Whole-genome association analysis of treatment response in obsessive-compulsive disorder.

Up to 30% of patients with obsessive-compulsive disorder (OCD) exhibit an inadequate response to serotonin reuptake inhibitors (SRIs). To date, genetic predictors of OCD treatment response have not been systematically investigated using genome-wide association study (GWAS). To identify specific genetic variations potentially influencing SRI response, we conducted a GWAS study in 804 OCD patients with information on SRI response. SRI response was classified as 'response' (n=514) or 'non-response' (n=290), based on self-report. We used the more powerful Quasi-Likelihood Score Test (the MQLS test) to conduct a genome-wide association test correcting for relatedness, and then used an adjusted logistic model to evaluate the effect size of the variants in probands. The top single-nucleotide polymorphism (SNP) was rs17162912 (P=1.76 × 10(-8)), which is near the DISP1 gene on 1q41-q42, a microdeletion region implicated in neurological development. The other six SNPs showing suggestive evidence of association (P<10(-5)) were rs9303380, rs12437601, rs16988159, rs7676822, rs1911877 and rs723815. Among them, two SNPs in strong linkage disequilibrium, rs7676822 and rs1911877, located near the PCDH10 gene, gave P-values of 2.86 × 10(-6) and 8.41 × 10(-6), respectively. The other 35 variations with signals of potential significance (P<10(-4)) involve multiple genes expressed in the brain, including GRIN2B, PCDH10 and GPC6. Our enrichment analysis indicated suggestive roles of genes in the glutamatergic neurotransmission system (false discovery rate (FDR)=0.0097) and the serotonergic system (FDR=0.0213). Although the results presented may provide new insights into genetic mechanisms underlying treatment response in OCD, studies with larger sample sizes and detailed information on drug dosage and treatment duration are needed

A Decision Support Tool for the Selection of Promoting Actions to Encourage Collaboration in Projects for the Agriculture Sector

[EN] Development and innovation agencies promote consortiums of agricultural stakeholders to collaborate in the proposal of projects for public calls. To achieve this partnerships, these agencies should select between different promoting actions to be performed with two objectives: maximize the number of project proposals presented and minimize the resources invested. To support agencies with these decisions, a computer tool based on a multi-objective integer linear programming model is proposed. To deal with the two objectives the weighting sum method is implemented. The model is validated in different scenarios by means a realistic case of an agency in Brittany (France). The results show the conflict between the two objectives considered and the dependency of the solutions on the scenarios defined. As a conclusion it can be stated that: 1) decision-makers should be careful in defining the weights of each objective and 2) the impact of the different promoting actions on the level of stakeholders¿ participation should be precisely estimated.The authors acknowledge the support of the project 691249, RUCAPS: "Enhancing and implementing knowledge based ICT solutions within high risk and uncertain conditions for agriculture production systems", funded by the European Union¿s research and innovation programme under the H2020 Marie Sk¿odowska-Curie Actions.Alemany Díaz, MDM.; Alarcón Valero, F.; Pérez Perales, D.; Guyon, C. (2020). A Decision Support Tool for the Selection of Promoting Actions to Encourage Collaboration in Projects for the Agriculture Sector. IFIP Advances in Information and Communication Technology. 598:534-545. https://doi.org/10.1007/978-3-030-62412-5_44S534545598European Comission Funded Programs. https://ec.europa.eu/programmes/horizon2020Zoie, C., Radulescu, M.: Decision analysis for the project selection problem under risk. IFAC Proc. 34(8), 445–450 (2001)Sadi-Nezhad, S.: A state-of-art survey on project selection using MCDM techniques. J. Project Manage. 2, 1–10 (2017)Caballero, H.C., Chopra, S., Schmidt, E.K.: Project portfolio selection using mathematical programming and optimization methods. In: Paper presented at PMI® Global Congress 2012–North America, Vancouver, British Columbia, Canada, Newtown Square, PA, Project Management Institute (2012)Ahmad, B., Haq, I.: Project selection techniques, relevance and applications in Pakistan. Int. J. Technol. Res. 4, 52–60 (2016)Inuiguchi, M., Ramı́k, J.: Possibilistic linear programming: a brief review of fuzzy mathematical programming and a comparison with stochastic programming in portfolio selection problem. Fuzzy Sets Syst. 111(1), 3–28 (2000)Stewart, R., Mohamed, S.: IT/IS projects selection using multi-criteria utility theory. Log. Inf. Manage. 15(4), 254–270 (2002)Alzober, W., Yaakub, A.R.: Integrated model for MCDM: selection contractor in Malaysian construction industry. In: Applied Mechanics and Materials 548, pp. 1587–1595. Trans Tech Publications (2014)Adhikary, P., Roy, P.K., Mazumdar, A.: Optimal renewable energy project selection: a multi-criteria optimization technique approach. Global J. Pure Appl. Math. 11(5), 3319–3329 (2015)Strang, K.D.: Portfolio selection methodology for a nuclear project. Project Manage. J. 42(2), 81–93 (2011)Benjamin, C.O.: A linear goal-programming model for public-sector project selection. J. Oper. Res. Soc. 36(1), 13–23 (1985)Coronado, J.R., Pardo-Mora, E.M., Valero, M.: A multi-objective model for selection of projects to finance new enterprise SMEs in Colombia. J. Ind. Eng. Manage. 4(3), 407–417 (2011)Mat, N.A.C., Cheung, Y.: Partner selection: criteria for successful collaborative network. In: 20th Australian Conference on Information Systems, pp. 631–641 (2009)Camarinha-Matos, L.M., Afsarmanesh, H.: Collaborative Networks. In: Wang, K., Kovacs, G.L., Wozny, M., Fang, M. (eds.) PROLAMAT 2006. IIFIP, vol. 207, pp. 26–40. Springer, Boston, MA (2006). https://doi.org/10.1007/0-387-34403-9_4Paixão, M., Sbragia, R., Kruglianskas, I.: Factors for selecting partners in innovation projects–evidences from alliances in the Brazilian petrochemical leader. Rev. Admin. Innov. São Paulo 11(2), 241–272 (2014)Duisters, D., Duysters, G., de Man, A.P.: The partner selection process: steps, effectiveness, governance. Ann. Hematol. 2, 7–25 (2011)Zhang, X.: Criteria for selecting the private-sector partner in public-private partnerships. J. Constr. Eng. Manage. 131(6), 631–644 (2005

