| 1. |
- Moberg, Christina, et al.
(författare)
-
De unga gör helt rätt när de stämmer staten
- 2022
-
Ingår i: Aftonbladet. - 1103-9000.
-
Tidskriftsartikel (populärvet., debatt m.m.)abstract
- 1 620 forskare och lärare i forskarvärlden: Vi ställer oss bakom Auroras klimatkrav
|
|
| 2. |
|
|
| 3. |
|
|
| 4. |
- Tesi, Bianca, et al.
(författare)
-
Diagnostic yield and clinical impact of germline sequencing in children with CNS and extracranial solid tumors : a nationwide, prospective Swedish study
- 2024
-
Ingår i: The Lancet Regional Health. - : Elsevier. - 2666-7762. ; 39
-
Tidskriftsartikel (refereegranskat)abstract
- BackgroundChildhood cancer predisposition (ChiCaP) syndromes are increasingly recognized as contributing factors to childhood cancer development. Yet, due to variable availability of germline testing, many children with ChiCaP might go undetected today. We report results from the nationwide and prospective ChiCaP study that investigated diagnostic yield and clinical impact of integrating germline whole-genome sequencing (gWGS) with tumor sequencing and systematic phenotyping in children with solid tumors.MethodsgWGS was performed in 309 children at diagnosis of CNS (n = 123, 40%) or extracranial (n = 186, 60%) solid tumors and analyzed for disease-causing variants in 189 known cancer predisposing genes. Tumor sequencing data were available for 74% (227/309) of patients. In addition, a standardized clinical assessment for underlying predisposition was performed in 95% (293/309) of patients.FindingsThe prevalence of ChiCaP diagnoses was 11% (35/309), of which 69% (24/35) were unknown at inclusion (diagnostic yield 8%, 24/298). A second-hit and/or relevant mutational signature was observed in 19/21 (90%) tumors with informative data. ChiCaP diagnoses were more prevalent among patients with retinoblastomas (50%, 6/12) and high-grade astrocytomas (37%, 6/16), and in those with non-cancer related features (23%, 20/88), and ≥2 positive ChiCaP criteria (28%, 22/79). ChiCaP diagnoses were autosomal dominant in 80% (28/35) of patients, yet confirmed de novo in 64% (18/28). The 35 ChiCaP findings resulted in tailored surveillance (86%, 30/35) and treatment recommendations (31%, 11/35).InterpretationOverall, our results demonstrate that systematic phenotyping, combined with genomics-based diagnostics of ChiCaP in children with solid tumors is feasible in large-scale clinical practice and critically guides personalized care in a sizable proportion of patients.
|
|
| 5. |
- Tesi, Bianca, et al.
(författare)
-
Diagnostic yield and clinical impact of germline sequencing in children with CNS and extracranial solid tumors : a nationwide, prospective Swedish study
- 2024
-
Ingår i: The Lancet Regional Health. - : Elsevier. - 2666-7762. ; 39
-
Tidskriftsartikel (refereegranskat)abstract
- Background: Childhood cancer predisposition (ChiCaP) syndromes are increasingly recognized as contributing factors to childhood cancer development. Yet, due to variable availability of germline testing, many children with ChiCaP might go undetected today. We report results from the nationwide and prospective ChiCaP study that investigated diagnostic yield and clinical impact of integrating germline whole-genome sequencing (gWGS) with tumor sequencing and systematic phenotyping in children with solid tumors.Methods: gWGS was performed in 309 children at diagnosis of CNS (n = 123, 40%) or extracranial (n = 186, 60%) solid tumors and analyzed for disease-causing variants in 189 known cancer predisposing genes. Tumor sequencing data were available for 74% (227/309) of patients. In addition, a standardized clinical assessment for underlying predisposition was performed in 95% (293/309) of patients.Findings: The prevalence of ChiCaP diagnoses was 11% (35/309), of which 69% (24/35) were unknown at inclusion (diagnostic yield 8%, 24/298). A second-hit and/or relevant mutational signature was observed in 19/21 (90%) tumors with informative data. ChiCaP diagnoses were more prevalent among patients with retinoblastomas (50%, 6/12) and high-grade astrocytomas (37%, 6/16), and in those with non-cancer related features (23%, 20/88), and ≥2 positive ChiCaP criteria (28%, 22/79). ChiCaP diagnoses were autosomal dominant in 80% (28/35) of patients, yet confirmed de novo in 64% (18/28). The 35 ChiCaP findings resulted in tailored surveillance (86%, 30/35) and treatment recommendations (31%, 11/35).Interpretation: Overall, our results demonstrate that systematic phenotyping, combined with genomics-based diagnostics of ChiCaP in children with solid tumors is feasible in large-scale clinical practice and critically guides personalized care in a sizable proportion of patients.Funding: The study was supported by the Swedish Childhood Cancer Fund and the Ministry of Health and Social Affairs.
|
|
| 6. |
- Thor, Anna, et al.
(författare)
-
Primary retroperitoneal lymph node dissection as treatment for low-volume metastatic seminoma in a population-based cohort : the Swedish Norwegian testicular cancer group experience
- 2024
-
Ingår i: European Urology Open Science. - : Elsevier. - 2666-1691 .- 2666-1683. ; 65, s. 13-19
-
Tidskriftsartikel (refereegranskat)abstract
- Background and objective: There is an unmet need to avoid long-term morbidity associated with standard cytotoxic treatment for low-volume metastatic seminoma. Our aim was to assess the oncological efficacy and surgical safety of retroperitoneal lymph node dissection (RPLND) as treatment in a population-based cohort of metastatic seminoma patients with limited retroperitoneal lymphadenopathy.Methods: Sixty-two seminoma patients in Norway and Sweden were included in the cohort from 2019 to 2022. Patients with lymphadenopathy ≤3 cm, having primary clinical stage (CS) IIA/B or CS I with a relapse, were operated with uni- or bilateral template RPLND, open or robot assisted. The outcome measures included surgical complications as per Clavien-Dindo, and Kaplan-Meier survival estimates for 24-mo progression-free survival (PFS) and overall survival (OS).Key findings and limitations: In the cohort, 33 (53%) had CS I with a relapse during surveillance, six (10%) CS I with a relapse following adjuvant chemotherapy, and 23 (37%) initial CS IIA/B. Metastatic seminoma was verified in 58 patients (94%) with a median largest diameter of 18 mm (interquartile range [IQR] 13–24). Robot-assisted RPLND was performed in 40 patients (65%). Clavien-Dindo III complications were observed in three patients (5%); no grade ≥IV complications occurred. Eighteen patients (29%) received adjuvant chemotherapy after surgery. The median follow-up was 23 mo (IQR 16–30), and recurrence occurred in six patients (10%) after a median of 8 mo (IQR 4–14). PFS was 90% (95% confidence interval: 0.86–1) and OS was 100% at 24 mo.Conclusions and clinical implications: RPLND as primary treatment is an option for selected low-stage seminomas with a limited burden of disease, showing low complications and low relapse rates, with the potential to reduce long-term morbidity.Patient summary: In seminoma patients with limited metastatic spread, surgery is a treatment option offering an alternative to chemotherapy or radiation. This paper covers the first 62 patients operated in Norway and Sweden.
|
|
| 7. |
- Fagerlind Ståhl, Anna-Carin, et al.
(författare)
-
Longitudinal association between psychological demands and burnout for employees experiencing a high versus a low degree of job resources
- 2018
-
Ingår i: BMC Public Health. - : BMC. - 1471-2458. ; 18
-
Tidskriftsartikel (refereegranskat)abstract
- Background: Exhaustion and burnout are common causes for sickness absence. This study examines the relationship between psychological demands and burnout over time, and if environmental support modifies the longitudinal relationship between psychological demands and burnout at baseline, with burnout measured 2 years subsequently. Methods: A questionnaire was sent to employees in seven Swedish organizations in 2010-2012 with follow-up after 2 years, n = 1722 responded (64%). Linear regressions were used to examine the associations between burnout and psychological demands at baseline and burnout at follow-up. Stratified regression models examined if relationships between burnout and psychological demands at baseline on burnout at follow-up differed for employees in supportive versus unsupportive work environments. Results: Burnout and psychological demands at baseline were associated with burnout at follow-up, after adjustment for study covariates. No significant differences were observed between estimates for psychological demands and burnout among respondents in supportive work environments versus those in unsupportive work environments. Conclusions: This study shows that high demands are associated with greater risk of burnout, regardless of level of other work supports. This has implications for prevention of sick leave due to burnout and for rehabilitation, where demands such as work pace, workload and conflicting demands at work may need to be reduced.
|
|
| 8. |
- Gerdtsson, Axel, et al.
