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1.
  • Aho, Sonja, et al. (författare)
  • Impact of Primary Tumor Location on Demographics, Resectability, Outcomes, and Quality of Life in Finnish Metastatic Colorectal Cancer Patients (Subgroup Analysis of the RAXO Study)
  • 2024
  • Ingår i: Cancers. - : MDPI. - 2072-6694. ; 16:5
  • Tidskriftsartikel (refereegranskat)abstract
    • Simple Summary The location of the primary tumor in the right colon, left colon, or rectum affects the efficacy of biological drugs used in the treatment of metastatic colorectal cancer, but how? We examined how the primary tumor location affects disease characteristics, treatability, quality of life, and outcome in a real-life study population of 1080 Finnish patients in the RAXO study. The primary tumor location correlates with the location of metastases, the frequency of gene mutations, how often metastases can be operated upon, long-term survival after curative surgery or palliative chemotherapy, and the quality of life during the disease trajectory. The primary tumor location is a helpful surrogate for clinicians working with metastatic colorectal cancer patients in estimating the clinical course of the disease. This study cannot identify the reasons for the associations, i.e., whether it is the primary location per se, the different mutations, or other reasons.Abstract The primary tumor location (PTL) is associated with the phenotype, metastatic sites, mutations, and outcomes of metastatic colorectal cancer (mCRC) patients, but this has mostly been studied according to sidedness (right vs. left sided). We studied right colon vs. left colon vs. rectal PTL in a real-life study population (n = 1080). Health-related quality of life (HRQoL) was assessed multi-cross-sectionally with QLQ-C30, QLQ-CR29, EQ-5D, and 15D. A chi-square, Kaplan-Meier, and Cox regression were used to compare the groups. The PTL was in the right colon in 310 patients (29%), the left colon in 396 patients (37%), and the rectum in 375 patients (35%). The PTL was associated with distinct differences in metastatic sites during the disease trajectory. The resectability, conversion, and resection rates were lowest in the right colon, followed by the rectum, and were highest in the left colon. Overall survival was shortest for right colon compared with left colon or rectal PTL (median 21 vs. 35 vs. 36 months), with the same trends after metastasectomy or systemic therapy only. PTL also remained statistically significant in a multivariable model. The distribution of symptoms varied according to PTL, especially between the right colon (with general symptoms of metastases) and rectal PTL (with sexual- and bowel-related symptoms). mCRC, according to PTL, behaves differently regarding metastatic sites, resectability of the metastases, outcomes of treatment, and HRQoL.
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2.
  • Do, Ron, et al. (författare)
  • Common variants associated with plasma triglycerides and risk for coronary artery disease
  • 2013
  • Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 45:11, s. 1345-
  • Tidskriftsartikel (refereegranskat)abstract
    • Triglycerides are transported in plasma by specific triglyceride-rich lipoproteins; in epidemiological studies, increased triglyceride levels correlate with higher risk for coronary artery disease (CAD). However, it is unclear whether this association reflects causal processes. We used 185 common variants recently mapped for plasma lipids (P < 5 x 10(-8) for each) to examine the role of triglycerides in risk for CAD. First, we highlight loci associated with both low-density lipoprotein cholesterol (LDL-C) and triglyceride levels, and we show that the direction and magnitude of the associations with both traits are factors in determining CAD risk. Second, we consider loci with only a strong association with triglycerides and show that these loci are also associated with CAD. Finally, in a model accounting for effects on LDL-C and/or high-density lipoprotein cholesterol (HDL-C) levels, the strength of a polymorphism's effect on triglyceride levels is correlated with the magnitude of its effect on CAD risk. These results suggest that triglyceride-rich lipoproteins causally influence risk for CAD.
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3.
  • Erkki, Heikkola, et al. (författare)
  • Multiobjective Optimization of an Ultrasonic Transducer using NIMBUS
  • 2006
  • Ingår i: Ultrasonics. - : Elsevier BV. - 0041-624X .- 1874-9968. ; 44:4, s. 368-380
  • Tidskriftsartikel (refereegranskat)abstract
    • The optimal design of an ultrasonic transducer is a multiobjective optimization problem since the final outcome needs to satisfy several conflicting criteria. Simulation tools are often used to avoid expensive and time-consuming experiments, but even simulations may be inefficient and lead to inadequate results if they are based only on trial and error. In this work, the interactive multiobjective optimization method NIMBUS is applied in designing a high-power ultrasonic transducer. The performance of the transducer is simulated with a finite element model, and three design goals are formulated as objective functions to be minimized. To find an appropriate compromise solution, additional preference information is needed from a decision maker, who in our case is an expert in transducer design. A realistic design problem is formulated, and an interactive solution process is described. Our findings demonstrate that interactive multiobjective optimization methods, combined with numerical simulation models, can efficiently help in finding new solution approaches and possibilities as well as new understanding of real-life problems as entirenesses. In this case, the decision maker found a solution that was better with respect to all three objectives than the conventional unoptimized design.
