| 1. |
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| 2. |
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| 3. |
- Martinsson, Ulla, et al.
(författare)
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Complications after proton radiotherapy in children, focusing on severe late complications. A complete Swedish cohort 2008-2019
- 2023
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Ingår i: ACTA ONCOLOGICA. - : Taylor & Francis. - 0284-186X .- 1651-226X. ; 62:10, s. 1348-1356
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Tidskriftsartikel (refereegranskat)abstract
- Background: Proton radiotherapy (RT) is an attractive tool to deliver local therapy with minimal dose to uninvolved tissue, however, not suitable for all patients. The aim was to explore complications, especially severe late complications (grades 3-4), following proton RT delivered to a complete Swedish cohort of paediatric patients aged <18 years treated 2008-2019.Material and Methods: Data was downloaded from a national registry. Complications with a possible causation with RT are reported. Proton treatments until July 2015 was performed with a fixed horizontal 172 MeV beam (The Svedberg Laboratory (TSL), Uppsala) in a sitting position and thereafter with gantry-based pencil-beam scanning technique (Skandion Clinic, Uppsala) in a supine position.Results: 219 courses of proton RT (77 at TSL and 142 at Skandion) were delivered to 212 patients (mean age 9.2 years) with various tumour types (CNS tumours 58%, sarcomas 26%, germ cell tumours 7%). Twenty-five patients had severe acute complications (skin, mucous membrane, pharynx/oesophagus, larynx, upper gastrointestinal canal, lower gastrointestinal canal, eyes, ears). Fifteen patients had severe late complications; with increased proportion over time: 4% at 1-year follow-up (FU), 5% at 3-year, 11% at 5-year. Organs affected were skin (1 patient), subcutaneous tissue (4), salivary glands (1), upper GI (1), bone (7), joints (2), CNS (2), PNS (1), eyes (1) and ears (5). Twenty-one of the 28 patients with 10-year FU had at least one late complication grades 1-4 and fourteen of them had more than one (2-5 each).Conclusion: The most important result of our study is the relatively low proportion of severe late complications, comparable with other proton studies on various tumours. Furthermore, the numbers of late complications are lower than our own data set on a mixed population of photon and proton treated paediatric patients, assuring the safety of using proton therapy also in the clinical practice.
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| 4. |
- Nilsson Hammar, Anna, et al.
(författare)
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Introduction
- 2022
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Ingår i: Gender, materiality, and Politics : Essays on the making of power - Essays on the making of power. - 9789189361379 ; , s. 7-21
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Bokkapitel (övrigt vetenskapligt/konstnärligt)
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| 5. |
- Tesi, Bianca, et al.
(författare)
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Diagnostic yield and clinical impact of germline sequencing in children with CNS and extracranial solid tumors : a nationwide, prospective Swedish study
- 2024
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Ingår i: The Lancet Regional Health. - : Elsevier. - 2666-7762. ; 39
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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.
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| 6. |
- Tesi, Bianca, et al.
(författare)
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Diagnostic yield and clinical impact of germline sequencing in children with CNS and extracranial solid tumors : a nationwide, prospective Swedish study
- 2024
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Ingår i: The Lancet Regional Health. - : Elsevier. - 2666-7762. ; 39
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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.
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| 7. |
- Andersson, Anne, 1966-, et al.
(författare)
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Adherence to adjuvant endocrine therapy after breast cancer in Sweden 2008-2010 : a nationwide survey
- 2019
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Ingår i: JOURNAL OF CLINICAL ONCOLOGY. - : American Society of Clinical Oncology. - 0732-183X. ; 37:15
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- Background: In estrogen receptor (ER) positive early breast cancer (EBC) adjuvant endocrine therapy (AET) is crucial to reduce recurrence and mortality. Previous studies have shown that adherence to AET is lower than expected and could negatively affect outcome. Since the year of 2000, BC patients in Sweden are treated in accordance to national guidelines. Treatment is offered at a low cost for the patient. The aim of the study was to estimate the adherence to AET in Sweden by regions and age groups. Methods: Women with a first primary EBC diagnosis 2008-2010 were identified through the Swedish Cancer Registry (SCR). Individual tumour and treatment data were retrieved from the Swedish National Breast Cancer Registry (SNBCR). Patients with ER negative tumours, small tumours (≤ 10 mm) and metastatic disease was excluded from the study since there were no indication to AET. Likewise, were individuals with AET registered to be administered by a third part excluded. Dispensed treatment from pharmacies was obtained through the Swedish Prescription Registry and medication possession rate (MPR) was calculated as number of dispensed doses divided by treatment duration in days. Good adherence to treatment in a patient was set at MPR ≥ 80 %. Adherence was calculated for 3 and 5 years. Results: Twenty-one thousand sixteen (21 016) individuals with a first primary BC between 2008 and 2010 was identified through SCR of which 20 596 were registered in the SNBCR. A total of 10 176 met the inclusion criteria in the study. Adherence after 3 years was 88.0 % and after 5 years 82.5 %. Adherence differed between regions in Sweden and was positively associated with age at diagnosis between 41-74 years. Urban areas had a lower adherence than rural areas (80.7 % vs 83.6 %; p= <0.001). Conclusions: Adherence to AET in Sweden was good, although there were differences by age and urban and rural areas. Further studies are needed to identify factors affecting differences in adherence, with the purpose of initiate actions to increase adherence to AET in ER positive EBC patients.
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| 8. |
- Andersson, Leif, et al.
(författare)
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ZBED6 : the birth of a new transcription factor in the common ancestor of placental mammals
- 2010
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Ingår i: Transcription. - : Informa UK Limited. - 2154-1272 .- 2154-1264. ; 1:3, s. 144-148
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Tidskriftsartikel (refereegranskat)abstract
- A DNA transposon integrated into -the genome of a primitive mammal some 200 million years ago and, millions of years later, it evolved an essential function in the common ancestor of all placental mammals. This protein, now named ZBED6, was recently discovered because a mutation disrupting one of its binding sites, in an intron of the IGF2 gene, makes pigs grow more muscle. These findings have revealed a new mechanism for regulating muscle growth as well as a novel transcription factor that appears to be of major importance for transcriptional regulation in placental mammals.
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| 9. |
- Barlow, Lotti, et al.
(författare)
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Nationellt fackspråk för vård och omsorg : Slutrapport
- 2011
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Rapport (populärvet., debatt m.m.)abstract
- SammanfattningEtt tillgängligt och använt nationellt fackspråk ska bidra till en god och säker vård och omsorg. Det ska även medverka till att kvaliteten och resultaten på området ska kunna följas upp och jämföras på ett mer effektivt sätt. Slutrapporten presenterar resultatet av projektet Nationellt fackspråk för vård och omsorg samt förslag till förvaltning och utveckling.ResultatetResultatet innefattar bland annat att det internationella begreppssystemet Snomed CT är översatt till svenska och att det är förberett för förvaltning och distribution. Socialstyrelsen har även tagit fram och testat metoder för förvaltning och utveckling av det nationella fackspråket i sin helhet. Därtill har representanter för målgrupperna informerats och fått kunskap.Rapporten innehåller en utförlig beskrivning av det nationella fackspråkets sammantagna innehåll: Socialstyrelsens termbank, klassifikationer och kodverk, den svenska versionen av Snomed CT, metoder för utveckling och förvaltning samt regler för användning.Förvaltning, införande och resursbehovI rapporten finns förslag till hur hela det nationella fackspråket kan tas omhand av Socialstyrelsen och hur det kan införas i vården och omsorgen. Projektets övergång till en långsiktigt hållbar organisation kräver resurser. Därför redogör rapporten för det förväntade resursbehovet för förvaltning och utveckling. Bland annat föreslås en treårig utbildningsinsats samt stimulansbidrag för införande.Krav på styrning, samordning och förtydligat ansvarRapporten betonar behovet av en samlad och medveten styrning av utvecklingen inom området. Socialstyrelsen vill ha en samordnande roll i utvecklingen och förvaltningen av det nationella fackspråket. Myndigheten föreslås få det initiala ansvaret för att utbilda användare och att driva frågor om det nationella fackspråket.Vidare vill Socialstyrelsen få ett uttalat mandat att samordna de nationella aktiviteter som drivs med koppling till Snomed CT. Rapporten pekar ut några särskilt prioriterade områden som myndigheten borde få i uppdrag att arbeta vidare inom.Kunskapsstyrning och normgivningEn viktig slutsats i rapporten är att användningen av det nationella fackspråket behöver regleras för att målet om ökad säkerhet för klienter och patienter ska kunna uppnås. I dagsläget bedöms föreskrifter vara den metod som bäst kan garantera ett brett genomförande.Målgrupper för slutrapportenSlutrapporten riktar sig till beslutsfattare i kommuner och landsting, vård- och omsorgspersonal med särskilt intresse eller ansvar för dokumentationsfrågor och professionella organisationer. Den riktar sig också till terminologiansvariga i kommuner och landsting, IT-direktörer, IT-leverantörer samt aktörer inom den nationella strategin för eHälsa.
