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Sökning: WFRF:(Holmberg David)

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1.
  • Hamadani, Mehdi, et al. (författare)
  • Early Failure of Frontline Rituximab-Containing Chemo-immunotherapy in Diffuse Large B Cell Lymphoma Does Not Predict Futility of Autologous Hematopoietic Cell Transplantation
  • 2014
  • Ingår i: Biology of blood and marrow transplantation. - : Elsevier BV. - 1083-8791 .- 1523-6536. ; 20:11, s. 1729-1736
  • Tidskriftsartikel (refereegranskat)abstract
    • The poor prognosis for patients with diffuse large B cell lymphoma (DLBCL) who relapse within 1 year of initial diagnosis after first-line rituximab-based chemo-immunotherapy has created controversy about the role of autologous transplantation (HCT) in this setting. We compared autologous HCT outcomes for chemosensitive DLBCL patients between 2000 and 2011 in 2 cohorts based on time to relapse from diagnosis. The early rituximab failure (ERF) cohort consisted of patients with primary refractory disease or those with first relapse within 1 year of initial diagnosis. The ERF cohort was compared with those relapsing >1 year after initial diagnosis (late rituximab failure [LRF] cohort). ERF and LRF cohorts included 300 and 216 patients, respectively. Nonrelapse mortality (NRM), progression/relapse, progression-free survival (PFS), and overall survival (OS) of ERF versus LRF cohorts at 3 years were 9% (95% confidence interval [CI], 6% to 13%) versus 9% (95% CI, 5% to 13%), 47% (95% CI, 41% to 52%) versus 39% (95% CI, 33% to 46%), 44% (95% CI, 38% to 50%) versus 52% (95% CI, 45% to 59%), and 50% (95% CI, 44% to 56%) versus 67% (95% CI, 60% to 74%), respectively. On multivariate analysis, ERF was not associated with higher NRM (relative risk [RR], 1.31; P = .34). The ERF cohort had a higher risk of treatment failure (progression/relapse or death) (RR, 2.08; P < .001) and overall mortality (RR, 3.75; P < .001) within the first 9 months after autologous HCT. Beyond this period, PFS and OS were not significantly different between the ERF and LRF cohorts. Autologous HCT provides durable disease control to a sizeable subset of DLBCL despite ERF (3-year PFS, 44%) and remains the standard-of-care in chemosensitive DLBCL regardless of the timing of disease relapse.
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2.
  • Dunér, David, et al. (författare)
  • Födelsen och döden
  • 2009
  • Ingår i: Förlossningskonst. Sydsvenska medicinhistoriska sällskapets årsskrift 2009. - 2000-0715. - 9789163355363 ; 2009, s. 7-10
  • Bokkapitel (övrigt vetenskapligt/konstnärligt)
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3.
  • Andersson, David, 1979, et al. (författare)
  • DN Debatt: LRF och Svenskt flyg svarar inte om klimatmålen
  • 2015
  • Ingår i: Dagens Nyheter. - 1101-2447.
  • Tidskriftsartikel (populärvet., debatt m.m.)abstract
    • Sammantaget ser vi inget i motdebattörernas argument som talar emot att införa styrmedel, till exempel konsumtionsskatter, inom dessa områden där inga stora tekniska lösningar finns i sikte, skriver 14 miljö- och energiforskare i slutrepliken till sin text om flyg- och köttskatt (26/2).
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4.
  • Andersson, David, 1979, et al. (författare)
  • Nu krävs kraftfulla åtgärder mot nötkött och flygresor
  • 2015
  • Ingår i: Dagens Nyheter. - 1101-2447. ; 2015-02-27
  • Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
    • Svenskarnas globala utsläpp från köttkonsumtion och flygresor motsvarar hälften av de totala utsläppen på hemmaplan. I vår rapport till Naturvårdsverket föreslår vi tydliga styrmedel – som nya skatter – för att begränsa konsumtionen på dessa områden, skriver 14 miljö- och energiforskare.
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5.
  • Bratt, Ola, et al. (författare)
  • The Study of Active Monitoring in Sweden (SAMS) : A randomized study comparing two different follow-up schedules for active surveillance of low-risk prostate cancer
  • 2013
  • Ingår i: Scandinavian Journal of Urology. - : Medical Journals Sweden AB. - 2168-1805 .- 2168-1813. ; 47:5, s. 347-355
  • Forskningsöversikt (refereegranskat)abstract
    • Objective. Only a minority of patients with low-risk prostate cancer needs treatment, but the methods for optimal selection of patients for treatment are not established. This article describes the Study of Active Monitoring in Sweden (SAMS), which aims to improve those methods. Material and methods. SAMS is a prospective, multicentre study of active surveillance for low-risk prostate cancer. It consists of a randomized part comparing standard rebiopsy and follow-up with an extensive initial rebiopsy coupled with less intensive follow-up and no further scheduled biopsies (SAMS-FU), as well as an observational part (SAMS-ObsQoL). Quality of life is assessed with questionnaires and compared with patients receiving primary curative treatment. SAMS-FU is planned to randomize 500 patients and SAMS-ObsQoL to include at least 500 patients during 5 years. The primary endpoint is conversion to active treatment. The secondary endpoints include symptoms, distant metastases and mortality. All patients will be followed for 10-15 years. Results. Inclusion started in October 2011. In March 2013, 148 patients were included at 13 Swedish urological centres. Conclusions. It is hoped that the results of SAMS will contribute to fewer patients with indolent, low-risk prostate cancer receiving unnecessary treatment and more patients on active surveillance who need treatment receiving it when the disease is still curable. The less intensive investigational follow-up in the SAMS-FU trial would reduce the healthcare resources allocated to this large group of patients if it replaced the present standard schedule.
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6.
  • Cornell, Robert F, et al. (författare)
  • Maintenance versus Induction Therapy Choice on Outcomes after Autologous Transplantation for Multiple Myeloma
  • 2017
  • Ingår i: Biology of blood and marrow transplantation. - : Elsevier BV. - 1083-8791 .- 1523-6536. ; 23:2, s. 269-277
  • Tidskriftsartikel (refereegranskat)abstract
    • Bortezomib (V), lenalidomide (R), cyclophosphamide (C), and dexamethasone (D) are components of the most commonly used modern doublet (RD, VD) or triplet (VRD, CVD) initial induction regimens before autologous hematopoietic cell transplantation (AHCT) for multiple myeloma (MM) in the United States. In this study we evaluated 693 patients receiving "upfront" AHCT after initial induction therapy with modern doublet or triplet regimens using data reported to the Center for International Blood and Marrow Transplant Research from 2008 to 2013. Analysis was limited to those receiving a single AHCT after 1 line of induction therapy within 12 months from treatment initiation for MM. In multivariate analysis, progression-free survival (PFS) and overall survival were similar irrespective of induction regimen. However, high-risk cytogenetics and nonreceipt of post-transplant maintenance/consolidation therapy were associated with higher risk of relapse. Patients receiving post-transplant therapy had significantly improved 3-year PFS versus no post-transplant therapy (55% versus 39%, P = .0001). This benefit was most evident in patients not achieving at least a complete response post-AHCT (P = .005). In patients receiving upfront AHCT, the choice of induction regimen (doublet or triplet therapies) appears to be of lower impact than use of post-transplant therapy.
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7.
  • Holmberg, Carl Jacob, et al. (författare)
  • The efficacy of immune checkpoint blockade for melanoma in-transit with or without nodal metastases - A multicenter cohort study
  • 2022
  • Ingår i: EUROPEAN JOURNAL OF CANCER. - : Elsevier BV. - 0959-8049 .- 1879-0852. ; 40:16
  • Tidskriftsartikel (refereegranskat)abstract
    • Purpose: Guidelines addressing melanoma in-transit metastasis (ITM) recommend immune checkpoint inhibitors (ICI) as a first-line treatment option, despite the fact that there are no efficacy data available from prospective trials for exclusively ITM disease. The study aims to analyze the outcome of patients with ITM treated with ICI based on data from a large cohort of patients treated at international referral clinics. Methods: A multicenter retrospective cohort study of patients treated between January 2015 and December 2020 from Australia, Europe, and the USA, evaluating treatment with ICI for ITM with or without nodal involvement (AJCC8 N1c, N2c, and N3c) and without distant disease (M0). Treatment was with PD-1 inhibitor (nivolumab or pembrolizumab) and/or CTLA-4 inhibitor (ipilimumab). The response was evaluated according to the RECIST criteria modified for cutaneous lesions. Results: A total of 287 patients from 21 institutions in eight countries were included. Immunotherapy was first-line treatment in 64 (22%) patients. PD-1 or CTLA-4 inhibitor monotherapy was given in 233 (81%) and 23 (8%) patients, respectively, while 31 (11%) received both in combination. The overall response rate was 56%, complete response (CR) rate was 36%, and progressive disease (PD) rate was 32%. Median PFS was ten months (95% CI 7.4-12.6 months) with a one-, two-, and five-year PFS rate of 48%, 33%, and 18%, respectively. Median MSS was not reached, and the one-, two-, and five-year MSS rates were 95%, 83%, and 71%, respectively. Conclusion: Systemic immunotherapy is an effective treatment for melanoma ITM. Future studies should evaluate the role of systemic immunotherapy in the context of multimodality therapy, including locoregional treatments such as surgery, intralesional therapy, and regional therapies.
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9.
