Identification and characterization of in vitro expanded hematopoietic stem cells.

Hematopoietic stem cells (HSCs) cultured outside the body are the fundamental component of a wide range of cellular and gene therapies. Recent efforts have achieved > 200-fold expansion of functional HSCs, but their molecular characterization has not been possible since the majority of cells are non-HSCs and single cell-initiated cultures have substantial clone-to-clone variability. Using the Fgd5 reporter mouse in combination with the EPCR surface marker, we report exclusive identification of HSCs from non-HSCs in expansion cultures. By directly linking single-clone functional transplantation data with single-clone gene expression profiling, we show that the molecular profile of expanded HSCs is similar to proliferating fetal HSCs and reveals a gene expression signature, including Esam, Prdm16, Fstl1, and Palld, that can identify functional HSCs from multiple cellular states. This "repopulation signature" (RepopSig) also enriches for HSCs in human datasets. Together, these findings demonstrate the power of integrating functional and molecular datasets to better derive meaningful gene signatures and opens the opportunity for a wide range of functional screening and molecular experiments previously not possible due to limited HSC numbers.

A systematic review of the socioeconomic impact of mechanical thrombectomy for acute ischemic stroke.

BACKGROUND: Mechanical Thrombectomy (MT) is an efficacious treatment for severe acute ischemic stroke patients. However, access to MT is limited in many parts of the world, partly due to economic barriers. The purpose of this systematic review is to provide an updated frame about the socioeconomic impact of MT. METHODS: To carry out this systematic review we used the PRISMA guidelines. We included scientific articles analyzing the socioeconomic impact of MT for acute ischemic stroke, in which MT was compared to best medical therapy (BMT). The online databases of Pubmed, Scopus and Web of Science were used as main sources of information. To carry out the comparative analysis, the incremental cost-effectiveness ratio (ICER) was used, relating the cost to quality-adjusted life-year (QALY). Risk of bias was assessed with the Consensus Health Economic Criteria (CHEC) and the Consolidated Health Economic Evaluation Reporting Standards (CHEERS). RESULTS: Eight hundred thirty-two studies were identified in this systematic review. As a result, studies that used cost-effectiveness analysis show that MT saves costs in the long term and cost-utility analysis show that the cost per QALY is reasonable with a mean ICER value of $14242.36/QALY. CONCLUSIONS: MT has a favorable socioeconomic impact, as derived from cost-effectiveness and cost-utility analyses. Therefore, public policies should encourage the implementation of MT for stroke patients around the world.

Thrombectomy versus Medical Management for Isolated Anterior Cerebral Artery Stroke: An International Multicenter Registry Study.

Background Evidence supporting a potential benefit of thrombectomy for distal medium vessel occlusions (DMVOs) of the anterior cerebral artery (ACA) is, to the knowledge of the authors, unknown. Purpose To compare the clinical and safety outcomes between mechanical thrombectomy (MT) and best medical treatment (BMT) with or without intravenous thrombolysis for primary isolated ACA DMVOs. Materials and Methods Treatment for Primary Medium Vessel Occlusion Stroke, or TOPMOST, is an international, retrospective, multicenter, observational registry of patients treated for DMVO in daily practice. Patients treated with thrombectomy or BMT alone for primary ACA DMVO distal to the A1 segment between January 2013 and October 2021 were analyzed and compared by one-to-one propensity score matching (PSM). Early outcome was measured by the median improvement of National Institutes of Health Stroke Scale (NIHSS) scores at 24 hours. Favorable functional outcome was defined as modified Rankin scale scores of 0-2 at 90 days. Safety was assessed by the occurrence of symptomatic intracerebral hemorrhage and mortality. Results Of 154 patients (median age, 77 years; quartile 1 [Q1] to quartile 3 [Q3], 66-84 years; 80 men; 94 patients with MT; 60 patients with BMT) who met the inclusion criteria, 110 patients (median age, 76 years; Q1-Q3, 67-83 years; 50 men; 55 patients with MT; 55 patients with BMT) were matched. DMVOs were in A2 (82 patients; 53%), A3 (69 patients; 45%), and A3 (three patients; 2%). After PSM, the median 24-hour NIHSS point decrease was -2 (Q1-Q3, -4 to 0) in the thrombectomy and -1 (Q1-Q3, -4 to 1.25) in the BMT cohort (P = .52). Favorable functional outcome (MT vs BMT, 18 of 37 [49%] vs 19 of 39 [49%], respectively; P = .99) and mortality (MT vs BMT, eight of 37 [22%] vs 12 of 39 [31%], respectively; P = .36) were similar in both groups. Symptomatic intracranial hemorrhage occurred in three (2%) of 154 patients. Conclusion Thrombectomy appears to be a safe and technically feasible treatment option for primary isolated anterior cerebral artery occlusions in the A2 and A3 segment with clinical outcomes similar to best medical treatment with and without intravenous thrombolysis. © RSNA, 2023 Supplemental material is available for this article. See also the editorial by Zhu and Wang in this issue.

