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Sökning: WFRF:(Pugh E)

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  • Michailidou, Kyriaki, et al. (författare)
  • Association analysis identifies 65 new breast cancer risk loci.
  • 2017
  • Ingår i: Nature. - : Nature Publishing Group. - 0028-0836 .- 1476-4687. ; 551:7678, s. 92-94
  • Tidskriftsartikel (refereegranskat)abstract
    • Breast cancer risk is influenced by rare coding variants in susceptibility genes, such as BRCA1, and many common, mostly non-coding variants. However, much of the genetic contribution to breast cancer risk remains unknown. Here we report the results of a genome-wide association study of breast cancer in 122,977 cases and 105,974 controls of European ancestry and 14,068 cases and 13,104 controls of East Asian ancestry. We identified 65 new loci that are associated with overall breast cancer risk at P < 5 × 10-8. The majority of credible risk single-nucleotide polymorphisms in these loci fall in distal regulatory elements, and by integrating in silico data to predict target genes in breast cells at each locus, we demonstrate a strong overlap between candidate target genes and somatic driver genes in breast tumours. We also find that heritability of breast cancer due to all single-nucleotide polymorphisms in regulatory features was 2-5-fold enriched relative to the genome-wide average, with strong enrichment for particular transcription factor binding sites. These results provide further insight into genetic susceptibility to breast cancer and will improve the use of genetic risk scores for individualized screening and prevention.
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  • Furukawa, Toshi A., et al. (författare)
  • Dismantling, optimising, and personalising internet cognitive behavioural therapy for depression : a systematic review and component network meta-analysis using individual data
  • 2021
  • Ingår i: Lancet psychiatry. - London, United Kingdom : Elsevier. - 2215-0374 .- 2215-0366. ; 8:6, s. 500-511
  • Forskningsöversikt (refereegranskat)abstract
    • Findings We identified 76 RCTs, including 48 trials contributing individual participant data (11 704 participants) and 28 trials with aggregate data (6474 participants). The participants' weighted mean age was 42.0 years and 12 406 (71%) of 17 521 reported were women. There was suggestive evidence that behavioural activation might be beneficial (iMD -1.83 [95% credible interval (CrI) -2.90 to -0.80]) and that relaxation might be harmful (1.20 [95% CrI 0.17 to 2.27]). Baseline severity emerged as the strongest prognostic factor for endpoint depression. Combining human and automated encouragement reduced dropouts from treatment (incremental odds ratio, 0.32 [95% CrI 0.13 to 0.93]). The risk of bias was low for the randomisation process, missing outcome data, or selection of reported results in most of the included studies, uncertain for deviation from intended interventions, and high for measurement of outcomes. There was moderate to high heterogeneity among the studies and their components. 511
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  • Huyghe, Jeroen R., et al. (författare)
  • Discovery of common and rare genetic risk variants for colorectal cancer
  • 2019
  • Ingår i: Nature Genetics. - : Nature Publishing Group. - 1061-4036 .- 1546-1718. ; 51:1, s. 76-
  • Tidskriftsartikel (refereegranskat)abstract
    • To further dissect the genetic architecture of colorectal cancer (CRC), we performed whole-genome sequencing of 1,439 cases and 720 controls, imputed discovered sequence variants and Haplotype Reference Consortium panel variants into genome-wide association study data, and tested for association in 34,869 cases and 29,051 controls. Findings were followed up in an additional 23,262 cases and 38,296 controls. We discovered a strongly protective 0.3% frequency variant signal at CHD1. In a combined meta-analysis of 125,478 individuals, we identified 40 new independent signals at P < 5 x 10(-8), bringing the number of known independent signals for CRC to similar to 100. New signals implicate lower-frequency variants, Kruppel-like factors, Hedgehog signaling, Hippo-YAP signaling, long noncoding RNAs and somatic drivers, and support a role for immune function. Heritability analyses suggest that CRC risk is highly polygenic, and larger, more comprehensive studies enabling rare variant analysis will improve understanding of biology underlying this risk and influence personalized screening strategies and drug development.
