| 1. |
- Wang, Zhaoming, et al.
(författare)
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Imputation and subset-based association analysis across different cancer types identifies multiple independent risk loci in the TERT-CLPTM1L region on chromosome 5p15.33
- 2014
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Ingår i: Human Molecular Genetics. - : Oxford University Press (OUP). - 0964-6906 .- 1460-2083. ; 23:24, s. 6616-6633
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Tidskriftsartikel (refereegranskat)abstract
- Genome-wide association studies (GWAS) have mapped risk alleles for at least 10 distinct cancers to a small region of 63 000 bp on chromosome 5p15.33. This region harbors the TERT and CLPTM1L genes; the former encodes the catalytic subunit of telomerase reverse transcriptase and the latter may play a role in apoptosis. To investigate further the genetic architecture of common susceptibility alleles in this region, we conducted an agnostic subset-based meta-analysis (association analysis based on subsets) across six distinct cancers in 34 248 cases and 45 036 controls. Based on sequential conditional analysis, we identified as many as six independent risk loci marked by common single-nucleotide polymorphisms: five in the TERT gene (Region 1: rs7726159, P = 2.10 × 10(-39); Region 3: rs2853677, P = 3.30 × 10(-36) and PConditional = 2.36 × 10(-8); Region 4: rs2736098, P = 3.87 × 10(-12) and PConditional = 5.19 × 10(-6), Region 5: rs13172201, P = 0.041 and PConditional = 2.04 × 10(-6); and Region 6: rs10069690, P = 7.49 × 10(-15) and PConditional = 5.35 × 10(-7)) and one in the neighboring CLPTM1L gene (Region 2: rs451360; P = 1.90 × 10(-18) and PConditional = 7.06 × 10(-16)). Between three and five cancers mapped to each independent locus with both risk-enhancing and protective effects. Allele-specific effects on DNA methylation were seen for a subset of risk loci, indicating that methylation and subsequent effects on gene expression may contribute to the biology of risk variants on 5p15.33. Our results provide strong support for extensive pleiotropy across this region of 5p15.33, to an extent not previously observed in other cancer susceptibility loci.
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| 2. |
- Fazey, Ioan, et al.
(författare)
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Transforming knowledge systems for life on Earth : Visions of future systems and how to get there
- 2020
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Ingår i: Energy Research & Social Science. - : Elsevier. - 2214-6296 .- 2214-6326. ; 70
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Tidskriftsartikel (refereegranskat)abstract
- Formalised knowledge systems, including universities and research institutes, are important for contemporary societies. They are, however, also arguably failing humanity when their impact is measured against the level of progress being made in stimulating the societal changes needed to address challenges like climate change. In this research we used a novel futures-oriented and participatory approach that asked what future envisioned knowledge systems might need to look like and how we might get there. Findings suggest that envisioned future systems will need to be much more collaborative, open, diverse, egalitarian, and able to work with values and systemic issues. They will also need to go beyond producing knowledge about our world to generating wisdom about how to act within it. To get to envisioned systems we will need to rapidly scale methodological innovations, connect innovators, and creatively accelerate learning about working with intractable challenges. We will also need to create new funding schemes, a global knowledge commons, and challenge deeply held assumptions. To genuinely be a creative force in supporting longevity of human and non-human life on our planet, the shift in knowledge systems will probably need to be at the scale of the enlightenment and speed of the scientific and technological revolution accompanying the second World War. This will require bold and strategic action from governments, scientists, civic society and sustained transformational intent.
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| 3. |
- Satizabal, Claudia L., et al.
(författare)
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Genetic architecture of subcortical brain structures in 38,851 individuals
- 2019
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Ingår i: Nature Genetics. - : Nature Publishing Group. - 1061-4036 .- 1546-1718. ; 51:11, s. 1624-
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Tidskriftsartikel (refereegranskat)abstract
- Subcortical brain structures are integral to motion, consciousness, emotions and learning. We identified common genetic variation related to the volumes of the nucleus accumbens, amygdala, brainstem, caudate nucleus, globus pallidus, putamen and thalamus, using genome-wide association analyses in almost 40,000 individuals from CHARGE, ENIGMA and UK Biobank. We show that variability in subcortical volumes is heritable, and identify 48 significantly associated loci (40 novel at the time of analysis). Annotation of these loci by utilizing gene expression, methylation and neuropathological data identified 199 genes putatively implicated in neurodevelopment, synaptic signaling, axonal transport, apoptosis, inflammation/infection and susceptibility to neurological disorders. This set of genes is significantly enriched for Drosophila orthologs associated with neurodevelopmental phenotypes, suggesting evolutionarily conserved mechanisms. Our findings uncover novel biology and potential drug targets underlying brain development and disease.
