| 1. |
- Alkner, Sara, et al.
(författare)
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Protocol for the T-REX-trial: tailored regional external beam radiotherapy in clinically node-negative breast cancer patients with 1-2 sentinel node macrometastases - an open, multicentre, randomised non-inferiority phase 3 trial.
- 2023
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Ingår i: BMJ open. - 2044-6055. ; 13:9
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Tidskriftsartikel (refereegranskat)abstract
- Modern systemic treatment has reduced incidence of regional recurrences and improved survival in breast cancer (BC). It is thus questionable whether regional radiotherapy (RT) is still beneficial in patients with sentinel lymph node (SLN) macrometastasis. Postoperative regional RT is associated with an increased risk of arm morbidity, pneumonitis, cardiac disease and secondary cancer. Therefore, there is a need to individualise regional RT in relation to the risk of recurrence.In this multicentre, prospective randomised trial, clinically node-negative patients with oestrogen receptor-positive, HER2-negative BC and 1-2 SLN macrometastases are eligible. Participants are randomly assigned to receive regional RT (standard arm) or not (intervention arm). Regional RT includes the axilla level I-III, the supraclavicular fossa and in selected patients the internal mammary nodes. Both groups receive RT to the remaining breast. Chest-wall RT after mastectomy is given in the standard arm, but in the intervention arm only in cases of widespread multifocality according to national guidelines. RT quality assurance is an integral part of the trial.The trial aims to include 1350 patients between March 2023 and December 2028 in Sweden and Norway. Primary outcome is recurrence-free survival (RFS) at 5years. Non-inferiority will be declared if outcome in the de-escalation arm is not >4.5percentage units below that with regional RT, corresponding to an HR of 1.41 assuming 88% 5-year RFS with standard treatment. Secondary outcomes include locoregional recurrence, overall survival, patient-reported arm morbidity and health-related quality of life. Gene expression analysis and tumour tissue-based studies to identify prognostic and predictive markers for benefit of regional RT are included.The trial protocol is approved by the Swedish Ethics Authority (Dnr-2022-02178-01, 2022-05093-02, 2023-00826-02, 2023-03035-02). Results will be presented at scientific conferences and in peer-reviewed journals.NCT05634889.
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| 2. |
- Bengtsson, Lisa, et al.
(författare)
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Probabilistic Safety Goals for Nuclear Power Plants; Phases 2-4 : Final Report
- 2011
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Rapport (övrigt vetenskapligt/konstnärligt)abstract
- Safety goals are defined in different ways in different countries and also used differently. Many countries are presently developing them in connection to the transfer to risk-informed regulation of both operating nuclear power plants (NPP) and new designs. However, it is far from self-evident how probabilistic safety criteria should be defined and used. On one hand, experience indicates that safety goals are valuable tools for the interpretation of results from a probabilistic safety assessment (PSA), and they tend to enhance the realism of a risk assessment. On the other hand, strict use of probabilistic criteria is usually avoided. A major problem is the large number of different uncertainties in a PSA model, which makes it difficult to demonstrate the compliance with a probabilistic criterion. Further, it has been seen that PSA results can change a lot over time due to scope extensions, revised operating experience data, method development, changes in system requirements, or increases of level of detail, mostly leading to an increase of the frequency of the calculated risk. This can cause a problem of consistency in the judgments.This report presents the results from the second, third and fourth phases of the project (2007–2009), which have dealt with providing guidance related to the resolution of some specific problems, such as the problem of consistency in judgement, comparability of safety goals used in different industries, the relationship between criteria on different levels, and relations between criteria for level 2 and 3 PSA. In parallel, additional context information has been provided. This was achieved by extending the international overview by contributing to and benefiting from a survey on PSA safety criteria which was initiated in 2006 within the OECD/NEA Working Group Risk.The results from the project can be used as a platform for discussions at the utilities on how to define and use quantitative safety goals. The results can also be used by safety authorities as a reference for risk-informed regulation. The outcome can have an impact on the requirements on PSA, e.g., regarding quality, scope, level of detail, and documen¬tation. Finally, the results can be expected to support on-going activities concerning risk-informed applications.The project provides a comprehensive state-of-the-art description and has contributed to clarifying the history of safety goals both nationally and internationally, the concepts involved in defining and applying probabilistic safety criteria, and the international status and trends in general. It has identified critical issues and the main problem areas. Finally, the project provides useful recommendations and guidance on the definition and application of criteria.Furthermore, the project makes it possible to define criteria stringently, improving the possibilities of argumentation on safety. Generally, this supports efficient use of criteria, yielding more useful PSA results. In this connection, the introduction of ALARP type criteria is judged to provide a very useful way of balancing stringency with the necessary flexibility. There is a possibility of making more active use of lower level criteria. This makes the connection to defence in depth more evident, and opens the perspective of increased control of defence in depth by use of probabilistic methods, including the use as design tools. There is an opportunity for comparison of risk of different NPPs, as well as of comparison of NPP risk with other risks in society. This is judged to provide an opportunity for improved communication on risks with non-PSA experts and with the public in general. However, a necessary condition for meaningful comparisons is to agree on the scope of PSA and methods applied.Obviously, there will also be challenges in the future definition and application of probabilistic safety criteria. These include very general aspects, such as the interpretation of the probability, quality aspects of PSA, and the definition of meaningful and consistent risk criteria for different usages. The need and usefulness of subsidiary criteria has been stressed in the project, but there is obviously also a challenge in defining a relevant set of criteria on different levels. Defining criteria for L(E)RF is complex, especially if release criteria are defined as subsidiary for societal and individual risk. Finally, it will be a challenge to develop coherent application procedures relative to the criteria defined.