(författare)
-
Initial surveillance in men with marker negative clinical stage IIA non-seminomatous germ cell tumours
- 2024
-
Ingår i: BJU INTERNATIONAL. - : John Wiley & Sons. - 1464-4096 .- 1464-410X.
-
Tidskriftsartikel (refereegranskat)abstract
- Objectives To assess whether extended surveillance with repeated computed tomography (CT) scans for patients with clinical stage IIA (CS IIA; <2 cm abdominal node involvement) and negative markers (Mk-) non-seminomatous germ cell tumours (NSGCTs) can identify those with true CS I. To assess the rate of benign lymph nodes, teratoma, and viable cancer in retroperitoneal lymph node dissection (RPLND) histopathology for patients with CS IIA Mk- NSGCT. Patients and methods Observational prospective population-based study of patients diagnosed 2008-2019 with CS IIA Mk- NSGCT in the Swedish and Norwegian Testicular Cancer Group (SWENOTECA) registry. Patients were managed with surveillance, with CT scans, and tumour markers every sixth week for a maximum of 18 weeks. Patients with radiological regression were treated as CS I, if progression with chemotherapy, and remaining CS IIA Mk- disease with RPLND. The end-point was the number and percentage of patients down-staged to CS I on surveillance and rate of RPLND histopathology presented as benign, teratoma, or viable cancer. Results Overall, 126 patients with CS IIA Mk- NSGCT were included but 41 received therapy upfront. After surveillance for a median (range) of 6 (6-18) weeks, 23/85 (27%) patients were in true CS I and four (5%) progressed. Of the remaining 58 patients with lasting CS IIA Mk- NSGCT, 16 received chemotherapy and 42 underwent RPLND. The RPLND histopathology revealed benign lymph nodes in 11 (26%), teratoma in two (6%), and viable cancer in 29 (70%) patients. Conclusions Surveillance with repeated CT scans can identify patients in true CS I, thus avoiding overtreatment. The RPLND histopathology in patients with CS IIA Mk- NSGCT had a high rate of cancer and a low rate of teratoma.
|
|
| 9. |
- Gerdtsson, Axel, et al.
(författare)
-
Unilateral or Bilateral Retroperitoneal Lymph Node Dissection in Nonseminoma Patients with Postchemotherapy Residual Tumour? Results from RETROP, a Population-based Mapping Study by the Swedish Norwegian Testicular Cancer Group
- 2022
-
Ingår i: European Urology Oncology. - : Elsevier BV. - 2588-9311. ; 5:2, s. 235-243
-
Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: The distribution of retroperitoneal lymph node metastases for patients with nonseminoma and a residual tumour of 10-49 mm in a population-based setting is unknown. This information is needed to justify selection of patients for a unilateral template resection. OBJECTIVE: To describe the location of retroperitoneal metastases and recurrences in patients with nonseminoma germ cell tumour (NSGCT) with a residual tumour of 10-49 mm. DESIGN, SETTING, AND PARTICIPANTS: RETROP is a population-based prospective observational mapping study of 213 patients in Sweden and Norway with a retroperitoneal residual tumour of 10-49 mm who underwent postchemotherapy retroperitoneal lymph node dissection for metastatic NSGCT during 2007-2014 with median follow-up of 100 mo. Patients were classified according to the testis primary tumour and the distribution of unilateral or bilateral lymph node metastases (with reference to the aorta) present on pre- and/or postchemotherapy computed tomography (CT) scans. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The distribution and rate of teratoma or cancer in unilateral or bilateral retroperitoneal fields and the location and rate of retroperitoneal recurrence were measured. RESULTS AND LIMITATIONS: In total, 65% of the patients had unilateral retroperitoneal lymph node metastases (RLNMs) on CT scans. Patients with unilateral RLNMs had a low risk of contralateral teratoma or cancer (1.6% for right- and 2.6% for left-sided NSGCT) or retroperitoneal recurrence (0% for right- and 4% for left-sided NSGCT). A weakness of the study is that the pathology specimen could not be fully designated to one specific area for some of the patients. CONCLUSIONS: Men with postchemotherapy residual disease of 10-49 mm and unilateral metastases on pre- and postchemotherapy CT scans have a low risk of contralateral disease and should be considered for a unilateral template resection. PATIENT SUMMARY: The surgeon can use computed tomography (CT) scans in deciding on the extent of lymph node dissection in patients with testicular cancer.
|
|
| 10. |
- Höök, Kristina, et al.
(författare)
-
Design Processes for Bodily Interaction
- 2010
-
Ingår i: At the workshop Artifacts in Design: Representation, Ideation, and Process, CHI, Atlanda, USA, April 2010.. - : ACM Press.
-
Konferensbidrag (övrigt vetenskapligt/konstnärligt)
|
|
| 11. |
- Leitao, Charles Dahlsson, et al.
(författare)
-
Conditionally activated affibody-based prodrug targeting EGFR demonstrates improved tumor selectivity
-
Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- Safety and efficacy of cancer-targeting treatments can be improved by conditional activation conferred by the distinct milieu of the tumour microenvironment. Proteases are intricately involved in tumorigenesis and commonly dysregulated with elevated expression and activity. Design of prodrug molecules with protease-dependent activation has the potential to increase tumor-selective targeting, while decreasing the exposure to healthy tissues, thus improving safety, allowing for administration of higher doses or use of more aggressive treatment options, leading to higher therapeutic efficacy. We have previously performed in vitro characterizations of an affibody-based prodrug approach for protease-mediated targeting of EGFR. In this study we demonstrate the potential for selective tumor-targeting and shielded uptake in healthy tissues in vivo using tumor-bearing mice for an EGFR-targeting affibody prodrug.
|
|
| 12. |
- Leitao, Charles Dahlsson, 1992-, et al.
(författare)
-
Conditionally activated affibody-based prodrug targeting EGFR demonstrates improved tumour selectivity
- 2023
-
Ingår i: Journal of Controlled Release. - : Elsevier BV. - 0168-3659 .- 1873-4995. ; 357, s. 185-195
-
Tidskriftsartikel (refereegranskat)abstract
- Safety and efficacy of cancer-targeting treatments can be improved by conditional activation enabled by the distinct milieu of the tumour microenvironment. Proteases are intricately involved in tumourigenesis and commonly dysregulated with elevated expression and activity. Design of prodrug molecules with protease -dependent activation has the potential to increase tumour-selective targeting while decreasing exposure to healthy tissues, thus improving the safety profile for patients. Higher selectivity could also allow for adminis-tration of higher doses or use of more aggressive treatment options, leading to higher therapeutic efficacy. We have previously developed an affibody-based prodrug with conditional targeting of EGFR conferred by an anti-idiotypic affibody masking domain (ZB05). We could show that binding to endogenous EGFR on cancer cells in vitro was restored following proteolytic removal of ZB05. In this study we evaluate a novel affibody-based pro -drug design, which incorporates a protease substrate sequence recognized by cancer-associated proteases and demonstrate the potential of this approach for selective tumour-targeting and shielded uptake in healthy tissues in vivo using tumour-bearing mice. This may widen the therapeutic index of cytotoxic EGFR-targeted thera-peutics by decreasing side effects, improving selectivity of drug delivery, and enabling the use of more potent cytotoxic drugs.
|
|
| 13. |
- Lindell, Lina, 1977-, et al.
(författare)
-
Journey to the destination: a circular tourism economy : a training program for the hospitality industry to facilitate a transition towards increased circularity in the South Baltic Region
- 2019
-
Rapport (övrigt vetenskapligt/konstnärligt)abstract
- Being aware of the extent of the tourism industry and that it is ever growing, which is also encouraged in many individual countries by the national and regional governments, it is evident that the tourism industry is an essential target group for introducing circular concepts and implementing circular solutions. Yet, this sector has so far received little attention in the literature and initiatives on circularity.Circular Economy (CE) goes beyond “green” or “environmental”, it includes all aspects of a community and challenges us to create solutions that are completely different from what we are used to. It also invites us to open up and interact with other stakeholders and the general public.In your hands is the first training material in circular economy specifically developed for small to medium sized companies of the tourism industry in the South Baltic Region. It is a small but important step in the direction towards circularity and a wellbeing society. Through this work we have shown that despite cultural challenges and regional differences there is a shared, common interest in making tourism more sustainable and even to work together towards a transformation of the hospitality industry. This common vision has been stronger than the challenges we faced in making this work and this is what will ensure the continued growing awareness on circularity and its integration in different sectors in our communities. In this work we have featured some of the groundbreaking experts in this field, and some of the first good practices from our regions. They are all courageous pioneers in a field that with time will become the norm. In fact, in the 10th Annual Forum of the EU strategy for the Baltic Sea Region (12-13/6/2019, Gdansk, Poland), CE was highlighted as the pathway to reach prosperity and wellbeing in the Baltic Sea Region.
|
|
| 14. |
- Olofsson, Sven-Erik, et al.