Adsorption Behavior of the Coenzyme NADH at the Carbon/Electrolyte Interface Determined by Neutron Reflectometry.

The adsorption behavior of ß-nicotinamide adenine dinucleotide (NADH) at the carbon/electrolyte interface has been studied using a combination of neutron reflectometry (NR) and solution depletion isotherms. Coupling the NR technique with an electrochemical cell allowed in situ observation of the reversible adsorption and desorption of the molecule at the electrode surface over a range of applied potentials. The overall surface coverage was low (30-50%), suggesting adsorption only at specific defect sites on the surface. Isotherms conducted over a range of temperatures were used to extract thermodynamic parameters, which implied strong physisorption via electrostatic interactions. In addition, changes in the outermost layer of the carbon electrode were observed as the applied potential was varied, which were confirmed with ex situ X-ray reflectivity measurements (XRR). X-ray photoelectron spectroscopy (XPS) measurements of the carbon surface demonstrated the majority of carbon atoms were in an sp2 state.

Reciprocating instrumentation for endodontic treatment of primary molars: 24-month randomized clinical trial.

BACKGROUND: Although reciprocating instrumentation has been extensively studied for permanent teeth, stronger evidence for its use in primary teeth is lacking. AIM: The aim of this randomized clinical trial was to compare the efficacy of endodontic treatment in primary molars using reciprocating (RECIP) and manual (MAN) instrumentation techniques after 24 months. DESIGN: Primary molars with indication of endodontic treatment were randomly divided into two groups: MAN and RECIP. Treatments were performed, and root canals were filled with calcium hydroxide and iodoform paste. Teeth were later restored with bulk-fill composite resin and re-evaluated after 6, 12, 18, and 24 months. The primary outcome was the success of the endodontic treatment evaluated by Cox regression analysis adjusted by cluster and success rate after 24 months in the intention-to-treat (ITT) population. Instrumentation time, discomfort, postoperative pain, and quality of root canal filling were also evaluated as secondary endpoints. RESULTS: A total of 151 primary win 107 children were included, and 137 were followed up for 24 months. Success rate of teeth allocated to the MAN group was 57.3% and 55.3% for RECIP (p = .792); MAN instrumentation, however, was more time-consuming (p = .005). CONCLUSION: The efficacy of endodontic treatment in primary molars using reciprocating and manual instrumentation is similar after 24 months.

Nonrestorative treatment of initial caries lesion in primary teeth: a systematic review and network meta-analysis.

OBJECTIVE: To identify the best available approach to avoid initial caries lesions progression in primary teeth. MATERIALS AND METHODS: Search was performed in MEDLINE/Pubmed, Web of Science, Embase and CENTRAL databases until March 2021. Studies compared treatment options to avoid the initial caries lesion progression with at least 12 months of follow-up were included. Network meta-analyses were conducted considering the non-progression of caries lesions as an outcome. RESULTS: Potentially eligible studies were screened (n = 2820) and eleven were included. Six studies evaluated the use of fluoride varnish, resin infiltration, sealing, and toothbrushing/flossing on proximal initial caries lesions. When considering occlusal surfaces, only two studies evaluating the ozone gas, fluoride varnish, resin infiltration, and sealants were included. For buccal/lingual surfaces, three studies evaluating toothbrushing, CPP-ACP paste, fluoride varnish, and resin infiltration were included. For all types of surfaces, the resin infiltration showed the best probability to avoid the progression of initial caries lesions. CONCLUSION: The limited number of included studies, most with a high risk of bias and lack of hard outcomes, such as frank cavitation, makes it not feasible to recommend a specific management approach for initial caries lesion control in primary teeth with a high certainty of evidence. PROSPERO: #CRD42016037781.

