15 research outputs found
Meta-analyses identify 13 loci associated with age at menopause and highlight DNA repair and immune pathways
No full textTo newly identify loci for age at natural menopause, we carried out a meta-analysis of 22 genome-wide association studies (GWAS) in 38,968 women of European descent, with replication in up to 14,435 women. In addition to four known loci, we identified 13 loci newly associated with age at natural menopause (at P < 5 × 10(-8)). Candidate genes located at these newly associated loci include genes implicated in DNA repair (EXO1, HELQ, UIMC1, FAM175A, FANCI, TLK1, POLG and PRIM1) and immune function (IL11, NLRP11 and PRRC2A (also known as BAT2)). Gene-set enrichment pathway analyses using the full GWAS data set identified exoDNase, NF-κB signaling and mitochondrial dysfunction as biological processes related to timing of menopause
Trypanosomatids are common and diverse parasites of Drosophila
No full textDrosophila melanogaster is an important model system of immunity and parasite resistance, yet most studies use parasites that do not naturally infect this organism. We have studied trypanosomatids in natural populations to assess the prevalence and diversity of these gut parasites. We collected several species of Drosophila from Europe and surveyed them for trypanosomatids using conserved primers for two genes. We have used the conserved GAPDH sequence to construct a phylogenetic tree and the highly variable spliced leader RNA to assay genetic diversity. All 5 of the species that we examined were infected, and the average prevalence ranged from 1 to 6%. There are several different groups of trypanosomatids, related to other monoxenous Trypanosomatidae. These may represent new trypanosomatid species and were found in different species of European Drosophila from different geographical locations. The detection of a little studied natural pathogen in D. melanogaster and related species provides new opportunities for research into both the Drosophila immune response and the evolution of hosts and parasites.</p
Life is Cheap: Using Mortality Bonds to Hedge Aggregate Mortality Risk
No full textUsing the widely-cited Lee-Carter mortality model, we quantify aggregate mortality risk as the risk that the average annuitant lives longer than is predicted by the model, and we conclude that annuity business exposes insurance companies to substantial mortality risk. We calculate that a markup of 3.7% on an annuity premium (or else shareholders%u2019 capital equal to 3.7% of the expected present value of annuity payments) would reduce the probability of insolvency resulting from uncertain aggregate mortality trends to 5% and a markup of 5.4% would reduce the probability of insolvency to 1%. Using the same model, we find that a projection scale commonly referred to by the insurance industry underestimates aggregate mortality improvements. Annuities that are priced on that projection scale without any conservative margin appear to be substantially underpriced. Insurance companies could deal with aggregate mortality risk by transferring it to financial markets through mortality-contingent bonds, one of which has recently been offered. We calculate the returns that investors would have obtained on such bonds had they been available over a long period. Using both the Capital and the Consumption Capital Asset Pricing Models, we determine the risk premium that investors would have required on such bonds. At plausible coefficients of risk aversion, annuity providers should be able to hedge aggregate mortality risk via such bonds at a very low cost.
EVOLUTIONARY GENETICS: CONCEPTS AND CASE STUDIES
No full textContributors -- Pt. I. Principles of evolutionary genetics -- 1. From Mendel to molecules: a brief history of evolutionary genetics / Michael R. Dietrich -- 2. Genetic variation / Marta L. Wayne and Michael M. Miyamoto -- Box 2.1. Maternal effects / Timothy A. Mousseau -- 3. Maturation / David Houle and Alexey Kondrashov -- 4. Natural selection / Michael J. Wade -- Box 4.1. Defining and measuring fitness / Daphne J. Fairbairn -- 5. Stochastic processes in evolution / John H. Gillespie -- Box 5.1. The probability of extinction of an allele -- Box 5.2. Mutational landscape model -- 6. Genetics and evolution in structured populations / Charles J. Goodnight -- Box 6.1. Epistasis and the conversion of genetic variance / Jason B. Wolf -- 7. Detecting selection