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| 4. |
- Denti, Leif, 1983, et al.
(författare)
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Sweden's largest Facebook study
- 2012
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Rapport (övrigt vetenskapligt/konstnärligt)abstract
- The emergence of the Internet has made it easier for people to socially interact than ever before. Today, the most popular channel is Facebook with over 845 million users world wide. In Sweden, the number of users amount to approximately half of the population. We had two aims with this study. First, we investigate which areas of Facebook usage that Swedish Facebook users consider more important vis-a-vis less important. We were also interested in how users convey their persona through their status updates, including what they status update about, and the underlying reasons for updating one’s status. Second, we investigate what psychological effects Facebook may induce. More specifically, we look at the psychological constructs self-esteem and well-being in relation to Facebook usage. We surveyed 1011 Swedish Facebook users with our questionnaires, measuring respondents’ Facebook usage patterns, well-being and self-esteem. Our analyses revealed that on average Swedish women spend 81 minutes per day on Facebook, whereas Swedish men are logged on to the site about 64 minutes per day. Generally, Facebook is used for social network maintenance, such as maintaining contact with people one doesn’t meet so often. However, Facebook is seldom used for meeting new people. Another finding is that Facebook users generally tend to update their status about positive events, major events and when they are feeling well, rather than negative events and when they are feeling bad. Women seem to be more engaged and active on Facebook than men, agreeing that a vast number of uses is significantly more important. Furthermore, women tend to write more about their thoughts and feelings, whereas twice as many men state that they provoke others on Facebook. Pertaining to Facebook’s psychological effects, the amount of time spent on Facebook had no relationship with self-esteem when controlling for gender, age, education and income. $is result runs counter to previous findings. However, women who spend more time on Facebook report feeling less happy and feel less content with their lives. For men, this relationship was not evident. The study teaches that Facebook is used as a tool for affiliating with friends and family, as well as a personal showcase, where users show their positive sides. Herein lies also a danger. When Facebook users compare their own lives with others’ seemingly more successful careers and happy relationships, they may feel that their own lives are less successful in comparison.
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| 7. |
- Holmberg, Rebecka, et al.
(författare)
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Antiviral treatments reduce severity of diabetes in Ljungan virus-infected CD-1 mice and delay onset in diabetes-prone BB rats
- 2009
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Ingår i: Microbiology and immunology. - : Wiley. - 0385-5600 .- 1348-0421. ; 53:10, s. 567-572
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Tidskriftsartikel (refereegranskat)abstract
- The effects of LV in two different species, CD-1 mice, without a genetic disposition for diabetes, and BB rats prone to T1D were examined. Male CD-1 mice that had been exposed to LV in utero developed a type 2-like diabetes with increased blood glucose, insulin levels and epididymal fat at the age of 10-15 weeks. Combination therapy including LV-antiserum and an antiviral drug, Pleconaril, significantly reduced the levels of blood glucose and insulin and the amount of abdominal fat. In BB rats, LV has been found in both prediabetic- and diabetic diabetes-prone rats, as well as in diabetes-resistant rats. To evaluate whether the presence of LV has any influence on the onset of T1D, prediabetic BB rats were treated with an antiserum against LV or a combination of the antiviral drugs Pleconaril and Ribavirin. In the group treated with antiviral drugs, the onset was significantly delayed. These results indicate that the presence of LV can be involved in the pathogenesis of diabetes in these animal models.