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| 10. |
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| 11. |
- Ek, Anna, et al.
(författare)
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Physical Activity and Mobile Phone Apps in the Preschool Age: Perceptions of Teachers and Parents
- 2019
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Ingår i: JMIR mhealth and uhealth. - : JMIR Publications. - 2291-5222. ; 7:4
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND:Physical activity (PA) is already beneficial at the preschool age. In many countries, young children spend most of their days in the preschool setting, making it a common arena for PA interventions. Mobile health tools are becoming increasingly popular to promote PA in different populations; however, little is known about the interest for and how the preschool setting could incorporate such a tool.OBJECTIVE:This study aimed to examine how teachers and parents perceive PA in preschool-aged children in general and their perceptions of how a mobile phone app could be used to promote PA in the preschool setting.METHODS:Semistructured interviews were conducted with 15 teachers (93%, [14/15] women, mean age 43.5 years, 47%, [7/15] with a university degree and 10 parents [91%, 9/10] women, mean age 38.9 years, all with a university degree) recruited from 2 urban preschools in central Sweden. The interviews were recorded, fully transcribed, coded, and analyzed using thematic analysis by means of an inductive approach.RESULTS:The analysis revealed 4 themes: (1) children are physically active by nature, (2) the environment as a facilitator or a barrier, (3) prerequisites of the adult world, and (4) an app in the preschool setting-challenges and possibilities. Parents and teachers perceived preschoolers as being spontaneously physically active; however, high-intensity PA was perceived as low. The PA was specifically performed during the day in the preschool. Identified facilitators of PA were access to safe and engaging outdoor environments such as forests, spacious indoor areas, and adult involvement. Adult involvement was considered especially important for children preferring sedentary activities. Identified barriers for PA were restricted indoor and outdoor space, rules for indoor activities, and lack of adult involvement because of time constraints. The teachers perceived that they had limited skills and experiences using apps in general, although they also acknowledged the increasing role of technological tools in the curriculum. Thus, the teachers expressed an interest for an app designed as a support tool for them, especially for situations when PA was limited because of perceived barriers. They suggested the app to include accessible information regarding the health benefits of PA in children linked to a library of activities for different settings and seasons. Parents suggested interactive app features including problem-solving tasks and music and dance, but not video clips as they made children passive.CONCLUSIONS:Vigorous PA was perceived as low in preschool-aged children. Future tailoring of interventions in the preschool setting should work around barriers and support facilitators to PA, especially PA of high intensity. In such work, an app could serve as a source of inspiration for PA in different ages, settings, and seasons and thus reduce environmental and structural inequalities in the preschool setting.
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| 12. |
- Gyllén, Jenny, 1968, et al.
(författare)
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Important sources of information to support self-management for families of children with pediatric cataracts – based on PECARE Sweden/Sahlgrenska University Hospital
- 2015
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Ingår i: International Journal of Ophthalmic Practice. - : Mark Allen Group. - 2044-5504 .- 2052-2851. ; 6:1, s. 23-29
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Tidskriftsartikel (refereegranskat)abstract
- ABSTRACT Purpose The aim of this study was to improve treatment concordance by investigating important sources of information on self-management for families of children with pediatric cataracts, from the perspective of parents and ophthalmologists. Methods This mixed-method study involved a deductive approach using a questionnaire administered to 69 families of children operated on and registered with the Swedish Pediatric Cataract Register (PECARE Sweden) in southern Sweden, as well as 30 pediatric ophthalmologists who monitored the patients upon their return to the local health care facility. An inductive approach was applied using analysis of open-ended questions about self-management. Both groups were asked about their perception of the value of strategies for providing information, and the timing of this. Results The response rate was 68% for families and 93% for ophthalmologists. Both groups agreed that ophthalmology visits were the most important source of information, followed by information in writing and online. Parents of children diagnosed before the age of 3 months were more likely to prefer written information. Content analysis revealed that a person-centred care is important. Conclusion Parents, particularly of the youngest children, requested more and directed information. By promoting self-management, a person-centred care may play a decisive role in treatment outcome.
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| 13. |
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| 14. |
- Hjelmér, Ida, et al.
(författare)
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Quality of life among female childhood cancer survivors with and without premature ovarian insufficiency
- 2023
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Ingår i: Journal of Cancer Survivorship. - : Springer Science and Business Media LLC. - 1932-2259 .- 1932-2267. ; 17:1, s. 101-109
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: Due to an increase in survival, a growing population of childhood cancer survivors (CCS) is present. However, female CCS are at risk of developing premature ovarian insufficiency (POI) after cancer treatment. POI involves a decreased chance of conceiving and the increased infertility state has a large impact on affected individuals’ health and mental life. The objective of this study was to investigate health state and well-being among female CCS with and without POI and healthy controls (HC). Methods: Female CCS treated in southern Sweden between 1964 and 2008 were included. Each patient was matched with a HC. The final study population included 167 female CCS and 164 HC that were examined between October 2010 and January 2015 at the Reproductive Medicine Centre at Skåne University Hospital in Malmö, Sweden. All participants, except for two HCs, answered an EQ-5D-3L questionnaire for measuring health state including a visual analogue scale (VAS) for estimating well-being. Results: There were 22 CCS with POI, none of the HC had POI. The mean health state differed among groups (unadjusted: P = 0.002; adjusted: P = 0.007). A difference in mean experienced well-being among groups was noted (unadjusted: P = 0.003; adjusted: P = 0.012). Lowest well-being was found in the CCS group with POI (P = 0.024). Conclusions: Female CCS have a significantly decreased health state and well-being. Female CCS with POI additionally have the lowest self-estimated well-being. Implications for Cancer Survivors: Female CCS with POI should be identified early in order to give them adequate information and support.
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| 15. |
- Jönbrink, Anna Karin, et al.
(författare)
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Create Competitiveness In A Sustainable Society : - Use Ecodesign, In Cooperation
- 2011
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Ingår i: Design for Innovative Value Towards a Sustainable Society. - Dordrecht : Springer Science+Business Media B.V.. ; , s. 430-433
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Konferensbidrag (refereegranskat)abstract
- This paper will describe a new methodology for the use of Ecodesign, where various competences are combined to obtain high quality results. The competences needed are: Environmental experts, who can evaluate the environmental performance of a product or service through Life Cycle Assessment, LCA, material- and process experts for the materials and processes in the targeted product or service, experts of the final product or service who can provide high quality data for the LCA. This cross functional team can develop new products or services, with high performance combined with low environmental impact, applying ecodesign when cooperating closely. Using this methodology is a feasible way to obtain improved competitiveness for the industry in a sustainable society.