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4.
  • Heid, Iris M, et al. (författare)
  • Meta-analysis identifies 13 new loci associated with waist-hip ratio and reveals sexual dimorphism in the genetic basis of fat distribution
  • 2010
  • Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 42:11, s. 949-960
  • Tidskriftsartikel (refereegranskat)abstract
    • Waist-hip ratio (WHR) is a measure of body fat distribution and a predictor of metabolic consequences independent of overall adiposity. WHR is heritable, but few genetic variants influencing this trait have been identified. We conducted a meta-analysis of 32 genome-wide association studies for WHR adjusted for body mass index (comprising up to 77,167 participants), following up 16 loci in an additional 29 studies (comprising up to 113,636 subjects). We identified 13 new loci in or near RSPO3, VEGFA, TBX15-WARS2, NFE2L3, GRB14, DNM3-PIGC, ITPR2-SSPN, LY86, HOXC13, ADAMTS9, ZNRF3-KREMEN1, NISCH-STAB1 and CPEB4 (P = 1.9 × 10⁻⁹ to P = 1.8 × 10⁻⁴⁰) and the known signal at LYPLAL1. Seven of these loci exhibited marked sexual dimorphism, all with a stronger effect on WHR in women than men (P for sex difference = 1.9 × 10⁻³ to P = 1.2 × 10⁻¹³). These findings provide evidence for multiple loci that modulate body fat distribution independent of overall adiposity and reveal strong gene-by-sex interactions.
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6.
  • Immanen, Juha, et al. (författare)
  • Characterization of cytokinin signaling and homeostasis gene families in two hardwood tree species : Populus trichocarpa and Prunus persica
  • 2013
  • Ingår i: BMC Genomics. - : BioMed Central. - 1471-2164. ; 14, s. 885-
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Through the diversity of cytokinin regulated processes, this phytohormone has a profound impact on plant growth and development. Cytokinin signaling is involved in the control of apical and lateral meristem activity, branching pattern of the shoot, and leaf senescence. These processes influence several traits, including the stem diameter, shoot architecture, and perennial life cycle, which define the development of woody plants. To facilitate research about the role of cytokinin in regulation of woody plant development, we have identified genes associated with cytokinin signaling and homeostasis pathways from two hardwood tree species. Results: Taking advantage of the sequenced black cottonwood (Populus trichocarpa) and peach (Prunus persica) genomes, we have compiled a comprehensive list of genes involved in these pathways. We identified genes belonging to the six families of cytokinin oxidases (CKXs), isopentenyl transferases (IPTs), LONELY GUY genes (LOGs), two-component receptors, histidine containing phosphotransmitters (HPts), and response regulators (RRs). All together 85 Populus and 45 Prunus genes were identified, and compared to their Arabidopsis orthologs through phylogenetic analyses. Conclusions: In general, when compared to Arabidopsis, differences in gene family structure were often seen in only one of the two tree species. However, one class of genes associated with cytokinin signal transduction, the CKI1-like family of two-component histidine kinases, was larger in both Populus and Prunus than in Arabidopsis.
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8.
