| 1. |
- Belfrage, Emma, et al.
(författare)
-
Predictive and Prognostic Biomarkers in Patients With Mycosis Fungoides and Sézary Syndrome (BIO-MUSE) : Protocol for a Translational Study
- 2024
-
Ingår i: JMIR Research Protocols. - 1929-0748. ; 13
-
Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Cutaneous T-cell lymphoma (CTCL) is a rare group of lymphomas that primarily affects the skin. Mycosis fungoides (MF) is the most common form of CTCL and Sézary syndrome (SS) is more infrequent. Early stages (IA-IIA) have a favorable prognosis, while advanced stages (IIB-IVB) have a worse prognosis. Around 25% of patients with early stages of the disease will progress to advanced stages. Malignant skin-infiltrating T-cells in CTCL are accompanied by infiltrates of nonmalignant T-cells and other immune cells that produce cytokines that modulate the inflammation. Skin infection, often with Staphylococcus aureus, is frequent in advanced stages and can lead to sepsis and death. S. aureus has also been reported to contribute to the progression of the disease. Previous reports indicate a shift from Th1 to Th2 cytokine production and dysfunction of the skin barrier in CTCL. Treatment response is highly variable and often unpredictable, and there is a need for new predictive and prognostic biomarkers.OBJECTIVE: This prospective translational study aims to identify prognostic biomarkers in the blood and skin of patients with MF and SS.METHODS: The Predictive and Prognostic Biomarkers in Patients With MF and SS (BIO-MUSE) study aims to recruit 120 adult patients with MF or SS and a control group of 20 healthy volunteers. The treatments will be given according to clinical routine. The sampling of each patient will be performed every 3 months for 3 years. The blood samples will be analyzed for lactate dehydrogenase, immunoglobulin E, interleukins, thymus and activation-regulated chemokine, and lymphocyte subpopulations. The lymphoma microenvironment will be investigated through digital spatial profiling and single-cell RNA sequencing. Microbiological sampling and analysis of skin barrier function will be performed. The life quality parameters will be evaluated. The results will be evaluated by the stage of the disease.RESULTS: Patient inclusion started in 2021 and is still ongoing in 2023, with 18 patients and 20 healthy controls enrolled. The publication of selected translational findings before the publication of the main results of the trial is accepted.CONCLUSIONS: This study aims to investigate blood and skin with a focus on immune cells and the microbiological environment to identify potential new prognostic biomarkers in MF and SS.TRIAL REGISTRATION: ClinicalTrials.gov NCT04904146; https://www.clinicaltrials.gov/study/NCT04904146.INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/55723.
|
|
| 2. |
- Belfrage, Sara, et al.
(författare)
-
Ethical problems in traffic research
- 2006
-
Ingår i: TRA - TRANSPORT RESEARCH ARENA EUROPE 2006.
-
Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- Traffic research gives rise to many types of ethical issues. In this paper we focus on ethical issues that arise when human beings are directly affected in the performance of research, by comparing traffic research to the ethical requirements imposed on biomedical research. After introducing the basic ethical requirements on biomedical research, each of the major requirements is discussed in relation to traffic research. We identify the main areas where biomedical research and traffic research differ, and where the ethical requirements from the former cannot easily be transferred to the latter. Finally, we argue that there is a need for systematic studies of the ethics of traffic research and point to some of the issues that need to be addressed (A). For the covering abstract of the conference see ITRD E212343
|
|
| 3. |
- Belfrage, Sara, 1977-
(författare)
-
Exploitative,irresistible and coercive offers. : Why research participants should be paid well or not at all.
