GWAS for executive function and processing speed suggests involvement of the CADM2 gene

To identify common variants contributing to normal variation in two specific domains of cognitive functioning, we conducted a genome-wide association study (GWAS) of executive functioning and information processing speed in non-demented older adults from the CHARGE (Cohorts for Heart and Aging Research in Genomic Epidemiology) consortium. Neuropsychological testing was available for 5429-32 070 subjects of European ancestry aged 45 years or older, free of dementia and clinical stroke at the time of cognitive testing from 20 cohorts in the discovery phase. We analyzed performance on the Trail Making Test parts A and B, the Letter Digit Substitution Test (LDST), the Digit Symbol Substitution Task (DSST), semantic and phonemic fluency tests, and the Stroop Color and Word Test. Replication was sought in 1311-21860 subjects from 20 independent cohorts. A significant association was observed in the discovery cohorts for the single-nucleotide polymorphism (SNP) rs17518584 (discovery P-value=3.12 × 10(-8)) and in the joint discovery and replication meta-analysis (P-value=3.28 × 10(-9) after adjustment for age, gender and education) in an intron of the gene cell adhesion molecule 2 (CADM2) for performance on the LDST/DSST. Rs17518584 is located about 170 kb upstream of the transcription start site of the major transcript for the CADM2 gene, but is within an intron of a variant transcript that includes an alternative first exon. The variant is associated with expression of CADM2 in the cingulate cortex (P-value=4 × 10(-4)). The protein encoded by CADM2 is involved in glutamate signaling (P-value=7.22 × 10(-15)), gamma-aminobutyric acid (GABA) transport (P-value=1.36 × 10(-11)) and neuron cell-cell adhesion (P-value=1.48 × 10(-13)). Our findings suggest that genetic variation in the CADM2 gene is associated with individual differences in information processing speed.Molecular Psychiatry advance online publication, 14 April 2015; doi:10.1038/mp.2015.37

Targeted Next-Generation Sequencing Analysis of 1,000 Individuals with Intellectual Disability.

To identify genetic causes of intellectual disability (ID), we screened a cohort of 986 individuals with moderate to severe ID for variants in 565 known or candidate ID-associated genes using targeted next-generation sequencing. Likely pathogenic rare variants were found in ∼11% of the cases (113 variants in 107/986 individuals: ∼8% of the individuals had a likely pathogenic loss-of-function [LoF] variant, whereas ∼3% had a known pathogenic missense variant). Variants in SETD5, ATRX, CUL4B, MECP2, and ARID1B were the most common causes of ID. This study assessed the value of sequencing a cohort of probands to provide a molecular diagnosis of ID, without the availability of DNA from both parents for de novo sequence analysis. This modeling is clinically relevant as 28% of all UK families with dependent children are single parent households. In conclusion, to diagnose patients with ID in the absence of parental DNA, we recommend investigation of all LoF variants in known genes that cause ID and assessment of a limited list of proven pathogenic missense variants in these genes. This will provide 11% additional diagnostic yield beyond the 10%-15% yield from array CGH alone.Action Medical Research (SP4640); the Birth Defect Foundation (RG45448); the Cambridge National Institute for Health Research Biomedical Research Centre (RG64219); the NIHR Rare Diseases BioResource (RBAG163); Wellcome Trust award WT091310; The Cell lines and DNA bank of Rett Syndrome, X-linked mental retardation and other genetic diseases (member of the Telethon Network of Genetic Biobanks (project no. GTB12001); the Genetic Origins of Congenital Heart Disease Study (GO-CHD)- funded by British Heart Foundation (BHF)This is the final version of the article. It first appeared from Wiley via http://dx.doi.org/10.1002/humu.2290

Prognostic model to predict postoperative acute kidney injury in patients undergoing major gastrointestinal surgery based on a national prospective observational cohort study.

