| 1. |
- Ademuyiwa, Adesoji O., et al.
(author)
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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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In: BMJ Global Health. - : BMJ Publishing Group Ltd. - 2059-7908. ; 1:4
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Journal article (peer-reviewed)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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| 2. |
- Hibar, Derrek P., et al.
(author)
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Novel genetic loci associated with hippocampal volume
- 2017
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In: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 8
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Journal article (peer-reviewed)abstract
- The hippocampal formation is a brain structure integrally involved in episodic memory, spatial navigation, cognition and stress responsiveness. Structural abnormalities in hippocampal volume and shape are found in several common neuropsychiatric disorders. To identify the genetic underpinnings of hippocampal structure here we perform a genome-wide association study (GWAS) of 33,536 individuals and discover six independent loci significantly associated with hippocampal volume, four of them novel. Of the novel loci, three lie within genes (ASTN2, DPP4 and MAST4) and one is found 200 kb upstream of SHH. A hippocampal subfield analysis shows that a locus within the MSRB3 gene shows evidence of a localized effect along the dentate gyrus, subiculum, CA1 and fissure. Further, we show that genetic variants associated with decreased hippocampal volume are also associated with increased risk for Alzheimer's disease (r(g) = -0.155). Our findings suggest novel biological pathways through which human genetic variation influences hippocampal volume and risk for neuropsychiatric illness.
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| 3. |
- Thompson, Paul M., et al.
(author)
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The ENIGMA Consortium : large-scale collaborative analyses of neuroimaging and genetic data
- 2014
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In: BRAIN IMAGING BEHAV. - : Springer Science and Business Media LLC. - 1931-7557 .- 1931-7565. ; 8:2, s. 153-182
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Journal article (peer-reviewed)abstract
- The Enhancing NeuroImaging Genetics through Meta-Analysis (ENIGMA) Consortium is a collaborative network of researchers working together on a range of large-scale studies that integrate data from 70 institutions worldwide. Organized into Working Groups that tackle questions in neuroscience, genetics, and medicine, ENIGMA studies have analyzed neuroimaging data from over 12,826 subjects. In addition, data from 12,171 individuals were provided by the CHARGE consortium for replication of findings, in a total of 24,997 subjects. By meta-analyzing results from many sites, ENIGMA has detected factors that affect the brain that no individual site could detect on its own, and that require larger numbers of subjects than any individual neuroimaging study has currently collected. ENIGMA's first project was a genome-wide association study identifying common variants in the genome associated with hippocampal volume or intracranial volume. Continuing work is exploring genetic associations with subcortical volumes (ENIGMA2) and white matter microstructure (ENIGMA-DTI). Working groups also focus on understanding how schizophrenia, bipolar illness, major depression and attention deficit/hyperactivity disorder (ADHD) affect the brain. We review the current progress of the ENIGMA Consortium, along with challenges and unexpected discoveries made on the way.
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| 4. |
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| 5. |
- Pattaro, Cristian, et al.
(author)
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Genetic associations at 53 loci highlight cell types and biological pathways relevant for kidney function
- 2016
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In: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 7
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Journal article (peer-reviewed)abstract
- Reduced glomerular filtration rate defines chronic kidney disease and is associated with cardiovascular and all-cause mortality. We conducted a meta-analysis of genome-wide association studies for estimated glomerular filtration rate (eGFR), combining data across 133,413 individuals with replication in up to 42,166 individuals. We identify 24 new and confirm 29 previously identified loci. Of these 53 loci, 19 associate with eGFR among individuals with diabetes. Using bioinformatics, we show that identified genes at eGFR loci are enriched for expression in kidney tissues and in pathways relevant for kidney development and transmembrane transporter activity, kidney structure, and regulation of glucose metabolism. Chromatin state mapping and DNase I hypersensitivity analyses across adult tissues demonstrate preferential mapping of associated variants to regulatory regions in kidney but not extra-renal tissues. These findings suggest that genetic determinants of eGFR are mediated largely through direct effects within the kidney and highlight important cell types and biological pathways.
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| 6. |
- Akinkuolie, Akintunde O, et al.
(author)
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Group IIA Secretory Phospholipase A2, Vascular Inflammation, and Incident Cardiovascular Disease.
- 2019
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In: Arteriosclerosis, thrombosis, and vascular biology. - 1524-4636. ; 39:6, s. 1182-1190
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Journal article (peer-reviewed)abstract
- Objective- Inflammation is a causal risk factor for cardiovascular disease (CVD). sPLA2-IIA (group IIA secretory phospholipase A2) plays an integral role in regulating vascular inflammation. Although studies investigated sPLA2-IIA in secondary prevention, we prospectively evaluated sPLA2-IIA mass and genetic variants with CVD events in a primary prevention population with chronic inflammation. Approach and Results- The JUPITER trial (Justification for the Use of Statins in Prevention: An Intervention Trial Evaluating Rosuvastatin) randomized participants with LDL (low-density lipoprotein) <130 mg/dL and hsCRP (high-sensitivity C-reactive protein) ≥2 mg/L to high-intensity rosuvastatin versus placebo. Baseline and 1-year plasma sPLA2-IIA mass was measured (N=11269 baseline; N=9620 1 year). We also identified genetic variants influencing sPLA2-IIA using genome-wide association and examined them with CVD. Three hundred thirteen incident CVD events occurred during follow-up. Baseline sPLA2-IIA mass (median, 25th-75th percentile: 3.81, 2.49-6.03 ng/mL) was associated with increased risk of CVD: risk factor-adjusted hazard ratio (95% CI; P) per SD increment: 1.22 (1.08-1.38; P=0.002). This remained significant (1.18; 1.04-1.35; P=0.01) after incrementally adjusting for hsCRP. Similar estimates were observed in rosuvastatin and placebo groups ( P treatment interaction>0.05). The rs11573156C variant in PLA2G2A (encoding sPLA2-IIA) had the strongest effect on sPLA2-II: median (25th-75th percentile, ng/mL) for CC and GG genotypes: 2.79 (1.97-4.01) and 7.38 (5.38-10.19), respectively; and had nonsignificant trend for higher CVD risk (hazard ratio, 1.11; 95% CI, 0.89-1.38; P=0.34). Conclusions- In the JUPITER population recruited on chronic inflammation, sPLA2-IIA mass was associated with CVD risk relating to vascular inflammation not fully reflected by hsCRP. Additional studies, including larger functional genetic and clinical studies, are needed to determine whether sPLA2-IIA may be a potential pharmacological target for primary prevention of CVD. Clinical Trial Registration- URL: http://www.clinicaltrials.gov . Unique identifier: NCT00239681.
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| 7. |
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| 8. |
- Artigas Soler, María, et al.
(author)
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Genome-wide association and large-scale follow up identifies 16 new loci influencing lung function.
- 2011
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In: Nature genetics. - : Springer Science and Business Media LLC. - 1546-1718 .- 1061-4036. ; 43:11, s. 1082-90
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Journal article (peer-reviewed)abstract
- Pulmonary function measures reflect respiratory health and are used in the diagnosis of chronic obstructive pulmonary disease. We tested genome-wide association with forced expiratory volume in 1 second and the ratio of forced expiratory volume in 1 second to forced vital capacity in 48,201 individuals of European ancestry with follow up of the top associations in up to an additional 46,411 individuals. We identified new regions showing association (combined P < 5 × 10(-8)) with pulmonary function in or near MFAP2, TGFB2, HDAC4, RARB, MECOM (also known as EVI1), SPATA9, ARMC2, NCR3, ZKSCAN3, CDC123, C10orf11, LRP1, CCDC38, MMP15, CFDP1 and KCNE2. Identification of these 16 new loci may provide insight into the molecular mechanisms regulating pulmonary function and into molecular targets for future therapy to alleviate reduced lung function.