Impact of early childhood caries severity on oral health-related quality of life among preschool children in Mexico: A cross-sectional study.

BACKGROUND: Information is scarce on Early Childhood Caries (ECC) in Mexican preschool children and its impact on quality of life. AIM: To evaluate the ECC prevalence and its impact on OHRQoL in 3-5 years-old Mexican children according to disease severity. DESIGN: Caries was determined at two thresholds: (1) children with at least one caries lesion (ICDAS-1-6) and (2) children with at least one lesion in dentin (ICDAS-3-6). OHRQoL was assessed through the Mexican Early Childhood Oral Health Impact Scale (M-ECOHIS). Associations among caries severity, M-ECOHIS, and other variables were assessed by ordinal logistic regression. RESULTS: A total of 409 children participated (53.8% girls, 46.2% boys). Caries prevalence was 82.2% considering all lesions, and 45.0% for dentinal lesions. Significant linear trends (p < .05) among caries levels and categories of exposure were found for socioeconomic variables, dietary habits, and toothbrushing habits. Attending rural private schools (OR = 1.39, 95%CI = 1.11-1.72; p < .01), two main meals/day (OR = 2.75, 95%CI = 1.26-6.03; p = .01) and unsupervised toothbrushing (OR = 3.20, 95%CI = 1.96-5.24; p < .01) increased the risk to have high caries severity levels. M-ECOHIS scores were statistically significant associated with caries levels (χ2 (4)  = 175.85, p < .01; trend across groups z = 12.63 Prob > |z| < 0.01). CONCLUSIONS: M-ECOHIS was significantly associated with caries severity. Type of school, age groups, parents' educational level, family income, and living conditions were correlated with caries, showing how distinctive risk indicators were associated with different caries stages.

Efficacy of an iodoform-based filling material for pulpectomy of primary teeth: A 24-month non-inferiority randomized clinical trial.

AIM: The aim of this non-inferiority randomized clinical trial was to compare the efficacy of an iodoform-based paste (Guedes-Pinto -(GP)) as a filling material in pulpectomies of primary teeth, and a standard material composed by calcium hydroxide and iodoform (CaOH/Iodof paste; Vitapex® ). DESIGN: A total of 104 teeth from 61 children (3-8 years old) were randomly allocated to two groups according to filling materials. Children were followed up for 24 months. The primary endpoint was the treatment success rate evaluated through clinical and radiographic examinations at follow-up, and the secondary outcome was the analysis of the canal filling quality. Differences in the proportion of treatment success was calculated based on 95% confidence intervals (95% CI) and with the Miettinen and Nurminen method in the intention-to-treat population, considering a -20% of the non-inferiority limit. RESULTS: From 104 randomized teeth, 102 were followed up after 24 months (attrition rate of 1.9%). The success rate of teeth treated with the GP paste was 86.8% (95% CI: 69.9-94.9) and 78.4% (95% CI: 61.8-89.1) with the CaOH/Iodof paste. Consequently, a non-inferiority of the GP paste was observed when compared to the CaOH/Iodof paste (P < .001). CONCLUSION: The GP paste has a non-inferior success rate than the CaOH/Iodof paste used as filling material for pulpectomy in primary teeth.

Negligible therapeutic impact, false-positives, overdiagnosis and lead-time are the reasons why radiographs bring more harm than benefits in the caries diagnosis of preschool children.

