bluuebunny/crossref_metadata_2025 huggingface dataset:
The inclusion of historical control data may reduce the power of a confirmatory study
Authors: Cuffe Robert L.
Published: March 2011

Large sample sizes in clinical trials increase the cost of clinical research and delay the availability of new treatments. Fewer patients could be recruited into clinical trials if historical data on the comparator could be used reliably in a trial's analysis. However, old trials may bias rather than augment data from a new trial if, for example, the standard of care has improved over time. A hierarchical model for the data from the current and historical trials decreases the weight given to the historical data in line with the discrepancy between the results from the different trials. This reduces the risk of substantial bias. This paper shows that this down‐weighting is not sufficiently sensitive to differences in the response rates between trials. Motivated by recent trials in HIV, this paper proposes and examines a more conservative weighting of historical data. Simulation showed that both the standard hierarchical and the proposed weighting of historical data led to Type II error rates worse than those attained by ignoring the historical data completely. This underlines the risks of including historical data in the primary analysis of a trial for which strict control of error rates is paramount. Copyright © 2011 John Wiley & Sons, Ltd.
Estimating standard errors for life expectancies based on complex survey data with mortality follow‐up: A case study using the National Health Interview Survey Linked Mortality Files
Authors: Schenker Nathaniel , Parsons Van L. , Lochner Kimberly A. , Wheatcroft Gloria , Pamuk Elsie R.
Published: March 2011

Life expectancy is an important measure for health research and policymaking. Linking individual survey records to mortality data can overcome limitations in vital statistics data used to examine differential mortality by permitting the construction of death rates based on information collected from respondents at the time of interview and facilitating estimation of life expectancies for subgroups of interest. However, use of complex survey data linked to mortality data can complicate the estimation of standard errors. This paper presents a case study of approaches to variance estimation for life expectancies based on life tables, using the National Health Interview Survey Linked Mortality Files. The approaches considered include application of Chiang's traditional method, which is straightforward but does not account for the complex design features of the data; balanced repeated replication (BRR), which is more complicated but accounts more fully for the design features; and compromise, ‘hybrid’ approaches, which can be less difficult to implement than BRR but still account partially for the design features. Two tentative conclusions are drawn. First, it is important to account for the effects of the complex sample design, at least within life‐table age intervals. Second, accounting for the effects within age intervals but not across age intervals, as is done by the hybrid methods, can yield reasonably accurate estimates of standard errors, especially for subgroups of interest with more homogeneous characteristics among their members. Published in 2011 by John Wiley & Sons, Ltd.
Entwerfen von leichten Dachtragwerken aus Glas und Stahl
Authors: Kloft Harald , Fäth Klaus , Wilhelm Viktor
Published: March 2011

Die Leichtigkeit von Dachtragwerken wird nicht durch Minimierung der Masse erzielt. Auch die Verwendung der Werkstoffe Glas und Stahl ist per se noch kein Garant für die filigrane Erscheinung einer Konstruktion. Der Entwurf von leichten Dachtragwerken aus Glas und Stahl gestaltet sich vielmehr als Optimierungsaufgabe von intelligenter Verteilung der Masse und gezielter Nutzung der Leistungsfähigkeit der beiden Werkstoffe. Wesentlicher Aspekt ist die Abstimmung des Tragwerksentwurfes auf die architektonische Entwurfsidee und die örtlichen Randbedingungen. Dies erfordert von Beginn an eine enge Zusammenarbeit von Architekt und Ingenieur.

In dem Beitrag werden die Entwurfsprozesse von drei leichten Dachtragwerken aus Stahl und Glas vorgestellt und die Rolle des entwerfenden Ingenieurs diskutiert. Die Tragwerke wurden von Klaus Fäth und Harald Kloft, als Inhaber des Ingenieurbüros osd – office for structural design, Frankfurt/M., in Zusammenarbeit mit Viktor Wilhelm, Stuttgart, geplant.

