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- Adamsson Eryd, Samuel, et al.
(författare)
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Blood pressure and complications in individuals with type 2 diabetes and no previous cardiovascular disease: national population based cohort study
- 2016
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Ingår i: Bmj-British Medical Journal. - : BMJ. - 1756-1833. ; 354
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVES To compare the risk associated with systolic blood pressure that meets current recommendations (that is, below 140 mm Hg) with the risk associated with lower levels in patients who have type 2 diabetes and no previous cardiovascular disease. Population based cohort study with nationwide clinical registries, 2006-12. The mean follow-up was 5.0 years. 187 106 patients registered in the Swedish national diabetes register who had had type 2 diabetes for at least a year, age 75 or younger, and with no previous cardiovascular or other major disease. Clinical events were obtained from the hospital discharge and death registers with respect to acute myocardial infarction, stroke, a composite of acute myocardial infarction and stroke (cardiovascular disease), coronary heart disease, heart failure, and total mortality. Hazard ratios were estimated for different levels of baseline systolic blood pressure with clinical characteristics and drug prescription data as covariates. The group with the lowest systolic blood pressure (110-119 mm Hg) had a significantly lower risk of non-fatal acute myocardial infarction (adjusted hazard ratio 0.76, 95% confidence interval 0.64 to 0.91; P=0.003), total acute myocardial infarction (0.85, 0.72 to 0.99; P=0.04), non-fatal cardiovascular disease (0.82, 0.72 to 0.93; P=0.002), total cardiovascular disease (0.88, 0.79 to 0.99; P=0.04), and non-fatal coronary heart disease (0.88, 0.78 to 0.99; P=0.03) compared with the reference group (130-139 mm Hg). There was no indication of a J shaped relation between systolic blood pressure and the endpoints, with the exception of heart failure and total mortality. Lower systolic blood pressure than currently recommended is associated with significantly lower risk of cardiovascular events in patients with type 2 diabetes. The association between low blood pressure and increased mortality could be due to concomitant disease rather than antihypertensive treatment.
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| 2. |
- Adamsson, Jenni, 1977, et al.
(författare)
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Novel immunostimulatory agent based on CpG oligodeoxynucleotide linked to the nontoxic B subunit of cholera toxin.
- 2006
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Ingår i: Journal of immunology (Baltimore, Md. : 1950). - 0022-1767. ; 176:8, s. 4902-13
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Tidskriftsartikel (refereegranskat)abstract
- In this study, we report the development of a novel, rationally designed immunostimulatory adjuvant based on chemical conjugation of CpG oligodeoxynucleotide (ODN) to the nontoxic B subunit of cholera toxin (CTB). We demonstrate that the immunostimulatory effects of CpG can be dramatically enhanced by conjugation to CTB. Thus, CpG ODN linked to CTB (CTB-CpG) was shown to be a more potent stimulator of proinflammatory cytokine and chemokine responses in murine splenocytes and human PBMCs than those of CpG ODN alone in vitro. The presence of CpG motif, but not modified phosphorothioate ODN backbone, was found to be critical for the enhanced immunostimulatory effects of CTB-CpG. Our mode-of-action studies, including studies on cells from specifically gene knockout mice suggest that similar to CpG, CTB-CpG exerts its immunostimulatory effects through a TLR9/MyD88- and NF-kappaB-dependent pathway. Surprisingly, and as opposed to CpG ODN, CTB-CpG-induced immunity was shown to be independent of endosomal acidification and resistant to inhibitory ODN. Furthermore, preincubation of CTB-CpG with GM1 ganglioside reduced the immunostimulatory effects of CTB-CpG to those of CpG ODN alone. Interestingly, conjugation of CpG ODN to CTB confers an enhanced cross-species activity to CpG ODN. Furthermore, using tetanus toxoid as a vaccine Ag for s.c. immunization, CTB-CpG markedly enhanced the Ag-specific IgG Ab response and altered the specific pattern of Ab isotypes toward a Th1 type response. To our knowledge, CTB is the first nontoxic derivative of microbial toxins discovered that when chemically linked to CpG remarkably augments the CpG-mediated immune responses.
