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- Abe, O, et al.
(author)
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Effects of chemotherapy and hormonal therapy for early breast cancer on recurrence and 15-year survival: an overview of the randomised trials
- 2005
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In: The Lancet. - 1474-547X. ; 365:9472, s. 1687-1717
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Journal article (peer-reviewed)abstract
- Background Quinquennial overviews (1985-2000) of the randomised trials in early breast cancer have assessed the 5-year and 10-year effects of various systemic adjuvant therapies on breast cancer recurrence and survival. Here, we report the 10-year and 15-year effects. Methods Collaborative meta-analyses were undertaken of 194 unconfounded randomised trials of adjuvant chemotherapy or hormonal therapy that began by 1995. Many trials involved CMF (cyclophosphamide, methotrexate, fluorouracil), anthracycline-based combinations such as FAC (fluorouracil, doxombicin, cyclophosphamide) or FEC (fluorouracil, epirubicin, cyclophosphamide), tamoxifen, or ovarian suppression: none involved taxanes, trastuzumab, raloxifene, or modem aromatase inhibitors. Findings Allocation to about 6 months of anthracycline-based polychemotherapy (eg, with FAC or FEC) reduces the annual breast cancer death rate by about 38% (SE 5) for women younger than 50 years of age when diagnosed and by about 20% (SE 4) for those of age 50-69 years when diagnosed, largely irrespective of the use of tamoxifen and of oestrogen receptor (ER) status, nodal status, or other tumour characteristics. Such regimens are significantly (2p=0 . 0001 for recurrence, 2p<0 . 00001 for breast cancer mortality) more effective than CMF chemotherapy. Few women of age 70 years or older entered these chemotherapy trials. For ER-positive disease only, allocation to about 5 years of adjuvant tamoxifen reduces the annual breast cancer death rate by 31% (SE 3), largely irrespective of the use of chemotherapy and of age (<50, 50-69, &GE; 70 years), progesterone receptor status, or other tumour characteristics. 5 years is significantly (2p<0 . 00001 for recurrence, 2p=0 . 01 for breast cancer mortality) more effective than just 1-2 years of tamoxifen. For ER-positive tumours, the annual breast cancer mortality rates are similar during years 0-4 and 5-14, as are the proportional reductions in them by 5 years of tamoxifen, so the cumulative reduction in mortality is more than twice as big at 15 years as at 5 years after diagnosis. These results combine six meta-analyses: anthracycline-based versus no chemotherapy (8000 women); CMF-based versus no chemotherapy (14 000); anthracycline-based versus CMF-based chemotherapy (14 000); about 5 years of tamoxifen versus none (15 000); about 1-2 years of tamoxifen versus none (33 000); and about 5 years versus 1-2 years of tamoxifen (18 000). Finally, allocation to ovarian ablation or suppression (8000 women) also significantly reduces breast cancer mortality, but appears to do so only in the absence of other systemic treatments. For middle-aged women with ER-positive disease (the commonest type of breast cancer), the breast cancer mortality rate throughout the next 15 years would be approximately halved by 6 months of anthracycline-based chemotherapy (with a combination such as FAC or FEC) followed by 5 years of adjuvant tamoxifen. For, if mortality reductions of 38% (age <50 years) and 20% (age 50-69 years) from such chemotherapy were followed by a further reduction of 31% from tamoxifen in the risks that remain, the final mortality reductions would be 57% and 45%, respectively (and, the trial results could well have been somewhat stronger if there had been full compliance with the allocated treatments). Overall survival would be comparably improved, since these treatments have relatively small effects on mortality from the aggregate of all other causes. Interpretation Some of the widely practicable adjuvant drug treatments that were being tested in the 1980s, which substantially reduced 5-year recurrence rates (but had somewhat less effect on 5-year mortality rates), also substantially reduce 15-year mortality rates. Further improvements in long-term survival could well be available from newer drugs, or better use of older drugs.
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- Alström, Per, et al.
(author)
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Description of a new species of Phylloscopus from Vietnam and Laos.
- 2010
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In: Ibis. - 0019-1019 .- 1474-919X. ; 152:1, s. 145-168
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Journal article (peer-reviewed)abstract
- A new species of Phylloscopus warbler, which we name Phylloscopus calciatilis Limestone Leaf Warbler, is described from central and northern Vietnam and central and northern Laos; it probably also breeds in southernmost China. In morphology, the new species is very similar to Sulphur-breasted Warbler Phylloscopus ricketti, but it is smaller with a proportionately larger bill and rounder wing. Its song and calls are diagnostic. Based on mitochondrial and nuclear DNA, the new species is most closely related to P. ricketti and Yellow-vented Warbler Phylloscopus cantator, and it is inferred to be sister to the latter. The mitochondrial divergences between these three species are at the low end of the variation found in other species of Phylloscopus and Seicercus warblers, but greater than in other taxa generally treated as subspecies. Possible introgressive hybridization between the new species and P. ricketti is discussed, but more data are needed to establish whether it does occur and, if it does, to what extent. The new species appears to have a restricted breeding range in limestone karst environments, where it is locally common and therefore not under any immediate threat. In view of the recognition of the new species, all previous records of P. ricketti sensu lato need to be re-evaluated.
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7. |
- Antoniou, A. C., et al.
(author)
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Common breast cancer susceptibility alleles and the risk of breast cancer for BRCA1 and BRCA2 mutation carriers : Implications for risk prediction
- 2010
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In: Cancer Research. - : American Association for Cancer Research. - 0008-5472 .- 1538-7445. ; 70:23, s. 9742-9754
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Journal article (peer-reviewed)abstract
- The known breast cancer susceptibility polymorphisms in FGFR2, TNRC9/TOX3, MAP3K1, LSP1, and 2q35 confer increased risks of breast cancer for BRCA1 or BRCA2 mutation carriers. We evaluated the associations of 3 additional single nucleotide polymorphisms (SNPs), rs4973768 in SLC4A7/NEK10, rs6504950 in STXBP4/COX11, and rs10941679 at 5p12, and reanalyzed the previous associations using additional carriers in a sample of 12,525 BRCA1 and 7,409 BRCA2 carriers. Additionally, we investigated potential interactions between SNPs and assessed the implications for risk prediction. The minor alleles of rs4973768 and rs10941679 were associated with increased breast cancer risk for BRCA2 carriers (per-allele HR = 1.10, 95% CI: 1.03-1.18, P = 0.006 and HR = 1.09, 95% CI: 1.01-1.19, P = 0.03, respectively). Neither SNP was associated with breast cancer risk for BRCA1 carriers, and rs6504950 was not associated with breast cancer for either BRCA1 or BRCA2 carriers. Of the 9 polymorphisms investigated, 7 were associated with breast cancer for BRCA2 carriers (FGFR2, TOX3, MAP3K1, LSP1, 2q35, SLC4A7, 5p12, P = 7 × 10-11 - 0.03), but only TOX3 and 2q35 were associated with the risk for BRCA1 carriers (P = 0.0049, 0.03, respectively). All risk-associated polymorphisms appear to interact multiplicatively on breast cancer risk for mutation carriers. Based on the joint genotype distribution of the 7 risk-associated SNPs in BRCA2 mutation carriers, the 5% of BRCA2 carriers at highest risk (i.e., between 95th and 100th percentiles) were predicted to have a probability between 80% and 96% of developing breast cancer by age 80, compared with 42% to 50% for the 5% of carriers at lowest risk. Our findings indicated that these risk differences might be sufficient to influence the clinical management of mutation carriers.
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8. |
- Antoniou, A. C., et al.
