| 31. |
- Johannsson, Gudmundur, 1960, et al.
(författare)
-
Long-Term Safety of Growth Hormone in Adults With Growth Hormone Deficiency: Overview of 15 809 GH-Treated Patients
- 2022
-
Ingår i: Journal of Clinical Endocrinology & Metabolism. - : The Endocrine Society. - 0021-972X .- 1945-7197. ; 107:7, s. 1906-1919
-
Tidskriftsartikel (refereegranskat)abstract
- Context Data on long-term safety of growth hormone (GH) replacement in adults with GH deficiency (GHD) are needed. Objective We aimed to evaluate the safety of GH in the full KIMS (Pfizer International Metabolic Database) cohort. Methods The worldwide, observational KIMS study included adults and adolescents with confirmed GHD. Patients were treated with GH (Genotropin [somatropin]; Pfizer, NY) and followed through routine clinical practice. Adverse events (AEs) and clinical characteristics (eg, lipid profile, glucose) were collected. Results A cohort of 15 809 GH-treated patients were analyzed (mean follow-up of 5.3 years). AEs were reported in 51.2% of patients (treatment-related in 18.8%). Crude AE rate was higher in patients who were older, had GHD due to pituitary/hypothalamic tumors, or adult-onset GHD. AE rate analysis adjusted for age, gender, etiology, and follow-up time showed no correlation with GH dose. A total of 606 deaths (3.8%) were reported (146 by neoplasms, 71 by cardiac/vascular disorders, 48 by cerebrovascular disorders). Overall, de novo cancer incidence was comparable to that in the general population (standard incidence ratio 0.92; 95% CI, 0.83-1.01). De novo cancer risk was significantly lower in patients with idiopathic/congenital GHD (0.64; 0.43-0.91), but similar in those with pituitary/hypothalamic tumors or other etiologies versus the general population. Neither adult-onset nor childhood-onset GHD was associated with increased de novo cancer risks. Neutral effects were observed in lipids/fasting blood glucose levels. Conclusion These final KIMS cohort data support the safety of long-term GH replacement in adults with GHD as prescribed in routine clinical practice.
|
|
| 32. |
|
|
| 33. |
- Marini, E., et al.
(författare)
-
Understanding the evolution and dust formation of carbon stars in the Large Magellanic Cloud via the JWST
- 2021
-
Ingår i: Astronomy and Astrophysics. - : EDP SCIENCES S A. - 0004-6361 .- 1432-0746. ; 647
-
Tidskriftsartikel (refereegranskat)abstract
- Context. Carbon stars have been, and still are, extensively studied. Given their complex internal structure and their peculiar chemical composition, they are living laboratories in which we can test stellar structure and evolution theories of evolved stars. Furthermore, they are the most relevant dust manufacturers, thus playing a crucial role in the evolution of galaxies. Aims. We aim to study the dust mineralogy of the circumstellar envelope of carbon stars in the Large Magellanic Cloud (LMC) to achieve a better understanding of the dust formation process in the outflow of these objects. We intend to investigate the expected distribution of carbon stars in the observational planes built with the filters of the Mid-Infrared Instrument (MIRI) mounted onboard the James Webb Space Telescope (JWST) to select the best planes allowing an exhaustive characterisation of the stars. Methods. We compared the synthetic spectral energy distributions, obtained by modelling asymptotic giant branch stars and the dust formation process in the wind, with the spectra of carbon stars in the LMC, taken with the Infrared Spectrograph onboard the Spitzer Space Telescope. From the detailed comparison between synthetic modelling and observation we characterise the individual sources and derive the detailed mineralogy of the dust in the circumstellar envelope. Results. The sample of stars considered here is composed of stars of diverse mass, formation epoch, degree of obscuration, and metallicity. We find that precipitation of MgS on SiC seeds is common to all non-metal-poor carbon stars. Solid carbon is the dominant dust component, with percentages above 80% in all cases; a percentage between 10% and 20% of carbon dust is under the form of graphite, the remaining being amorphous carbon. Regarding the observational planes based on the MIRI filters, the colour-magnitude ([F770W]-[F1800W], [F1800W]) plane allows the best understanding of the degree of obscuration of the stars, while the ([F1800W]- [F2550W], [F1800W]) diagram allows better discrimination among stars of different metallicities.
|
|
| 34. |
|
|
| 35. |
- Palmqvist, Sebastian, et al.
