| 1. |
|
|
| 2. |
- Clausen, Henning, et al.
(författare)
-
Newborn Screening for High-Risk Congenital Heart Disease by Dried Blood Spot Biomarker Analysis.
- 2024
-
Ingår i: JAMA Network Open. - 2574-3805. ; 7:6
-
Tidskriftsartikel (refereegranskat)abstract
- Importance Congenital heart disease (CHD) is the most common human organ malformation, affecting approximately 1 of 125 newborns globally.Objectives Assessing the performance of 2 diagnostic tests using minimal amounts of dried blood spots (DBS) to identify high-risk CHD compared with controls in a Swedish cohort of neonates.Design, Setting, and Participants This diagnostic study took place in Sweden between 2019 and 2023 and enrolled full-term babies born between 2005 and 2023. All cases were identified through centralized pediatric cardiothoracic surgical services in Lund and Gothenburg, Sweden. Controls were followed up for 1 year to ensure no late presentations of high-risk CHD occurred. Cases were verified through surgical records and echocardiography.Exposure High-risk CHD, defined as cases requiring cardiac surgical management during infancy due to evolving signs of heart failure or types in which the postnatal circulation depends on patency of the arterial duct. Using 3-μL DBS samples, automated quantitative tests for NT-proBNP and interleukin 1 receptor-like 1 (IL-1 RL1; formerly known as soluble ST2) were compared against established CHD screening methods.Main Outcomes and Measures Performance of DBS tests to detect high-risk CHD using receiver operating characteristic curves; Bland-Altman and Pearson correlation analyses to compare IL-1 RL1 DBS with plasma blood levels.Results A total of 313 newborns were included (mean [SD] gestational age, 39.4 [1.3] weeks; 181 [57.8%] male). Mean (SD) birthweight was 3495 (483) grams. Analyzed DBS samples included 217 CHD cases and 96 controls. Among the CHD cases, 188 participants (89.3%) were high-risk types, of which 73 (38.8%) were suspected prenatally. Of the 188 high-risk cases, 94 (50.0%) passed pulse oximetry screening and 36 (19.1%) were initially discharged after birth without diagnoses. Combining NT-proBNP and IL-1 RL1 tests performed well in comparison with existing screening methods and enabled additional identification of asymptomatic babies with receiver operating characteristic area under the curve 0.95 (95% CI, 0.93-0.98).Conclusions and relevance In this diagnostic study, NT-proBNP and IL-1 RL1 DBS assays identified high-risk CHD in a timely manner, including in asymptomatic newborns, and improved overall screening performance in this cohort from Sweden. Prospective evaluation of this novel approach is warranted.
|
|
| 3. |
|
|
| 4. |
|
|
| 5. |
|
|
| 6. |
- Henriksson, Malin, 1981-, et al.
(författare)
-
"Om nåt skulle hända" : Ett gestaltningsprojekt om ungas upplevelser av otrygghet i utemiljöer
- 2016
-
Rapport (populärvet., debatt m.m.)abstract
- Under 2016 producerade Statens väg- och transportforskningsinstitut (VTI) tillsammans med Östergötlands museum en vandringsutställning om ungas upplevelser av otrygghet. Projektet finansierades av Boverket inom utlysningen ”stöd till utvecklingsprojekt för jämställda offentliga miljöer i städer och tätorter”. Projektet utgår från problematiken att ungdomars upplevelser av otrygghet sällan kommer till uttryck i stadsplaneringen. Inte heller i forskningen om upplevelser av våld och otrygghet i det offentliga rummet uppmärksammas ungdomar i särskilt hög grad. Samtidigt förflyttar sig ungdomar som grupp mer än andra grupper och vistas i högre grad utomhus. De är också utomhus på andra tidpunkter än vuxna, på kvällen och natten. Vidare är ungdomar, oavsett kön, mer utsatta för våld utomhus än andra grupper. Det är därför att utveckla nya verktyg för att belysa ungdomars erfarenheter av otrygghet i utomhusmiljöer.Underlaget för utställningen utgjordes av gruppintervjuer med ett fyrtiotal ungdomar (killar, tjejer och transpersoner) mellan 13 och 20 år. Den feministiska metoden minnesarbete användes för att underlätta samtal om trygghet, otrygghet och rädsla. Metoden går ut på att deltagarna i en grupp skriver individuella minnen på ett på förhand bestämt tema. Minnena tolkas sedan kollektivt i gruppen.Intervjuerna tolkades och bearbetades av projektgruppen. Utifrån tolkningsprocessen gestaltades ungdomarnas erfarenheter dels fotografiskt och dels i text. Fyra fiktiva karaktärer togs fram och i utställningen får besökaren följa dem hem. Milo, David, Jo och Semira har alla olika erfarenheter och upplever olika moment i staden och hemresan som otrygga. Vidare togs en pedagogisk handledning fram. Den pedagogiska handledningen innehåller förslag på övningar som fördjupar utställningens teman. Den fungerar som ett stöd för skolor som hyr utställningen och kan användas av lärare i undervisningen. Pedagoger från Östergötlands museum kan vidare leda lektioner som bygger på handledningen om skolan så önskar.Projektet avslutades med en fyra veckor lång turné där ungdomar i olika åldrar fick ta del av utställningen och arbeta med den pedagogiskt. Turnén utvärderades med genomgående goda resultat.Projektet bidrar avslutningsvis till att stärka planeringen av jämställda miljöer på två sätt. För det första ger utställningen insikter om hur unga människor upplever trygghet i utemiljöer. För det andra är utställningen ett verktyg som gör det möjligt att praktiskt arbeta med frågorna pedagogiskt i skolmiljöer, eller i stadsplaneringssammanhang med planerare och andra aktörer.