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| 9. |
- Barucca, G., et al.
(author)
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The potential of Λ and Ξ- studies with PANDA at FAIR
- 2021
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In: European Physical Journal A. - : Springer Nature. - 1434-6001 .- 1434-601X. ; 57:4
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Journal article (peer-reviewed)abstract
- The antiproton experiment PANDA at FAIR is designed to bring hadron physics to a new level in terms of scope, precision and accuracy. In this work, its unique capability for studies of hyperons is outlined. We discuss ground-state hyperons as diagnostic tools to study non-perturbative aspects of the strong interaction, and fundamental symmetries. New simulation studies have been carried out for two benchmark hyperon-antihyperon production channels: p¯ p→ Λ¯ Λ and p¯ p→ Ξ¯ +Ξ-. The results, presented in detail in this paper, show that hyperon-antihyperon pairs from these reactions can be exclusively reconstructed with high efficiency and very low background contamination. In addition, the polarisation and spin correlations have been studied, exploiting the weak, self-analysing decay of hyperons and antihyperons. Two independent approaches to the finite efficiency have been applied and evaluated: one standard multidimensional efficiency correction approach, and one efficiency independent approach. The applicability of the latter was thoroughly evaluated for all channels, beam momenta and observables. The standard method yields good results in all cases, and shows that spin observables can be studied with high precision and accuracy already in the first phase of data taking with PANDA.
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| 10. |
- Berglind, Daniel, et al.
(author)
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An eHealth program versus a standard care supervised health program and associated health outcomes in individuals with mobility disability : study protocol for a randomized controlled trial.
- 2018
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In: Trials. - : Springer Science and Business Media LLC. - 1745-6215. ; 19:1
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Journal article (peer-reviewed)abstract
- BACKGROUND: Young adults with mobility disability (MD) are less likely to engage in regular physical activity (PA) compared with their able-bodied peers and inactive adults with a MD are more likely to report one or more chronic diseases compared to those who are physically active. Despite the vast amount of research published in the field of PA interventions over the past decades, little attention has been focused on interventions aiming to increase PA among individuals with MD. Thus, we propose to compare the effects of an eHealth program compared to a usual care supervised health program on levels of PA and other health behaviors.METHODS: The current intervention will use a randomized controlled trial (RCT) design with two treatment groups (an eHealth program and a usual care supervised health program) in young adults with newly acquired MD. In total, 110 young adults (aged 18-40 years) with a MD, acquired within the past 3 years, will be recruited to participate in a 12-week intervention. The primary study outcome is accelerometer-measured time spent in moderate to vigorous PA. Secondary outcomes includes health-related quality of life, depression, stress, fitness, body composition, diet, musculoskeletal pain, motivation to exercise and work ability.DISCUSSION: There is a lack of RCTs investigating effective ways to increase levels of PA in young adults with MD. Increased levels of PA among this physically inactive population have the potential to substantially improve health-related outcomes, possibly more so than in the general population. The trial will put strong emphasis on optimizing exercise adherence and investigating feasibility in the two treatment programs. The Ethical Review Board (EPN) at Karolinska Institutet has approved the study (2017/1206-31/1).TRIAL REGISTRATION: International Standard Randomised Controlled Trial Number (ISRCTN), reference number ISRCTN22387524 . Prospectively registered February 4, 2018.
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| 11. |
- Bishop, Kevin, et al.
(author)
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The hydrology of the covered catchment
- 1998
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In: Experimental Reversal of Acid Rain Effects: the Gårdsjön Project. - : John Wiley & Sons. ; , s. 109-135
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Book chapter (peer-reviewed)
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| 12. |
- Boen, Rune, et al.
(author)
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Beyond the global brain differences : intraindividual variability differences in 1q21.1 distal and 15q11.2 bp1-bp2 deletion carriers
- 2024
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In: Biological Psychiatry. - 0006-3223 .- 1873-2402. ; 95:2, s. 147-160
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Journal article (peer-reviewed)abstract
- Background: Carriers of the 1q21.1 distal and 15q11.2 BP1-BP2 copy number variants exhibit regional and global brain differences compared with noncarriers. However, interpreting regional differences is challenging if a global difference drives the regional brain differences. Intraindividual variability measures can be used to test for regional differences beyond global differences in brain structure.Methods: Magnetic resonance imaging data were used to obtain regional brain values for 1q21.1 distal deletion (n = 30) and duplication (n = 27) and 15q11.2 BP1-BP2 deletion (n = 170) and duplication (n = 243) carriers and matched noncarriers (n = 2350). Regional intra-deviation scores, i.e., the standardized difference between an individual's regional difference and global difference, were used to test for regional differences that diverge from the global difference.Results: For the 1q21.1 distal deletion carriers, cortical surface area for regions in the medial visual cortex, posterior cingulate, and temporal pole differed less and regions in the prefrontal and superior temporal cortex differed more than the global difference in cortical surface area. For the 15q11.2 BP1-BP2 deletion carriers, cortical thickness in regions in the medial visual cortex, auditory cortex, and temporal pole differed less and the prefrontal and somatosensory cortex differed more than the global difference in cortical thickness.Conclusions: We find evidence for regional effects beyond differences in global brain measures in 1q21.1 distal and 15q11.2 BP1-BP2 copy number variants. The results provide new insight into brain profiling of the 1q21.1 distal and 15q11.2 BP1-BP2 copy number variants, with the potential to increase understanding of the mechanisms involved in altered neurodevelopment.
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| 13. |
- Borg, Michael A., et al.
(author)
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Maltese Antibiotic Stewardship Programme in the Community (MASPIC): Protocol of a prospective quasiexperimental social marketing intervention
- 2017
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In: BMJ Open. - : BMJ Publishing Group: Open Access / BMJ Publishing Group. - 2044-6055. ; 7:9
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Journal article (peer-reviewed)abstract
- Introduction Antibiotic misuse is a key driver of antibiotic resistance. In 2015/2016, Maltese respondents reported the highest proportions of antibiotic consumption in Europe. Since antibiotics are prescription-only medicines in Malta, research on effective strategies targeting general practitioners' (GPs) knowledge and behaviour is needed. Multifaceted behaviour change (BC) interventions are likely to be effective. Social marketing (SM) can provide the tools to promote sustained BC; however, its utilisation in Europe is limited. This paper aims to describe the design and methods of a multifaceted SM intervention aimed at changing Maltese GPs' antibiotic prescribing behaviour for patients with acute respiratory tract infections (aRTIs). Methods and analysis This 4-year quasiexperimental intervention study will be carried out in Malta and includes three phases: preintervention, intervention and postintervention. The preintervention phase intends to gain insight into the practices and attitudes of GPs, pharmacists and parents through interviews, focus group discussions and antibiotic prescribing surveillance. A 6-month intervention targeting GPs will be implemented following assessment of their prescribing intention and readiness for BC. The intervention will likely comprise: prescribing guidelines, patient educational materials, delayed antibiotic prescriptions and GP education. Outcomes will be evaluated in the postintervention phase through questionnaires based on the theory of planned behaviour and stages-of-change theory, as well as postintervention surveillance. The primary outcome will be the antibiotic prescribing rate for all patients with aRTIs. Secondary outcomes will include the proportion of diagnosis-specific antibiotic prescription and symptomatic relief medication prescribed, and the change in GPs stage-of-change and their intention to prescribe antibiotics. Ethics and dissemination The project received ethical approval from the University of Malta's Research Ethics Committee. Should this intervention successfully decrease antibiotic prescribing, it may be scaled up locally and transferred to similar settings.
