35 research outputs found
The Predatory Museum
The common perception of museum can be found in a series of descriptive positive and uplifting adjectives such as educational, quiet, contemplative, trustworthy, truthful, accurate, authentic, safe, knowledgeable, and etc. Little thought is given to the mechanisms employed by which museums have reached such lofty heights in the eyes of individuals and communities alike. To most, it is perceived as a place of exploration and learning through the display and interpretation of cultural objects o..
Familial deletion 18p syndrome: case report
BACKGROUND: Deletion 18p is a frequent deletion syndrome characterized by dysmorphic features, growth deficiencies, and mental retardation with a poorer verbal performance. Until now, five families have been described with limited clinical description. We report transmission of deletion 18p from a mother to her two daughters and review the previous cases. CASE PRESENTATION: The proband is 12 years old and has short stature, dysmorphic features and moderate mental retardation. Her sister is 9 years old and also has short stature and similar dysmorphic features. Her cognitive performance is within the borderline to mild mental retardation range. The mother also presents short stature. Psychological evaluation showed moderate mental retardation. Chromosome analysis from the sisters and their mother revealed the same chromosomal deletion: 46, XX, del(18)(p11.2). Previous familial cases were consistent regarding the transmission of mental retardation. Our family differs in this regard with variable cognitive impairment and does not display poorer verbal than non-verbal abilities. An exclusive maternal transmission is observed throughout those families. Women with del(18p) are fertile and seem to have a normal miscarriage rate. CONCLUSION: Genetic counseling for these patients should take into account a greater range of cognitive outcome than previously reported
Outcomes in pediatric studies of medium-chain acyl-coA dehydrogenase (MCAD) deficiency and phenylketonuria (PKU): a review.
BACKGROUND: Inherited metabolic diseases (IMDs) are a group of individually rare single-gene diseases. For many IMDs, there is a paucity of high-quality evidence that evaluates the effectiveness of clinical interventions. Clinical effectiveness trials of IMD interventions could be supported through the development of core outcome sets (COSs), a recommended minimum set of standardized, high-quality outcomes and associated outcome measurement instruments to be incorporated by all trials in an area of study. We began the process of establishing pediatric COSs for two IMDs, medium-chain acyl-CoA dehydrogenase (MCAD) deficiency and phenylketonuria (PKU), by reviewing published literature to describe outcomes reported by authors, identify heterogeneity in outcomes across studies, and assemble a candidate list of outcomes.
METHODS: We used a comprehensive search strategy to identify primary studies and guidelines relevant to children with MCAD deficiency and PKU, extracting study characteristics and outcome information from eligible studies including outcome measurement instruments for select outcomes. Informed by an established framework and a previously published pediatric COS, outcomes were grouped into five, mutually-exclusive, a priori core areas: growth and development, life impact, pathophysiological manifestations, resource use, and death.
RESULTS: For MCAD deficiency, we identified 83 outcomes from 52 articles. The most frequently represented core area was pathophysiological manifestations, with 33 outcomes reported in 29/52 articles (56%). Death was the most frequently reported outcome. One-third of outcomes were reported by a single study. The most diversely measured outcome was cognition and intelligence/IQ for which eight unique measurement instruments were reported among 14 articles. For PKU, we identified 97 outcomes from 343 articles. The most frequently represented core area was pathophysiological manifestations with 31 outcomes reported in 281/343 articles (82%). Phenylalanine concentration was the most frequently reported outcome. Sixteen percent of outcomes were reported by a single study. Similar to MCAD deficiency, the most diversely measured PKU outcome was cognition and intelligence/IQ with 39 different instruments reported among 82 articles.
CONCLUSIONS: Heterogeneity of reported outcomes and outcome measurement instruments across published studies for both MCAD deficiency and PKU highlights the need for COSs for these diseases, to promote the use of meaningful outcomes and facilitate comparisons across studies
Diagnosis of late-onset Pompe disease and other muscle disorders by next-generation sequencing
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Retinal lipid and glucose metabolism dictates angiogenesis through the lipid sensor Ffar1
Tissues with high metabolic rates often use lipids, as well as glucose, for energy, conferring a survival advantage during feast and famine1. Current dogma suggests that high-energyâconsuming photoreceptors depend on glucose2, 3. Here we show that the retina also uses fatty acid ÎČ-oxidation for energy. Moreover, we identify a lipid sensor, free fatty acid receptor 1 (Ffar1), that curbs glucose uptake when fatty acids are available. Very-low-density lipoprotein receptor (Vldlr), which is present in photoreceptors4 and is expressed in other tissues with a high metabolic rate, facilitates the uptake of triglyceride-derived fatty acid5, 6. In the retinas of Vldlrâ/â mice with low fatty acid uptake6 but high circulating lipid levels, we found that Ffar1 suppresses expression of the glucose transporter Glut1. Impaired glucose entry into photoreceptors results in a dual (lipid and glucose) fuel shortage and a reduction in the levels of the Krebs cycle intermediate α-ketoglutarate (α-KG). Low α-KG levels promotes stabilization of hypoxia-induced factor 1a (Hif1a) and secretion of vascular endothelial growth factor A (Vegfa) by starved Vldlrâ/â photoreceptors, leading to neovascularization. The aberrant vessels in the Vldlrâ/â retinas, which invade normally avascular photoreceptors, are reminiscent of the vascular defects in retinal angiomatous proliferation, a subset of neovascular age-related macular degeneration (AMD)7, which is associated with high vitreous VEGFA levels in humans. Dysregulated lipid and glucose photoreceptor energy metabolism may therefore be a driving force in macular telangiectasia, neovascular AMD and other retinal diseases
