Search for copy number variants in chromosomes 15q11-q13 and 22q11.2 in obsessive compulsive disorder

<p>Abstract</p> <p>Background</p> <p>Obsessive-compulsive disorder (OCD) is a clinically and etiologically heterogeneous syndrome. The high frequency of obsessive-compulsive symptoms reported in subjects with the 22q11.2 deletion syndrome (DiGeorge/velocardiofacial syndrome) or Prader-Willi syndrome (15q11-13 deletion of the paternally derived chromosome), suggests that gene dosage effects in these chromosomal regions could increase risk for OCD. Therefore, the aim of this study was to search for microrearrangements in these two regions in OCD patients.</p> <p>Methods</p> <p>We screened the 15q11-13 and 22q11.2 chromosomal regions for genomic imbalances in 236 patients with OCD using multiplex ligation-dependent probe amplification (MLPA).</p> <p>Results</p> <p>No deletions or duplications involving 15q11-13 or 22q11.2 were identified in our patients.</p> <p>Conclusions</p> <p>Our results suggest that deletions/duplications of chromosomes 15q11-13 and 22q11.2 are rare in OCD. Despite the negative findings in these two regions, the search for copy number variants in OCD using genome-wide array-based methods is a highly promising approach to identify genes of etiologic importance in the development of OCD.</p

International Consensus Statement on Rhinology and Allergy: Rhinosinusitis

Background: The 5 years since the publication of the first International Consensus Statement on Allergy and Rhinology: Rhinosinusitis (ICAR‐RS) has witnessed foundational progress in our understanding and treatment of rhinologic disease. These advances are reflected within the more than 40 new topics covered within the ICAR‐RS‐2021 as well as updates to the original 140 topics. This executive summary consolidates the evidence‐based findings of the document. Methods: ICAR‐RS presents over 180 topics in the forms of evidence‐based reviews with recommendations (EBRRs), evidence‐based reviews, and literature reviews. The highest grade structured recommendations of the EBRR sections are summarized in this executive summary. Results: ICAR‐RS‐2021 covers 22 topics regarding the medical management of RS, which are grade A/B and are presented in the executive summary. Additionally, 4 topics regarding the surgical management of RS are grade A/B and are presented in the executive summary. Finally, a comprehensive evidence‐based management algorithm is provided. Conclusion: This ICAR‐RS‐2021 executive summary provides a compilation of the evidence‐based recommendations for medical and surgical treatment of the most common forms of RS

Calibrations in 1994 of the gamma-spectroscopy set-ups in use at the Laboratory of Radiation Research for routine measurement and for measurement during major nuclear accidents

Om de activiteit van preparaten met gammastraling uitzendende nucliden te bepalen heeft het Laboratorium voor Stralingsonderzoek (LSO) de beschikking over een aantal halfgeleiderdetectoren. Deze opstellingen worden per preparaatvorm gekalibreerd voor de efficintie waarmee gemeten wordt. Dit rapport beschrijft de resultaten van de preparaatkalibraties voor het reguliere onderzoeksprogramma en de preparaatkalibraties voor metingen tijdens alarmsituaties. Ook worden een aantal analyses en berekeningen geevalueerd die hebben geleid tot een beter begrip van de resultaten. Het is gebleken dat de grootste onzekerheid in de preparaatkalibraties het gevolg is van een inhomogene verdeling van de activiteit over het preparaat. Bij de preparaatvorm 'teldoos 250 ml' is de homogeniteit nagenoeg perfect met als resultaat de best reproducerende metingen. De activiteit op het 'koolfilter' is niet homogeen verdeeld maar blijft gelokaliseerd op de plaats waar het is aangebracht. Vloeistofscintillatie metingen hebben voor het 'URENCO' en 'glasvezelfilter' aangetoond dat de activiteit zich na het drogen vooral op de rand van het filter bevindt. Bij het koolpatroon blijkt dat de injectiediepte (verschillend per experimentator) een grote rol speelt bij het bepalen van de detectorefficintie. Deze variatie in de hoogte van de activiteitspositie is ook van belang bij het 'HVS filterpakket'. De teldoos gevuld met melk- of grasas geeft bij grotere vulhoogten (30 en 40 mm) sterke afwijkingen in de meetuitkomsten. Dit is waarschijnlijk het gevolg van een minder goede homogeniteit. In de praktijk komen deze vulhoogten nauwelijks voor, zodat hiervoor voortaan niet meer gekalibreerd zal worden. Voor iedere preparaatvorm is een foutenanalyse uitgevoerd. Het blijkt dat de meeste fouten groter zijn dan 10%. Het criterium dat momenteel wordt gehanteerd voor acceptatie van een kalibratie is een verschil van minder dan 10% met de kalibratie van het voorgaande jaar. Wellicht moet dit criterium worden vervangen door een preparaat specifiek criterium. Berekeningen die gemaakt zijn om de telefficientie van ingewikkelde preparaten te modelleren komen overeen met hetgeen is waargenomen in de experimenten. Ze kunnen goed gebruikt worden om de gemaakte aannamen over de activiteitsverdelingen te onderbouwen.This report describes the calibrations in 1994 of the gamma-spectroscopy set-ups in use at the Laboratory of Radiation Research (LSO). The set-ups are calibrated for different matrices which are measured routinely in the monitoring program and matrices which are measured during major nuclear accidents. The calibration results are analysed and calculations are performed that have led to an improved understanding of the results.HIMH/TSSP HIMH/C