  • Levine, Hagai, et al. (författare)
  • Male reproductive health statement (XIIIth international symposium on Spermatology, may 9th-12th 2018, Stockholm, Sweden
  • 2018
  • Ingår i: Basic and Clinical Andrology. - : Springer Science and Business Media LLC. - 2051-4190. ; 28:1
  • Tidskriftsartikel (refereegranskat)abstract
    • On the occasion of the XIIIth International Symposium on Spermatology held from 9 to 13 May 2018 in Stockholm (Sweden), participants (guest speakers and audience) collectively felt the need to make a public statement on the general issue of male reproductive health. Our intention is to raise awareness of what we believe is a neglected area of research despite alarming situations around the world. The disclosure strategy desired by the co-authors is to bring it to the attention of the greatest number partly by considering co-publication in the various periodicals dealing with Reproductive Biology and Andrology. BaCA's editorial office accepted this mission and found it natural that our periodical, the official journal of the French Andrology Society (SALF), should carry this message.
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11.
  • Perez-Valera, Mario, et al. (författare)
  • Angiotensin-Converting Enzyme 2 (SARS-CoV-2 receptor) expression in human skeletal muscle
  • 2021
  • Ingår i: Scandinavian Journal of Medicine and Science in Sports. - : John Wiley & Sons. - 0905-7188 .- 1600-0838. ; 31:12, s. 2249-2258
  • Tidskriftsartikel (refereegranskat)abstract
    • The study aimed to determine the levels of skeletal muscle Angiotensin-Converting Enzyme 2 (ACE2, the SARS-CoV-2 receptor) protein expression in men and women and assess whether ACE2 expression in skeletal muscle is associated with cardiorespiratory fitness and adiposity. The level of ACE2 in vastus lateralis muscle biopsies collected in previous studies from 170 men (age:19-65 yrs, weight:56-137 kg, BMI:23-44) and 69 women (age:18-55 yrs, weight:41-126 kg, BMI:22-39) was analysed in duplicate by western blot. VO2max was determined by ergospirometry and body composition by DXA. ACE2 protein expression was 1.8-fold higher in women than men (p=0.001, n=239). This sex difference disappeared after accounting for the percentage of body fat (fat %), VO2max per kg of legs lean mass (VO2max-LLM) and age (p=0.47). Multiple regression analysis showed that the fat % (β=0.47) is the main predictor of the variability in ACE2 protein expression in skeletal muscle, explaining 5.2 % of the variance. VO2max-LLM had also predictive value (β=0.09). There was a significant fat % by VO2max-LLM interaction, such that for subjects with low fat %, VO2max-LLM was positively associated with ACE2 expression while as fat % increased the slope of the positive association between VO2max-LLM and ACE2 was reduced. In conclusion, women express higher amounts of ACE2 in their skeletal muscles than men. This sexual dimorphism is mainly explained by sex differences in fat % and cardiorespiratory fitness. The percentage of body fat is the main predictor of the variability in ACE2 protein expression in human skeletal muscle.
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12.
  • Rudenstam, Carl-Magnus, 1930, et al. (författare)
  • Randomized trial comparing axillary clearance versus no axillary clearance in older patients with breast cancer: first results of International Breast Cancer Study Group Trial 10-93.
  • 2006
  • Ingår i: Journal of clinical oncology : official journal of the American Society of Clinical Oncology. - 1527-7755. ; 24:3, s. 337-44
  • Tidskriftsartikel (refereegranskat)abstract
    • PURPOSE: Axillary clearance in early breast cancer aims to improve locoregional control and provide staging information but is associated with undesirable morbidity. We therefore investigated whether avoiding axillary surgery in older women would result in improved quality of life (QL) with similar disease-free survival (DFS) and overall survival (OS). PATIENTS AND METHODS: Between 1993 and 2002, women > or = 60 years old with clinically node-negative operable breast cancer in whom adjuvant tamoxifen was considered indicated regardless of pathologic nodal status were randomly assigned to primary surgery plus axillary clearance (Sx + Ax) followed by tamoxifen (Tam) versus Sx without Ax followed by Tam for 5 consecutive years. The primary end point was QL reported by the patient and by physician assessment. RESULTS: A total of 473 patients (234 to Sx + Ax, 239 to Sx) were randomly assigned. The median age was 74 years; 80% had estrogen receptor-positive disease. In both the patients' subjective assessment of their QL and the physicians' perception of the patients' QL, the largest adverse QL effects of Ax were observed from baseline to the first postoperative assessment, but the differences tended to disappear in 6 to 12 months. At a median follow-up of 6.6 years, results for Sx + Ax and Sx yielded similar DFS (6-year DFS, 67% v 66%; hazard ratio [HR] Sx + Ax/Sx, 1.06; 95% CI, 0.79 to 1.42; P = .69) and OS (6-year OS, 75% v 73%; HR Sx + Ax/Sx, 1.05; 95% CI, 0.76 to 1.46; P = .77). CONCLUSION: Avoiding axillary clearance for women > or = 60 years old who have clinically node-negative disease and receive Tam for endocrine-responsive disease yields similar efficacy with better early QL.
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13.
  • Sharma, Manish, et al. (författare)
  • Older Patients with Myeloma Derive Similar Benefit from Autologous Transplantation
  • 2014
  • Ingår i: Biology of blood and marrow transplantation. - : Elsevier BV. - 1083-8791 .- 1523-6536. ; 20:11, s. 1796-1803
  • Tidskriftsartikel (refereegranskat)abstract
    • Autologous hematopoietic cell transplantation (AHCT) for plasma cell myeloma is performed less often in people >70 years old than in people <= 70 years old. We analyzed 11,430 AHCT recipients for plasma cell myeloma prospectively reported to the Center for International Blood and Marrow Transplant Research between 2008 and 2011, representing the majority of US AHCT activity during this period. Survival (OS) was compared in 3 cohorts: ages 18 to 59 years (n = 5818), 60 to 69 years (n = 4666), and >70 years (n = 946). Median OS was not reached for any cohort. In multivariate analysis, increasing age was associated with mortality (P = .0006). Myeloma-specific mortality was similar among cohorts at 12%, indicating an age-related effect on nonmyeloma mortality. Analyses were performed in a representative subgroup comparing relapse rate, progression-free survival (PFS), and nonrelapse mortality (NRM). One-year NRM was 0% for age >70 years and 2% for other ages (P = not significant). The three-year relapse rate was 56% in age 18 to 59 years, 61% in age 60 to 69 years, and 63% age >70 (P = not significant). Three-year PFS was similar at 42% in age 18 to 59 years, 38% in age 60 to 69 years, and 33% in age >70 years (P = not significant). Postrelapse survival was significantly worse for the older cohort (P = .03). Older subjects selected for AHCT derived similar antimyeloma benefit without worse NRM, relapse rate, or PFS.
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14.
  • Thomsen, Frederik B., et al. (författare)
  • Prediction of metastatic prostate cancer by prostate-specific antigen in combination with T stage and Gleason Grade : Nationwide, population-based register study
  • 2020
  • Ingår i: PLOS ONE. - : PUBLIC LIBRARY SCIENCE. - 1932-6203. ; 15:1
  • Tidskriftsartikel (refereegranskat)abstract
    • The objective was to investigate the proportion of men with metastatic prostate cancer in groups defined by T stage, Gleason Grade Group (GGG) and serum levels of prostate-specific antigen (PSA) and if PSA can be used to rule in metastatic prostate cancer when combined with T stage and GGG. We identified 102,076 men in Prostate Cancer data Base Sweden 4.0 who were diagnosed with prostate cancer in 2006-2016. Risk of metastases was assessed for PSA stratified on T stage and five-tiered GGG. For men who had not undergone bone imaging, we used multiple imputation to classify metastatic prostate cancer. Advanced T stage, high GGG and high PSA were related to bone metastases. For example: only 79/38 190 (0.2%) of men with T1-2 and GGG 1 had PSA above 500 ng/mL, and 29/79 (44%) of these men had metastases; whereas 1 154/7 018 (16%) of men with T3-4 and GGG 5 had PSA above 500 ng/ml and 1 088/1 154 (94%) of these men had metastases. However, no PSA cut-off could accurately identify the majority of men with metastatic prostate cancer (i.e. high sensitivity) while also correctly classifying most men without metastasis (i.e. high specificity). In conclusion, these results support the use of imaging to confirm bone metastases in men with advanced prostate cancer as no PSA level in combination with T stage and GGG could accurately rule in metastatic prostate cancer and thereby safely omit bone imaging.
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15.