  • Lehtinen, Matti, et al. (författare)
  • Human papillomavirus vaccine efficacy against invasive, HPV-positive cancers : Population-based follow-up of a cluster-randomised trial
  • 2021
  • Ingår i: BMJ Open. - : BMJ. - 2044-6055. ; 11:12
  • Tidskriftsartikel (refereegranskat)abstract
    • Background Human papillomavirus (HPV) vaccination protects against HPV, a necessary risk factor for cervical cancer. We now report results from population-based follow-up of randomised cohorts that vaccination provides HPV-type-specific protection against invasive cancer. Methods Individually and/or cluster randomised cohorts of HPV-vaccinated and non-vaccinated women were enrolled in 2002-2005. HPV vaccine cohorts comprised originally 16-17 year-old HPV 16/18-vaccinated PATRICIA (NCT00122681) and 012 trial (NCT00169494) participants (2465) and HPV6/11/16/18-vaccinated FUTURE II (NCT00092534) participants (866). Altogether, 3341 vaccines were followed by the Finnish Cancer Registry in the same way as 16 526 non-HPV-vaccinated controls. The control cohort stemmed from 15 665 originally 18-19 years-old women enrolled in 2003 (6499) or 2005 (9166) and 861 placebo recipients of the FUTURE II trial. The follow-up started 6 months after the clinical trials in 2007 and 2009 and ended in 2019. It was age aligned for the cohorts. Findings During a follow-up time of up to 11 years, we identified 17 HPV-positive invasive cancer cases (14 cervical cancers, 1 vaginal cancer, 1 vulvar cancer and 1 tongue cancer) in the non-HPV-vaccinated cohorts and no cases in the HPV-vaccinated cohorts. HPV typing of diagnostic tumour blocks found HPV16 in nine cervical cancer cases, HPV18, HPV33 and HPV52 each in two cases and HPV45 in one cervical cancer case. The vaginal, vulvar and tongue cancer cases were, respectively, positive for HPV16, HPV52/66 and HPV213. Intention-to-treat vaccine efficacy against all HPV-positive cancers was 100% (95% CI 2 to 100, p<0.05). Interpretation Vaccination is effective against invasive HPV-positive cancer. Trial registration number NCT00122681, Post-results; NCT00169494, Post-results; NCT00092534, Post-results.
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9.
  • Peteri, Ulla Kaisa, et al. (författare)
  • Urokinase plasminogen activator mediates changes in human astrocytes modeling fragile X syndrome
  • 2021
  • Ingår i: GLIA. - : Wiley. - 0894-1491 .- 1098-1136. ; 69:12, s. 2947-2962
  • Tidskriftsartikel (refereegranskat)abstract
    • The function of astrocytes intertwines with the extracellular matrix, whose neuron and glial cell-derived components shape neuronal plasticity. Astrocyte abnormalities have been reported in the brain of the mouse model for fragile X syndrome (FXS), the most common cause of inherited intellectual disability, and a monogenic cause of autism spectrum disorder. We compared human FXS and control astrocytes generated from human induced pluripotent stem cells and we found increased expression of urokinase plasminogen activator (uPA), which modulates degradation of extracellular matrix. Several pathways associated with uPA and its receptor function were activated in FXS astrocytes. Levels of uPA were also increased in conditioned medium collected from FXS hiPSC-derived astrocyte cultures and correlated inversely with intracellular Ca2+ responses to activation of L-type voltage-gated calcium channels in human astrocytes. Increased uPA augmented neuronal phosphorylation of TrkB within the docking site for the phospholipase-Cγ1 (PLCγ1), indicating effects of uPA on neuronal plasticity. Gene expression changes during neuronal differentiation preceding astrogenesis likely contributed to properties of astrocytes with FXS-specific alterations that showed specificity by not affecting differentiation of adenosine triphosphate (ATP)-responsive astrocyte population. To conclude, our studies identified uPA as an important regulator of astrocyte function and demonstrated that increased uPA in human FXS astrocytes modulated astrocytic responses and neuronal plasticity.
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10.