-
Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- This paper starts with the assumption that it ismorally problematic when people in need are offered money in exchange forresearch participation if the amount offered is unfair. Such offers are called“coercive”, and the degree of coerciveness is said to be determined by theoffer’s potential to cause exploitation and its irresistibility. Depending onwhat view we take on the possibility to compensate for the sacrifices made byresearch participants, a wish to avoid “coercive offers” leads to policyrecommendations concerning payment for participation. For sacrifices consideredcompensable we ought to offer either no payment or payment at a level deemedfair, while for sacrifices deemed incompensable we always ought to offer nopayment.
|
|
| 4. |
- Belfrage, Sara, 1977-
(författare)
-
Exploiting gift-giving
- 2014
-
Ingår i: Ethical Perspectives. - 1370-0049 .- 1783-1431. ; 21:3, s. 371-400
-
Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- It is commonly thought that transactions that are the result of voluntary gift-giving do not constitute exploitation. This paper argues that exploitation is indeed possible in such situations, by showing how gift-giving can fulfil the two commonly proposed criteria for exploitation, namely that in an interaction between two persons one receives disproportionally little and the other disproportionally much of the resulting benefits, and that this disproportion is caused by the latter making inappropriate use of a disadvantage of the former. A theoretical approach to what such inappropriate use would amount to in cases of gift-giving is lacking. The paper therefore aims at spelling out such an approach. The method of reflective equilibrium inspires this endeavour, which proceeds by testing intuitions about examples that embody a set of possible conditions. It is concluded that three of the conditions are necessary for exploitation of gift-giving, namely (1) the giver incurs a loss, (2) the recipient has aimed for the gift, and (3) the gift is undeserved.
|
|
| 5. |
- Belfrage, Sara, 1977-
(författare)
-
In the name of research : Essays on the ethical treatment of human research subjects
- 2014
-
Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Essay 1: Traffic research shares a fundamental dilemma with other areas of empirical research in which humans are potentially put at risk. Research is justified because it can improve safety in the long run. Nevertheless, people can be harmed in the research situation. Hence, we need to balance short-term risks against long-term safety improvements, much as in other areas of research with human subjects. In this paper we focus on ethical issues that arise when human beings are directly affected in the performance of research by examining how the ethical requirements in biomedical research can inform traffic research. After introducing the basic ethical requirements on biomedical research, each of the major requirements is discussed in relation to traffic research. We identify the main areas where biomedical research and traffic research differ, and where the ethical requirements from the former cannot easily be transferred to the latter. We then point to some of the issues that need to be addressed for a systematic approach to the ethics of traffic research.Essay 2: The requirement of always obtaining participants’ informed consent in research with human subjects cannot always be met, for a variety of reasons. In this paper, research situations where informed consent is unobtainable are described and categorised. Some of these kinds of situations, common in biomedicine and psychology, have been previously much discussed, whereas others, more prevalent in for example infrastructure research, introduce new perspectives. The advancement of new technology may lead to an increase in research of these kinds. The paper also provides a review of methods intended to compensate for a lack of consent and their applicability and usefulness for the different categories of situations are discussed, thereby providing insights into one important aspect of relevance for the question of permitting research without informed consent: how well that which informed consent is meant to safeguard can be achieved by other means.Essay 3: This paper starts with the assumption that it is morally problematic when people in need are offered money in exchange for research participation if the amount offered is unfair. Such offers are called “coercive”, and the degree of coerciveness is said to be determined by the offer’s potential to cause exploitation and its irresistibility. Depending on what view we take on the possibility to compensate for the sacrifices made by research participants, a wish to avoid “coercive offers” leads to policy recommendations concerning payment for participation. For sacrifices considered compensable we ought to offer either no payment or payment at a level deemed fair, while for sacrifices deemed incompensable we always ought to offer no payment.Essay 4: It is commonly thought that transactions that are the result of voluntary gift-giving do not constitute exploitation. This paper argues that exploitation is indeed possible in such situations, by showing how gift-giving can fulfil the two commonly proposed criteria for exploitation, namely that in an interaction between two persons one receives disproportionally little and the other disproportionally much of the resulting benefits, and that this disproportion is caused by the latter making inappropriate use of a disadvantage of the former. A theoretical approach to what such inappropriate use would amount to in cases of gift-giving is lacking. The paper therefore aims at spelling out such an approach. The method of reflective equilibrium inspires this endeavour, which proceeds by testing intuitions about examples that embody a set of possible conditions. It is concluded that three of the conditions are necessary for exploitation of gift-giving, namely (1) the giver incurs a loss, (2) the recipient has aimed for the gift, and (3) the gift is undeserved.