BACKGROUND: To evaluate the clinical course and interventions required during two years of follow-up of dental surfaces of deciduous molars diagnosed, and consequently treated, by two different strategies: diagnosis made by clinical examination alone or associated with radiographs. METHODS: This is a secondary analysis of a two-arm randomized clinical trial with parallel groups related to the diagnostic strategy for caries detection in preschool children. 216 children (3-6 years old) were followed-up for two years. All dental surfaces were diagnosed by visual inspection and later, through radiographic assessment. Baseline treatment was made in accordance with the results obtained by visual inspection performed alone or combined with radiographic method, considering the allocated group. Dental surfaces with no restoration needs, or those restored at the beginning of the study were followed-up for two years. The treatment decision was made according to the allocated group. The outcome was the occurrence of failure (a new caries lesion or a restoration replacement) during the follow-up. RESULTS: 4383 proximal and occlusal surfaces of deciduous molars in 216 preschool children were diagnosed and treated according to the abovementioned diagnostic strategies and followed-up for 24 months. The assessment of radiographs made change the initial decision reached by visual inspection in about 30% of the surfaces when all types of interventions were considered. However, most disagreements occurred for initial lesions, where radiographs tended to underestimate them. Discordances between methods occurred in less than 5% of all surfaces when considered lesions requiring operative treatment. For discrepancy cases, the placed interventions guided by following the radiographic results did not present less failures against those made following only visual inspection. As a matter of fact, the use of radiographs in the diagnostic strategy for caries detection in children brought more harms than benefits due to the occurrence of false-positives, overdiagnosis and lead-time bias. CONCLUSIONS: Simultaneous association of visual inspection and radiographic assessment for caries detection in preschool children causes more harms than benefits, and therefore, visual inspection should be conducted alone in the regular clinical practice. Trial registration Clinicaltrials.gov platform: NCT02078453, registered on 5th March 2014.

Ultraflat Gold QCM Electrodes Fabricated with Pressure-Forming Template Stripping for Protein Studies at the Nanoscale.

Single-molecule imaging of proteins using atomic force microscopy (AFM) is crucially dependent on protein attachment to ultraflat substrates. The template-stripping (TS) technique, which can be used to create large areas of atomically flat gold, has been used to great effect for this purpose. However, this approach requires an epoxy, which can swell in solution, causing surface roughening and substantially increasing the thickness of any sample, preventing its use on acoustic resonators in liquid. Diffusion bonding techniques should circumvent this problem but cannot be used on samples containing patterned features with mismatched heights because of cracking and poor transfer. Here, we describe a new technique called pressure-forming TS (PTS), which permits an ultraflat (0.35 ± 0.05 nm root-mean-square roughness) layer of gold to be transferred to the surface of a patterned substrate at low temperature and pressure. We demonstrate this technique by modifying a quartz crystal microbalance (QCM) sensor to contain an ultraflat gold surface. Standard QCM chips have substantial roughness, preventing AFM imaging of proteins on the surface after measurement. With our approach, there is no need to run samples in parallel: the modified QCM chip is flat enough to permit high-contrast AFM imaging after adsorption studies have been conducted. The PTS-QCM chips are then used to demonstrate adsorption of bovine serum albumin in comparison to rough QCM chips. The ability to attach thin layers of ultraflat metals to surfaces of heterogeneous nature without epoxy will have many applications in diverse fields where there is a requirement to observe nanoscale phenomena with multiple techniques, including surface and interfacial science, optics, and biosensing.

Impact of the radiographic method on treatment decisions related to dental caries in primary molars: a before-after study.

OBJECTIVES: To evaluate the impact of radiographic examination on changes of treatment decision related to dental caries compared to decisions guided by visual inspection alone in primary molars. MATERIALS AND METHODS: A total of 126 children aged 3-6 years who had sought dental assistance were randomly selected and examined by two calibrated examiners using visual inspection. A treatment plan regarding dental caries was generated based on this assessment. The same examiners then evaluated two bitewing radiographs, creating an additional treatment plan guided by concurrent assessment of both visual and radiographic methods. Occlusal and proximal surfaces of primary molars received a treatment decision as follows: (i) no treatment, (ii) non-operative treatment, and (iii) operative treatment. The frequency of changes in the treatment decision after radiographic examination was calculated, with subsequent Poisson multilevel regression analysis to evaluate variables influencing such changes. RESULTS: Changes from "no treatment" decided with visual inspection to "non-operative treatment" after radiographic evaluation occurred in 52 surfaces (3.2%), and changes to "operative treatment" were observed in 46 dental surfaces (2.8%). Furthermore, 50 surfaces (6.2%) had their treatment decision changed from non-operative to operative treatment after radiographic assessment. In addition, changes were significantly more frequent in children with higher caries experience, on proximal surfaces and in 1st primary molars. CONCLUSIONS: The impact of radiographic examination on changes in the treatment decision of primary molars made with visual inspection is modest. Changes are more frequent in children with higher caries experience and in proximal surfaces. CLINICAL RELEVANCE: The benefits of the radiographic method for detecting caries in children, as a protocol in the diagnostic process, seem to be overestimated; the impact of this method on changes in treatment decision made by visual examination alone is low. Radiographs could be, however, useful in particular conditions, such as in children with high caries experience.