  • Potts, Courtney, et al. (författare)
  • A Multilingual Digital Mental Health and Well-Being Chatbot (ChatPal): Pre-Post Multicenter Intervention Study
  • 2023
  • Ingår i: Journal of Medical Internet Research. - : JMIR Publications. - 1438-8871. ; 25
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: In recent years, advances in technology have led to an influx of mental health apps, in particular the development of mental health and well-being chatbots, which have already shown promise in terms of their efficacy, availability, and accessibility. The ChatPal chatbot was developed to promote positive mental well-being among citizens living in rural areas. ChatPal is a multilingual chatbot, available in English, Scottish Gaelic, Swedish, and Finnish, containing psychoeducational content and exercises such as mindfulness and breathing, mood logging, gratitude, and thought diaries.Objective: The primary objective of this study is to evaluate a multilingual mental health and well-being chatbot (ChatPal) to establish if it has an effect on mental well-being. Secondary objectives include investigating the characteristics of individuals that showed improvements in well-being along with those with worsening well-being and applying thematic analysis to user feedback.Methods: A pre-post intervention study was conducted where participants were recruited to use the intervention (ChatPal) for a 12-week period. Recruitment took place across 5 regions: Northern Ireland, Scotland, the Republic of Ireland, Sweden, and Finland. Outcome measures included the Short Warwick-Edinburgh Mental Well-Being Scale, the World Health Organization-Five Well-Being Index, and the Satisfaction with Life Scale, which were evaluated at baseline, midpoint, and end point. Written feedback was collected from participants and subjected to qualitative analysis to identify themes.Results: A total of 348 people were recruited to the study (n=254, 73% female; n=94, 27% male) aged between 18 and 73 (mean 30) years. The well-being scores of participants improved from baseline to midpoint and from baseline to end point; however, improvement in scores was not statistically significant on the Short Warwick-Edinburgh Mental Well-Being Scale (P=.42), the World Health Organization-Five Well-Being Index (P=.52), or the Satisfaction With Life Scale (P=.81). Individuals that had improved well-being scores (n=16) interacted more with the chatbot and were significantly younger compared to those whose well-being declined over the study (P=.03). Three themes were identified from user feedback, including “positive experiences,” “mixed or neutral experiences,” and “negative experiences.” Positive experiences included enjoying exercises provided by the chatbot, while most of the mixed, neutral, or negative experiences mentioned liking the chatbot overall, but there were some barriers, such as technical or performance errors, that needed to be overcome.Conclusions: Marginal improvements in mental well-being were seen in those who used ChatPal, albeit nonsignificant. We propose that the chatbot could be used along with other service offerings to complement different digital or face-to-face services, although further research should be carried out to confirm the effectiveness of this approach. Nonetheless, this paper highlights the need for blended service offerings in mental health care.
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11.
  • Potts, Courtney, et al. (författare)
  • Insights and lessons learned from trialling a mental health chatbot in the wild
  • 2021
  • Ingår i: 2021 IEEE Symposium on Computers and Communications (ISCC). - : IEEE. ; , s. 1-6
  • Konferensbidrag (refereegranskat)abstract
    • This study reports on the development and ‘in the wild’ trialling of a chatbot (ChatPal) which promotes good mental wellbeing. A stakeholder-centered approach for design was adopted where end users, mental health professionals and service users were involved in the design which was centered around positive psychology. In the wild usage of the chatbot was investigated from Jul-20-Mar-21. Exploratory analyses of usage metrics were carried out using the event log data. User tenure, unique usage days, total chatbot interactions and average daily interactions were used in K-means clustering to identify user archetypes. The chatbot was used by a variety of age groups (18-65+) and genders, mainly those living in Ireland. K-means clustering identified three clusters: sporadic users (n=4), frequent transient users (n=38) and abandoning users (n=169) each with distinct usage characteristics. This study highlights the importance of event log data analysis for making improvements to the mental health chatbot.
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12.
  • Raatikainen, Kaisa J., et al. (författare)
  • Pathways towards a sustainable future envisioned by early-career conservation researchers
  • 2021
  • Ingår i: CONSERVATION SCIENCE AND PRACTICE. - : John Wiley & Sons. - 2578-4854. ; 3:9
  • Tidskriftsartikel (refereegranskat)abstract
    • Scientists have warned decision-makers about the severe consequences of the global environmental crisis since the 1970s. Yet ecological degradation continues and little has been done to address climate change. We investigated early-career conservation researchers' (ECR) perspectives on, and prioritization of, actions furthering sustainability. We conducted a survey (n = 67) and an interactive workshop (n = 35) for ECR attendees of the 5th European Congress of Conservation Biology (2018). Building on these data and discussions, we identified ongoing and forthcoming advances in conservation science. These include increased transdisciplinarity, science communication, advocacy in conservation, and adoption of a transformation-oriented social-ecological systems approach to research. The respondents and participants had diverse perspectives on how to achieve sustainability. Reformist actions were emphasized as paving the way for more radical changes in the economic system and societal values linked to the environment and inequality. Our findings suggest that achieving sustainability requires a strategy that (1) incorporates the multiplicity of people's views, (2) places a greater value on nature, and (3) encourages systemic transformation across political, social, educational, and economic realms on multiple levels. We introduce a framework for ECRs to inspire their research and practice within conservation science to achieve real change in protecting biological diversity.
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13.
