| 1. |
- Andersson, Ulrika, 1977, et al.
(författare)
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Larmar och gör sig till (inledningskapitel)
- 2017
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Ingår i: Larmar och gör sig till. - Göteborg : Göteborgs universitet. - 0284-4788. - 9789189673397 ; , s. 11-35
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Bokkapitel (refereegranskat)
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| 2. |
- Ansari, Daniel, et al.
(författare)
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Early-onset pancreatic cancer : a population-based study using the SEER registry
- 2019
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Ingår i: Langenbeck's Archives of Surgery. - : Springer Science and Business Media LLC. - 1435-2443 .- 1435-2451. ; 404:5, s. 565-571
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Tidskriftsartikel (refereegranskat)abstract
- Background: Early-onset pancreatic cancer (< 50 years, EOPC) is uncommon and limited data exist on clinical presentation and long-term survival. The aim of this study was to compare outcomes between patients with EOPC and those with later-onset pancreatic cancer (≥ 50 years, LOPC) using a large population-based cohort. Methods: The Surveillance, Epidemiology, and End Results (SEER) database was queried to identify patients with a microscopically confirmed pancreatic ductal adenocarcinoma for the period 2004 to 2016. Propensity score matching was used to compare overall survival (OS) and cancer-specific survival (CSS) between patients with EOPC and LOPC. The EOPC and LOPC patients were paired 1:1 on propensity scores based on gender, tumor location, tumor size, AJCC stage, and treatment details. Results: The overall cohort included 72,906 patients with pancreatic ductal adenocarcinoma, including 4523 patients with EOPC (6.2%). EOPC patients were diagnosed at a more advanced AJCC stage (p < 0.001) compared with LOPC patients and received significantly more treatment, including surgery (p < 0.001), radiation (p < 0.001), and chemotherapy (p < 0.001). Following propensity score matching, 3172 EOPC patients were matched to 3172 LOPC patients, alleviating any covariate differences between the groups. The matched analysis showed that EOPC was associated with poorer 5-year OS (6.1% vs 8.6%, p = 0.003) and 5-year CSS (6.7% vs 9.7%, p < 0.001). In multivariable Cox regression analysis, EOPC remained significantly associated with adverse OS and CSS. Subgroup analyses showed that EOPC was associated with adverse 5-year OS (17.7% vs 26.9%, p < 0.001) and 5-year CSS (18.9% vs 29.7%, p < 0.001) in operated patients. After multivariable analysis, EOPC remained significantly associated with OS and CSS. For patients that did not undergo surgery, the OS and CSS remained dismal without any significant differences between the groups. Conclusion: To our knowledge, this is the largest study to compare the outcome of EOPC vs LOPC, as well as the first to use propensity score matching methodology for this purpose. The findings demonstrate that EOPC is diagnosed at a later stage and the matched survival analysis demonstrated reduced OS and CSS. We suggest that pancreatic cancer in young patients may have a unique tumor biology, which may be of importance for risk stratification and patient counseling.
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| 3. |
- Ansari, Daniel, et al.
(författare)
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The hippo signaling pathway in pancreatic cancer
- 2019
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Ingår i: Anticancer research. - : Anticancer Research USA Inc.. - 0250-7005 .- 1791-7530. ; 39:7, s. 3317-3321
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Forskningsöversikt (refereegranskat)abstract
- Hippo signaling is a key regulator of organ size, tissue hemostasis and regeneration. Dysregulation of the Hippo pathway has been recognized in a variety of human cancers, including pancreatic cancer. YES-associated protein (YAP) and transcriptional coactivator with PDZ-binding motif (TAZ) are the two major downstream effectors of the Hippo pathway. YAP and TAZ have been found to promote pancreatic tumor development and progression, even in the absence of mutant Kirsten RAS (KRAS). Pancreatic cancer is associated with an abundant stromal reaction leading to tumor growth and immune escape. It has been found that YAP and TAZ modulate behavior of pancreatic stellate cells and recruitment of tumor-associated macrophages and myeloid-derived suppressor cells. Moreover, YAP and TAZ are associated with chemoresistance and poor prognosis in pancreatic cancer. This review dissects the role of Hippo signaling in pancreatic cancer, focusing on molecular mechanisms and prospects for future intervention.
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| 4. |
- Ansari, Daniel, et al.
