Background: Recent advances in automation technologies have enabled the use of flow cytometry for high throughput screening, generating large complex data sets often in clinical trials or drug discovery settings. However, data management and data analysis methods have not advanced sufficiently far from the initial small-scale studies to support modeling in the presence of multiple covariates.

Background-Valvular heart disease (VHD), which often leads to atrial fibrillation (AF), and AF both cause ion-channel remodeling. We evaluated the ion-channel gene expression profile of VHD patients, in permanent AF (AF-VHD) or in sinus rhythm (SR-VHD), in comparison with patients without AF or VHD, respectively. Methods and Results-We used microarrays containing probes for human ion-channel and Ca 2ϩ -regulator genes to quantify mRNA expression in atrial tissues from 7 SR-VHD patients and 11 AF-VHD patients relative to 11 control patients in SR without structural heart disease (SR-CAD). From the data set, we selected for detailed analysis 59 transcripts expressed in the human heart. SR-VHD patients differentially expressed 24/59 ion-channel and Ca 2ϩ -regulator transcripts. There was significant overlap between VHD groups, with 66% of genes altered in SR-VHD patients being similarly modified in AF-VHD. Statistical differences between the AF-and SR-VHD groups identified the specific molecular portrait of AF, which involved 12 genes that were further confirmed by real-time reverse transcription-polymerase chain reaction. For example, phospholamban, the ␤-subunit MinK (KCNE1) and MIRP2 (KCNE3), and the 2-pore potassium channel TWIK-1 were upregulated in AF-VHD compared with SR-VHD, whereas the T-type calcium-channel Cav3.1 and the transient-outward potassium channel Kv4.3 were downregulated. Two-way hierarchical clustering separated SR-VHD from AF-VHD patients. AF-related changes in L-type Ca 2ϩ -current and inward-rectifier current were confirmed at protein and functional levels. Finally, for 13 selected genes, SR restoration reversed ion-channel remodeling. Conclusions-VHD

SummaryTo investigate regulatory processes and protective mechanisms leading to desiccation tolerance (DT) in seeds, 16086-element microarrays were used to monitor changes in the transcriptome of desiccation-sensitive 3-mmlong radicles of Medicago truncatula seeds at different time points during incubation in a polyethylene glycol (PEG) solution at )1.7 MPa, resulting in a gradual re-establishment of DT. Gene profiling was also performed on embryos before and after the acquisition of DT during maturation. More than 1300 genes were differentially expressed during the PEG incubation. A large number of genes involved in C metabolism are expressed during the re-establishment of DT. Quantification of C reserves confirms that lipids, starch and oligosaccharides were mobilised, coinciding with the production of sucrose during the early osmotic adjustment. Several clusters of gene profiles were identified with different time-scales. Genes expressed early during the PEG incubation belonged to classes involved in early stress and adaptation responses. Interestingly, several regulatory genes typically expressed during abiotic/drought stresses were also upregulated during maturation, arguing for the partial overlap of ABA-dependent and -independent regulatory pathways involved in both drought and DT. At later time points, in parallel to the re-establishment of DT, upregulated genes are comparable with those involved in late seed maturation. Concomitantly, a massive repression of genes belonging to numerous classes occurred, including cell cycle, biogenesis, primary and energy metabolism. The re-establishment of DT in the germinated radicles appears to concur with a partial return to the quiescent state prior to germination.

IntroductionIn order to study social health inequalities, contextual (or ecologic) data may constitute an appropriate alternative to individual socioeconomic characteristics. Indices can be used to summarize the multiple dimensions of the neighborhood socioeconomic status. This work proposes a statistical procedure to create a neighborhood socioeconomic index.MethodsThe study setting is composed of three French urban areas. Socioeconomic data at the census block scale come from the 1999 census. Successive principal components analyses are used to select variables and create the index. Both metropolitan area-specific and global indices are tested and compared. Socioeconomic categories are drawn with hierarchical clustering as a reference to determine “optimal” thresholds able to create categories along a one-dimensional index.ResultsAmong the twenty variables finally selected in the index, 15 are common to the three metropolitan areas. The index explains at least 57% of the variance of these variables in each metropolitan area, with a contribution of more than 80% of the 15 common variables.ConclusionsThe proposed procedure is statistically justified and robust. It can be applied to multiple geographical areas or socioeconomic variables and provides meaningful information to public health bodies. We highlight the importance of the classification method. We propose an R package in order to use this procedure.

