| 1. |
- Danaei, Goodarz, et al.
(författare)
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Effects of diabetes definition on global surveillance of diabetes prevalence and diagnosis: a pooled analysis of 96 population-based studies with 331288 participants
- 2015
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Ingår i: The Lancet Diabetes & Endocrinology. - 2213-8595 .- 2213-8587. ; 3:8, s. 624-637
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Tidskriftsartikel (refereegranskat)abstract
- Background Diabetes has been defined on the basis of different biomarkers, including fasting plasma glucose (FPG), 2-h plasma glucose in an oral glucose tolerance test (2hOGTT), and HbA(1c). We assessed the effect of different diagnostic definitions on both the population prevalence of diabetes and the classification of previously undiagnosed individuals as having diabetes versus not having diabetes in a pooled analysis of data from population-based health examination surveys in different regions. Methods We used data from 96 population-based health examination surveys that had measured at least two of the biomarkers used for defining diabetes. Diabetes was defined using HbA(1c) (HbA(1c) >= 6 . 5% or history of diabetes diagnosis or using insulin or oral hypoglycaemic drugs) compared with either FPG only or FPG-or-2hOGTT definitions (FPG >= 7 . 0 mmol/L or 2hOGTT >= 11 . 1 mmol/L or history of diabetes or using insulin or oral hypoglycaemic drugs). We calculated diabetes prevalence, taking into account complex survey design and survey sample weights. We compared the prevalences of diabetes using different definitions graphically and by regression analyses. We calculated sensitivity and specificity of diabetes diagnosis based on HbA1c compared with diagnosis based on glucose among previously undiagnosed individuals (ie, excluding those with history of diabetes or using insulin or oral hypoglycaemic drugs). We calculated sensitivity and specificity in each survey, and then pooled results using a random-effects model. We assessed the sources of heterogeneity of sensitivity by meta-regressions for study characteristics selected a priori. Findings Population prevalence of diabetes based on FPG- or-2hOGTT was correlated with prevalence based on FPG alone (r= 0 . 98), but was higher by 2-6 percentage points at different prevalence levels. Prevalence based on HbA(1c) was lower than prevalence based on FPG in 42 . 8% of age-sex-survey groups and higher in another 41 . 6%; in the other 15 . 6%, the two definitions provided similar prevalence estimates. The variation across studies in the relation between glucose-based and HbA(1c)-based prevalences was partly related to participants' age, followed by natural logarithm of per person gross domestic product, the year of survey, mean BMI, and whether the survey population was national, subnational, or from specific communities. Diabetes defined as HbA(1c) 6 . 5% or more had a pooled sensitivity of 52 . 8% (95% CI 51 . 3-54 . 3%) and a pooled specificity of 99 . 74% (99 . 71-99 . 78%) compared with FPG 7 . 0 mmol/L or more for diagnosing previously undiagnosed participants; sensitivity compared with diabetes defined based on FPG-or-2hOGTT was 30 . 5% (28 . 7-32 . 3%). None of the preselected study-level characteristics explained the heterogeneity in the sensitivity of HbA(1c) versus FPG. Interpretation Different biomarkers and definitions for diabetes can provide different estimates of population prevalence of diabetes, and differentially identify people without previous diagnosis as having diabetes. Using an HbA(1c)-based definition alone in health surveys will not identify a substantial proportion of previously undiagnosed people who would be considered as having diabetes using a glucose-based test.
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| 2. |
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| 3. |
- Docherty, Anna R, et al.
(författare)
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GWAS Meta-Analysis of Suicide Attempt: Identification of 12 Genome-Wide Significant Loci and Implication of Genetic Risks for Specific Health Factors.