(författare)
-
Population-Based Study of Treatment Guided by Tumor Marker Decline in Patients With Metastatic Nonseminomatous Germ Cell Tumor : A Report From the Swedish-Norwegian Testicular Cancer Group
- 2011
-
Ingår i: Journal of Clinical Oncology. - 0732-183X .- 1527-7755. ; 29:15, s. 2032-2039
-
Tidskriftsartikel (refereegranskat)abstract
- Purpose From 1995 to 2003, 603 adult patients from Sweden and Norway with metastatic testicular nonseminomatous germ cell tumor (NSGCT) were included prospectively in a population-based protocol with strict guidelines for staging, treatment, and follow-up. Patients with extragonadal primary tumor or previous treatment for contralateral testicular tumor were excluded. The basic strategy was to individualize treatment according to initial tumor marker response. Methods Initial treatment for all patients was two courses of standard bleomycin, etoposide, and cisplatin (BEP), with tumor markers analyzed weekly. Good response was defined as a half-life (t(1/2)) for alpha-fetoprotein (AFP) of <= 7 days and/or for beta-human chorionic gonadotropin (beta-HCG) of <= 3 days. Patients with prolonged marker t(1/2) (ie, poor response) received intensification with addition of ifosfamide (BEP-if/PEI) in step 1. If poor response continued, the treatment was intensified with high-dose chemotherapy with stem-cell rescue as step 2. Results Overall, 99% of all patients with metastatic testicular NSGCT in the population were included in the protocol. Median follow-up was 8.2 years. Seventy-seven percent of the patients were treated with BEP alone; 18% received intensification step 1%, and 5% received intensification step 2. Grouped according to International Germ Cell Consensus Classification, 10-year overall survival was 94.7% in good-prognosis patients, 90.0% in intermediate-prognosis patients, and 67.4% in poor-prognosis patients. Conclusion With detailed treatment protocols and a dedicated collaborative group of specialists, treatment results comparable to those reported from large single institutions can be achieved at national level. With the treatment principles used in Swedish-Norwegian Testicular Cancer Group study SWENOTECA IV, the survival of intermediate-prognosis patients is remarkable and close to that of good-prognosis patients.
|
|
| 15. |
|
|
| 16. |
- Rinne, Sara S., et al.
(författare)
-
Targeting Tumor Cells Overexpressing the Human Epidermal Growth Factor Receptor 3 with Potent Drug Conjugates Based on Affibody Molecules
- 2022
-
Ingår i: Biomedicines. - : MDPI AG. - 2227-9059. ; 10:6
-
Tidskriftsartikel (refereegranskat)abstract
- Increasing evidence suggests that therapy targeting the human epidermal growth factor receptor 3 (HER3) could be a viable route for targeted cancer therapy. Here, we studied a novel drug conjugate, ZHER3-ABD-mcDM1, consisting of a HER3-targeting affibody molecule, coupled to the cytotoxic tubulin polymerization inhibitor DM1, and an albumin-binding domain for in vivo half-life extension. ZHER3-ABD-mcDM1 showed a strong affinity to the extracellular domain of HER3 (K-D 6 nM), and an even stronger affinity (KD 0.2 nM) to the HER3-overexpressing pancreatic carcinoma cell line, BxPC-3. The drug conjugate showed a potent cytotoxic effect on BxPC-3 cells with an IC50 value of 7 nM. Evaluation of a radiolabeled version, [99mTc]Tc-ZHER3-ABD-mcDM1, showed a relatively high rate of internalization, with a 27% internalized fraction after 8 h. Further in vivo evaluation showed that it could target BxPC-3 (pancreatic carcinoma) and DU145 (prostate carcinoma) xenografts in mice, with an uptake peaking at 6.3 +/- 0.4% IA/g at 6 h post-injection for the BxPC-3 xenografts. The general biodistribution showed uptake in the liver, lung, salivary gland, stomach, and small intestine, organs known to express murine ErbB3 naturally. The results from the study show that ZHER3-ABD-mcDM1 is a highly potent and selective drug conjugate with the ability to specifically target HER3 overexpressing cells. Further pre-clinical and clinical development is discussed.
|
|
| 17. |
- Ståhl, Göran, et al.
(författare)
-
National inventory of landscapes in Sweden (NILS) : scope, design, and experiences from establishing a multi-scale biodiversity monitoring system
- 2011
-
Ingår i: Environmental Monitoring & Assessment. - : Springer Science and Business Media LLC. - 0167-6369 .- 1573-2959. ; 173:1-4, s. 579-595
-
Tidskriftsartikel (refereegranskat)abstract
- The landscape-level and multiscale biodiversity monitoring program National Inventory of Landscapes in Sweden (NILS) was launched in 2003. NILS is conducted as a sample-based stratified inventory that acquires data across several spatial scales, which is accomplished by combining aerial photo interpretation with field inventory. A total of 631 sample units are distributed across the land base of Sweden, of which 20% are surveyed each year. By 2007 NILS completed the first 5-year inventory phase. As the reinventory in the second 5-year phase (2008-2012) proceeds, experiences and insights accumulate and reflections are made on the setup and accomplishment of the monitoring scheme. In this article, the emphasis is placed on background, scope, objectives, design, and experiences of the NILS program. The main objective to collect data for and perform analyses of natural landscape changes, degree of anthropogenic impact, prerequisites for natural biological diversity and ecological processes at landscape scale. Different environmental conditions that can have direct or indirect effects on biological diversity are monitored. The program provides data for national and international policy and offers an infrastructure for other monitoring program and research projects. NILS has attracted significant national and international interest during its relatively short time of existence; the number of stakeholders and cooperation partners steadily increases. This is constructive and strengthens the incentive for the multiscale monitoring approach.
|
|
| 18. |
- Tandstad, Torgrim, et al.
(författare)
-
Management of Seminomatous Testicular Cancer : A Binational Prospective Population-Based Study From the Swedish Norwegian Testicular Cancer Study Group
- 2011
-
Ingår i: Journal of Clinical Oncology. - 0732-183X .- 1527-7755. ; 29:6, s. 719-725
-
Tidskriftsartikel (refereegranskat)abstract
- Purpose: A binational, population-based treatment protocol was established to prospectively treat and follow patients with seminomatous testicular cancer. The aim was to standardize care for all patients with seminoma to further improve the good results expected for this disease. Patients and Methods From 2000 to 2006, a total of 1,384 Norwegian and Swedish patients were included in the study. Treatment in clinical stage 1 (CS1) was surveillance, adjuvant radiotherapy, or adjuvant carboplatin. In metastatic disease, recommended treatment was radiotherapy in CS2A and cisplatin-based chemotherapy in CS2B or higher. Results At a median follow-up of 5.2 years, 5-year cause-specific survival was 99.6%. In CS1, 14.3% (65 of 512) of patients relapsed following surveillance, 3.9% (seven of 188) after carboplatin, and 0.8% (four of 481) after radiotherapy. We could not identify any factors predicting relapse in CS1 patients who were subjected to surveillance only. In CS2A, 10.9% (three of 29) patients relapsed after radiotherapy compared with no relapses in CS2A/B patients (zero of 73) treated with chemotherapy (P = .011). Conclusion An international, population-based treatment protocol for testicular seminoma is feasible with excellent results. Surveillance remains a good option for CS1 patients. No factors predicted relapse in CS1 patients on surveillance. Despite resulting in a lower rate of relapse than with adjuvant carboplatin, adjuvant radiotherapy has been abandoned in the Swedish and Norwegian Testicular Cancer Project (SWENOTECA) as a recommended treatment option because of concerns of induction of secondary cancers. The higher number of relapses in radiotherapy-treated CS2A patients when compared with chemotherapy-treated CS2A/B patients is of concern. Late toxicity of cisplatin-based chemotherapy versus radiotherapy must be considered in CS2A patients.
|
|
| 19. |
- Tandstad, T., et al.