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| 14. |
- Cabeza, Roberto, et al.
(author)
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Maintenance, reserve and compensation : the cognitive neuroscience of healthy ageing
- 2018
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In: Nature Reviews Neuroscience. - : Nature Publishing Group. - 1471-003X .- 1471-0048. ; 19:11, s. 701-710
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Research review (peer-reviewed)abstract
- Cognitive ageing research examines the cognitive abilities that are preserved and/or those that decline with advanced age. There is great individual variability in cognitive ageing trajectories. Some older adults show little decline in cognitive ability compared with young adults and are thus termed ‘optimally ageing’. By contrast, others exhibit substantial cognitive decline and may develop dementia. Human neuroimaging research has led to a number of important advances in our understanding of the neural mechanisms underlying these two outcomes. However, interpreting the age-related changes and differences in brain structure, activation and functional connectivity that this research reveals is an ongoing challenge. Ambiguous terminology is a major source of difficulty in this venture. Three terms in particular — compensation, maintenance and reserve — have been used in a number of different ways, and researchers continue to disagree about the kinds of evidence or patterns of results that are required to interpret findings related to these concepts. As such inconsistencies can impede progress in both theoretical and empirical research, here, we aim to clarify and propose consensual definitions of these terms.
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| 15. |
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| 16. |
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| 17. |
- Cronjé, Héléne T., et al.
(author)
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Genetic evidence implicating natriuretic peptide receptor-3 in cardiovascular disease risk : a Mendelian randomization study
- 2023
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In: BMC Medicine. - 1741-7015. ; 21:1
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Journal article (peer-reviewed)abstract
- Background: C-type natriuretic peptide (CNP) is a known target for promoting growth and has been implicated as a therapeutic opportunity for the prevention and treatment of cardiovascular disease (CVD). This study aimed to explore the effect of CNP on CVD risk using the Mendelian randomization (MR) framework. Methods: Instrumental variables mimicking the effects of pharmacological intervention on CNP were identified as uncorrelated genetic variants located in the genes coding for its primary receptors, natriuretic peptide receptors-2 and 3 (NPR2 and NPR3), that associated with height. We performed MR and colocalization analyses to investigate the effects of NPR2 signalling and NPR3 function on CVD outcomes and risk factors. MR estimates were compared to those obtained when considering height variants from throughout the genome. Results: Genetically-proxied reduced NPR3 function was associated with a lower risk of CVD, with odds ratio (OR) 0.74 per standard deviation (SD) higher NPR3-predicted height, and 95% confidence interval (95% CI) 0.64–0.86. This effect was greater in magnitude than observed when considering height variants from throughout the genome. For CVD subtypes, similar MR associations for NPR3-predicted height were observed when considering the outcomes of coronary artery disease (0.75, 95% CI 0.60–0.92), stroke (0.69, 95% CI 0.50–0.95) and heart failure (0.77, 95% CI 0.58–1.02). Consideration of CVD risk factors identified systolic blood pressure (SBP) as a potential mediator of the NPR3-related CVD risk lowering. For stroke, we found that the MR estimate for NPR3 was greater in magnitude than could be explained by a genetically predicted SBP effect alone. Colocalization results largely supported the MR findings, with no evidence of results being driven by effects due to variants in linkage disequilibrium. There was no MR evidence supporting effects of NPR2 on CVD risk, although this null finding could be attributable to fewer genetic variants being identified to instrument this target. Conclusions: This genetic analysis supports the cardioprotective effects of pharmacologically inhibiting NPR3 receptor function, which is only partly mediated by an effect on blood pressure. There was unlikely sufficient statistical power to investigate the cardioprotective effects of NPR2 signalling.
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| 18. |
- Edlund, Karolina, et al.
(author)
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CD99 is a novel prognostic stromal marker in non-small cell lung cancer
- 2012
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In: International Journal of Cancer. - : Wiley. - 0020-7136 .- 1097-0215. ; 131:10, s. 2264-2273
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Journal article (peer-reviewed)abstract
- The complex interaction between cancer cells and the microenvironment plays an essential role in all stages of tumourigenesis. Despite the significance of this interplay, alterations in protein composition underlying tumourstroma interactions are largely unknown. The aim of this study was to identify stromal proteins with clinical relevance in non-small cell lung cancer (NSCLC). A list encompassing 203 stromal candidate genes was compiled based on gene expression array data and available literature. The protein expression of these genes in human NSCLC was screened using the Human Protein Atlas. Twelve proteins were selected that showed a differential stromal staining pattern (BGN, CD99, DCN, EMILIN1, FBN1, PDGFRB, PDLIM5, POSTN, SPARC, TAGLN, TNC and VCAN). The corresponding antibodies were applied on tissue microarrays, including 190 NSCLC samples, and stromal staining was correlated with clinical parameters. Higher stromal expression of CD99 was associated with better prognosis in the univariate (p = 0.037) and multivariate (p = 0.039) analysis. The association was independent from the proportion of tumour stroma, the fraction of inflammatory cells and clinical and pathological parameters like stage, performance status and tumour histology. The prognostic impact of stromal CD99 protein expression was confirmed in an independent cohort of 240 NSCLC patients (p = 0.008). Furthermore, double-staining confocal fluorescence microscopy showed that CD99 was expressed in stromal lymphocytes as well as in cancer-associated fibroblasts. Based on a comprehensive screening strategy the membrane protein CD99 was identified as a novel stromal factor with clinical relevance. The results support the concept that stromal properties have an important impact on tumour progression.
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| 19. |
- Ekstedt, Mirjam, et al.
(author)
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Sleep, physical activity and BMI in six to ten-year-old children measured by accelerometry: a cross-sectional study.
- 2013
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In: International Journal of Behavioral Nutrition and Physical Activity. - : Springer Science and Business Media LLC. - 1479-5868. ; 22:10, s. 82-89
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Journal article (peer-reviewed)abstract
- BACKGROUND:The aim of this study is to describe the relationship between objective measures of sleep, physical activity and BMI in Swedish pre-adolescents. The day-to-day association between physical activity and sleep quality as well as week-day and weekend pattern of sleep is also described.METHOD:We conducted a cross sectional study consisted of a cohort of 1.231 children aged six to ten years within the Stockholm county area. Sleep and physical activity were measured by accelerometry during seven consecutive days. Outcome measures are total sleep time, sleep efficiency, sleep start and sleep end; physical activity intensity divided into: sedentary (<1.5 METS), light (1.5 to 3 METS) and moderate-to-vigorous (> 3 METS); and Body Mass Index standard deviations score, BMIsds.RESULTS:Total sleep time decreased with increasing age, and was shorter in boys than girls on both weekdays and weekends. Late bedtime but consistent wake-up time during weekends made total sleep time shorter on weekends than on weekdays. Day-to-day within-subject analysis revealed that moderate-to-vigorous intense physical activity promoted an increased sleep efficiency the following night (CI < 0.001 to 0.047), while total sleep time was not affected (CI -0.003 to 0.043). Neither sleep duration (CI -0.024 to 0.022) nor sleep efficiency (CI -0.019 to 0.028) affected mean physical activity level the subsequent day. The between-subject analysis indicates that the sleep of children characterized by high moderate-to-vigorous physical activity during the day was frequently interrupted (SE = -.23, P < .01). A negative association between BMIsds and sleep duration was found (-.10, p < .01).CONCLUSIONS:Short sleep duration was associated with high BMI in six to ten year old children. This study underscores the importance of consistent bedtimes throughout the week for promoting sleep duration in preadolescents. Furthermore, this study suggests that a large proportion of intensive physical activity during the day might promote good sleep quality.