(författare)
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The role of PEDF in pancreatic cancer
- 2019
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Ingår i: Anticancer research. - : Anticancer Research USA Inc.. - 0250-7005 .- 1791-7530. ; 39:7, s. 3311-3315
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Forskningsöversikt (refereegranskat)abstract
- Pigment epithelium-derived factor (PEDF) is an important antiangiogenic and antitumorigenic factor in a variety of cancer forms, including pancreatic cancer. PEDF is mainly secreted as a soluble monomeric glycoprotein. In human pancreatic cancer PEDF levels are decreased, both in the tissue and serum. The decrease is associated with increased tumor angiogenesis, fibrosis, inflammation, autophagy, occurrence of liver metastasis and worse prognosis. In murine models, loss of PEDF is sufficient to induce invasive carcinoma and this phenotype is associated with large lesions characterized by poor differentiation. Lentiviral gene transfer of PEDF has resulted in decreased microvessel density and has inhibited tumor growth. Herein we review the multifunctional role of PEDF in pancreatic cancer and its therapeutic potential.
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| 5. |
- Arvidsson, Daniel, et al.
(författare)
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Physical Activity and Concordance between Objective and Perceived Walkability.
- 2012
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Ingår i: Medicine & Science in Sports & Exercise. - 1530-0315. ; 44, s. 280-287
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Tidskriftsartikel (refereegranskat)abstract
- PURPOSE:: To investigate concordance between objective and perceived neighborhood walkability, their associations with self-reported walking and objective physical activity, and sociodemographic characteristics of individuals in neighborhoods with objectively assessed high walkability who misperceive it as low. METHODS:: In 1,925 individuals aged 20-66 years, recruited from administrative areas in the city of Stockholm, Sweden, of both high and low neighborhood walkability, objective neighborhood walkability was assessed within a 1,000m radius of each individual's residential address using Geographic Information Systems (GIS). Perceived walkability was based on the Neighborhood Environment Walkability Scale (NEWS). Walking was assessed using the International Physical Activity Questionnaire (IPAQ), and total physical activity and moderate-to-vigorous physical activity (MVPA) by an accelerometer (ActiGraph). Sociodemographic characteristics were self-reported. RESULTS:: Objective and perceived neighborhood walkability agreed in 67.0% of the individuals, with kappa=0.34 (95% CI: 0.30-0.38). One-third of the individuals in neighborhoods with objectively assessed high walkability misperceived it as low. This non-concordance was more common among older and married/cohabiting individuals. After adjustment for sociodemographic characteristics, high objective neighborhood walkability was associated with 35.0 (95% CI: 14.6-64.6) and 10.5 (95% CI: -5.2-28.5) more minutes/week of walking for transportation and leisure, respectively, and 2.8 (95% CI: 0.9-5.0) more minutes/day of MVPA. High perceived neighborhood walkability was associated with 41.5 (95% CI: 15.8-62.9) and 21.8 (95% CI: 2.8-40.0) more minutes/week of walking for transportation and leisure, respectively, and 1.7 (95% CI: -0.3-3.7) more minutes/day of MVPA. CONCLUSIONS:: Objective and perceived neighborhood walkability both contribute to the amount of walking and objective physical activity. Both measures of neighborhood walkability may be important factors to target in interventions aiming at increasing physical activity.
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| 6. |
- Atabaki-Pasdar, Naeimeh, et al.
(författare)
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Inferring causal pathways between metabolic processes and liver fat accumulation: an IMI DIRECT study
- 2021
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Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- Type 2 diabetes (T2D) and non-alcoholic fatty liver disease (NAFLD) often co-occur. Defining causal pathways underlying this relationship may help optimize the prevention and treatment of both diseases. Thus, we assessed the strength and magnitude of the putative causal pathways linking dysglycemia and fatty liver, using a combination of causal inference methods.Measures of glycemia, insulin dynamics, magnetic resonance imaging (MRI)-derived abdominal and liver fat content, serological biomarkers, lifestyle, and anthropometry were obtained in participants from the IMI DIRECT cohorts (n=795 with new onset T2D and 2234 individuals free from diabetes). UK Biobank (n=3641) was used for modelling and replication purposes. Bayesian networks were employed to infer causal pathways, with causal validation using two-sample Mendelian randomization.Bayesian networks fitted to IMI DIRECT data identified higher basal insulin secretion rate (BasalISR) and