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| 16. |
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| 17. |
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| 18. |
- Kadowaki, Åsa, 1966-, et al.
(författare)
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Education of the primary health care staff based on acceptance and commitment therapy is associated with reduced sick leave in a prospective controlled trial
- 2021
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Ingår i: BMC Family Practice. - : BMC. - 1471-2296. ; 22:1
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Tidskriftsartikel (refereegranskat)abstract
- Background: The use of cognitive behavioral therapy (CBT) to cope with mental distress and pain issues has helped many patients in primary health care in Sweden. However, the effects of CBT to reduce sick leave has not been equally convincing. Acceptance and Commitment Therapy (ACT) is an evolution of traditional CBT and we aimed to study if education based on ACT of the staff rather than the patients could reduce sick leave in primary health care. Methods: This was a prospective trial in 6 primary health care centers in Kalmar (total amount of registered subjects of 28,930) in which the staff (physicians, nurses and therapists) received group-based education according to ACT during 2018 and 2019. The effects were compared with 5 similarly sized control health care centers in the neighboring Region of Jonkoping in which no such education took place. The main aim was to study changes in sick leave in the 6 primary care centers of Kalmar and to keep track of more general trends by studying sick leave also in Jonkoping, letting sick leave in the year 2017 to be the reference period for both areas. Results: The staff at the health care centers in Kalmar reported to having attended a mean of 5.2 +/- 2 educational ACT-sessions with psychiatrist Kadowaki in Kalmar. Sick leave for ICD-10 F43 (reaction to severe stress and related adjustment-disorders) was reduced from a mean value of 28.7 +/- 9.1ongoing sick leaves/month in 2017 to 22.6 +/- 7.0 sick leaves/month in 2018 (-21%, p = 0.033) and to 18.1 +/- 10 sick leaves/month in 2019 (-37%, p = 0.038). The corresponding sick leave for any diagnosis (total sick leave) was reduced from 132 +/- 39 sick leaves/month in 2017 to 118 +/- 38 sick leaves/month in 2018 (-11%, p = 0.056) and to 102 +/- 37 sick leaves/month in 2019 (-21%, p = 0.021). The corresponding sick leave comparisons in the control health centers did not show any significant changes (all p-values >= 0.24). Conclusions: Total monthly mean sick leave was reduced 21% in the health care centers in Kalmar during the second year of the educational ACT intervention of the staff while it was unchanged in Jonkoping. This suggests a significant effect to induce a reduction in long-term sick leave for patients in primary health care in which the staff received education according to ACT. The results of this trial could serve as a basis for a randomized trial in order to ascertain causality.
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| 19. |
- Kumlin, Anna-Sofia, et al.
(författare)
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Improved Statistics on Process Emissions and Flaring
- 2004
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Rapport (övrigt vetenskapligt/konstnärligt)abstract
- SMED was involved in two projects concerning the EU emission trading scheme1 in the years 2003 and 2004. During these projects deficits in data used by SMED to report emissions of CO2 to the EU Monitoring Mechanism and the UNFCCC were observed. Deficits include lack of activity data on the use of carbon-containing input materials within in the iron and steel industry and the production of light expanded clay aggregate (LECA). Deficits also include lack of activity data on the use of limestone and dolomite as well as flaring of excess gases, at a few plants from various industry sectors.1 EU Directive 2003/87/EC on establishing a scheme for greenhouse gas emission allowance trading within the Community and the amending Council Directive 96/61/EC2 Ministry of Industry, Employment and Communications, Sweden’s National Allocation Plan (2004-04-22), http://www.regeringen.se/content/1/c6/01/90/18/e9286dc2.pdf3 Revised IPCC Guidelines for National Greenhouse Gas Inventories: Workbook 2.13.2Within this project new activity data have been collected. Emissions have been updated and completed on the basis of collected data and data from the inquiry sent to concerned companies in order to establish the Swedish national allocation plan (NAP) for the EU emission trading scheme2 (from here on referred to as "the inquiry for the Swedish NAP") in the winter of 2004.For the iron and steel sector emissions from stationary combustion (CRF/NFR 1A2a) and from processes (CRF 2C1) have been updated. Updated emissions in CRF 2C1 are a result of new activity data on the use of carbon-containing input materials, such as electrodes, coal and coke, that are used to reduce iron ore or optimise conditions in the smelt. These emissions are defined as process emissions in the IPCC Guidelines.3 In earlier submissions these emissions have only partly been included in CRF 2C1, some emissions were completely lacking and some were incorrectly reported in CRF/NFR 1A2a. The emissions that were incorrectly reported in CRF/NFR 1A2a have been updated and reallocated to CRF 2C1. Emissions in CRF 2C1 have been completed with data from eight additional plants. The whole time series has been updated in Submission 2005.The production of light expanded clay aggregate gives rise to process emissions of CO2 that have not been known nor reported in earlier submissions. Emissions arise from the use of limestone, clay and additives and amounted to 6,308 ton CO2 in 2003. The whole time series for CRF 2A7 has been updated in Submission 2005.The use of limestone and dolomite was found to be more extensive than what had been known for earlier submissions. New activity data on the use of limestone and dolomite has been collected from nine plants. The whole time series for CRF 2A3 has been updated. The results show higher emission levels, but the difference between 1990 and 2003 is smaller in Submission 2005 compared to Submission 2004.Flaring of excess gases was found to be more extensive than what had been known for earlier submissions. New activity data has been collected from nine plants: four refineries, three steel producers, one chemical industry and one pulp producer. Calculated emissions will be reported in CRF 1B in Submission 2005 to the EU Monitoring Mechanism, the UNFCCC and the CLRTAP.
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| 20. |
- Lindskog, Annika, 1982, et al.
(författare)
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Melanocortin 1 receptor agonists reduce proteinuria.
- 2010
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Ingår i: Journal of the American Society of Nephrology : JASN. - 1533-3450 .- 1046-6673. ; 21:8, s. 1290-8
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Tidskriftsartikel (refereegranskat)abstract
- Membranous nephropathy is one of the most common causes of nephrotic syndrome in adults. Recent reports suggest that treatment with adrenocorticotropic hormone (ACTH) reduces proteinuria, but the mechanism of action is unknown. Here, we identified gene expression of the melanocortin receptor MC1R in podocytes, glomerular endothelial cells, mesangial cells, and tubular epithelial cells. Podocytes expressed most MC1R protein, which colocalized with synaptopodin but not with an endothelial-specific lectin. We treated rats with passive Heymann nephritis (PHN) with MS05, a specific MC1R agonist, which significantly reduced proteinuria compared with untreated PHN rats (P < 0.01). Furthermore, treatment with MC1R agonists improved podocyte morphology and reduced oxidative stress. In summary, podocytes express MC1R, and MC1R agonism reduces proteinuria, improves glomerular morphology, and reduces oxidative stress in nephrotic rats with PHN. These data may explain the proteinuria-reducing effects of ACTH observed in patients with membranous nephropathy, and MC1R agonists may provide a new therapeutic option for these patients.