  • Womersley, Freya C., et al. (författare)
  • Identifying priority sites for whale shark ship collision management globally
  • 2024
  • Ingår i: SCIENCE OF THE TOTAL ENVIRONMENT. - 0048-9697 .- 1879-1026. ; 934
  • Tidskriftsartikel (refereegranskat)abstract
    • The expansion of the world 's merchant fleet poses a great threat to the ocean 's biodiversity. Collisions between ships and marine megafauna can have population-level consequences for vulnerable species. The Endangered whale shark ( Rhincodon typus ) shares a circumglobal distribution with this expanding fleet and tracking of movement pathways has shown that large vessel collisions pose a major threat to the species. However, it is not yet known whether they are also at risk within aggregation sites, where up to 400 individuals can gather to feed on seasonal bursts of planktonic productivity. These "constellation " sites are of significant ecological, socioeconomic and cultural value. Here, through expert elicitation, we gathered information from most known constellation sites for this species across the world ( >50 constellations and >13,000 individual whale sharks). We defined the spatial boundaries of these sites and their overlap with shipping traffic. Sites were then ranked based on relative levels of potential collision danger posed to whale sharks in the area. Our results showed that researchers and resource managers may underestimate the threat posed by large ship collisions due to a lack of direct evidence, such as injuries or witness accounts, which are available for other, sub-lethal threat categories. We found that constellations in the Arabian Sea and adjacent waters, the Gulf of Mexico, the Gulf of California, and Southeast and East Asia, had the greatest level of collision threat. We also identified 39 sites where peaks in shipping activity coincided with peak seasonal occurrences of whale sharks, sometimes across several months. Simulated collision mitigation options estimated potentially minimal impact to industry, as most whale shark core habitat areas were small. Given the threat posed by vessel collisions, a coordinated, multi-national approach to mitigation is needed within priority whale shark habitats to ensure collision protection for the species.
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17.
  • Alsmark, Cecilia M., et al. (författare)
  • The louse-borne human pathogen Bartonella quintana is a genomic derivative of the zoonotic agent Bartonella henselae
  • 2004
  • Ingår i: Proceedings of the National Academy of Sciences of the United States of America. - : Proceedings of the National Academy of Sciences. - 0027-8424 .- 1091-6490. ; 101:26, s. 9716-9721
  • Tidskriftsartikel (refereegranskat)abstract
    • We present the complete genomes of two human pathogens, Bartonella quintana (1,581,384 bp) and Bartonella henselae (1,931,047 bp). The two pathogens maintain several similarities in being transmitted by insect vectors, using mammalian reservoirs, infecting similar cell types (endothelial cells and erythrocytes) and causing vasculoproliferative changes in immunocompromised hosts. A primary difference between the two pathogens is their reservoir ecology. Whereas B. quintana is a specialist, using only the human as a reservoir, B. henselae is more promiscuous and is frequently isolated from both cats and humans. Genome comparison elucidated a high degree of overall similarity with major differences being B. henselae specific genomic islands coding for filamentous hemagglutinin, and evidence of extensive genome reduction in B. quintana, reminiscent of that found in Rickettsia prowazekii. Both genomes are reduced versions of chromosome I from the highly related pathogen Brucella melitensis. Flanked by two rRNA operons is a segment with similarity to genes located on chromosome II of B. melitensis, suggesting that it was acquired by integration of megareplicon DNA in a common ancestor of the two Bartonella species. Comparisons of the vector-host ecology of these organisms suggest that the utilization of host-restricted vectors is associated with accelerated rates of genome degradation and may explain why human pathogens transmitted by specialist vectors are outnumbered by zoonotic agents, which use vectors of broad host ranges.
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18.
  • Andersson, David, 1979, et al. (författare)
  • Greenhouse gas emissions and subjective well-being: An analysis of Swedish households
  • 2014
  • Ingår i: Ecological Economics. - : Elsevier BV. - 0921-8009. ; 102, s. 75-82
  • Tidskriftsartikel (refereegranskat)abstract
    • In the contemporary discussion on society's transformation towards long-termclimate targets, it is often implicitly assumed that behavioral changes, unlike technological changes, would lead to reductions in human wellbeing.However, this assumption has been questioned by researchers, who instead argue that people may live better lives by consuming less and reduce their environmental impact in the process. In this study we explore the relationship between greenhouse gas emissions and subjective well-being, using a sample of 1000 Swedish respondents.Our results show that there is no strong link between an individual's emissions and subjectivewellbeing. We also analyze the relationship between specific emission-intensive activities and subjective well-being and find thatnone of the activities examined correlates with subjective well-being. Finally, we explore a hypothesis put forward in the literature, suggesting that a poor work-life balance, long commuting distances, and materialistic values may decrease individuals' subjective well-being and increase greenhouse gas emissions. Our results indicate that materialistic values do correlate with lower levels of well-being and to some extent also with highergreenhouse gas emissions.
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19.
  • Andersson, David, 1978, et al. (författare)
  • Reflections on evaluating Challenge Lab by applying a proposed scheme for Sustainability Transition Experiments
  • 2016
  • Ingår i: IST 2016 Book of Conference Papers.
  • Konferensbidrag (refereegranskat)abstract
    • The Challenge Lab (CLab) is a neutral arena for triple helix stakeholders and an educational platform for master students to addresses complex challenges and system lockins. By the end of its third year, the CLab will have hosted nearly 100 students, producing 23 master thesis projects and 13 course projects. We present an evaluative case using the scheme proposed by Luederitz et al. (2016) for sustainability transition experiments which includes four main questions and a set of indicators for each question. We end with some general reflections on the evaluation method.
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20.
  • Arnaiz, Aitor, et al. (författare)
  • A New Integrated E-maintenance Concept
  • 2010. - 1
  • Ingår i: E-maintenance. - London : Springer. - 9781849962049 - 9781849962056 ; , s. 61-82
  • Bokkapitel (refereegranskat)abstract
    • This chapter outlines the work done in Dynamite project (http://DYNAMITE.vtt.fi), as well as the resulting concept nicknamed as DynaWeb. DynaWeb represents the link between Dynamite and the e-maintenance technologies described in previous chapters and results in a global framework where all technologies can participate within an advanced maintenance solution.This chapter serves as an introduction to the rest of the chapters dealing with specific technologies that have been converted into ‘capabilities’, such as intelligent sensors, wireless communications, intelligent web services or smart PDAs, as well as to the final demonstrations
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21.
  • Arthur, Rhonda, et al. (författare)
  • Association between baseline serum glucose, triglycerides and total cholesterol, and prostate cancer risk categories
  • 2016
  • Ingår i: Cancer Medicine. - : Wiley. - 2045-7634. ; 5:6, s. 1307-1318
  • Tidskriftsartikel (refereegranskat)abstract
    • Lifestyle-related risk factors such as hyperglycemia and dyslipidemia have been associated with several cancers. However, studies exploring their link with prostate cancer (PCa) clinicopathological characteristics are sparse and inconclusive. Here, we investigated the associations between serum metabolic markers and PCa clinicopathological characteristics. The study comprised 14,294 men from the Swedish Apolipoprotein MOrtality RISk (AMORIS) cohort who were diagnosed with PCa between 1996 and 2011. Univariate and multivariable logistic regression were used to investigate the relation between glucose, triglycerides and total cholesterol and PCa risk categories, PSA, Gleason score, and T-stage. Mean age at time of PCa diagnosis was 69 years. Men with glucose levels >6.9 mmol/L tend to have PSA<4 mu g/L, while those with glucose levels of 5.6-6.9 mmol/L had a greater odds of PSA>20 mu g/L compared to PSA 4.0-9.9 mu g/L. Hypertriglyceridemia was also positively associated with PSA>20 mu g/L. Hyperglycemic men had a greater odds of intermediate-and high-grade PCa and advanced stage or metastatic PCa. Similarly, hypertriglyceridemia was positively associated with high-grade PCa. There was also a trend toward an increased odds of intermediate risk localized PCa and advanced stage PCa among men with hypertriglyceridemia. Total cholesterol did not have any statistically significant association with any of the outcomes studied. Our findings suggest that high serum levels of glucose and triglycerides may influence PCa aggressiveness and severity. Further investigation on the role of markers of glucose and lipid metabolism in influencing PCa aggressiveness and severity is needed as this may help define important targets for intervention.
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22.
  • Arthur, Rhonda, et al. (författare)
  • Serum glucose, triglycerides, and cholesterol in relation to prostate cancer death in the Swedish AMORIS study
  • 2019
  • Ingår i: Cancer Causes and Control. - : Springer. - 0957-5243 .- 1573-7225. ; 30:2, s. 195-206
  • Tidskriftsartikel (refereegranskat)abstract
    • Purpose: Lifestyle-related conditions such as obesity are associated with prostate cancer progression, but the associations with hyperglycemia and dyslipidemia are unclear. This study, therefore, aims to examine the association of glucose, triglycerides, and total cholesterol with prostate cancer death. Methods: From the Swedish AMORIS cohort, we selected 14,150 men diagnosed with prostate cancer between 1996 and 2011 who had prediagnostic measurements of serum glucose, triglycerides, and total cholesterol. Multivariable Cox proportional hazards regressionmodels were used to determine the hazard ratios for death in relation to the aforementioned metabolic markers. Results: Using clinical cut-off points, a non-significant positive association was observed between glucose and prostate cancer death. When compared to those with glucose in the lowest quartile, those in the highest quartile had greater risk of prostate cancer death (HR 1.19; 95% CI 1.02-1.39). However, neither total cholesterol nor triglycerides were associated with prostate cancer death. Glucose and triglycerides were positively associated with overall, cardiovascular, and other deaths. Hypercholesterolemia was only associated with risk of CVD death. Conclusion: Our results suggest that glucose levels may influence prostate cancer survival, but further studies using repeated measurements are needed to further elucidate how glucose levels may influence prostate cancer progression.
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23.