AI is a viable alternative to high throughput screening: a 318-target study
: High throughput screening (HTS) is routinely used to identify bioactive small molecules. This requires physical compounds, which limits coverage of accessible chemical space. Computational approaches combined with vast on-demand chemical libraries can access far greater chemical space, provided that the predictive accuracy is sufficient to identify useful molecules. Through the largest and most diverse virtual HTS campaign reported to date, comprising 318 individual projects, we demonstrate that our AtomNetÂź convolutional neural network successfully finds novel hits across every major therapeutic area and protein class. We address historical limitations of computational screening by demonstrating success for target proteins without known binders, high-quality X-ray crystal structures, or manual cherry-picking of compounds. We show that the molecules selected by the AtomNetÂź model are novel drug-like scaffolds rather than minor modifications to known bioactive compounds. Our empirical results suggest that computational methods can substantially replace HTS as the first step of small-molecule drug discovery
Experimental study on the behaviour of partially encased composite columns made with light welded H steel shapes under compressive axial loads
Lâintervention dans les groupes de dĂ©veloppement de lâemployabilitĂ©Â : entre ce quâon en dit et ce qui sây fait
Le taux de chĂŽmage Ă©levĂ© provoque une hausse vertigineuse des exigences de performance pour celles et pour ceux qui cherchent un emploi. Les programmes dâinsertion socioprofessionnelle nĂ©gligent de considĂ©rer que le chĂŽmage est structurel et se fondent principalement sur la recherche de compatibilitĂ© « personne-travail ». Les intervenantes et les intervenants sont ainsi placĂ©s dans une situation contradictoire : prĂ©parer au travail dans un contexte de pĂ©nurie de lâemploi. Comment ces acteurs maintiennent-ils leur Ă©quilibre entre les programmes officiels (le prescrit), les modĂšles dâaction quâils Ă©pousent (le professĂ©) et ce quâils peuvent faire (le pratiquĂ©) ? Pour rĂ©pondre Ă cette question, il convient dâexaminer les stratĂ©gies de dĂ©fense quâils dĂ©ploient pour sâadapter, mais aussi les compĂ©tences quâils ont dĂ©veloppĂ©es dans lâaction pour influencer le cours des choses.The high rate of unemployment has prompted a dizzying increase in performance requirements for those seeking work. Programs for socioprofessional integration omit consideration of the fact that unemployment is structural and founded mainly on the search for âperson-jobâ compatibility. Thus employability workers are put in a contradictory situation: they prepare people for work in a context of job shortage. How do these actors maintain balance between official programming (what is prescribed), the models for action they espouse (what is professed), and what they can actually do (what is practised). To answer this question, it is useful to examine not just the defense strategies used to adjust, but also the competencies these workers develop in action to influence the course of events.La tasa elevada de desempleo provoca un alza vertiginosa de las exigencias de rendimiento para aquellos que buscan un empleo. Los programas de inserciĂłn socioprofesionales no consideran que el desempleo es estructural y se basan principalmente en la bĂșsqueda de compatibilidad âpersona-trabajoâ Los consultantes se colocan asi en una posiciĂłn contradictoria: preparar al trabajo en un contexto de escasez de empleo. ÂżCĂłmo mantienen estos actores su equilibrio entre los programas oficiales (lo prescrito), los modelos de acciĂłn que toman (lo profesado) y lo que pueden hacer (lo practicado)? Para responder a esta pregunta, conviene examinar las estrategias de defensa que ellos despliegan para adaptarse asi como las competencias que han desarrollado en la acciĂłn para influenciar el curso de las cosas.Die hohe Arbeitslosenquote bewirkt immer höhere Leistungsanforderungen an die Arbeitssucher. Die PlĂ€ne fĂŒr sozio-professionelle Eingliederung berĂŒcksichtigen nicht den Umstand, dass die Arbeitslosigkeit strukturell ist, und legen vor allem Wert auf Person-Arbeit- Vereinbarkeit. Die Beamten sind somit in einer schwierigen Lage: sie mĂŒssen auf ArbeitsplĂ€tze hin ausbilden, die es nicht gibt. Wie behalten diese Ausbilder ihr Gleichgewicht bei zwischen den offiziellen PlĂ€nen (dem Vorgeschriebenen), den von ihnen verteidigten Aktionsmodellen (dem Verteidigten) und dem, was sie tatsĂ€chlich machen können (dem Machbaren)? Um diese Frage zu beantworten, ist es ratsam, die von ihnen eingesetzten Anpassungsstrategien und die Kompetenzen zu untersuchen, die sie in der Praxis entwickelt haben, um den Lauf der Dinge zu beeinflussen
Neonatal Urine Screening Program in the Province of Quebec: Technological Upgrade from Thin Layer Chromatography to Tandem Mass Spectrometry
The Quebec Neonatal Urine Screening Program was initiated in 1971 with overall screening inception of newborns in 1973. Forty-seven years later, over 3.5 million babies have been screened for up to 25 inborn errors of metabolism divided into two groups: (1) urea cycle disorders and organic acidurias; and (2) disorders of amino acid metabolism and transport. The main goal of this preventive genetic medicine program is the detection of treatable diseases before the onset of clinical symptoms. Urine specimens from 21-day-old babies are collected and dried on filter paper by parents at home. The participation is voluntary with a high compliance rate over the years (~90%). Specimens are analyzed by thin layer chromatography (TLC). The main objective of this evaluative research project was to assess the feasibility of a technological upgrade towards mass spectrometry. A 2.85-min flow injection method was devised, normal values established, and abnormal profiles confirmed using second-tier tests. The validated assays are sensitive, specific, and suitable for populational screening, as well as for high-risk screening laboratories. Triple H syndrome, which would not be detected in newborns by blood screening at two days of age was found to be positive in the urine of an affected patient