at the molecular level / Michael W. Nachman -- 8. Rates of molecular evolution / Francisco Rodríguez-Trelles, Rosa Tarrío and Francisco J. Ayala -- Box 8.1. Timing evolutionary events with a molecular clock -- Box 8.2. Testing the hypothesis of the molecular clock -- 9. Weak selection on noncoding gene features / Ying Chen and Wolfgang Stephan -- 10. Evolution of eukaryotic genome structure / Dmitri A. Petrov and Jonathan F. Wendel -- 11. New genes, new functions: gene family evolution and phylogenetics / Joe Thornton -- 12. Gene genealogies / Noah A. Rosenberg -- Box 12.1. Horizontal inheritance -- Pt. III. From genotype to phenotype -- 13. Gene function and molecular evolution / Simon C. Lovell -- Box 13.1. The role of gene interaction networks in evolution / Stephen R. Proulx -- 14. Evolution of multidomain proteins / László Patthy -- 15. Evolutionary developmental bioethics / David L. Stern -- Box 15.1. Hox genes -- Box 15.2. Functional assays in nonmodel organisms -- 16. Canalization / Mark L. Siegal and Aviv Bergman -- Box 16.1. Computational modeling of the evolution of gene regulatory networks -- 17. Evolutionary epigenetics / Eva Jablonka and Marion J. Lamb -- Pt. IV. Quantitative genetics and selection -- 18. Evolutionary quantitative genetics / Derek A. Roff -- Box 18.1. Individual fitness surfaces and multivariate selection / Jason B. Wolf -- 19. Genetic architecture of quantitative variation / James M. Cheverud -- Box 19.1. Genotypic values: additivity, dominance, and epistasis -- Box 19.2. Genic values and genetic variances -- Box 19.3. How to perform a QTL analysis -- Box 19.4. Evolutionary morphometrics / Christian Peter Klingenberg -- Box 19.5. Modularity / Jason G. Mezey -- 20. Evolution of genetic variance-covariance structure / Patrick C. Phillips and Katrina L. McGuigan -- Box 20.1. What is a covariance? -- Box 20.2. Pleiotropic effects -- Box 20.3. Evolution of the G matrix -- 21. Genotype-environment interactions and evolution / Samuel M. Scheiner -- 22. Genetics of sexual selection / Allen J. Moore and Patricia J. Moore -- 23. Social selection / Steven A. Frank -- Box 23.1. Coefficients of relatedness -- Pt. V. Genetics of speciation -- Box. Species concepts / James Mallet -- 24. The evolution of reproductive isolating barriers / Norman A. Johnson -- 25. Genetics of reproductive isolation and species differences in model organisms / Pawel Michalak and Mohamed A.F. Noor -- Box 25.1. The Dobzhansky-Muller model -- 26. Natural hyrbridization / Michael L. Arnold and John M. Burke -- Box 26.1. Potential outcomes of natural hybridization -- 27. Population bottlenecks and founder effects / Lisa Marie Meffert -- Box 27.1. Models of the shifts in selection pressures experienced by bottlenecked populations -- 28. Theory of phylogenetic estimation / Ashley N. Egan and Keith A. Crandall -- Box 28.1. Philosophical and methodological differences in phylogenetics -- 29. Evolutionary genetics of host-parasite interactions / Paula X. Kover -- Box 29.1. The coevolutionary consequences of tolerance versus resistance -- Box 29.2. Arabidopis as a model organism in evolutionary genetics / Kentara K. Shimizu and Michael D. Puruggaman -- Box 29.3. Evolution of virulence -- 30. The evolutionary genetics of senescence / Daniel E.L. Promislow and Anne M. Bronikowski -- Box 30.1. Demography of an age-structured population -- Box 30.2. Drosophila as a model organism in evolutionary biology / Jeffrey R. Powell -- 31. Experimental evolution / Adam K. Chippindale -- Box 31.1. E. coli as a model organism in evolutionary genetics / Richard E. Lenski -- 32. Evolutionary conservation genetics / Richard Frankham -- Glossary -- References -- Inde
Pulmonary arterial hypertension associated with abatacept treatment for rheumatoid arthritis: A case report
No full textImpact of a structured referral algorithm on the ability to monitor adherence to appropriate use criteria for transthoracic echocardiography
No full textAbstract
Background
Many free-form-text referral requisitions for transthoracic echocardiography (TTE) provide insufficient information to adequately evaluate their adherence to Appropriate Use Criteria (AUC). We developed a structured referral requisition algorithm based on requisition deficiencies identified retrospectively in a derivation cohort of 1303 TTE referrals and evaluated the performance of the algorithm in a consecutive series of cardiology outpatient referrals.