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| 21. |
- Nyström, Anna-Maja, 1976-
(författare)
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RAS-MAPK syndromes - a Clinical and Molecular Investigation
- 2009
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The RAS-MAPK syndromes are a group of clinically and genetically related disorders, characterized by cardiac defects, facial dysmorphism, cutaneous abnormalities and neurocognitive impairment. The pathogenesis is dysregulation of the RAS-MAPK pathway, and several genes within the pathway are involved. The present thesis aimed at identifying genetic causes in three of the RAS-MAPK syndromes - Noonan syndrome (NS), cardio-facio-cutaneous syndrome (CFC) and Neurofibromatosis-Noonan syndrome (NFNS) - and at correlating genotype with phenotype. A mutation analysis of six genes associated with the RAS-MAPK syndromes in NS and CFC patients revealed mutations in 10/31 patients. The results suggested more complex genetic overlap and genetic heterogeneity among these syndromes than previously believed. Subsequently, gene dosage imbalances of seven RAS-MAPK-syndrome-related genes were investigated in mutation-negative patients. A multiplex ligation-dependent probe amplification strategy was developed that excluded copy number changes of these genes as a common mechanism in NS. Genetic causes of clinical variability in NS were investigated where an atypical and severe NS patient was described. In addition, multiple café-au-lait (CAL) spots affected the patient and four otherwise healthy family members. Molecular analysis of four candidate genes revealed a previously described de novo PTPN11 mutation and an inherited NF1 variant in the patient. Neither of them explained the CAL spots trait, which consequently represented a distinct entity. The results suggested that the atypical and severe phenotype in the patient could be a consequence of an additive effect. Finally, a family displaying NFNS was investigated clinically and molecularly revealing a novel mutation in the GAP-domain of NF1. Furthermore, the results suggested that other RAS-MAPK-syndrome-related genes are not involved in NFNS. A proposal of prioritizing the GAP-domain of NF1 in NFNS was presented. Conclusively, these studies contribute to further understanding of the RAS-MAPK syndromes and facilitate the diagnostic process and future prognosis prediction.
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| 22. |
- Poulikidou, Sofia, 1984, et al.
(författare)
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Impacts on fuel producers and customers of conflicting rules for life cycle assessment
- 2022
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Rapport (övrigt vetenskapligt/konstnärligt)abstract
- The use of life cycle assessment (LCA) as a tool for estimating the environmental performance of a product or service in a holistic and systematic manner is increasing. Fuel producers may need to apply different methodological frameworks to be used in different contexts; internally for product development activities as well as externally for communication with customers or authorities. Different LCA frameworks may vary in scope, system boundaries (i.e. life cycle stages to be considered) or modelling requirements (such as data demands but also more detailed methodological features). They may also vary in terms of information they can provide in relation to the environmental performance of the product. Those variations could lead to conflicting outcomes and conclusions and may also increase complexity for the LCA practitioner leading to high competence and resource requirements. Within the research project: Impacts on fuel producers and customers of conflicting rules for LCA , the requirements of different LCA frameworks and their implications to fuel producers are investigated. Focus has been given on three specific frameworks that are identified as relevant or potentially relevant for fuel producers, namely: the recast of the EU Renewable Energy Directive (referred to here as RED II), the EU framework for Product Environmental Footprint (PEF), and the framework of Environmental Product Declaration (EPD). The aim of the project is to increase understanding on the different LCA frameworks available and identify whether the multitude of such frameworks gives conflicting recommendations for environmental improvements and fuel choices. The three LCA frameworks listed above were applied in case studies. To illustrate the potential differences that the different frameworks may lead to, a variation of production pathways and feedstocks were selected including first generation as well as advanced biofuels. Based on the results obtained it can be concluded that applying all three frameworks is not a straightforward task. The methods contain fundamental differences and are at different levels of development, maturity, and adoption. In certain situations, they can lead to diverging conclusions as a result of different quantitative outcomes for a specific production pathway, thus influencing decision making processes in different directions. Understanding those differences and underlying assumptions is important for understanding the variations in outcome. The result for a specific fuel could differ substantially depending on the framework applied and the assumptions and interpretations made when applying this framework. Certain methodological parameters were identified to have a greater impact on the results than others: • The three frameworks diverge in the methods applied for modelling waste management, which can be very important for the results when the biofuel is produced from waste. • The frameworks diverge in what approaches are allowed for modelling processes with multiple products. This can be very important for the results when the fuel is co-produced with other products. • The frameworks also diverge in how the electricity supply is modelled. This is not very important for the results in most of our case studies, because the production of these biofuels does not require a lot of electricity. The study confirms that applying a framework like EPD or PEF in addition to RED II would require significant supplementary efforts. Not only because of different rules which were often contradicting or difficult to interpret but also because of additional data and reporting requirements. The need for expertise and resources is increasing for fuel producers to be able to provide EPD and PEF compliant assessments. To enhance the development and harmonization of LCA approaches this project stresses the need for product specific rules (in the form of Product Environmental Category Rules (PEFCR) and Product Category Rules (PCR)) for renewable fuels. Future versions of all three studied frameworks should be clearer on how specific methodological choices are to be applied (e.g., when it comes to allocation and multifunctional processes) as well as when it comes to model electricity supply. RED for example shall be clearer on how to define the electricity region while EPD guidelines on how to define the electricity market. Although it is not realistic to aim for a single unified LCA framework, the biofuel PCR and PEFCR can be developed with RED in mind. Some aspects of the PEF methodology can perhaps also be integrated into RED III that is currently under development. This would enhance the broader adoption of the frameworks among fuel producers. Finally, the involvement and engagement of the industry, and fuel producers themselves is very important. Industry initiatives are essential for the development of biofuel PCR and PEFCR while the general development of the three frameworks can also be influenced. In this study, we also investigated the relationship between the LCA frameworks and schemes for chain of custody certification (CoCC), in particular schemes for mass balance certifications (MBC) to investigate to what extent these schemes complement or overlap with LCA. The purpose of MBC schemes and LCA are different, in the sense that the first aim at verifying the sources and sustainability of total amounts of raw materials used by tracking them throughout the value chain, while the second at quantifying specific environmental impact. The system boundaries are similar, since both cover the entire value chain, but may be applied differently depending on the detailed frameworks applied and choices made in applying the MBC schemes. By identifying and clearly illustrating the variations among the studied frameworks the study enhances application, development, and harmonization of LCA, in a broader perspective, informs LCA practitioners but also decision makers and provides insights on how the identified challenges can be addressed.
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| 23. |
- Adelöf, Anna, et al.
(författare)
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Förvaltning av SNOMED CT som en del i det nationella fackspråket för vård och omsorg
- 2011
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Rapport (populärvet., debatt m.m.)abstract
- Förvaltningsrapporten fokuserar på Snomed CT, eftersom det redan i dag finns rutiner för förvaltningar av termbanken och nationella hälsorelaterade klassifikationer. Ett särskilt utvecklingsarbete kommer att krävas för dessa delar.Rapporten tar upp syfte och mål med förvaltningen. Utöver det redogör rapporten för vilka konkreta ansvarsområden som ingår i förvaltningen av Snomed CT. Målet för förvaltningen är att Socialstyrelsen regelbundet ska kunna tillhandahålla en kontrollerad och uppdaterad release av Snomed CT. Det skulle möjliggöra användning inom vård och omsorg. Rapporten tar även upp behovet av kompetens, utbildning och finansiella resurser.
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| 24. |
- Ahlström, Christer, et al.