(author)
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Common variants in LSP1, 2q35 and 8q24 and breast cancer risk for BRCA1 and BRCA2 mutation carriers
- 2009
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In: Human Molecular Genetics. - [Antoniou, Antonis C.; McGuffog, Lesley; Peock, Susan; Cook, Margaret; Frost, Debra; Oliver, Clare; Platte, Radka; Pooley, Karen A.; Easton, Douglas F.] Univ Cambridge, Dept Publ Hlth & Primary Care, Canc Res UK Genet Epidemiol Unit, Cambridge, England. [Sinilnikova, Olga M.; Leone, Melanie] Univ Lyon, CNRS, Hosp Civils Lyon,Ctr Leon Berard,UMR5201, Unite Mixte Genet Constitut Canc Frequents, Lyon, France. [Healey, Sue; Spurdle, Amanda B.; Beesley, Jonathan; Chen, Xiaoqing; Chenevix-Trench, Georgia] Queensland Inst Med Res, Brisbane, Qld 4029, Australia. [Nevanlinna, Heli; Heikkinen, Tuomas] Univ Helsinki, Cent Hosp, Dept Obstet & Gynecol, FIN-00290 Helsinki, Finland. [Simard, Jacques] Univ Laval, Quebec City, PQ, Canada. [Simard, Jacques] Univ Quebec, Ctr Hosp, Canada Res Chair Oncogenet, Canc Genom Lab, Quebec City, PQ, Canada. Peter MacCallum Canc Inst, Melbourne, Vic 3002, Australia. [Neuhausen, Susan L.; Ding, Yuan C.] Univ Calif Irvine, Dept Epidemiol, Irvine, CA USA. [Couch, Fergus J.; Wang, Xianshu; Fredericksen, Zachary] Mayo Clin, Rochester, MN USA. [Peterlongo, Paolo; Peissel, Bernard; Radice, Paolo] Fdn IRCCS Ist Nazl Tumori, Milan, Italy. [Peterlongo, Paolo; Radice, Paolo] Fdn Ist FIRC Oncol Molecolare, Milan, Italy. [Bonanni, Bernardo; Bernard, Loris] Ist Europeo Oncol, Milan, Italy. [Viel, Alessandra] IRCCS, Ctr Riferimento Oncol, Aviano, Italy. [Bernard, Loris] Cogentech, Consortium Genom Technol, Milan, Italy. [Szabo, Csilla I.] Mayo Clin, Coll Med, Dept Lab Med & Pathol, Rochester, MN USA. [Foretova, Lenka] Masaryk Mem Canc Inst, Dept Canc Epidemiol & Genet, Brno, Czech Republic. [Zikan, Michal] Charles Univ Prague, Dept Biochem & Expt Oncol, Fac Med 1, Prague, Czech Republic. [Claes, Kathleen] Ghent Univ Hosp, Ctr Med Genet, B-9000 Ghent, Belgium. [Greene, Mark H.; Mai, Phuong L.] US Natl Canc Inst, Clin Genet Branch, Rockville, MD USA. [Rennert, Gad; Lejbkowicz, Flavio] CHS Natl Canc Control Ctr, Haifa, Israel. [Rennert, Gad; Lejbkowicz, Flavio] Carmel Hosp, Dept Community Med & Epidemiol, Haifa, Israel. [Rennert, Gad; Lejbkowicz, Flavio] B Rappaport Fac Med, Haifa, Israel. [Andrulis, Irene L.; Glendon, Gord] Canc Care Ontario, Ontario Canc Genet Network, Toronto, ON M5G 2L7, Canada. [Andrulis, Irene L.] Mt Sinai Hosp, Fred A Litwin Ctr Canc Genet, Samuel Lunenfeld Res Inst, Toronto, ON, Canada. [Andrulis, Irene L.] Univ Toronto, Dept Mol Genet, Toronto, ON, Canada. [Gerdes, Anne-Marie; Thomassen, Mads] Odense Univ Hosp, Dept Biochem Pharmacol & Genet, DK-5000 Odense, Denmark. [Sunde, Lone] Aarhus Univ Hosp, Dept Clin Genet, DK-8000 Aarhus, Denmark. [Caligo, Maria A.] Univ Pisa, Div Surg Mol & Ultrastructural Pathol, Dept Oncol, Pisa, Italy. [Caligo, Maria A.] Pisa Univ Hosp, Pisa, Italy. [Laitman, Yael; Kontorovich, Tair; Cohen, Shimrit; Friedman, Eitan] Chaim Sheba Med Ctr, Susanne Levy Gertner Oncogenet Unit, IL-52621 Tel Hashomer, Israel. [Kaufman, Bella] Chaim Sheba Med Ctr, Inst Oncol, IL-52621 Tel Hashomer, Israel. [Kaufman, Bella; Friedman, Eitan] Tel Aviv Univ, Sackler Sch Med, IL-69978 Tel Aviv, Israel. [Dagan, Efrat; Baruch, Ruth Gershoni] Rambam Med Ctr, Genet Inst, Haifa, Israel. [Harbst, Katja] Lund Univ, Dept Oncol, S-22100 Lund, Sweden. [Barbany-Bustinza, Gisela; Rantala, Johanna] Karolinska Univ Hosp, Dept Clin Genet, Stockholm, Sweden. [Ehrencrona, Hans] Uppsala Univ, Dept Genet & Pathol, Uppsala, Sweden. [Karlsson, Per] Sahlgrenska Univ, Dept Oncol, Gothenburg, Sweden. [Domchek, Susan M.; Nathanson, Katherine L.] Univ Penn, Philadelphia, PA 19104 USA. [Osorio, Ana; Benitez, Javier] Ctr Invest Biomed Red Enfermedades Raras CIBERERE, Inst Salud Carlos III, Madrid, Spain. [Osorio, Ana; Benitez, Javier] Spanish Natl Canc Ctr CNIO, Human Canc Genet Programme, Human Genet Grp, Madrid, Spain. [Blanco, Ignacio] Catalan Inst Oncol ICO, Canc Genet Counseling Program, Barcelona, Spain. [Lasa, Adriana] Hosp Santa Creu & Sant Pau, Genet Serv, Barcelona, Spain. [Hamann, Ute] Deutsch Krebsforschungszentrum, Neuenheimer Feld 580 69120, D-6900 Heidelberg, Germany. [Hogervorst, Frans B. L.] Netherlands Canc Inst, Dept Pathol, Family Canc Clin, NL-1066 CX Amsterdam, Netherlands. [Rookus, Matti A.] Netherlands Canc Inst, Dept Epidemiol, Amsterdam, Netherlands. [Collee, J. Margriet] Erasmus Univ, Dept Clin Genet, Rotterdam Family Canc Clin, Med Ctr, NL-3000 DR Rotterdam, Netherlands. [Devilee, Peter] Dept Genet Epidemiol, Leiden, Netherlands. [Wijnen, Juul] Leiden Univ, Med Ctr, Ctr Human & Clin Genet, Leiden, Netherlands. [Ligtenberg, Marjolijn J.] Radboud Univ Nijmegen, Med Ctr, Dept Human Genet, NL-6525 ED Nijmegen, Netherlands. [van der Luijt, Rob B.] Univ Utrecht, Med Ctr, Dept Clin Mol Genet, NL-3508 TC Utrecht, Netherlands. [Aalfs, Cora M.] Univ Amsterdam, Acad Med Ctr, Dept Clin Genet, NL-1105 AZ Amsterdam, Netherlands. [Waisfisz, Quinten] Vrije Univ Amsterdam, Med Ctr, Dept Clin Genet, Amsterdam, Netherlands. [van Roozendaal, Cornelis E. P.] Univ Med Ctr, Dept Clin Genet, Maastricht, Netherlands. [Evans, D. Gareth; Lalloo, Fiona] Cent Manchester Univ Hosp, NHS Fdn Trust, Manchester Acad Hlth Sci Ctr, Manchester, Lancs, England. [Eeles, Rosalind] Inst Canc Res, Translat Canc Genet Team, London SW3 6JB, England. [Eeles, Rosalind] Royal Marsden NHS Fdn Trust, London, England. [Izatt, Louise] Guys Hosp, Clin Genet, London SE1 9RT, England. [Davidson, Rosemarie] Ferguson Smith Ctr Clin Genet, Glasgow, Lanark, Scotland. [Chu, Carol] Yorkshire Reg Genet Serv, Leeds, W Yorkshire, England. [Eccles, Diana] Princess Anne Hosp, Wessex Clin Genet Serv, Southampton, Hants, England. [Cole, Trevor] Birmingham Womens Hosp Healthcare, NHS Trust, W Midlands Reg Genet Serv, Birmingham, W Midlands, England. [Hodgson, Shirley] Univ London, Dept Canc Genet, St Georges Hosp, London, England. [Godwin, Andrew K.; Daly, Mary B.] Fox Chase Canc Ctr, Philadelphia, PA 19111 USA. [Stoppa-Lyonnet, Dominique] Univ Paris 05, Paris, France. [Stoppa-Lyonnet, Dominique] Inst Curie, INSERM U509, Serv Genet Oncol, Paris, France. [Buecher, Bruno] Inst Curie, Dept Genet, Paris, France. [Bressac-de Paillerets, Brigitte; Remenieras, Audrey; Lenoir, Gilbert M.] Inst Cancrol Gustave Roussy, Dept Genet, Villejuif, France. [Bressac-de Paillerets, Brigitte] Inst Cancerol Gustave Roussy, INSERM U946, Villejuif, France. [Caron, Olivier] Inst Cancerol Gustave Roussy, Dept Med, Villejuif, France. [Lenoir, Gilbert M.] Inst Cancerol Gustave Roussy, CNRS FRE2939, Villejuif, France. [Sevenet, Nicolas; Longy, Michel] Inst Bergonie, Lab Genet Constitutionnelle, Bordeaux, France. [Longy, Michel] Inst Bergonie, INSERM U916, Bordeaux, France. [Ferrer, Sandra Fert] Hop Hotel Dieu, Ctr Hosp, Lab Genet Chromosom, Chambery, France. [Prieur, Fabienne] CHU