Factors Associated with Surrogate Self-Efficacy in Decision-Making for Patients with End-Stage Renal Disease.

AIM: The aim of the study is to assess which factors are associated with self-efficacy for making these decisions in surrogates of end-stage kidney disease patients. MATERIALS AND METHODS: Cross-sectional study conducted in the hemodialysis clinic of a private hospital in Mexico City. A total of 124 surrogates of patients in hemodialysis were included in the study. Self-efficacy for decision-making was assessed with the Family Decision-Making Self-Efficacy Scale. As factors related to decision-making self-efficacy, sociodemographic data, health information, and professional help received for dealing with end-of-life issues were assessed in both patients and surrogates. Functional status and advanced directives of the patient as well as prior experience in decision-making of the surrogates were also included. Logistic regression models were used to establish the associations. RESULTS: The mean age of participants was 49.4 years (standard deviation: 14). Factors associated to decision-making self-efficacy were awareness of the surrogate about the terminal disease of the patient (P < 0.001), prior conversation between the surrogate and the patient about end-of-life preferences (P = 0.037), time between the patient was told dialysis was required and accepting it inferior to 1 month (P = 0.016), and visual impairment of the patient (0.040). CONCLUSIONS: This study provides information of which factors are associated with self-effectiveness in surrogates of terminally ill renal patients so that strategies based on these considerations might be implemented in the future.

The Influence of Cognitive Bias on Caries Lesion Detection in Preschool Children.

We aimed to evaluate whether children's caries experience exerts an influence on the performance of visual and radiographic methods in detecting nonevident proximal caries lesions in primary molars. Eighty children (3-6 years old) were selected and classified as having a lower (≤3 decayed, missing, or filled surfaces; dmf-s) or higher (> 3 dmf-s) caries experience. Two calibrated examiners then assessed 526 proximal surfaces for caries lesions using visual and radiographic methods. As a reference standard, 2 other examiners checked the surfaces after temporary separation. Noncavitated and cavitated lesion thresholds were considered and Poisson multilevel regression analyses were conducted to evaluate the influence of caries experience on the performance of diagnostic strategies. Accuracy parameters stratified by caries experience were also derived. A statistically significant influence of caries experience was observed only for visual inspection, with more false-positive results in children with a higher caries experience at the noncavitated lesion threshold, and more false results at the cavitated threshold. The detection of noncavitated caries lesions in children with a higher caries experience was overestimated (specificity = 0.696), compared to children with a lower caries experience (specificity = 0.918), probably due to confirmation bias. However, the examiners underestimated the detection of cavitated lesions in children with a higher caries experience (sensitivity = 0.143) compared to lower-caries-experience children (sensitivity = 0.222), possibly because of representativeness bias. The radiographic method was not influenced by children's caries experience. In conclusion, children's caries experience influences the performance of visual inspection in detecting proximal caries lesions in primary teeth, evidencing the occurrence of cognitive biases.

A Reinforcement Learning Model Equipped with Sensors for Generating Perception Patterns: Implementation of a Simulated Air Navigation System Using ADS-B (Automatic Dependent Surveillance-Broadcast) Technology.