Background: Acute illness, existing co-morbidities and surgical stress response can all contribute to postoperative acute kidney injury (AKI) in patients undergoing major gastrointestinal surgery. The aim of this study was prospectively to develop a pragmatic prognostic model to stratify patients according to risk of developing AKI after major gastrointestinal surgery. Methods: This prospective multicentre cohort study included consecutive adults undergoing elective or emergency gastrointestinal resection, liver resection or stoma reversal in 2-week blocks over a continuous 3-month period. The primary outcome was the rate of AKI within 7 days of surgery. Bootstrap stability was used to select clinically plausible risk factors into the model. Internal model validation was carried out by bootstrap validation. Results: A total of 4544 patients were included across 173 centres in the UK and Ireland. The overall rate of AKI was 14·2 per cent (646 of 4544) and the 30-day mortality rate was 1·8 per cent (84 of 4544). Stage 1 AKI was significantly associated with 30-day mortality (unadjusted odds ratio 7·61, 95 per cent c.i. 4·49 to 12·90; P < 0·001), with increasing odds of death with each AKI stage. Six variables were selected for inclusion in the prognostic model: age, sex, ASA grade, preoperative estimated glomerular filtration rate, planned open surgery and preoperative use of either an angiotensin-converting enzyme inhibitor or an angiotensin receptor blocker. Internal validation demonstrated good model discrimination (c-statistic 0·65). Discussion: Following major gastrointestinal surgery, AKI occurred in one in seven patients. This preoperative prognostic model identified patients at high risk of postoperative AKI. Validation in an independent data set is required to ensure generalizability

Modulation of growth and angiogenic potential of oral squamous carcinoma cells in vitro using salvianolic acid B

<p>Abstract</p> <p>Background</p> <p>Our previous studies showed that Salvianolic acid B (Sal B) inhibited 7,12-dimethylbenz[a]anthracene (DMBA)-induced oral carcinogenesis in hamsters and such anti-cancer effects might be related to the inhibition of angiogenesis. This study was aimed to further investigate the anti-proliferative effect of Sal B on the most common type of oral cancer, oral squamous cell carcinoma (OSCC) and the possible mechanisms of action with respect to angiogenesis inhibition.</p> <p>Methods</p> <p>Two well-characterized oral squamous cell carcinoma cell lines, CAL27 and SCC4, and premalignant leukoplakia cells were treated with different concentrations of Sal B. Cytotoxicity was assessed by MTT assay. cDNA microarray was utilized to evaluate the expression of 96 genes known to be involved in modulating the biological processes of angiogenesis. Real-time reverse transcription-polymerase chain reaction analysis was conducted to confirm the cDNA microarray data.</p> <p>Results</p> <p>Sal B induced growth inhibition in OSCC cell lines but had limited effects on premalignant cells. A total of 17 genes showed a greater than 3-fold change when comparing Sal B treated OSCC cells to the control. Among these genes, HIF-1α, TNFα and MMP9 are specifically inhibited, expression of THBS2 was up-regulated.</p> <p>Conclusions</p> <p>Sal B has inhibitory effect on OSCC cell growth. The antitumor effect can be attributed to anti-angiogenic potential induced by a decreased expression of some key regulator genes of angiogenesis. Sal B may be a promising modality for treating oral squamous cell carcinoma.</p

The Immune Cell Composition in Barrett's Metaplastic Tissue Resembles That in Normal Duodenal Tissue

