The clinical significance of serum and bronchoalveolar lavage inflammatory cytokines in patients at risk for Acute Respiratory Distress Syndrome

BACKGROUND: The predictive role of many cytokines has not been well defined in Acute Respiratory Distress Syndrome (ARDS). METHODS: We measured prospectively IL-4, IL-6, IL-6 receptor, IL-8, and IL-10, in the serum and bronchoalveolar lavage fluid (BALF) in 59 patients who were admitted to ICU in order to identify predictive factors for the course and outcome of ARDS. The patients were divided into three groups: those fulfilling the criteria for ARDS (n = 20, group A), those at risk for ARDS and developed ARDS within 48 hours (n = 12, group B), and those at risk for ARDS but never developed ARDS (n = 27, group C). RESULTS: An excellent negative predictive value for ARDS development was found for IL-6 in BALF and serum (100% and 95%, respectively). IL-8 in BALF and IL-8 and IL-10 serum levels were higher in non-survivors in all studied groups, and were associated with a high negative predictive value. A significant correlation was found between IL-8 and APACHE score (r = 0.60, p < 0.0001). Similarly, IL-6 and IL-6r were highly correlated with PaO2/FiO2 (r = -0.27, p < 0.05 and r = -0.55, p < 0.0001, respectively). CONCLUSIONS: BALF and serum levels of the studied cytokines on admission may provide valuable information for ARDS development in patients at risk, and outcome in patients either in ARDS or in at risk for ARDS

A ROC analysis-based classification method for landslide susceptibility maps

[EN] A landslide susceptibility map is a crucial tool for landuse spatial planning and management in mountainous areas. An essential issue in such maps is the determination of susceptibility thresholds. To this end, the map is zoned into a limited number of classes. Adopting one classification system or another will not only affect the map's readability and final appearance, but most importantly, it may affect the decision-making tasks required for effective land management. The present study compares and evaluates the reliability of some of the most commonly used classification methods, applied to a susceptibility map produced for the area of La Marina (Alicante, Spain). A new classification method based on ROC analysis is proposed, which extracts all the useful information from the initial dataset (terrain characteristics and landslide inventory) and includes, for the first time, the concept of misclassification costs. This process yields a more objective differentiation of susceptibility levels that relies less on the intrinsic structure of the terrain characteristics. The results reveal a considerable difference between the classification methods used to define the most susceptible zones (in over 20% of the surface) and highlight the need to establish a standard method for producing classified susceptibility maps. The method proposed in the study is particularly notable for its consistency, stability and homogeneity, and may mark the starting point for consensus on a generalisable classification method.Cantarino-Martí, I.; Carrión Carmona, MÁ.; Goerlich-Gisbert, F.; Martínez Ibáñez, V. (2018). A ROC analysis-based classification method for landslide susceptibility maps. Landslides. 1-18. doi:10.1007/s10346-018-1063-4S118Armstrong MP, Xiao N, Bennett DA (2003) Using genetic algorithms to create multicriteria class intervals for choropleth maps. 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Demonstration of Protein-Based Human Identification Using the Hair Shaft Proteome

YesHuman identification from biological material is largely dependent on the ability to characterize genetic polymorphisms in DNA. Unfortunately, DNA can degrade in the environment, sometimes below the level at which it can be amplified by PCR. Protein however is chemically more robust than DNA and can persist for longer periods. Protein also contains genetic variation in the form of single amino acid polymorphisms. These can be used to infer the status of non-synonymous single nucleotide polymorphism alleles. To demonstrate this, we used mass spectrometry-based shotgun proteomics to characterize hair shaft proteins in 66 European-American subjects. A total of 596 single nucleotide polymorphism alleles were correctly imputed in 32 loci from 22 genes of subjects’ DNA and directly validated using Sanger sequencing. Estimates of the probability of resulting individual non-synonymous single nucleotide polymorphism allelic profiles in the European population, using the product rule, resulted in a maximum power of discrimination of 1 in 12,500. Imputed non-synonymous single nucleotide polymorphism profiles from European–American subjects were considerably less frequent in the African population (maximum likelihood ratio = 11,000). The converse was true for hair shafts collected from an additional 10 subjects with African ancestry, where some profiles were more frequent in the African population. Genetically variant peptides were also identified in hair shaft datasets from six archaeological skeletal remains (up to 260 years old). This study demonstrates that quantifiable measures of identity discrimination and biogeographic background can be obtained from detecting genetically variant peptides in hair shaft protein, including hair from bioarchaeological contexts.The Technology Commercialization Innovation Program (Contracts #121668, #132043) of the Utah Governors Office of Commercial Development, the Scholarship Activitie

Whole Transcriptome Sequencing Reveals Gene Expression and Splicing Differences in Brain Regions Affected by Alzheimer's Disease