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| 4. |
- Ademuyiwa, Adesoji O., et al.
(författare)
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Determinants of morbidity and mortality following emergency abdominal surgery in children in low-income and middle-income countries
- 2016
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Ingår i: BMJ Global Health. - : BMJ Publishing Group Ltd. - 2059-7908. ; 1:4
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Tidskriftsartikel (refereegranskat)abstract
- Background: Child health is a key priority on the global health agenda, yet the provision of essential and emergency surgery in children is patchy in resource-poor regions. This study was aimed to determine the mortality risk for emergency abdominal paediatric surgery in low-income countries globally.Methods: Multicentre, international, prospective, cohort study. Self-selected surgical units performing emergency abdominal surgery submitted prespecified data for consecutive children aged <16 years during a 2-week period between July and December 2014. The United Nation's Human Development Index (HDI) was used to stratify countries. The main outcome measure was 30-day postoperative mortality, analysed by multilevel logistic regression.Results: This study included 1409 patients from 253 centres in 43 countries; 282 children were under 2 years of age. Among them, 265 (18.8%) were from low-HDI, 450 (31.9%) from middle-HDI and 694 (49.3%) from high-HDI countries. The most common operations performed were appendectomy, small bowel resection, pyloromyotomy and correction of intussusception. After adjustment for patient and hospital risk factors, child mortality at 30 days was significantly higher in low-HDI (adjusted OR 7.14 (95% CI 2.52 to 20.23), p<0.001) and middle-HDI (4.42 (1.44 to 13.56), p=0.009) countries compared with high-HDI countries, translating to 40 excess deaths per 1000 procedures performed.Conclusions: Adjusted mortality in children following emergency abdominal surgery may be as high as 7 times greater in low-HDI and middle-HDI countries compared with high-HDI countries. Effective provision of emergency essential surgery should be a key priority for global child health agendas.
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| 5. |
- Andersson, Christopher B., et al.
(författare)
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Conceptualizing the diverse values of nature and their contributions to people
- 2022
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Ingår i: The Methodological Assessment Report on The Diverse Values and Valuation of Nature. - : Intergovernmental Science-Policy Platform on Biodiversity and Ecosystem Services. ; , s. 55
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Bokkapitel (populärvet., debatt m.m.)abstract
- Humanity confronts multiple socio-environmental crises that are also a values crisis (e.g., biodiversity loss, climate change, emergent diseases) {2.1.1; 2.1.2}. There is consensus that environmental decision-making can be enhanced by being more inclusive of nature’s diverse values {2.1.1}. Yet, understanding nature’s values requires grasping different conceptualizations of the ways people interpret and experience human-nature relationships, such as worldviews informed by different knowledge systems, cultures, languages and disciplines. Better engagement of this diversity offers opportunities to make policies more rigorous, effective and inclusive {2.1.2}. Chapter 2 aims to help decision-makers characterize and assess different conceptualizations of the diverse values of nature and how they are expressed, formed and changed (Figure 2.1). It uses scoping, systematic and critical reviews, complemented with regionally- and thematically balanced case studies to assess academic literature, government policies and indigenous and local knowledge (ILK). Findings provide conceptual background for subsequent chapters and insights for decision-makers to engage, manage and incorporate the conceptual diversity of values in governance frameworks that have impact on nature and its contributions to people (Figure 2.2). Key messages highlight (i) concepts that help diagnose policy-relevant challenges and opportunities and (ii) guidance to use these concepts in solutions to achieve better conceptual, practical and ethical outcomes {2.1}.
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| 6. |
- Andersson, Karl Erik, et al.
