A random forest algorithm to improve the Lee–Carter mortality forecasting: impact on q-forward

Increased life expectancy in developed countries has led researchers to pay more attention to mortality projection to anticipate changes in mortality rates. Following the scheme proposed in Deprez et al. (Eur Actuar J 7(2):337–352, 2017) and extended by Levantesi and Pizzorusso (Risks 7(1):26, 2019), we propose a novel approach based on the combination of random forest and two-dimensional P-spline, allowing for accurate mortality forecasting. This approach firstly provides a diagnosis of the limits of the Lee–Carter mortality model through the application of the random forest estimator to the ratio between the observed deaths and their estimated values given by a certain model, while the two-dimensional P-spline are used to smooth and project the random forest estimator in the forecasting phase. Further considerations are devoted to assessing the demographic consistency of the results. The model accuracy is evaluated by an out-of-sample test. Finally, we analyze the impact of our model on the pricing of q-forward contracts. All the analyses have been carried out on several countries by using data from the Human Mortality Database and considering the Lee–Carter model

¡NUNCA Más Un México Sin Nosotros! um Estudo Sobre As Novas Representações do Indígena Construídas Pelo Movimento Zapatista Mexicano (1994-1996)

Durante a década de 80 do século XX, diante da mobilização dos indígenas em diversos países latino-americanos, muito se especulou acerca de quem ou o que estaria por trás dos movimentos étnicos. Não se admitia a possibilidade de que os indígenas fossem capazes de se organizar politicamente sem a intervenção de algum agente externo. Por isso, serem reconhecidos como sujeitos dignos e autônomos, capazes de definir as diretrizes de seu próprio desenvolvimento e construir alternativas para a superação da situação de marginalização em que se encontram, são reivindicações cruciais dos movimentos indígenas contemporâneos. A substituição de uma imagem negativa do índio por uma representação positiva pode ser considerada uma estratégia importante da luta política que vem sendo travada pelos índios. Por isso, este trabalho lança luz sobre a dimensão simbólica da resistência zapatista no México e busca identificar as novas representações produzidas pelo movimento que objetiva transformar o indígena em símbolo da luta e da resistência contra a exploração e o esquecimento. Palavras-chave: movimentos indígenas, representações, resistência

Diagnostic delay does not influence survival of pancreatic cancer patients

Background: Most pancreatic ductal adenocarcinoma patients present with advanced disease. Whether it is possible to increase survival by earlier diagnosis is unclear. Objective: The purpose of this study was to investigate the association between presenting complaints and risk factors for pancreatic cancer with diagnostic delay, stage and survival. Methods: This was a single-centre retrospective cohort study. Consecutive patients were interviewed and data on demographics, medical history, risk factors and complaints leading to pancreatic ductal adenocarcinoma diagnosis and disease stage were recorded. Diagnostic delay was considered as time between first complaint and diagnosis. Patients received appropriate treatments and their outcome was recorded in a dedicated database. The Chi-square test for comparison of categorical variables and the Mann–Whitney test for continuous variables were employed with Bonferroni corrections. Correlation between continuous variables was evaluated by means of the Spearman correlation coefficient. Survival analysis was performed with the Kaplan–Meier method and a log-rank test. Results: The median diagnostic delay for 477 pancreatic ductal adenocarcinoma patients was two months (interquartile range 1–5), being significantly shorter for patients presenting with jaundice compared with those with pain, weight loss, diabetes (p < 0.001). The global rate of metastatic disease at diagnosis was 40%, being only 22% in those presenting with jaundice. The median diagnostic delay, however, was not significantly different among disease stages but was significantly longer in patients with a body mass index>25 kg/m2. The median survival time was seven months. Factors associated with worse survival at the multivariable analysis were older age (hazard ratio 1.02 per year), metastatic disease (hazard ratio 2.12) and pain as presenting complaint (hazard ratio 1.32), while diagnostic delay was not. Conclusion: While some complaints are associated with a shorter diagnostic delay and less advanced disease stage, we could not demonstrate that delay is associated with survival, possibly suggesting that prevention rather than early recognition is important to tackle pancreatic cancer lethality

Structural and connectivity parameters reveal spared connectivity in young patients with non-progressive compared to slow-progressive cerebellar ataxia

INTRODUCTION: Within Pediatric Cerebellar Ataxias (PCAs), patients with non-progressive ataxia (NonP) surprisingly show postural motor behavior comparable to that of healthy controls, differently to slow-progressive ataxia patients (SlowP). This difference may depend on the building of compensatory strategies of the intact areas in NonP brain network. METHODS: Eleven PCAs patients were recruited: five with NonP and six with SlowP. We assessed volumetric and axonal bundles alterations with a multimodal approach to investigate whether eventual spared connectivity between basal ganglia and cerebellum explains the different postural motor behavior of NonP and SlowP patients. RESULTS: Cerebellar lobules were smaller in SlowP patients. NonP patients showed a lower number of streamlines in the cerebello-thalamo-cortical tracts but a generalized higher integrity of white matter tracts connecting the cortex and the basal ganglia with the cerebellum. DISCUSSION: This work reveals that the axonal bundles connecting the cerebellum with basal ganglia and cortex demonstrate a higher integrity in NonP patients. This evidence highlights the importance of the cerebellum-basal ganglia connectivity to explain the different postural motor behavior of NonP and SlowP patients and support the possible compensatory role of basal ganglia in patients with stable cerebellar malformation