|
|
| 7. |
- Jonsson, Elin, et al.
(författare)
-
Determination of drug effect on tumour cells, host animal toxicity and drug pharmacokinetics in a hollow-fibre model in rats
- 2000
-
Ingår i: Cancer Chemotherapy and Pharmacology. - : Springer Science and Business Media LLC. - 0344-5704 .- 1432-0843. ; 46:6, s. 493-500
-
Tidskriftsartikel (refereegranskat)abstract
- PURPOSE Based on the previously published hollow-fibre assay mainly used for early in vivo anticancer drug screening, we wanted to develop an extended hollow-fibre model in which antitumour activity, haematological toxicity and pharmacokinetics could be studied in the same animal. METHOD The breast cancer cell lines MDA-MB-231 and MCF-7 were cultured in semipermeable hollow fibres. The fibres were implanted subcutaneously into immunocompetent male Sprague Dawley rats, and the rats were treated with 5-fluorouracil (5-FU, 125 mg/kg), epirubicin (EPI, 10 mg/kg) or cyclophosphamide (CP, 120 mg/kg) intraperitoneally, the new cyanoguanidine CHS 828 (375 mg/kg or 75 mg/kg x 5) orally, or vehicle only. After 6 days the fibres were retrieved and the cell density was evaluated. Haematological parameters were monitored and two to four samples per animal were drawn to determine the pharmacokinetic parameters in NONMEM. RESULTS Drug treatment had generally low effects on the tumour cells. Of the standard drugs (5-FU, EPI and CP), only CP exerted a statistically significant antiproliferative effect. CHS 828 had only a minor effect as a single dose, but divided into five daily doses had a pronounced effect on both cell lines. 5-FU, EPI and CP all caused a marked decrease in leucocytes, platelets and haemoglobin, while CHS 828 did not seem to affect these parameters. The pharmacokinetics of 5-FU and EPI were in accordance with previously established pharmacokinetic models. The pharmacokinetics of CP and CHS 828 were both described by one-compartment models. CONCLUSIONS This study illustrates the possibility of measuring antitumour effect, haematological toxicity and pharmacokinetics in the same animal using the hollow-fibre model.
|
|
| 8. |
|
|
| 9. |
- Lindhagen, Elin, et al.
(författare)
-
Pharmacodynamic differences between species exemplified by the novel anticancer agent CHS 828
- 2004
-
Ingår i: Drug development research. - : Wiley. - 0272-4391 .- 1098-2299. ; 61:4, s. 218-226
-
Tidskriftsartikel (refereegranskat)abstract
- When a candidate drug enters clinical trials, decisions regarding dosing are mainly based on animal data. Occasionally, toxicity problems are faced in the clinic because of unexpected species differences in pharmacokinetics or pharmacodynamics between humans and preclinical species. Fludarabine and topotecan are examples of such drugs. In the first clinical trials of the new agent CHS 828, the maximum tolerated dose was reached earlier than expected from animal data. This paper discusses the issue of species differences in the development of anticancer drugs, and preclinical models for detection and quantification of such differences. Pharmacokinetic and hematological toxicity data of CHS 828 from studies in rats and humans are presented. In vitro sensitivity to CHS 828 and some established cytotoxic agents was measured in lymphocytes from humans and rats and in a panel of human and rodent cell-lines. 10–100 times higher CHS 828 exposure was tolerated by rats than by patients. In both in vitro cell systems, CHS 828 showed higher potency in human cells compared to rodent cells. A species difference was evident also for fludarabine, but not for doxorubicin and cisplatin. CHS 828 pharmacokinetics were similar across species. In conclusion, the lower tolerance of CHS 828 in humans than in rats could be detected in vitro in cultures of peripheral lymphocytes. Preclinical studies of species differences could help the interpretation of in vivo effect studies as well as the choice of starting dose for clinical trials. We suggest peripheral lymphocytes from different species as a potential model system for such studies.
|
|
| 10. |
- 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
|
|