(författare)
-
One course of adjuvant BEP in clinical stage I nonseminoma mature and expanded results from the SWENOTECA group
- 2014
-
Ingår i: Annals of Oncology. - : Elsevier BV. - 0923-7534 .- 1569-8041. ; 25:11, s. 2167-2172
-
Tidskriftsartikel (refereegranskat)abstract
- The SWENOTECA group treated 517 clinical stage I nonseminoma patients with one course of adjuvant BEP in a prospective study. The median follow-up is 7.9 years. One course of adjuvant BEP reduced the risk of relapse by over 90%. The relapse rates were 1.6% in low-risk disease and 3.2% in high-risk disease. One course of adjuvant BEP should be considered a standard adjuvant treatment option.SWENOTECA has since 1998 offered patients with clinical stage I (CS I) nonseminoma, adjuvant chemotherapy with one course of bleomycin, etoposide and cisplatin (BEP). The aim has been to reduce the risk of relapse, sparing patients the need of toxic salvage treatment. Initial results on 312 patients treated with one course of adjuvant BEP, with a median follow-up of 4.5 years, have been previously published. We now report mature and expanded results. In a prospective, binational, population-based risk-adapted treatment protocol, 517 Norwegian and Swedish patients with CS I nonseminoma received one course of adjuvant BEP. Patients with lymphovascular invasion (LVI) in the primary testicular tumor were recommended one course of adjuvant BEP. Patients without LVI could choose between surveillance and one course of adjuvant BEP. Data for patients receiving one course of BEP are presented in this study. At a median follow-up of 7.9 years, 12 relapses have occurred, all with IGCCC good prognosis. The latest relapse occurred 3.3 years after adjuvant treatment. The relapse rate at 5 years was 3.2% for patients with LVI and 1.6% for patients without LVI. Five-year cause-specific survival was 100%. The updated and expanded results confirm a low relapse rate following one course of adjuvant BEP in CS I nonseminoma. One course of adjuvant BEP should be considered a standard treatment in CS I nonseminoma with LVI. For patients with CS I nonseminoma without LVI, one course of adjuvant BEP is also a treatment option.
|
|
| 20. |
|
|
| 21. |
- Adolfsson, Margareta, 1950-, et al.
(författare)
-
Participation as the Focus of Intervention: Cultural Diversity and Universal Characteristics
- 2011
-
Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- Participation as a construct can be applied on all ecological levels from participation for individual children in their everyday life to participation for all as a societal goal. It is defined in the ICF-CY as involvement in a life situation. Participation is occurring at the nodal point between children and their environments. Contexts vary with socio-economical standards, culture and geographical characteristics and thus also the expressions of participation. This presentation will discuss cultural diversity in children’s participation in relation to the universal characteristics of participation defined as “being there” and participation defined as “degree of engagement while being there”. The utility of the ICF-CY as a tool to analyze universal characteristics and cultural diversity in conditions for, and actual experiences of, participation are examined in findings from five studies: 1) Maxwell et al. have analyzed national, regional and local educational policy documents in Scotland and Sweden regarding children in need of special support in relation to conditions for participation and participation; 2) Ståhl et al. have linked and compared ICF-CY codes to information regarding children’s health in Child Health Care and School Health Care and analyzed whether biomedical or participation information is the focus of the information; 3) Adolfsson et al. have collected and compared data from respondents in Sweden, the USA, and Portugal concerning what professionals consider to be important everyday situations for child participation; 4) Klang et al. has studied domains of participation and environment related to child and caregiver interaction in a Russian context to identify factors related to participation; and 5) Ullenhag et al. have studied participation in leisure activities and leisure activity preferences of Swedish children and compared with data from the Netherlands and Canada using the same questionnaire.
|
|
| 22. |
- Albertsson, Anna-Karin, et al.
(författare)
-
PLUS Borås : Om professionsutveckling och dokumentation
- 2009
-
Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- PLUS betyder Projekt för Läsutveckling, Utvärdering och Samverkan. Det handlar om lässtimulerande arbete bland barn från nyfödd upp till 16 år och omfattar alltså alla barn- och skolbibliotekarier i Borås. Folkbiblioteken i Borås består av Stadsbiblioteket och nio kommundelsbibliotek. I kommundelarna är skol- och folkbiblioteken samorganiserade eller i nära samverkan. Samtliga högstadieskolor och flera låg- och mellanstadieskolor har fackutbildade bibliotekarier. Alla folkbiblioteksenheter har barnbibliotekarietjänster. Stadsbiblioteket ansvarar för att barnbibliotekarier och skolbibliotekarier träffas regelbundet i sina respektive nätverk. Läsfrämjande arbete bedrivs på alla bibliotek, drygt trettio personer arbetar med det på varsitt håll. Det finns mycket kunskap och gedigen erfarenhet men tid för reflektion och bollande med idéer för inspiration och metodikutveckling är mycket begränsad. Idéer till projektets innehåll baseras i strävan att knyta alla bibliotekarier som arbetar med språk- och läsutvecklingen till en gemensam bas och därmed skapa förutsättningar för ett utvecklingsarbete i hela kommunen.
|
|
| 23. |
- Allard, Anna, et al.
(författare)
-
Demands on monitoring
- 2023
-
Ingår i: Monitoring Biodiversity : Combining Environmental and Social Data. - London : Routledge. - 9781032015934 ; , s. 34-58
-
Bokkapitel (refereegranskat)abstract
- This chapter provides a short overview of the types of processes for reporting as well as legislation that governs why and how monitoring is undertaken and some of the ways in which stakeholders are involved at different levels. Because monitoring for the policy side is, by default, mandated monitoring, this type becomes the focus of this chapter, while noting that many policies and legislation may have been prompted by the results of question-driven monitoring, pointing out areas of concern. In fact, the iterative process of monitoring, analysis, and reporting to a government that, in turn, changes the policies to better fit concerns or issues needing addressing can be seen as a co-development.Whereas the previous chapter illustrated what monitoring is, this chapter illustrates some of the demands on monitoring in legislation and policy, where they outline what monitoring is asked to contribute. The chapter reviews legislation on the global scene, on the community level of the European Union, and at national levels in the areas of water bodies and semi-aquatic, agricultural, urban, and forested semi-natural or natural landscapes.
|
|
| 24. |
- Allard, Anna, et al.
(författare)
-
INSTRUKTION FÖR BILDTOLKNINGSARBETET VID NATIONELL INVENTERING AV LANDSKAPET I SVERIGE NILS ÅR 2003
- 2003
-
Rapport (övrigt vetenskapligt/konstnärligt)abstract
- Denna manual är utarbetad för att användas vid flygbildstolkningsarbetet inom det nationella miljöövervakningsprogrammet Nationell Inventering av Landskapet i Sverige (NILS). NILS är en del av Naturvårdsverkets nationella miljöövervakning och omfattar alla landmiljöer – jordbruksmark, våtmark, bebyggd miljö, skogmark, kust och fjäll. Operativt drivs programmet av Sveriges lantbruksuniversitet, Institutionen för skoglig resurshushållning och geomatik i Umeå. Manualen är framtagen som en del i metodutvecklingsarbetet med NILS. Förutom författarna till manualen har ett stort antal personer bidragit med synpunkter och delar av texten. Ett stort tack till Per-Anders Esseen, Anders Glimskär, Mats Högström, Per Löfgren, Ronny Löfstrand och Anki Weibull från Sveriges Lantbruksuniversitet samt Margareta Ihse Stockholms Universitet, Ola Inghe Naturvårdsverket, Anneli Mattisson Länsstyrelsen i Stockholm och Sture Westerberg Länsstyrelsen i Norrbotten. Manualen inleds med en beskrivning av NILS-programmet och en översiktlig beskrivning hur inventeringen är uppbyggd. Därefter följer en mer detaljerad beskrivning av flygbildstolkningsarbetet. I slutet av manualen finns tolkningsinstruktioner och definitioner på olika begrepp som används i tolkningsarbetet.
|
|
| 25. |
|
|
| 26. |
- Allard, Anna, et al.
