIDS-indicator disease and the period of diagnosis. A bivariate analysis was carried out to find out if the health level variables changed in accordance with the independent variables. Using the independent variables which had a statistically significant link with the level of health variables, a multivariate linear regression model, disaggregated by gender, was constructed. Results Amongst the women, we found a model which explained the level of health of 64.9%: a link was found between a higher level of health (lower DALYs) and not intravenous drug use, the province of residence, being diagnosed during the HAART era and older age at the time of diagnosis. Amongst the men, we found a model which explained the level of health of 64.4%: a link was found between a higher level of health (lower DALYs) and intravenous drug use, the province of residence, being diagnosed during the HAART era and older age at the time of diagnosis. Conclusion A higher level of health (lower DALY) amongst both men and women was found to be linked to not be intravenous drug user, the province of residence, being diagnosed during the HAART era and older age at the time of diagnosis.