PROBING THE PRECAMBRIAN GEODYNAMO: ANALYSIS OF THE GEOMAGNETIC FIELD BEHAVIOR AND CALIBRATION OF PSEUDO-THELLIER PALEOINTENSITY METHOD FOR MESOPROTEROZOIC ROCKS

Understanding the geomagnetic field direction and strength (e.g., paleomagnetism and paleointensity, respectively) recorded by Precambrian rocks is essential to obtain insight into the nature and evolution of the Earth’s early geodynamo and for constraining models of planetary evolution. Major milestones of our planet’s history, such as beginning of plate tectonics, development of the atmosphere and life, took place during the first four billion years. However, the available data on the Earth’s magnetic field in the Precambrian are very limited, especially the information about the field intensity which represents one of the most challenging aspect of paleomagnetic research. Many Precambrian rocks are not suitable for paleointensity determinations with the most commonly used Thellier double-heating method because of their geological and experimental alteration. Complementing the Precambrian paleomagnetic and paleointensity database and improving alternative paleointensity techniques is essential to better our understanding of the Earth. This dissertation presents the results of investigations of the Precambrian geomagnetic field direction and strength, and the results of a methodological study of the pseudo-Thellier experimental protocol for absolute paleointensity determination. Detailed paleomagnetic and rock magnetic observations were performed on rocks emplaced ~1100 Ma during the formation of the North-American Mid-Continent Rift. The identification of three independent paleomagnetic directions in the Baraga and Marquette dikes and their comparison to the Mesoproterozoic Apparent Polar Wonder Path (the so-called Logan loop) permitted the estimation of the relative timescale for their intrusion (Chapter 2). The Shaw paleointensity results on the dikes from Baraga and Marquette areas yielded consistent intensity values of ~14.4 μT and ~20.4 μT corresponding to a VDM of ~2 x 1022 Am2 and 3.3 x 1022 Am2, respectively. The detailed paleomagnetic analysis of the ~1094 Ma Greenstone flow, one of the largest large flows on the planet, was applied to evaluate the various scenarios of emplacement and cooling of the flow and to assess the paleosecular variation of the geomagnetic field (Chapter 3). The results of an experimental study using the combination of the pseudo-Thellier and Shaw experimental protocols on synthetic and natural magnetite-bearing samples suggest that the calibrated pseudo-Thellier method can xii provide absolute paleointensity estimates for Precambrian rock equivalent to the results from conventional heating methods (Chapter 4). The paleointensity values (2-3 x 1022Am2) obtained from the Baraga and Marquette dikes are low in comparison to the average field strength value (~8.0 x 1022 Am2) for the last 10 Myr but agree with some low paleointensity determinations from other Precambrian rocks. These results suggest that the Baraga-Marquette dikes intruded during a period where the geomagnetic field was weak. However, a possibility of underestimating the field strength due to the presence of thermochemical remanent magnetization cannot be ruled out

Meta-analysis of predictive models to assess the clinical validity and utility for patient-centered medical decision making: application to the CAncer of the Prostate Risk Assessment (CAPRA)

Background: The Cancer of the Prostate Risk Assessment (CAPRA) score was designed and validated several times to predict the biochemical recurrence-free survival after a radical prostatectomy. Our objectives were, first, to study the clinical validity of the CAPRA score, and, second, to assess its clinical utility for stratified medicine from an original patient-centered approach. Methods: We proposed a meta-analysis based on a literature search using MEDLINE. Observed and predicted biochemical-recurrence-free survivals were compared to assess the calibration of the CAPRA score. Discriminative capacities were evaluated by estimating the summary time-dependent ROC curve. The clinical utility of the CAPRA score was evaluated according to the following stratified decisions: active monitoring for low-risk patients, prostatectomy for intermediate-risk patients, or radio-hormonal therapy for high risk patients. For this purpose, we assessed CAPRA’s clinical utility in terms of its ability to maximize time-dependent utility functions (i.e. Quality-Adjusted Life-Years – QALYs). Results: We identified 683 manuscripts and finally retained 9 studies. We reported good discriminative capacities with an area under the SROCt curve at 0.73 [95%CI from 0.67 to 0.79], while graphical calibration seemed acceptable. Nevertheless, we also described that the CAPRA score was unable to discriminate between the three medical alternatives, i.e. it did not allow an increase in the number of life years in perfect health (QALYs) of patients with prostate cancer. Conclusions: We confirmed the prognostic capacities of the CAPRA score. In contrast, we were not able to demonstrate its clinical usefulness for stratified medicine from a patient-centered perspective. Our results also highlighted the confusion between clinical validity and utility. This distinction should be better considered in order to develop predictive tools useful in practice