  • Ræbild, Anders, et al. (författare)
  • Polyploidy – A tool in adapting trees to future climate changes? A review of polyploidy in trees
  • 2024
  • Ingår i: Forest Ecology and Management. - : Elsevier. - 0378-1127 .- 1872-7042. ; 560, s. 121767-121767
  • Forskningsöversikt (refereegranskat)abstract
    • Polyploidy, or genome doubling, has occurred repeatedly through plant evolution. While polyploid plants are used extensively in agriculture and horticulture, they have so far found limited use in forestry. Here we review the potentials of polyploid trees under climate change, and investigate if there is support for increased use. We find that polyploid trees like other plants have consistent increases in cell sizes compared to diploids, and that leaf-area based rates of photosynthesis tend to increase with increasing levels of ploidy. While no particular trend could be discerned in terms of biomass between trees of different ploidy levels, physiology is affected by polyploidization and several studies point towards a high potential for polyploid trees to adapt to drought stress. The ploidy level of most tree species is unknown, and analysis of geographical patterns in frequencies of polyploid trees are inconclusive. Artificial polyploid trees are often created by colchicine and in a few cases these have been successfully applied in forestry, but the effects of induced polyploidization in many economically important tree species remains untested. Polyploids would also be increasingly useful in tree breeding programs, to create synthetic hybrids or sterile triploids that could control unwanted spreading of germplasm in nature. In conclusion, this review suggests that polyploid trees may be superior under climate change in some cases, but that the potential of polyploids is not yet fully known and should be evaluated on a case-to-case basis for different tree species.
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14.
  • Randall, Ricardo S., et al. (författare)
  • AINTEGUMENTA and the D-type cyclin CYCD3;1 regulate root secondary growth and respond to cytokinins
  • 2015
  • Ingår i: Biology Open. - : The Company of Biologists. - 2046-6390. ; 4:10, s. 1229-1236
  • Tidskriftsartikel (refereegranskat)abstract
    • Higher plant vasculature is characterized by two distinct developmental phases. Initially, a well-defined radial primary pattern is established. In eudicots, this is followed by secondary growth, which involves development of the cambium and is required for efficient water and nutrient transport and wood formation. Regulation of secondary growth involves several phytohormones, and cytokinins have been implicated as key players, particularly in the activation of cell proliferation, but the molecular mechanisms mediating this hormonal control remain unknown. Here we show that the genes encoding the transcription factor AINTEGUMENTA (ANT) and the D-type cyclin CYCD3;1 are expressed in the vascular cambium of Arabidopsis roots, respond to cytokinins and are both required for proper root secondary thickening. Cytokinin regulation of ANT and CYCD3 also occurs during secondary thickening of poplar stems, suggesting this represents a conserved regulatory mechanism.
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15.
  • Ripatti, Samuli, et al. (författare)
  • A multilocus genetic risk score for coronary heart disease: case-control and prospective cohort analyses
  • 2010
  • Ingår i: The Lancet. - 1474-547X. ; 376:9750, s. 1393-1400
  • Tidskriftsartikel (refereegranskat)abstract
    • Background Comparison of patients with coronary heart disease and controls in genome-wide association studies has revealed several single nucleotide polymorphisms (SNPs) associated with coronary heart disease. We aimed to establish the external validity of these findings and to obtain more precise risk estimates using a prospective cohort design. Methods We tested 13 recently discovered SNPs for association with coronary heart disease in a case-control design including participants differing from those in the discovery samples (3829 participants with prevalent coronary heart disease and 48 897 controls free of the disease) and a prospective cohort design including 30 725 participants free of cardiovascular disease from Finland and Sweden. We modelled the 13 SNPs as a multilocus genetic risk score and used Cox proportional hazards models to estimate the association of genetic risk score with incident coronary heart disease. For case-control analyses we analysed associations between individual SNPs and quintiles of genetic risk score using logistic regression. Findings In prospective cohort analyses, 1264 participants had a first coronary heart disease event during a median 10.7 years' follow-up (IQR 6.7-13.6). Genetic risk score was associated with a first coronary heart disease event. When compared with the bottom quintile of genetic risk score, participants in the top quintile were at 1.66-times increased risk of coronary heart disease in a model adjusting for traditional risk factors (95% CI 1.35-2.04, p value for linear trend=7.3x10(-10)). Adjustment for family history did not change these estimates. Genetic risk score did not improve C index over traditional risk factors and family history (p=0.19), nor did it have a significant effect on net reclassification improvement (2.2%, p=0.18); however, it did have a small effect on integrated discrimination index (0.004, p=0.0006). Results of the case-control analyses were similar to those of the prospective cohort analyses. Interpretation Using a genetic risk score based on 13 SNPs associated with coronary heart disease, we can identify the 20% of individuals of European ancestry who are at roughly 70% increased risk of a first coronary heart disease event. The potential clinical use of this panel of SNPs remains to be defined.
