Learning difficulties : a portuguese perspective of a universal issue

In this article we present findings of a study that was conducted with the purpose of deepening the knowledge about the field of learning difficulties in Portugal. Therefore, within these findings we will discuss across several cultural boundaries, themes related with the existence of learning difficulties as a construct, the terminology, the political, social and scientific influences on the field, and the models of identification and of ongoing school support for students. While addressing the above-mentioned themes we will draw attention to the different, yet converging, international understandings of learning difficulties

Global surveillance of cancer survival 1995-2009: analysis of individual data for 25,676,887 patients from 279 population-based registries in 67 countries (CONCORD-2)

BACKGROUND: Worldwide data for cancer survival are scarce. We aimed to initiate worldwide surveillance of cancer survival by central analysis of population-based registry data, as a metric of the effectiveness of health systems, and to inform global policy on cancer control. METHODS: Individual tumour records were submitted by 279 population-based cancer registries in 67 countries for 25·7 million adults (age 15-99 years) and 75,000 children (age 0-14 years) diagnosed with cancer during 1995-2009 and followed up to Dec 31, 2009, or later. We looked at cancers of the stomach, colon, rectum, liver, lung, breast (women), cervix, ovary, and prostate in adults, and adult and childhood leukaemia. Standardised quality control procedures were applied; errors were corrected by the registry concerned. We estimated 5-year net survival, adjusted for background mortality in every country or region by age (single year), sex, and calendar year, and by race or ethnic origin in some countries. Estimates were age-standardised with the International Cancer Survival Standard weights. FINDINGS: 5-year survival from colon, rectal, and breast cancers has increased steadily in most developed countries. For patients diagnosed during 2005-09, survival for colon and rectal cancer reached 60% or more in 22 countries around the world; for breast cancer, 5-year survival rose to 85% or higher in 17 countries worldwide. Liver and lung cancer remain lethal in all nations: for both cancers, 5-year survival is below 20% everywhere in Europe, in the range 15-19% in North America, and as low as 7-9% in Mongolia and Thailand. Striking rises in 5-year survival from prostate cancer have occurred in many countries: survival rose by 10-20% between 1995-99 and 2005-09 in 22 countries in South America, Asia, and Europe, but survival still varies widely around the world, from less than 60% in Bulgaria and Thailand to 95% or more in Brazil, Puerto Rico, and the USA. For cervical cancer, national estimates of 5-year survival range from less than 50% to more than 70%; regional variations are much wider, and improvements between 1995-99 and 2005-09 have generally been slight. For women diagnosed with ovarian cancer in 2005-09, 5-year survival was 40% or higher only in Ecuador, the USA, and 17 countries in Asia and Europe. 5-year survival for stomach cancer in 2005-09 was high (54-58%) in Japan and South Korea, compared with less than 40% in other countries. By contrast, 5-year survival from adult leukaemia in Japan and South Korea (18-23%) is lower than in most other countries. 5-year survival from childhood acute lymphoblastic leukaemia is less than 60% in several countries, but as high as 90% in Canada and four European countries, which suggests major deficiencies in the management of a largely curable disease. INTERPRETATION: International comparison of survival trends reveals very wide differences that are likely to be attributable to differences in access to early diagnosis and optimum treatment. Continuous worldwide surveillance of cancer survival should become an indispensable source of information for cancer patients and researchers and a stimulus for politicians to improve health policy and health-care systems

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

Age at first birth in women is genetically associated with increased risk of schizophrenia

Prof. Paunio on PGC:n jäsenPrevious studies have shown an increased risk for mental health problems in children born to both younger and older parents compared to children of average-aged parents. We previously used a novel design to reveal a latent mechanism of genetic association between schizophrenia and age at first birth in women (AFB). Here, we use independent data from the UK Biobank (N = 38,892) to replicate the finding of an association between predicted genetic risk of schizophrenia and AFB in women, and to estimate the genetic correlation between schizophrenia and AFB in women stratified into younger and older groups. We find evidence for an association between predicted genetic risk of schizophrenia and AFB in women (P-value = 1.12E-05), and we show genetic heterogeneity between younger and older AFB groups (P-value = 3.45E-03). The genetic correlation between schizophrenia and AFB in the younger AFB group is -0.16 (SE = 0.04) while that between schizophrenia and AFB in the older AFB group is 0.14 (SE = 0.08). Our results suggest that early, and perhaps also late, age at first birth in women is associated with increased genetic risk for schizophrenia in the UK Biobank sample. These findings contribute new insights into factors contributing to the complex bio-social risk architecture underpinning the association between parental age and offspring mental health.Peer reviewe