- 2023
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Ingår i: The American journal of psychiatry. - : American Psychiatric Association Publishing. - 1535-7228 .- 0002-953X. ; 180:10, s. 723-738
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Tidskriftsartikel (refereegranskat)abstract
- Suicidal behavior is heritable and is a major cause of death worldwide. Two large-scale genome-wide association studies (GWASs) recently discovered and cross-validated genome-wide significant (GWS) loci for suicide attempt (SA). The present study leveraged the genetic cohorts from both studies to conduct the largest GWAS meta-analysis of SA to date. Multi-ancestry and admixture-specific meta-analyses were conducted within groups of significant African, East Asian, and European ancestry admixtures.This study comprised 22 cohorts, including 43,871 SA cases and 915,025 ancestry-matched controls. Analytical methods across multi-ancestry and individual ancestry admixtures included inverse variance-weighted fixed-effects meta-analyses, followed by gene, gene-set, tissue-set, and drug-target enrichment, as well as summary-data-based Mendelian randomization with brain expression quantitative trait loci data, phenome-wide genetic correlation, and genetic causal proportion analyses.Multi-ancestry and European ancestry admixture GWAS meta-analyses identified 12 risk loci at p values <5×10-8. These loci were mostly intergenic and implicated DRD2, SLC6A9, FURIN, NLGN1, SOX5, PDE4B, and CACNG2. The multi-ancestry SNP-based heritability estimate of SA was 5.7% on the liability scale (SE=0.003, p=5.7×10-80). Significant brain tissue gene expression and drug set enrichment were observed. There was shared genetic variation of SA with attention deficit hyperactivity disorder, smoking, and risk tolerance after conditioning SA on both major depressive disorder and posttraumatic stress disorder. Genetic causal proportion analyses implicated shared genetic risk for specific health factors.This multi-ancestry analysis of suicide attempt identified several loci contributing to risk and establishes significant shared genetic covariation with clinical phenotypes. These findings provide insight into genetic factors associated with suicide attempt across ancestry admixture populations, in veteran and civilian populations, and in attempt versus death.
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| 4. |
- Haas, Brian J., et al.
(författare)
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Genome sequence and analysis of the Irish potato famine pathogen Phytophthora infestans
- 2009
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 461:7262, s. 393-398
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Tidskriftsartikel (refereegranskat)abstract
- Phytophthora infestans is the most destructive pathogen of potato and a model organism for the oomycetes, a distinct lineage of fungus-like eukaryotes that are related to organisms such as brown algae and diatoms. As the agent of the Irish potato famine in the mid-nineteenth century, P. infestans has had a tremendous effect on human history, resulting in famine and population displacement(1). To this day, it affects world agriculture by causing the most destructive disease of potato, the fourth largest food crop and a critical alternative to the major cereal crops for feeding the world's population(1). Current annual worldwide potato crop losses due to late blight are conservatively estimated at $6.7 billion(2). Management of this devastating pathogen is challenged by its remarkable speed of adaptation to control strategies such as genetically resistant cultivars(3,4). Here we report the sequence of the P. infestans genome, which at similar to 240 megabases (Mb) is by far the largest and most complex genome sequenced so far in the chromalveolates. Its expansion results from a proliferation of repetitive DNA accounting for similar to 74% of the genome. Comparison with two other Phytophthora genomes showed rapid turnover and extensive expansion of specific families of secreted disease effector proteins, including many genes that are induced during infection or are predicted to have activities that alter host physiology. These fast-evolving effector genes are localized to highly dynamic and expanded regions of the P. infestans genome. This probably plays a crucial part in the rapid adaptability of the pathogen to host plants and underpins its evolutionary potential.
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| 5. |
- Keasar, Chen, et al.
(författare)
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An analysis and evaluation of the WeFold collaborative for protein structure prediction and its pipelines in CASP11 and CASP12
- 2018
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Ingår i: Scientific Reports. - : NATURE PUBLISHING GROUP. - 2045-2322. ; 8
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Tidskriftsartikel (refereegranskat)abstract
- Every two years groups worldwide participate in the Critical Assessment of Protein Structure Prediction (CASP) experiment to blindly test the strengths and weaknesses of their computational methods. CASP has significantly advanced the field but many hurdles still remain, which may require new ideas and collaborations. In 2012 a web-based effort called WeFold, was initiated to promote collaboration within the CASP community and attract researchers from other fields to contribute new ideas to CASP. Members of the WeFold coopetition (cooperation and competition) participated in CASP as individual teams, but also shared components of their methods to create hybrid pipelines and actively contributed to this effort. We assert that the scale and diversity of integrative prediction pipelines could not have been achieved by any individual lab or even by any collaboration among a few partners. The models contributed by the participating groups and generated by the pipelines are publicly available at the WeFold website providing a wealth of data that remains to be tapped. Here, we analyze the results of the 2014 and 2016 pipelines showing improvements according to the CASP assessment as well as areas that require further adjustments and research.
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| 6. |
- Komatsu, Kimberly J., et al.