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16.
  • Salojarvi, Jarkko, et al. (författare)
  • Genome sequencing and population genomic analyses provide insights into the adaptive landscape of silver birch
  • 2017
  • Ingår i: Nature Genetics. - : NATURE PUBLISHING GROUP. - 1061-4036 .- 1546-1718. ; 49:6, s. 904-912
  • Tidskriftsartikel (refereegranskat)abstract
    • Silver birch (Betula pendula) is a pioneer boreal tree that can be induced to flower within 1 year. Its rapid life cycle, small (440-Mb) genome, and advanced germplasm resources make birch an attractive model for forest biotechnology. We assembled and chromosomally anchored the nuclear genome of an inbred B. pendula individual. Gene duplicates from the paleohexaploid event were enriched for transcriptional regulation, whereas tandem duplicates were overrepresented by environmental responses. Population resequencing of 80 individuals showed effective population size crashes at major points of climatic upheaval. Selective sweeps were enriched among polyploid duplicates encoding key developmental and physiological triggering functions, suggesting that local adaptation has tuned the timing of and cross-talk between fundamental plant processes. Variation around the tightly-linked light response genes PHYC and FRS10 correlated with latitude and longitude and temperature, and with precipitation for PHYC. Similar associations characterized the growth-promoting cytokinin response regulator ARR1, and the wood development genes KAK and MED5A.
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17.
  • Speliotes, Elizabeth K., et al. (författare)
  • Association analyses of 249,796 individuals reveal 18 new loci associated with body mass index
  • 2010
  • Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 42:11, s. 937-948
  • Tidskriftsartikel (refereegranskat)abstract
    • Obesity is globally prevalent and highly heritable, but its underlying genetic factors remain largely elusive. To identify genetic loci for obesity susceptibility, we examined associations between body mass index and ~2.8 million SNPs in up to 123,865 individuals with targeted follow up of 42 SNPs in up to 125,931 additional individuals. We confirmed 14 known obesity susceptibility loci and identified 18 new loci associated with body mass index (P < 5 × 10−8), one of which includes a copy number variant near GPRC5B. Some loci (at MC4R, POMC, SH2B1 and BDNF) map near key hypothalamic regulators of energy balance, and one of these loci is near GIPR, an incretin receptor. Furthermore, genes in other newly associated loci may provide new insights into human body weight regulation.
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18.
  • Sweeney, Colm, et al. (författare)
  • Can Chatbots Help Support a Person’s Mental Health? Perceptions and Views from Mental Healthcare Professionals and Experts
  • 2021
  • Ingår i: ACM Transactions on Computing for Healthcare. - : ACM Digital Library. - 2691-1957 .- 2637-8051. ; 2:3
  • Tidskriftsartikel (refereegranskat)abstract
    • The objective of this study was to understand the attitudes of professionals who work in mental health regarding the use of conversational user interfaces, or chatbots, to support people’s mental health and wellbeing. This study involves an online survey to measure the awareness and attitudes of mental healthcare professionals and experts. The findings from this survey show that more than half of the participants in the survey agreed that there are benefits associated with mental healthcare chatbots (65%, p < 0.01). The perceived importance of chatbots was also relatively high (74%, p < 0.01), with more than three-quarters (79%, p < 0.01) of respondents agreeing that mental healthcare chatbots could help their clients better manage their own health, yet chatbots are overwhelmingly perceived as not adequately understanding or displaying human emotion (86%, p < 0.01). Even though the level of personal experience with chatbots among professionals and experts in mental health has been quite low, this study shows that where they have been used, the experience has been mostly satisfactory. This study has found that as years of experience increased, there was a corresponding increase in the belief that healthcare chatbots could help clients better manage their own mental health.
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19.