Projection of the future EU forest CO 2

Forests of the European Union (EU) have been intensively managed for decades, and they have formed a significant sink for carbon dioxide (CO2) from the atmosphere over the past 50 years. The reasons for this behavior are multiple, among them are: forest aging, area expansion, increasing plant productivity due to environmental changes of many kinds, and, most importantly, the growth rates of European foest having been higher than harvest rates. EU countries have agreed to reduce total emissions of GHG by 20% in 2020 compared to 1990, excluding the forest sink. A relevant question for climate policy is: how long will the current sink of EU forests be maintained in the near future? And could it be affected by other mitigation measures such as bioenergy? In this article we assess tradeoffs of bioenergy use and carbon sequestration at large scale and describe results of the comparison of two advanced forest management models that are used to project CO2 emission and removals from EU forests until 2030. EFISCEN, a detailed statistical matrix model and G4M, a geographically explicit economic forestry model, use scenarios of future harvest rates and forest growth information to estimate the future carbon balance of forest biomass. Two scenarios were assessed: the EU baseline scenario and the EU reference scenario (including additional bioenergy and climate policies). Our projections suggest a significant decline of the sink until 2030 in the baseline scenario of about 25-40% (or 65-125 Mt CO2) compared to the models' 2010 estimate. Including additional bioenergy targets of EU member states has an effect on the development of this sink, which is not accounted in the EU emission reduction target. A sensitivity analysis was performed on the role of future wood demand and proved the importance of this driver for the future sink development

An AP4B1 frameshift mutation in siblings with intellectual disability and spastic tetraplegia further delineates the AP-4 deficiency syndrome

Abdollahpour H, Alawi M, Kortüm F, et al. An AP4B1 frameshift mutation in siblings with intellectual disability and spastic tetraplegia further delineates the AP-4 deficiency syndrome. European Journal of Human Genetics. 2015;23(2):256-259.The recently proposed adaptor protein 4 (AP-4) deficiency syndrome comprises a group of congenital neurological disorders characterized by severe intellectual disability (ID), delayed or absent speech, hereditary spastic paraplegia, and growth retardation. AP-4 is a heterotetrameric protein complex with important functions in vesicle trafficking. Mutations in genes affecting different subunits of AP-4, including AP4B1, AP4E1, AP4S1, and AP4M1, have been reported in patients with the AP-4 deficiency phenotype. We describe two siblings from a non-consanguineous couple who presented with severe ID, absent speech, microcephaly, growth retardation, and progressive spastic tetraplegia. Whole-exome sequencing in the two patients identified the novel homozygous 2-bp deletion c.1160_1161delCA (p.(Thr387Argfs*30)) in AP4B1. Sanger sequencing confirmed the mutation in the siblings and revealed it in the heterozygous state in both parents. The AP4B1-associated phenotype has previously been assigned to spastic paraplegia-47. Identification of a novel AP4B1 alteration in two patients with clinical manifestations highly similar to other individuals with mutations affecting one of the four AP-4 subunits further supports the observation that loss of AP-4 assembly or functionality underlies the common clinical features in these patients and underscores the existence of the clinically recognizable AP-4 deficiency syndrome