Over the last few decades, a number of reinforcement learning techniques have emerged, and different reinforcement learning-based applications have proliferated. However, such techniques tend to specialize in a particular field. This is an obstacle to their generalization and extrapolation to other areas. Besides, neither the reward-punishment (r-p) learning process nor the convergence of results is fast and efficient enough. To address these obstacles, this research proposes a general reinforcement learning model. This model is independent of input and output types and based on general bioinspired principles that help to speed up the learning process. The model is composed of a perception module based on sensors whose specific perceptions are mapped as perception patterns. In this manner, similar perceptions (even if perceived at different positions in the environment) are accounted for by the same perception pattern. Additionally, the model includes a procedure that statistically associates perception-action pattern pairs depending on the positive or negative results output by executing the respective action in response to a particular perception during the learning process. To do this, the model is fitted with a mechanism that reacts positively or negatively to particular sensory stimuli in order to rate results. The model is supplemented by an action module that can be configured depending on the maneuverability of each specific agent. The model has been applied in the air navigation domain, a field with strong safety restrictions, which led us to implement a simulated system equipped with the proposed model. Accordingly, the perception sensors were based on Automatic Dependent Surveillance-Broadcast (ADS-B) technology, which is described in this paper. The results were quite satisfactory, and it outperformed traditional methods existing in the literature with respect to learning reliability and efficiency.

Oral health status of children and young adults with autism spectrum disorders: systematic review and meta-analysis.

BACKGROUND: Individuals with special needs are often affected by oral disorders such as dental caries and periodontal disease. Current data regarding prevalence of these conditions in individuals with autism spectrum disorders (ASD) are controversial. AIM: To conduct a systematic review and meta-analysis to verify the prevalence of dental caries and periodontal disease in individuals with ASD, especially children and young adults. DESIGN: Searches were conducted through MEDLINE/PubMed, Web of Science, and Scopus databases in December 2015. Studies were included if fulfilled the following eligibility criteria: to evaluate the oral health status of individuals with ASD; to be an observational study; and to assess the prevalence of dental caries and/or periodontal disease. Meta-analyses were conducted considering prevalence of dental caries and periodontal disease in individuals as outcome. RESULTS: Search strategy identified 928 potentially relevant articles and seven of them were included in this review. All included studies reported dental caries prevalence, and the pooled prevalence was 60.6% (95% CI: 44.0-75.1). Moreover, only three studies showed prevalence of periodontal disease, resulting in pooled prevalence of 69.4% (95% CI: 47.6-85.0). CONCLUSION: Prevalence of dental caries and periodontal disease in children and young adults with ASD can be considered as high, pointing to the need for oral health policies focused on these individuals.

[Results of the First Mexican Consensus of Vaccination in the Adult]. / Resultados del Primer Consenso Mexicano de Vacunación en el Adulto.

For years our efforts have been focused on vaccination during childhood. Today we know that this is not enough to ensure health in the rest of the life. Childhood is as important as any other stage and, therefore, vaccination must be permanent and differentiated, according to our age, throughout life. Introducing a life course perspective in vaccination programs, with emphasis on adult vaccination, particularly in older adults, offers us the opportunity to review the performance of health programs, actions, and services in the field of immunization, as well as strengthening health promotion actions. In this context, the first Mexican Consensus on Adult Vaccination was carried out in a joint effort of the National Institute of Geriatrics, bringing together a group of specialists who worked on three central objectives: establishing vaccination guidelines throughout the life course, with emphasis on new vaccines; defining priority groups according to their risk factors; and contributing to the effort to promote healthy aging.

[First Mexican Consensus of Vaccination in Adults]. / 1º Consenso Mexicano de Vacunación en el Adulto.

For years our efforts have been focused on vaccination during childhood. Today we know that this is not enough to ensure health in the rest of the life. Childhood is as important as any other stage and, therefore, vaccination must be permanent and differentiated, according to our age, throughout life. Introducing a life course perspective in vaccination programs, with emphasis on adult vaccination, particularly in older adults, offers us the opportunity to review the performance of health programs, actions, and services in the field of immunization, as well as strengthening health promotion actions. In this context, the first Mexican Consensus on Adult Vaccination was carried out in a joint effort of the National Institute of Geriatrics, bringing together a group of specialists who worked on three central objectives: establishing vaccination guidelines throughout the life course, with emphasis on new vaccines; defining priority groups according to their risk factors; and contributing to the effort to promote healthy aging.

Influence of aortic regurgitation after TAVI on left ventricular filling pattern.