St Etienne, Serv Genet Clin Chromosom, St Etienne, France. [Goldgar, David] Univ Utah, Dept Dermatol, Salt Lake City, UT 84112 USA. [Miron, Alexander; Yassin, Yosuf] Dana Farber Canc Inst, Boston, MA 02115 USA. [John, Esther M.] No Calif Canc Ctr, Fremont, CA USA. [John, Esther M.] Stanford Univ, Sch Med, Stanford, CA 94305 USA. [Buys, Saundra S.] Univ Utah, Hlth Sci Ctr, Huntsman Canc Inst, Salt Lake City, UT USA. [Hopper, John L.] Univ Melbourne, Melbourne, Australia. [Terry, Mary Beth] Columbia Univ, New York, NY USA. [Singer, Christian; Gschwantler-Kaulich, Daphne; Staudigl, Christine] Med Univ Vienna, Div Special Gynecol, Dept OB GYN, Vienna, Austria. [Hansen, Thomas V. O.] Univ Copenhagen, Rigshosp, Dept Clin Biochem, DK-2100 Copenhagen, Denmark. [Barkardottir, Rosa Bjork] Landspitali Univ Hosp, Dept Pathol, Reykjavik, Iceland. [Kirchhoff, Tomas; Pal, Prodipto; Kosarin, Kristi; Offit, Kenneth] Mem Sloan Kettering Canc Ctr, Dept Med, Clin Genet Serv, New York, NY 10021 USA. [Piedmonte, Marion] Roswell Pk Canc Inst, GOG Stat & Data Ctr, Buffalo, NY 14263 USA. [Rodriguez, Gustavo C.] Evanston NW Healthcare, NorthShore Univ Hlth Syst, Evanston, IL 60201 USA. [Wakeley, Katie] Tufts Univ, New England Med Ctr, Boston, MA 02111 USA. [Boggess, John F.] Univ N Carolina, Chapel Hill, NC 27599 USA. [Basil, Jack] St Elizabeth Hosp, Edgewood, KY 41017 USA. [Schwartz, Peter E.] Yale Univ, Sch Med, New Haven, CT 06510 USA. [Blank, Stephanie V.] New York Univ, Sch Med, New York, NY 10016 USA. [Toland, Amanda E.] Ohio State Univ, Dept Internal Med, Columbus, OH 43210 USA. [Toland, Amanda E.] Ohio State Univ, Div Human Canc Genet, Ctr Comprehens Canc, Columbus, OH 43210 USA. [Montagna, Marco; Casella, Cinzia] IRCCS, Ist Oncologico Veneto, Immunol & Mol Oncol Unit, Padua, Italy. [Imyanitov, Evgeny N.] NN Petrov Inst Res Inst, St Petersburg, Russia. [Allavena, Anna] Univ Turin, Dept Genet Biol & Biochem, Turin, Italy. [Schmutzler, Rita K.; Versmold, Beatrix; Arnold, Norbert] Univ Cologne, Dept Obstet & Gynaecol, Div Mol Gynaeco Oncol, Cologne, Germany. [Engel, Christoph] Univ Leipzig, Inst Med Informat Stat & Epidemiol, Leipzig, Germany. [Meindl, Alfons] Tech Univ Munich, Dept Obstet & Gynaecol, Munich, Germany. [Ditsch, Nina] Univ Munich, Dept Obstet & Gynecol, Munich, Germany. Univ Schleswig Holstein, Dept Obstet & Gynaecol, Campus Kiel, Germany. [Niederacher, Dieter] Univ Duesseldorf, Dept Obstet & Gynaecol, Mol Genet Lab, Dusseldorf, Germany. [Deissler, Helmut] Univ Ulm, Dept Obstet & Gynaecol, Ulm, Germany. [Fiebig, Britta] Univ Regensburg, Inst Human Genet, Regensburg, Germany. [Suttner, Christian] Univ Heidelberg, Inst Human Genet, Heidelberg, Germany. [Schoenbuchner, Ines] Univ Wurzburg, Inst Human Genet, D-8700 Wurzburg, Germany. [Gadzicki, Dorothea] Med Univ, Inst Cellular & Mol Pathol, Hannover, Germany. [Caldes, Trinidad; de la Hoya, Miguel] Hosp Clinico San Carlos 28040, Madrid, Spain. : Oxford University Press. - 0964-6906 .- 1460-2083. ; 18:22, s. 4442-4456
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Journal article (peer-reviewed)abstract
- Genome-wide association studies of breast cancer have identified multiple single nucleotide polymorphisms (SNPs) that are associated with increased breast cancer risks in the general population. In a previous study, we demonstrated that the minor alleles at three of these SNPs, in FGFR2, TNRC9 and MAP3K1, also confer increased risks of breast cancer for BRCA1 or BRCA2 mutation carriers. Three additional SNPs rs3817198 at LSP1, rs13387042 at 2q35 and rs13281615 at 8q24 have since been reported to be associated with breast cancer in the general population, and in this study we evaluated their association with breast cancer risk in 9442 BRCA1 and 5665 BRCA2 mutation carriers from 33 study centres. The minor allele of rs3817198 was associated with increased breast cancer risk only for BRCA2 mutation carriers [hazard ratio (HR) = 1.16, 95% CI: 1.07-1.25, P-trend = 2.8 × 10-4]. The best fit for the association of SNP rs13387042 at 2q35 with breast cancer risk was a dominant model for both BRCA1 and BRCA2 mutation carriers (BRCA1: HR = 1.14, 95% CI: 1.04-1.25, P = 0.0047; BRCA2: HR = 1.18 95% CI: 1.04-1.33, P = 0.0079). SNP rs13281615 at 8q24 was not associated with breast cancer for either BRCA1 or BRCA2 mutation carriers, but the estimated association for BRCA2 mutation carriers (per-allele HR = 1.06, 95% CI: 0.98-1.14) was consistent with odds ratio estimates derived from population-based case-control studies. The LSP1 and 2q35 SNPs appear to interact multiplicatively on breast cancer risk for BRCA2 mutation carriers. There was no evidence that the associations vary by mutation type depending on whether the mutated protein is predicted to be stable or not.
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9. |
- Ashton, Stephanie, et al.
(author)
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The Index of Intrusion Control (IIC) : Capturing individual variability in intentional intrusion control in the laboratory
- 2024
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In: Behavior Research Methods. - : Springer Nature. - 1554-351X .- 1554-3528. ; 56:4, s. 4061-4072
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Journal article (peer-reviewed)abstract
- Intrusive memories can be downregulated using intentional memory control, as measured via the Think/No-Think paradigm. In this task, participants retrieve or suppress memories in response to an associated reminder cue. After each suppression trial, participants rate whether the association intruded into awareness. Previous research has found that repeatedly exerting intentional control over memory intrusions reduces their frequency. This decrease is often summarised with a linear index, which may miss more complex patterns characterising the temporal dynamics of intrusion control. The goal of this paper is to propose a novel metric of intrusion control that captures those dynamic changes over time as a single index. Results from a mega-analysis of published datasets revealed that the change in intrusion frequencies across time is not purely linear, but also includes non-linear dynamics that seem best captured by a log function of the number of suppression attempts. To capture those linear and non-linear dynamics, we propose the Index of Intrusion Control (IIC), which relies on the integral of intrusion changes across suppression attempts. Simulations revealed that the IIC best captured the linear and non-linear dynamics of intrusion suppression when compared with other linear or non-linear indexes of control, such as the regression slope or Spearman correlation, respectively. Our findings demonstrate how the IIC may therefore act as a more reliable metric to capture individual differences in intrusion control, and examine the role of non-linear dynamics characterizing the conscious access to unwanted memories.