(författare)
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Global change effects on plant communities are magnified by time and the number of global change factors imposed
- 2019
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Ingår i: Proceedings of the National Academy of Sciences of the United States of America. - : National Academy of Sciences. - 0027-8424 .- 1091-6490. ; 116:36, s. 17867-17873
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Tidskriftsartikel (refereegranskat)abstract
- Accurate prediction of community responses to global change drivers (GCDs) is critical given the effects of biodiversity on ecosystem services. There is consensus that human activities are driving species extinctions at the global scale, but debate remains over whether GCDs are systematically altering local communities worldwide. Across 105 experiments that included over 400 experimental manipulations, we found evidence for a lagged response of herbaceous plant communities to GCDs caused by shifts in the identities and relative abundances of species, often without a corresponding difference in species richness. These results provide evidence that community responses are pervasive across a wide variety of GCDs on long-term temporal scales and that these responses increase in strength when multiple GCDs are simultaneously imposed.Global change drivers (GCDs) are expected to alter community structure and consequently, the services that ecosystems provide. Yet, few experimental investigations have examined effects of GCDs on plant community structure across multiple ecosystem types, and those that do exist present conflicting patterns. In an unprecedented global synthesis of over 100 experiments that manipulated factors linked to GCDs, we show that herbaceous plant community responses depend on experimental manipulation length and number of factors manipulated. We found that plant communities are fairly resistant to experimentally manipulated GCDs in the short term (<10 y). In contrast, long-term (≥10 y) experiments show increasing community divergence of treatments from control conditions. Surprisingly, these community responses occurred with similar frequency across the GCD types manipulated in our database. However, community responses were more common when 3 or more GCDs were simultaneously manipulated, suggesting the emergence of additive or synergistic effects of multiple drivers, particularly over long time periods. In half of the cases, GCD manipulations caused a difference in community composition without a corresponding species richness difference, indicating that species reordering or replacement is an important mechanism of community responses to GCDs and should be given greater consideration when examining consequences of GCDs for the biodiversity–ecosystem function relationship. Human activities are currently driving unparalleled global changes worldwide. Our analyses provide the most comprehensive evidence to date that these human activities may have widespread impacts on plant community composition globally, which will increase in frequency over time and be greater in areas where communities face multiple GCDs simultaneously.
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| 7. |
- Titov, Nickolai, et al.
(författare)
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ICBT in routine care : A descriptive analysis of successful clinics in five countries
- 2018
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Ingår i: Internet Interventions. - : Elsevier. - 2214-7829. ; 13, s. 108-115
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Forskningsöversikt (refereegranskat)abstract
- Clinical trials have demonstrated the efficacy of internet delivered cognitive behaviour therapy (ICBT) for anxiety and depression. However, relatively little is known about the context, operations, and outcomes of ICBT when administered as part of routine care. This paper describes the setting, relationship to existing health services, procedures for referral, assessment, treatment, patients and outcomes of ICBT clinics in Sweden, Denmark, Norway, Canada and Australia. All five clinics provide services free or at low cost to patients. All have systems of governance to monitor quality of care, patient safety, therapist performance and data security. All five clinics include initial assessments by clinicians and between 10 and 20 min of therapist support during each week. Published reports of outcomes all demonstrate large clinical improvement, low rates of deterioration, and high levels of patient satisfaction. Services that require a face to face assessment treat smaller numbers of patients and have fewer patients from remote locations. The paper shows that therapist-guided ICBT can be a valuable part of mental health services for anxiety and depression. Important components of successful ICBT services are rigorous governance to maintain a high standard of clinical care, and the measurement and reporting of outcomes.
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| 8. |
- Titov, Nickolai, et al.
(författare)
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MindSpot Clinic : An Accessible, Efficient, and Effective Online Treatment Service for Anxiety and Depression.