(författare)
-
An accurate fully automated panel of plasma biomarkers for Alzheimer's disease
- 2023
-
Ingår i: Alzheimers & Dementia. - : Wiley. - 1552-5260 .- 1552-5279. ; 19:4, s. 1204-1215
-
Tidskriftsartikel (refereegranskat)abstract
- Introduction There is a great need for fully automated plasma assays that can measure amyloid beta (A beta) pathology and predict future Alzheimer's disease (AD) dementia. Methods Two cohorts (n = 920) were examined: Panel A+ (n = 32 cognitively unimpaired [CU], n = 106 mild cognitive impairment [MCI], and n = 89 AD) and BioFINDER-1 (n = 461 CU, n = 232 MCI). Plasma A beta 42/A beta 40, phosphorylated tau (p-tau)181, two p-tau217 variants, ApoE4 protein, neurofilament light, and GFAP were measured using Elecsys prototype immunoassays. Results The best biomarker for discriminating A beta-positive versus A beta-negative participants was A beta 42/A beta 40 (are under the curve [AUC] 0.83-0.87). Combining A beta 42/A beta 40, p-tau181, and ApoE4 improved the AUCs significantly (0.90 to 0.93; P< 0.01). Adding additional biomarkers had marginal effects (Delta AUC <= 0.01). In BioFINDER, p-tau181, p-tau217, and ApoE4 predicted AD dementia within 6 years in CU (AUC 0.88) and p-tau181, p-tau217, and A beta 42/A beta 40 in MCI (AUC 0.87). Discussion The high accuracies for A beta pathology and future AD dementia using fully automated instruments are promising for implementing plasma biomarkers in clinical trials and clinical routine.
|
|
| 36. |
- Reijers, S. J. M., et al.
(författare)
-
Variation in response rates to isolated limb perfusion in different soft-tissue tumour subtypes: an international multi-centre study
- 2023
-
Ingår i: European Journal of Cancer. - 0959-8049. ; 190
-
Tidskriftsartikel (refereegranskat)abstract
- Objective: The aim of this study was to investigate the response rates of different extremity soft-tissue sarcoma subtypes (eSTS) after isolated limb perfusion (ILP), based on an international multi-centre study. Materials and methods: The retrospective cohort comprised eSTS patients from 17 specialised ILP centres that underwent melphalan-based ILP, with or without recombinant human tumour necrosis factor (rhTNF & alpha;) (TM-ILP and M-ILP, respectively). Response was measured on imaging (magnetic resonance imaging) and/or clinical response, for which M-ILPs were excluded. Results: A total of 1109 eSTS patients were included. The three most common histological subtypes were undifferentiated pleomorphic sarcoma (17%, n = 184), synovial sarcoma (16%, n = 175) and myxofibrosarcoma (8%, n = 87). rhTNF & alpha; was used in 93% (TM-ILP) and resulted in a significantly better overall response rate (ORR, p = 0.031) and complete responses (CR, p < 0.001) in comparison to M-ILP, without significant differences among histological subgroups. The ORR of TM-ILP was 68%, including 17% CR. Also, 80% showed progressive disease. Significantly higher response rates were shown for Kaposi sarcoma (KS) with 42% CR and 96% ORR (both p < 0.001), and significantly higher CR rates for angiosarcoma (AS, 45%, p < 0.001) and clear cell sarcoma (CCS, 31%, p = 0.049). ILP was followed by resection & LE; 6 months in 80% of the patients. The overall limb salvage rate was 88%, without significant differences among histological subgroups, but was significantly higher for ILP responders compared to non-responders (93% versus 76%, p < 0.001). Conclusion: ILP resulted in high response and LRS among all eSTS subtypes, however, with significant differences between subtypes with most promising results for KS, AS and CCS.
|
|
| 37. |
|
|
| 38. |
- Burkhardt, J., et al.
(författare)
-
Modelling the dynamic chemical interactions of atmospheric ammonia with leaf surface wetness in a managed grassland canopy
- 2009
-
Ingår i: Biogeosciences. - Göttingen : Copernicus Publications. - 1726-4170 .- 1726-4189. ; 6:1, s. 67-84
-
Tidskriftsartikel (refereegranskat)abstract
- Ammonia exchange fluxes between grassland and the atmosphere were modelled on the basis of stomatal compensation points and leaf surface chemistry, and compared with measured fluxes during the GRAMINAE intensive measurement campaign in spring 2000 near Braunschweig, Germany. Leaf wetness and dew chemistry in grassland were measured together with ammonia fluxes and apoplastic NH4+ and H+ concentration, and the data were used to apply, validate and further develop an existing model of leaf surface chemistry and ammonia exchange. Foliar leaf wetness which is known to affect ammonia fluxes may be persistent after the end of rainfall, or sustained by recondensation of water vapour originating from the ground or leaf transpiration, so measured leaf wetness values were included in the model. pH and ammonium concentrations of dew samples collected from grass were compared to modelled values.The measurement period was divided into three phases: a relatively wet phase followed by a dry phase in the first week before the grass was cut, and a second drier week after the cut. While the first two phases were mainly characterised by ammonia deposition and occasional short emission events, regular events of strong ammonia emissions were observed during the post-cut period. A single-layer resistance model including dynamic cuticular and stomatal exchange could describe the fluxes well before the cut, but after the cut the stomatal compensation points needed to numerically match measured fluxes were much higher than the ones measured by bioassays, suggesting another source of ammonia fluxes. Considerably better agreement both in the direction and the size range of fluxes were obtained when a second layer was introduced into the model, to account for the large additional ammonia source inherent in the leaf litter at the bottom of the grass canopy. Therefore, this was found to be a useful extension of the mechanistic dynamic chemistry model by keeping the advantage of requiring relatively little site-specific information.
|
|
| 39. |
|
|
| 40. |
|
|
