Substance use among individuals with intellectual disabilities living independently in Flanders

Background: Over the past decades, there has been increased scientific and clinical interest in substance use among individuals with intellectual disabilities (ID). Despite raised interest and awareness in the topic, lack of supportive data on prevalence and risk factors highlights the need for ongoing research. The aims of this cross-sectional multicenter study were to examine the nature and extent of substance use in individuals with ID living independently, to investigate group differences in substance use and related problems, and to explore the role of substance-related knowledge and attitudes in substance use behaviors. Method: Participants were 123 individuals with mild to moderate ID receiving support from independent living services. Data were gathered by means of a structured interview strategy (i.e. the Substance Use and Misuse in Intellectual Disability - Questionnaire; SumID-Q). Results: Findings revealed that rates of lifetime use of licit and illicit substances were higher than those found in earlier studies among individuals with ID and the general population. While cannabis use was the only illicit substance reported, current tobacco and alcohol use were shown to be highly prevalent (48%-45.5%). Rates for the latter were similar to earlier studies among community samples of individuals with ID. In contrast to our hypotheses, few group differences in substance use behaviors were observed. Male gender was associated with age of onset of alcohol and tobacco use and tobacco use-related problems, while younger age was found to be associated with lifetime use of cannabis. No evidence was found regarding the role of knowledge; however, smokers and alcohol users rated tobacco and alcohol use more positively. Conclusion: This study demonstrated that individuals with ID living independently use a wide range of licit and illicit substances and present divergent levels and patterns of substance use. Notwithstanding the role of personal choice in substance use, more research is needed to better understand the nature and extent of substance use and related problems, as well as the role of substance-related knowledge and attitudes in individuals with ID

Relighting Egyptian rock art : rapid, accurate HD imaging of prehistoric petroglyphs

Within the framework of the project “Tracing Palaeolithic Aurochs: Rock Art Survey in Upper Egypt”, financed by the National Geographic Society, the authors participated in the long standing tradition of Belgian rock art research in Egypt. Under the direction of Dr. Dirk Huyge, extensive stretches of rock formations along wadi’s in the Eastern Desert between Edfu and Kom Ombo were surveyed in October-November 2014 for the presence of more prehistoric rock art sites, similar to the ones already discovered and studied by the Belgian team in this same region at Qurta and el-Hosh (Huyge et al 2007, 2011, 2012; Huyge 2009). This contribution focuses uniquely on a new component introduced to the 2014 mission: the development and testing of HD imaging techniques for rapid and accurate field recording of the sites with petroglyphs. Multi-light reflectance and 3D photogrammetry techniques were tested on their reliability and operability for a survey in the field

The application of Computed Tomography for characterising the pore structure of building materials

Flow and transport phenomena in porous media play a significant role in various fields of science and technology, comprising a spectrum from medical sciences over material sciences to soil and rock sciences. Also in building materials, the transfer of moisture and heat play a crucial role when assessing their properties and performances. Hence, three-dimensional analyses of the pore structure of building materials are becoming progressively more important in recent years, to obtain more accurate interpretations and simulations of their characteristics. Computed tomography has proven to be an excellent and versatile tool to perform these analyses non-destructively. The reconstruction of the pore structure is of high importance for establishing accurate models, as it plays a crucial role in determining important characteristics of building materials. These models allow to better understand the results of corresponding laboratory tests and in the near future might replace these time consuming experiments. In this paper the added value of Computed Tomography characterization will be demonstrated based on two case studies. The first will focus on the accurate simulation of moisture transfer while in the second one CT datasets are used to overcome a multiscale problem regarding the simulation of the effective thermal conductivity

Evaluation of relative quantification of alternatively spliced transcripts using droplet digital PCR

Introduction: For the relative quantification of isoform expression, RT-qPCR has been the gold standard for over a decade. More recently, digital PCR is becoming widely implemented, as it is promised to be more accurate, sensitive and less affected by inhibitors, without the need for standard curves. In this study we evaluated RT-qPCR versus RT-droplet digital PCR (ddPCR) for the relative quantification of isoforms in controls and carriers of the splice site mutation BRCA1 c.212+3A>G, associated with increased expression of several isoforms. Materials and methods: RNA was extracted from EBV cell lines of controls and heterozygous BRCA1 c.212+3A>G carriers. Transcript-specific plasmids were available to determine the efficiency, precision, reproducibility and accuracy of each method. Results: Both ddPCR and RT-qPCR were able to accurately quantify all targets and showed the same LOB, LOD and LOQ; also precision and reproducibility were similar. Both techniques have the same dynamic range and linearity at biologically relevant template concentrations. However, a significantly higher cost and workload was required for ddPCR experiments. Conclusions: Our study recognizes the potential and validity of digital PCR but shows the value of a highly optimized qPCR for the relative quantification of isoforms. Cost efficiency and simplicity turned out to be better for RT-qPCR. Keywords: Reverse transcriptase polymerase chain reaction, Alternative splicing, Droplet digital PC

