| 1. |
|
|
| 2. |
- Altomare, D., et al.
(författare)
-
Plasma biomarkers for Alzheimer's disease: a field-test in a memory clinic
- 2023
-
Ingår i: Journal of Neurology Neurosurgery and Psychiatry. - 0022-3050. ; 94:6
-
Tidskriftsartikel (refereegranskat)abstract
- Background The key Alzheimer's disease (AD) biomarkers are traditionally measured with techniques/exams that are either expensive (amyloid-positron emission tomography (PET) and tau-PET), invasive (cerebrospinal fluid A beta 42 and p-tau 181), or poorly specific (atrophy on MRI and hypometabolism on fluorodeoxyglucose-PET). Recently developed plasma biomarkers could significantly enhance the efficiency of the diagnostic pathway in memory clinics and improve patient care. This study aimed to: (1) confirm the correlations between plasma and traditional AD biomarkers, (2) assess the diagnostic accuracy of plasma biomarkers as compared with traditional biomarkers, and (3) estimate the proportion of traditional exams potentially saved thanks to the use of plasma biomarkers. Methods Participants were 200 patients with plasma biomarkers and at least one traditional biomarker collected within 12 months. Results Overall, plasma biomarkers significantly correlated with biomarkers assessed through traditional techniques: up to r=0.50 (p<0.001) among amyloid, r=0.43 (p=0.002) among tau, and r=-0.23 (p=0.001) among neurodegeneration biomarkers. Moreover, plasma biomarkers showed high accuracy in discriminating the biomarker status (normal or abnormal) determined by using traditional biomarkers: up to area under the curve (AUC)=0.87 for amyloid, AUC=0.82 for tau, and AUC=0.63 for neurodegeneration status. The use of plasma as a gateway to traditional biomarkers using cohort-specific thresholds (with 95% sensitivity and 95% specificity) could save up to 49% of amyloid, 38% of tau, and 16% of neurodegeneration biomarkers. Conclusion The implementation of plasma biomarkers could save a remarkable proportion of more expensive traditional exams, making the diagnostic workup more cost-effective and improving patient care.
|
|
| 3. |
- Hermanussen, M, et al.
(författare)
-
Adolescent growth: genes, hormones and the peer group.
- 2014
-
Ingår i: Pediatric endocrinology reviews : PER. Proceedings of the 20th Aschauer Soiree, held at Glücksburg castle, Germany, 15th to 17th November 2013.. - 1565-4753. ; 11:3, s. 341-53
-
Konferensbidrag (refereegranskat)abstract
- The association between poverty, malnutrition, illness and poor socioeconomic conditions on the one side, and poor growth and short adult stature on the other side, is well recognized. Yet, the simple assumption by implication that poor growth and short stature result from poor living conditions, should be questioned. Recent evidence on the impact of the social network on adolescent growth and adult height further challenges the traditional concept of growth being a mirror of health. Twenty-nine scientists met at Glücksburg castle, Northern Germany, November 15th - 17th 2013, to discuss genetic, endocrine, mathematical and psychological aspects and related issues, of child and adolescent growth and final height.
|
|
| 4. |
- Schijven, Dick, et al.
(författare)
-
Large-scale analysis of structural brain asymmetries in schizophrenia via the ENIGMA consortium
- 2023
-
Ingår i: Proceedings of the National Academy of Sciences of the United States of America. - : Proceedings of the National Academy of Sciences (PNAS). - 0027-8424 .- 1091-6490. ; 120:14
-
Tidskriftsartikel (refereegranskat)abstract
- Left-right asymmetry is an important organizing feature of the healthy brain that may be altered in schizophrenia, but most studies have used relatively small samples and heterogeneous approaches, resulting in equivocal findings. We carried out the largest case-control study of structural brain asymmetries in schizophrenia, with MRI data from 5,080 affected individuals and 6,015 controls across 46 datasets, using a single image analysis protocol. Asymmetry indexes were calculated for global and regional cortical thickness, surface area, and subcortical volume measures. Differences of asymmetry were calculated between affected individuals and controls per dataset, and effect sizes were meta-analyzed across datasets. Small average case-control differences were observed for thickness asymmetries of the rostral anterior cingulate and the middle temporal gyrus, both driven by thinner left-hemispheric cortices in schizophrenia. Analyses of these asymmetries with respect to the use of antipsychotic medication and other clinical variables did not show any significant associations. Assessment of age- and sex-specific effects revealed a stronger average leftward asymmetry of pallidum volume between older cases and controls. Case-control differences in a multivariate context were assessed in a subset of the data (N = 2,029), which revealed that 7% of the variance across all structural asymmetries was explained by case-control status. Subtle case-control differences of brain macrostructural asymmetry may reflect differences at the molecular, cytoarchitectonic, or circuit levels that have functional relevance for the disorder. Reduced left middle temporal cortical thickness is consistent with altered left-hemisphere language network organization in schizophrenia.
|
|
| 5. |
|
|
| 6. |
|
|
| 7. |
|
|
| 8. |
- Skarpengland, T, et al.