(författare)
-
Manual for Aerial Photo Interpretation in the National Inventory of Landscapes in Sweden : NILS
- 2003
-
Rapport (övrigt vetenskapligt/konstnärligt)abstract
- This manual is developed for the aerial photo interpretation work within the Swedish monitoring programme National Inventory of Landscapes in Sweden (NILS).NILS is a part of the national environmental monitoring activities of the Swedish Environmental Protection Agency (EPA) and includes all terrestrial environments – agricultural lands, wetlands, urban environments, forests, and coastal and alpine areas. Operationally, the programme is conducted by the Swedish University of Agricultural Sciences, Department of Forest Resource Management and Geomatics in Umeå.The manual is prepared as part of the methodology development work within NILS. In addition to the authors, some external reviewers have given their comments on the text and also contributed with material. Special thanks to Per-Anders Esseen, Anders Glimskär, Mats Högström, Per Löfgren, Ronny Löfstrand, Anki Weibull (all from the Swedish University of Agricultural Sciences), Margareta Ihse (Stockholm University) Ola Inghe (Swedish Environmental Protection Agency), Anneli Mattisson (County of Stockholm), and Sture Westerberg (County of Norrbotten). We would also like to thank Ylva melin and Heather Reese for the translation work to the English language.Following this introduction, the manual describes the NILS programme and outlines the structure of the inventory. This is followed by a detailed description of how the aerial photo interpretation is performed. Finally, instructions and definitions for the interpretation work are given. Some of the figures are mad in Swedish, but explanatory texts are given to the figures.
|
|
| 27. |
- Altai, Mohamed, et al.
(författare)
-
188Re-ZHER2:V2, a promising affibody-based targeting agent against HER2-expressing tumors : preclinical assessment
- 2014
-
Ingår i: Journal of nuclear medicine : official publication, Society of Nuclear Medicine. - : Society of Nuclear Medicine. - 0161-5505 .- 1535-5667 .- 2159-662X. ; 55:11, s. 8-1842
-
Tidskriftsartikel (refereegranskat)abstract
- UNLABELLED: Affibody molecules are small (7 kDa) nonimmunoglobulin scaffold proteins with favorable tumor-targeting properties. Studies concerning the influence of chelators on biodistribution of (99m)Tc-labeled Affibody molecules demonstrated that the variant with a C-terminal glycyl-glycyl-glycyl-cysteine peptide-based chelator (designated ZHER2:V2) has the best biodistribution profile in vivo and the lowest renal retention of radioactivity. The aim of this study was to evaluate (188)Re-ZHER2:V2 as a potential candidate for radionuclide therapy of human epidermal growth factor receptor type 2 (HER2)-expressing tumors.METHODS: ZHER2:V2 was labeled with (188)Re using a gluconate-containing kit. Targeting of HER2-overexpressing SKOV-3 ovarian carcinoma xenografts in nude mice was studied for a dosimetry assessment.RESULTS: Binding of (188)Re-ZHER2:V2 to living SKOV-3 cells was demonstrated to be specific, with an affinity of 6.4 ± 0.4 pM. The biodistribution study showed a rapid blood clearance (1.4 ± 0.1 percentage injected activity per gram [%ID/g] at 1 h after injection). The tumor uptake was 14 ± 2, 12 ± 2, 5 ± 2, and 1.8 ± 0.5 %IA/g at 1, 4, 24, and 48 h after injection, respectively. The in vivo targeting of HER2-expressing xenografts was specific. Already at 4 h after injection, tumor uptake exceeded kidney uptake (2.1 ± 0.2 %IA/g). Scintillation-camera imaging showed that tumor xenografts were the only sites with prominent accumulation of radioactivity at 4 h after injection. Based on the biokinetics, a dosimetry evaluation for humans suggests that (188)Re-ZHER2:V2 would provide an absorbed dose to tumor of 79 Gy without exceeding absorbed doses of 23 Gy to kidneys and 2 Gy to bone marrow. This indicates that future human radiotherapy studies may be feasible.CONCLUSION: (188)Re-ZHER2:V2 can deliver high absorbed doses to tumors without exceeding kidney and bone marrow toxicity limits.
|
|
| 28. |
- Altai, Mohamed, et al.
(författare)
-
Influence of Molecular Design on the Targeting Properties of ABD-Fused Mono- and Bi-Valent Anti-HER3 Affibody Therapeutic Constructs
- 2018
-
Ingår i: Cells. - : MDPI AG. - 2073-4409. ; 7:10
-
Tidskriftsartikel (refereegranskat)abstract
- Overexpression of human epidermal growth factor receptor type 3 (HER3) is associated with tumour cell resistance to HER-targeted therapies. Monoclonal antibodies (mAbs) targeting HER3 are currently being investigated for treatment of various types of cancers. Cumulative evidence suggests that affibody molecules may be appropriate alternatives to mAbs. We previously reported a fusion construct (3A3) containing two HER3-targeting affibody molecules flanking an engineered albumin-binding domain (ABD 035) included for the extension of half-life in circulation. The 3A3 fusion protein (19.7 kDa) was shown to delay tumour growth in mice bearing HER3-expressing xenografts and was equipotent to the mAb seribantumab. Here, we have designed and explored a series of novel formats of anti-HER3 affibody molecules fused to the ABD in different orientations. All constructs inhibited heregulin-induced phosphorylation in HER3-expressing BxPC-3 and DU-145 cell lines. Biodistribution studies demonstrated extended the half-life of all ABD-fused constructs, although at different levels. The capacity of our ABD-fused proteins to accumulate in HER3-expressing tumours was demonstrated in nude mice bearing BxPC-3 xenografts. Formats where the ABD was located on the C-terminus of affibody binding domains (3A, 33A, and 3A3) provided the best tumour targeting properties in vivo. Further development of these promising candidates for treatment of HER3-overexpressing tumours is therefore justified.
|
|
| 29. |
- Altai, Mohamed, et al.
(författare)
-
Order of amino acids in C-terminal cysteine-containing peptide-based chelators influences cellular processing and biodistribution of Tc-99m-labeled recombinant Affibody molecules
- 2012
-
Ingår i: Amino Acids. - : Springer Science and Business Media LLC. - 0939-4451 .- 1438-2199. ; 42:5, s. 1975-1985
-
Tidskriftsartikel (refereegranskat)abstract
- Affibody molecules constitute a novel class of molecular display selected affinity proteins based on non-immunoglobulin scaffold. Preclinical investigations and pilot clinical data have demonstrated that Affibody molecules provide high contrast imaging of tumor-associated molecular targets shortly after injection. The use of cysteine-containing peptide-based chelators at the C-terminus of recombinant Affibody molecules enabled site-specific labeling with the radionuclide Tc-99m. Earlier studies have demonstrated that position, composition and the order of amino acids in peptide-based chelators influence labeling stability, cellular processing and biodistribution of Affibody molecules. To investigate the influence of the amino acid order, a series of anti-HER2 Affibody molecules, containing GSGC, GEGC and GKGC chelators have been prepared and characterized. The affinity to HER2, cellular processing of Tc-99m-labeled Affibody molecules and their biodistribution were investigated. These properties were compared with that of the previously studied Tc-99m-labeled Affibody molecules containing GGSC, GGEC and GGKC chelators. All variants displayed picomolar affinities to HER2. The substitution of a single amino acid in the chelator had an appreciable influence on the cellular processing of Tc-99m. The biodistribution of all Tc-99m-labeled Affibody molecules was in general comparable, with the main difference in uptake and retention of radioactivity in excretory organs. The hepatic accumulation of radioactivity was higher for the lysine-containing chelators and the renal retention of Tc-99m was significantly affected by the amino acid composition of chelators. The order of amino acids influenced renal uptake of some conjugates at 1 h after injection, but the difference decreased at later time points. Such information can be helpful for the development of other scaffold protein-based imaging and therapeutic radiolabeled conjugates.
|
|
| 30. |
- Altai, Mohamed, et al.
(författare)
-
Selection of an optimal cysteine-containing peptide-based chelator for labeling of affibody molecules with (188)Re.