Abstract-Gene-expression changes in atrial fibrillation patients reflect both underlying heart-disease substrates and changes because of atrial fibrillation-induced atrial-tachycardia remodeling. These are difficult to separate in clinical investigations. This study assessed time-dependent mRNA expression-changes in canine models of atrial-tachycardia remodeling and congestive heart failure. Five experimental groups (5 dogs/group) were submitted to atrial (ATP, 400 bpm ϫ24 hours, 1 or 6 weeks) or ventricular (VTP, 240 bpm ϫ24 hours or 2 weeks) tachypacing. The expression of Ϸ21,700 transcripts was analyzed by microarray in isolated left-atrial cardiomyocytes and (for 18 genes) by real-time RT-PCR. Protein-expression changes were assessed by Western blot. In VTP, a large number of significant mRNA-expression changes occurred after both 24 hours (2209) and 2 weeks (2720). In ATP, fewer changes occurred at 24 hours (242) and fewer still (87) at 1 week, with no statistically-significant alterations at 6 weeks. Expression changes in VTP varied over time in complex ways. Extracellular matrix-related transcripts were strongly upregulated by VTP consistent with its pathophysiology, with 8 collagen-genes upregulated Ͼ10-fold, fibrillin-1 8-fold and MMP2 4.5-fold at 2 weeks (time of fibrosis) but unchanged at 24 hours. Other extracellular matrix genes (eg, fibronectin, lysine oxidase-like 2) increased at both time-points (Ϸ10, Ϸ5-fold respectively). In ATP, mRNA-changes almost exclusively represented downregulation and were quantitatively smaller. This study shows that VTP-induced congestive heart failure and ATP produce qualitatively different temporally-evolving patterns of gene-expression change, and that specific transcriptomal responses associated with atrial fibrillation versus underlying heart disease substrates must be considered in assessing gene-expression changes in man. Key Words: arrhythmia Ⅲ remodeling Ⅲ genomic A trial fibrillation (AF) is the most common sustained cardiac rhythm disorder, and with the aging of the population both the prevalence and economic impact of AF are increasing progressively. 1 Although the mechanistic basis of AF remains incompletely understood, active research promises to provide new insights that may lead to improved therapeutic options. 2,3 A variety of animal models have been used to assess AF pathophysiology under controlled conditions. Atrial tachyarrhythmias, including AF itself, alter atrial electrophysiology in ways that promote AF vulnerability. [4][5][6] Experimentally-induced congestive heart failure (CHF) also creates a substrate for AF maintenance, but by quite different mechanisms. 7 The atrial-tachycardia remodeling paradigm shows prominent changes in ion-channel function that lead to action-potential abbreviation and the promotion of atrial reentry. 8,9 CHF-induced ionic-current changes do not promote reentry but may favor ectopic-impulse formation, 10 and CHF-induced fibrosis promotes reentry by interfering with intraatrial conduction. 7 The molecular basis of AF ...

BackgroundPregnant women are a vulnerable population. Although regular follow-ups are recommended during pregnancy, not all pregnant women seek care. This pilot study wanted to assess whether the integration of data from administrative health information systems and socio-economic features allows identifying disparities in prenatal care trajectories.MethodsPrenatal care trajectories were extracted from the permanent sample of the French health insurance information system linked to the hospital discharge information system. The records of 2518 women who gave birth without complications in France in 2009 were analyzed. State sequence data analysis was performed to identify homogeneous groups of prenatal care trajectories. Socio-economic data were used to characterize their living environment.ResultsWe identified three groups of homogeneous prenatal care trajectories: (i) women with relatively high prenatal care consumption (~11 %), (ii) women with no prenatal care (~21 %), and (iii) women with an intermediate level of prenatal care (~66 %). Analysis of the socio-economic data demonstrated the association between disparities in prenatal care trajectories and the women’s living environment. Women with relatively high care consumption generally lived in socio-economically privileged areas (better education levels, employment status and housing conditions) compared with women with few or no prenatal care.ConclusionsAlthough ecological, our approach demonstrates that data from health administrative information systems could be used to describe prenatal care. However, more individual variables and an improvement of the data quality are needed to efficiently monitor the content and timing of prenatal care. Moreover, state sequence analysis, which was used in this context for the first time, proves to be an interesting approach to explore care trajectories. Finally, the integration of heterogeneous sources of data, including contextual information, might help identifying areas that require health promotion actions toward vulnerable populations, such as pregnant women.Electronic supplementary materialThe online version of this article (doi:10.1186/s12913-015-0857-5) contains supplementary material, which is available to authorized users.

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Background This study aimed to investigate overall and sex-specific excess all-cause mortality since the inception of the COVID-19 pandemic until August 2020 among 22 countries. Methods Countries reported weekly or monthly all-cause mortality from January 2015 until the end of June or August 2020. Weekly or monthly COVID-19 deaths were reported for 2020. Excess mortality for 2020 was calculated by comparing weekly or monthly 2020 mortality (observed deaths) against a baseline mortality obtained from 2015–2019 data for the same week or month using two methods: (i) difference in observed mortality rates between 2020 and the 2015–2019 average and (ii) difference between observed and expected 2020 deaths. Results Brazil, France, Italy, Spain, Sweden, the UK (England, Wales, Northern Ireland and Scotland) and the USA demonstrated excess all-cause mortality, whereas Australia, Denmark and Georgia experienced a decrease in all-cause mortality. Israel, Ukraine and Ireland demonstrated sex-specific changes in all-cause mortality. Conclusions All-cause mortality up to August 2020 was higher than in previous years in some, but not all, participating countries. Geographical location and seasonality of each country, as well as the prompt application of high-stringency control measures, may explain the observed variability in mortality changes.