| 51. |
- Holmberg, Carl Jacob, et al.
(författare)
-
The efficacy of immune checkpoint blockade for melanoma in-transit with or without nodal metastases - A multicenter cohort study
- 2022
-
Ingår i: EUROPEAN JOURNAL OF CANCER. - : Elsevier BV. - 0959-8049 .- 1879-0852. ; 40:16
-
Tidskriftsartikel (refereegranskat)abstract
- Purpose: Guidelines addressing melanoma in-transit metastasis (ITM) recommend immune checkpoint inhibitors (ICI) as a first-line treatment option, despite the fact that there are no efficacy data available from prospective trials for exclusively ITM disease. The study aims to analyze the outcome of patients with ITM treated with ICI based on data from a large cohort of patients treated at international referral clinics. Methods: A multicenter retrospective cohort study of patients treated between January 2015 and December 2020 from Australia, Europe, and the USA, evaluating treatment with ICI for ITM with or without nodal involvement (AJCC8 N1c, N2c, and N3c) and without distant disease (M0). Treatment was with PD-1 inhibitor (nivolumab or pembrolizumab) and/or CTLA-4 inhibitor (ipilimumab). The response was evaluated according to the RECIST criteria modified for cutaneous lesions. Results: A total of 287 patients from 21 institutions in eight countries were included. Immunotherapy was first-line treatment in 64 (22%) patients. PD-1 or CTLA-4 inhibitor monotherapy was given in 233 (81%) and 23 (8%) patients, respectively, while 31 (11%) received both in combination. The overall response rate was 56%, complete response (CR) rate was 36%, and progressive disease (PD) rate was 32%. Median PFS was ten months (95% CI 7.4-12.6 months) with a one-, two-, and five-year PFS rate of 48%, 33%, and 18%, respectively. Median MSS was not reached, and the one-, two-, and five-year MSS rates were 95%, 83%, and 71%, respectively. Conclusion: Systemic immunotherapy is an effective treatment for melanoma ITM. Future studies should evaluate the role of systemic immunotherapy in the context of multimodality therapy, including locoregional treatments such as surgery, intralesional therapy, and regional therapies.
|
|
| 52. |
|
|
| 53. |
|
|
| 54. |
- Salinas, Ener, 1957, et al.
(författare)
-
A new technique for reducing extremely low frequency magnetic field emissions affecting large building structures
- 2007
-
Ingår i: Environmentalist. - 0251-1088 .- 1573-2991. ; 27:4, s. 571-576
-
Tidskriftsartikel (refereegranskat)abstract
- When large structures such as residentialcompounds or public buildings are under the influence ofextremely low frequency (ELF) magnetic fields, such asthe one generated by a system of railways fed by16.67 Hz, standard methods of designing shieldingstructures by numerical methods usually fail. The lattercan be explained by the difficulty posed in the computingprocess by the large aspect ratios involved due to thinlayers of metal (a few millimetres or centimetres) incontrast to the large dimensions of the affected structure(several tens of meters). In some cases one has to utilizespecial approximations such as surface conductivity,which are not easy to handle when the designed shieldingstructure is clearly three -dimensional. Other alternativessuch as experimentation in situ are very costly. Here, anew technique is presented of mitigating the field byusing three-dimensional propagation of induced currentsoptimizing the field reduction factors and minimizing thecost of shielding material. The particular designingmethod is a hybrid of numerical simulations combinedwith lab experimentation using scaled models of the largestructure. The method is rather cost-effective and flexible as various designs can be easily tested. Results are presented in the form of magnetic field values, at various locations in the buildings, before and after this mitigation technique is applied.
|
|
| 55. |
|
|
| 56. |
- Attard, Thohmas. M., et al.
(författare)
-
Supercritical extraction as an effective first-step in a maize stover biorefinery
- 2015
-
Ingår i: RSC Advances. - : Royal Society of Chemistry. - 2046-2069. ; 5:54, s. 43831-43838
-
Tidskriftsartikel (refereegranskat)abstract
- Supercritical carbon dioxide (scCO2) has been investigated for the generation of valuable waxy compounds and as an added-value technology in a holistic maize stover biorefinery. ScCO2 extraction and fractionation was carried out prior to hydrolysis and fermentation of maize stover. Fractionation of the crude extracts by scCO2 resulted in wax extracts having different compositions and melting temperatures, enabling their utilisation in different applications. One such fraction demonstrated significant potential as a renewable defoaming agent in washing machine detergent formulations. Furthermore, scCO2 extraction has been shown to have a positive effect on the downstream processing of the maize stover. Fermentation of the scCO2 extracted maize stover hydrolysates exhibited a higher glucose consumption and greater potential growth for surfactant (in comparison with non-scCO2 treated stover) axnd ethanol production (a 40% increase in overall ethanol production after scCO2 pre-treatment). This work represents an important development in the extraction of high value components from low value wastes and demonstrates the benefits of using scCO2 extraction as a first-step in biomass processing, including enhancing downstream processing of the biomass for the production of 2nd generation biofuels as part of an integrated holistic biorefinery.
|
|
| 57. |
- Axelsson, Emma L., et al.