(författare)
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Fit-for-duty test for estimation of drivers sleepiness level: Eye movements improve the sleep/wake predictor
- 2013
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Ingår i: Transportation Research Part C. - : Elsevier. - 0968-090X .- 1879-2359. ; 26, s. 20-32
-
Tidskriftsartikel (refereegranskat)abstract
- Driver sleepiness contributes to a considerable proportion of road accidents, and a fit-for-duty test able to measure a drivers sleepiness level might improve traffic safety. The aim of this study was to develop a fit-for-duty test based on eye movement measurements and on the sleep/wake predictor model (SWP, which predicts the sleepiness level) and evaluate the ability to predict severe sleepiness during real road driving. Twenty-four drivers participated in an experimental study which took place partly in the laboratory, where the fit-for-duty data were acquired, and partly on the road, where the drivers sleepiness was assessed. A series of four measurements were conducted over a 24-h period during different stages of sleepiness. Two separate analyses were performed; a variance analysis and a feature selection followed by classification analysis. In the first analysis it was found that the SWP and several eye movement features involving anti-saccades, pro-saccades, smooth pursuit, pupillometry and fixation stability varied significantly with different stages of sleep deprivation. In the second analysis, a feature set was determined based on floating forward selection. The correlation coefficient between a linear combination of the acquired features and subjective sleepiness (Karolinska sleepiness scale, KSS) was found to be R = 0.73 and the correct classification rate of drivers who reached high levels of sleepiness (KSS andgt;= 8) in the subsequent driving session was 82.4% (sensitivity = 80.0%, specificity = 84.2% and AUC = 0.86). Future improvements of a fit-for-duty test should focus on how to account for individual differences and situational/contextual factors in the test, and whether it is possible to maintain high sensitive/specificity with a shorter test that can be used in a real-life environment, e.g. on professional drivers.
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| 25. |
- Al-Manasir, Nodar, et al.
(författare)
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Effects of Temperature and pH on the Contraction and Aggregation of Microgels in Aqueous Suspensions
- 2009
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Ingår i: Journal of Physical Chemistry B. - : American Chemical Society (ACS). - 1520-6106 .- 1520-5207. ; 113:32, s. 11115-11123
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Tidskriftsartikel (refereegranskat)abstract
- Chemically cross-linked poly(N-isopropylacrylamide) (PNIPAM) microgels and PNIPAM with different amounts of acrylic acid groups (PNIPAM-co-PAA) were synthesized and the temperature-induced aggregation behaviors of aqueous suspensions of these microgels were investigated mainly with the aid of dynamic light scattering (DLS) and turbidimetry. The DLS results show that the particles at all conditions shrink at temperatures up to approximately the lower critical solution temperature (LCST), but the relative contraction effect is larger for the microgels without acid groups or for microgels with added anionic surfactant (SDS). A significant depression of the cloud point is found in suspensions of PNIPAM with very low concentrations of SDS. The compression of the microgels cannot be traced from the turbidity results, but rather the values of the turbidity increase in this temperature interval. This phenomenon is discussed in the framework of a theoretical model. At temperatures above LCST, the size of the microgels without attached charged groups in a very dilute suspension is unaffected by temperature, while the charged particles (pH 7 and 11) continue to collapse with increasing temperature over the entire domain. In this temperature range, low-charged particles of higher concentration and particles containing acrylic acid groups at low pH (pH 2) aggregate, and macroscopic phase separation is approached at higher temperatures. This study demonstrates how the stabilization of microgels can be affected by factors such as polymer concentration, addition of ionic surfactant to particles without charged acid groups, amount of charged groups in the polymer, and pH.
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| 26. |
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| 27. |
- Alger, Susanne, 1967-
(författare)
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Licence to drive : the importance of reliability for the validity of the Swedish driving licence test
- 2019
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Licentiatavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Background: The Swedish driving licence test is a criterion-referenced test resulting in a pass or fail. It currently consists of two parts - a theory test with 65 multiple-choice items and a practical driving test where at least 25 minutes are spent driving in traffic. It is a high-stakes test in the sense that the results are used to determine whether the test-taker should be allowed to drive a car without supervision. As the only other requirements for obtaining a licence is a few hours of hazard education (and a short introduction if you intend to drive with a lay instructor) it is important that the test result, in terms of pass or fail, is reliable and valid. If this is not the case it could have detrimental effects on traffic safety. Examining all relevant aspects is beyond the scope of this licentiate thesis so I have focused on reliability.Methods Reliability for both the theoretical and practical test results was examined. As these are very different types of tests the types of reliability examined also differed. In order to examine inter-rater reliability of the driving test 83 examiners were accompanied by one of five selected supervising examiners for a day of tests. All in all 535 tests were conducted with two examiners assessing the same performance. At the end of the day the examiners compared notes and tried to determine the reason for any inconsistencies. Both examiners and students also filled in questionnaires with questions about background and preparation. As for studying decision consistency and decision accuracy of the theory test, three test versions (a total of around 12,000 tests) were examined with the help of methods devised by Subkoviak (Subkoviak, 1976, 1988) and Hanson & Brennan (Brennan, 2004; Hanson & Brennan, 1990).Results The results from two research studies concerning reliability were presented. Study I focused on inter-rater reliability in the driving test and in 93 per cent of cases the examiners made the same assessment. For the tests where their opinions differed there was no correlation to any of the background variables or other variables examined except for three, which had logical explanations and did not constitute a problem. Although there were cases where the differences were due to different stances on matters of interpretation the most common suggested cause was the placement in the car (back seat vs. front seat). Although the supervising examiners gave both praise and criticism as to how the test was carried out the study does not answer the question whether the tests were equal in terms of composition and difficulty.In Study II the focus was on decision consistency and decision accuracy in the theory test. Three versions of the theory tests were examined and, on the whole, found to be fairly similar in terms of item difficulty and score distribution, but the mean was so close to the cut-score (i.e. the score required to pass) that the pass rate differed somewhat between versions. Agreement coefficients were around .80 for all test versions (between .79 and .82 depending on method). Classification accuracy indicated an .87 probability of a correct classification.Conclusion It is important to examine the reliability and validity of the driving licence test since a misclassification can have serious consequences in terms of traffic safety. In the studies included here the rate of agreement between examiners is deemed as satisfactory. It would be preferable if the classification consistency and classification accuracy, as estimated by the methods used, were higher for the theory test, given its importance.While reliability in terms of agreement between raters/examiners or consistency and accuracy of classification are routinely examined in other contexts, such as large-scale educational testing, this is not often done for the driving licence tests. At the same time, the methods used here can be transferred to contexts where such properties are generally not examined. Collecting information about test-takers and examiners, like in Study I, can provide evidence concerning possible bias.Examining to what extent decisions are consistent is one important aspect of collecting evidence that shows that test results can be used to draw conclusions about driver competence. Still, regardless of outcome, validation is a process that never ends. There is always reason to examine various aspects and make further improvements. There are also many other relevant aspects to examine. A prerequisite for the validity of the score interpretation of a criterion-referenced test like this one is that the cut-score is appropriate and the content relevant. This should therefore be the subject of further research as the validation process continues.
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| 28. |
- Alghamdi, Azza
(författare)
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Approximation of pluricomplex Green functions : A probabilistic approach
- 2018
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- This PhD thesis focuses on probabilistic methods of approximation of pluricomplex Green functions and is based on four papers.The thesis begins with a general introduction to the use of pluricomplex Green functions in multidimensional complex analysis and a review of their main properties. This is followed by short description of the main results obtained in the enclosed papers.In Paper I, we study properties of the metric space of pluriregular sets, that is zero sets of continuous pluricomplex Green functions. The best understood non-trivial examples of such sets are composite Julia sets, obtained by iteration of finite families of polynomial mappings in several complex variables. We prove that the so-called chaos game is applicable in the case of such sets. We also visualize some composite Julia sets using escape time functions and Monte Carlo simulation.In Paper II, we extend results in Paper I to the case of infinite compact families of proper polynomials mappings. With composition as the semigroup operation, we generate families of infinite iterated function systems with compact attractors. We show that such attractors can be approximated probabilistically in a manner of the classic chaos game.In Paper III, we study numerical approximation and visualisation of pluricomplex Green functions based on the Monte-Carlo integration. Unlike alternative methods that rely on locating a sequence of carefully chosen finite sets of points satisfying some optimal conditions for approximation purposes, our approach is simpler and more direct by relying on generation of pseudorandom points. We examine numerically the errors of approximation for some simple geometric shapes for which the pluricomplex Green functions are known. If the pluricomplex Green functions are not known, the errors in Monte Carlo integration can be expressed with the aid of statistics in terms of confidence intervals.Finally, in Paper IV, we study how perturbations of an orthonomalization procedure influence the resulting approximate Bergman functions. To this end we consider the concept of near orthonormality of a finite set of vectors in an inner product space, understood as closeness of the Gram matrix of those vectors to the identity matrix. We provide estimates for the errors resulting from using nearly orthogonal bases instead of orthogonal ones. The motivation for this work comes from Paper III: when Gram matrices are calculated via Monte Carlo integration, the outcomes of standard orthogonalisation algorithms are nearly orthonormal bases.