(författare)
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Are there relevant animal models to set research priorities in LUTD? ICI-RS 2019
- 2020
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Ingår i: Neurourology and Urodynamics. - : Wiley. - 0733-2467 .- 1520-6777. ; 39:S3, s. 9-15
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Forskningsöversikt (refereegranskat)abstract
- Aim: To discuss animal models of lower urinary tract disorders (LUTD) and their translational impact. Methods: Report of discussions based on presented literature-search based reviews relevant for the purpose. Results: Animal models can be used to investigate fundamental biological mechanisms, but also as tools to elucidate aspects of the pathogenesis of disease and to provide early evidence of any safety risk. Several different models may be required to obtain information that can have a translational impact. The term “translational research” covers not only the process of directly transferring knowledge from basic sciences to human trials to produce new drugs, devices, and treatment options for patients (T1 type translation) but also the implementation of early clinical research findings (phases I-III) into practice to improve care for patients (T2 type). Direct transfer of animal data to T2 is rarely possible, and the process often does not continue after the first trials in humans (phase I). It should be emphasized that many preclinical observations do not have (and do not need to have) immediate translational impact. Conclusions: No single animal model can mimic the complexity of the human disease. Still, animal models can be useful for gaining information on LUT function in humans, for elucidating pathophysiological mechanisms, and for the definition of targets for future drugs to treat LUT disorders.
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| 7. |
- Andersson, Maria L.E., et al.
(författare)
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Autoantibodies to Disease-Related Proteins in Joints as Novel Biomarkers for the Diagnosis of Rheumatoid Arthritis
- 2023
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Ingår i: Arthritis & Rheumatology. - : Wiley. - 2326-5191 .- 2326-5205. ; 75:7, s. 1110-1119
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Tidskriftsartikel (refereegranskat)abstract
- Objective. This study was undertaken to develop and characterize a multiplex immunoassay for detection of autoantibodies against peptides derived from proteins known to play a role in development of arthritis and that are also expressed in joints.Methods. We selected peptides from the human counterpart of proteins expressed in the joints, based on mouse models that showed these to be targeted by pathogenic or regulatory antibodies in vivo. Using bead-based flow immunoassays measuring IgG antibodies, we selected triple helical or cyclic peptides, containing the epitopes, to avoid collinear reactivity. We characterized the analytical performance of the immunoassay and then validated it in 3 independent rheumatoid arthritis (RA) cohorts (n = 2,110), Swedish age- and sex-matched healthy controls, and patients with osteoarthritis (OA), patients with psoriatic arthritis (PsA), and patients with systemic lupus erythematosus (SLE).Results. Screening assays showed 5 peptide antigens that discriminated RA patients from healthy controls with 99% specificity (95% confidence interval [CI] 98-100%). In our validation studies, we reproduced the discriminatory capacity of the autoantibodies in 2 other RA cohorts, showing that the autoantibodies had high discriminatory capacity for RA versus OA, PsA, and SLE. The novel biomarkers identified 22.5% (95% CI 19-26%) of early RA patients seronegative for anti-cyclic citrullinated peptide and rheumatoid factor. The usefulness of the biomarkers in identifying seronegative RA patients was confirmed in validation studies using 2 independent cohorts of RA patients and cohorts of patients with OA, PsA, and SLE.Conclusion. A multiplex immunoassay with peptides from disease-related proteins in joints was found to be useful for detection of specific autoantibodies in RA serum. Of note, this immunoassay had high discriminatory capacity for early seronegative RA.
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| 8. |
- Ansari, Daniel, et al.
(författare)
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Surveillance after surgery for pancreatic cancer : a global scoping review of guidelines and a nordic survey of contemporary practice
- 2024
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Ingår i: Scandinavian Journal of Gastroenterology. - : Taylor & Francis. - 0036-5521 .- 1502-7708.