Endometrial cancer in elderly women: which disease, which surgical management? A systematic review of the literature

International audienceObjective: Endometrial cancer primarily affects elderly women. The aim of the present literature review is to define the population of elderly women with this disease and to define the characteristics of this cancer in elderly people as well as its surgical treatment. Materials and Methods: A systematic review of the English-language literature of the last 20 years indexed in the PubMed database. Results Endometrial cancer is more aggressive in elderly women. However, surgical staging performed in elderly patients is often not concomitant with the disease’s aggressiveness in this group. Mini-invasive surgery is performed less often, for no obvious reason. Of note, oncogeriatric evaluation was not usually ruled out to determine the most appropriate surgical modality. Conclusion: Studies are needed to evaluate surgical management of endometrial cancer in elderly women, notably with the aid of oncogeriatric scores to predict surgical morbidity

Intrinsic paleointensity bias and the long-term history of the geodynamo

Many geodynamo models predict an inverse relationship between geomagnetic reversal frequency and field strength. However, most of the absolute paleointensity data, obtained predominantly by the Thellier method from bulk volcanic rocks, fail to confirm this relationship. Although low paleointensities are commonly observed during periods of high reversal rate (notably, in the late Jurassic), higher than present-day intensity values are rare during periods of no or few reversals (superchrons). We have identified a fundamental mechanism that results in a pervasive and previously unrecognized low-field bias that affects most paleointensity data in the global database. Our results provide an explanation for the discordance between the experimental data and numerical models, and lend additional support to an inverse relationship between the reversal rate and field strength as a fundamental property of the geodynamo. We demonstrate that the accuracy of future paleointensity analyses can be improved by integration of the Thellier protocol with low-temperature demagnetizations

Optimal threshold estimator of a prognostic marker by maximizing a time-dependent expected utility function for a patient-centered stratified medicine

International audienceDefining thresholds of prognostic markers is essential for stratified medicine. Such thresholds are mostly estimated from purely statistical measures regardless of patient preferences potentially leading to unacceptable medical decisions. Quality-Adjusted Life-Years are a widely used preferences-based measure of health outcomes. We develop a time-dependent Quality-Adjusted Life-Years-based expected utility function for censored data that should be maximized to estimate an optimal threshold. We performed a simulation study to compare estimated thresholds when using the proposed expected utility approach and purely statistical estimators. Two applications illustrate the usefulness of the proposed methodology which was implemented in the R package ROCt ( www.divat.fr ). First, by reanalysing data of a randomized clinical trial comparing the efficacy of prednisone vs. placebo in patients with chronic liver cirrhosis, we demonstrate the utility of treating patients with a prothrombin level higher than 89%. Second, we reanalyze the data of an observational cohort of kidney transplant recipients: we conclude to the uselessness of the Kidney Transplant Failure Score to adapt the frequency of clinical visits. Applying such a patient-centered methodology may improve future transfer of novel prognostic scoring systems or markers in clinical practice

A mini-review of quality of life as an outcome in prostate cancer trials: patient-centered approaches are needed to propose appropriate treatments on behalf of patients

Abstract Background Patients with prostate cancer (PC) may be ready to make trade-offs between their quantity and their quality of life. For instance, elderly patients may prefer the absence of treatment if it is associated with a low-risk of disease progression, compared to treatments aiming at preventing disease progression but with a substantial deterioration of their Health-Related Quality of Life (HRQoL). Therefore, it seems relevant to compare the treatments by considering both survival and HRQoL. In this mini-review, the aim was to question whether the potential trade-offs between survival and HRQoL are considered in high impact factor journals. Methods The study was conducted from the PubMed database for recent papers published between May 01, 2013, and May 01, 2015. We also restricted our search to nine medical journals with 2013 impact factor > 15. Results Among the 30 selected studies, only six collected individual HRQoL as a secondary endpoint by using the Functional Assessment of Cancer Therapy-Prostate (FACT-P) questionnaire. In four studies, the time to HRQoL change was analyzed, but its definitions varied. In two studies, the mean changes in HRQoL between the baseline and the 12- or 16-week follow-up were analyzed. None of the six studies reported in a single endpoint both the quantity and the quality of life. Conclusions Our mini-review, which only focused on recent publications in journals with high-impact, suggests moving PC clinical research towards patient-centered outcomes-based studies. This may help physicians to propose the most appropriate treatment on behalf of patients. We recommend the use of indicators such as Quality-Adjusted Life-Years (QALYs) as principal endpoint in future clinical trials