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10. |
- Bachelet, Delphine, et al.
(author)
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Occurrence of Anti-Drug Antibodies against Interferon-Beta and Natalizumab in Multiple Sclerosis : A Collaborative Cohort Analysis
- 2016
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In: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 11:11
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Journal article (peer-reviewed)abstract
- Immunogenicity of biopharmaceutical products in multiple sclerosis is a frequent side effect which has a multifactorial etiology. Here we study associations between anti-drug antibody (ADA) occurrence and demographic and clinical factors. Retrospective data from routine ADA test laboratories in Sweden, Denmark, Austria and Germany (Dusseldorf group) and from one research study in Germany (Munich group) were gathered to build a collaborative multi-cohort dataset within the framework of the ABIRISK project. A subset of 5638 interferon-beta (IFN beta)-treated and 3440 natalizumab-treated patients having data on at least the first two years of treatment were eligible for interval-censored time-to-event analysis. In multivariate Cox regression, IFN beta-1a subcutaneous and IFN beta-1b subcutaneous treated patients were at higher risk of ADA occurrence compared to IFN beta-1a intramuscular-treated patients (pooled HR = 6.4, 95% CI 4.9-8.4 and pooled HR = 8.7, 95% CI 6.6-11.4 respectively). Patients older than 50 years at start of IFN beta therapy developed ADA more frequently than adult patients younger than 30 (pooled HR = 1.8, 95% CI 1.4-2.3). Men developed ADA more frequently than women (pooled HR = 1.3, 95% CI 1.1-1.6). Interestingly we observed that in Sweden and Germany, patients who started IFN beta in April were at higher risk of developing ADA (HR = 1.6, 95% CI 1.1-2.4 and HR = 2.4, 95% CI 1.5-3.9 respectively). This result is not confirmed in the other cohorts and warrants further investigations. Concerning natalizumab, patients older than 45 years had a higher ADA rate (pooled HR = 1.4, 95% CI 1.0-1.8) and women developed ADA more frequently than men (pooled HR = 1.4, 95% CI 1.0-2.0). We confirmed previously reported differences in immunogenicity of the different types of IFN beta. Differences in ADA occurrence by sex and age are reported here for the first time. These findings should be further investigated taking into account other exposures and biomarkers.
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11. |
- Bartha, Erzsebet, et al.
(author)
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Cost-effectiveness Analysis of Goal-directed Hemodynamic Treatment of Elderly Hip Fracture Patients : Before Clinical Research Starts
- 2012
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In: Anesthesiology. - : Lippincott Williams & Wilkins. - 0003-3022 .- 1528-1175. ; 117:3, s. 519-530
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Journal article (peer-reviewed)abstract
- Background: Health economic evaluations are increasingly used to make the decision to adopt new medical interventions. Before such decisions, various stakeholders have invested in clinical research. But health economic factors are seldom considered in research funding decisions. Cost-effectiveness analysis could be informative before the launch of clinical research projects, particularly when a targeted intervention is resource-intensive, total cost for the trial is very high, and expected gain of health benefits is uncertain. This study analyzed cost-effectiveness using a decision analytic model before initiating a large clinical research project on goal-directed hemodynamic treatment of elderly patients with hip fracture.Methods: A probabilistic decision analytic cost-effectiveness model was developed; the model contains a decision tree for the postoperative short-term outcome and a Markov structure for long-term outcome. Clinical effect estimates, costs, health-related quality-of-life measures, and long-term survival constituted model input that was extracted from clinical trials, national databases, and surveys. Model output consisted of estimated medical care costs related to quality-adjusted life-years.Results: In the base care analysis, goal-directed hemodynamic treatment reduced average medical care costs by €1,882 and gained 0.344 qualilty-adjusted life-years. In 96.5% of the simulations, goal-directed hemodynamic treatment is less costly and provides more quality-adjusted life-years. The results are sensitive to clinical effect size variations, although goal-directed hemodynamic treatment seems to be cost-effective even with moderate clinical effect.Conclusion: This study demonstrates that cost-effectiveness analysis is feasible, meaningful, and recommendable before launch of costly clinical research projects.
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12. |
- Bartha, Erzsebet, et al.
(author)
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Cost-effectiveness Analysis of Goal-directed Hemodynamic Treatment of Elderly Hip Fracture Patients
- 2012
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In: Anesthesiology. - : ASA Publishers. - 0003-3022 .- 1528-1175. ; 117:3, s. 519-530
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Journal article (peer-reviewed)abstract
- BackgroundHealth economic evaluations are increasingly used to make the decision to adopt new medical interventions. Before such decisions, various stakeholders have invested in clinical research. But health economic factors are seldom considered in research funding decisions. Cost-effectiveness analyses could be informative before the launch of clinical research projects, particularly when a targeted intervention is resource-intensive, total cost for the trial is very high, and expected gain of health benefits is uncertain. This study analyzed cost-effectiveness using a decision analytic model before initiating a large clinical research project on goal-directed hemodynamic treatment of elderly patients with hip fracture.MethodsA probabilistic decision analytic cost-effectiveness model was developed; the model contains a decision tree for the postoperative short-term outcome and a Markov structure for long-term outcome. Clinical effect estimates, costs, health-related quality-of-life measures, and long-term survival constituted model input that was extracted from clinical trials, national databases, and surveys. Model output consisted of estimated medical care costs related to quality-adjusted life-years.ResultsIn the base case analysis, goal-directed hemodynamic treatment reduced average medical care costs by €1,882 and gained 0.344 quality-adjusted life-years. In 96.5% of the simulations, goal-directed hemodynamic treatment is less costly and provides more quality-adjusted life-years. The results are sensitive to clinical effect size variations, although goal-directed hemodynamic treatment seems to be cost-effective even with moderate clinical effect.ConclusionThis study demonstrates that cost-effectiveness analysis is feasible, meaningful, and recommendable before launch of costly clinical research projects.
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14. |
- Bartha, Erzsebet, et al.
(author)
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Value of information: interim analysis of a randomized, controlled trial of goal-directed hemodynamic treatment for aged patients
- 2013
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In: Trials. - : BioMed Central. - 1745-6215. ; 14
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Journal article (peer-reviewed)abstract
- BackgroundA randomized, controlled trial, intended to include 460 patients, is currently studying peroperative goal-directed hemodynamic treatment (GDHT) of aged hip-fracture patients. Interim efficacy analysis performed on the first 100 patients was statistically uncertain; thus, the trial is continuing in accordance with the trial protocol. This raised the present investigation’s main question: Is it reasonable to continue to fund the trial to decrease uncertainty? To answer this question, a previously developed probabilistic cost-effectiveness model was used. That model depicts (1) a choice between routine fluid treatment and GDHT, given uncertainty of current evidence and (2) the monetary value of further data collection to decrease uncertainty. This monetary value, that is, the expected value of perfect information (EVPI), could be used to compare future research costs. Thus, the primary aim of the present investigation was to analyze EVPI of an ongoing trial with interim efficacy observed.MethodsA previously developed probabilistic decision analytic cost-effectiveness model was employed to compare the routine fluid treatment to GDHT. Results from the interim analysis, published trials, the meta-analysis, and the registry data were used as model inputs. EVPI was predicted using (1) combined uncertainty of model inputs; (2) threshold value of society’s willingness to pay for one, quality-adjusted life-year; and (3) estimated number of future patients exposed to choice between GDHT and routine fluid treatment during the expected lifetime of GDHT.ResultsIf a decision to use GDHT were based on cost-effectiveness, then the decision would have a substantial degree of uncertainty. Assuming a 5-year lifetime of GDHT in clinical practice, the number of patients who would be subject to future decisions was 30,400. EVPI per patient would be €204 at a €20,000 threshold value of society’s willingness to pay for one quality-adjusted life-year. Given a future population of 30,400 individuals, total EVPI would be €6.19 million.ConclusionsIf future trial costs are below EVPI, further data collection is potentially cost-effective. When applying a cost-effectiveness model, statements such as ‘further research is needed’ are replaced with ‘further research is cost-effective and ‘further funding of a trial is justified’.