  • Beckmann, Kerri, et al. (författare)
  • Androgen Deprivation Therapies and Changes in Comorbidity : A Comparison of Gonadotropin-releasing Hormone Agonists and Antiandrogen Monotherapy as Primary Therapy in Men with High-risk Prostate Cancer
  • 2019
  • Ingår i: European Urology. - : ELSEVIER SCIENCE BV. - 0302-2838 .- 1873-7560. ; 75:4, s. 676-683
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Some studies suggest that gonadotropin-releasing hormone (GnRH) agonists are associated with higher risk of adverse events than antiandrogens (AAs) monotherapy. However, it has been unclear whether this is due to indication bias.Objective: To investigate rates of change in comorbidity for men on GnRH agonists versus AA monotherapy in a population-based register study.Design, setting, and participants: Men with advanced nonmetastatic prostate cancer (PCa) who received primary AA (n = 2078) or GnRH agonists (n = 4878) and age- and area-matched PCa-free men were selected from Prostate Cancer Database Sweden 3.0. Increases in comorbidity were measured using the Charlson Comorbidity Index (CCI), from 5 yr before through to 5 yr after starting androgen deprivation therapy (ADT).Outcome measures and statistical methods: Multivariable linear regression was used to determine differences in excess rate of CCI change before and after ADT initiation. Risk of any incremental change in CCI following ADT was assessed using multivariable Cox regression analyses.Results and limitations: Men on GnRH agonists experienced a greater difference in excess rate of CCI change after starting ADT than men on AA monotherapy (5.6% per yr, p < 0.001). Risk of any new CCI change after ADT was greater for GnRH agonists than for AA (hazard ratio, 1.32; 95% confidence interval, 1.20-144).Conclusions: Impact on comorbidity was lower for men on AA monotherapy than for men on GnRH agonists. Our results should be confirmed through randomised trials of effectiveness and adverse effects, comparing AA monotherapy and GnRH agonists in men with advanced nonmetastatic PCa who are unsuitable for curative treatment.Patient summary: Hormone therapies for advanced prostate cancer can increase the risk of other diseases (eg, heart disease, diabetes). This study compared two common forms of hormone therapy and found that the risk of another serious disease was higher for those on gonadotropin-releasing hormone agonists than for those on antiandrogen monotherapy.
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24.
  • Beijert, Irene J., et al. (författare)
  • The importance of being grade 3 : a plea for a three-tier hybrid classification system for grade in primary non–muscle-invasive bladder cancer
  • 2024
  • Ingår i: European Urology. - : Elsevier. - 0302-2838 .- 1873-7560.
  • Tidskriftsartikel (refereegranskat)abstract
    • Grade is an important determinant of progression in non–muscle-invasive bladder cancer. Although the World Health Organization (WHO) 2004/2016 grading system is recommended, other systems such as WHO1973 and WHO1999 are still widely used. Recently, a hybrid (three-tier) system was proposed, separating WHO2004/2016 high grade (HG) into HG/grade 2 (G2) and HG/G3 while maintaining low grade. We assessed the prognostic performance of HG/G3 and HG/G2. Three independent cohorts with 9712 primary (first diagnosis) Ta-T1 bladder tumors were analyzed. Time to progression was analyzed with cumulative incidence functions and Cox regression models. Harrell's C-index was used to assess discrimination. Time to progression was significantly shorter for HG/G3 than for HG/G2 in multivariable analyses (cohort 1: hazard ratio [HR] = 1.92; cohort 2: HR = 2.51, and cohort 3: HR = 1.69). Corresponding progression risks at 5 yr were 18%, 20%, and 18% for HG/G3 versus 7.3%, 7.5%, and 9.3% for HG/G2, respectively. Cox models using hybrid grade performed better than models with WHO2004/2016 (all cohorts; p < 0.001). For the three cohorts, C-indices for WHO2004/2016 were 0.69, 0.62, and 0.75, while, for hybrid grade, C-indices were 0.74, 0.68, and 0.78, respectively. Subdividing the HG category into HG/G2 and HG/G3 stratifies time to progression and supports the recommendation to adopt the hybrid grading system for Ta/T1 bladder cancers.
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25.
  • Berclaz, Corinne, et al. (författare)
  • Label-free fast 3D coherent imaging reveals pancreatic islet micro-vascularization and dynamic blood flow
  • 2016
  • Ingår i: Biomedical Optics Express. - 2156-7085. ; 7:11, s. 4569-4580
  • Tidskriftsartikel (refereegranskat)abstract
    • In diabetes, pancreatic ß-cells play a key role. These cells are clustered within structures called islets of Langerhans inside the pancreas and produce insulin, which is directly secreted into the blood stream. The dense vascularization of islets of Langerhans is critical for maintaining a proper regulation of blood glucose homeostasis and is known to be affected from the early stage of diabetes. The deep localization of these islets inside the pancreas in the abdominal cavity renders their in vivo visualization a challenging task. A fast label-free imaging method with high spatial resolution is required to study the vascular network of islets of Langerhans. Based on these requirements, we developed a label-free and three-dimensional imaging method for observing islets of Langerhans using extended-focus Fourier domain Optical Coherence Microscopy (xfOCM). In addition to structural imaging, this system provides threedimensional vascular network imaging and dynamic blood flow information within islets of Langerhans. We propose our method to deepen the understanding of the interconnection between diabetes and the evolution of the islet vascular network.
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26.
  • Berglund, Anders, et al. (författare)
  • Differences according to socioeconomic status in the management and mortality in men with high risk prostate cancer
  • 2012
  • Ingår i: European Journal of Cancer. - : Elsevier BV. - 0959-8049 .- 1879-0852. ; 48:1, s. 75-84
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Outcomes for many cancer forms are associated with socioeconomic status (SES).We investigated if SES was associated with management and mortality in men with high risk prostate cancer.Material and methods: A nation-wide population-based cohort in Prostate Cancer Data Base Sweden (PCBaSe), a merged database including data on incident prostate cancer identified in the National Prostate Cancer Register (NPCR) between 1997 and 2006. High risk PCa was defined as T3 tumour, and/or Gleason score 8–10 and/or PSA 20–50 ng/mL. Use of bone scan, curative treatment, and mortality in relation to SES was assessed by logistic, Cox, and competing risk regression with hazard ratios (HR), sub-distributed HR and 95% confidence intervals (CI) adjusted for co-morbidity, age, calendar period and clinical subgroups.Results: Amongst 17,522 high risk prostate cancer patients, a bone scan was more often performed in higher white-collar than in blue-collar workers (OR 1.30; 95% CI 1.21–1.40). Amongst men without metastases, the likelihood of intention to treat was higher in higher white-collar workers (OR 1.43; 95% CI 1.28–1.57). In men who received curative treatment, the likelihood was higher to undergo radical prostatectomy for higher white-collar patients (OR 1.29; 95% CI 1.10–1.47). In men without metastases, not only overall mortality was lower amongst higher white-collar workers (HR, 0.76; 95% CI 0.60–0.97), but also prostate cancer-specific mortality (sHR 0.70; 95% CI, 0.49–0.99).Conclusions: We conclude that socioeconomic disparities in the management and mortality in men with high risk prostate cancer exist also within the setting of a National Health Care System aiming to provide care on equal terms to all residents.
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27.
  • Berglund, Lars, et al. (författare)
  • Which patients with persistent mechanical low back pain will respond to high load motor control training?
  • 2011
  • Ingår i: Physiotherapy. - 0031-9406 .- 1873-1465. ; 97:Suppl. 1, s. eS124-eS125
  • Tidskriftsartikel (refereegranskat)abstract
    • Purpose: The aim of this study was to explore variables influencing success or failure of eight weeks of high load motor control training with the conventional deadlift exercise.Relevance: Researching viable exercises for rehabilitation of specific sub-groups of persistent low back pain is relevant for physical therapists in order to develop tailored treatment regimes for patients with persistent low back pain. This study contributes to this research by exploring which variables characterize the ideal patient for the conventional deadlift exercise.Participants: Thirty-five patients with persistent mechanical low back pain were recruited consecutively from two occupational health care services in Umeå, Sweden . Inclusion and exclusion criteria were designed to include patients with persistent mechanical low back pain.Methods: The study design was a prospective cohort study. The intervention consisted of eight weeks of training with the conventional deadlift exercise. To discriminate between patients with a successful or failed outcome of treatment, change in the patient-specific functional scale was used and a cut-off at 50 % improvement was set. Possible predictive variables collected at baseline included physical activity level, pain intensity (Visual Analogue Scale), activity limitation (the Roland and Morris Disability Questionnaire and the Patient-Specific Functional Scale), kinesiophobia (Tampa Scale of Kinesiophobia), specific anamnestic questions regarding patients' history and symptoms of low back pain, test of active movement control of the low back, trunk muscle endurance(Prone bridge test, Side-bridge test, Biering-Sörensen test) and lift strength (static two-hand lift test), two-point discrimination of the low back and ultrasound imaging of the mm. multifidi.Analysis: Student´s T-test for normally distributed continuous data, Mann Whitney for non-normally distributed continuous data and chi-square tests or Fisher´s Exact tests for categorical variables were used for analyses of differences between the success and the failure group.Results: No significant differences between groups were found in background, anamnestic or physical performance variables. After eight weeks of training, 15 patients (43 %) were categorized as treatment success and 20 patients (57 %) were categorized as treatment failure according to the cut-off set for the PSFS. The patients reported difficulty in performing a wide variation of activities, ranging from not being able to sit for longer than 15 minutes, to stand upright and watch their children play football games, and to not being able to run long distances, play football or perform different lifting tasks.Conclusions: We conclude that the conventional deadlift exercise may be considered a possible exercise to improve patients' activity limitations, if administered by a therapist experienced in resistance training and analyzing movement patterns. However, further research is needed to explore which variables can define patients in the successful and in the failure group, respectively.Implications: The results of this study imply that the conventional deadlift exercise can be used in treatment of patients with mechanical low back pain in order to increase activity limitation. However, it is still unclear on what grounds treatment with the conventional deadlift exercise is indicated to achieve these results.
