44 research outputs found
Early- Onset Stroke and Vasculopathy Associated with Mutations in ADA2
Adenosine deaminase 2 (ADA2) is an enzyme involved in purine metabolism and a growth factor that influences the development of endothelial cells and leukocytes. This study shows that defects in ADA2 cause recurrent fevers, vascular pathologic features, and mild immunodeficiency. Patients with autoinflammatory disease sometimes present with clinical findings that encompass multiple organ systems.(1) Three unrelated children presented to the National Institutes of Health (NIH) Clinical Center with intermittent fevers, recurrent lacunar strokes, elevated levels of acute-phase reactants, livedoid rash, hepatosplenomegaly, and hypogammaglobulinemia. Collectively, these findings do not easily fit with any of the known inherited autoinflammatory diseases. Hereditary or acquired vascular disorders can have protean manifestations yet be caused by mutations in a single gene. Diseases such as the Aicardi-Goutieres syndrome,(2),(3) polypoidal choroidal vasculopathy,(4) sickle cell anemia,(5) livedoid vasculopathy,(6) and the small-vessel vasculitides(7),(8) are examples of systemic ...</p
Comprehensive analysis of epigenetic clocks reveals associations between disproportionate biological ageing and hippocampal volume
The concept of age acceleration, the difference between biological age and chronological age, is of growing interest, particularly with respect to age-related disorders, such as Alzheimer’s Disease (AD). Whilst studies have reported associations with AD risk and related phenotypes, there remains a lack of consensus on these associations. Here we aimed to comprehensively investigate the relationship between five recognised measures of age acceleration, based on DNA methylation patterns (DNAm age), and cross-sectional and longitudinal cognition and AD-related neuroimaging phenotypes (volumetric MRI and Amyloid-β PET) in the Australian Imaging, Biomarkers and Lifestyle (AIBL) and the Alzheimer’s Disease Neuroimaging Initiative (ADNI). Significant associations were observed between age acceleration using the Hannum epigenetic clock and cross-sectional hippocampal volume in AIBL and replicated in ADNI. In AIBL, several other findings were observed cross-sectionally, including a significant association between hippocampal volume and the Hannum and Phenoage epigenetic clocks. Further, significant associations were also observed between hippocampal volume and the Zhang and Phenoage epigenetic clocks within Amyloid-β positive individuals. However, these were not validated within the ADNI cohort. No associations between age acceleration and other Alzheimer’s disease-related phenotypes, including measures of cognition or brain Amyloid-β burden, were observed, and there was no association with longitudinal change in any phenotype. This study presents a link between age acceleration, as determined using DNA methylation, and hippocampal volume that was statistically significant across two highly characterised cohorts. The results presented in this study contribute to a growing literature that supports the role of epigenetic modifications in ageing and AD-related phenotypes
Uncovering the heterogeneity and temporal complexity of neurodegenerative diseases with Subtype and Stage Inference
The heterogeneity of neurodegenerative diseases is a key confound to disease understanding and treatment development, as study cohorts typically include multiple phenotypes on distinct disease trajectories. Here we introduce a machine-learning technique\u2014Subtype and Stage Inference (SuStaIn)\u2014able to uncover data-driven disease phenotypes with distinct temporal progression patterns, from widely available cross-sectional patient studies. Results from imaging studies in two neurodegenerative diseases reveal subgroups and their distinct trajectories of regional neurodegeneration. In genetic frontotemporal dementia, SuStaIn identifies genotypes from imaging alone, validating its ability to identify subtypes; further the technique reveals within-genotype heterogeneity. In Alzheimer\u2019s disease, SuStaIn uncovers three subtypes, uniquely characterising their temporal complexity. SuStaIn provides fine-grained patient stratification, which substantially enhances the ability to predict conversion between diagnostic categories over standard models that ignore subtype (p = 7.18
7 10 124 ) or temporal stage (p = 3.96
7 10 125 ). SuStaIn offers new promise for enabling disease subtype discovery and precision medicine
De levenslange vrijheidsstraf
ARTIKELEN: 1. D. van Zyl Smit - De levenslange vrijheidsstraf internationaal vergeleken 2. V.H. Glerum - Levenslange gevangenisstraf: uitlevering en overlevering aan Nederland 3. D.J.G.J. Cornelissen - Het advies van de rechter in de gratieprocedure levenslanggestraften 4. W.F. van Hattum - Het aanzien van de Staat; over de praktijk van tenuitvoerlegging van de levenslange straf 5. M.S. Fleisher - 'Levenslang': schadebeperking door levenslange gevangenisstraffen 6. G. de Jonge - Naar een compensatoir regime voor levenslang- en zeer langgestraften 7. P.C. Braun - Perspectiefverlies bij levenslange gevangenisstraf en longstay-tbs-kader; overeenkomsten en verschillen 8. T. de Bont en S. Meijer - Perspectief voor levenslanggestraften? 9. Boekrecensie door E.F.J.C. van Ginneken over: Leven na een levenslange gevangenisstraf 10.
Internetsites. SAMENVATTING: Nederland neemt met zijn strenge uitleg van levenslange straf een uitzonderingspositie in Europa in. De meeste landen kennnen een aan rechterlijke toetsing onderhevige regeling die voorziet in de mogelijkheid van voorwaardelijke vrijlating nadat een substantieel deel van de straf is uitgezeten. Nederland kent alleen de aan politieke besluitvorming onderworpen gratieregeling. Tegen deze achtergrond is er alle aanleiding om in dit themanummer ook aandacht te besteden aan de internationale context waarbinnen het Nederlandse beleid ten aanzien van de levenslange gevangenisstraf vorm heeft gekregen, evenals aan de discussies over dit onderwerp in andere landen