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| 20. |
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| 21. |
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| 22. |
- Fransson, Eleonor, 1971-, et al.
(author)
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Job strain as a risk factor for leisure-time physical inactivity : an individual-participant meta-analysis of up to 170,000 men and women
- 2012
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In: American Journal of Epidemiology. - Cary : Oxford University Press. - 0002-9262 .- 1476-6256. ; 176:12, s. 1078-1089
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Research review (peer-reviewed)abstract
- Unfavorable work characteristics, such as low job control and too high or too low job demands, have been suggested to increase the likelihood of physical inactivity during leisure time, but this has not been verified in large-scale studies. The authors combined individual-level data from 14 European cohort studies (baseline years from 19851988 to 20062008) to examine the association between unfavorable work characteristics and leisure-time physical inactivity in a total of 170,162 employees (50 women; mean age, 43.5 years). Of these employees, 56,735 were reexamined after 29 years. In cross-sectional analyses, the odds for physical inactivity were 26 higher (odds ratio 1.26, 95 confidence interval: 1.15, 1.38) for employees with high-strain jobs (low control/high demands) and 21 higher (odds ratio 1.21, 95 confidence interval: 1.11, 1.31) for those with passive jobs (low control/low demands) compared with employees in low-strain jobs (high control/low demands). In prospective analyses restricted to physically active participants, the odds of becoming physically inactive during follow-up were 21 and 20 higher for those with high-strain (odds ratio 1.21, 95 confidence interval: 1.11, 1.32) and passive (odds ratio 1.20, 95 confidence interval: 1.11, 1.30) jobs at baseline. These data suggest that unfavorable work characteristics may have a spillover effect on leisure-time physical activity.
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| 23. |
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| 24. |
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| 25. |
- Heikkila, Katriina, et al.
(author)
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Job Strain and Alcohol Intake : A Collaborative Meta-Analysis of Individual-Participant Data from 140 000 Men and Women
- 2012
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In: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 7:7, s. Art. no. e40101-
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Journal article (peer-reviewed)abstract
- Background: The relationship between work-related stress and alcohol intake is uncertain. In order to add to the thus far inconsistent evidence from relatively small studies, we conducted individual-participant meta-analyses of the association between work-related stress (operationalised as self-reported job strain) and alcohol intake. Methodology and Principal Findings: We analysed cross-sectional data from 12 European studies (n = 142 140) and longitudinal data from four studies (n = 48 646). Job strain and alcohol intake were self-reported. Job strain was analysed as a binary variable (strain vs. no strain). Alcohol intake was harmonised into the following categories: none, moderate (women: 1-14, men: 1-21 drinks/week), intermediate (women: 15-20, men: 22-27 drinks/week) and heavy (women: > 20, men: > 27 drinks/week). Cross-sectional associations were modelled using logistic regression and the results pooled in random effects meta-analyses. Longitudinal associations were examined using mixed effects logistic and modified Poisson regression. Compared to moderate drinkers, non-drinkers and (random effects odds ratio (OR): 1.10, 95% CI: 1.05, 1.14) and heavy drinkers (OR: 1.12, 95% CI: 1.00, 1.26) had higher odds of job strain. Intermediate drinkers, on the other hand, had lower odds of job strain (OR: 0.92, 95% CI: 0.86, 0.99). We found no clear evidence for longitudinal associations between job strain and alcohol intake. Conclusions: Our findings suggest that compared to moderate drinkers, non-drinkers and heavy drinkers are more likely and intermediate drinkers less likely to report work-related stress.
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| 26. |
- Heikkilä, Katriina, et al.
(author)
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Work stress and risk of cancer: meta-analysis of 5700 incident cancer events in 116 000 European men and women
- 2013
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In: The BMJ. - : BMJ. - 1756-1833. ; 345:f165
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Journal article (peer-reviewed)abstract
- Objective To investigate whether work related stress, measured and defined as job strain, is associated with the overall risk of cancer and the risk of colorectal, lung, breast, or prostate cancers.Design Meta-analysis of pooled prospective individual participant data from 12 European cohort studies including 116 056 men and women aged 17-70 who were free from cancer at study baseline and were followed-up for a median of 12 years. Work stress was measured and defined as job strain, which was self reported at baseline. Incident cancers (all n=5765, colorectal cancer n=522, lung cancer n=374, breast cancer n=1010, prostate cancer n=865) were ascertained from cancer, hospital admission, and death registers. Data were analysed in each study with Cox regression and the study specific estimates pooled in meta-analyses. Models were adjusted for age, sex, socioeconomic position, body mass index (BMI), smoking, and alcohol intakeResults A harmonised measure of work stress, high job strain, was not associated with overall risk of cancer (hazard ratio 0.97, 95% confidence interval 0.90 to 1.04) in the multivariable adjusted analyses. Similarly, no association was observed between job strain and the risk of colorectal (1.16, 0.90 to 1.48), lung (1.17, 0.88 to 1.54), breast (0.97, 0.82 to 1.14), or prostate (0.86, 0.68 to 1.09) cancers. There was no clear evidence for an association between the categories of job strain and the risk of cancer.Conclusions These findings suggest that work related stress, measured and defined as job strain, at baseline is unlikely to be an important risk factor for colorectal, lung, breast, or prostate cancers.
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| 27. |
- Johnson, Toby, et al.
(author)
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Blood Pressure Loci Identified with a Gene-Centric Array.
- 2011
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In: American Journal of Human Genetics. - : Elsevier BV. - 1537-6605 .- 0002-9297. ; 89:6, s. 688-700
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Journal article (peer-reviewed)abstract
- Raised blood pressure (BP) is a major risk factor for cardiovascular disease. Previous studies have identified 47 distinct genetic variants robustly associated with BP, but collectively these explain only a few percent of the heritability for BP phenotypes. To find additional BP loci, we used a bespoke gene-centric array to genotype an independent discovery sample of 25,118 individuals that combined hypertensive case-control and general population samples. We followed up four SNPs associated with BP at our p < 8.56× 10(-7) study-specific significance threshold and six suggestively associated SNPs in a further 59,349 individuals. We identified and replicated a SNP at LSP1/TNNT3, a SNP at MTHFR-NPPB independent (r(2) = 0.33) of previous reports, and replicated SNPs at AGT and ATP2B1 reported previously. An analysis of combined discovery and follow-up data identified SNPs significantly associated with BP at p < 8.56× 10(-7) at four further loci (NPR3, HFE, NOS3, and SOX6). The high number of discoveries made with modest genotyping effort can be attributed to using a large-scale yet targeted genotyping array and to the development of a weighting scheme that maximized power when meta-analyzing results from samples ascertained with extreme phenotypes, in combination with results from nonascertained or population samples. Chromatin immunoprecipitation and transcript expression data highlight potential gene regulatory mechanisms at the MTHFR and NOS3 loci. These results provide candidates for further study to help dissect mechanisms affecting BP and highlight the utility of studying SNPs and samples that are independent of those studied previously even when the sample size is smaller than that in previous studies.
