Molecular diagnosis of developmental disorders

ABSTRACT Idiopathic developmental disorders (DDs) affect ~1% of the population worldwide. This being a considerable amount, efforts are being made to elucidate the disease mechanisms. One or several genetic factors cause 30-40% of DDs, and only 10% are caused by environmental factors. The remaining 50% of DD patients go undiagnosed, mostly due to a lack of diagnostic techniques. The cause in most undiagnosed cases is though to be a genetic factor or a combination of genetic and environmental factors. Despite the surge of new technologies entering the market, their implementation into diagnostic laboratories is hampered by costs, lack of information about the expected diagnostic yield, and the wide range of selection. This study evaluates new microarray methods in diagnosing idiopathic DDs, providing information about their added diagnostic value. Study I analysed 150 patients by array comparative genomic hybridization (array CGH, 44K and 244K), with a subsequent 18% diagnostic yield. These results are supported by other studies, indicating an enourmous added diagnostic value of array CGH, compared with conventional cytogenetic analysis. Nevertheless, 80% of the patients remained undiagnosed in Study I. In an effort to diagnose more patients, in Study IV the resolution was increased from 8.9 Kb of the 244K CGH array to 0.7 Kb, by using a single-nucleotide polymorphism (SNP) array. However, no additional pathogenic changes were detected in the 35 patients assessed, and thus, for diagnostic purposes, an array platform with ca 9 Kb resolution appears adequate. The recent vast increase in reports of detected aberrations and associated phenotypes has enabled characterization of several new syndromes first based on a common aberration and thereafter by delineation of common clinical characteristics. In Study II, a familial deletion at 9q22.2q22.32 with variable penetrance was described. Despite several reports of aberrations in the adjacent area at 9q associated with Gorlin syndrome, the patients in this family had a unique phenotype and did not present with the syndrome. In Study III, a familial duplication of chromosome 6p22.2 was described. The duplication caused increased expression of an important enzyme of the γ-aminobutyric acid (GABA) degradation pathway, causing oxidative stress of the brain, and thus, very likely, the mild mental retardation of these patients. These two case studies attempted to pinpoint candidate genes and to resolve the pathogenic mechanism causing the clinical characteristics of the patients. Presenting rare genetic and clinical findings to the international science and medical community enables interpretation of similar findings in other patients. The added value of molecular karyotyping in patients with idiopathic DD is evident. As a first line of testing, arrays with a median resolution of at least 9 Kb should be considered and further characterization of detected aberrations undertaken when possible. Diagnostic whole-exome sequencing may be the best option for patients who remain undiagnosed after high-resolution array analysis.

A critical review of the definition of FRA resonance frequency of transformers as per IEEE Std C57.149-2012

The explanation of resonance given in IEEE Std C57.149-2012 to define resonance during frequency response analysis (FRA) measurements on transformers implicitly uses the conditions prevalent during resonance in a series R-L-C circuit. This dependence is evident from the two assertions made in the definition, viz., resulting in zero net reactive impedance, and, accompanied by a zero value appearing in the phase angle of the frequency response function. These two conditions are satisfied (at resonance) only in a series R-L-C circuit and certainly not in a transformer, as has been assumed in the Standard. This can be proved by considering a ladder-network model. Circuit analysis of this ladder network reveals the origin of this fallacy and proves that, at resonance, neither is the ladder network purely resistive and nor is the phase angle (between input voltage and input current) always zero. Also, during FRA measurements, it is often seen that phase angle does not traverse the conventional cyclic path from +90 degrees to -90 degrees (or vice versa) at all resonant frequencies. This peculiar feature can also be explained using pole-zero maps. Simple derivations, simulations and experimental results on an actual winding are presented. In summary, authors believe that this study dispels existing misconceptions about definition of FRA resonance and provides material for its correction in IEEE Std C57.149-2012. (C) 2014 Elsevier B.V. All rights reserved.