|
|
| 6. |
- Belfrage, Sara
(författare)
-
Without informed consent
- 2013
-
Ingår i: Moral, Ethical, and Social Dilemmas in the Age of Technology. - : IGI Global. - 9781466629325 ; , s. 291-305
-
Bokkapitel (övrigt vetenskapligt/konstnärligt)abstract
- The requirement of always obtaining participants' informed consent in research with human subjects cannot always be met, for a variety of reasons. This paper describes and categorises research situations where informed consent is unobtainable. Some of these kinds of situations, common in biomedicine and psychology, have been previously discussed, whereas others, for example, those more prevalent in infrastructure research, introduce new perspectives. The advancement of new technology may lead to an increase in research of these kinds. The paper also provides a review of methods intended to compensate for lack of consent, and their applicability and usefulness for the different categories of situations are discussed. The aim of this is to provide insights into one important aspect of the question of permitting research without informed consent, namely, how well that which informed consent is meant to safeguard can be achieved by other means.
|
|
| 7. |
- Belfrage, Sara
(författare)
-
Without Informed Consent
- 2011
-
Ingår i: International Journal of Technoethics. - : IGI Global. - 1947-3451 .- 1947-346X. ; 2:3, s. 48-61
-
Tidskriftsartikel (refereegranskat)abstract
- The requirement of always obtaining participants’ informed consent in research with human subjects cannot always be met, for a variety of reasons. This paper describes and categorises research situations where informed consent is unobtainable. Some of these kinds of situations, common in biomedicine and psychology, have been previously discussed, whereas others, for example, those more prevalent in infrastructure research, introduce new perspectives. The advancement of new technology may lead to an increase in research of these kinds. The paper also provides a review of methods intended to compensate for lack of consent, and their applicability and usefulness for the different categories of situations are discussed. The aim of this is to provide insights into one important aspect of the question of permitting research without informed consent, namely, how well that which informed consent is meant to safeguard can be achieved by other means.
|
|
| 8. |
- Kalliara, Eirini, et al.
(författare)
-
Spatially Guided and Single Cell Tools to Map the Microenvironment in Cutaneous T-Cell Lymphoma
- 2023
-
Ingår i: Cancers. - 2072-6694. ; 15:8, s. 1-15
-
Tidskriftsartikel (refereegranskat)abstract
- Mycosis fungoides (MF) and Sézary syndrome (SS) are two closely related clinical variants of cutaneous T-cell lymphomas (CTCL). Previously demonstrated large patient-to-patient and intra-patient disease heterogeneity underpins the importance of personalized medicine in CTCL. Advanced stages of CTCL are characterized by dismal prognosis, and the early identification of patients who will progress remains a clinical unmet need. While the exact molecular events underlying disease progression are poorly resolved, the tumor microenvironment (TME) has emerged as an important driver. In particular, the Th1-to-Th2 shift in the immune response is now commonly identified across advanced-stage CTCL patients. Herein, we summarize the role of the TME in CTCL evolution and the latest studies in deciphering inter- and intra-patient heterogeneity. We introduce spatially resolved omics as a promising technology to advance immune-oncology efforts in CTCL. We propose the combined implementation of spatially guided and single-cell omics technologies in paired skin and blood samples. Such an approach will mediate in-depth profiling of phenotypic and molecular changes in reactive immune subpopulations and malignant T cells preceding the Th1-to-Th2 shift and reveal mechanisms underlying disease progression from skin-limited to systemic disease that collectively will lead to the discovery of novel biomarkers to improve patient prognostication and the design of personalized treatment strategies.
|
|