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| 28. |
- Josefsson, Maria, 1979-, et al.
(author)
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Causal inference with longitudinal outcomes and non-ignorable drop-out : Estimating the effect of living alone on cognitive decline
- 2016
-
In: The Journal of the Royal Statistical Society, Series C. - : Oxford University Press (OUP). - 0035-9254 .- 1467-9876. ; 65:1, s. 131-144
-
Journal article (peer-reviewed)abstract
- We develop a model to estimate the causal effect of living arrangement (living alone versus living with someone) on cognitive decline based on a 15-year prospective cohort study, where episodic memory function is measured every 5 years. One key feature of the model is the combination of propensity score matching to balance confounding variables between the two living arrangement groups—to reduce bias due to unbalanced covariates at baseline, with a pattern–mixture model for longitudinal data—to deal with non-ignorable dropout. A fully Bayesian approach allows us to convey the uncertainty in the estimation of the propensity score and subsequent matching in the inference of the causal effect of interest. The analysis conducted adds to previous studies in the literature concerning the protective effect of living with someone, by proposing a modelling approach treating living arrangement as an exposure.
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| 29. |
- Jäderling, Fredrik, et al.
(author)
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Accuracy in local staging of prostate cancer by adding a three-dimensional T2-weighted sequence with radial reconstructions in magnetic resonance imaging
- 2018
-
In: Acta Radiologica Open. - : Sage Publications. - 2058-4601. ; 7:2
-
Journal article (peer-reviewed)abstract
- Background: The evidence supporting the use of magnetic resonance imaging (MRI) in prostate cancer detection has been established, but its accuracy in local staging is questioned. Purpose: To investigate the additional value of multi-planar radial reconstructions of a three-dimensional (3D) T2-weighted (T2W) MRI sequence, intercepting the prostate capsule perpendicularly, for improving local staging of prostate cancer. Material and Methods: Preoperative, bi-parametric prostate MRI examinations in 94 patients operated between June 2014 and January 2015 where retrospectively reviewed by two experienced abdominal radiologists. Each patient was presented in two separate sets including diffusion-weighted imaging, without and with the 3D T2W set that included radial reconstructions. Each set was read at least two months apart. Extraprostatic tumor extension (EPE) was assessed according to a 5-point grading scale. Sensitivity and specificity for EPE was calculated and presented as receiver operating characteristics (ROC) with area under the curve (AUC), using histology from whole-mount prostate specimen as gold standard. Inter-rater agreement was calculated for the two different reading modes using Cohen's kappa. Results: The AUC for detection of EPE for Readers 1 and 2 in the two-dimensional (2D) set was 0.70 and 0.68, respectively, and for the 2D+3D set 0.62 and 0.65, respectively. Inter-rater agreement (Reader 1 vs. Reader 2) on EPE using Cohen's kappa for the 2D and 2D+3D set, respectively, was 0.42 and 0.17 (i.e. moderate and poor agreement, respectively). Conclusion: The addition of 3D T2W MRI with radial reconstructions did not improve local staging in prostate cancer.
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| 30. |
- Jäderling, Fredrik, et al.
(author)
-
Preoperative staging using magnetic resonance imaging and risk of positive surgical margins after prostate-cancer surgery
- 2019
-
In: Prostate Cancer and Prostatic Diseases. - : Nature Publishing Group. - 1365-7852 .- 1476-5608. ; 22:3, s. 391-398
-
Journal article (peer-reviewed)abstract
- Background: It is unclear whether preoperative staging using Magnetic Resonance Imaging (MRI) reduces the risk of positive margins in prostate cancer. We aimed to assess the effect on surgical margins and degree of nerve sparing of a pelvic MRI presented at a preoperative MRI conference. Methods: Single institution, observational cohort study including 1037 men that underwent robot assisted radical prostatectomy between October 2013 and June 2015. Of these, 557 underwent a preoperative MRI combined with a preoperative MRI conference and 410 did not. With whole-mount prostate specimen histopathology as gold standard we assessed the ability of MRI in finding the index tumor and the sensitivity and specificity for extra prostatic extension. We calculated relative risks for positive surgical margins and non-nerve sparing procedure, adjusting for preoperative risk factors using stabilized inverse-probability weighting. Results: MRI detected the index tumor in 80% of the cases. Non-organ confined disease (pT3) at histology was present in the MRI and the non-MRI group in 42% and 24%, respectively. Rate of positive surgical margins comparing the MRI and non-MRI groups was 26.7% and 33.7%, respectively, relative risk 0.79 [95% CI 0.65-0.96], weighted relative risk (wRR) 0.69 [95% CI 0.55-0.86]. The wRR of extensive positive surgical margins was 0.45 [95% CI 0.31-0.67]. Undergoing MRI was also associated with an increased risk of being operated with a non-nerve sparing technique (wRR, 1.84 [95% CI 1.11-3.03]). Conclusions: Our study suggests that preoperative prostate MRI in combination with a preoperative MRI conference affects the degree of nerve-sparing surgery and reduces positive surgical margins.
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| 31. |
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| 32. |
- Keutzer, Lina, et al.
(author)
-
Machine Learning and Pharmacometrics for Prediction of Pharmacokinetic Data : Differences, Similarities and Challenges Illustrated with Rifampicin
- 2022
-
In: Pharmaceutics. - : MDPI. - 1999-4923. ; 14:8
-
Journal article (peer-reviewed)abstract
- Pharmacometrics (PM) and machine learning (ML) are both valuable for drug development to characterize pharmacokinetics (PK) and pharmacodynamics (PD). Pharmacokinetic/pharmacodynamic (PKPD) analysis using PM provides mechanistic insight into biological processes but is time- and labor-intensive. In contrast, ML models are much quicker trained, but offer less mechanistic insights. The opportunity of using ML predictions of drug PK as input for a PKPD model could strongly accelerate analysis efforts. Here exemplified by rifampicin, a widely used antibiotic, we explore the ability of different ML algorithms to predict drug PK. Based on simulated data, we trained linear regressions (LASSO), Gradient Boosting Machines, XGBoost and Random Forest to predict the plasma concentration-time series and rifampicin area under the concentration-versus-time curve from 0-24 h (AUC(0-24h)) after repeated dosing. XGBoost performed best for prediction of the entire PK series (R-2: 0.84, root mean square error (RMSE): 6.9 mg/L, mean absolute error (MAE): 4.0 mg/L) for the scenario with the largest data size. For AUC(0-24h) prediction, LASSO showed the highest performance (R-2: 0.97, RMSE: 29.1 h center dot mg/L, MAE: 18.8 h center dot mg/L). Increasing the number of plasma concentrations per patient (0, 2 or 6 concentrations per occasion) improved model performance. For example, for AUC(0-24h) prediction using LASSO, the R-2 was 0.41, 0.69 and 0.97 when using predictors only (no plasma concentrations), 2 or 6 plasma concentrations per occasion as input, respectively. Run times for the ML models ranged from 1.0 s to 8 min, while the run time for the PM model was more than 3 h. Furthermore, building a PM model is more time- and labor-intensive compared with ML. ML predictions of drug PK could thus be used as input into a PKPD model, enabling time-efficient analysis.