- 2014
-
Ingår i: European Journal of Medicinal Chemistry. - : Elsevier BV. - 0223-5234 .- 1768-3254. ; 87, s. 519-28
-
Tidskriftsartikel (refereegranskat)abstract
- Affibody molecules constitute a class of small (7 kDa) scaffold proteins that can be engineered to have excellent tumor targeting properties. High reabsorption in kidneys complicates development of affibody molecules for radionuclide therapy. In this study, we evaluated the influence of the composition of cysteine-containing C-terminal peptide-based chelators on the biodistribution and renal retention of (188)Re-labeled anti-HER2 affibody molecules. Biodistribution of affibody molecules containing GGXC or GXGC peptide chelators (where X is G, S, E or K) was compared with biodistribution of a parental affibody molecule ZHER2:2395 having a KVDC peptide chelator. All constructs retained low picomolar affinity to HER2-expressing cells after labeling. The biodistribution of all (188)Re-labeled affibody molecules was in general comparable, with the main observed difference found in the uptake and retention of radioactivity in excretory organs. The (188)Re-ZHER2:V2 affibody molecule with a GGGC chelator provided the lowest uptake in all organs and tissues. The renal retention of (188)Re-ZHER2:V2 (3.1 ± 0.5 %ID/g at 4 h after injection) was 55-fold lower than retention of the parental (188)Re-ZHER2:2395 (172 ± 32 %ID/g). We show that engineering of cysteine-containing peptide-based chelators can be used for significant improvement of biodistribution of (188)Re-labeled scaffold proteins, particularly reduction of their uptake in excretory organs.
|
|
| 31. |
- Altai, Mohamed, et al.
(författare)
-
Selection of an optimal cysteine-containing peptide-based chelator for labeling of Affibody molecules with 188-Re
- 2013
-
Ingår i: European Journal of Nuclear Medicine and Molecular Imaging. - : Springer Science and Business Media LLC. - 1619-7070 .- 1619-7089. ; 40:Suppl. 2, s. S219-S220
-
Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Affibody molecules constitute a class of small (7 kDa) scaffold proteins that can be engineered to have excellent tumor targeting properties. High reabsorption in kidneys complicates development of affibody molecules for radionuclide therapy. In this study, we evaluated the influence of the composition of cysteine-containing C-terminal peptide-based chelators on the biodistribution and renal retention of 188Re-labeled anti-HER2 affibody molecules. Biodistribution of affibody molecules containing GGXC or GXGC peptide chelators (where X is G, S, E or K) was compared with biodistribution of a parental affibody molecule ZHER2:2395 having a KVDC peptide chelator. All constructs retained low picomolar affinity to HER2-expressing cells after labeling. The biodistribution of all 188Re-labeled affibody molecules was in general comparable, with the main observed difference found in the uptake and retention of radioactivity in excretory organs. The 188Re-ZHER2:V2 affibody molecule with a GGGC chelator provided the lowest uptake in all organs and tissues. The renal retention of 188Re-ZHER2:V2 (3.1±0.5 %ID/g at 4 h after injection) was 55-fold lower than retention of the parental 188Re-ZHER2:2395 (172±32 %ID/g). We show that engineering of cysteine-containing peptide-based chelators can be used for significant improvement of biodistribution of 188Re-labeled scaffold proteins, particularly reduction of their uptake in excretory organs.
|
|
| 32. |
|
|
| 33. |
- Andersson, Ken G, et al.
(författare)
-
Comparative evaluation of 111In-labeled NOTA‑conjugated affibody molecules for visualization of HER3 expression in malignant tumors
- 2015
-
Ingår i: Oncology Reports. - : Spandidos Publications. - 1021-335X .- 1791-2431. ; 34:2, s. 1042-8
-
Tidskriftsartikel (refereegranskat)abstract
- Expression of human epidermal growth factor receptor type 3 (HER3) in malignant tumors has been associated with resistance to a variety of anticancer therapies. Several anti-HER3 monoclonal antibodies are currently under pre-clinical and clinical development aiming to overcome HER3-mediated resistance. Radionuclide molecular imaging of HER3 expression may improve treatment by allowing the selection of suitable patients for HER3-targeted therapy. Affibody molecules are a class of small (7kDa) high-affinity targeting proteins with appreciable potential as molecular imaging probes. In a recent study, we selected affibody molecules with affinity to HER3 at a low picomolar range. The aim of the present study was to develop an anti-HER3 affibody molecule suitable for labeling with radiometals. The HEHEHE-Z08698-NOTA and HEHEHE-Z08699-NOTA HER3-specific affibody molecules were labeled with indium‑111 (111In) and assessed invitro and invivo for imaging properties using single photon emission computed tomography (SPECT). Labeling of HEHEHE-Z08698-NOTA and HEHEHE-Z08699-NOTA with 111In provided stable conjugates. Invitro cell tests demonstrated specific binding of the two conjugates to HER3-expressing BT‑474 breast carcinoma cells. In mice bearing BT‑474 xenografts, the tumor uptake of the two conjugates was receptor‑specific. Direct invivo comparison of 111In-HEHEHE-Z08698-NOTA and 111In-HEHEHE-Z08699‑NOTA demonstrated that the two conjugates provided equal radioactivity uptake in tumors, although the tumor-to-blood ratio was improved for 111In-HEHEHE-Z08698-NOTA [12±3 vs. 8±1, 4h post injection (p.i.)] due to more efficient blood clearance. 111In-HEHEHE-Z08698-NOTA is a promising candidate for imaging of HER3-expression in malignant tumors using SPECT. Results of the present study indicate that this conjugate could be used for patient stratification for anti-HER3 therapy.
|
|
| 34. |
- Andersson, Ken G., et al.
(författare)
-
Feasibility of imaging of epidermal growth factor receptor expression with ZEGFR:2377 affibody molecule labeled with Tc-99m using a peptide-based cysteine-containing chelator
- 2016
-
Ingår i: International Journal of Oncology. - : SPANDIDOS. - 1019-6439 .- 1791-2423. ; 49:6, s. 2285-2293
-
Tidskriftsartikel (refereegranskat)abstract
- The epidermal growth factor receptor (EGFR) is overexpressed in a number of malignant tumors and is a molecular target for several specific anticancer antibodies and tyrosine kinase inhibitors. The overexpression of EGFR is a predictive biomarker for response to several therapy regimens. Radionuclide molecular imaging might enable detection of EGFR overexpression by a non-invasive procedure and could be used repeatedly. Affibody molecules are engineered scaffold proteins, which could be selected to have a high affinity and selectivity to predetermined targets. The anti-EGFR ZEGFR:2377 affibody molecule is a potential imaging probe for EGFR detection. The use of the generator-produced radionuclide Tc-99m should facilitate clinical translation of an imaging probe due to its low price, availability and favorable dosimetry of the radionuclide. In the present study, we evaluated feasibility of ZEGFR:2377 labeling with Tc-99m using a peptide-based cysteine-containing chelator expressed at the C-terminus of ZEGFR:2377. The label was stable in vitro under cysteine challenge. In addition, Tc-99m-ZEGFR:2377 was capable of specific binding to EGFR-expressing cells with high affinity (274 pM). Studies in BALB/C nu/nu mice bearing A431 xenografts demonstrated that Tc-99m-ZEGFR:2377 accumulates in tumors in an EGFR-specific manner. The tumor uptake values were 3.6 1 and 2.5 0.4% ID/g at 3 and 24 h after injection, respectively. The corresponding tumor-to-blood ratios were 1.8 0.4 and 8 3. The xenografts were clearly visualized at both time-points. This study demonstrated the potential of Tc-99m-labeled ZEGFR:2377 for imaging of EGFR in vivo.
|
|
| 35. |
- Anne Cochrane, Karen, et al.
(författare)
-
Body Maps : A Generative Tool for Soma-based Design
- 2022
-
Ingår i: ACM International Conference Proceeding Series. - New York, NY, USA : Association for Computing Machinery. - 9781450391474
-
Konferensbidrag (refereegranskat)abstract
- Body maps are visual documents, where somatic experiences can be drawn onto a graphical representation of an outline of the human body. They hold the ability to capture complex and non-explicit emotions and somatic felt sensations, elaborating narratives that cannot be simply spoken. We present an illustrative example of "how-to"complete a body map, together with four case studies that provide examples of using body maps in design research. We identify five uses of body maps as generative tools for soma-based design, ranging from sampling bodily experience, heightening bodily self-awareness, understanding changing bodily experience over time, identifying patterns of bodily experience, and transferring somatic experiential qualities into physical designs. The different requirements for scaffolding the use of body maps in user-centred design versus first-person autobiographical design research are discussed. We provide this Pictorial as a resource for designers and researchers who wish to integrate body maps into their practice. © 2022 Owner/Author.
|
|
| 36. |
- Assenhöj, Maria, et al.