Scalable design of an IMS cross-flow micro-generator/ion detector

Ion-mobility spectrometry (IMS) is an analytical technique used to separate and identify ionized gas molecules based on their mobility in a carrier buffer gas. Such methods come in a large variety of versions that currently allow ion identification at and above the millimeter scale. Here, we present a design for a cross-flow-IMS method able to generate and detect ions at the sub-millimeter scale. We propose a novel ion focusing strategy and tested it in a prototype device using Nitrogen as a sample gas, and also with simulations using four different sample gases. By introducing an original lobular ion generation localized to a few ten of microns and substantially simplifying the design, our device is able to keep constant laminar flow conditions for high flow rates. In this way, it avoids the turbulences in the gas flow, which would occur in other ion-focusing cross-flow methods limiting their performance at the sub-millimeter scale. Scalability of the proposed design can contribute to improve resolving power and resolution of currently available cross-flow methods.Comment: 14 pages, 10 figures, revised regular paper, minor correction

Medical Informatics Platform (MIP): A Pilot Study Across Clinical Italian Cohorts

Introduction: With the shift of research focus to personalized medicine in Alzheimer's Dementia (AD), there is an urgent need for tools that are capable of quantifying a patient's risk using diagnostic biomarkers. The Medical Informatics Platform (MIP) is a distributed e-infrastructure federating large amounts of data coupled with machine-learning (ML) algorithms and statistical models to define the biological signature of the disease. The present study assessed (i) the accuracy of two ML algorithms, i.e., supervised Gradient Boosting (GB) and semi-unsupervised 3C strategy (Categorize, Cluster, Classify—CCC) implemented in the MIP and (ii) their contribution over the standard diagnostic workup. / Methods: We examined individuals coming from the MIP installed across 3 Italian memory clinics, including subjects with Normal Cognition (CN, n = 432), Mild Cognitive Impairment (MCI, n = 456), and AD (n = 451). The GB classifier was applied to best discriminate the three diagnostic classes in 1,339 subjects, and the CCC strategy was used to refine the classical disease categories. Four dementia experts provided their diagnostic confidence (DC) of MCI conversion on an independent cohort of 38 patients. DC was based on clinical, neuropsychological, CSF, and structural MRI information and again with addition of the outcome from the MIP tools. / Results: The GB algorithm provided a classification accuracy of 85% in a nested 10-fold cross-validation for CN vs. MCI vs. AD discrimination. Accuracy increased to 95% in the holdout validation, with the omission of each Italian clinical cohort out in turn. CCC identified five homogeneous clusters of subjects and 36 biomarkers that represented the disease fingerprint. In the DC assessment, CCC defined six clusters in the MCI population used to train the algorithm and 29 biomarkers to improve patients staging. GB and CCC showed a significant impact, evaluated as +5.99% of increment on physicians' DC. The influence of MIP on DC was rated from “slight” to “significant” in 80% of the cases. / Discussion: GB provided fair results in classification of CN, MCI, and AD. CCC identified homogeneous and promising classes of subjects via its semi-unsupervised approach. We measured the effect of the MIP on the physician's DC. Our results pave the way for the establishment of a new paradigm for ML discrimination of patients who will or will not convert to AD, a clinical priority for neurology

MRI data quality assessment for the RIN - Neuroimaging Network using the ACR phantoms

PURPOSE: Generating big-data is becoming imperative with the advent of machine learning. RIN-Neuroimaging Network addresses this need by developing harmonized protocols for multisite studies to identify quantitative MRI (qMRI) biomarkers for neurological diseases. In this context, image quality control (QC) is essential. Here, we present methods and results of how the RIN performs intra- and inter-site reproducibility of geometrical and image contrast parameters, demonstrating the relevance of such QC practice. METHODS: American College of Radiology (ACR) large and small phantoms were selected. Eighteen sites were equipped with a 3T scanner that differed by vendor, hardware/software versions, and receiver coils. The standard ACR protocol was optimized (in-plane voxel, post-processing filters, receiver bandwidth) and repeated monthly. Uniformity, ghosting, geometric accuracy, ellipse’s ratio, slice thickness, and high-contrast detectability tests were performed using an automatic QC script. RESULTS: Measures were mostly within the ACR tolerance ranges for both T1- and T2-weighted acquisitions, for all scanners, regardless of vendor, coil, and signal transmission chain type. All measurements showed good reproducibility over time. Uniformity and slice thickness failed at some sites. Scanners that upgraded the signal transmission chain showed a decrease in geometric distortion along the slice encoding direction. Inter-vendor differences were observed in uniformity and geometric measurements along the slice encoding direction (i.e. ellipse’s ratio). CONCLUSIONS: Use of the ACR phantoms highlighted issues that triggered interventions to correct performance at some sites and to improve the longitudinal stability of the scanners. This is relevant for establishing precision levels for future multisite studies of qMRI biomarkers