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| 33. |
- Kivimäki, Mika, et al.
(author)
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Association between socioeconomic status and the development of mental and physical health conditions in adulthood : a multi-cohort study
- 2020
-
In: The Lancet Public Health. - : Elsevier. - 2468-2667. ; 5:3, s. e140-e149
-
Journal article (peer-reviewed)abstract
- Background: Socioeconomic disadvantage is a risk factor for many diseases. We characterised cascades of these conditions by using a data-driven approach to examine the association between socioeconomic status and temporal sequences in the development of 56 common diseases and health conditions. Methods: In this multi-cohort study, we used data from two Finnish prospective cohort studies: the Health and Social Support study and the Finnish Public Sector study. Our pooled prospective primary analysis data comprised 109 246 Finnish adults aged 17–77 years at study entry. We captured socioeconomic status using area deprivation and education at baseline (1998–2013). Participants were followed up for health conditions diagnosed according to the WHO International Classification of Diseases until 2016 using linkage to national health records. We tested the generalisability of our findings with an independent UK cohort study—the Whitehall II study (9838 people, baseline in 1997, follow-up to 2017)—using a further socioeconomic status indicator, occupational position. Findings: During 1 110 831 person-years at risk, we recorded 245 573 hospitalisations in the Finnish cohorts; the corresponding numbers in the UK study were 60 946 hospitalisations in 186 572 person-years. Across the three socioeconomic position indicators and after adjustment for lifestyle factors, compared with more advantaged groups, low socioeconomic status was associated with increased risk for 18 (32·1%) of the 56 conditions. 16 diseases formed a cascade of inter-related health conditions with a hazard ratio greater than 5. This sequence began with psychiatric disorders, substance abuse, and self-harm, which were associated with later liver and renal diseases, ischaemic heart disease, cerebral infarction, chronic obstructive bronchitis, lung cancer, and dementia. Interpretation: Our findings highlight the importance of mental health and behavioural problems in setting in motion the development of a range of socioeconomically patterned physical illnesses. Policy and health-care practice addressing psychological health issues in social context and early in the life course could be effective strategies for reducing health inequalities. Funding: UK Medical Research Council, US National Institute on Aging, NordForsk, British Heart Foundation, Academy of Finland, and Helsinki Institute of Life Science.
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| 34. |
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| 35. |
- Koch, Felix-Sebastian, et al.
(author)
-
Procedural memory in infancy: Evidence from implicit sequence learning in an eye-tracking paradigm
- 2020
-
In: Journal of experimental child psychology (Print). - : ELSEVIER SCIENCE INC. - 0022-0965 .- 1096-0457. ; 191
-
Journal article (peer-reviewed)abstract
- Procedural memory underpins the learning of skills and habits. It is often tested in children and adults with sequence learning on the serial reaction time (SRT) task, which involves manual motor control. However, due to infants slowly developing control of motor actions, most procedures that require motor control cannot be examined in infancy. Here, we investigated procedural memory using an SRT task adapted for infants. During the task, images appeared at one of three locations on a screen, with the location order following a five-item recurring sequence. Three blocks of recurring sequences were followed by a random-order fourth block and finally another block of recurring sequences. Eye movement data were collected for infants (n = 35) and adults (n = 31). Reaction time was indexed by calculating the saccade latencies for orienting to each image as it appeared. The entire protocol took less than 3 min. Sequence learning in the SRT task can be operationalized as an increase in latencies in the random block as compared with the preceding and following sequence blocks. This pattern was observed in both the infants and adults. This study is the first to report learning in an SRT task in infants as young as 9 months. This SRT protocol is a promising procedure for measuring procedural memory in infants. (C) 2019 Elsevier Inc. All rights reserved.
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| 36. |
- Kostka, Kristin, et al.
(author)
-
Unraveling COVID-19: A Large-Scale Characterization of 4.5 Million COVID-19 Cases Using CHARYBDIS.
- 2022
-
In: Clinical epidemiology. - 1179-1349. ; 14, s. 369-384
-
Journal article (peer-reviewed)abstract
- Routinely collected real world data (RWD) have great utility in aiding the novel coronavirus disease (COVID-19) pandemic response. Here we present the international Observational Health Data Sciences and Informatics (OHDSI) Characterizing Health Associated Risks and Your Baseline Disease In SARS-COV-2 (CHARYBDIS) framework for standardisation and analysis of COVID-19 RWD.We conducted a descriptive retrospective database study using a federated network of data partners in the United States, Europe (the Netherlands, Spain, the UK, Germany, France and Italy) and Asia (South Korea and China). The study protocol and analytical package were released on 11th June 2020 and are iteratively updated via GitHub. We identified three non-mutually exclusive cohorts of 4,537,153 individuals with a clinical COVID-19 diagnosis or positive test, 886,193 hospitalized with COVID-19, and 113,627 hospitalized with COVID-19 requiring intensive services.We aggregated over 22,000 unique characteristics describing patients with COVID-19. All comorbidities, symptoms, medications, and outcomes are described by cohort in aggregate counts and are readily available online. Globally, we observed similarities in the USA and Europe: more women diagnosed than men but more men hospitalized than women, most diagnosed cases between 25 and 60 years of age versus most hospitalized cases between 60 and 80 years of age. South Korea differed with more women than men hospitalized. Common comorbidities included type 2 diabetes, hypertension, chronic kidney disease and heart disease. Common presenting symptoms were dyspnea, cough and fever. Symptom data availability was more common in hospitalized cohorts than diagnosed.We constructed a global, multi-centre view to describe trends in COVID-19 progression, management and evolution over time. By characterising baseline variability in patients and geography, our work provides critical context that may otherwise be misconstrued as data quality issues. This is important as we perform studies on adverse events of special interest in COVID-19 vaccine surveillance.
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| 37. |
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| 38. |
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| 39. |
- Lai, Zhennan, et al.
(author)
-
Aquaporin gene therapy corrects Sjogren's syndrome phenotype in mice
- 2016
-
In: Proceedings of the National Academy of Sciences of the United States of America. - : Proceedings of the National Academy of Sciences. - 0027-8424 .- 1091-6490. ; 113:20, s. 5694-5699
-
Journal article (peer-reviewed)abstract
- Primary Sjogren's syndrome (pSS) is a chronic autoimmune disease that is estimated to affect 35 million people worldwide. Currently, no effective treatments exist for Sjogren's syndrome, and there is a limited understanding of the physiological mechanisms associated with xerostomia and hyposalivation. The present work revealed that aquaporin 5 expression, a water channel critical for salivary gland fluid secretion, is regulated by bone morphogenetic protein 6. Increased expression of this cytokine is strongly associated with the most common symptom of primary Sjogren's syndrome, the loss of salivary gland function. This finding led us to develop a therapy in the treatment of Sjogren's syndrome by increasing the water permeability of the gland to restore saliva flow. Our study demonstrates that the targeted increase of gland permeability not only resulted in the restoration of secretory gland function but also resolved the hallmark salivary gland inflammation and systemic inflammation associated with disease. Secretory function also increased in the lacrimal gland, suggesting this local therapy could treat the systemic symptoms associated with primary Sjogren's syndrome.
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| 40. |
- Lennerling, Annette, 1963, et al.