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| 8. |
- Holmberg, Rebecka, et al.
(författare)
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Lowering apolipoprotein CIII delays onset of type 1 diabetes
- 2011
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Ingår i: Proceedings of the National Academy of Sciences of the United States of America. - : National Academy of Sciences. - 0027-8424 .- 1091-6490. ; 108:26, s. 10685-10689
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Tidskriftsartikel (refereegranskat)abstract
- Serum levels of apolipoprotein CIII (apoCIII) are increased in type 1 diabetic patients, and when β cells are exposed to these diabetic sera, apoptosis occurs, an effect abolished by an antibody against apoCIII. We have investigated the BB rat, an animal model that develops a human-like type 1 diabetes, and found that apoCIII was also increased in sera from prediabetic rats. This increase in apoCIII promoted β-cell death. The endogenous levels of apoCIII were reduced by treating prediabetic animals with an antisense against this apolipoprotein, resulting in a significantly delayed onset of diabetes. ApoCIII thus serves as a diabetogenic factor, and intervention with this apolipoprotein in the prediabetic state can arrest disease progression. These findings suggest apoCIII as a target for the treatment of type 1 diabetes.
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| 9. |
- Jennbacken, Karin, et al.
(författare)
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Phenotypic Screen with the Human Secretome Identifies FGF16 as Inducing Proliferation of iPSC-Derived Cardiac Progenitor Cells
- 2019
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Ingår i: International Journal of Molecular Sciences. - : MDPI. - 1661-6596 .- 1422-0067. ; 20:23
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Tidskriftsartikel (refereegranskat)abstract
- Paracrine factors can induce cardiac regeneration and repair post myocardial infarction by stimulating proliferation of cardiac cells and inducing the anti-fibrotic, antiapoptotic, and immunomodulatory effects of angiogenesis. Here, we screened a human secretome library, consisting of 923 growth factors, cytokines, and proteins with unknown function, in a phenotypic screen with human cardiac progenitor cells. The primary readout in the screen was proliferation measured by nuclear count. From this screen, we identified FGF1, FGF4, FGF9, FGF16, FGF18, and seven additional proteins that induce proliferation of cardiac progenitor cells. FGF9 and FGF16 belong to the same FGF subfamily, share high sequence identity, and are described to have similar receptor preferences. Interestingly, FGF16 was shown to be specific for proliferation of cardiac progenitor cells, whereas FGF9 also proliferated human cardiac fibroblasts. Biosensor analysis of receptor preferences and quantification of receptor abundances suggested that FGF16 and FGF9 bind to different FGF receptors on the cardiac progenitor cells and cardiac fibroblasts. FGF16 also proliferated naive cardiac progenitor cells isolated from mouse heart and human cardiomyocytes derived from induced pluripotent cells. Taken together, the data suggest that FGF16 could be a suitable paracrine factor to induce cardiac regeneration and repair.
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| 10. |
- Kouros, Ioannis, et al.
(författare)
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Temperament, but not childhood trauma, distinguishes borderline personality disorder from bipolar disorder and ADHD
- 2024
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Ingår i: Nordic Journal of Psychiatry. - : Taylor & Francis. - 0803-9488 .- 1502-4725. ; 78:1, s. 79-86
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Tidskriftsartikel (refereegranskat)abstract
- BackgroundThe aim of this study was to investigate if temperament and experience of childhood trauma differed between young psychiatric patients with borderline personality disorder (BPD), bipolar disorder (BD) and attention-deficit/hyperactivity disorder (ADHD).MethodsDiagnoses were based on the Structured Clinical Interview for DSM Axis I and Axis II. Temperament was assessed by the Temperament and Character Inventory (TCI) and childhood trauma by the Early Trauma Inventory-Self Report-Short Form (ETI-SR-SF). Temperament and childhood trauma were compared between the BPD group (n = 19) and the non-BPD group (BD/ADHD) (n = 95). Interactions between trauma and temperament were evaluated using a logistic regression model with a BPD diagnosis as outcome variable.ResultsParticipants in the BPD group showed higher novelty seeking (NS) and harm avoidance (HA). Traumatic experiences in childhood were common but the BPD group differed very little from the others in this regard. The interaction between temperament and trauma had low explanatory power for a BPD diagnosis in this sample.ConclusionTemperament might be useful to distinguish BPD when symptoms of impulsivity and affective instability are evaluated in psychiatric patients. The results from the interaction analysis support the multifactorial background to BPD.
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