Effective connectivity reveals strategy differences in an expert calculator

Mathematical reasoning is a core component of cognition and the study of experts defines the upper limits of human cognitive abilities, which is why we are fascinated by peak performers, such as chess masters and mental calculators. Here, we investigated the neural bases of calendrical skills, i.e. the ability to rapidly identify the weekday of a particular date, in a gifted mental calculator who does not fall in the autistic spectrum, using functional MRI. Graph-based mapping of effective connectivity, but not univariate analysis, revealed distinct anatomical location of “cortical hubs” supporting the processing of well-practiced close dates and less-practiced remote dates: the former engaged predominantly occipital and medial temporal areas, whereas the latter were associated mainly with prefrontal, orbitofrontal and anterior cingulate connectivity. These results point to the effect of extensive practice on the development of expertise and long term working memory, and demonstrate the role of frontal networks in supporting performance on less practiced calculations, which incur additional processing demands. Through the example of calendrical skills, our results demonstrate that the ability to perform complex calculations is initially supported by extensive attentional and strategic resources, which, as expertise develops, are gradually replaced by access to long term working memory for familiar material

Quality assessment, variability and reproducibility of anatomical measurements derived from T1-weighted brain imaging: The RIN–Neuroimaging Network case study

Initiatives for the collection of harmonized MRI datasets are growing continuously, opening questions on the reliability of results obtained in multi-site contexts. Here we present the assessment of the brain anatomical variability of MRI-derived measurements obtained from T1-weighted images, acquired according to the Standard Operating Procedures, promoted by the RIN-Neuroimaging Network. A multicentric dataset composed of 77 brain T1w acquisitions of young healthy volunteers (mean age = 29.7 ± 5.0 years), collected in 15 sites with MRI scanners of three different vendors, was considered. Parallelly, a dataset of 7 “traveling” subjects, each undergoing three acquisitions with scanners from different vendors, was also used. Intra-site, intra-vendor, and inter-site variabilities were evaluated in terms of the percentage standard deviation of volumetric and cortical thickness measures. Image quality metrics such as contrast-to-noise and signal-to-noise ratio in gray and white matter were also assessed for all sites and vendors. The results showed a measured global variability that ranges from 11% to 19% for subcortical volumes and from 3% to 10% for cortical thicknesses. Univariate distributions of the normalized volumes of subcortical regions, as well as the distributions of the thickness of cortical parcels appeared to be significantly different among sites in 8 subcortical (out of 17) and 21 cortical (out of 68) regions of i nterest in the multicentric study. The Bland-Altman analysis on “traveling” brain measurements did not detect systematic scanner biases even though a multivariate classification approach was able to classify the scanner vendor from brain measures with an accuracy of 0.60 ± 0.14 (chance level 0.33)

Multi-centre and multi-vendor reproducibility of a standardized protocol for quantitative susceptibility Mapping of the human brain at 3T

Quantitative Susceptibility Mapping (QSM) is an MRI-based technique allowing the non-invasive quantification of iron content and myelination in the brain. The RIN – Neuroimaging Network established an optimized and harmonized protocol for QSM across ten sites with 3T MRI systems from three different vendors to enable multicentric studies. The assessment of the reproducibility of this protocol is crucial to establish susceptibility as a quantitative biomarker. In this work, we evaluated cross-vendor reproducibility in a group of six traveling brains. Then, we recruited fifty-one volunteers and measured the variability of QSM values in a cohort of healthy subjects scanned at different sites, simulating a multicentric study. Both voxelwise and Region of Interest (ROI)-based analysis on cortical and subcortical gray matter were performed. The traveling brain study yielded high structural similarity (∼0.8) and excellent reproducibility comparing maps acquired on scanners from two different vendors. Depending on the ROI, we reported a quantification error ranging from 0.001 to 0.017 ppm for the traveling brains. In the cohort of fifty-one healthy subjects scanned at nine different sites, the ROI-dependent variability of susceptibility values, of the order of 0.005–0.025 ppm, was comparable to the result of the traveling brain experiment. The harmonized QSM protocol of the RIN – Neuroimaging Network provides a reliable quantification of susceptibility in both cortical and subcortical gray matter regions and it is ready for multicentric and longitudinal clinical studies in neurological and pychiatric diseases