BACKGROUND: Paravalvular aortic regurgitation after transcatheter aortic valve implantation is associated with a hemodynamic deterioration and a poor outcome. We aim to determine the early hemodynamic effect of paravalvular aortic regurgitation in relation with the change in the left ventricle filling pattern and to assess their clinical outcome. MATERIAL AND METHODS: Eighty-two consecutive patients referred for transcatheter aortic valve implantation were included. Patients were classified according to the change in the left ventricular filling pattern, and significant paravalvular aortic regurgitation (grade ≥ 2) was reported. Follow-up and incidence of death and hospitalization for heart failure were reported. RESULTS: Sixteen patients (19·5%) presented a worsening of left ventricular filling pattern. The incidence of significant paravalvular aortic regurgitation was higher in the group with a worsening of left ventricular filling pattern (56·3% vs. 19·7%; P = 0·009). In the multivariate analysis, the only variable significantly associated with the worsening of left ventricular filling pattern was the significant paravalvular aortic regurgitation (OR 4·84; 95% CI 1·23 - 19·1; P = 0·024). During the follow-up (642·5 days), there was a higher incidence of the endpoint of death or hospitalization for heart failure in the group with a worsening of left ventricular filling pattern (62·5% vs. 31·8%; P = 0·042) and a lower event-free survival rate (long rank test = 0·013). CONCLUSIONS: The presence of a significant paravalvular aortic regurgitation is associated with a worsening in parameters of diastolic function. This finding should alert the cardiologist as patients with a worsening of left ventricular filling pattern present a higher incidence of paravalvular aortic regurgitation and a less favourable outcome.

Empowering patients through eHealth: a case report of a pan-European project.

BACKGROUND: This paper crystallises the experience developed by the pan-European PALANTE Consortium in dealing with the generation of relevant evidence from heterogeneous eHealth services for patient empowerment in nine European Regions. The European Commission (EC) recently funded a number of pan-European eHealth projects aimed at empowering European patients/citizens thus transforming the traditional patient/citizen role in the management of their health (e.g., PALANTE, SUSTAIN, CARRE, HeartCycle, Empower). However, the heterogeneity of the healthcare systems, of the implemented services and of the target patients, the use of ad-hoc definitions of the salient concepts and the development of small-size experiences have prevented the dissemination of "global" results and the development of cumulative knowledge. The main challenge has been the generation of large-scale evidence from heterogeneous small-size experiences. DISCUSSION: Three lessons have been collectively learnt during the development of the PALANTE project, which involves 9 sites that have implemented different eHealth services for empowering different typologies of patients. These lessons have been refined progressively through project meetings, reviews with the EC Project Officer and Reviewers. The paper illustrates the ten steps followed to develop the three lessons. The first lesson learnt is about how EC-funded projects should develop cumulative knowledge by avoiding self-crafted measures of outcome and by adopting literature-grounded definitions and scales. The second lesson learnt is about how EC-funded projects should identify ambitious, cross-pilot policy and research questions that allow pooling of data from across heterogeneous experiences even if a multi-centre study design was not agreed before. The third lesson learnt is about how EC-funded projects should open their collections of data and make them freely-accessible to the scientific community shortly after the conclusion of the project in order to guarantee the replicability of results and conclusions. SUMMARY: The three lessons might provide original elements for fuelling the ongoing debate about the capability of the EC to develop evidence-based policies by pooling evidence from heterogeneous, local experiences.

A general framework for time series data mining based on event analysis: application to the medical domains of electroencephalography and stabilometry.

There are now domains where information is recorded over a period of time, leading to sequences of data known as time series. In many domains, like medicine, time series analysis requires to focus on certain regions of interest, known as events, rather than analyzing the whole time series. In this paper, we propose a framework for knowledge discovery in both one-dimensional and multidimensional time series containing events. We show how our approach can be used to classify medical time series by means of a process that identifies events in time series, generates time series reference models of representative events and compares two time series by analyzing the events they have in common. We have applied our framework on time series generated in the areas of electroencephalography (EEG) and stabilometry. Framework performance was evaluated in terms of classification accuracy, and the results confirmed that the proposed schema has potential for classifying EEG and stabilometric signals. The proposed framework is useful for discovering knowledge from medical time series containing events, such as stabilometric and electroencephalographic time series. These results would be equally applicable to other medical domains generating iconographic time series, such as, for example, electrocardiography (ECG).