Methods
The validation cohort comprised 286 consecutive TTE outpatient cardiology referrals over a 2-week period. The relevant AUC indication was identified from information extracted from the free-form-text requisition. The structured referral algorithm was applied prospectively to the same cohort using information from the free-form-text requisition, electronic medical record and ordering clinicians. Referrals were classified as appropriate, uncertain, non-adherent (inappropriate) or unclassifiable based on the American College of Cardiology Foundation 2011 AUC.
Results
Only 28.7 % of free-form-text requisitions provided adequate information to identify the relevant AUC indication, as compared to 94.4 % of referrals using the structured referral algorithm (p < 0.001). The structured algorithm improved identification in the AUC categories of general evaluation of cardiac structure/function (100 % vs. 43.0 %, p < 0.001); valvular function (100 % vs. 23.0 %, p < 0.001); hypertension, heart failure or cardiomyopathy (100 % vs. 20.3 %, p < 0.001); and adult congenital heart disease (100 % vs. 0 %, p < 0.001). By applying the algorithm, the number of identifiable non-adherent studies increased from 2.6 to 10.4 % (p <0.001).
Conclusions
Use of a structured TTE referral algorithm, as opposed to a free-form-text requisition, allowed the vast majority of referrals to be monitored for AUC adherence and facilitated the identification of potentially inappropriate referrals
Happiness and sex difference in life expectancy
No full textThis paper examines the effects of happiness on the sex gap in life expectancy. Utilizing a cross-country data set, it first inspects the reverse effect of the life expectancy gap on happiness and demonstrates that the life expectancy gap negatively affects happiness through the composition of marital status. Taking this reverse causality into account, it shows that happiness is significant on explaining the differences in the life expectancy gap between countries. As national average happiness increases, the sex difference in life expectancy decreases. This is consistent with the findings that psychological stress (unhappiness)adversely affects survival and that the effect of psychological stress on mortality is more severe for men. This result provides an indirect evidence that happiness affects survival even at the national aggregate level.economic and social development, life expectancy
Vitamins and bone health: Beyond calcium and vitamin D
No full textOsteoporosis is a major health disorder associated with an increased risk of fracture. Nutrition is among the modifiable factors that influence the risk of osteoporosis and fracture. Calcium and vitamin D play important roles in improving bone mineral density and reducing the risk of fracture. Other vitamins appear to play a role in bone health as well. In this review, the findings of studies that related the intake and-or the status of vitamins other than vitamin D to bone health in animals and humans are summarized. Studies of vitamin A showed inconsistent results. Excessive, as well as insufficient, levels of retinol intake may be associated with