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Forskningsöversikt (refereegranskat)abstract
- Objectives: Most patients with pancreatic cancer who have undergone surgical resection eventually develop disease recurrence. This study aimed to investigate whether there is evidence to support routine surveillance after pancreatic cancer surgery, with a secondary aim of analyzing the implementation of surveillance strategies in the Nordic countries.Materials and Methods: A scoping review was conducted to identify clinical practice guidelines globally and research studies relating to surveillance after pancreatic cancer resection. This was followed by a survey among 20 pancreatic units from four Nordic countries to assess their current practice of follow-up for operated patients.Results: Altogether 16 clinical practice guidelines and 17 research studies were included. The guidelines provided inconsistent recommendations regarding postoperative surveillance of pancreatic cancer. The clinical research data were mainly based on retrospective cohort studies with low level of evidence and lead-time bias was not addressed. Active surveillance was recommended in Sweden and Denmark, but not in Norway beyond the post-operative/adjuvant period. Finland had no national recommendations for surveillance. The Nordic survey revealed a wide variation in reported practice among the different units. About 75% (15 of 20 units) performed routine postoperative surveillance. Routine CA 19-9 testing was used by 80% and routine CT by 67% as part of surveillance. About 73% of centers continued follow-up until 5 years postoperatively.Conclusion: Evidence for routine long-term (i.e. 5 years) surveillance after pancreatic cancer surgery remains limited. Most pancreatic units in the Nordic countries conduct regular follow-up, but protocols vary.
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| 9. |
- Berman, Anne H, et al.
(författare)
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Teaching digital mental health treatment in theory and practice : a proof-of-concept pilot and feasibility study
- 2023
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Ingår i: International Journal of Behavioral Medicine. ; , s. 66-66, s. 6-7
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Konferensbidrag (refereegranskat)abstract
- Objective: The labor market for mental health professionals increasingly requires competency in digital mental health treatment (DMHT). This presentation targets DMHT practitioners as course developers and teachers, describing proof-of-concept findings based on a) development of a remotely delivered DMHT course; and b) results from a qualitative evaluation of students’ experiences from the first course round.Methods: The course syllabus was developed through two structured workshops, attended by 11 stakeholders with DMHT experience. For the qualitative evaluation, interviews with seven women participants in the first course round were analyzed according to an inductive, phenomenographic approach.Results: The course development process established a 12-week syllabus covering historical development and evidence for DMHT and an 8-week DMHT clinical practicum treating students with common mental health problems. Examination was formulated as individual case reports encompassing reflections on a) the therapist and client roles; b) ethical aspects of DMHT; and c) future innovations for DMHT. The course is offered via a standard learning management system, with the practicum completed on a separate DMHT platform. The qualitative analysis of the first pilot course round, where students role-played therapists and clients, yielded six themes: overall course experience, treatment program and platform, therapist role, client role, supervision and the alliance.Conclusions: This proof-of-concept procedure led to course establishment in two formats: as an ordinary elective course for advanced clinical psychology students, and as a stand-alone national course for health professionals with basic psychotherapy training. Following local adaptation, the course could be replicated at additional universities globally.
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| 10. |
- Berman, Anne H., et al.
(författare)
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Teaching digital mental health treatment in theory and practice : A proof-of-concept pilot and feasibility study
- 2023
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Ingår i: International Journal of Behavioral Medicine. - : Springer. - 1070-5503 .- 1532-7558. ; 30, s. S67-S67
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Background: Improving relationship dynamics positively impacts both partners’ health among couples. However, few studies have investigated sexual and gender minority (SGM) couples’ relationship goals and their experiences toward achieving them.Purpose: The present study investigated SGM couples’ experiences that centered on them working toward or maintaining their relationship goals over time.Method: From a cohort study with SGM couples, a purposive sample of 40 couples was selected and interviewed over Zoom. Interviews were individual-level, semi-structured, and recorded. Thematic analysis was used to analyze the transcripts.Results: Approximately half of the 40 couples identified as gay male couples, a third as lesbian couples, and about one-fifth as queer or gender minority couples. Top three reported relationship goals were 1) improving communication, 2) working on finances, and 3) enhancing intimacy. Feeling emotionally connected, career-related decisions, and improving sexual satisfaction were other commonly reported goals. Overall, most partners felt they made progress toward at least 1 of their 3 relationship goals within the prior 6 months. However, perceived relationship goal progress varied extensively between partners across couple groups. Facilitator-related themes about relationship goal progress included dyadic efforts, having a support system including professional help, and planning. Barrier-related themes included nonexistent or minimal effort, different communication styles, employment and economical struggles, and competing life and health priorities.Conclusion(s): Dyadic efforts and support systems were key toward someone working toward or maintaining their relationships goals. Findings suggest key relationship functioning areas to target in a future multiple health behavior change intervention for SGM couples.
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