MRI-derived excess visceral fat (VAT) accumulation as the features of dysmetabolism most likely to cause liver fat accumulation; the unconditional probability of fatty liver (>5%) increased significantly when conditioning on high levels of BasalISR and VAT (by 23%, 32% respectively; 40% for both). Analyses in UK Biobank yielded comparable results. MR confirmed most causal pathways predicted by the Bayesian networks.Here, BasalISR had the highest causal effect on fatty liver predisposition, providing mechanistic evidence underpinning the established association of NAFLD and T2D. BasalISR may represent a pragmatic biomarker for NAFLD prediction in clinical practice.Competing Interest StatementHR is an employee and shareholder of Sanofi. MIM: The views expressed in this article are those of the author(s) and not necessarily those of the NHS, the NIHR, or the Department of Health. MIM has served on advisory panels for Pfizer, NovoNordisk and Zoe Global, has received honoraria from Merck, Pfizer, Novo Nordisk and Eli Lilly, and research funding from Abbvie, Astra Zeneca, Boehringer Ingelheim, Eli Lilly, Janssen, Merck, NovoNordisk, Pfizer, Roche, Sanofi Aventis, Servier, and Takeda. As of June 2019, MIM is an employee of Genentech, and a holder of Roche stock. AM is a consultant for Lilly and has received research grants from several diabetes drug companies. PWF has received research grants from numerous diabetes drug companies and fess as consultant from Novo Nordisk, Lilly, and Zoe Global Ltd. He is currently the Scientific Director in Patient Care at the Novo Nordisk Foundation. Other authors declare non competing interests.Funding StatementThe work leading to this publication has received support from the Innovative Medicines Initiative Joint Undertaking under grant agreement 115317 (DIRECT) resources of which are composed of financial contribution from the European Union Seventh Framework Programme (FP7/2007-2013) and EFPIA companies in kind contribution. NAP is supported in part by Henning och Johan Throne-Holsts Foundation, Hans Werthen Foundation, an IRC award from the Swedish Foundation for Strategic Research and a European Research Council award ERC-2015-CoG - 681742_NASCENT. HPM is supported by an IRC award from the Swedish Foundation for Strategic Research and a European Research Council award ERC-2015-CoG - 681742_NASCENT. AGJ is supported by an NIHR Clinician Scientist award (17/0005624). RK is funded by the Novo Nordisk Foundation (NNF18OC0031650) as part of a postdoctoral fellowship, an IRC award from the Swedish Foundation for Strategic Research and a European Research Council award ERC-2015-CoG - 681742_NASCENT. AK, PM, HF, JF and GNG are supported by an IRC award from the Swedish Foundation for Strategic Research and a European Research Council award ERC-2015-CoG - 681742_NASCENT. TJM is funded by an NIHR clinical senior lecturer fellowship. S.Bru acknowledges support from the Novo Nordisk Foundation (grants NNF17OC0027594 and NNF14CC0001). ATH is a Wellcome Trust Senior Investigator and is also supported by the NIHR Exeter Clinical Research Facility. JMS acknowledges support from Science for Life Laboratory (Plasma Profiling Facility), Knut and Alice Wallenberg Foundation (Human Protein Atlas) and Erling-Persson Foundation (KTH Centre for Precision Medicine). MIM is supported by the following grants; Wellcome (090532, 098381, 106130, 203141, 212259); NIH (U01-DK105535). PWF is supported by an IRC award from the Swedish Foundation for Strategic Research and a European Research Council award ERC-2015-CoG - 681742_NASCENT. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.Author DeclarationsI confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained.YesThe details of the IRB/oversight body that provided approval or exemption for the research described are given below:Approval for the study protocol was obtained from each of the regional research ethics review boards separately (Lund, Sweden: 20130312105459927, Copenhagen, Denmark: H-1-2012-166 and H-1-2012-100, Amsterdam, Netherlands: NL40099.029.12, Newcastle, Dundee and Exeter, UK: 12/NE/0132), and all participants provided written informed consent at enrolment. The research conformed to the ethical principles for medical research involving human participants outlined in the Declaration of Helsinki.All necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived.YesI understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance).YesI have followed all appropriate research reporting guidelines and uploaded the relevant EQUATOR Network research reporting checklist(s) and other pertinent material as supplementary files, if applicable.YesAuthors agree to make data and materials supporting the results or analyses presented in their paper available upon reasonable request
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| 7. |
- Atroshi, Isam, et al.
(författare)
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Low calcaneal bone mineral density and the risk of distal forearm fracture in women and men: a population-based case-control study.