compromised bone health. Deficiencies in vitamin B, along with the consequent elevated homocysteine level, are associated with bone loss, decreased bone strength, and increased risk of fracture. Deficiencies in vitamins C, E, and K are also associated with compromised bone health; this effect may be modified by smoking, estrogen use or hormonal therapy after menopause, calcium intake, and vitamin D. These findings highlight the importance of adequate nutrition in preserving bone mass and reducing the risk of osteoporosis and fractures. © 2011 International Life Sciences Institute.Abrahamsen B, 2003, J BONE MINER RES, V18, P723, DOI 10.1359-jbmr.2003.18.4.723; Anderson JJB, 1996, J NUTR, V126, pS1153; Baines M, 2007, BONE, V40, P730, DOI 10.1016-j.bone.2006.10.008; Baron JA, 2001, ARCH INTERN MED, V161, P983, DOI 10.1001-archinte.161.7.983; Basu S, 2001, BIOCHEM BIOPH RES CO, V288, P275, DOI 10.1006-bbrc.2001.5747; Binkley N, 2009, J BONE MINER RES, V24, P983, DOI [10.1359-jbmr.081254, 10.1359-JBMR.081254]; Bode MK, 2000, ATHEROSCLEROSIS, V152, P531, DOI 10.1016-S0021-9150(00)00548-7; Bolton-Smith C, 2007, J BONE MINER RES, V22, P509, DOI 10.1359-JBMR.070116; Bonjour JP, 1997, J CLIN INVEST, V99, P1287, DOI 10.1172-JCI119287; Booth SL, 2000, AM J CLIN NUTR, V71, P1201; Braam LAJLM, 2003, CALCIFIED TISSUE INT, V73, P21, DOI 10.1007-s00223-002-2084-4; Cagnacci A, 2003, BONE, V33, P956, DOI 10.1016-j.bone.2003.07.001; CARMEL R, 1988, NEW ENGL J MED, V319, P70, DOI 10.1056-NEJM198807143190202; CHAN D, 1990, BIOCHEM J, V269, P175; CHEUNG AM, 2008, PLOS MED, V5; CHO DY, 1975, AM J VET RES, V36, P1597; Cockayne S, 2006, ARCH INTERN MED, V166, P1256, DOI 10.1001-archinte.166.12.1256; de Bree A, 2005, EUR J CLIN NUTR, V59, P480, DOI 10.1038-sj.ejcn.1602097; DHEM A, 1984, FOOD CHEM TOXICOL, V22, P199, DOI 10.1016-0278-6915(84)90127-3; Dhonukshe-Rutten RAM, 2005, J BONE MINER RES, V20, P921, DOI 10.1359-JBMR.050202; Dhonukshe-Rutten RAM, 2003, J NUTR, V133, P801; DICKSON I, 1985, BIOCHEM J, V226, P789; Fairfield KM, 2002, JAMA-J AM MED ASSOC, V287, P3116, DOI 10.1001-jama.287.23.3116; FELL HB, 1956, BR MED B, V121, P35; Feskanich D, 1999, AM J CLIN NUTR, V69, P74; Feskanich D, 2002, JAMA-J AM MED ASSOC, V287, P47, DOI 10.1001-jama.287.1.47; FRANKEL TL, 1986, J NUTR, V116, P578; FUJII K, 1979, FEBS LETT, V97, P193, DOI 10.1016-0014-5793(79)80082-4; Gallo A M, 1996, Pediatr Nurs, V22, P369; Garett IR, 1990, J CLIN INVEST, V85, P632, DOI DOI 10.1172-JCI114485; GEELEN JAG, 1979, CRC CR REV TOXICOL, V6, P351, DOI 10.3109-10408447909043651; Golbahar J, 2004, BONE, V35, P760, DOI 10.1016-j.bone.2004.04.018; Hall SL, 1998, CALCIFIED TISSUE INT, V63, P183, DOI 10.1007-s002239900512; HART JP, 1985, J CLIN ENDOCR METAB, V60, P1268; HERMANN M, 2005, CLIN CHEM LAB MED, V43, P1118; HERMANN M, 2005, CLIN CHEM, V51, P2348; HERNANDEZAVILA M, 1993, EPIDEMIOLOGY, V4, P128, DOI 10.1097-00001648-199303000-00008; Herrmann M, 2009, BONE, V44, P467, DOI 10.1016-j.bone.2008.10.051; HODGES SJ, 1993, J BONE MINER RES, V8, P1241; HODGES SJ, 1991, BONE, V12, P387, DOI 10.1016-8756-3282(91)90027-G; Hotchkiss CE, 2006, COMPARATIVE MED, V56, P502; HOUGH S, 