Genome-wide association study in obsessive-compulsive disorder: results from the OCGAS.

Obsessive-compulsive disorder (OCD) is a psychiatric condition characterized by intrusive thoughts and urges and repetitive, intentional behaviors that cause significant distress and impair functioning. The OCD Collaborative Genetics Association Study (OCGAS) is comprised of comprehensively assessed OCD patients with an early age of OCD onset. After application of a stringent quality control protocol, a total of 1065 families (containing 1406 patients with OCD), combined with population-based samples (resulting in a total sample of 5061 individuals), were studied. An integrative analyses pipeline was utilized, involving association testing at single-nucleotide polymorphism (SNP) and gene levels (via a hybrid approach that allowed for combined analyses of the family- and population-based data). The smallest P-value was observed for a marker on chromosome 9 (near PTPRD, P=4.13 × 10(-)(7)). Pre-synaptic PTPRD promotes the differentiation of glutamatergic synapses and interacts with SLITRK3. Together, both proteins selectively regulate the development of inhibitory GABAergic synapses. Although no SNPs were identified as associated with OCD at genome-wide significance level, follow-up analyses of genome-wide association study (GWAS) signals from a previously published OCD study identified significant enrichment (P=0.0176). Secondary analyses of high-confidence interaction partners of DLGAP1 and GRIK2 (both showing evidence for association in our follow-up and the original GWAS study) revealed a trend of association (P=0.075) for a set of genes such as NEUROD6, SV2A, GRIA4, SLC1A2 and PTPRD. Analyses at the gene level revealed association of IQCK and C16orf88 (both P<1 × 10(-)(6), experiment-wide significant), as well as OFCC1 (P=6.29 × 10(-)(5)). The suggestive findings in this study await replication in larger samples

Why do poor adults rate their oral health poorly?

The document attached has been archived with permission from the Australian Dental Association. An external link to the publisher’s copy is included.Background: The reasons why socioeconomic circumstances are associated with oral health are not well understood. This study investigated whether psychosocial factors might play an explanatory role. Methods: Cross-sectional survey data were used from the 1999 National Dental Telephone Interview Survey together with information from an accompanying questionnaire sent to adult interviewees. Household income and self-rated oral health were assessed with single items and life dissatisfaction, personal constraint and perceived stress were evaluated with standard psychometric scales. Bivariate associations were tested using chisquare and ANOVA and odds ratios estimated for low self-rated oral health using logistic regression. Results: Response to the questionnaire was 64.6 per cent and analysis was limited to dentate adults (n=3678). Low household income was positively associated with low self-rated oral health. Higher dissatisfaction with life, personal constraint and perceived stress scores were associated with low income and with low self-rated oral health. After adjusting for gender, age, income and missing teeth, adults with high personal constraint scores had greater odds of low self-rated oral health (OR 1.26; 1.10-1.43) as had adults with higher perceived stress scores (OR 1.69; 1.34-2.13). Conclusion: Psychosocial factors are important in understanding pathways between socioeconomic position and oral health status.A.E. Sanders and A.J. Spence