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28.
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29.
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30.
  • Brynolfsson, Patrik, et al. (författare)
  • Technical note : adapting a GE SIGNA PET/MR scanner for radiotherapy
  • 2018
  • Ingår i: Medical physics (Lancaster). - : Wiley-Blackwell Publishing Inc.. - 0094-2405. ; 45:8, s. 3546-3550
  • Tidskriftsartikel (refereegranskat)abstract
    • Purpose: Simultaneous collection of PET and MR data for radiotherapy purposes are useful for, for example, target definition and dose escalations. However, a prerequisite for using PET/MR in the radiotherapy workflow is the ability to image the patient in treatment position. The aim of this work was to adapt a GE SIGNA PET/MR scanner to image patients for radiotherapy treatment planning and evaluate the impact on signal-to-noise (SNR) of the MR images, and the accuracy of the PET attenuation correction. Method: A flat tabletop and a coil holder were developed to image patients in the treatment position, avoid patient contour deformation, and facilitate attenuation correction of flex coils. Attenuation corrections for the developed hardware and an anterior array flex coil were also measured and implemented to the PET/MR system to minimize PET quantitation errors. The reduction of SNR in the MR images due to the added distance between the coils and the patient was evaluated using a large homogenous saline-doped water phantom, and the activity quantitation errors in PET imaging were evaluated with and without the developed attenuation corrections. Result: We showed that the activity quantitation errors in PET imaging were within ±5% when correcting for attenuation of the flat tabletop, coil holder, and flex coil. The SNR of the MRI images were reduced to 74% using the tabletop, and 66% using the tabletop and coil holders. Conclusion: We present a tabletop and coil holder for an anterior array coil to be used with a GE SIGNA PET/MR scanner, for scanning patients in the radiotherapy work flow. Implementing attenuation correction of the added hardware from the radiotherapy setup leads to acceptable PET image quantitation. The drop in SNR in MR images may require adjustment of the imaging protocols.
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31.
  • Calbet, Jose A. L., et al. (författare)
  • Exercise Preserves Lean Mass and Performance during Severe Energy Deficit : The Role of Exercise Volume and Dietary Protein Content
  • 2017
  • Ingår i: Frontiers in Physiology. - : Frontiers Media SA. - 1664-042X. ; 8
  • Tidskriftsartikel (refereegranskat)abstract
    • The loss of fat-free mass (FFM) caused by very-low-calorie diets (VLCD) can be attenuated by exercise. The aim of this study was to determine the role played by exercise and dietary protein content in preserving the lean mass and performance of exercised and non-exercised muscles, during a short period of extreme energy deficit (similar to 23 MJ deficit/day). Fifteen overweight men underwent three consecutive experimental phases: baseline assessment (PRE), followed by 4 days of caloric restriction and exercise (CRE) and then 3 days on a control diet combined with reduced exercise (CD). During CRE, the participants ingested a VLCD and performed 45 min of one-arm cranking followed by 8 h walking each day. The VLCD consisted of 0.8 g/kg body weight/day of either whey protein (PRO, n = 8) or sucrose (SU, n = 7). FFM was reduced after CRE (P < 0.001), with the legs and the exercised arm losing proportionally less FFM than the control arm [57% (P < 0.05) and 29% (P = 0.05), respectively]. Performance during leg pedaling, as reflected by the peak oxygen uptake and power output (Wpeak), was reduced after CRE by 15 and 12%, respectively (P < 0.05), and recovered only partially after CD. The deterioration of cycling performance was more pronounced in the whey protein than sucrose group (P < 0.05). Wpeak during arm cranking was unchanged in the control arm, but improved in the contralateral arm by arm cranking. There was a linear relationship between the reduction in whole-body FFM between PRE and CRE and the changes in the cortisol/free testosterone ratio (C/FT), serum isoleucine, leucine, tryptophan, valine, BCAA, and EAA (r = -0.54 to -0.71, respectively, P < 0.05). C/FT tended to be higher in the PRO than the SU group following CRE (P = 0.06). In conclusion, concomitant low-intensity exercise such as walking or arm cranking even during an extreme energy deficit results in remarkable preservation of lean mass. The intake of proteins alone may be associated with greater cortisol/free testosterone ratio and is not better than the ingestion of only carbohydrates for preserving FFM and muscle performance in interventions of short duration.
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32.
  • Cardinale, Daniele A., 1982-, et al. (författare)
  • Superior Intrinsic Mitochondrial Respiration in Women Than in Men.
  • 2018
  • Ingår i: Frontiers in Physiology. - : Frontiers Media SA. - 1664-042X. ; 9
  • Tidskriftsartikel (refereegranskat)abstract
    • Sexual dimorphism is apparent in humans, however, to date no studies have investigated mitochondrial function focusing on intrinsic mitochondrial respiration (i.e., mitochondrial respiration for a given amount of mitochondrial protein) and mitochondrial oxygen affinity (p50mito) in relation to biological sex in human. A skeletal muscle biopsy was donated by nine active women, and ten men matched for maximal oxygen consumption (VO2max) and by nine endurance trained men. Intrinsic mitochondrial respiration, assessed in isolated mitochondria, was higher in women compared to men when activating complex I (CIP) and complex I+II (CI+IIP) (p < 0.05), and was similar to trained men (CIP, p = 0.053; CI+IIP, p = 0.066). Proton leak and p50mito were higher in women compared to men independent of VO2max. In conclusion, significant novel differences in mitochondrial oxidative function, intrinsic mitochondrial respiration and p50mito exist between women and men. These findings may represent an adaptation in the oxygen cascade in women to optimize muscle oxygen uptake to compensate for a lower oxygen delivery during exercise.
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33.
  • Carter, H Ballentine, et al. (författare)
  • Early detection of prostate cancer : AUA Guideline
  • 2013
  • Ingår i: Journal of Urology. - : Ovid Technologies (Wolters Kluwer Health). - 0022-5347 .- 1527-3792. ; 190:2, s. 419-426
  • Tidskriftsartikel (refereegranskat)abstract
    • PURPOSE:The guideline purpose is to provide the urologist with a framework for the early detection of prostate cancer in asymptomatic average risk men.MATERIALS AND METHODS:A systematic review was conducted and summarized evidence derived from over 300 studies that addressed the predefined outcomes of interest (prostate cancer incidence/mortality, quality of life, diagnostic accuracy and harms of testing). In addition to the quality of evidence, the panel considered values and preferences expressed in a clinical setting (patient-physician dyad) rather than having a public health perspective. Guideline statements were organized by age group in years (age <40; 40 to 54; 55 to 69; ≥ 70).RESULTS:Except prostate specific antigen-based prostate cancer screening, there was minimal evidence to assess the outcomes of interest for other tests. The quality of evidence for the benefits of screening was moderate, and evidence for harm was high for men age 55 to 69 years. For men outside this age range, evidence was lacking for benefit, but the harms of screening, including over diagnosis and overtreatment, remained. Modeled data suggested that a screening interval of two years or more may be preferred to reduce the harms of screening.CONCLUSIONS:The Panel recommended shared decision-making for men age 55 to 69 years considering PSA-based screening, a target age group for whom benefits may outweigh harms. Outside this age range, PSA-based screening as a routine could not be recommended based on the available evidence.
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34.
  • Castaman, Giancarlo, et al. (författare)
  • Response to desmopressin is influenced by the genotype and phenotype in type 1 von Willebrand disease (VWD): results from the European Study MCMDM-1VWD
  • 2008
  • Ingår i: Blood. - : American Society of Hematology. - 1528-0020 .- 0006-4971. ; 111:7, s. 3531-3539
  • Tidskriftsartikel (refereegranskat)abstract
    • We have prospectively evaluated the biologic response to desmopressin in 77 patients with type 1 von Willebrand disease (VWD) enrolled within the Molecular and Clinical Markers for the Diagnosis and Management of type 1 VWD project. Complete response to desmopressin was defined as an increase of both ristocetin cofactor activity (VWF:RCo) and factor VIII coagulant activity (FVIII:C) to 50 IU/dL or higher and partial response as VWF: RCo or FVIII:C lower than 50 IU/dL after infusion, but at least 3-fold the basal level. Complete response was observed in 83% of patients; partial in 13%; and no response in 4%. Patients with some abnormality of VWF multimeric pattern had significantly lower basal FVIII:C and VWF, lower VWF:RCo/Ag ratio, and less complete responses to desmopressin than patients with a normal multimeric pattern (P =.002). Patients with mutations at codons 1130 and 1205 in the D'-D3 domain had the greatest relative increase, but shortest FVIII and VWF half-lives after infusion. Most partial and nonresponsive patients had mutations in the A1-A3 domains. Response to desmopressin in these VWD patients seemed to be associated with the location of the causative mutation. The presence of subtle multimeric abnormalities did not hamper potential clinically useful responses, as in typical type 1 VWD.
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35.