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| 4. |
- Adamsson, Niklas, 1977-
(författare)
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Interdisciplinary integration in complex product development : managerial implications of embedding software in manufactured goods
- 2007
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Incorporating electronics and software systems into manufactured goods is becoming very common in manufacturing companies. New technical functions, increased flexibility, and compensation for mechanical design weaknesses are some key drivers of this technological change in our everyday products. The automotive industry exemplifies this trend, since approximately 80–90% of new functions in cars are based on electronics and software, and it is expected that at least a third of the total cost of a car will eventually be accounted for by electronics and software. However, one of the main downsides of this technological trend is the increasing number of quality issues related to these new technologies, something usually claimed to be a result of the increased product development complexity. Previous research into product development management has mainly concentrated on either physical products or software systems, but not concurrently on both. Additionally, much of the research has concentrated on issues of integrating marketing, R&D, and manufacturing in these companies, and has treated the engineering disciplines in R&D as a homogenous group. Motivated by this change in technology content and the lack of research into complex product development and especially into integration between engineering disciplines, the present work investigates how to increase operational performance in multidisciplinary engineering organizations. This work has especially focused on interdisciplinary integration and the feasibility of various so-called integration mechanisms, such as building common physical facilities, job rotation programs, the implementation and use of information and communications technology, and computer-aided engineering tools. Both qualitative and quantitative research has been performed, involving 11 different companies and over 300 respondents. Supported by the present findings, it is demonstrated that interdisciplinary integration is a crucial factor to consider, and it is concluded that certain integration mechanisms stand out as more important than others. Organizational structure, work procedures and methods, training, social systems, and computer-aided engineering were the five types of mechanisms that displayed the greatest potential for improvement. It is further concluded that the ability to successfully match the body of practices to current products is essential, since there is a high risk of current practices becoming out-dated with respect to the technology content. Furthermore, inadequate identification of or managerial ability to establish the currently most important interfaces complicate the choice of trade-offs between various technologies that are found to be essential to cope with the inherent dynamic complexity. The organizational powerbase is often re-positioned in the studied organizations, and the loss of decisive power can result in a demoralizing ignorance of newly established disciplines and their design practices. Additionally, rigid structures and counterproductive traditions can reduce the potential gains accruing from new boundary-spanning innovations, so organizational responsibilities and mandates must be declared unambiguously, in many cases differently from how they have been in the past. Based on these conclusions, it is suggested that managers in organizations like those studied must be able to do the following: cultivate software knowledge in all parts and levels of the product development organization; reassess their recruitment strategies; organize for interdisciplinary collaboration; articulate and communicate the technology fusion strategy to all disciplines; and realize and disseminate the fact that product launches do not only concern manufacturability.
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| 8. |
- Alarcon, Sonia, et al.
(författare)
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Endocrine, metabolic and apical effects of in utero and lactational exposure to non-dioxin-like 2,2 ',3,4,4 ',5,5 '-heptachlorobiphenyl (PCB 180) : A postnatal follow-up study in rats
- 2021
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Ingår i: Reproductive Toxicology. - : Elsevier. - 0890-6238 .- 1873-1708. ; 102, s. 109-127
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Tidskriftsartikel (refereegranskat)abstract
- PCB 180 is a persistent and abundant non-dioxin-like PCB (NDL-PCB). We determined the developmental toxicity profile of ultrapure PCB 180 in developing offspring following in utero and lactational exposure with the focus on endocrine, metabolic and retinoid system alterations. Pregnant rats were given total doses of 0, 10, 30, 100, 300 or 1000 mg PCB 180/kg bw on gestational days 7-10 by oral gavage, and the offspring were sampled on postnatal days (PND) 7, 35 and 84. Decreased serum testosterone and triiodothyronine concentrations on PND 84, altered liver retinoid levels, increased liver weights and induced 7-pentoxyresorufin O-dealkylase (PROD) activity were the sensitive effects used for margin of exposure (MoE) calculations. Liver weights were increased together with induction of the metabolizing enzymes cytochrome P450 (CYP) 2B1, CYP3A1, and CYP1A1. Less sensitive effects included decreased serum estradiol and increased luteinizing hormone levels in females, decreased prostate and seminal vesicle weight and increased pituitary weight in males, increased cortical bone area and thickness of tibial diaphysis in females and decreased cortical bone mineral density in males. Developmental toxicity profiles were partly different in male and female offspring, males being more sensitive to increased liver weight, PROD induction and decreased thyroxine concentrations. MoE assessment indicated that the 95th percentile of current maternal PCB 180 concentrations do not exceed the estimated tolerable human lipid-based PCB 180 concentration. Although PCB 180 is much less potent than dioxin-like compounds, it shares several toxicological targets suggesting a potential for interactions.