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| 29. |
- Allanson, Judith E., et al.
(författare)
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Cardio-Facio-Cutaneous Syndrome : Does Genotype Predict Phenotype?
- 2011
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Ingår i: American Journal of Medical Genetics, Part C: Seminars in Medical Genetics. - : Wiley. - 1552-4868. ; 157C:2, s. 129-135
-
Tidskriftsartikel (refereegranskat)abstract
- Cardio-facio-cutaneous (CFC) syndrome is a sporadic multiple congenital anomalies/mental retardation condition principally caused by mutations in BRAF, MEK1, and MEK2. Mutations in KRAS and SHOC2 lead to a phenotype with overlapping features. In approximately 10-30% of individuals with a clinical diagnosis of CFC, a mutation in one of these causative genes is not found. Cardinal features of CFC include congenital heart defects, a characteristic facial appearance, and ectodermal abnormalities. Additional features include failure to thrive with severe feeding problems, moderate to severe intellectual disability and short stature with relative macrocephaly. First described in 1986, more than 100 affected individuals are reported. Following the discovery of the causative genes, more information has emerged on the breadth of clinical features. Little, however, has been published on genotype-phenotype correlations. This clinical study of 186 children and young adults with mutation-proven CFC syndrome is the largest reported to date. BRAF mutations are documented in 140 individuals (similar to 75%), while 46 (similar to 25%) have a mutation in MEK 1 or MEK 2. The age range is 6 months to 32 years, the oldest individual being a female from the original report [Reynolds et al. (1986); Am J Med Genet 25:413-427]. While some clinical data on 136 are in the literature, 50 are not previously published. We provide new details of the breadth of phenotype and discuss the frequency of particular features in each genotypic group. Pulmonary stenosis is the only anomaly that demonstrates a statistically significant genotype-phenotype correlation, being more common in individuals with a BRAF mutation.
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| 30. |
- Andershed, Henrik, 1975-, et al.
(författare)
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Bokens bakgrund, syfte, innehåll och målgrupp
- 2010. - 1
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Ingår i: Ungdomar som begår brott. - Stockholm : Gothia Förlag AB. - 9789172056664 ; , s. 13-24
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Bokkapitel (övrigt vetenskapligt/konstnärligt)
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| 31. |
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| 32. |
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| 33. |
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| 34. |
- Andersson, Rebecca, et al.
(författare)
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Differential role of cytosolic Hsp70s in longevity assurance and protein quality control
- 2021
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Ingår i: PLoS Genetics. - : Public Library of Science (PLoS). - 1553-7404 .- 1553-7390. ; 17:1
-
Tidskriftsartikel (refereegranskat)abstract
- 70 kDa heat shock proteins (Hsp70) are essential chaperones of the protein quality control network; vital for cellular fitness and longevity. The four cytosolic Hsp70's in yeast, Ssa1-4, are thought to be functionally redundant but the absence of Ssa1 and Ssa2 causes a severe reduction in cellular reproduction and accelerates replicative aging. In our efforts to identify which Hsp70 activities are most important for longevity assurance, we systematically investigated the capacity of Ssa4 to carry out the different activities performed by Ssa1/2 by overproducing Ssa4 in cells lacking these Hsp70 chaperones. We found that Ssa4, when overproduced in cells lacking Ssa1/2, rescued growth, mitigated aggregate formation, restored spatial deposition of aggregates into protein inclusions, and promoted protein degradation. In contrast, Ssa4 overproduction in the Hsp70 deficient cells failed to restore the recruitment of the disaggregase Hsp104 to misfolded/aggregated proteins, to fully restore clearance of protein aggregates, and to bring back the formation of the nucleolus-associated aggregation compartment. Exchanging the nucleotide-binding domain of Ssa4 with that of Ssa1 suppressed this 'defect' of Ssa4. Interestingly, Ssa4 overproduction extended the short lifespan of ssa1 Delta ssa2 Delta mutant cells to a lifespan comparable to, or even longer than, wild type cells, demonstrating that Hsp104-dependent aggregate clearance is not a prerequisite for longevity assurance in yeast. Author summary All organisms have proteins that network together to stabilize and protect the cell throughout its lifetime. One of these types of proteins are the Hsp70s (heat shock protein 70). Hsp70 proteins take part in folding other proteins to their functional form, untangling proteins from aggregates, organize aggregates inside the cell and ensure that damaged proteins are destroyed. In this study, we investigated three closely related Hsp70 proteins in yeast; Ssa1, 2 and 4, in an effort to describe the functional difference of Ssa4 compared to Ssa1 and 2 and to answer the question: What types of cellular stress protection are necessary to reach a normal lifespan? We show that Ssa4 can perform many of the same tasks as Ssa1 and 2, but Ssa4 doesn't interact in the same manner as Ssa1 and 2 with other types of proteins. This leads to a delay in removing protein aggregates created after heat stress. Ssa4 also cannot ensure that misfolded proteins aggregate correctly inside the nucleus of the cell. However, this turns out not to be necessary for yeast cells to achieve a full lifespan, which shows us that as long as cells can prevent aggregates from forming in the first place, they can reach a full lifespan.
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| 35. |
- Andersson-Sköld, Yvonne, 1957-, et al.
(författare)
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Coal tar-containing asphalt : Resource or hazardous waste?
- 2007
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Ingår i: Journal of Industrial Ecology. - : Wiley-Blackwell. - 1088-1980 .- 1530-9290. ; 11:4, s. 99-116
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Tidskriftsartikel (refereegranskat)abstract
- Coal tar was used in Sweden for the production of asphalt and for the drenching of stabilization gravel until 1973. The tar has high concentrations of polycyclic aromatic hydrocarbons (PAH), some of which may be strongly carcinogenic. Approximately 20 million tonnes of tar-containing asphalt is present in the public roads in Sweden. Used asphalt from rebuilding can be classified as hazardous waste according to the Swedish Waste Act. The cost of treating the material removed as hazardous waste can be very high due to the large amount that has to be treated, and the total environmental benefit is unclear. The transport of used asphalt to landfill or combustion will affect other environmental targets. The present project, based on three case studies of road projects in Sweden, evaluates the consequences of four scenarios for handling the material: reuse, landfill, biological treatment, and incineration. The results show that reuse of the coal tar-containing materials in new road construction is the most favorable alternative in terms of cost, material use, land use, energy consumption, and air emissions.