  • Cazzaniga, Walter, et al. (författare)
  • Mortality after radical prostatectomy in a matched contemporary cohort in Sweden compared to the Scandinavian Prostate Cancer Group 4 (SPCG-4) study
  • 2019
  • Ingår i: BJU International. - : Wiley. - 1464-4096 .- 1464-410X. ; 123:3, s. 421-428
  • Tidskriftsartikel (refereegranskat)abstract
    • OBJECTIVE: To investigate if results in terms of absolute risk in mature randomised trials are relevant for contemporary decision-making. To do so, we compared the outcome for men in the radical prostatectomy (RP) arm of the Scandinavian Prostate Cancer Group Study number 4 (SPCG-4) randomised trial with matched men treated in a contemporary era before and after compensation for the grade migration and grade inflation that have occurred since the 1980s.PATIENTS AND METHODS: A propensity score-matched analysis of prostate cancer mortality and all-cause mortality in the SPCG-4 and matched men in the National Prostate Cancer Register (NPCR) of Sweden treated in 1998-2006 was conducted. Cumulative incidence of prostate cancer mortality and all-cause mortality was calculated. Cox proportional hazards regression analyses were used to estimate hazard ratios (HR) and 95% confidence intervals (CIs) for a matching on original Gleason Grade Groups (GGG) and second, matching with GGG increased one unit for men in the NPCR.RESULTS: Matched men in the NPCR treated in 2005-2006 had half the risk of prostate cancer mortality compared to men in the SPCG-4 (HR 0.46, 95% CI 0.19-1.14). In analysis of men matched on an upgraded GGG in the NPCR, this difference was mitigated (HR 0.73, 95% CI 0.36-1.47).CONCLUSIONS: Outcomes after RP for men in the SPCG-4 cannot be directly applied to men in the current era, mainly due to grade inflation and grade migration. However, by compensating for changes in grading, similar outcomes after RP were seen in the SPCG-4 and NPCR. In order to compare historical trials with current treatments, data on temporal changes in detection, diagnostics, and treatment have to be accounted for.
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36.
  • Cho, Eunyoung, et al. (författare)
  • Alcohol intake and colorectal cancer : a pooled analysis of 8 cohort studies
  • 2004
  • Ingår i: Annals of Internal Medicine. - : American College of Physicians. - 0003-4819 .- 1539-3704. ; 140:8, s. 603-613
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: Epidemiologic studies have generally reported positive associations between alcohol consumption and risk for colorectal cancer. However, findings related to specific alcoholic beverages or different anatomic sites in the large bowel have been inconsistent. OBJECTIVE: To examine the relationship of total alcohol intake and intake from specific beverages to the incidence of colorectal cancer and to evaluate whether other potential risk factors modify the association. DESIGN: Pooled analysis of primary data from 8 cohort studies in 5 countries. SETTING: North America and Europe. PARTICIPANTS: 489,979 women and men with no history of cancer other than nonmelanoma skin cancer at baseline. MEASUREMENTS: Alcohol intake was assessed in each study at baseline by using a validated food-frequency questionnaire. RESULTS: During a maximum of 6 to 16 years of follow-up across the studies, 4687 cases of colorectal cancer were documented. In categorical analyses, increased risk for colorectal cancer was limited to persons with an alcohol intake of 30 g/d or greater (approximately > or =2 drinks/d), a consumption level reported by 4% of women and 13% of men. Compared with nondrinkers, the pooled multivariate relative risks were 1.16 (95% CI, 0.99 to 1.36) for persons who consumed 30 to less than 45 g/d and 1.41 (CI, 1.16 to 1.72) for those who consumed 45 g/d or greater. No significant heterogeneity by study or sex was observed. The association was evident for cancer of the proximal colon, distal colon, and rectum. No clear difference in relative risks was found among specific alcoholic beverages. LIMITATIONS: The study included only one measure of alcohol consumption at baseline and could not investigate lifetime alcohol consumption, alcohol consumption at younger ages, or changes in alcohol consumption during follow-up. It also could not examine drinking patterns or duration of alcohol use. CONCLUSIONS: A single determination of alcohol intake correlated with a modest relative elevation in colorectal cancer rate, mainly at the highest levels of alcohol intake.
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37.
  • Chowdhury, Simon, et al. (författare)
  • Causes of death in men with prostate cancer : an analysis of 50,000 men from the Thames Cancer Registry.
  • 2013
  • Ingår i: BJU International. - : Wiley. - 1464-4096 .- 1464-410X. ; 112:2, s. 182-189
  • Tidskriftsartikel (refereegranskat)abstract
    • OBJECTIVE: To investigate causes of death in a UK cohort of patients with prostate cancer.PATIENTS AND METHODS: We examined causes of death in a UK cohort of 50,066 men with prostate cancer diagnosed between 1997 and 2006 reported to the Thames Cancer Registry (TCR) and followed-up to the end of 2007. The underlying cause of death was taken from the death certificate. Uptake of PSA screening was low in the UK during the period studied. We examined the relationship between cause of death and patient characteristics at diagnosis including age, cancer stage, and treatment (≤6 months of diagnosis).RESULTS: In all, 20,181 deaths occurred during the period; 49.8% recorded as being due to prostate cancer, 17·8% to cardiovascular disease, 11·6% to other cancers, and 20·7% to other causes. Irrespective of age, cancer stage, or treatment ≤6 months of diagnosis, prostate cancer was an important cause of death ranging from 31·6% to 74·3% of all deaths in different subgroups.CONCLUSION: For men with prostate cancer diagnosed in a setting where uptake of PSA screening is low, our findings challenge the belief that prostate cancer is not an important cause of death.
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38.
  • Colleoni, Marco, et al. (författare)
  • Site of primary tumor has a prognostic role in operable breast cancer: the international breast cancer study group experience.
  • 2005
  • Ingår i: Journal of clinical oncology : official journal of the American Society of Clinical Oncology. - 0732-183X. ; 23:7, s. 1390-400
  • Tidskriftsartikel (refereegranskat)abstract
    • PURPOSE: Cancer presenting at the medial site of the breast may have a worse prognosis compared with tumors located in external quadrants. For medial tumors, axillary lymph node staging may not accurately reflect the metastatic potential of the disease. PATIENTS AND METHODS: Eight-thousand four-hundred twenty-two patients randomly assigned to International Breast Cancer Study Group clinical trials between 1978 and 1999 were classified as medial site (1,622; 19%) or lateral, central, and other sites (6,800; 81%). Median follow-up was 11 years. RESULTS: A statistically significant difference was observed for patients with medial tumors versus those with nonmedial tumors in disease-free survival (DFS; 10-year DFS, 46% v 48%; HR, 1.10; 95% CI, 1.02 to 1.18; P = .01) and overall survival (10-year OS 59% v 61%; HR, 1.09; 1.01 to 1.19; P = .04). This difference increased after adjustment for other prognostic factors (HR, 1.22; 95% CI, 1.13 to 1.32 for DFS; and HR, 1.24; 95% CI, 1.14 to 1.35 for OS; both P = .0001). The risk of relapse for patients with medial presentation was largest for the node-negative cohort and for patients with tumors larger than 2 cm. In the subgroup of 2,931 patients with negative axillary lymph nodes, 10-year DFS was 61% v 67%, and OS was 73% v 80% for medial versus nonmedial sites, respectively (HR 1.33; 95% CI, 1.15 to 1.54; P = .0001 for DFS; and HR 1.40; 95% CI, 1.17 to 1.67; P = .0003 for OS). CONCLUSION: Tumor site has a significant prognostic utility, especially for axillary lymph node-negative disease, that should be considered in therapeutic algorithms. New staging procedures such as biopsy of the sentinel internal mammary nodes or novel imaging methods should be further studied in patients with medial tumors.
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39.
  • de Rinaldis, Emanuele, et al. (författare)
  • Integrated genomic analysis of triple-negative breast cancers reveals novel microRNAs associated with clinical and molecular phenotypes and sheds light on the pathways they control
  • 2013
  • Ingår i: BMC Genomics. - : Springer Science and Business Media LLC. - 1471-2164. ; 14, s. 643-
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: This study focuses on the analysis of miRNAs expression data in a cohort of 181 well characterised breast cancer samples composed primarily of triple-negative (ER/PR/HER2-negative) tumours with associated genome-wide DNA and mRNA data, extensive patient follow-up and pathological information.RESULTS: We identified 7 miRNAs associated with prognosis in the triple-negative tumours and an additional 7 when the analysis was extended to the set of all ER-negative cases. miRNAs linked to an unfavourable prognosis were associated with a broad spectrum of motility mechanisms involved in the invasion of stromal tissues, such as cell-adhesion, growth factor-mediated signalling pathways, interaction with the extracellular matrix and cytoskeleton remodelling. When we compared different intrinsic molecular subtypes we found 46 miRNAs that were specifically expressed in one or more intrinsic subtypes. Integrated genomic analyses indicated these miRNAs to be influenced by DNA genomic aberrations and to have an overall influence on the expression levels of their predicted targets. Among others, our analyses highlighted the role of miR-17-92 and miR-106b-25, two polycistronic miRNA clusters with known oncogenic functions. We showed that their basal-like subtype specific up-regulation is influenced by increased DNA copy number and contributes to the transcriptional phenotype as well as the activation of oncogenic pathways in basal-like tumours.CONCLUSIONS: This study analyses previously unreported miRNA, mRNA and DNA data and integrates these with pathological and clinical information, from a well-annotated cohort of breast cancers enriched for triple-negative subtypes. It provides a conceptual framework, as well as integrative methods and system-level results and contributes to elucidate the role of miRNAs as biomarkers and modulators of oncogenic processes in these types of tumours.