The present-day chemical composition of the SMC from UVES spectra of the sharp-lined, B-type dwarf AV 304

High-resolution spectroscopic VLT/UVES observations are presented for the B-type main-sequence star, AV 304, in the Small Magellanic Cloud (SMC). These spectra have been analysed using LTE model-atmosphere techniques, to derive stellar atmospheric parameters and chemical compositions. As AV 304 is located within the hydrogen burning main-sequence band, its chemical composition should reflect that of the SMC interstellar medium (ISM). A detailed line-by-line differential analysis has been undertaken relative to a Galactic comparison star. A general metal deficiency for the a-process elements O, Si & S of -0.43 +/- 0.05 dex is found for AV 304, with iron having a similar underabundance. Oxygen may be relatively over- abundant by similar to0.1 dex and carbon and aluminium underabundant by similar to0.2 dex. A large nitrogen underabundance (of -1.2 dex relative to hydrogen and -0.7 dex relative to iron) is found. This is interpreted in terms of the CNO bi-cycle having been suppressed in the SMC. Furthermore, the large nitrogen deficiency is in excellent agreement with that found for SMC H II regions. Indeed, this represents a first for stellar astrophysics - confirming the low base-line nitrogen composition of the SMC ISM (viz. 12+log(N/H) similar to 6.66 +/- 0.10 dex).

Suomenmaan kartta Karta öfver Stor-furstendömet Finland med stöd af de tillförlitligaste karta verk och officiella väga-uppgifter, meddelande af samteliga länestyrelserne i landet, äfvensom andra bidrag författad af Berndt Ad. Lindeman

1 kartta :, vär. ;, 119 x 67 cm, kansi 26 x 18 cm

Karta öfver storfurstendömet Finland sammandragen, med stöd af de tillförlitligaste kartor uti general landtmäteri kontoret samt särskildte benäget meddelade upplysningar, uppå K. E. Holms förlag, af A. W. Eklund /

1 kartta :, vär. ;, lehti 88,7 x 58 cm

Post- och väg-karta öfver stor furstendömet Finland, med stöd af kartor utgifne af general landtmäteri contoiret, general staben, St Petersburgska postamtet, herrar Schubert, Ekelund, Brummer, von Knorring med flere och tillförlitligaste väga-uppgifter af alla storfurstendömets herrar gouverneurer samt enskilta bidrag utarbetad åren 1846 och 1848 af Berndt Ad. Lindeman postmästare

1 kartta :, vär. ;, 102 x 70 cm, [1:1231722], skalan är en million 231722 del af naturliga storleken

Protetisk rehabilitering av ett parodontalt destruerat bett – ett patientfall

Parodontit är en folksjukdom, som genom inflammationsprocesser skadar tändernas parodontologiska fastsättningsmekanism och kan leda till tandförlust. Om bettet är funktionellt nedsatt och estetiskt otillfredställande finns det skäl att rehabilitera bettet. Eftersom generaliserad parodontit ofta försvagar delvis eller alla tänders fastsättningsmekanism eller destruerar det, är det en utmaning vid rehabilitering av bettet. Rehabiliteringsformen kan vara en fast brokonstruktion, avtagbar partiell protes, implantat eller implantatstödd konstruktion och täckprotes. I detta arbete behandlas problematiken med en litteraturöversikt och ett patientfall. Som material i litteraturöversikten används relevanta artiklar och allmänt accepterad litteratur inom ämnesområdet. Arbetets patientfall hade en medelsvår parodontit i generaliserad form. Både sjukdomen parodontit och flera periapikala inflammationsprocesser har lett till stora tandförlustområden i övre käkens bakre tandregioner. Slutsatsen för litteraturöversikten är att en fast brokonstruktion i första hand rekommenderas eftersom den fördelar bettbelastningen optimalt, skenar fast rörliga tänder, inte ackumulerar plack och är lätt att anpassa sig till för patienten. Även de andra rehabiliteringsformerna är fördelaktiga vid rätta indikationer. Alternativen för patientens bettrehabilitering var en fast brokonstruktion, implantatstödd brokonstruktion och avtagbar partiell protes. På grund av patientens ekonomiska situation och rehabiliteringsbehov av båda bakre tandregionerna i övre käken rehabiliterades bettet med en partiell protes. Planerna var att med en parodontologiskt konservativ preprotetisk vård kunna tillverka en ensidig friändsprotes och undvika en dubbelsidig friändsprotes. Slutligen tillverkades en dubbelsidig friändsprotes för att få en stabil och framförallt långsiktig protetisk rehabilitering av bettet. Oberoende av rehabiliteringsformen är en noggrann grundvård och ett regelbundet uppföljningssystem ett krav för en lyckad vård och ett långvarigt slutresultat.