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| 36. |
- Annerberg, Anna, 1972-
(författare)
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Gymnasielärares skrivpraktiker : skrivande som professionell handling i en digitaliserad skola
- 2016
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The aim of this thesis is to contribute to deeper knowledge about the writing practices of teachers in upper secondary school. Schools are under constant pressure to respond to the needs and expectations of an ever-changing society and political intentions. A major factor in this change which is taking place in schools is digitalization. Another factor is the adoption of new governing principles for schools involving management by goals and results, which brings increased demands for written documentation of teachers' work.In order to describe and problematize this development the thesis is based on a combination of Critical Discourse Analysis and New Literacy (Clark and Ivanič, 1997). The theoretical framework rests upon an understanding of writing as social action and the idea that texts both affect and are affected by the social environment. The empirical study focuses on twelve teachers and their writing practices, analyzed during week-long field visits over three years. The teachers' talk about their writing is used together with analyses of texts and images to investigate parts of teachers' writing which, according to the teachers, are considered complex and problematic.The findings indicate significant differences between the writing practices of the individual teachers, where each teacher has his or her own system of texts fulfilling different purposes. Despite these differences it is still possible to identify recurrent themes in the discursive conditions for teachers' writing: efficiency, reuse, authority, audit, relationships to addressees, and room to maneuver. The study illustrates possible dilemmas for teachers' writing at the intersection of teachers' professional responsibility and demands for accountability.
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| 37. |
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| 38. |
- Barbosa, Edna J L, 1961, et al.
(författare)
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Extracellular water and blood pressure in adults with growth hormone (GH) deficiency: a genotype-phenotype association study.
- 2014
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Ingår i: PloS one. - : Public Library of Science (PLoS). - 1932-6203. ; 9:8
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Tidskriftsartikel (refereegranskat)abstract
- Growth hormone deficiency (GHD) in adults is associated with decreased extracellular water volume (ECW). In response to GH replacement therapy (GHRT), ECW increases and blood pressure (BP) reduces or remains unchanged. Our primary aim was to study the association between polymorphisms in genes related to renal tubular function with ECW and BP before and 1 year after GHRT. The ECW measures using bioimpedance analysis (BIA) and bioimpedance spectroscopy (BIS) were validated against a reference method, the sodium bromide dilution method (Br(-)).
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| 39. |
- Barbosa, Edna J L, 1961, et al.
(författare)
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Genotypes associated with lipid metabolism contribute to differences in serum lipid profile of GH-deficient adults before and after GH replacement therapy.
- 2012
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Ingår i: European journal of endocrinology / European Federation of Endocrine Societies. - 1479-683X .- 0804-4643. ; 167:3, s. 353-62
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Tidskriftsartikel (refereegranskat)abstract
- bjective: GH deficiency (GHD) in adults is associated with an altered serum lipid profile that responds to GH replacement therapy (GHRT). This study evaluated the influence of polymorphisms in genes related to lipid metabolism on serum lipid profile before and after 1 year of GHRT in adults. Design and methods: In 318 GHD patients, total cholesterol (TC) serum concentrations, LDL-C, HDL-C, and triglycerides (TG) were assessed. Using a candidate gene approach, 20 single nucleotide polymorphisms (SNPs) were genotyped. GH dose was individually titrated to obtain normal serum IGF1 concentrations. Results: At baseline, the minor alleles of cholesteryl ester transfer protein (CETP) gene SNPs rs708272 and rs1800775 were associated with higher serum TC and apolipoprotein E (APOE) gene SNP rs7412 with lower TC concentrations; CETP SNPs rs708272, rs1800775, and rs3764261 and apolipoprotein B (APOB) gene SNP rs693 with higher serum HDL-C; APOE SNP rs7412, peroxisome proliferator-activated receptor gamma (PPARG) gene SNP rs10865710 with lower LDL-C, and CETP SNP rs1800775 with higher LDL-C; and APOE/C1/C4/C2 cluster SNP rs35136575 with lower serum TG. After treatment, APOB SNP rs676210 GG genotype was associated with larger reductions in TC and LDL-C and PPARG SNP rs10865710 CC genotype with greater TC reduction. All associations remained significant when adjusted for age, sex, and BMI. Conclusions: In GHD adults, multiple SNPs in genes related to lipid metabolism contributed to individual differences in baseline serum lipid profile. The GH treatment response in TC and LDL-C was influenced by polymorphisms in the APOB and PPARG genes.
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| 40. |
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| 41. |
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| 42. |
- Birkeland, Kare I., et al.
(författare)
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Cardiovascular mortality and morbidity in patients with type 2 diabetes following initiation of sodium-glucose co-transporter-2 inhibitors versus other glucose-lowering drugs (CVD-REAL Nordic) : A Multinational Observational Analysis
- 2017
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Ingår i: The Lancet Diabetes and Endocrinology. - New York : Elsevier. - 2213-8587 .- 2213-8595. ; 5:9, s. 709-717
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Tidskriftsartikel (refereegranskat)abstract
- Background In patients with type 2 diabetes and a high cardiovascular risk profile, the sodium-glucose co-transporter-2 (SGLT2) inhibitors empagliflozin and canagliflozin have been shown to lower cardiovascular morbidity and mortality. Using real-world data from clinical practice, we aimed to compare cardiovascular mortality and morbidity in new users of SGLT2 inhibitors versus new users of other glucose-lowering drugs, in a population with a broad cardiovascular risk profile. Methods CVD-REAL Nordic was an observational analysis of individual patient-level data from the Prescribed Drug Registers, Cause of Death Registers, and National Patient Registers in Denmark, Norway, and Sweden. All patients who filled a prescription for glucose-lowering drugs between 2012 and 2015 were included and followed up until Dec 31, 2015. Patients were divided into new users of SGLT2 inhibitors and new users of other glucose-lowering drugs. Each SGLT2 inhibitor user was matched with three users of other glucose-lowering drugs by use of propensity scores. Hazard ratios (HRs) were estimated by country (Cox survival model) and weighted averages were calculated. Cardiovascular outcomes investigated were cardiovascular mortality, major adverse cardiovascular events (cardiovascular mortality, myocardial infarction, and ischaemic or haemorrhagic stroke), hospital events for heart failure (inpatient or outpatient visit with a primary diagnosis of heart failure), non-fatal myocardial infarction, non-fatal stroke, and atrial fibrillation. We also assessed incidence of severe hypoglycaemia. Findings Matched SGLT2 inhibitor (n=22 830) and other glucose-lowering drug (n=68 490) groups were well balanced at baseline, with a mean follow-up of 0.9 (SD 4.1) years (80 669 patient-years) and mean age of 61 (12.0) years; 40% (36 362 of 91 320) were women and prevalence of cardiovascular disease was 25% (22 686 of 91 320). 94% of the total SGLT2 inhibitor exposure time was for use of dapagliflozin, with 5% for empagliflozin, and 1% for canagliflozin. Compared with other glucose-lowering drugs, use of SGLT2 inhibitors was associated with decreased risk of cardiovascular mortality (HR 0.53 [95% CI 0.40-0.71]), major adverse cardiovascular events (0.78 [0.69-0.87]), and hospital events for heart failure (0.70 [0.61-0.81]; p<0.0001 for all). We did not identify significant differences between use of SGLT2 inhibitors and use of other glucose-lowering drugs for non-fatal myocardial infarction, non-fatal stroke, or atrial fibrillation. Compared with other glucose-lowering drugs, use of SGLT2 inhibitors was associated with a decreased risk of severe hypoglycaemia (HR 0.76 [0.65-0.90]; p=0.001). For cardiovascular mortality, the differences were similar for the 25% of individuals with cardiovascular disease at baseline and those without (HR 0.60 [0.42-0.85] vs 0.55 [0.34-0.90]), while for major adverse cardiovascular events the HR in the group with cardiovascular disease at baseline was 0.70 (0.59-0.83) versus 0.90 (0.76-1.07) in the group without. Interpretation In a population of patients with type 2 diabetes and a broad cardiovascular risk profile, SGLT2 inhibitor use was associated with reduced cardiovascular disease and cardiovascular mortality compared with use of other glucose-lowering drugs-a finding consistent with the results of clinical trials in patients at high cardiovascular risk.