BACKGROUND AND OBJECTIVE: Barrett's esophagus (BE) is characterized by the transition of squamous epithelium into columnar epithelium with intestinal metaplasia. The increased number and types of immune cells in BE have been indicated to be due to a Th2-type inflammatory process. We tested the alternative hypothesis that the abundance of T-cells in BE is caused by a homing mechanism that is found in the duodenum. PATIENTS AND METHODS: Biopsies from BE and duodenal tissue from 30 BE patients and duodenal tissue from 18 controls were characterized by immmunohistochemistry for the presence of T-cells and eosinophils(eos). Ex vivo expanded T-cells were further phenotyped by multicolor analysis using flowcytometry. RESULTS: The high percentage of CD4(+)-T cells (69±3% (mean±SEM/n = 17, by flowcytometry)), measured by flowcytometry and immunohistochemistry, and the presence of non-activated eosinophils found in BE by immunohistochemical staining, were not different from that found in duodenal tissue. Expanded lymphocytes from these tissues had a similar phenotype, characterized by a comparable but low percentage of αE(CD103) positive CD4(+)cells (44±5% in BE, 43±4% in duodenum of BE and 34±7% in duodenum of controls) and a similar percentage of granzyme-B(+)CD8(+) cells(44±5% in BE, 33±6% in duodenum of BE and 36±7% in duodenum of controls). In addition, a similar percentage of α4β7(+) T-lymphocytes (63±5% in BE, 58±5% in duodenum of BE and 62±8% in duodenum of controls) was found. Finally, mRNA expression of the ligand for α4β7, MAdCAM-1, was also similar in BE and duodenal tissue. No evidence for a Th2-response was found as almost no IL-4(+)-T-cells were seen. CONCLUSION: The immune cell composition (lymphocytes and eosinophils) and expression of intestinal adhesion molecule MAdCAM-1 is similar in BE and duodenum. This supports the hypothesis that homing of lymphocytes to BE tissue is mainly caused by intestinal homing signals rather than to an active inflammatory response

Effect of telemedicine follow-up care of leg and foot ulcers: a systematic review

BACKGROUND: Leg ulcers and diabetes-related foot ulcers are frequent and costly complications of their underlying diseases and thus represent a critical issue for public health. Since the population is aging, the prevalence of these conditions will probably increase considerably and require more resources. Treatment of leg and foot ulcers often demands frequent contact with the health care system, may pose great burden on the patient, and involves follow-up in both primary and specialist care. Telemedicine provides potential for more effective care management of leg and foot ulcers. The objective of this systematic review of the literature was to assess the effect of telemedicine follow-up care on clinical, behavioral or organizational outcomes among patients with leg and foot ulcers. METHODS: We searched Ovid MEDLINE (1980–), Ovid EMBASE (1980–), Clinical Trials in the Cochrane Library (via Wiley), Ebsco CINAHL with Fulltext (1981–) and SveMed + (1977–) up to May 2014 for relevant articles. We considered randomized controlled trials, non-randomized trials, controlled before-after studies and prospective cohort studies for inclusion and selected studies according to predefined criteria. Three reviewers independently assessed the included studies using the Cochrane Collaboration risk-of-bias tool. We performed a narrative synthesis of results and assessed the strength of evidence for each outcome using GRADE (grading of recommendations, assessment, development and evaluation). RESULTS: Only one non-randomized study was included. The study (n = 140) measured the effect of real-time interactive video consultation compared with face-to-face follow-up on healing time, adjusted healing ratio and the number of ulcers at 12 weeks among patients with neuropathic forefoot ulcerations. There were no statistically significant differences in results of the different outcomes between patients receiving telemedicine and traditional follow-up. We assessed the study to have a high risk of bias. CONCLUSIONS: There is insufficient evidence available to unambiguously determine whether telemedicine consultation of leg and foot ulcers is as effective as traditional follow-up