(författare)
-
Neil3-dependent base excision repair regulates lipid metabolism and prevents atherosclerosis in Apoe-deficient mice
- 2016
-
Ingår i: Scientific reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 6, s. 28337-
-
Tidskriftsartikel (refereegranskat)abstract
- Increasing evidence suggests that oxidative DNA damage accumulates in atherosclerosis. Recently, we showed that a genetic variant in the human DNA repair enzyme NEIL3 was associated with increased risk of myocardial infarction. Here, we explored the role of Neil3/NEIL3 in atherogenesis by both clinical and experimental approaches. Human carotid plaques revealed increased NEIL3 mRNA expression which significantly correlated with mRNA levels of the macrophage marker CD68. Apoe−/−Neil3−/− mice on high-fat diet showed accelerated plaque formation as compared to Apoe−/− mice, reflecting an atherogenic lipid profile, increased hepatic triglyceride levels and attenuated macrophage cholesterol efflux capacity. Apoe−/−Neil3−/− mice showed marked alterations in several pathways affecting hepatic lipid metabolism, but no genotypic alterations in genome integrity or genome-wide accumulation of oxidative DNA damage. These results suggest a novel role for the DNA glycosylase Neil3 in atherogenesis in balancing lipid metabolism and macrophage function, potentially independently of genome-wide canonical base excision repair of oxidative DNA damage.
|
|
| 9. |
- Baumeister, Hannah, et al.
(författare)
-
A generalizable data-driven model of atrophy heterogeneity and progression in memory clinic settings
-
Ingår i: Brain : a journal of neurology. - 1460-2156. ; 147:7, s. 2400-2413
-
Tidskriftsartikel (refereegranskat)abstract
- Memory clinic patients are a heterogeneous population representing various aetiologies of pathological aging. It is unknown if divergent spatiotemporal progression patterns of brain atrophy, as previously described in Alzheimer's disease (AD) patients, are prevalent and clinically meaningful in this group of older adults. To uncover distinct atrophy subtypes, we applied the Subtype and Stage Inference (SuStaIn) algorithm to baseline structural MRI data from 813 participants enrolled in the DELCODE cohort (mean ± SD age = 70.67 ± 6.07 years, 52% females). Participants were cognitively unimpaired (CU; n = 285) or fulfilled diagnostic criteria for subjective cognitive decline (SCD; n = 342), mild cognitive impairment (MCI; n = 118), or dementia of the Alzheimer's type (n = 68). Atrophy subtypes were compared in baseline demographics, fluid AD biomarker levels, the Preclinical Alzheimer Cognitive Composite (PACC-5), as well as episodic memory and executive functioning. PACC-5 trajectories over up to 240 weeks were examined. To test if baseline atrophy subtype and stage predicted clinical trajectories before manifest cognitive impairment, we analysed PACC-5 trajectories and MCI conversion rates of CU and SCD participants. Limbic-predominant and hippocampal-sparing atrophy subtypes were identified. Limbic-predominant atrophy first affected the medial temporal lobes, followed by further temporal and, finally, the remaining cortical regions. At baseline, this subtype was related to older age, more pathological AD biomarker levels, APOE ε4 carriership, and an amnestic cognitive impairment. Hippocampal-sparing atrophy initially occurred outside the temporal lobe with the medial temporal lobe spared up to advanced atrophy stages. This atrophy pattern also affected individuals with positive AD biomarkers and was associated with more generalised cognitive impairment. Limbic-predominant atrophy, in all and in only unimpaired participants, was linked to more negative longitudinal PACC-5 slopes than observed in participants without or with hippocampal-sparing atrophy and increased the risk of MCI conversion. SuStaIn modelling was repeated in a sample from the Swedish BioFINDER-2 cohort. Highly similar atrophy progression patterns and associated cognitive profiles were identified. Cross-cohort model generalizability, both on the subject and group level, were excellent, indicating reliable performance in previously unseen data. The proposed model is a promising tool for capturing heterogeneity among older adults at early at-risk states for AD in applied settings. The implementation of atrophy subtype- and stage-specific end-points may increase the statistical power of pharmacological trials targeting early AD.
|
|
| 10. |
- Nash, Gerard, et al.