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| 43. |
- Björnson Granqvist, Anna, 1974, et al.
(författare)
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Impaired glomerular and tubular antioxidative defense mechanisms in nephrotic syndrome.
- 2010
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Ingår i: American journal of physiology. Renal physiology. - : American Physiological Society. - 1522-1466 .- 1931-857X. ; 299:4
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Tidskriftsartikel (refereegranskat)abstract
- The molecular mechanisms behind acquired nephrotic syndrome (NS) are still largely unknown. One possible explanation for the development of proteinuria is oxidative damage to the glomerular cells. Our hypothesis was that the oxidative defense is weakened in NS, and we focused on measurements of the oxidative-antioxidative status in the glomerular and tubular parts of the nephron. Gene expression was analyzed in renal biopsies from patients with NS. In addition, to compare the acute and chronic phases of the disease, we studied puromycin-treated rats. In the biopsy material, the expression of enzymes involved in the antioxidative defense was higher in the tubulointerstitial compartment than in the glomerular cells. Real-time PCR analysis revealed a decreased glomerular expression in nephrotic kidneys for the antioxidant enzymes catalase and glutathione peroxidase-3, and -4. The tubular gene expression was downregulated for catalase, glutathione peroxidase-3, and thioredoxin reductase-1 and -2. The altered gene expression was accompanied by increased lipid peroxidation in urine. In rats, serum concentrations of ascorbyl-free radicals, measured with electron spin resonance, were elevated in the acute phase of the disease, suggesting increased oxidative stress in the circulation. In addition, we saw an increase in the plasma antioxidant capacity combined with a decreased oxidation of proteins in sera from nephrotic rats, but not from humans. In conclusion, there is a marked downregulation of several antioxidative enzymes in nephrotic kidneys, especially in glomerular structures. Our data suggest that oxidative damage to glomerular cells may contribute significantly to the course and prognosis of nephrotic syndrome.
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| 44. |
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| 45. |
- Bondeson, Marie-Louise, et al.
(författare)
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Connexin 26 (GJB2) mutations in two Swedish patients with atypical Vohwinkel (mutilating keratoderma plus deafness) and KID syndrome both extensively treated with acitretin
- 2006
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Ingår i: Acta Dermato-Venereologica. - : Medical Journals Sweden AB. - 0001-5555 .- 1651-2057. ; 86:6, s. 503-508
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Tidskriftsartikel (refereegranskat)abstract
- Neuroectodermal syndromes involving the skin and inner ear may be associated with mutations in connexin proteins, which form gap junctions important for intercellular communication. Vohwinkel syndrome (keratodermia mutilans with hearing loss) and keratitis-ichthyosis-deafness (KID) syndrome are rare ectodermal dysplasias associated with dominant mutations in the GJB2 gene encoding connexin 26. We report here two patients, one with KID and one with Vohwinkel syndrome. Both displayed unusual clinical features and responded well to long-term treatment with oral retinoid. Mutation analysis revealed a novel GJB2 mutation p.Gly59Ser in the patient with Vohwinkel syndrome, whereas a recurrent mutation (p.Asp50Asn) was found in the patient with KID syndrome. The clinical features, particularly a proneness to skin cancer in the patient with Vohwinkel syndrome, are discussed in relation to the identified genotypes.
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| 46. |
- Borssen, Magnus, et al.
(författare)
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hTERT promoter methylation and telomere length in childhood acute lymphoblastic leukemia-associations with immunophenotype and cytogenetic subgroup
- 2011
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Ingår i: Experimental Hematology. - New York : Elsevier. - 0301-472X .- 1873-2399. ; 39:12, s. 1144-1151
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Tidskriftsartikel (refereegranskat)abstract
- Telomere maintenance, important for long-term cell survival and malignant transformation, is directed by a multitude of factors, including epigenetic mechanisms, and has been implicated in outcomes for patients with leukemia. In the present study, the objective was to investigate the biological and clinical significance of telomere length and promoter methylation of the human telomerase reverse transcriptase gene in childhood acute lymphoblastic leukemia. A cohort of 169 childhood acute lymphoblastic leukemias was investigated for telomere length, human telomerase reverse transcriptase gene promoter methylation status, genomic aberrations, immunophenotype, and clinical outcomes. Methylation of the core promoter of the human telomerase reverse transcriptase (hTERT) gene was demonstrated in 24% of diagnostic samples, with a significant difference between B-cell precursor (n = 130) and T-cell acute lymphoblastic leukemia (ALL) (n = 17) cases (18% and 72%, respectively; p < 0.001). No remission sample demonstrated hTERT promoter methylation (n = 40). Within the B-cell precursor group, t(12;21)(p13;q22) [ETV6/RUNX1] cases (n = 19) showed a much higher frequency of hTERT methylation than high-hyperdiploid (51 61 chromosomes) ALL (n = 44) (63% and 7%, respectively; p < 0.001). hTERT messenger RNA levels were negatively associated with methylation status and, in the t(12;21) group, methylated cases had shorter telomeres (p = 0.017). In low-risk B-cell precursor patients (n = 101), long telomeres indicated a worse prognosis. The collected data from the present study indicate that the telomere biology in childhood ALL has clinical implications and reflects molecular differences between diverse ALL subgroups. (C) 2011 ISEH - Society for Hematology and Stem Cells. Published by Elsevier Inc.
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| 47. |
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| 48. |
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| 49. |
- Bylund, Johan, 1975, et al.
(författare)
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Proinflammatory activity of a cecropin-like antibacterial peptide from Helicobacter pylori
- 2001
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Ingår i: Antimicrob Agents Chemother. ; 45:6, s. 1700-4
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Tidskriftsartikel (refereegranskat)abstract
- Helicobacter pylori, the bacterial pathogen associated with gastritis and peptic ulcers, is highly successful in establishing infection in the human gastric mucosa, a process typically associated with massive infiltration of inflammatory cells. Colonization of the mucosa is suggested to be facilitated by H. pylori-produced cecropin-like peptides with antibacterial properties, giving the microbe a competitive advantage over other bacteria. We show that a cecropin-like antibacterial peptide from H. pylori, Hp(2-20), not only has a potent bactericidal effect but also induces proinflammatory activities in human neutrophils, e.g., upregulation of integrins (Mac-1), induction of chemotaxis, and activation of the oxygen radical producing NADPH-oxidase. Furthermore, we show that these effects are mediated through binding of Hp(2-20) to the promiscuous, G-protein-linked lipoxin A(4) receptor-formyl peptide-like receptor 1.
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| 50. |
- Cappelletto, Elia, et al.
(författare)
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Impact of Post Manufacturing Handling of Protein-Based Biologic Drugs on Product Quality and User Centricity
- 2024
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Ingår i: Journal of Pharmaceutical Sciences. - : Elsevier B.V.. - 0022-3549 .- 1520-6017.
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Forskningsöversikt (refereegranskat)abstract
- This article evaluates the current gaps around the impact of post-manufacturing processes on the product qualities of protein-based biologics, with a focus on user centricity. It includes the evaluation of the regulatory guidance available, describes a collection of scientific literature and case studies to showcase the impact of post-manufacturing stresses on product and dosing solution quality. It also outlines the complexity of clinical handling and the need for communication, and alignment between drug providers, healthcare professionals, users, and patients. Regulatory agencies provide clear expectations for drug manufacturing processes, however, guidance supporting post-product manufacturing handling is less defined and often misaligned. This is problematic as the pharmaceutical products experience numerous stresses and processes which can potentially impact drug quality, safety and efficacy. This article aims to stimulate discussion amongst pharmaceutical developers, health care providers, device manufacturers, and public researchers to improve these processes. Patients and caregivers' awareness can be achieved by providing relevant educational material on pharmaceutical product handling.
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