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6.
  • Jung, Christian, et al. (författare)
  • A comparison of very old patients admitted to intensive care unit after acute versus elective surgery or intervention
  • 2019
  • Ingår i: Journal of critical care. - : W B SAUNDERS CO-ELSEVIER INC. - 0883-9441 .- 1557-8615. ; 52, s. 141-148
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: We aimed to evaluate differences in outcome between patients admitted to intensive care unit (ICU) after elective versus acute surgery in a multinational cohort of very old patients (80 years; VIP). Predictors of mortality, with special emphasis on frailty, were assessed.Methods: In total, 5063 VIPs were induded in this analysis, 922 were admitted after elective surgery or intervention, 4141 acutely, with 402 after acute surgery. Differences were calculated using Mann-Whitney-U test and Wilcoxon test. Univariate and multivariable logistic regression were used to assess associations with mortality.Results: Compared patients admitted after acute surgery, patients admitted after elective surgery suffered less often from frailty as defined as CFS (28% vs 46%; p < 0.001), evidenced lower SOFA scores (4 +/- 5 vs 7 +/- 7; p < 0.001). Presence of frailty (CFS >4) was associated with significantly increased mortality both in elective surgery patients (7% vs 12%; p = 0.01), in acute surgery (7% vs 12%; p = 0.02).Conclusions: VIPs admitted to ICU after elective surgery evidenced favorable outcome over patients after acute surgery even after correction for relevant confounders. Frailty might be used to guide clinicians in risk stratification in both patients admitted after elective and acute surgery. 
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  • Appeltans, W., et al. (författare)
  • The Magnitude of Global Marine Species Diversity
  • 2012
  • Ingår i: Current Biology. - 0960-9822. ; 22:23, s. 2189-2202
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: The question of how many marine species exist is important because it provides a metric for how much we do and do not know about life in the oceans. We have compiled the first register of the marine species of the world and used this baseline to estimate how many more species, partitioned among all major eukaryotic groups, may be discovered. Results: There are similar to 226,000 eukaryotic marine species described. More species were described in the past decade (similar to 20,000) than in any previous one. The number of authors describing new species has been increasing at a faster rate than the number of new species described in the past six decades. We report that there are similar to 170,000 synonyms, that 58,000-72,000 species are collected but not yet described, and that 482,000-741,000 more species have yet to be sampled. Molecular methods may add tens of thousands of cryptic species. Thus, there may be 0.7-1.0 million marine species. Past rates of description of new species indicate there may be 0.5 +/- 0.2 million marine species. On average 37% (median 31%) of species in over 100 recent field studies around the world might be new to science. Conclusions: Currently, between one-third and two-thirds of marine species may be undescribed, and previous estimates of there being well over one million marine species appear highly unlikely. More species than ever before are being described annually by an increasing number of authors. If the current trend continues, most species will be discovered this century.
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8.
  • Bowden, John A., et al. (författare)
  • Harmonizing lipidomics : NIST interlaboratory comparison exercise for lipidomics using SRM 1950-Metabolites in Frozen Human Plasma
  • 2017
  • Ingår i: Journal of Lipid Research. - : American Society for Biochemistry and Molecular Biology. - 0022-2275 .- 1539-7262. ; 58:12, s. 2275-2288
  • Tidskriftsartikel (refereegranskat)abstract
    • As the lipidomics field continues to advance, self-evaluation within the community is critical. Here, we performed an interlaboratory comparison exercise for lipidomics using Standard Reference Material (SRM) 1950-Metabolites in Frozen Human Plasma, a commercially available reference material. The interlaboratory study comprised 31 diverse laboratories, with each laboratory using a different lipidomics workflow. A total of 1,527 unique lipids were measured across all laboratories and consensus location estimates and associated uncertainties were determined for 339 of these lipids measured at the sum composition level by five or more participating laboratories. These evaluated lipids detected in SRM 1950 serve as community-wide benchmarks for intra-and interlaboratory quality control and method validation. These analyses were performed using nonstandardized laboratory-independent workflows. The consensus locations were also compared with a previous examination of SRM 1950 by the LIPID MAPS consortium.jlr While the central theme of the interlaboratory study was to provide values to help harmonize lipids, lipid mediators, and precursor measurements across the community, it was also initiated to stimulate a discussion regarding areas in need of improvement.