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40.
  • Dhakal, Binod, et al. (författare)
  • Hematopoietic cell transplantation utilization and outcomes for primary plasma cell leukemia in the current era
  • 2020
  • Ingår i: Leukemia. - : SPRINGERNATURE. - 0887-6924 .- 1476-5551. ; 34:12, s. 3338-3347
  • Tidskriftsartikel (refereegranskat)abstract
    • The outcomes of patients with primary plasma cell leukemia (pPCL) after undergoing hematopoietic cell transplantation (HCT) in the novel agent era are unknown. We report outcomes of 348 patients with pPCL receiving autologous (auto-) HCT (n = 277) and allogeneic (allo-) HCT (n = 71) between 2008 and 2015. Median age was 60 years and 56 years for auto- and allo-HCT respectively. For auto-HCT, the 4-year outcomes were: non-relapse mortality (NRM) 7% (4-11%), relapse (REL) 76% (69-82%), progression-free survival (PFS) 17% (13-23%), and overall survival (OS) 28% (22-35%). Karnofsky performance status (KPS) > 90 and >= very good partial response (VGPR) predicted superior OS in multi-variate analysis for auto-HCT. For allo-HCT, the 4-year outcomes were: NRM 12% (5-21%), REL 69% (56-81%), PFS 19% (10-31%), and OS 31% (19-44%). Compared with prior CIBMTR pPCL patients (1995-2006), inferior survival was noted in the current cohort (3-year OS, 39% vs. 38% in allo-HCT, and 62% vs. 35% in auto-HCT) respectively. However, we noted an increased HCT utilization, from 12% (7-21%) in 1995 to 46% (34-64%) in 2009 using SEER data (available till 2009). Despite modern induction translating to higher proportion receiving HCT, the outcomes remain poor in pPCL patients, mainly derived by high relapse rates post-HCT.
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41.
  • Dinka, David, et al. (författare)
  • Adding value with 3D visualization and haptic forces to radiosurgery - A small theory-based, quasi-experimental study
  • 2006
  • Ingår i: Journal of medical systems. - : Springer Science and Business Media LLC. - 0148-5598 .- 1573-689X. ; 30:4, s. 293-301
  • Tidskriftsartikel (refereegranskat)abstract
    • This study investigates the use of 3D representation and haptic technology in radiosurgery. The users, experienced users of the Leksell GammaKnife, prefer the 3D representation for constructing a first draft of their plan for neurosurgical intervention. When it comes to the final adjustments, however, they still choose the traditional 2D representation and interaction devices. The perceived control over the radiosurgical process is not considered adequate using the 3D interaction methods. Practitioners do not consider the haptic forces implemented in this test system useful. Possible explanations for these findings are discussed in the paper. © Springer Science+Business Media, Inc. 2006.
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42.
  • Duarte, Nádia, 1977- (författare)
  • Molecular and cellular mechanisms contributing to the pathogenesis of autoimmune diabetes
  • 2005
  • Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
    • Type 1 diabetes is an autoimmune disorder determined both by genetic and environmental factors. The Non-obese diabetic (NOD) mouse is one of the best animal models of this disease. It spontaneously develops diabetes through a process resembling the human pathogenesis. The strong association of NOD Type 1 diabetes to the MHC region and the existence of other diabetes susceptibility loci are also in parallel with the human disease. The identity of the genetic factors and biological function mediated by these loci remain, however, largely unknown. Like in other autoimmune diseases, defects in tolerance mechanisms are thought to be at the origin of type 1 diabetes. Accordingly, defects in both central and peripheral tolerance mechanisms have been reported in the NOD mouse model. Using a subphenotype approach that aimed to dissect the disease into more simple phenotypes, we have addressed this issue. In paper I, we analyzed resistance to dexamethasone-induced apoptosis in NOD immature thymocytes previously mapped to the Idd6 locus. Using a set of congenic mice carrying B6-derived Idd6 regions on a NOD background and vice-versa we could restrict the Idd6 locus to an 8cM region on the telomeric end of chromosome 6 and the control of apoptosis resistance to a 3cM region within this area. In paper II, further analysis of diabetes incidence in these congenic mice separated the genes controlling these two traits, excluding the region controlling the resistance to apoptosis as directly mediating susceptibility to diabetes. These results also allowed us to further restrict the Idd6 locus to a 3Mb region. Expression analysis of genes in this chromosomal region highlighted the Lrmp/Jaw1 gene as a prime candidate for Idd6. Lrmp encodes an endoplasmatic reticulum resident protein. Papers III and IV relate to peripheral tolerance mechanisms. Several T cell populations with regulatory functions have been implicated in type 1 diabetes. In paper III, we analyzed NOD transgenic mice carrying a diverse CD1d-restricted TCR αVa3.2b9), named 24abNOD mice. The number of nonclassical NKT cells was found to be increased in these mice and almost complete protection from diabetes was observed. These results indicate a role for nonclassical NKT cells in the regulation of autoimmune diabetes. In paper IV, we studied the effects of introducing the diverse CD1d-restricted TCR (Va3.2b9) in immunodeficient NOD Rag-/- mice (24abNODRag-/- mice). This resulted in a surprising phenotype with inflammation of the ears and augmented presence of mast cells as well as spleenomegaly and hepatomegaly associated with extended fibrosis and increased numbers of mast cells and eosinophils in the tissues. These observations supported the notion that NKT cells constitute an “intermediary” cell type, not only able to elicit the innate immune system to mount an inflammatory response, but also able to interact with the adaptive immune system affecting the action of effector T cells in an autoimmune situation. In this context the 24abNODRag-/- mice provide an appropriate animal model for studying the interaction of NKT cells with both innate and adaptive components of the immune systemα.
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43.
  • Edberg, Niklas J. T., et al. (författare)
  • Effects of Saturn's magnetospheric dynamics on Titan's ionosphere
  • 2015
  • Ingår i: Journal of Geophysical Research - Space Physics. - 2169-9380 .- 2169-9402. ; 120:10, s. 8884-8898
  • Tidskriftsartikel (refereegranskat)abstract
    • We use the Cassini Radio and Plasma Wave Science/Langmuir probe measurements of the electron density from the first 110 flybys of Titan to study how Saturn's magnetosphere influences Titan's ionosphere. The data is first corrected for biased sampling due to varying solar zenith angle and solar energy flux (solar cycle effects). We then present results showing that the electron density in Titan's ionosphere, in the altitude range 1600-2400km, is increased by about a factor of 2.5 when Titan is located on the nightside of Saturn (Saturn local time (SLT) 21-03h) compared to when on the dayside (SLT 09-15 h). For lower altitudes (1100-1600km) the main dividing factor for the ionospheric density is the ambient magnetospheric conditions. When Titan is located in the magnetospheric current sheet, the electron density in Titan's ionosphere is about a factor of 1.4 higher compared to when Titan is located in the magnetospheric lobes. The factor of 1.4 increase in between sheet and lobe flybys is interpreted as an effect of increased particle impact ionization from approximate to 200eV sheet electrons. The factor of 2.5 increase in electron density between flybys on Saturn's nightside and dayside is suggested to be an effect of the pressure balance between thermal plus magnetic pressure in Titan's ionosphere against the dynamic pressure and energetic particle pressure in Saturn's magnetosphere.
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44.
  • Engholm, Gerda, et al. (författare)
  • Colorectal cancer survival in the Nordic countries and the United Kingdom : Excess mortality risk analysis of 5 year relative period survival in the period 1999 to 2000
  • 2007
  • Ingår i: International Journal of Cancer. - : Wiley. - 0020-7136 .- 1097-0215. ; 121:5, s. 1115-1122
  • Tidskriftsartikel (refereegranskat)abstract
    • A deficit in colorectal cancer survival in Denmark and in the UK compared to Sweden, Norway and Finland was found in the EUROCARE studies. We set out to explore if these differences still exist. Patients diagnosed with colorectal cancer as their first invasive cancer at age 15-89 in the period 1994-2000 were identified using data from 11 cancer registries in the UK and from four Nordic countries. Five-year relative period survival using deaths in 1999-2000 following cancers diagnosed in 1994-2000 was analysed with excess mortality risk modelling. Follow-up time since diagnosis with age as an effect-modifier in the first half year was the most important factor with the highest excess risk of death immediately after diagnosis and with higher age and decreasing with length of follow-up. Variations between countries were bigger in the first half year following diagnosis than in the interval 0.5-5 years with about 30% higher risk in UK and Denmark. The differences between countries are still substantial and the order has not changed, even if the five year relative survival has improved since the EUROCARE studies. Patient management, diagnostics, and comorbidity likely explain the excess deaths in UK and Denmark during the first 6 months. The effect of stage and quality of management and treatment should be examined in population based studies with detailed patient information. Use of more detailed age-intervals than conventionally applied in survival studies proved to be important in statistical modelling and is recommended for future studies.
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45.