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15. |
- Björkstrand, Johannes, et al.
(author)
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The effect of mindfulness training on extinction retention
- 2019
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In: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 9
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Journal article (peer-reviewed)abstract
- Anxiety and trauma related disorders are highly prevalent, causing suffering and high costs for society. Current treatment strategies, although effective, only show moderate effect-sizes when compared to adequate control groups demonstrating a need to develop new forms of treatment or optimize existing ones. In order to achieve this, an increased understanding of what mechanisms are involved is needed. An emerging literature indicates that mindfulness training (MFT) can be used to treat fear and anxiety related disorders, but the treatment mechanisms are unclear. One hypothesis, largely based on findings from neuroimaging studies, states that MFT may improve extinction retention, but this has not been demonstrated empirically. To investigate this question healthy subjects either completed a 4-week MFT- intervention delivered through a smart-phone app (n = 14) or were assigned to a waitlist (n = 15). Subsequently, subjects participated in a two-day experimental protocol using pavlovian aversive conditioning, evaluating acquisition and extinction of threat-related responses on day 1, and extinction retention on day 2. Results showed that the MFT group displayed reduced spontaneous recovery of threat related arousal responses, as compared to the waitlist control group, on day 2. MFT did not however, have an effect on either the acquisition or extinction of conditioned responses day 1. This clarifies the positive effect of MFT on emotional functioning and could have implications for the treatment of anxiety and trauma related disorders.
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16. |
- Carlsson, Ingegerd, et al.
(author)
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Effects of a Daytime Nap on Primed and Repeated Remote Associates Tests and Relations with Divergent Creativity
- 2019
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In: Creativity Research Journal. - : Informa UK Limited. - 1532-6934 .- 1040-0419. ; 31:2, s. 207-214
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Journal article (peer-reviewed)abstract
- The effect of napping versus wakefulness was studied on primed and repeated Remote Associate Tests (RATs) and on divergent creativity tests. The participants were 42 students from the USA, studying international courses at a Swedish university. The hypotheses for the RATs were (1), when the correct answers were primed before the nap, the RAT should be solved better for those who entered REM sleep, compared to those with no REM sleep or a resting condition; and (2), when retested the RAT should be solved better after a nap than after rest. For the creativity tests, hypothesis (3) was that creativity should be higher after the nap than after rest. Hypothesis 1 and hypothesis 3 were not supported. Hypothesis 2 was supported in an ANOVA. The REM group improved more than the rest group on the repeated RAT. Also, the No-REM and rest groups differed, strengthening the importance of both REM and No-REM sleep for creative problem-solving.
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17. |
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18. |
- Davidson, Bo, 1956-, et al.
(author)
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Learning in production systems : a study of operator work in highly automated process and manufacturing industry
- 1999
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Doctoral thesis (other academic/artistic)abstract
- The aim of this monograph is to study the work of operators with regard to the conditions of developmental on-the-job learning. This objective can be further described in the following questions: (1) What characterizes the conditions of developmental on-the-job learning for operators in highly automated industry? (2) How are the conditions realized of developmental on-the-job learning? (3) What is the importance of vocational education, personnel training and on-the-job learning as regards their effects on the operators' vocational competence?Based on activity theory and action theory we have chosen to define learning as relatively lasting changes in the competence of an individual as a result of the individual's participation in an activity. Learning can imply internalization of various aspects of the characteristics of the activity and also externalization of new courses of action. The empirical part of the study have been conducted as casestudies in two process industries and two manufacturing industries.The main findings indicate that the conditions for developmental learning largely depends upon the precence of challenging problems in the activity and wide degrees of freedom for the operators. When working with these problems the conditions for learning are also dependent upon an integrated or informally open work organization that offers possibilities for participating in problem-solving, a multitude of tools that are continuously developed, high and clear demands on knowledge and skills that can be applied and developed in the day-to-day work.The findings indicate that the conditions of learning are shaped by factors that facilitate long-term development over time, for both the company and the operators (e.g. with regard to a stable market or traditions in the company) and a management that puts a premium on long-term development of the activities and operators' work, for instance by development of production, products, organization and competence.What is the importance of vocational education, personnel training and on-the-job learning as regards their effects on the operators' vocational competence? On-the-job learning is the most important form of leaming for operators working in the process industry. Learning by vocational education is an important form of learning for operators who work in manufacturing industry. If the vocational education is closely coupled to the work activities the importance of this form of learning increases.
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19. |
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20. |
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21. |
- Davidson, Bo, 1956-, et al.
(author)
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Operatörsarbete och lärande i högautomatiserad produktion
- 2004
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In: Lärande och förändring i orgnisationer. - Lund : Studentlitteratur. - 9144035152 - 9789144035154 ; , s. 41-63
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Book chapter (other academic/artistic)abstract
- I fokus för denna antologi står frågor om lärande, förändring och ledarskap inom olika typer av verksamhet. Syftet är att bidra till en bred genomlysning av dessa begrepp utifrån såväl teoretiska som empiriska analyser. Vi vill härigenom försöka utmana vanligt förekommande uppfattningar om lärande, förändring och ledarskap. Framställningen baseras i stor utsträckning på egna studier som genomförts under de senaste åren. Dessa studier har i samtliga fall utgått från människors dagliga arbete i olika lokala verksamheter - inom företag, hälso- och sjukvård, omsorgsverksamhet och skola. De studier som redovisas speglar därmed också vardagen på arbetsplatser inom olika sektorer av svenskt arbetsliv. I flera av studierna har det också varit möjligt att studera dessa verksamheter över längre tid och på så sätt belysa de studerade processernas drivkrafter och inre dynamik. Boken kan användas som kurslitteratur vid universitet och högskolor samt som fördjupningslitteratur i anslutning till ledar- eller personalutbildningar. Den vänder sig också till forskare, politiker, företrädare för arbetsmarknadens parter samt praktiskt verksamma med intresse för frågor om lärande, kompetensutveckling och förändringsprocessser i organisationer
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22. |
- Davidson, Bo, 1956-, et al.
(author)
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Operatörsarbete och yrkeskunnande
- 1992
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In: 3:e nordiska arbetskonferensen i forskning om folkupplysning och vuxenundervisning,1992. ; , s. 1-10
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Conference paper (other academic/artistic)
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23. |
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24. |
- Davidson, Per, et al.
(author)
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A daytime nap does not increase mnemonic discrimination ability
- 2020
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In: Journal of Sleep Research. - : Wiley-Blackwell. - 0962-1105 .- 1365-2869.
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Journal article (peer-reviewed)abstract
- It has been proposed that sleep readies the brain for novel learning, and previous work has shown that sleep loss impairs the ability to encode new memories. In the present study, we examined if a daytime nap would increase mnemonic discrimination (MD) performance. MD is the ability to differentiate between memories that are similar but not identical. Participants performed the Mnemonic Similarity Task (MST) twice, once in the morning and once in the afternoon. The goal of this task is to distinguish stimuli that have been seen before from novel stimuli that are similar but not identical. After the morning MST, participants were randomly allocated into either a sleep or a wake group. The sleep group had a 2-hr nap opportunity, whereas the wake group spent a similar amount of time passively resting. All participants then performed a second MST in the afternoon with a novel set of images. Results did not show any support for increased MD ability after a nap. There was, however, a correlation showing that an increase in sleepiness between sessions predicted a decrease in MD performance. Future work must systematically examine how strong sleep manipulations that are needed for sleep to have an effect on encoding ability, as well as which kind of memory tasks that are sensitive to sleep manipulations. More knowledge about the relationship between sleep and the ability to differentiate similar memories from each other is important because impaired MD ability has previously been reported in various groups in which sleep disturbances are also common.
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25. |
- Davidson, Per, et al.