  • Teslovich, Tanya M., et al. (författare)
  • Biological, clinical and population relevance of 95 loci for blood lipids
  • 2010
  • Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 466:7307, s. 707-713
  • Tidskriftsartikel (refereegranskat)abstract
    • Plasma concentrations of total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol and triglycerides are among the most important risk factors for coronary artery disease (CAD) and are targets for therapeutic intervention. We screened the genome for common variants associated with plasma lipids in >100,000 individuals of European ancestry. Here we report 95 significantly associated loci (P<5 x 10(-8)), with 59 showing genome-wide significant association with lipid traits for the first time. The newly reported associations include single nucleotide polymorphisms (SNPs) near known lipid regulators (for example, CYP7A1, NPC1L1 and SCARB1) as well as in scores of loci not previously implicated in lipoprotein metabolism. The 95 loci contribute not only to normal variation in lipid traits but also to extreme lipid phenotypes and have an impact on lipid traits in three non-European populations (East Asians, South Asians and African Americans). Our results identify several novel loci associated with plasma lipids that are also associated with CAD. Finally, we validated three of the novel genes-GALNT2, PPP1R3B and TTC39B-with experiments in mouse models. Taken together, our findings provide the foundation to develop a broader biological understanding of lipoprotein metabolism and to identify new therapeutic opportunities for the prevention of CAD.
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21.
  • Uutela, Aki, et al. (författare)
  • Resectability, conversion, metastasectomy and outcome according to RAS and BRAF status for metastatic colorectal cancer in the prospective RAXO study
  • 2022
  • Ingår i: British Journal of Cancer. - : Springer Nature. - 0007-0920 .- 1532-1827. ; 127:4, s. 686-694
  • Tidskriftsartikel (refereegranskat)abstract
    • Background Outcomes after metastasectomy for metastatic colorectal cancer (mCRC) vary with RAS and BRAF mutational status, but their effects on resectability and conversion rates have not been extensively studied. Methods This substudy of the prospective RAXO trial included 906 patients recruited between 2011 and 2018. We evaluated repeated centralised resectability assessment, conversion/resection rates and overall survival (OS), according to RAS and BRAF status. Results Patients included 289 with RAS and BRAF wild-type (RAS and BRAFwt), 529 with RAS mutated (RASmt) and 88 with BRAF mutated (BRAFmt) mCRC. Metastatic prevalence varied between the RAS and BRAFwt/RASmt/BRAFmt groups, for liver (78%/74%/61%), lung (24%/35%/28%) and peritoneal (15%/15%/32%) metastases, respectively. Upfront resectability (32%/29%/15%), conversion (16%/13%/7%) and resection/local ablative therapy (LAT) rates (45%/37%/17%) varied for RASa and BRAFwt/RASmt/BRAFmt, respectively. Median OS for patients treated with resection/LAT (n = 342) was 83/69/30 months, with 5-year OS-rates of 67%/60%/24%, while systemic therapy-only patients (n = 564) had OS of 29/21/15 months with 5-year OS-rates of 11%/6%/2% in RAS and BRAFwt/RASmt/BRAFmt, respectively. Resection/LAT was associated with improved OS in all subgroups. Conclusions There were significant differences in resectability, conversion and resection/LAT rates according to RAS and BRAF status. OS was also significantly longer for RAS and BRAFwt versus either mutant. Patients only receiving systemic therapy had poorer long-term survival, with variation according to molecular status.
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22.
  • Willer, Cristen J., et al. (författare)
  • Discovery and refinement of loci associated with lipid levels
  • 2013
  • Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 45:11, s. 1274-1283
  • Tidskriftsartikel (refereegranskat)abstract
    • Levels of low-density lipoprotein (LDL) cholesterol, high-density lipoprotein (HDL) cholesterol, triglycerides and total cholesterol are heritable, modifiable risk factors for coronary artery disease. To identify new loci and refine known loci influencing these lipids, we examined 188,577 individuals using genome-wide and custom genotyping arrays. We identify and annotate 157 loci associated with lipid levels at P < 5 x 10(-8), including 62 loci not previously associated with lipid levels in humans. Using dense genotyping in individuals of European, East Asian, South Asian and African ancestry, we narrow association signals in 12 loci. We find that loci associated with blood lipid levels are often associated with cardiovascular and metabolic traits, including coronary artery disease, type 2 diabetes, blood pressure, waist-hip ratio and body mass index. Our results demonstrate the value of using genetic data from individuals of diverse ancestry and provide insights into the biological mechanisms regulating blood lipids to guide future genetic, biological and therapeutic research.
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