  • Espinoza, Fredrik, et al. (författare)
  • Intrusiveness management for focused, efficient, and enjoyable activities
  • 2007
  • Ingår i: The Disappearing Computer. - Berlin / Heidelberg : Springer. - 9783540727255 ; , s. 143-157
  • Bokkapitel (refereegranskat)abstract
    • When technologies for distributed activities develop, in particular the rapidly developing mobile technology, a larger part of our time will be spent connected to our various distributed contexts. When we meet physically we bring technology, both artifacts and services, which enable us to participate in these non-local contexts. Potentially this is a threat to focused and efficient activities due to the intrusiveness of the technology. Our aim is to contribute to the restoration of a number of the desirable properties of traditional local technology-free contexts. The intrusiveness itself is caused by at least four typical phenomena that have influenced current technology: • Focus-demanding and clearly distinguishable artifacts like phones or PCs explicitly mediate interaction with the distributed context • The functionality of services is traditionally based upon the assumption that communication is a deterministic flow of passive information, which for example, does not include information of the participants´ current context • Services in general perform individually and without coordinated communication schemes • The switches between contexts introduce a high cognitive load as each distributed context typically has its own system of characteristic objects and rules. In the FEEL project, we have developed a system called “Focused, Efficient and Enjoyable Local Activities with Intrusiveness Management” (FEELIM) that constitutes an intermediate alternative between the technology-dense and technology-free environments, which addresses the problems cited above. This research is based on a collaborative and cooperative setting where problems of intrusiveness management are confounded by several users meeting and cooperating together as opposed to isolated users dealing with similar problems of interruption management (Chen 2004; Ho 2005).
  •  
46.
  • Franca, José Adalberto, 1979- (författare)
  • Innovation in Complex Products and Systems (CoPS) : The Coordination of Technology Development within Networks and Projects
  • 2023
  • Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
    • Complex Product and Systems (CoPS) has been considered a cornerstone of a national innovation strategy. Telecommunications network systems, aircrafts, gas turbines and weapon systems are example of CoPS, and their management are characterized distinctly different from mass-market commodity goods. CoPS developments play an important role in shaping the modern industrial dynamics, since most, if not all, modern commodity goods and services depend on CoPS for their production. Following society’s increasing dependence on CoPS with ever increasing complexity, more research is needed to further uncover the innovation processes that occurs during the long-term evolution and maturation of technologies and tailored solutions needed for CoPS. This technology evolution, from the discovery of basic scientific principles until the development of technology demonstrators and products, usually happens within R&D projects executed and coordinated by a wide range of net-worked actors, from universities, SMEs, large firms, research institutes, industrial organizations and funding agencies.  Hence, it is important to highlight the perspectives of networks and pro-jects to better understand the innovation process during the development of CoPS. In this context, this Thesis aims to explore the coordination of technology development addressing networks and projects, since the latter are usually considered the main unit of analysis for CoPS innovations and require high levels of coordination efforts within a network of diversified actors.   For this purpose, a case study methodology is used with a systematic combining approach, where the theoretical framework, empirical fieldwork, and case analysis are continuously revisited in an iterative way.  By describing and integrating the perspectives of networks and projects, it is suggested that projects are a crucial unit of analysis for understanding network dynamics since they are the mechanisms that enable inter-actions and collaborations for the development of relationships, which ultimately, creates a shared identity.  The results show how diverse actors from different strategic nets can interact to develop a research agenda, coordinate the network of actors and direct the technology path where the research agenda potentially con-tributes to shape a network of R&D projects enabling the network actors to position and reposition themselves. Contributions are made to the CoPS literature and the dichotomy between managing within and managing of the network. It is discussed how network capabilities can be a key component in a network alignment process and their relationship with systems integration, the core capability of a CoPS leading firm. It is suggested that, when the networked actors want to improve their net-work position, they need to identify matching strategic nets, position themselves and contribute to the shaping of their value systems aligning with their strategies. In his context, the Technology Readiness Levels (TRL) become an essential tool to make this matching since it communicates to the whole network, the outputs of their efforts in a standardized way. 
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47.
  •  
48.
  • Galvan-Alvarez, Victor, et al. (författare)
  • Antioxidant enzymes and Nrf2/Keap1 in human skeletal muscle: Influence of age, sex, adiposity and aerobic fitness
  • 2023
  • Ingår i: Free Radical Biology & Medicine. - : Elsevier Inc.. - 0891-5849 .- 1873-4596. ; 209:Part 2, s. 282-291
  • Tidskriftsartikel (refereegranskat)abstract
    • Whether a higher aerobic fitness is associated with increased expression of antioxidant enzymes and their regulatory factors in skeletal muscle remains unknown. Although oestrogens could promote a higher antioxidant capacity in females, it remains unknown whether a sex dimorphism exists in humans regarding the antioxidant capacity of skeletal muscle. Thus, the aim was to determine the protein expression levels of the antioxidant enzymes SOD1, SOD2, catalase and glutathione reductase (GR) and their regulatory factors Nrf2 and Keap1 in 189 volunteers (120 males and 69 females) to establish whether sex differences exist and how age, VO2max and adiposity influence these. For this purpose, vastus lateralis muscle biopsies were obtained in all participants under resting and unstressed conditions. No significant sex differences in Nrf2, Keap1, SOD1, SOD2, catalase and GR protein expression levels were observed after accounting for VO2max, age and adiposity differences. Multiple regression analysis indicates that the VO2max in mL.kg LLM−1.min−1can be predicted from the levels of SOD2, Total Nrf2 and Keap1 (R = 0.58, P < 0.001), with SOD2 being the main predictor explaining 28 % of variance in VO2max, while Nrf2 and Keap1 explained each around 3 % of the variance. SOD1 protein expression increased with ageing in the whole group after accounting for differences in VO2max and body fat percentage. Overweight and obesity were associated with increased pSer40-Nrf2, pSer40-Nrf2/Total Nrf2 ratio and SOD1 protein expression levels after accounting for differences in age and VO2max. Overall, at the population level, higher aerobic fitness is associated with increased basal expression of muscle antioxidant enzymes, which may explain some of the benefits of regular exercise.
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49.
  • Gedeborg, Rolf, et al. (författare)
  • An Aggregated Comorbidity Measure Based on History of Filled Drug Prescriptions : Development and Evaluation in Two Separate Cohorts
  • 2021
  • Ingår i: Epidemiology. - : Lippincott Williams & Wilkins. - 1044-3983 .- 1531-5487. ; 32:4, s. 607-615
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: The ability to account for comorbidity when estimating survival in a population diagnosed with cancer could be improved by using a drug comorbidity index based on filled drug prescriptions.Methods: We created a drug comorbidity index from age-stratified univariable associations between filled drug prescriptions and time to death in 326,450 control males randomly selected from the general population to men with prostate cancer. We also evaluated the index in 272,214 control females randomly selected from the general population to women with breast cancer.Results: The new drug comorbidity index predicted survival better than the Charlson Comorbidity Index (CCI) and a previously published prescription index during 11 years of follow-up. The concordance (C)-index for the new index was 0.73 in male and 0.76 in the female population, as compared with a C-index of 0.67 in men and 0.69 in women for the CCI. In men of age 75-84 years with CCI = 0, the median survival time was 7.1 years (95% confidence interval [CI] = 7.0, 7.3) in the highest index quartile. Comparing the highest to the lowest drug comorbidity index quartile resulted in a hazard ratio (HR) of 2.2 among men (95% CI = 2.1, 2.3) and 2.4 among women (95% CI = 2.3, 2.6).Conclusions: A new drug comorbidity index based on filled drug prescriptions improved prediction of survival beyond age and the CCI alone. The index will allow a more accurate baseline estimation of expected survival for comparing treatment outcomes and evaluating treatment guidelines in populations of people with cancer.
  •  
50.
  • George, Gincy, et al. (författare)
  • Long-term adherence to GnRH agonists in men with prostate cancer : A nation-wide population-based study in prostate cancer data base Sweden
  • 2020
  • Ingår i: Scandinavian journal of urology. - : Informa UK Limited. - 2168-1805 .- 2168-1813. ; 54:1, s. 20-26
  • Tidskriftsartikel (refereegranskat)abstract
    • Aim: Gonadotropin-releasing hormone (GnRH) agonists are used to treat men with prostate cancer (PCa). To date, no study has fully assessed patterns of adherence to GnRH agonists. We investigated patterns of adherence to GnRH agonists using data from Prostate Cancer data Base Sweden (PCBaSe).Methods: PCBaSe links the National Prostate Cancer Register (NPCR) Sweden to other healthcare registers and demographic databases. Men on primary or secondary GnRH agonists between 2006-2013 entered the study 45 days after GnRH agonists' initiation (run-in period) and exited at 3 years. Medication possession ratio quantified adherents (≥80%). Multivariable logistic regression models included age, injection interval, PCa risk categories, Charlson Comorbidity Index, prior PCa treatment, civil status and year of GnRH initiation. Odds ratios (OR) and 95% confidence intervals (CI) expressed odds of adherence.Results: Men on primary GnRH agonists (n = 8,105) were more adherent with increasing age (75-84 years compared to ≤65 years OR: 1.49; 95% CI: 1.23-1.81), longer injection intervals (365 days compared to 90 days OR: 3.29; 95% CI: 2.52-4.30) and higher PCa risk categories at diagnosis (distant metastasis compared to low risk PCa OR: 3.56; 95% CI: 2.54-5.00). Men on secondary GnRH agonists (n = 4,738) were more adherent with increasing age (≥85 years compared to ≤65 years OR: 1.65; 95% CI: 1.23-2.22) and prior PCa treatment (anti-androgens compared to deferred treatment OR: 1.50; 95% CI: 1.23-1.82), (radiotherapy compared to deferred treatment OR: 1.35; 95% CI: 1.11-1.64).Conclusions: Longer injection intervals could be addressed in the clinical setting to improve adherence.
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