Application of association rules to determine building typological classes for seismic damage predictions at regional scale. The case study of Basel

Assessing seismic vulnerability at large scales requires accurate attribution of individual buildings to more general typological classes that are representative of the seismic behavior of the buildings sharing same attributes. One-by-one evaluation of all buildings is a time-and-money demanding process. Detailed individual evaluations are only suitable for strategic buildings, such as hospitals and other buildings with a central role in the emergency post-earthquake phase. For other buildings simplified approaches are needed. The definition of a taxonomy that contains the most widespread typological classes as well as performing the attribution of the appropriate class to each building are central issues for reliable seismic assessment at large scales. A fast, yet accurate, survey process is needed to attribute a correct class to each building composing the urban system. Even surveying buildings with the goal to determine classes is not as time demanding as detailed evaluations of each building, this process still requires large amounts of time and qualified personnel. However, nowadays several databases are available and provide useful information. In this paper, attributes that are available in such public databases are used to perform class attribution at large scales based on previous data-mining on a small subset of an entire city. The association-rule learning (ARL) is used to find links between building attributes and typological classes. Accuracy of wide spreading these links learned on <250 buildings of a specific district is evaluated in terms of class attribution and seismic vulnerability prediction. By considering only three attributes available on public databases (i.e., period of construction, number of floors, and shape of the roof) the time needed to provide seismic vulnerability scenarios at city scale is significantly reduced, while accuracy is reduced by <5%

Identification of three novel Toxoplasma gondii rhoptry proteins

The rhoptries are key secretory organelles from apicomplexan parasites that contain proteins involved in invasion and modulation of the host cell. Some rhoptry proteins are restricted to the posterior bulb (ROPs) and others to the anterior neck (RONs). As many rhoptry proteins have been shown to be key players in Toxoplasma invasion and virulence, it is important to identify, understand and characterise the biological function of the components of the rhoptries. In this report, we identified putative novel rhoptry genes by identifying Toxoplasma genes with similar cyclical expression profiles as known rhoptry protein encoding genes. Using this approach we identified two new rhoptry bulb (ROP47 and ROP48) and one new rhoptry neck protein (RON12). ROP47 is secreted and traffics to the host cell nucleus, RON12 was not detected at the moving junction during invasion. Deletion of ROP47 or ROP48 in a type II strain did not show major influence in in vitro growth or virulence in mice.United States. National Institutes of Health (R01-AI080621

Neighbourhood cohesion and mental wellbeing among older adults:A mixed methods approach

There is now a body of evidence that demonstrates strong links between neighbourhood characteristics and mental health and wellbeing. There is an increasing interest in how this relationship varies for individuals of different ages. Understanding the link between neighbourhood and wellbeing for older adults is of particular significance, given the changing age structure of the population and the desire among policy makers and practitioners to promote healthy and active ageing. This paper provides further evidence on the nature and strength of the link between individual perceptions of neighbourhood belonging and mental wellbeing among those over age fifty using both qualitative and quantitative data from three British cohort studies. Between 2008 and 2011 quantitative data were collected from 10,312 cohort members, and 230 of them took part in qualitative biographical interviews.Quantitative analysis confirms that there is a moderate association between neighbourhood cohesion and wellbeing measured at the individual level in each of the three cohorts. This association persists after controlling for a range of covariates including personality. The association between neighbourhood cohesion and wellbeing is stronger for individuals in the older two cohorts than in the younger cohort.Using qualitative biographical interviews with 116 men and 114 women we illustrate how individuals talk about their sense of neighbourhood belonging. The importance of social participation as a mechanism for promoting neighbourhood belonging, and the use of age and life stage as characteristics to describe and define neighbours, is clear. In addition, the qualitative interviews point to the difficulties of using a short battery of questions to capture the varied and multi-dimensional nature of neighbourhood relations.<br/

Inhibition of voltage-gated sodium channels by sumatriptan bioisosteres

Voltage-gated sodium channels are known to play a pivotal role in perception and transmission of pain sensations. Gain-of-function mutations in the genes encoding the peripheral neuronal sodium channels, hNav1.7-1.9, cause human painful diseases. Thus while treatment of chronic pain remains an unmet clinical need, sodium channel blockers are considered as promising druggable targets. In a previous study, we evaluated the analgesic activity of sumatriptan, an agonist of serotonin 5HT1B/D receptors, and some new chiral bioisosteres, using the hot plate test in the mouse. Interestingly, we observed that the analgesic effectiveness was not necessarily correlated to serotonin agonism. In this study, we evaluated whether sumatriptan and its congeners may inhibit heterologously expressed hNav1.7 sodium channels using the patch-clamp method. We show that sumatriptan blocks hNav1.7 channels only at very high, supratherapeutic concentrations. In contrast, its three analogs, namely 20b, (R)-31b, and (S)-22b, exert a dose and use-dependent sodium channel block. At 0.1 and 10 Hz stimulation frequencies, the most potent compound, (S)-22b, was 4.4 and 1.7 fold more potent than the well-known sodium channel blocker mexiletine. The compound induces a negative shift of voltage dependence of fast inactivation, suggesting higher affinity to the inactivated channel. Accordingly, we show that (S)-22b likely binds the conserved local anesthetic receptor within voltage-gated sodium channels. Combining these results with the previous ones, we hypothesize that use-dependent sodium channel blockade contributes to the analgesic activity of (R)-31b and (S)-22b. These later compounds represent promising lead compounds for the development of efficient analgesics, the mechanism of action of which may include a dual action on sodium channels and 5HT1D receptors

A Griscelli syndrome type 2 murine model of hemophagocytic lymphohistiocytosis (HLH)