(author)
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A daytime nap does not increase mnemonic discrimination ability
- 2020
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In: Journal of Sleep Research. - : Wiley-Blackwell Publishing Ltd. - 0962-1105 .- 1365-2869.
-
Journal article (peer-reviewed)abstract
- It has been proposed that sleep readies the brain for novel learning, and previous work has shown that sleep loss impairs the ability to encode new memories. In the present study, we examined if a daytime nap would increase mnemonic discrimination (MD) performance. MD is the ability to differentiate between memories that are similar but not identical. Participants performed the Mnemonic Similarity Task (MST) twice, once in the morning and once in the afternoon. The goal of this task is to distinguish stimuli that have been seen before from novel stimuli that are similar but not identical. After the morning MST, participants were randomly allocated into either a sleep or a wake group. The sleep group had a 2-hr nap opportunity, whereas the wake group spent a similar amount of time passively resting. All participants then performed a second MST in the afternoon with a novel set of images. Results did not show any support for increased MD ability after a nap. There was, however, a correlation showing that an increase in sleepiness between sessions predicted a decrease in MD performance. Future work must systematically examine how strong sleep manipulations that are needed for sleep to have an effect on encoding ability, as well as which kind of memory tasks that are sensitive to sleep manipulations. More knowledge about the relationship between sleep and the ability to differentiate similar memories from each other is important because impaired MD ability has previously been reported in various groups in which sleep disturbances are also common.
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26. |
- Davidson, Per, et al.
(author)
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A daytime nap does not increase pattern separation ability
- 2019
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In: Sleep. - 0161-8105 .- 1550-9109. ; 42:1, s. 42-42
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Journal article (peer-reviewed)abstract
- IntroductionA large body of studies has showed that the ability to learn new information is impaired when we are sleep deprived. Pattern separation (PS), the ability to form distinct memories for events that are highly similar and share overlapping features, has also previously been found to be impaired by sleep deprivation. In the present study, we examined if a daytime nap would increase PS performance.Methods108 young healthy participants came to the lab in the morning and completed the Mnemonic Similarity Task (MST). This task starts with an encoding phase where participants view images of common everyday objects and are asked to classify them as indoor or outdoor objects. During a subsequent memory test, participants view three different kinds of objects; ‘old’ objects that were also present during the encoding phase, ‘new’ objects that have not been seen before, and ‘lure’ objects that are similar to, but not exactly the same as, objects viewed during encoding. The task of the participants during the re-test is to say if the objects presented are ‘old’, ‘new’ or ‘similar’. This test gives two different outcome measures: General Recognition (GR) - the ability to separate old objects from new ones, and PS - the ability to separate similar objects from old ones. After this task, participants were randomly allocated to either a sleep or a wake group. The sleep group had a two-hour nap opportunity and the wake group spent an equal amount of time resting. After this delay interval, participants completed the MST for a second time with a new set of images.ResultsResults revealed no support for sleep in increasing either GR or PS ability. Within the sleep group, there were no correlations between changes in PS ability and time spent in any sleep stage.ConclusionPrevious studies that have found a role of sleep for PS ability has done so using larger manipulation of sleep. Based on the present study however, just a short daytime nap does not seem to have any effect on PS ability.
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27. |
- Davidson, Per, et al.
(author)
-
A daytime nap does not increase pattern separation ability
- 2019
-
In: Sleep. - : Oxford University Press. - 0161-8105 .- 1550-9109. ; 42:1, s. 42-42
-
Journal article (peer-reviewed)abstract
- Introduction A large body of studies has showed that the ability to learn new information is impaired when we are sleep deprived. Pattern separation (PS), the ability to form distinct memories for events that are highly similar and share overlapping features, has also previously been found to be impaired by sleep deprivation. In the present study, we examined if a daytime nap would increase PS performance. Methods 108 young healthy participants came to the lab in the morning and completed the Mnemonic Similarity Task (MST). This task starts with an encoding phase where participants view images of common everyday objects and are asked to classify them as indoor or outdoor objects. During a subsequent memory test, participants view three different kinds of objects; ‘old’ objects that were also present during the encoding phase, ‘new’ objects that have not been seen before, and ‘lure’ objects that are similar to, but not exactly the same as, objects viewed during encoding. The task of the participants during the re-test is to say if the objects presented are ‘old’, ‘new’ or ‘similar’. This test gives two different outcome measures: General Recognition (GR) - the ability to separate old objects from new ones, and PS - the ability to separate similar objects from old ones. After this task, participants were randomly allocated to either a sleep or a wake group. The sleep group had a two-hour nap opportunity and the wake group spent an equal amount of time resting. After this delay interval, participants completed the MST for a second time with a new set of images. Results Results revealed no support for sleep in increasing either GR or PS ability. Within the sleep group, there were no correlations between changes in PS ability and time spent in any sleep stage. Conclusion Previous studies that have found a role of sleep for PS ability has done so using larger manipulation of sleep. Based on the present study however, just a short daytime nap does not seem to have any effect on PS ability.
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28. |
- Davidson, Per, et al.
(author)
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A more generalized fear response after a daytime nap
- 2018
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In: Neurobiology of Learning and Memory. - : Elsevier. - 1074-7427 .- 1095-9564. ; 151, s. 18-27
-
Journal article (peer-reviewed)abstract
- The aim of this study was to examine how a daytime nap affected the consolidation of fear learning. Participants first underwent fear conditioning during which they were exposed to a large and a small circle. One of these was repeatedly paired with an electric shock (making it the CS+), whereas the other circle was never paired with the shock (the CS-). After a delay interval containing either a nap or wake, participants again viewed the CS+ and the CS- intermixed with eight novel circles that varied in size between the two stimuli seen before, as well as a blue triangle that served as a novel stimulus without prior fear relevance. We examined both fear retention (the difference between the CS+ and the CS-) as well as fear generalization (responses to the novel stimuli based on their similarity to the original CS+). Contrary to previous studies, results from the participants who acquired a differentiated fear response during the acquisition phase revealed that the wake group showed significantly larger skin conductance responses to the CS+ compared to the CS-, whereas no such difference was present in the sleep group. These results were not driven by differences in explicit memory or by differences in general reactivity. Analyzing responses to the novel stimuli revealed a tendency towards a more generalized response in the sleep group, with no differences between the CS+ and any other stimulus, whereas the wake group showed increased responses to the stimuli depending on their similarity to the original CS+. This effect was however only present when controlling for baseline differences in worry.
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29. |
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30. |
- Davidson, Per, et al.
(author)
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A more generalized fear response after a daytime nap
- 2018
-
In: Neurobiology of Learning and Memory. - : Elsevier BV. - 1074-7427 .- 1095-9564. ; 151, s. 18-27
-
Journal article (peer-reviewed)abstract
- The aim of this study was to examine how a daytime nap affected the consolidation of fear learning. Participants first underwent fear conditioning during which they were exposed to a large and a small circle. One of these was repeatedly paired with an electric shock (making it the CS+), whereas the other circle was never paired with the shock (the CS−). After a delay interval containing either a nap or wake, participants again viewed the CS+ and the CS− intermixed with eight novel circles that varied in size between the two stimuli seen before, as well as a blue triangle that served as a novel stimulus without prior fear relevance. We examined both fear retention (the difference between the CS+ and the CS−) and fear generalization (responses to the novel stimuli based on their similarity to the original CS+). Contrary to previous studies, results from the participants who acquired a differentiated fear response during the acquisition phase revealed that the wake group showed significantly larger skin conductance responses to the CS+ compared to the CS−, whereas no such difference was present in the sleep group. These results were not driven by differences in explicit memory or by differences in general reactivity. Analyzing responses to the novel stimuli revealed a tendency towards a more generalized response in the sleep group, with no differences between the CS+ and any other stimulus, whereas the wake group showed increased responses to the stimuli depending on their similarity to the original CS+. This effect was however only present when controlling for baseline differences in worry.
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31. |
- Davidson, Per, et al.
(author)
-
Does sleep selectively strengthen certain memories over others based on emotion and perceived future relevance?