- 2009
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Ingår i: Bone. - : Elsevier BV. - 1873-2763 .- 8756-3282. ; 45:4, s. 789-93
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: We used dual X-ray absorptiometry (DXA) to measure calcaneal bone mineral density (BMD) and estimate the prevalence of osteoporosis in a population with distal forearm fracture and a normative cohort. METHODS: Patients 20 to 80 years of age with distal forearm fracture treated at one emergency hospital during two consecutive years were invited to calcaneal BMD measurement; 270 women (81%) and 64 men (73%) participated. A DXA heel scanner estimated BMD (g/cm(2)) and T-scores. Osteoporosis was defined as T-score< or =-2.5 SD. Of the fracture cohort, 254 women aged 40-80 years and 27 men aged 60-80 years were compared with population-based control cohorts comprising 171 women in the age groups 50, 60, 70 and 80 years and 75 men in the age groups 60, 70, and 80 years. RESULTS: In the fracture population no woman below 40 years or man below 60 years of age had osteoporosis. In women aged 40-80 years the prevalence of osteoporosis in the distal forearm fracture cohort was 34% and in the population-based controls was 25%; the age-adjusted prevalence ratio (PR) was 1.32 (95% CI 1.00-1.76). In the subgroup of women aged 60-80 years the age-adjusted prevalence ratio of osteoporosis was 1.28 (95% CI 0.95-1.71). In men aged 60-80 years the prevalence of osteoporosis in the fracture cohort was 44% and in the population-based controls was 8% (PR 6.31, 95% CI 2.78-14.4). The age-adjusted odds ratio for fracture associated with a 1-SD reduction in calcaneal BMD was in women aged 40-80 years 1.4 (95% CI 1.1-1.8), in the subgroup of women aged 60-80 years 1.2 (95% CI 0.95-1.6), and in men aged 60-80 years 2.6 (95% CI 1.7-4.1). Among those aged 60-80 years the area under the ROC curve was in women 0.56 (95% CI 0.49-0.63) and in men 0.80 (95% CI 0.70-0.80). CONCLUSIONS: The age-adjusted prevalence of osteoporosis based on calcaneal BMD is higher in individuals with distal forearm fracture than in population-based controls. BMD impairment is associated with increased odds ratio for forearm fracture in both women and men but the differences between cases and controls are more pronounced in men than in women, which may have implications in fracture prevention.
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| 8. |
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| 9. |
- Bako, Laurent, et al.
(författare)
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Analysis of a nonsmooth optimization approach to robust estimation
- 2016
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Ingår i: Automatica. - : PERGAMON-ELSEVIER SCIENCE LTD. - 0005-1098 .- 1873-2836. ; 66, s. 132-145
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Tidskriftsartikel (refereegranskat)abstract
- In this paper, we consider the problem of identifying a linear map from measurements which are subject to intermittent and arbitrarily large errors. This is a fundamental problem in many estimation-related applications such as fault detection; state estimation in lossy networks, hybrid system identification, robust estimation, etc. The problem is hard because it exhibits some intrinsic combinatorial features. Therefore, obtaining an effective solution necessitates relaxations that are both solvable at a reasonable cost and effective in the sense that they can return the true parameter vector. The current paper discusses a nonsmooth convex optimization approach and provides a new analysis of its behavior. In particular, it is shown that under appropriate conditions on the data, an exact estimate can be recovered from data corrupted by a large (even infinite) number of gross errors. (C) 2016 Elsevier Ltd. All rights reserved.
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| 10. |
- Baussan, E., et al.
(författare)
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A very intense neutrino super beam experiment for leptonic CP violation discovery based on the European spallation source linac
- 2014
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Ingår i: Nuclear Physics B. - : Elsevier BV. - 0550-3213 .- 1873-1562. ; 885, s. 127-149
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Tidskriftsartikel (refereegranskat)abstract
- Very intense neutrino beams and large neutrino detectors will be needed in order to enable the discovery of CP violation in the leptonic sector. We propose to use the proton linac of the European Spoliation Source currently under construction in Lund, Sweden, to deliver, in parallel with the spoliation neutron production, a very intense, cost effective and high performance neutrino beam. The baseline program for the European Spoliation Source linac is that it will be fully operational at 5 MW average power by 2022, producing 2 GeV 2.86 ms long proton pulses at a rate of 14 Hz. Our proposal is to upgrade the linac to 10 MW average power and 28 Hz, producing 14 pulses/s for neutron production and 14 pulses/s for neutrino production. Furthermore, because of the high current required in the pulsed neutrino horn, the length of the pulses used for neutrino production needs to be compressed to a few mu s with the aid of an accumulator ring. A long baseline experiment using this Super Beam and a megaton underground Water Cherenkov detector located in existing mines 300-600 km from Lund will make it possible to discover leptonic CP violation at 5 sigma significance level in up to 50% of the leptonic Dirac CP-violating phase range. This experiment could also determine the neutrino mass hierarchy at a significance level of more than 3 sigma if this issue will not already have been settled by other experiments by then. The mass hierarchy performance could be increased by combining the neutrino beam results with those obtained from atmospheric neutrinos detected by the same large volume detector. This detector will also be used to measure the proton lifetime, detect cosmological neutrinos and neutrinos from supernova explosions. Results on the sensitivity to leptonic CP violation and the neutrino mass hierarchy are presented.
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