(författare)
-
Protein interaction, monocyte toxicity and immunogenic properties of cerium oxide crystals with 5% or 14% gadolinium, cobalt oxide and iron oxide nanoparticles–an interdisciplinary approach
- 2021
-
Ingår i: Nanotoxicology. - : Taylor and Francis Ltd.. - 1743-5390 .- 1743-5404. ; 15:8, s. 1035-1038
-
Tidskriftsartikel (refereegranskat)abstract
- Metal oxide nanoparticles are widely used in both consumer products and medical applications, but the knowledge regarding exposure-related health effects is limited. However, it is challenging to investigate nanoparticle interaction processes with biological systems. The overall aim of this project was to improve the possibility to predict exposure-related health effects of metal oxide nanoparticles through interdisciplinary collaboration by combining workflows from the pharmaceutical industry, nanomaterial sciences, and occupational medicine. Specific aims were to investigate nanoparticle-protein interactions and possible adverse immune reactions. Four different metal oxide nanoparticles; CeOx nanocrystals with 5% or 14% Gd, Co3O4, and Fe2O3, were characterized by dynamic light scattering and high-resolution transmission electron microscopy. Nanoparticle-binding proteins were identified and screened for HLA-binding peptides in silico. Monocyte interaction with nanoparticle–protein complexes was assessed in vitro. Herein, for the first time, immunogenic properties of nanoparticle-binding proteins have been characterized. The present study indicates that especially Co3O4-protein complexes can induce both ‘danger signals’, verified by the production of inflammatory cytokines and simultaneously bind autologous proteins, which can be presented as immunogenic epitopes by MHC class II. The clinical relevance of these findings should be further evaluated to investigate the role of metal oxide nanoparticles in the development of autoimmune disease. The general workflow identified experimental difficulties, such as nanoparticle aggregate formation and a lack of protein-free buffers suitable for particle characterization, protein analyses, as well as for cell studies. This confirms the importance of future interdisciplinary collaborations. © 2021 The Author(s).
|
|
| 37. |
- Atamanchuk, Dariia, 1987, et al.
(författare)
-
Detection of CO2 leakage from a simulated sub-seabed storage site using three different types of pCO2 sensors
- 2015
-
Ingår i: International Journal of Greenhouse Gas Control. - : Elsevier BV. - 1750-5836. ; 38, s. 121-134
-
Tidskriftsartikel (refereegranskat)abstract
- This work is focused on results from a recent controlled sub-seabed in situ carbon dioxide (CO2) releaseexperiment carried out during May–October 2012 in Ardmucknish Bay on the Scottish west coast. Threetypes of pCO2sensors (fluorescence, NDIR and ISFET-based technologies) were used in combination withmultiparameter instruments measuring oxygen, temperature, salinity and currents in the water columnat the epicentre of release and further away. It was shown that distribution of seafloor CO2 emissionsfeatures high spatial and temporal heterogeneity. The highest pCO2values (∼1250 atm) were detectedat low tide around a bubble stream and within centimetres distance from the seafloor. Further up in thewater column, 30–100 cm above the seabed, the gradients decreased, but continued to indicate elevatedpCO2at the epicentre of release throughout the injection campaign with the peak values between 400and 740atm. High-frequency parallel measurements from two instruments placed within 1 m fromeach other, relocation of one of the instruments at the release site and 2D horizontal mapping of therelease and control sites confirmed a localized impact from CO2emissions. Observed effects on the watercolumn were temporary and post-injection recovery took <7 days.A multivariate statistical approach was used to recognize the periods when the system was dominatedby natural forcing with strong correlation between variation in pCO2and O2, and when it was influencedby purposefully released CO2.Use of a hydrodynamic circulation model, calibrated with in situ data, was crucial to establishingbackground conditions in this complex and dynamic shallow water system.
|
|
| 38. |
|
|
| 39. |
- Balaam, Madeline, et al.
(författare)
-
Emotion Work in Experience-Centred Design
- 2019
-
Ingår i: CHI Conference on Human Factors in Computing Systems Proceedings (CHI 2019), May 4–9, 2019, Glasgow, Scotland UK. - New York, NY, USA : ACM.
-
Konferensbidrag (refereegranskat)abstract
- Experience Centred Design (ECD) implores us to develop empathic relationships and understanding of participants, to actively work with our senses and emotions within the design process. However, theories of experience-centred design do little to account for emotion work undertaken by design researchers when doing this. As a consequence, how a design researcher’s emotions are experienced, navigated and used as part of an ECD process are rarely published. So, while emotion is clearly a tool that we use, we don’t share with one another how, why and when it gets used. This has a limiting effect on how we understand design processes, and opportunities for training. Here, we share some of our experiences of working with ECD. We analyse these using Hochschild’s framework of emotion work to show how and where this work occurs. We use our analysis to question current ECD practices and provoke debate.
|
|
| 40. |
- Balaam, Madeline, et al.
(författare)
-
Intimate Touch
- 2020
-
Ingår i: interactions. - : Association for Computing Machinery. - 1072-5520 .- 1558-3449. ; 27:6, s. 14-17
-
Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)
|
|
| 41. |
- Bass, Tarek, et al.
(författare)
-
In vivo evaluation of a novel format of a bivalent HER3-targeting and albumin- binding therapeutic affibody construct
- 2017
-
Ingår i: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 7
-
Tidskriftsartikel (refereegranskat)abstract
- Overexpression of human epidermal growth factor receptor 3 (HER3) is involved in resistance to several therapies for malignant tumours. Currently, several anti-HER3 monoclonal antibodies are under clinical development. We introduce an alternative approach to HER3-targeted therapy based on engineered scaffold proteins, i.e. affibody molecules. We designed a small construct (22.5 kDa, denoted 3A3), consisting of two high-affinity anti-HER3 affibody molecules flanking an albumin-binding domain ABD, which was introduced for prolonged residence in circulation. In vitro, 3A3 efficiently inhibited growth of HER3-expressing BxPC-3 cells. Biodistribution in mice was measured using 3A3 that was site-specifically labelled with In-111 via a DOTA chelator. The residence time of In-111-DOTA-3A3 in blood was extended when compared with the monomeric affibody molecule. In-111-DOTA-3A3 accumulated specifically in HER3-expressing BxPC-3 xenografts in mice. However, In-111-DOTA-3A3 cleared more rapidly from blood than a size-matched control construct In-111-DOTA-TAT, most likely due to sequestering of 3A3 by mErbB3, the murine counterpart of HER3. Repeated dosing and increase of injected protein dose decreased uptake of In-111-DOTA-3A3 in mErbB3-expressing tissues. Encouragingly, growth of BxPC-3 xenografts in mice was delayed in an experimental (pilot-scale) therapy study using 3A3. We conclude that the 3A3 affibody format seems promising for treatment of HER3-overexpressing tumours.
|
|
| 42. |
- Bendix, Lars, et al.
(författare)
-
Issues and Challenges with Industrial-Strength Product Composition
- 2010
-
Konferensbidrag (refereegranskat)abstract
- One way to deal with product lines and products that have to exist in many variants is to use a component-based approach. This allows a lot of flexibility in creating new products and can reduce time and costs. However, the flexibility in composing products from a base of components is not without problems. Complexity increases in the composition process when combining many components to one large system – in particular because components may also exist in several revisions or variants. Furthermore, there are many different stakeholders involved in the development of new components and products and they all work at different levels of granularity and have different needs. From the analysis of a complex industrial context, we have identified a set of issues and challenges that need to be addressed for advanced product composition. A shared component base can work as a repository for storing facts and information about components and a rule-base will allow users to reason about configurations at a higher level such as completeness and consistency.
|
|
| 43. |
- Berglund, Emelie, et al.
(författare)
-
Spatial maps of prostate cancer transcriptomes reveal an unexplored landscape of heterogeneity
- 2018
-
Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 9
-
Tidskriftsartikel (refereegranskat)abstract
- Intra-tumor heterogeneity is one of the biggest challenges in cancer treatment today. Here we investigate tissue-wide gene expression heterogeneity throughout a multifocal prostate cancer using the spatial transcriptomics (ST) technology. Utilizing a novel approach for deconvolution, we analyze the transcriptomes of nearly 6750 tissue regions and extract distinct expression profiles for the different tissue components, such as stroma, normal and PIN glands, immune cells and cancer. We distinguish healthy and diseased areas and thereby provide insight into gene expression changes during the progression of prostate cancer. Compared to pathologist annotations, we delineate the extent of cancer foci more accurately, interestingly without link to histological changes. We identify gene expression gradients in stroma adjacent to tumor regions that allow for re-stratification of the tumor microenvironment. The establishment of these profiles is the first step towards an unbiased view of prostate cancer and can serve as a dictionary for future studies.
|
|
| 44. |
- Buckley, Patrick G, et al.