1988, ENDOCRINOLOGY, V122, P2933; Jacques PF, 2002, J NUTR, V132, P283; Jacques PF, 1999, NEW ENGL J MED, V340, P1449, DOI 10.1056-NEJM199905133401901; Johansson S, 2002, BONE, V31, P685, DOI 10.1016-S8756-3282(02)00910-9; Jorgensen L, 2011, OSTEOPOROSIS INT, V22, P1247, DOI 10.1007-s00198-010-1340-0; Kanai T, 1997, INT J GYNECOL OBSTET, V56, P25, DOI 10.1016-S0020-7292(96)02790-7; Kawahara TN, 2002, J NUTR, V132, P1169; Kim GS, 1996, METABOLISM, V45, P1443, DOI 10.1016-S0026-0495(96)90171-7; Kim HJ, 2006, FREE RADICAL BIO MED, V40, P1483, DOI 10.1016-j.freeradbiomed.2005.10.066; Kim Linda, 2003, Journal of Medicinal Food, V6, P79, DOI 10.1089-109662003322233468; Kipp DE, 1996, BONE, V18, P281, DOI 10.1016-8756-3282(95)00481-5; KNAPEN MHJ, 1989, ANN INTERN MED, V111, P1001; Kneissel M, 2005, BONE, V36, P202, DOI 10.1016-j.bone.2004.11.006; Kobayashi M, 2004, BONE, V35, P1136, DOI 10.1016-j.bone.2004.05.012; KONSIONG GJ, 1993, BRIT J HAEMATOL, V83, P100; Law MR, 1997, BRIT MED J, V315, P841; LAWSON JP, 1987, SKELETAL RADIOL, V16, P91; Lee JH, 2009, J BIOL CHEM, V284, P13725, DOI 10.1074-jbc.M806941200; Leveille SG, 1997, J EPIDEMIOL COMMUN H, V51, P479, DOI 10.1136-jech.51.5.479; Li M, 2004, BONE, V35, P1369, DOI 10.1016-j.bone.2004.09.008; Lim LS, 2004, OSTEOPOROSIS INT, V15, P552, DOI 10.1007-s00198-003-1577-y; Liu GM, 1997, J BIOL CHEM, V272, P32370, DOI 10.1074-jbc.272.51.32370; Lubec B, 1996, BBA-MOL BASIS DIS, V1315, P159, DOI 10.1016-0925-4439(95)00119-0; Macdonald HM, 2004, BONE, V35, P957, DOI 10.1016-j.bone.2004.05.018; Maiorano G, 1999, J ANIM SCI, V77, P2452; Maniam S, 2008, BASIC CLIN PHARMACOL, V103, P55, DOI 10.1111-j.1742-7843.2008.00241.x; Matsunaga S, 1999, CALCIFIED TISSUE INT, V65, P285, DOI 10.1007-s002239900700; MCGUIRE J, 1987, Dermatologica (Basel), V175, P169; McLean RR, 2004, J BONE MINER RES, V19, P410, DOI 10.1359-JBMR.0301261; McLean RR, 2004, NEW ENGL J MED, V350, P2042, DOI 10.1056-NEJMoa032739; Melhus H, 1998, ANN INTERN MED, V129, P770; Melhus H, 1999, J BONE MINER RES, V14, P129, DOI 10.1359-jbmr.1999.14.1.129; Mellanby E, 1941, J PHYSIOL-LONDON, V99, P467; MELLANBY E, 1947, J PHYSIOL-LONDON, V105, P382; Michaelsson K, 2003, NEW ENGL J MED, V348, P287, DOI 10.1056-NEJMoa021171; MICHAELSSON K, 1995, CALCIFIED TISSUE INT, V57, P86, DOI 10.1007-BF00298425; Miyao M, 2000, CALCIFIED TISSUE INT, V66, P190, DOI 10.1007-s002230010038; Morris MS, 2005, BONE, V37, P234, DOI 10.1016-j.bone.2005.04.017; OHISHI K, 1995, EUR J ENDOCRINOL, V133, P335; Pasco JA, 2006, J WOMENS HEALTH, V15, P295, DOI 10.1089-jwh.2006.15.295; PETERKOFSKY B, 1991, AM J CLIN NUTR, V54, pS1135; Peters BSE, 2010, ARQ BRAS ENDOCRINOL, V54, P179, DOI 10.1590-S0004-27302010000200014; PRICE PA, 1980, P NATL ACAD SCI-BIOL, V77, P2234, DOI 10.1073-pnas.77.4.2234; PRICE PA, 1988, ANNU REV NUTR, V8, P565; PRICE PA, 1980, J CLIN INVEST, V66, P878, DOI 10.1172-JCI109954; Promislow JHE, 2002, J BONE MINER RES, V17, P1349, DOI 10.1359-jbmr.2002.17.8.1349; Prynne CJ, 2006, AM J CLIN NUTR, V83, P1420; Rao Leticia G., 2003, Journal of Medicinal Food, V6, P69, DOI 10.1089-109662003322233459; Raposo B, 2004, ATHEROSCLEROSIS, V177, P1, DOI 