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| 9. |
- Ali, Imran, et al.
(författare)
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Cadmium-induced effects on cellular signaling pathways in the liver of transgenic estrogen reporter mice.
- 2012
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Ingår i: Toxicological Sciences. - : Oxford University Press (OUP). - 1096-6080 .- 1096-0929. ; 127:1, s. 66-75
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Tidskriftsartikel (refereegranskat)abstract
- Estrogen-like effects of cadmium (Cd) have been reported in several animal studies, and recent epidemiological findings suggest increased risk of hormone-dependent cancers after Cd exposure. The mechanisms underlying these effects are still under investigation. Our aim was to study the effects of Cd on cellular signaling pathways in vivo with special focus on estrogen signaling and to perform benchmark dose analysis on the effects. Transgenic adult ERE-luciferase male mice were exposed subcutaneously to 0.5-500 μg CdCl(2) per kg body weight (bw) or 17α-ethinylestradiol (EE2) for 3 days. These doses had no effects on organ and bw or testicular histology, indicating subtoxic exposure levels. The transgene luciferase, reporting genomic estrogen response, was significantly increased by EE2 but not by Cd. However, Cd significantly affected kinase phosphorylation and endogenous gene expression. Interestingly, gene expression changes displayed a traditional dose-response relationship, with benchmark dose levels for the expression of Mt1, Mt2, p53, c-fos, and Mdm2 being 92.9, 19.9, 7.6, 259, and 25.9 μg/kg bw, respectively, but changes in kinase phosphorylation were only detected at low exposure levels. Phosphorylation of Erk1/2 was significantly increased even in the lowest dose group, 0.5 μg/kg bw, rendering pErk1/2 a more sensitive sensor of exposure than changes in gene expression. Collectively, our data suggest that the effects triggered by Cd in vivo are markedly concentration dependent. Furthermore, we conclude that the estrogen-like effects of Cd are likely to result from a mechanism different from steroidal estrogens.
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| 10. |
- Bager, Johan-Emil, et al.
(författare)
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Treatment of hypertension in old patients without previous cardiovascular disease.
- 2019
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Ingår i: Journal of hypertension. - 1473-5598. ; 37:11, s. 2269-2279
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Tidskriftsartikel (refereegranskat)abstract
- The aim of this study was to compare the risk of cardiovascular disease (CVD) - nonfatal acute myocardial infarction (AMI) or stroke - at blood pressure levels that meet current recommendations with risk at lower levels, particularly in older patients.We identified patients with hypertension aged 40-90 years from a primary care register. Patients with a history of cancer, diabetes mellitus or CVD were excluded. Patients were divided into age groups (40-75 and 76-90), and four groups of SBP 110-129, 130-139 (reference), 140-149 and ≥150mmHg. We used the Kaplan-Meier estimator to study incidence of AMI, stroke and a composite of the two. Cox proportional-hazards regression was used to estimate hazard ratios for outcomes.We included 31704 patients: 26663 were 40-75 years old and 5041 were 76-90 years old. Mean follow-up was 2 years. Although no significant differences in risk of any outcome were found in the younger group, low blood pressure was associated with the lowest risk in the older group. Older patients in the 110-129mmHg group had a lower incidence of CVD (15.9/1000 vs. 25.3/1000 person-years) than the reference group. After adjustment for covariates, the hazard ratio of CVD in older patients in the 110-129mmHg group compared with the reference group was 0.60 (95% confidence interval 0.40-0.92).Blood pressure levels lower than those currently recommended are not harmful among older patients. The association between lower SBP and lesser risk of CVD may instead suggest a beneficial effect of lower SBP.
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