(författare)
-
Haemorheological result in a large multicentre study of claudicants treated with ketanserin
- 1990
-
Ingår i: Clinical Hemorheology. - New York, USA : Pergamon Press. - 0271-5198. ; 10, s. 321-327
-
Tidskriftsartikel (refereegranskat)abstract
- Abstract An international, multi-centre trial was carried out to test the haemorheological effects of ketanserin, a serotonin antagonist, after treatment of intermittent claudicants for 1 year. Haematological indices, whole blood viscosity, plasma viscosity and red cell and white cell filterabi1ity were measured using standardised techniques. Even so, inter-laboratory variability, and intra-laboratory changes in control values in some centres over the 1 year period proved to be major obstacles. The pooled data showed no evidence of haemorheological changes, although data from the single largest centre indicated slightly lowered haematocrit and blood and plasma viscosity. Any rheological effects of serotonin antagonists in intermittent claudicants are probably small and unlikely to be the main source of any clinical efficacy. In general, it would appear that standardisation and monitoring of laboratory techniques must be strictly carried out if there is to be any hope of successfully carrying out multi-centre haemorheological trials. . Key words: Blood Rheology; Claudication; Serotonin Antagonists;
|
|
| 11. |
- Pentcheva, R., et al.
(författare)
-
A combined DFT/LEED-approach for complex oxide surface structure determination : Fe3O4(001)
- 2008
-
Ingår i: Surface Science. - : Elsevier BV. - 0039-6028 .- 1879-2758. ; 602:7, s. 1299-1305
-
Tidskriftsartikel (refereegranskat)abstract
- A combination of density functional theory (DFT) calculations and low energy electron diffraction (LEED) analysis is used to determine the surface structure of Fe3O4 0 00). We find that the surface is rich in oxygen and the observed (root 2- x root 2-)R45 degrees reconstruction is a result of a Jahn-Teller distortion as established by recent DFT-calculations [R. Pentcheva, F. Wendler, H.L. Meyerheim, W. Moritz, N. Jedrecy, M. Scheffler, Phys. Rev. Lett. 94 (2005) 126101]. The corresponding Pendry reliability factor is 0.34. Furthermore, we investigate the influence of the preparation conditions (temperature, oxygen pressure) on the LEED intensities of natural and synthetic samples. The electron scattering phase shifts used in the analysis of the LEED spectra are derived from two methods, one based on the DFT electron densities and another employing an overlap of atomic potentials with optimized muffin-tin radii. Both approaches lead to similar results.
|
|
| 12. |
- Thelander, Claes, et al.
(författare)
-
Nanowire-based one-dimensional electronics
- 2006
-
Ingår i: Materials Today. - 1369-7021. ; 9:10, s. 28-35
-
Tidskriftsartikel (refereegranskat)abstract
- During the last half century, a dramatic downscaling of electronics has taken place, a miniaturization that the industry expects to continue for at least a decade. We present efforts to use the self-assembly of one-dimensional semiconductor nanowires(1) in order to bring new, high-performance nanowire devices as an add-on to mainstream Si technology. The nanowire approach offers a coaxial gate-dielectric-channel geometry that is ideal for further downscaling and electrostatic control, as well as heterostructure-based devices on Si wafers.
|
|
| 13. |
- Tischer, Thomas, et al.
(författare)
-
Management of anterior cruciate ligament revision in adults: the 2022 ESSKA consensus part III-indications for different clinical scenarios using the RAND/UCLA appropriateness method
- 2023
-
Ingår i: KNEE SURGERY SPORTS TRAUMATOLOGY ARTHROSCOPY. - 0942-2056 .- 1433-7347. ; 31:11, s. 4662-4672
-
Tidskriftsartikel (refereegranskat)abstract
- PurposeThe aim of the ESSKA 2022 consensus Part III was to develop patient-focused, contemporary, evidence-based, guidelines on the indications for revision anterior cruciate ligament surgery (ACLRev).MethodsThe RAND/UCLA Appropriateness Method (RAM) was used to provide recommendations on the appropriateness of surgical treatment versus conservative treatment in different clinical scenarios based on current scientific evidence in conjunction with expert opinion. A core panel defined the clinical scenarios with a moderator and then guided a panel of 17 voting experts through the RAM tasks. Through a two-step voting process, the panel established a consensus as to the appropriateness of ACLRev for each scenario based on a nine-point Likert scale (in which a score in the range 1-3 was considered 'inappropriate', 4-6 'uncertain', and 7-9 'appropriate').ResultsThe criteria used to define the scenarios were: age (18-35 years vs 36-50 years vs 51-60 years), sports activity and expectation (Tegner 0-3 vs 4-6 vs 7-10), instability symptoms (yes vs no), meniscus status (functional vs repairable vs non-functional meniscus), and osteoarthritis (OA) (Kellgren-Lawrence [KL] grade 0-I-II vs grade III). Based on these variables, a set of 108 clinical scenarios was developed. ACLRev was considered appropriate in 58%, inappropriate in 12% (meaning conservative treatment is indicated), and uncertain in 30%. Experts considered ACLRev appropriate for patients with instability symptoms, aged <= 50 years, regardless of sports activity level, meniscus status, and OA grade. Results were much more controversial in patients without instability symptoms, while higher inappropriateness was related to scenarios with older age (51-60 years), low sporting expectation, non-functional meniscus, and knee OA (KL III).ConclusionThis expert consensus establishes guidelines as to the appropriateness of ACLRev based on defined criteria and provides a useful reference for clinical practice in determining treatment indications.
|
|