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  • Hadjistavropoulos, H. D., et al. (författare)
  • Predicting Response to Therapist-Assisted Internet-Delivered Cognitive Behavior Therapy for Depression or Anxiety Within an Open Dissemination Trial
  • 2016
  • Ingår i: Behavior Therapy. - : Elsevier. - 0005-7894 .- 1878-1888. ; 47:2, s. 155-165
  • Tidskriftsartikel (refereegranskat)abstract
    • Therapist-assisted Internet-delivered cognitive behavior therapy (ICBT) is efficacious for treating anxiety and depression, but predictors of response to treatment when delivered in clinical practice are not well understood. In this study, we explored demographic, clinical, and program variables that predicted modules started and symptom improvement (i.e., Generalized Anxiety Disorder-7 or Patient Health Questionnaire-9 total scores over pre-, mid-, and posttreatment) within a previously published open dissemination trial (Hadjistavropoulos et al., 2014). The sample consisted of 195 patients offered 12 modules of therapist-assisted ICBT for depression or generalized anxiety; ICBT was delivered by therapists working in six geographically dispersed clinics. Consistent across ICBT for depression or generalized anxiety, starting fewer modules was associated with more phone calls from therapists reflecting that therapists tended to call patients who did not start modules as scheduled. Also consistent for both ICBT programs, greater pretreatment condition severity and completion of more modules was associated with superior ICBT-derived benefit. Other predictors of response to treatment varied across the two programs. Younger age, lower education, taking psychotropic medication, being in receipt of psychiatric care and lower comfort with written communication were associated with either fewer program starts or lower symptom improvement in one of the two programs. It is concluded that monitoring response to ICBT may be particularly important in patients with these characteristics. Research directions for identifying patients who are less likely to benefit from ICBT are discussed.
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10.
  • Hadjistavropoulos, H. D., et al. (författare)
  • Therapeutic Alliance in Internet-Delivered Cognitive Behaviour Therapy for Depression or Generalized Anxiety
  • 2017
  • Ingår i: Clinical Psychology and Psychotherapy. - : John Wiley & Sons. - 1063-3995 .- 1099-0879. ; 24:2, s. 451-461
  • Tidskriftsartikel (refereegranskat)abstract
    • There has been limited research on therapeutic alliance in the context of therapist-assisted Internet-delivered cognitive behaviour therapy (ICBT) when delivered in clinical practice. The present study investigated therapeutic alliance in ICBT delivered to patients seeking treatment for symptoms of depression (n=83) or generalized anxiety (n=112) as part of an open dissemination trial. ICBT was provided by 27 registered therapists or 28 graduate students working in six geographically dispersed clinics; therapist-assistance was delivered primarily through secure messages and occasionally telephone calls. The Generalized Anxiety Disorder-7 and Patient Health Questionnaire-9 were collected pre-, mid- and post-treatment, and the Therapeutic Alliance Questionnaire was assessed mid- and post-treatment. Therapeutic alliance ratings were high both at mid-treatment and post-treatment (above 80%). There was no relationship between therapeutic alliance ratings and improvement on primary outcomes. Among patients treated for depression, lower ratings of mid-treatment alliance were associated with concurrent treatment by a psychiatrist and fewer phone calls and emails from their therapist. Among patients treated for generalized anxiety, ratings of mid-treatment alliance were higher among registered providers as compared to graduate students. Multiple directions for future research on therapeutic alliance in ICBT are offered, including suggestions for developing a new measure of therapeutic alliance specific to ICBT and measuring therapeutic alliance throughout the treatment process.
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