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

Usual and unusual causes of extrahepatic cholestasis: Assessment with magnetic resonance cholangiography and fast MRI

Cholestasis may result from hepatocellular (intrahepatic) disease or biliary tract (extrahepatic) abnormalities. Etiologies causing extrahepatic cholestasis are extremely diverse and invasive procedures, such as endoscopic retrograde cholangiopancreatography (ERCP) and percutaneous transhepatic cholangiography (PTC), were previously required to establish the diagnosis. Due to refinements of magnetic resonance imaging (MRI) techniques, the patient with extrahepatic cholestasis currently can be evaluated noninvasively, and the information revealed frequently exceeds the findings obtained by ERCP and PTC. In this essay, we illustrate the classic MR cholangiographic (MRC) and MRI features of a variety of disorders causing extrahepatic cholestasis, including non-neoplastic disorders of the biliary tract (congenital abnormalities, infectious processes, iatrogenic disorders, and postsurgical complications) and neoplastic conditions (e.g., tumors of the pancreas, biliary tree, liver, ampulla, and regional lymph nodes). In most cases, familiarity with the key MRC features in addition to information obtained via cross-sectional MR images provide sufficient information for adequate lesion characterization

Quantitatives IT-Portfoliomanagement: Risiken von IT-Investitionen wertorientiert steuern

Zentraler Bestandteil des IT-Business-Alignments ist das IT-Portfoliomanagement (ITPM), d. h. die auf ökonomischen Kriterien beruhende Auswahl von IT-Projekten und deren Allokation zu einem Portfolio. In diesem Beitrag wird ein Ansatz zum quantitativen ITPM vorgestellt und dessen Umsetzung am Beispiel einer realen Fallstudie expliziert. - Im Ansatz wird der Fokus auf die integrierte Optimierung von Rendite und zeitpunktbezogenen Risiken sowie auf die Operationalisierbarkeit gelegt.Beide Punkte sind in bisherigen methodisch fundierten Verfahren nicht befriedigend berücksichtigt. - Die Steuerung einzelner Geschäftseinheiten über dezentrale IT-Budgets ist ökonomisch nicht sinnvoll, weshalb ein übergreifendes ITPM notwendig ist. - IT-Portfolios werden heute oftmals nur an Renditekennziffern gemessen. Dies ist zwar notwendig, aber nicht hinreichend. Vielmehr muss die Bewertung Risikoverbundeffekte gleichermaßen berücksichtigen, da heutzutage ca. 70% aller IT-Projekte durch Sachverhalte, die sich im Projektrisiko widerspiegeln, nicht planmäßig durchgeführt werden können

PET/CT-guided percutaneous liver mass biopsies and ablations: Targeting accuracy of a single 20 s breath-hold PET acquisition

Aim To determine whether a single 20 s breath-hold positron-emission tomography (PET) acquisition obtained during combined PET/computed tomography (CT)-guided percutaneous liver biopsy or ablation procedures has the potential to target 2-[18F]-fluoro-2-deoxy-d-glucose (FDG)-avid liver masses as accurately as up to 180 s breath-hold PET acquisitions. Materials and methods This retrospective study included 10 adult patients with 13 liver masses who underwent FDG PET/CT-guided percutaneous biopsies (n = 5) or ablations (n = 5). PET was acquired as nine sequential 20 s, monitored, same-level breath-hold frames and CT was acquired in one monitored breath-hold. Twenty, 40, 60, and 180 s PET datasets were reconstructed. Two blinded readers marked tumour centres on randomized PET and CT datasets. Three-dimensional spatial localization differences between PET datasets and either 180 s PET or CT were analysed using multiple regression analyses. Statistical tests were two-sided and p < 0.05 was considered significant. Results Targeting differences between 20 s PET and 180 s PET ranged from 0.7-20.3 mm (mean 5.3 \ub1 4.4 mm; median 4.3) and were not statistically different from 40 or 60 s PET (p = 0.74 and 0.91, respectively). Targeting differences between 20 s PET and CT ranged from 1.4-36 mm (mean 9.6 \ub1 7.1 mm; median 8.2 mm) and were not statistically different from 40, 60, or 180 s PET (p = 0.84, 0.77, and 0.35, respectively). Conclusion Single 20 s breath-hold PET acquisitions from PET/CT-guided percutaneous liver procedures have the potential to target FDG-avid liver masses with equivalent accuracy to 180 s summed, breath-hold PET acquisitions and may facilitate strategies that improve image registration and shorten procedure times