- 2015
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Ingår i: Psychiatric Services. - : American Psychiatric Association Publishing. - 1075-2730 .- 1557-9700. ; 66:10, s. 1043-1050
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: The main objective of this study was to report the feasibility of delivering online cognitive-behavioral therapy (iCBT) treatments for anxiety and depression in a national public mental health service.METHODS: A prospective noncontrolled cohort study was conducted of all patients who began assessment or treatment at the MindSpot Clinic from January through December 2013. Clinic services were used by a representative cross-section of the Australian population. Mean age at assessment was 36.4±13.0 years, and age range was 18-86 years. Patients completed one of four online courses over eight weeks, during which they received weekly support from a therapist via telephone or secure e-mail. Primary outcome measures were the nine-item Patient Health Questionnaire (PHQ-9) and the seven-item Generalized Anxiety Disorder scale (GAD-7) administered at posttreatment and three months posttreatment.RESULTS: A total of 10,293 adults who self-identified as having problems with anxiety or depression commenced assessment, and 7,172 completed the assessment and were eligible for analysis. Of these, 2,049 enrolled in a course and 1,471 completed the course, for a course completion rate of 71.8%. Moderate to large noncontrolled effect sizes (Cohen's d=.67-1.66, 95% confidence interval=.08-2.07) were found from assessment to three-month follow-up. At posttreatment and follow-up, reliable recovery ranged from 46.7% to 51.1%, and deterioration ranged from 1.9% to 3.8%. Mean total therapist time per patient was 111.8±61.6 minutes.CONCLUSIONS: The MindSpot Clinic produced treatment outcomes that were comparable to results from published clinical trials of iCBT. This model of service delivery represents an innovative method of providing accessible, low-cost, effective, and acceptable mental health services to many people who currently are not receiving care.
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| 9. |
- Titov, Nickolai, et al.
(författare)
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User characteristics and outcomes from a national digital mental health service : an observational study of registrants of the Australian MindSpot Clinic.
- 2020
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Ingår i: The Lancet Digital Health. - London, United Kingdom : The Lancet Publishing Group. - 2589-7500. ; 2:11, s. e582-e593
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Tidskriftsartikel (refereegranskat)abstract
- Background: Interest is growing in digital and telehealth delivery of mental health services, but data are scarce on outcomes in routine care. The federally funded Australian MindSpot Clinic provides online and telephone psychological assessment and treatment services to Australian adults. We aimed to summarise demographic characteristics and treatment outcomes of patients registered with MindSpot over the first 7 years of clinic operation.Methods: We used an observational design to review all patients who registered for assessment with the MindSpot Clinic between Jan 1, 2013, and Dec 31, 2019. We descriptively analysed the demographics, service preferences, and baseline symptoms of patients. Among patients enrolled in a digital treatment course, we evaluated scales of depression (Patient Health Questionnaire-9 [PHQ-9]) and anxiety (Generalized Anxiety Disorder 7-Item Scale [GAD-7]), as primary measures of treatment outcome, from the screening assessment to post-treatment and a 3 month follow-up. The Kessler Psychological Distress 10-Item Plus Scale was also used to assess changes in general distress and disability, and course satisfaction was measured post-treatment.Outcomes: A total of 121 652 screening assessments were started, of which 96 018 (78·9%) were completed. The mean age of patients was 35·7 years (SD 13·8) and 88 702 (72·9%) were women. Based on available assessment data, 36 866 (34·5%) of 106 811 participants had never previously spoken to a health professional about their symptoms, and most people self-reported symptoms of anxiety (88 879 [81·9%] of 108 494) or depression (78 803 [72·6%] of 108 494), either alone or in combination, at baseline. 21 745 patients started treatment in a therapist-guided online course, of whom 14 503 (66·7%) completed treatment (≥four of five lessons). Key trends in service use included an increase in the proportion of people using MindSpot primarily for assessment and information, from 52·6% in 2013 to 66·7% in 2019, while the proportion primarily seeking online treatment decreased, from 42·6% in 2013 to 26·7% in 2019. Effect sizes and percentage changes were large for estimated mean scores on the PHQ-9 and GAD-7 from assessment to post-treatment (PHQ-9, Cohen's d effect size 1·40 [95% CI 1·37-1·43]; and GAD-7, 1·45 [1·42-1·47]) and the 3 month follow-up (PHQ-9, 1·36 [1·34-1·38]; and GAD-7, 1·42 [1·40-1·44]); proportions of patients with reliable symptom deterioration (score increase of ≥6 points [PHQ-9] or ≥5 points [GAD-7]) were low post-treatment (of 13 058 respondents, 184 [1·4%] had symptom deterioration on the PHQ-9 and 282 [2·2%] on the GAD-7); and patient satisfaction rates were high (12 452 [96·6%] of 12 895 respondents would recommend the course and 12 433 [96·7%] of 12 860 reported the course worthwhile). We also observed small improvements in disability following treatment as measured by days out of role.Interpretation: Our findings indicate improvement in psychological symptoms and positive reception among patients receiving online mental health treatment. These results support the addition of digital services such as MindSpot as a component in contemporary national mental health systems.Funding: None.
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