(författare)
-
A full-coverage, high-resolution human chromosome 22 genomic microarrayfor clinical and research applications
- 2002
-
Ingår i: Human Molecular Genetics. - : Oxford University Press (OUP). - 0964-6906 .- 1460-2083. ; 11:25, s. 3221-3229
-
Tidskriftsartikel (refereegranskat)abstract
- We have constructed the first comprehensive microarray representing a human chromosome for analysis of DNA copy number variation. This chromosome 22 array covers 34.7 Mb, representing 1.1% of the genome, with an average resolution of 75 kb. To demonstrate the utility of the array, we have applied it to profile acral melanoma, dermatofibrosarcoma, DiGeorge syndrome and neurofibromatosis 2. We accurately diagnosed homozygous/heterozygous deletions, amplifications/gains, IGLV/IGLC locus instability, and breakpoints of an imbalanced translocation. We further identified the 14-3-3 eta isoform as a candidate tumor suppressor in glioblastoma. Two significant methodological advances in array construction were also developed and validated. These include a strictly sequence defined, repeat-free, and non-redundant strategy for array preparation. This approach allows an increase in array resolution and analysis of any locus; disregarding common repeats, genomic clone availability and sequence redundancy. In addition, we report that the application of phi29 DNA polymerase is advantageous in microarray preparation. A broad spectrum of issues in medical research and diagnostics can be approached using the array. This well annotated and gene-rich autosome contains numerous uncharacterized disease genes. It is therefore crucial to associate these genes to specific 22q-related conditions and this array will be instrumental towards this goal. Furthermore, comprehensive epigenetic profiling of 22q-located genes and high-resolution analysis of replication timing across the entire chromosome can be studied using our array.
|
|
| 45. |
- Carlberg, Konstantin
(författare)
-
Spatial Tissue Mapping on Joint Biopsies from Arthritis Patients
- 2021
-
Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Rheumatoid arthritis (RA) is a chronic inflammatory autoimmune disease that mainly affects joints, causing discomfort and pain that severely reduces the life quality of affected individuals. Its etiology is largely unknown, but some pathophysiological mechanisms have been identified. These include formation of anti-citrullinated protein antibodies (ACPAs) and rheumatic factors (RFs), local proliferation of mesenchymal cells, and recruitment of T- and B cells to the affected synovium. Lymphocyte infiltration results in elevated levels of cytokines such as Tumor Necrosis Factor alpha (TNF-α) and interleukin signaling, which in turn triggers protease activation that gradually degrades the synovium and underlying bone. In many cases RA can be effectively managed by early diagnosis followed by treatment with disease-modifying anti-rheumatic drugs (DMARDs). However, this is not true for all patients and there is currently no cure for RA. Synovial lesions in RA patients exhibit complex histopathological manifestations involving the formation of lymphoid follicles with highly organized Ectopic Lymphoid Structures (ELS). These have been extensively studied using immunostaining and other cytological methods, either by targeting a few specific molecular markers in tissue sections or by examining homogenized suspensions of complex samples, which causes a loss of local and spatial tissue information. This thesis reports the use of Spatial Transcriptomics (ST) to study gene expression in tissue samples from RA patients while preserving spatial information. The method was applied to RA biopsies from early onset and untreated RA to late-stage established disease with edema, providing comprehensive coverage of the spatio-temporal dynamics of the inflamed joints. Paper I introduces sRIN, a novel method of assessing the quality of RNA in tissue sections that is similar to RNA Integrity Number (RIN) analysis for bulk RNA but with single-cell resolution. The aim was to find ways of analyzing clinically rare samples for further processing with ST. Paper II uses ST to study tissue samples from RA joints with long-standing disease, using Spondyloarthritis (SpA) as a disease control. The resulting comprehensive transcriptomic data were used to perform in silico immune cell prediction and revealed how immune cell infiltration in RA differs from that in SpA in more detail than was previously possible using traditional pathological methods. As a follow up, Paper III investigates inflamed RA joints in even greater detail by using several adjacent tissue sections to build a three-dimensional atlas of assumed ELS areas. Finally, Paper IV uses four distinct technologies to study untreated early onset RA patients. Spatial tissue analysis with ST was combined with single cell RNA sequencing (scRNA-Seq) of fluorescence-activated cell sorted (FACS) B cells. These two methods were complemented with immunohistochemistry (IHC) for validation and sRIN to assess the quality of the clinical samples. B cells are known to play a key role in RA by producing self-reactive antibodies. This work showed that B cell maturation and ELS formation are detectable even in early onset RA, and revealed mechanisms supporting survival niches in hyperplastic joints. Overall, these studies shed new light on the complex nature of Rheumatoid arthritis, characterize the site of infection with greater granularity than was previously possible, and reveal novel disease patterns with clinical implications that warrant further study.
|
|
| 46. |
- Dahlsson Leitao, Charles, et al.
(författare)
-
Molecular Design of HER3-Targeting Affibody Molecules : Influence of Chelator and Presence of HEHEHE-Tag on Biodistribution of 68Ga-Labeled Tracers
- 2019
-
Ingår i: International Journal of Molecular Sciences. - : MDPI AG. - 1661-6596 .- 1422-0067. ; 20:5
-
Tidskriftsartikel (refereegranskat)abstract
- Affibody-based imaging of HER3 is a promising approach for patient stratification. We investigated the influence of a hydrophilic HEHEHE-tag ((HE)3-tag) and two different gallium-68/chelator-complexes on the biodistribution of Z08698 with the aim to improve the tracer for PET imaging. Affibody molecules (HE)3-Z08698-X and Z08698-X (X = NOTA, NODAGA) were produced and labeled with gallium-68. Binding specificity and cellular processing were studied in HER3-expressing human cancer cell lines BxPC-3 and DU145. Biodistribution was studied 3 h p.i. in Balb/c nu/nu mice bearing BxPC-3 xenografts. Mice were imaged 3 h p.i. using microPET/CT. Conjugates were stably labeled with gallium-68 and bound specifically to HER3 in vitro and in vivo. Association to cells was rapid but internalization was slow. Uptake in tissues, including tumors, was lower for (HE)3-Z08698-X than for non-tagged variants. The neutral [68Ga]Ga-NODAGA complex reduced the hepatic uptake of Z08698 compared to positively charged [68Ga]Ga-NOTA-conjugated variants. The influence of the chelator was more pronounced in variants without (HE)3-tag. In conclusion, hydrophilic (HE)3-tag and neutral charge of the [68Ga]Ga-NODAGA complex promoted blood clearance and lowered hepatic uptake of Z08698. [68Ga]Ga-(HE)3-Z08698-NODAGA was considered most promising, providing the lowest blood and hepatic uptake and the best imaging contrast among the tested variants.
|
|
| 47. |
|
|
| 48. |
- Erickson, Andrew, et al.
(författare)
-
The spatial landscape of clonal somatic mutations in benign and malignant tissue
-
Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- Defining the transition from benign to malignant tissue is fundamental to improve early diagnosis of cancer. Here, we provide an unsupervised approach to study spatial genome integrity in situ to gain molecular insight into clonal relationships. We employed spatially resolved transcriptomics to infer spatial copy number variations in >120 000 regions across multiple organs, in benign and malignant tissues. We demonstrate that genome-wide copy number variation reveals distinct clonal patterns within tumours and in nearby benign tissue. Our results suggest a model for how genomic instability arises in histologically benign tissue that may represent early events in cancer evolution. We highlight the power of an unsupervised approach to capture the molecular and spatial continuums in a tissue context and challenge the rationale for treatment paradigms, including focal therapy.
|
|
| 49. |
|
|
| 50. |
- Fagerberg, Petra, et al.
(författare)
-
Designing gestures for affective input: an analysis of shape, effort and valence
- 2003. - 1
-
Ingår i: MUM 2003. - Norrköping, Sweden : ACM Publications. - 1581138261 ; , s. 57-65
-
Konferensbidrag (refereegranskat)abstract
- We discuss a user-centered approach to incorporating affective expressions in interactive applications, and argue for a design that addresses both body and mind. In particular, we have studied the problem of finding a set of affective gestures. Based on previous work in movement analysis and emotion theory [Davies, Laban and Lawrence, Russell], and a study of an actor expressing emotional states in body movements, we have identified three underlying dimensions of movements and emotions: shape, effort and valence. From these dimensions we have created a new affective interaction model, which we name the affective gestural plane model. We applied this model to the design of gestural affective input to a mobile service for affective messages.
|
|