10.1016-j.atherosclerosis.2004.06.015; REDDI K, 1995, CYTOKINE, V7, P287, DOI 10.1006-cyto.1995.0034; Rejnmark L, 2004, OSTEOPOROSIS INT, V15, P872, DOI 10.1007-s00198-004-1618-1; Ribaya-Mercado JD, 2007, NUTR REV, V65, P425, DOI [10.1301-nr.2007.oct.425-438, 10.1301-nr.2007.oct.425–438]; RICO H, 1995, J BONE JOINT SURG BR, V77B, P148; ROSEN HN, 1993, AM J MED, V94, P62, DOI 10.1016-0002-9343(93)90121-5; RUIZ-MALDONADO R, 1987, Dermatologica (Basel), V175, P125; Sahni S, 2008, J NUTR, V138, P1931; SANESHIGE S, 1995, BIOCHEM J, V309, P721; Sato Y, 2005, JAMA-J AM MED ASSOC, V293, P1082, DOI 10.1001-jama.293.9.1082; SATTERFIELD D, 1988, OPHTHALMIC RES, V20, P227; SCHIMKE RN, 1965, JAMA-J AM MED ASSOC, V193, P87; SCHWARTZ ER, 1979, CALCIFIED TISSUE INT, V6, P201; SELHUB J, 1993, JAMA-J AM MED ASSOC, V270, P2693, DOI 10.1001-jama.270.22.2693; Shearer MJ, 1997, P NUTR SOC, V56, P915, DOI 10.1079-PNS19970099; Shiraishi A, 2002, CALCIFIED TISSUE INT, V71, P69, DOI 10.1007-s00223-001-2090-y; Shiraki M, 2000, J BONE MINER RES, V15, P515, DOI 10.1359-jbmr.2000.15.3.515; Stone KL, 2004, J CLIN ENDOCR METAB, V89, P1217, DOI 10.1210-jc.2003-030074; SUGIMOTO T, 1986, CALCIFIED TISSUE INT, V39, P171, DOI 10.1007-BF02555114; Suzuki Y, 2003, J Nutr Health Aging, V7, P296; Tamatani M, 1998, METABOLISM, V47, P195, DOI 10.1016-S0026-0495(98)90220-7; Tamura T, 2007, ARCH INTERN MED, V167, P94, DOI 10.1001-archinte.167.1.94-a; TRECHSEL U, 1987, J CLIN INVEST, V80, P1679, DOI 10.1172-JCI113257; TSUCHIYA H, 1994, BRIT J NUTR, V72, P745, DOI 10.1079-BJN19940076; TSUNENARI T, 1991, CALCIFIED TISSUE INT, V48, P18, DOI 10.1007-BF02555792; Tucker KL, 1999, AM J CLIN NUTR, V69, P727; Tucker KL, 2005, J BONE MINER RES, V20, P152, DOI 10.1059-JBMR.041018; van Meurs JBJ, 2004, NEW ENGL J MED, V350, P2033, DOI 10.1056-NEJMoa032546; VERMEER C, 1995, ANNU REV NUTR, V15, P1, DOI 10.1146-annurev.nutr.15.1.1; Watkins BA, 1996, P SOC EXP BIOL MED, V212, P153; Wolf RL, 2005, AM J CLIN NUTR, V82, P581; XU H, 1995, CALCIFIED TISSUE INT, V57, P293, DOI 10.1007-BF00298885; YANO K, 1985, AM J CLIN NUTR, V42, P877; Yazdanpanah N, 2007, BONE, V41, P987, DOI 10.1016-j.bone.2007.08.021; Zhang JJ, 2006, AM J EPIDEMIOL, V163, P9, DOI 10.1093-aje-kwj005; Zhu K, 2009, OSTEOPOROSIS INT, V20, P1183, DOI 10.1007-s00198-008-0804-y22262
The Effects of Graded Levels of Calorie Restriction : XIII. Global Metabolomics Screen Reveals Graded Changes in Circulating Amino Acids, Vitamins, and Bile Acids in the Plasma of C57BL/6 Mice
No full textWork toward having all the data from this series of papers online is currently ongoing. All significant metabolites in relation to CR manipulation are listed in Supplementary Material S1. Data on the nonsignificant metabolites are freely available for anyone who requests it from the corresponding author at [email protected] The study was supported by the UK Biotechnology and Biological Sciences Research Council BBSRC (BB/G009953/1 and BB/J020028/1 to J.R.S.) and a studentship of C.L.G. from the BBSRC EastBio Doctoral Training Partnership. C.L.G. received support from the laboratory of D.P.; D.P. was supported in part by NIH grant AGO49494.Peer reviewe