In Vitro-Reconstituted Nucleoids Can Block Mitochondrial DNA Replication and Transcription

SummaryThe mechanisms regulating the number of active copies of mtDNA are still unclear. A mammalian cell typically contains 1,000–10,000 copies of mtDNA, which are packaged into nucleoprotein complexes termed nucleoids. The main protein component of these structures is mitochondrial transcription factor A (TFAM). Here, we reconstitute nucleoid-like particles in vitro and demonstrate that small changes in TFAM levels dramatically impact the fraction of DNA molecules available for transcription and DNA replication. Compaction by TFAM is highly cooperative, and at physiological ratios of TFAM to DNA, there are large variations in compaction, from fully compacted nucleoids to naked DNA. In compacted nucleoids, TFAM forms stable protein filaments on DNA that block melting and prevent progression of the replication and transcription machineries. Based on our observations, we suggest that small variations in the TFAM-to-mtDNA ratio may be used to regulate mitochondrial gene transcription and DNA replication

Relations between lipoprotein(a) concentrations, LPA genetic variants, and the risk of mortality in patients with established coronary heart disease: a molecular and genetic association study

Background: Lipoprotein(a) concentrations in plasma are associated with cardiovascular risk in the general population. Whether lipoprotein(a) concentrations or LPA genetic variants predict long-term mortality in patients with established coronary heart disease remains less clear. Methods: We obtained data from 3313 patients with established coronary heart disease in the Ludwigshafen Risk and Cardiovascular Health (LURIC) study. We tested associations of tertiles of lipoprotein(a) concentration in plasma and two LPA single-nucleotide polymorphisms ([SNPs] rs10455872 and rs3798220) with all-cause mortality and cardiovascular mortality by Cox regression analysis and with severity of disease by generalised linear modelling, with and without adjustment for age, sex, diabetes diagnosis, systolic blood pressure, BMI, smoking status, estimated glomerular filtration rate, LDL-cholesterol concentration, and use of lipid-lowering therapy. Results for plasma lipoprotein(a) concentrations were validated in five independent studies involving 10 195 patients with established coronary heart disease. Results for genetic associations were replicated through large-scale collaborative analysis in the GENIUS-CHD consortium, comprising 106 353 patients with established coronary heart disease and 19 332 deaths in 22 studies or cohorts. Findings: The median follow-up was 9·9 years. Increased severity of coronary heart disease was associated with lipoprotein(a) concentrations in plasma in the highest tertile (adjusted hazard radio [HR] 1·44, 95% CI 1·14–1·83) and the presence of either LPA SNP (1·88, 1·40–2·53). No associations were found in LURIC with all-cause mortality (highest tertile of lipoprotein(a) concentration in plasma 0·95, 0·81–1·11 and either LPA SNP 1·10, 0·92–1·31) or cardiovascular mortality (0·99, 0·81–1·2 and 1·13, 0·90–1·40, respectively) or in the validation studies. Interpretation: In patients with prevalent coronary heart disease, lipoprotein(a) concentrations and genetic variants showed no associations with mortality. We conclude that these variables are not useful risk factors to measure to predict progression to death after coronary heart disease is established. Funding: Seventh Framework Programme for Research and Technical Development (AtheroRemo and RiskyCAD), INTERREG IV Oberrhein Programme, Deutsche Nierenstiftung, Else-Kroener Fresenius Foundation, Deutsche Stiftung für Herzforschung, Deutsche Forschungsgemeinschaft, Saarland University, German Federal Ministry of Education and Research, Willy Robert Pitzer Foundation, and Waldburg-Zeil Clinics Isny

Concerns about anti-angiogenic treatment in patients with glioblastoma multiforme

BACKGROUND: The relevance of angiogenesis inhibition in the treatment of glioblastoma multiforme (GBM) should be considered in the unique context of malignant brain tumours. Although patients benefit greatly from reduced cerebral oedema and intracranial pressure, this important clinical improvement on its own may not be considered as an anti-tumour effect. DISCUSSION: GBM can be roughly separated into an angiogenic component, and an invasive or migratory component. Although this latter component seems inert to anti-angiogenic therapy, it is of major importance for disease progression and survival. We reviewed all relevant literature. Published data support that clinical symptoms are tempered by anti-angiogenic treatment, but that tumour invasion continues. Unfortunately, current imaging modalities are affected by anti-angiogenic treatment too, making it even harder to define tumour margins. To illustrate this we present MRI, biopsy and autopsy specimens from bevacizumab-treated patients. Moreover, while treatment of other tumour types may be improved by combining chemotherapy with anti-angiogenic drugs, inhibiting angiogenesis in GBM may antagonise the efficacy of chemotherapeutic drugs by normalising the blood-brain barrier function. SUMMARY: Although angiogenesis inhibition is of considerable value for symptom reduction in GBM patients, lack of proof of a true anti-tumour effect raises concerns about the place of this type of therapy in the treatment of GBM