Polykinematic foreland basins initiated during orthogonal convergence and terminated by orogen-oblique strike-slip faulting: An example from the northeastern Variscan belt

An extensive early Carboniferous foreland basin (the Moravosilesian Culm Basin, MSCB) delineates the northeastern margin of the Bohemian Massif (Variscan orogenic belt). The basin overlays a complex suture between the outer Brunovistulia microplate, forming a promontory previously accreted to Laurussia, and inner Gondwana-derived units that form the remainder of the Bohemian Massif. Our structural, paleomagnetic and magnetic anisotropy data from the eastern portion of the MSCB indicate that its depositional architecture, internal fabric, and deformation by folding and faulting record a major switch from orthogonal convergence to orogen-oblique strike-slip shearing. First, the Brunovistulia microcontinent was subducted frontally towards W during ~346–335 Ma, followed by a shift of the subduction vector towards ~SSW at around 335–330 Ma. From ~330 Ma onwards, the underthrusting had ceased and the ~WNW–ESE dextral Elbe shear zone, related to the westward movement of Gondwana with respect to Laurussia, controlled deformation of this region. Displacement of the northerly Eastern Sudetes ‘block’ towards ~ESE produced regional ~WNW–ESE pure-shear shortening against the Brunovistulia indentor and resulted in an overall doubly-vergent structure of the MSCB. Simultaneously, the southerly Moldanubian unit was translated towards ~WNW, away from the Brunovistulian microplate, and likely contributed to an extensional regime related to orogenic collapse progressing outward from the internal domains of the Bohemian Massif. On a larger scale, we suggest that the MSCB is an illustrative example of a polykinematic foreland basin, where deposition, syn- to post-sedimentary deformation, and thus geodynamic processes changed significantly during basin evolution, starting off with microplate impingement into a continental margin reentrant and terminated by strike-slip shearing. Our data also do not support previous models for the tectonic development of the northeastern termination of the Variscan Belt, which suggested either a large-magnitude, vertical-axis oroclinal rotation of the foreland or its translation along an orogen-perpendicular strike-slip fault

An original approach was used to better evaluate the capacity of a prognostic marker using published survival curves

International audienceObjectives: Predicting chronic disease evolution from a prognostic marker is a key field of research in clinical epidemiology. However, the prognostic capacity of a marker is not systematically evaluated using the appropriate methodology. We proposed the use of simple equations to calculate time-dependent sensitivity and specificity based on published survival curves and other time-dependent indicators as pre-dictive values, likelihood ratios, and posttest probability ratios to reappraise prognostic marker accuracy.Study Design and Setting: The methodology is illustrated by back calculating time-dependent indicators from published articles presenting a marker as highly correlated with the time to event, concluding on the high prognostic capacity of the marker, and presenting the KaplaneMeier survival curves. The tools necessary to run these direct and simple computations are available online at http://www.divat.fr/ en/online-calculators/evalbiom.Results: Our examples illustrate that published conclusions about prognostic marker accuracy may be overoptimistic, thus giving potential for major mistakes in therapeutic decisions.Conclusion: Our approach should help readers better evaluate clinical articles reporting on prognostic markers. Time-dependent sensitivity and specificity inform on the inherent prognostic capacity of a marker for a defined prognostic time. Time-dependent predictive values, likelihood ratios, and posttest probability ratios may additionally contribute to interpret the marker's prognostic capacity

Additional file 2: of A mini-review of quality of life as an outcome in prostate cancer trials: patient-centered approaches are needed to propose appropriate treatments on behalf of patients

The Preferred Reporting Items for Systematic review and Meta-Analysis Protocols (PRISMA-P) checklist. (DOCX 16 kb