- 2021
-
In: Nature and Science of Sleep. - : Dove Medical Press Ltd.. - 1179-1608. ; 13, s. 1257-1306
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Journal article (peer-reviewed)abstract
- Sleep has been found to have a beneficial effect on memory consolidation. It has furthermore frequently been suggested that sleep does not strengthen all memories equally. The first aim of this review paper was to examine whether sleep selectively strengthens emotional declarative memories more than neutral ones. We examined this first by reviewing the literature focusing on sleep/wake contrasts, and then the literature on whether any specific factors during sleep preferentially benefit emotional memories, with a special focus on the often-suggested claim that rapid eye movement sleep primarily consolidates emotional memories. A second aim was to examine if sleep preferentially benefits memories based on other cues of future relevance such as reward, test-expectancy or different instructions during encoding. Once again, we first focused on studies comparing sleep and wake groups, and then on studies examining the contributions of specific factors during sleep (for each future relevance paradigm, respectively). The review revealed that although some support exists that sleep is more beneficial for certain kinds of memories based on emotion or other cues of future relevance, the majority of studies does not support such an effect. Regarding specific factors during sleep, our review revealed that no sleep variable has reliably been found to be specifically associated with the consolidation of certain kinds of memories over others based on emotion or other cues of future relevance.
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32. |
- Davidson, Per, et al.
(author)
-
Does sleep selectively strengthen certain memories over others based on emotion and perceived future relevance?
- 2021
-
In: Nature and Science of Sleep. - : Dove Medical Press Ltd.. - 1179-1608. ; 13, s. 1257-1306
-
Research review (peer-reviewed)abstract
- Sleep has been found to have a beneficial effect on memory consolidation. It has furthermore frequently been suggested that sleep does not strengthen all memories equally. The first aim of this review paper was to examine whether sleep selectively strengthens emotional declarative memories more than neutral ones. We examined this first by reviewing the literature focusing on sleep/wake contrasts, and then the literature on whether any specific factors during sleep preferentially benefit emotional memories, with a special focus on the often-suggested claim that rapid eye movement sleep primarily consolidates emotional memories. A second aim was to examine if sleep preferentially benefits memories based on other cues of future relevance such as reward, test-expectancy or different instructions during encoding. Once again, we first focused on studies comparing sleep and wake groups, and then on studies examining the contributions of specific factors during sleep (for each future relevance paradigm, respectively). The review revealed that although some support exists that sleep is more beneficial for certain kinds of memories based on emotion or other cues of future relevance, the majority of studies does not support such an effect. Regarding specific factors during sleep, our review revealed that no sleep variable has reliably been found to be specifically associated with the consolidation of certain kinds of memories over others based on emotion or other cues of future relevance.
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33. |
- Davidson, Per, et al.
(author)
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Go to bed and you MIGHT feel better in the morning – the effect of sleep on affective tone and intrusiveness of emotional memories
- 2021
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In: Current Sleep Medicine Reports. - : Springer Science and Business Media LLC. - 2198-6401. ; 7:2, s. 31-46
-
Research review (peer-reviewed)abstract
- Purpose of ReviewIt is important to examine what effect sleep has after an emotional experience. More knowledge about this topic could help inform us whether there are any potential sleep interventions that could help make sure that memories of negative emotional experiences are processed in the most adaptive manner possible.Recent FindingsFindings on the role of sleep in altering reactivity to emotional stimuli have been highly varied, with significant findings in opposite directions. A new exciting development in the field is several studies finding that sleep seems to make memories of negative experiences less intrusive.SummaryThis review has mainly aimed to give an overview of the field, and of which issues need to be resolved. We argue for there being a strong need for standardization of how data are analyzed and presented, as well as for better methods for determining to what extent the effects of sleep are specific for a particular memory, or represent general changes in emotional reactivity.
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34. |
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35. |
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36. |
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37. |
- Davidson, Per, et al.
(author)
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No effect of sleep on the generalization of fear learning
- 2014
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In: Journal of Sleep Research. - : Wiley-Blackwell Publishing Ltd. - 1365-2869 .- 0962-1105. ; 23
-
Journal article (other academic/artistic)abstract
- Objectives: Sleep has been shown to be involved both in emotion regulation and in the active processing of information. We combined these two concepts and tested if sleep affected the generalization of fear learning. Methods: In a fear conditioning paradigm, participants were shown images of a small and a big circle where one of them was paired with an aversive sound, making it the CS+. Fear was measured with skin conductance responses. Participants were then randomly divided into a sleep or a wake group. The sleep group took a 2 h nap while the wake group rested for 2 h. Participants were then exposed to the two circles seen before, combined with 8 novel circles that gradually varied in size from the small one to the big one. We looked at how many circle sizes away from the CS+ that participants still exhibited a fear response, and if this differed between the sleep and the wake group. Results: We found no effect of sleep on the slope of the generalization across the different circles. There was a main effect of circle size, F(1,25) = 10.42, P = 0.01, but no main effect of sleep/wake, F (1,25) = 0.40, P = 0.54, and no interaction between sleep/wake X circle size, F(1,25) = 0.62, P = 0.44. Conclusions: The fear conditioning manipulation worked, with a gradual increase of fear depending on the stimuli’s similarity to the CS+. However, there was no effect of sleep or wake, which could possibly be explained by that just a 2 h nap not being a sufficient sleep manipulation to detect any differences.
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38. |
- Davidson, Per, et al.
(author)
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Sleep and the generalization of fear learning
- 2016
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In: Journal of Sleep Research. - : Wiley-Blackwell. - 0962-1105 .- 1365-2869. ; 25:1, s. 88-95
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Journal article (peer-reviewed)abstract
- Fear conditioning is an important survival mechanism, as is the ability to generalize learned fear responses to stimuli that are similar to the original conditioned stimulus. Overgeneralization of fear learning, prominent in many anxiety disorders, is however highly maladaptive. Because sleep is involved in the consolidation of fear learning, and in active processing of information, the present study explored the effect of sleep on generalization of fear learning. Participants watched a random sequence of pictures of a small and a big circle, one of them coupled with an aversive sound. Then, after a delay period containing either a nap or wake, generalization was examined as participants watched the two circles again, together with eight novel circles that gradually varied in size between the former two. Results showed that the fear response increased as a function of similarity to the conditioned response. However, there was no difference in the degree of generalization between the sleep and the wake group.
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39. |
- Davidson, Per, et al.
(author)
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Sleep and the generalization of fear learning
- 2016
-
In: Journal of Sleep Research. - : Wiley-Blackwell Publishing Ltd. - 0962-1105 .- 1365-2869. ; 25:1, s. 88-95
-
Journal article (peer-reviewed)abstract
- Fear conditioning is an important survival mechanism, as is the ability to generalize learned fear responses to stimuli that are similar to the original conditioned stimulus. Overgeneralization of fear learning, prominent in many anxiety disorders, is however highly maladaptive. Because sleep is involved in the consolidation of fear learning, and in active processing of information, the present study explored the effect of sleep on generalization of fear learning. Participants watched a random sequence of pictures of a small and a big circle, one of them coupled with an aversive sound. Then, after a delay period containing either a nap or wake, generalization was examined as participants watched the two circles again, together with eight novel circles that gradually varied in size between the former two. Results showed that the fear response increased as a function of similarity to the conditioned response. However, there was no difference in the degree of generalization between the sleep and the wake group.
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40. |
- Davidson, Per, et al.
(author)
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Suppression-induced forgetting diminishes following a delay of either sleep or wake
- 2020
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In: Journal of Cognitive Psychology. - : Informa UK Limited. - 2044-5911 .- 2044-592X. ; 32:1, s. 4-26
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Journal article (peer-reviewed)abstract
- We investigated the duration of suppression-induced forgetting (SIF), and the extent to which retrieval suppression differs between negative and neutral memories. We further examined if SIF was differently affected by sleep versus wake during the delay interval between retrieval suppression and re-test. Fifty participants first learned to associate neutral words with either neutral or negative images. Then, a subset of the words was shown again, and participants were asked to either recall (Think), or to suppress retrieval of (No-Think) the associated images. Finally, a memory test for all items was performed either immediately after the Think/No-Think (T/NT) phase (No Delay), or after a 3.5 h delay interval containing either sleep or wake. Results revealed a SIF effect only in the No Delay group, indicating that this forgetting effect dissipates already after a 3.5 h delay interval. Negative items were experienced as more intrusive than neutral ones during the T/NT phase.