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Translational approach to address therapy in myotonia permanens due to a new SCN4A mutation

Objective: We performed a clinical, functional, and pharmacologic characterization of the novel p.P1158L Nav1.4 mutation identified in a young girl presenting a severe myotonic phenotype. Methods: Wild-type hNav1.4 channel and P1158L mutant were expressed in tsA201 cells for functional and pharmacologic studies using patch-clamp. Results: The patient shows pronounced myotonia, slowness of movements, and generalized muscle hypertrophy. Because of general discomfort with mexiletine, she was given flecainide with satisfactory response. In vitro, mutant channels show a slower current decay and a rightward shift of the voltage dependence of fast inactivation. The voltage dependence of activation and slow inactivation were not altered. Mutant channels were less sensitive to mexiletine, whereas sensitivity to flecainide was not altered. The reduced inhibition of mutant channels by mexiletine was also observed using clinically relevant drug concentrations in a myotonic-like condition. Conclusions: Clinical phenotype and functional alterations of P1158L support the diagnosis of myotonia permanens. Impairment of fast inactivation is consistent with the possible role of the channel domain III S4-S5 loop in the inactivation gate docking site. The reduced sensitivity of P1158L to mexiletine may have contributed to the unsatisfactory response of the patient. The success of flecainide therapy underscores the usefulness of in vitro functional studies to help in the choice of the best drug for each individual

Visual vs Fully Automatic Histogram-Based Assessment of Idiopathic Pulmonary Fibrosis (IPF) Progression Using Sequential Multidetector Computed Tomography (MDCT)

Objectives To describe changes over time in extent of idiopathic pulmonary fibrosis (IPF) at multidetector computed tomography (MDCT) assessed by semi-quantitative visual scores (VSs) and fully automatic histogram-based quantitative evaluation and to test the relationship between these two methods of quantification. Methods Forty IPF patients (median age: 70 y, interquartile: 62-75 years;M:F, 33: 7) that underwent 2 MDCT at different time points with a median interval of 13 months (interquartile: 10-17 months) were retrospectively evaluated. In-house software YACTA quantified automatically lung density histogram (10th-90th percentile in 5th percentile steps). Longitudinal changes in VSs and in the percentiles of attenuation histogram were obtained in 20 untreated patients and 20 patients treated with pirfenidone. Pearson correlation analysis was used to test the relationship between VSs and selected percentiles. Results In follow-up MDCT, visual overall extent of parenchymal abnormalities (OE) increased in median by 5 %/year (interquartile: 0 %/y;+11 %/y). Substantial difference was found between treated and untreated patients in HU changes of the 40th and of the 80th percentiles of density histogram. Correlation analysis between VSs and selected percentiles showed higher correlation between the changes (Delta) in OE and Delta 40th percentile (r=0.69;p<0.001) as compared to Delta 80th percentile (r=0.58;p<0.001);closer correlation was found between Delta ground-glass extent and Delta 40th percentile (r=0.66, p<0.001) as compared to Delta 80th percentile (r=0.47, p=0.002),while the Delta reticulations correlated better with the Delta 80th percentile (r=0.56, p<0.001) in comparison to Delta 40th percentile (r=0.43, p=0.003). Conclusions There is a relevant and fully automatically measurable difference at MDCT in VSs and in histogram analysis at one year follow-up of IPF patients, whether treated or untreated: Delta 40th percentile might reflect the change in overall extent of lung abnormalities, notably of ground-glass pattern;furthermore Delta 80th percentile might reveal the course of reticular opacities

Visual vs Fully Automatic Histogram-Based Assessment of Idiopathic Pulmonary Fibrosis (IPF) Progression Using Sequential Multidetector Computed Tomography (MDCT)

Objectives To describe changes over time in extent of idiopathic pulmonary fibrosis (IPF) at multidetector computed tomography (MDCT) assessed by semi-quantitative visual scores (VSs) and fully automatic histogram-based quantitative evaluation and to test the relationship between these two methods of quantification. Methods Forty IPF patients (median age: 70 y, interquartile: 62-75 years;M:F, 33: 7) that underwent 2 MDCT at different time points with a median interval of 13 months (interquartile: 10-17 months) were retrospectively evaluated. In-house software YACTA quantified automatically lung density histogram (10th-90th percentile in 5th percentile steps). Longitudinal changes in VSs and in the percentiles of attenuation histogram were obtained in 20 untreated patients and 20 patients treated with pirfenidone. Pearson correlation analysis was used to test the relationship between VSs and selected percentiles. Results In follow-up MDCT, visual overall extent of parenchymal abnormalities (OE) increased in median by 5 %/year (interquartile: 0 %/y;+11 %/y). Substantial difference was found between treated and untreated patients in HU changes of the 40th and of the 80th percentiles of density histogram. Correlation analysis between VSs and selected percentiles showed higher correlation between the changes (Delta) in OE and Delta 40th percentile (r=0.69;p<0.001) as compared to Delta 80th percentile (r=0.58;p<0.001);closer correlation was found between Delta ground-glass extent and Delta 40th percentile (r=0.66, p<0.001) as compared to Delta 80th percentile (r=0.47, p=0.002),while the Delta reticulations correlated better with the Delta 80th percentile (r=0.56, p<0.001) in comparison to Delta 40th percentile (r=0.43, p=0.003). Conclusions There is a relevant and fully automatically measurable difference at MDCT in VSs and in histogram analysis at one year follow-up of IPF patients, whether treated or untreated: Delta 40th percentile might reflect the change in overall extent of lung abnormalities, notably of ground-glass pattern;furthermore Delta 80th percentile might reveal the course of reticular opacities