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. Ann Assoc Am Geogr 93(3):595–623. https://doi.org/10.1111/1467-8306.9303005Atkinson P, Massari R (1998) Generalised linear modelling of susceptibility to landsliding in the central Apennines, Italy. Comput Geosci 24(4):373–385. https://doi.org/10.1016/S0098-3004(97)00117-9Ayalew L, Yamagishi H (2005) The application of GIS-based logistic regression for landslide susceptibility mapping in the Kakuda-Yahiko Mountains, Central Japan. Geomorphology 65(1–2):15–31. https://doi.org/10.1016/j.geomorph.2004.06.010Baeza C, Lantada N, Amorim S (2016) Statistical and spatial analysis of landslide susceptibility maps with different classification systems. Environ Earth Science 75:1318. https://doi.org/10.1007/s12665-016-6124-1Basofi A, Fariza A, Ahsan AS, Kamal IM (2015) A comparison between natural and head/tail breaks in LSI (landslide susceptibility index) classification for landslide susceptibility mapping: a case study in Ponorogo, East Java, Indonesia. 2015 International Conference on Science in Information Technology, pp 337–342Cantarino I (2013) Elaboración y validación de un modelo jerárquico derivado de SIOSE. Revista de Teledetección 39:5–21Carrara A, Crosta GB, Frattini P (2008) Comparing models of debris-flow susceptibility in the alpine environment. Geomorphology 94(3–4):353–378. https://doi.org/10.1016/j.geomorph.2006.10.033Chacón J, Irigaray C, Fernández T, El Hamdouni R (2006) Engineering geology maps: landslides and geographical information systems. Bull Eng Geol Environ 65(4):341–411Chung CJF, Fabbri AG (2003) Validation of spatial prediction models for landslide hazard mapping. Nat Hazards 30:451–472COPUT (1998) Lithology, exploitation of industrial rocks and landslide risk in the Valencian Community. Thematic Mapping Series. Department of Public Works of the Valencian Regional GovernmentDrummond C, Holte RC (2006) Cost curves: an improved method for visualizing classifier performance. Mach Learn 65(1):95–130Duman TY, Can T, Gokceoglu C, Nefeslioglu HA, Sonmez H (2006) Application of logistic regression for landslide susceptibility zoning of Cekmece Area, Istanbul, Turkey. Environ Geol 51(2):241–256. https://doi.org/10.1007/s00254-006-0322-1Evans IS (1977) The selection of class intervals. Transactions of the Institute of British Geographers. Contemp Cartograph 2(1):98–124. https://doi.org/10.2307/622195Fleiss JL, Levin B, Paik MC (2003) Statistical methods for rates and proportions, Book Series: Wiley Series in Probability and Statistics. John Wiley & Sons. Print ISBN: 9780471526292. doi: https://doi.org/10.1002/0471445428Foody GM (2004) Thematic map comparison: evaluating the statistical significance of differences in classification accuracy. Photogramm Eng Remote Sens 70(5):627–633Fotheringham AS, Brunsdon C, Charlton M (2000) Quantitative geography: perspectives on spatial data analysis. SAGE Publications, Thousand Oaks 270 ppFrattini P, Crosta G, Carrara A (2010) Techniques for evaluating the performance of landslide susceptibility models. Eng Geol 111(1–4):62–72. https://doi.org/10.1016/j.enggeo.2009.12.004Geisser S (1998) Comparing two tests used for diagnostic or screening processes. Stat Probability Lett 40:113–119Greiner M, Pfeiffer D, Smith RD (2000) Principles and practical application of the receiver-operating characteristic analysis for diagnostic tests. Prev Vet Med 45:23–41Günther A, Reichenbach P, Malet JP, van den Eeckhaut M, Hervás J, Dashwood C, Guzzetti F (2013) Tier-based approaches for landslide susceptibility assessment in Europe. Landslides 10:529–546. https://doi.org/10.1007/s10346-012-0349-1Günther A, Van Den Eeckhaut M, Malet J-P, Reichenbach P, Hervás J (2014) Climate-physiographically differentiated Pan-European landslide susceptibility assessment using spatial multi-criteria evaluation and transnational landslide information. Geomorphology 224:69–85Gupta RP, Kanungo DP, Arora MK, Sarkar S (2008) Approaches for comparative evaluation of raster GIS-based landslide susceptibility zonation maps. Int J Appl Earth Obs Geoinf 10(3):330–341. https://doi.org/10.1016/j.jag.2008.01.003Guzzetti