Quasi-Normal Modes of Stars and Black Holes

Perturbations of stars and black holes have been one of the main topics of relativistic astrophysics for the last few decades. They are of particular importance today, because of their relevance to gravitational wave astronomy. In this review we present the theory of quasi-normal modes of compact objects from both the mathematical and astrophysical points of view. The discussion includes perturbations of black holes (Schwarzschild, Reissner-Nordstr\"om, Kerr and Kerr-Newman) and relativistic stars (non-rotating and slowly-rotating). The properties of the various families of quasi-normal modes are described, and numerical techniques for calculating quasi-normal modes reviewed. The successes, as well as the limits, of perturbation theory are presented, and its role in the emerging era of numerical relativity and supercomputers is discussed.Comment: 74 pages, 7 figures, Review article for "Living Reviews in Relativity

Tree migration-rates : narrowing the gap between inferred post-glacial rates and projected rates

Faster-than-expected post-glacial migration rates of trees have puzzled ecologists for a long time. In Europe, post-glacial migration is assumed to have started from the three southern European peninsulas (southern refugia), where large areas remained free of permafrost and ice at the peak of the last glaciation. However, increasing palaeobotanical evidence for the presence of isolated tree populations in more northerly microrefugia has started to change this perception. Here we use the Northern Eurasian Plant Macrofossil Database and palaeoecological literature to show that post-glacial migration rates for trees may have been substantially lower (60–260 m yr–1) than those estimated by assuming migration from southern refugia only (115–550 m yr–1), and that early-successional trees migrated faster than mid- and late-successional trees. Post-glacial migration rates are in good agreement with those recently projected for the future with a population dynamical forest succession and dispersal model, mainly for early-successional trees and under optimal conditions. Although migration estimates presented here may be conservative because of our assumption of uniform dispersal, tree migration-rates clearly need reconsideration. We suggest that small outlier populations may be a key factor in understanding past migration rates and in predicting potential future range-shifts. The importance of outlier populations in the past may have an analogy in the future, as many tree species have been planted beyond their natural ranges, with a more beneficial microclimate than their regional surroundings. Therefore, climate-change-induced range-shifts in the future might well be influenced by such microrefugia

Fluid-structure interaction simulation of prosthetic aortic valves : comparison between immersed boundary and arbitrary Lagrangian-Eulerian techniques for the mesh representation

In recent years the role of FSI (fluid-structure interaction) simulations in the analysis of the fluid-mechanics of heart valves is becoming more and more important, being able to capture the interaction between the blood and both the surrounding biological tissues and the valve itself. When setting up an FSI simulation, several choices have to be made to select the most suitable approach for the case of interest: in particular, to simulate flexible leaflet cardiac valves, the type of discretization of the fluid domain is crucial, which can be described with an ALE (Arbitrary Lagrangian-Eulerian) or an Eulerian formulation. The majority of the reported 3D heart valve FSI simulations are performed with the Eulerian formulation, allowing for large deformations of the domains without compromising the quality of the fluid grid. Nevertheless, it is known that the ALE-FSI approach guarantees more accurate results at the interface between the solid and the fluid. The goal of this paper is to describe the same aortic valve model in the two cases, comparing the performances of an ALE-based FSI solution and an Eulerian-based FSI approach. After a first simplified 2D case, the aortic geometry was considered in a full 3D set-up. The model was kept as similar as possible in the two settings, to better compare the simulations' outcomes. Although for the 2D case the differences were unsubstantial, in our experience the performance of a full 3D ALE-FSI simulation was significantly limited by the technical problems and requirements inherent to the ALE formulation, mainly related to the mesh motion and deformation of the fluid domain. As a secondary outcome of this work, it is important to point out that the choice of the solver also influenced the reliability of the final results

External beam irradiation of myocardial carcinoid metastases: a case report

The heart is an exceedingly rare site of metastatic involvement in carcinoid tumors. Only nineteen cases have been described in the literature over the past 30 years. We report here on a patient who presented with progressive carcinoid syndrome despite surgical resection of her liver metastases. She was found to have cardiac metastases on inidium-111-pentetreotide scintigraphy and subsequently underwent external beam radiation to the heart resulting in symptomatic palliation of her syndrome and objective radiographic response. To our knowledge, this is the first reported case of metastatic cardiac carcinoid treated with external beam irradiation