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41. |
- Davidson, Per, et al.
(author)
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The association between mnemonic discrimination ability and differential fear learning
- 2021
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In: Journal of Behavior Therapy and Experimental Psychiatry. - : Elsevier Ltd.. - 0005-7916 .- 1873-7943. ; 75
-
Journal article (peer-reviewed)abstract
- Background and objectives: It is important to be able to learn which stimuli in our surroundings predict aversive outcomes. To maintain emotional well-being, it is similarly important to be able to learn which stimuli predict safety. The ability to discriminate between stimuli that predict danger and safety has been suggested to not only have an emotional component, but also a cognitive one. One such candidate mechanism is mnemonic discrimination (MD), the ability to differentiate between two memories that are similar but not identical. In the present study, we wanted to examine if MD performance helps to explain inter-individual differences in the ability to acquire a differentiated fear response during fear conditioning. Methods: Participants performed a task assessing MD ability, and then underwent a fear conditioning procedure. Fear responses were measured using skin conductance responses (SCRs). Results: Results revealed no support for MD ability being associated with to which degree a differentiated fear response was acquired, or with the time needed to acquire such a response. Limitations: Our only outcome measurement was SCRs. Future studies need to include fear ratings, expectancy ratings and neural responses. Future studies also need to examine this using a stimulus material where the conditioned stimulus and the safety stimulus are more difficult to distinguish from each other. Conclusions: If MD ability has a role in inhibiting overgeneralization of fear learning, this does not seem to be driven by MD already during the initial learning.
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42. |
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43. |
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44. |
- Davidson, Per, et al.
(author)
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The effect of sleep on intrusive memories in daily life : a systematic review and meta-analysis of trauma film experiments
- 2023
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In: Sleep. - : Oxford University Press. - 0161-8105 .- 1550-9109. ; 46:2
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Journal article (peer-reviewed)abstract
- Study objectives: To synthesize the literature on the effect of sleep versus wake on the frequency and distress of intrusive memories in everyday life after watching film clips with distressing content as a proxy for traumatic experiences.Methods: We conducted a systematic review by searching PubMed and PsychInfo. The last search was conducted on January 31 st 2022. We included experimental studies comparing sleep and wake groups on intrusions using ecological diary methods, whereas studies lacking a wake control condition or relying solely on intrusion-triggering tasks or retrospective questionnaires were excluded. Meta-analyses were performed to evaluate the results. Risks of biases were assessed following the Cochrane guidelines.Results: Across 7 effect sizes from 6 independent studies, sleep (n = 192), as compared to wake (n=175), significantly reduced the number of intrusive memories (Hedges' g = -0.26, p = .04, 95% CI [-0.50, -0.01]), but not the distress associated with them (Hedges' g = -0.14, p = .25, 95% CI [-0.38, 0.10]).Conclusions: Although the results suggest that sleep reduces the number of intrusions, there is a strong need for high-powered pre-registered studies to confirm this effect. Risks of biases in the reviewed work include the selection of the reported results, measurement of the outcome, and failure to adhere to the intervention. Limits with the current meta-analysis include the few number of studies, only including English-language studies, and the fact that it was not pre-registered.
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45. |
- Davidson, Per, et al.
(author)
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The Effect of Sleep on Intrusive Memories in Daily Life: A Systematic Review and Meta-analysis of Trauma Film Experiments
- 2022
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In: Sleep. - 1550-9109.
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Journal article (peer-reviewed)abstract
- Study objectives: Following traumatic events, people frequently experience distressing, involuntary memories of them (i.e., intrusions). Accumulating evidence suggests that sleep facilitates voluntary memory retrieval by supporting memory consolidation, but it is less clear what effect sleep has on intrusions. Recent research has used distressing film clips as a proxy for traumatizing events and examined whether sleep affects intrusions by prompting participants to record diaries of intrusions across several days after viewing the trauma film. We sought to synthesize the literature on sleep and intrusions by performing a meta-analysis.Methods: A total of 7 effect sizes from 6 independent studies were included in two meta-analyses examining the effect of sleep (n=192) compared to wake (n=175) on a) the number of intrusions and b) the mean distress associated with them. Results: There was a small significant effect where sleep reduced the number of intrusive memories (Hedges’ g = -0.26, p = .04, 95% CI [-0.50, -0.01]). Sleep did not significantly affect the average distress associated with intrusions (Hedges’ g = -0.14, p = .25, 95% CI [-0.38, 0.10]).Conclusions: Although sleep appears to reduce the number of intrusive memories of distressing films, high-powered studies are needed to examine the reproducibility of this effect. We discuss to which extent this effect is caused by sleep affecting the consolidation of these memories, and to which extent sleep simply makes it easier to consciously control which memories enter into awareness.
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- Davidson, Per
(author)
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Wake and be fine? : The effect of sleep on emotional memory
- 2017
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Doctoral thesis (other academic/artistic)abstract
- The aim of this thesis was to examine the effect of sleep on emotional memories. The first two studies examined the role of sleep in the generalization of fear learning and the third study examined how sleep affected the forgetting of unwanted emotional memories.In study 1, participants first underwent fear conditioning with a small and a large circle as the CS+ and the CS-. Next, after either a nap or an equal amount of time spent awake, participants viewed these two circles again, as well as eight novel circles that gradually varied in size in-between the former two. The results showed that fear conditioning was successful and that that there was a tendency towards the larger responses to the CS+ as compared to the CS- having been preserved during the delay interval but that there was no group difference. Analyzing responses to the novel stimuli revealed that fear responses increased as a function of their similarity to the CS+. This increase did however not differ between the groups, thus there was no support for that sleep or wake would differently affect the generalization of fear learning.In study 2, a similar design was used, but with electric shocks instead of the aversive sound, in order to elicit a stronger fear response. The results revealed that in the wake group, fear responses were larger to the CS+ compared to the CS-, whereas no such effect was observed after sleep. Similar results were evident for fear responses to the novel circles, indicating that after sleep, similarity to the CS+ was no longer a predictor of the degree of fear responding. The groups did not differ in general responsivity, but only in how their responses were distributed across the stimuli.In study 3, participants first learned associations between neutral words and images that were either negative or neutral. Then, in the Think/No-Think phase, a subset of these words were shown without the images, and participants were asked to either try to think of the image that they had previously been associated with (Think items) or to avoid all thoughts of the associated image (No-Think items). Then, memory was tested for all the items. Results revealed significant below baseline forgetting of the No-Think items in the group that was tested right after the conclusion of the No-Think phase. This forgetting effect had however disappeared after a longer delay interval, regardless of if it had contained sleep or wake, regardless of the emotionality of the images. Thus, we found no support that sleep and wake would differently affect the duration of this forgetting effect.
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- Davidsson, P., et al.
(author)
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No effect of sleep on the generalization of fear learning
- 2014
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In: Journal of sleep research. - : Wiley-Blackwell. - 1365-2869. ; 23, s. 7-
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Journal article (other academic/artistic)abstract
- Objectives: Sleep has been shown to be involved both in emotion regulation and in the active processing of information. We combined these two concepts and tested if sleep affected the generalization of fear learning.Methods: In a fear conditioning paradigm, participants were shown images of a small and a big circle where one of them was paired with an aversive sound, making it the CS+. Fear was measured with skin conductance responses. Participants were then randomly divided into a sleep or a wake group. The sleep group took a 2 h nap while the wake group rested for 2 h. Participants were then exposed to the two circles seen before, combined with 8 novel circles that gradually varied in size from the small one to the big one. We looked at how many circle sizes away from the CS+ that participants still exhibited a fear response, and if this differed between the sleep and the wake group.Results: We found no effect of sleep on the slope of the generalization across the different circles. There was a main effect of circle size, F(1,25) = 10.42, P = 0.01, but no main effect of sleep/wake, F (1,25) = 0.40, P = 0.54, and no interaction between sleep/wake X circle size, F(1,25) = 0.62, P = 0.44.Conclusions: The fear conditioning manipulation worked, with a gradual increase of fear depending on the stimuli’s similarity to the CS+. However, there was no effect of sleep or wake, which could possibly be explained by that just a 2 h nap not being a sufficient sleep manipulation to detect any differences.
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