F, Reichenbach P, Ardizzone F, Cardinali M, Galli M (2006) Estimating the quality of landslide susceptibility models. Geomorphology 81(1–2):166–184. https://doi.org/10.1016/j.geomorph.2006.04.007Hervás J (2017) El inventario de movimientos de ladera de España ALISSA: Metodología y análisis preliminar. In: Alonso E, Corominas J, Hürlimann M (Eds.), Taludes 2017. Proc. IX Simposio Nacional sobre Taludes y Laderas Inestables, Santander, 27–30 June 2017. CIMNE, Barcelona, pp. 629–639Jaedicke C, Van Den Eeckhaut M, Nadim F et al (2014) Identification of landslide hazard and risk ‘hotspots’ in Europe. Bull Eng Geol Environ 73:325. https://doi.org/10.1007/s10064-013-0541-0Jenks GF (1967) The data model concept in statistical mapping. Int Yearbook Cartograph 7:186–190Jiang B (2013) Head/tail breaks: a new classification scheme for data with a heavy-tailed distribution. Prof Geogr 65(3):482–494. https://doi.org/10.1080/00330124.2012.700499Kiang MY (2003) A comparative assessment of classification methods. Decis Support Syst 35(4):441–454. https://doi.org/10.1016/S0167-9236(02)00110-0Landis JR, Koch GG (1977) The measurement of observer agreement for categorical data. Biometrics 33(1):159–174Langping L, Hengxing L, Changbao G, Yongshuang Z, Quanwen L, Yuming W (2017) A modified frequency ratio method for landslide susceptibility assessment. Landslides 14:727–741. https://doi.org/10.1007/s10346-016-0771-xLee S (2007) Comparison of landslide susceptibility maps generated through multiple logistic regression for three test areas in Korea. Earth Surf Process Landforms 32:2133–2148. https://doi.org/10.1002/esp.1517Liu C, Frazier P, Kumar L (2007) Comparative assessment of the measures of thematic classification accuracy. Remote Sens Environ 107(4):606–616. https://doi.org/10.1016/j.rse.2006.10.010López-Ratón M, Rodríguez-Álvarez MX, Cadarso-Suárez C, Gude-Sampedro F (2014) Optimal cutpoints: an R package for selecting optimal cutpoints in diagnostic tests. J Stat Softw 61(8):4Malet JP, Puissant A, Mathieu A, Van Den Eeckhaut M, Fressard M (2013) Integrating spatial multi-criteria evaluation and expert knowledge for country-scale landslide susceptibility analysis: application to France. In: Margottini C, Canuti P, Sassa K (eds) Landslide science and practice. Springer, Berlin. https://doi.org/10.1007/978-3-642-31325-7_40McGee S (2002) Simplifying likelihood ratios. J Gen Intern Med 17:647–650Metz C (1978) Basic principles of ROC analysis. Semin Nucl Med VIII(4):183–198Nadim F, Kjekstad O, Peduzzi P, Herold C, Jaedicke C (2006) Global landslide and avalanche hotspots. Landslides 3:159–173. https://doi.org/10.1007/s10346-006-0036-1Ohlmacher G, Davis J (2003) Using multiple logistic regression and GIS technology to predict landslide hazard in northeast Kansas, USA. Eng Geol 69(3–4):331–343. https://doi.org/10.1016/S0013-7952(03)00069-3Powell RL, Matzke N, de Souza C Jr, Clark M, Numata I, Hess LL, Roberts DA (2004) Sources of error accuracy assessment of thematic land-cover maps in the Brazilian Amazon. Remote Sens Environ 90(2):221–234. https://doi.org/10.1016/j.rse.2003.12.007Saaty T (1980) The analytic hierarchy process. McGraw Hill, New YorkSmits PC, Dellepiane SG, Schowengerdt RA (1999) Quality assessment of image classification algorithms for land-cover mapping: a review and proposal for a cost-based approach. Int J Remote Sens 20:1461–1486Stehman SV, Czaplewski RL (1998) Design and analysis of thematic map accuracy assessment: fundamental principles. Remote Sens Environ 64:331–344Swets JA (1988) Measuring the accuracy of diagnostic systems. Science 240(4857):1285–1293Van Den Eeckhaut M, Hervás J, Jaedicke C, Malet J-P, Montanarella L, Nadim F (2012) Statistical modelling of Europe-wide landslide susceptibility using limited landslide inventory data. Landslides 8:357–369Varnes DJ (1984) Landslide hazard zonation: a review of principles and practice. Natural hazards. UNESCO, ParisZhu X (2016) GIS for environmental applications. Routledge, Abingdon, p 490Zweig MH, Campbell G (1993) Receiver-operating characteristic (ROC) plots: a fundamental evaluation tool in clinical medicine. Clin Chem 39(4):561–57