(author)
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Laparoscopic or open surgery for living donor nephrectomy factor for graft loss
- 2001
-
In: Nephrology Dialysis and Transplantation. - 1460-2385. ; 16:2, s. 383-6
-
Journal article (peer-reviewed)abstract
- BACKGROUND: The anterior extraperitoneal approach for living donor nephrectomy has been used in more than 700 living cases in the unit and proved to be safe for the donor. In 1998, laparoscopic nephrectomy was introduced as an option when technically feasible. We found it essential to investigate the consequences of the new technique. SUBJECTS AND METHODS: One hundred living donor kidney transplantations were performed from 1998 to June 2000, 45 with laparoscopic, 55 with open nephrectomy. The donors took part in a structured interview 4 weeks after the donation and their responses were categorized in three classes. RESULTS: In each group, one recipient had delayed initial function. The serum creatinine levels after 3 and 7 days or the GFR values after 6 months did not differ. One graft has been lost following laparoscopic nephrectomy and four after open surgery. For the laparoscopy donors, the median number of post-operative days in hospital was 5.0 days (range 2-9), vs 6.0 (4-8) after open surgery (NS). The requirement of opoid analgesics post-operatively was 5.0 doses (1-22) vs 6.0 (1-38) (P=0.02); and after 4 weeks, 23 of 45 laparoscopic donors were free of pain vs eight of 55 open nephrectomy donors (P=0.0004). Approximately one-third of all donors felt some restriction of physical activity and the majority complained of impaired physical energy. There were no differences between the groups. The duration of sick-leave after laparoscopic surgery was median 6 (2-19) weeks vs 7 (1-16) (NS). CONCLUSIONS: Laparoscopic nephrectomy is safe. Less post-operative pain is a definite advantage for the donor. PMID: 11158417 [PubMed - indexed for MEDLINE]
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| 41. |
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| 42. |
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| 43. |
- Lundström, Maria, et al.
(author)
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Postoperative delirium in old patients with femoral neck fracture : a randomized intervention study.
- 2007
-
In: Aging Clinical and Experimental Research. - 1594-0667 .- 1720-8319. ; 19:3, s. 178-186
-
Journal article (peer-reviewed)abstract
- BACKGROUND AND AIMS: Delirium is a common postoperative complication in elderly patients which has a serious impact on outcome in terms of morbidity and costs. We examined whether a postoperative multi-factorial intervention program can reduce delirium and improve outcome in patients with femoral neck fractures.METHODS: One hundred and ninety-nine patients, aged 70 years and over (mean age+/-SD, 82+/-6, 74% women), were randomly assigned to postoperative care in a specialized geriatric ward or a conventional orthopedic ward. The intervention consisted of staff education focusing on the assessment, prevention and treatment of delirium and associated complications. The staff worked as a team, applying comprehensive geriatric assessment, management and rehabilitation. Patients were assessed using the Mini Mental State Examination and the Organic Brain Syndrome Scale, and delirium was diagnosed according to DSM-IV criteria.RESULTS: The number of days of postoperative delirium among intervention patients was fewer (5.0+/-7.1 days vs 10.2+/-13.3 days, p=0.009) compared with controls. A lower proportion of intervention patients were delirious postoperatively than controls (56/102, 54.9% vs 73/97, 75.3%, p=0.003). Eighteen percent in the intervention ward and 52% of controls were delirious after the seventh postoperative day (p<0.001). Intervention patients suffered from fewer complications, such as decubitus ulcers, urinary tract infections, nutritional complications, sleeping problems and falls, than controls. Total postoperative hospitalization was shorter in the intervention ward (28.0+/-17.9 days vs 38.0+/-40.6 days, p=0.028).CONCLUSIONS: Patients with postoperative delirium can be successfully treated, resulting in fewer days of delirium, fewer other complications, and shorter length of hospitalization.
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| 44. |
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| 45. |
- Lövdén, Martin, et al.
(author)
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The extent of stability and change in episodic and semantic memory in old age : Demographic predictors of level and change
- 2004
-
In: The journals of gerontology. Series B, Psychological sciences and social sciences. - Washington, DC : Gerontological Society of America. - 1079-5014 .- 1758-5368. ; 59:3, s. 130-134
-
Journal article (peer-reviewed)abstract
- Structural stability and change in semantic and episodic memory performance as well as interindividual differences in 5-year changes in these constructs are examined within a sample of older adults (age rangeT1 = 60–80; n = 361). Interindividual differences in change were limited but significant. Stability coefficients were higher for semantic memory (.95) than for episodic memory (.87). Changes in episodic and semantic memory performance were strongly associated (r =.68). Across time, variances and covariances increased, and a tendency toward dedifferentiation in terms of increasing correlations was found. Chronological age was related to both level and change, but gender and education were only related to level of memory performance. Collectively, these results depict relatively high degrees of structural stability and stability of interindividual differences in declarative memory in old age.
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| 46. |
- Micke, Patrick, et al.
(author)
-
Gene Copy Number Aberrations Are Associated with Survival in Histologic Subgroups of Non-small Cell Lung Cancer
- 2011
-
In: Journal of Thoracic Oncology. - 1556-0864 .- 1556-1380. ; 6:11, s. 1833-1840
-
Journal article (peer-reviewed)abstract
- Introduction: Non-small cell lung cancer (NSCLC) is characterized by a multitude of genetic aberrations with unknown clinical impact. In this study, we aimed to identify gene copy number changes that correlate with clinical outcome in NSCLC. To maximize the chance to identify clinically relevant events, we applied a strategy involving two prognostically extreme patient groups. Methods: Short-term (<20 month; n = 53) and long-term survivors (>58 month; n = 47) were selected from a clinically well-characterized NSCLC patient cohort with available fresh frozen tumor specimens. The samples were analyzed using high-resolution single-nucleotide polymorphism array technology to assess gene copy number variations and array-based gene expression profiling. The molecular data were combined with information on clinical parameters. Results: Genetic aberrations were strongly associated with tumor histology. In adenocarcinoma (n = 50), gene copy number gains on chromosome 8q21-q24.3 (177 genes) were more frequent in long-term than in short-term survivors. In squamous cell carcinoma (n = 28), gains on chromosome 14q23.1-24.3 (133 genes) were associated with shorter survival, whereas losses in a neighboring region, 14q31.1-32.33 (110 genes), correlated with favorable outcome. In accordance with copy number gains and losses, messenger RNA expression levels of corresponding genes were increased or decreased, respectively. Conclusion: Comprehensive tumor profiling permits the integration of genomic, histologic, and clinical data. We identified gene copy number gains and losses, with corresponding changes in messenger RNA levels that were associated with prognosis in adenocarcinoma and squamous cell carcinoma of the lung.
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| 47. |
- Mikkelsen, Bent Egberg, et al.
(author)
-
Promotion of healthy eating in the workplace : a socio-nutritional approach
- 2008
-
Conference paper (other academic/artistic)abstract
- Purpose: Unhealthy eating and lifestyle as well as low physical activity is a growing problem and are estimated to be among the primary causes for the growth in obesity and overweight among the adult population. In the ‘settings approach’ institutions such as the workplace are seen as arenas in which eating behavioural patterns can be influenced. This arena tends to grow in importance as more companies provide workplace food with increasing nutritional attention and develop not only lunch offers, but also take away offers. However settings based scientific literature has shown that interventions tend to give only modest effect when sustainability of intervention is used as a measure.Methods: The paper is based on a review of literature on workplace healthy eating based projects and research, mainly with focus on Sweden and Denmark carried out in the Good Food at Work project.Results: Important elements in this kind of interventions are management commitment, education, supporting organisational structures, employee participation, and integrated perspective on risk factors at the workplace and the everyday life of employees.Discussion: The paper suggests that a socio nutritional approach to promotion of healthy eating at workplace is needed if workplace interventions are to be successful. It argues that a socio-technical approach (Clausen and Yoshinaka, 2007) where innovation is considered as a multi-stakeholder process in which interaction between the social constitution of the workplace (Seltz & Hildebrandt, 1989), the change agents, and societal influence (Thorsen et al, 2005) play an important role in the shaping of healthy workplace eating.