(författare)
-
Sleep problems and language development in toddlers with Williams syndrome
- 2013
-
Ingår i: Research in Developmental Disabilities. - : Elsevier BV. - 0891-4222 .- 1873-3379. ; 34, s. 3988-3996
-
Tidskriftsartikel (refereegranskat)abstract
- Sleep and related maternal beliefs were assessed in a narrow age range of 18 children with Williams syndrome (WS) and 18 typically developing (TD) children. WS is a rare genetic disorder characterised by a complex physical, cognitive and behavioural phenotype. High prevalence of sleep difficulties in older children and adults with WS have been reported. Parents completed 6 questionnaires: the Brief Infant Sleep Questionnaire, Infant Sleep Vignettes Interpretation Scale, Pittsburgh Sleep Quality Index of Parents, Child Behaviour Checklist, MacArthur Communicative Development Inventory for Infants - Words and Gestures, and the Major (ICD-10) Depression Inventory. Compared to TD children, those with WS had shorter night sleep, more night wakings and wakefulness according to parental report. Regression analyses revealed that a proportion of the variance in language development scores in WS children could be explained by night sleep duration. Compared to control parents, the mothers of the WS group were more likely to describe their child’s sleep as problematic and had higher rates of involvement with child sleep, yet they had a lesser tendency to interpret sleep problems as signs of distress and a greater tendency to emphasise limit setting. Approximately half of both groups of mothers experienced poor sleep quality. This was also related to maternal mood, and night wakefulness in the children with WS. This is the first study to quantify sleep difficulties in young children with WS in a narrow age range using maternal report. The possible negative effects on maternal sleep and mood, and the link between night sleep and language development in young children with WS, requires further detailed investigation. ?? 2013 Elsevier Ltd.
|
|
| 58. |
|
|
| 59. |
- Desai, Trishna A., et al.
(författare)
-
Identifying proteomic risk factors for overall, aggressive, and early onset prostate cancer using Mendelian Randomisation and tumour spatial transcriptomics
- 2024
-
Ingår i: EBioMedicine. - : Elsevier. - 2352-3964. ; 105
-
Tidskriftsartikel (refereegranskat)abstract
- Background Understanding the role of circulating proteins in prostate cancer risk can reveal key biological pathways and identify novel targets for cancer prevention. Methods We investigated the association of 2002 genetically predicted circulating protein levels with risk of prostate cancer overall, and of aggressive and early onset disease, using cis- pQTL Mendelian randomisation (MR) and colocalisation. Findings for proteins with support from both MR, after correction for multiple -testing, and colocalisation were replicated using two independent cancer GWAS, one of European and one of African ancestry. Proteins with evidence of prostate -speci fi c tissue expression were additionally investigated using spatial transcriptomic data in prostate tumour tissue to assess their role in tumour aggressiveness. Finally, we mapped risk proteins to drug and ongoing clinical trials targets. Findings We identi fi ed 20 proteins genetically linked to prostate cancer risk (14 for overall [8 speci fi c], 7 for aggressive [3 speci fi c], and 8 for early onset disease [2 speci fi c]), of which the majority replicated where data were available. Among these were proteins associated with aggressive disease, such as PPA2 [Odds Ratio (OR) per 1 SD increment = 2.13, 95% CI: 1.54 - 2.93], PYY [OR = 1.87, 95% CI: 1.43 - 2.44] and PRSS3 [OR = 0.80, 95% CI: 0.73 - 0.89], and those associated with early onset disease, including EHPB1 [OR = 2.89, 95% CI: 1.99 - 4.21], POGLUT3 [OR = 0.76, 95% CI: 0.67 - 0.86] and TPM3 [OR = 0.47, 95% CI: 0.34 - 0.64]. We con fi rmed an inverse association of MSMB with prostate cancer overall [OR = 0.81, 95% CI: 0.80 - 0.82], and also found an inverse association with both aggressive [OR = 0.84, 95% CI: 0.82 - 0.86] and early onset disease [OR = 0.71, 95% CI: 0.68 - 0.74]. Using spatial transcriptomics data, we identi fi ed MSMB as the genome-wide top -most predictive gene to distinguish benign regions from high grade cancer regions that comparatively had fi ve -fold lower MSMB expression. Additionally, ten proteins that were associated with prostate cancer risk also mapped to existing therapeutic interventions. Interpretation Our fi ndings emphasise the importance of proteomics for improving our understanding of prostate cancer aetiology and of opportunities for novel therapeutic interventions. Additionally, we demonstrate the added bene fi t of in-depth functional analyses to triangulate the role of risk proteins in the clinical aggressiveness of prostate tumours. Using these integrated methods, we identify a subset of risk proteins associated with aggressive and early onset disease as priorities for investigation for the future prevention and treatment of prostate cancer.
|
|
| 60. |
|
|