Recent studies strongly indicate that aberrations in the control of gene expression might contribute to the initiation and progression of Alzheimer's disease (AD). In particular, alternative splicing has been suggested to play a role in spontaneous cases of AD. Previous transcriptome profiling of AD models and patient samples using microarrays delivered conflicting results. This study provides, for the first time, transcriptomic analysis for distinct regions of the AD brain using RNA-Seq next-generation sequencing technology. Illumina RNA-Seq analysis was used to survey transcriptome profiles from total brain, frontal and temporal lobe of healthy and AD post-mortem tissue. We quantified gene expression levels, splicing isoforms and alternative transcript start sites. Gene Ontology term enrichment analysis revealed an overrepresentation of genes associated with a neuron's cytological structure and synapse function in AD brain samples. Analysis of the temporal lobe with the Cufflinks tool revealed that transcriptional isoforms of the apolipoprotein E gene, APOE-001, -002 and -005, are under the control of different promoters in normal and AD brain tissue. We also observed differing expression levels of APOE-001 and -002 splice variants in the AD temporal lobe. Our results indicate that alternative splicing and promoter usage of the APOE gene in AD brain tissue might reflect the progression of neurodegeneration

A rapid screening tool for psychological distress in children 3--6years old: results of a validation study.

International audienceABSTRACT: BACKGROUND: The mental health needs of young children in humanitarian contexts often remain unaddressed. The lack of a validated, rapid and simple tool for screening combined with few mental health professionals able to accurately diagnose and provide appropriate care mean that young children remain without care. Here, we present the results of the principle cross-cultural validation of the "Psychological Screening for Young Children aged 3 to 6" (PSYCAa3-6). The PSYCa 3--6 is a simple scale for children 3 to 6 years old administered by non-specialists, to screen young children in crises and thereby refer them to care if needed. METHODS: This study was conducted in Maradi, Niger. The scale was translated into Hausa, using corroboration of independent translations. A cross-cultural validation was implemented using quantitative and qualitative methods. A random sample of 580 mothers or caregivers of children 3 to 6 years old were included. The tool was psychometrically examined and diagnostic properties were assessed comparing the PSYCa 3--6 against a clinical interview as the gold standard. RESULTS: The PSYCa 3--6 Hausa version demonstrated good concurrent validity, as scores correlated with the gold standard and the Clinical Global Impression Severity Scale (CGI-S) [rho = 0.41, p-value = 0.00]. A reduction procedure was used to reduce the scale from 40 to 22 items. The test-retest reliability of the PSYCa 3--6 was found to be high (ICC 0.81, CI95% [0.68; 0.89]). In our sample, although not the purpose of this study, approximately 54 of 580 children required subsequent follow-up with a psychologist. CONCLUSIONS: To our knowledge, this is the first validation of a screening scale for children 3 to 6 years old with a cross-cultural validation component, for use in humanitarian contexts. The Hausa version of the PSYCa 3--6 is a reliable and a valuable screening tool for psychological distress. Further studies to replicate our findings and additional validations of the PSYCa 3--6 in other populations may help improve the delivery of mental health care to children

Altered Connectivity Pattern of Hubs in Default-Mode Network with Alzheimer's Disease: An Granger Causality Modeling Approach

Background: Evidences from normal subjects suggest that the default-mode network (DMN) has posterior cingulate cortex (PCC), medial prefrontal cortex (MPFC) and inferior parietal cortex (IPC) as its hubs; meanwhile, these DMN nodes are often found to be abnormally recruited in Alzheimer’s disease (AD) patients. The issues on how these hubs interact to each other, with the rest nodes of the DMN and the altered pattern of hubs with respect to AD, are still on going discussion for eventual final clarification. Principal Findings: To address these issues, we investigated the causal influences between any pair of nodes within the DMN using Granger causality analysis and graph-theoretic methods on resting-state fMRI data of 12 young subjects, 16 old normal controls and 15 AD patients respectively. We found that: (1) PCC/MPFC/IPC, especially the PCC, showed the widest and distinctive causal effects on the DMN dynamics in young group; (2) the pattern of DMN hubs was abnormal in AD patients compared to old control: MPFC and IPC had obvious causal interaction disruption with other nodes; the PCC showed outstanding performance for it was the only region having causal relation with all other nodes significantly; (3) the altered relation between hubs and other DMN nodes held potential as a noninvasive biomarker of AD. Conclusions: Our study, to the best of our knowledge, is the first to support the hub configuration of the DMN from the perspective of causal relationship, and reveal abnormal pattern of the DMN hubs in AD. Findings from young subject

A user's guide to the Encyclopedia of DNA elements (ENCODE)

The mission of the Encyclopedia of DNA Elements (ENCODE) Project is to enable the scientific and medical communities to interpret the human genome sequence and apply it to understand human biology and improve health. The ENCODE Consortium is integrating multiple technologies and approaches in a collective effort to discover and define the functional elements encoded in the human genome, including genes, transcripts, and transcriptional regulatory regions, together with their attendant chromatin states and DNA methylation patterns. In the process, standards to ensure high-quality data have been implemented, and novel algorithms have been developed to facilitate analysis. Data and derived results are made available through a freely accessible database. Here we provide an overview of the project and the resources it is generating and illustrate the application of ENCODE data to interpret the human genome