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| 48. |
- Mikkelsen, Bent Egberg, et al.
(author)
-
Promotion of healthy eating in the workplace : a socio-nutritional approach
- 2008
-
Conference paper (other academic/artistic)abstract
- Purpose: Unhealthy eating and lifestyle as well as low physical activity is a growing problem and are estimated to be among the primary causes for the growth in obesity and overweight among the adult population. In the ‘settings approach’ institutions such as the workplace are seen as arenas in which eating behavioural patterns can be influenced. This arena tends to grow in importance as more companies provide workplace food with increasing nutritional attention and develop not only lunch offers, but also take away offers. However settings based scientific literature has shown that interventions tend to give only modest effect when sustainability of intervention is used as a measure. Methods: The paper is based on a review of literature on workplace healthy eating based projects and research, mainly with focus on Sweden and Denmark carried out in the Good Food at Work project. Results: Important elements in this kind of interventions are management commitment, education, supporting organisational structures, employee participation, and integrated perspective on risk factors at the workplace and the everyday life of employees. Discussion: The paper suggests that a socio nutritional approach to promotion of healthy eating at workplace is needed if workplace interventions are to be successful. It argues that a socio-technical approach (Clausen and Yoshinaka, 2007) where innovation is considered as a multi-stakeholder process in which interaction between the social constitution of the workplace (Seltz & Hildebrandt, 1989), the change agents, and societal influence (Thorsen et al, 2005) play an important role in the shaping of healthy workplace eating.
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| 49. |
- Morales, Daniel R, et al.
(author)
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Renin-angiotensin system blockers and susceptibility to COVID-19: an international, open science, cohort analysis.
- 2021
-
In: The Lancet Digital health. - 2589-7500. ; 3:2
-
Journal article (peer-reviewed)abstract
- Angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) have been postulated to affect susceptibility to COVID-19. Observational studies so far have lacked rigorous ascertainment adjustment and international generalisability. We aimed to determine whether use of ACEIs or ARBs is associated with an increased susceptibility to COVID-19 in patients with hypertension.In this international, open science, cohort analysis, we used electronic health records from Spain (Information Systems for Research in Primary Care [SIDIAP]) and the USA (Columbia University Irving Medical Center data warehouse [CUIMC] and Department of Veterans Affairs Observational Medical Outcomes Partnership [VA-OMOP]) to identify patients aged 18 years or older with at least one prescription for ACEIs and ARBs (target cohort) or calcium channel blockers (CCBs) and thiazide or thiazide-like diuretics (THZs; comparator cohort) between Nov 1, 2019, and Jan 31, 2020. Users were defined separately as receiving either monotherapy with these four drug classes, or monotherapy or combination therapy (combination use) with other antihypertensive medications. We assessed four outcomes: COVID-19 diagnosis; hospital admission with COVID-19; hospital admission with pneumonia; and hospital admission with pneumonia, acute respiratory distress syndrome, acute kidney injury, or sepsis. We built large-scale propensity score methods derived through a data-driven approach and negative control experiments across ten pairwise comparisons, with results meta-analysed to generate 1280 study effects. For each study effect, we did negative control outcome experiments using a possible 123 controls identified through a data-rich algorithm. This process used a set of predefined baseline patient characteristics to provide the most accurate prediction of treatment and balance among patient cohorts across characteristics. The study is registered with the EU Post-Authorisation Studies register, EUPAS35296.Among 1355349 antihypertensive users (363785 ACEI or ARB monotherapy users, 248915 CCB or THZ monotherapy users, 711799 ACEI or ARB combination users, and 473076 CCB or THZ combination users) included in analyses, no association was observed between COVID-19 diagnosis and exposure to ACEI or ARB monotherapy versus CCB or THZ monotherapy (calibrated hazard ratio [HR] 0·98, 95% CI 0·84-1·14) or combination use exposure (1·01, 0·90-1·15). ACEIs alone similarly showed no relative risk difference when compared with CCB or THZ monotherapy (HR 0·91, 95% CI 0·68-1·21; with heterogeneity of >40%) or combination use (0·95, 0·83-1·07). Directly comparing ACEIs with ARBs demonstrated a moderately lower risk with ACEIs, which was significant with combination use (HR 0·88, 95% CI 0·79-0·99) and non-significant for monotherapy (0·85, 0·69-1·05). We observed no significant difference between drug classes for risk of hospital admission with COVID-19, hospital admission with pneumonia, or hospital admission with pneumonia, acute respiratory distress syndrome, acute kidney injury, or sepsis across all comparisons.No clinically significant increased risk of COVID-19 diagnosis or hospital admission-related outcomes associated with ACEI or ARB use was observed, suggesting users should not discontinue or change their treatment to decrease their risk of COVID-19.Wellcome Trust, UK National Institute for Health Research, US National Institutes of Health, US Department of Veterans Affairs, Janssen Research & Development, IQVIA, South Korean Ministry of Health and Welfare Republic, Australian National Health and Medical Research Council, and European Health Data and Evidence Network.
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| 50. |
- Moreno-Martos, David, et al.
(author)
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Characteristics and outcomes of COVID-19 patients with COPD from the United States, South Korea, and Europe
- 2023
-
In: Wellcome Open Research. - : F1000 Research Ltd. - 2398-502X. ; 7
-
Journal article (peer-reviewed)abstract
- Background: Characterization studies of COVID-19 patients with chronic obstructive pulmonary disease (COPD) are limited in size and scope. The aim of the study is to provide a large-scale characterization of COVID-19 patients with COPD. Methods: We included thirteen databases contributing data from January-June 2020 from North America (US), Europe and Asia. We defined two cohorts of patients with COVID-19 namely a ‘diagnosed’ and ‘hospitalized’ cohort. We followed patients from COVID-19 index date to 30 days or death. We performed descriptive analysis and reported the frequency of characteristics and outcomes among COPD patients with COVID-19. Results: The study included 934,778 patients in the diagnosed COVID-19 cohort and 177,201 in the hospitalized COVID-19 cohort. Observed COPD prevalence in the diagnosed cohort ranged from 3.8% (95%CI 3.5-4.1%) in French data to 22.7% (95%CI 22.4-23.0) in US data, and from 1.9% (95%CI 1.6-2.2) in South Korean to 44.0% (95%CI 43.1-45.0) in US data, in the hospitalized cohorts. COPD patients in the hospitalized cohort had greater comorbidity than those in the diagnosed cohort, including hypertension, heart disease, diabetes and obesity. Mortality was higher in COPD patients in the hospitalized cohort and ranged from 7.6% (95%CI 6.9-8.4) to 32.2% (95%CI 28.0-36.7) across databases. ARDS, acute renal failure, cardiac arrhythmia and sepsis were the most common outcomes among hospitalized COPD patients. Conclusion: COPD patients with COVID-19 have high levels of COVID-19-associated comorbidities and poor COVID-19 outcomes. Further research is required to identify patients with COPD at high risk of worse outcomes.
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