Designing lightweight roof structures of glass and steel. Lightness of roof structures does not mean to minimize the building mass. As well, the use of glass and steel will not guarantee a sophisticated appearance of a construction. Designing a lightweight, transparent structure is much more a task of optimization by intelligent arrangement of the building mass and by the defined use of the materials glass and steel. An essential aspect is the structural design in relation to the architectural idea and the urban context. All together, this needs a close cooperation of architect and engineer from the very beginning of a design process.

In the following three lightweight roof structures are presented and the role of the engineers will be discussed. All projects are designed by Klaus Fäth and Harald Kloft, the principals of the Frankfurt based engineering practice osd – office for structural design in close cooperation with Viktor Wilhelm from Stuttgart.
Einsatz von tragenden Glaselementen in Glasbrücken und Glaspavillions
Authors: Wellershoff Frank , Sendelbach Michael , Schmitt Felix
Published: March 2011

Mit der zunehmenden Erforschung und Akzeptanz von Glaselementen im konstruktiven Ingenieurbau werden reale Anwendungen mit vertretbarem Prüf‐ und Genehmigungsaufwand umsetzbar. Das Stabilitätsverhalten von Glaselementen aus Mehrfachverbundglas ist in den letzten Jahren umfangreich erforscht worden, so dass Glasstützen und Glasträger mit den vorgeschlagenen Stabilitätsnachweisen und ergänzenden FE‐Analysen gut dimensioniert werden können. Die Planung, Bauteilprüfung und Montage aktueller Glasbrücken und Glaspavillions für die permanente öffentliche Nutzung wird vorgestellt. Neben den projektbezogenen Stabilitätsprüfungen der Glasbauteile wird besonders auf die Anschlüsse sowie auf die Montage der Elemente eingegangen. Glasbrücken wurden in 2010 errichtet im “Eaton Center” in Calgary und im “Ritz‐Carlton Hotel” in Toronto. Glasstützen und deren Anschlüsse wurden entworfen und getestet für den U‐Bahn Eingang “Willy‐Brandt‐Platz” in Frankfurt und für den Glaspavillion im “Kravis Center” in Los Angeles.

Use of structural glass elements in glass bridges and glass pavilions. The use of structural glass elements becomes more and more accepted due to the increasing knowledge based on recent research projects. Real applications are meanwhile possible with realistic time and cost efforts for the approval by the building authorities. The stability of multi‐laminated glass elements has been intensively investigated in the recent years. Glass columns and glass beams can meanwhile be dimensioned based on the related publications and additional FE‐analysis. The design and the erections of current glass bridges and glass pavilions for the public use are described. Project specific stability tests and detailed connection tests are shown. Glass bridges have been erected in 2010 in the “Eaton Centre” in Calgary and in the “Ritz‐Carlton Hotel” in Toronto. Glass columns and their connections have been designed and tested for the Subway station “Willy Brandt Platz” in Frankfurt and the glass pavilion in the “Kravis Center” in Los Angeles.
Leicht und transparent – eine Glasbrücke in Lissabon
Authors: Keil Andreas , Straub Klaus
Published: March 2011

Das “Centre of the Unknown”, eine erst kürzlich fertiggestellte biomedizinische Forschungseinrichtung der Champalimaud‐Stiftung in Lissabon, Portugal, wurde von den Architekten Charles Correa Associates aus Mumbai, Indien, entworfen. Es besteht aus zwei Gebäudekomplexen, in denen die Forschungslabors, ein Auditorium und Ausstellungsbereich sowie die Büros der Stiftung Platz finden. Das “Centre of the Unknown” befindet sich im Stadtteil Belém, hier mündet der Fluss Tejo in den Atlantischen Ozean. Diese Lage ist von besonderer historischer Bedeutung, denn von hier aus setzten die portugiesischen Pioniere im 15. und 16. Jahrhundert die Segel, um das “Unbekannte” zu entdecken.

Ein optisches Highlight ist die leichte, 21 m lange Glasbrücke mit einer Hülle aus gebogenen Scheiben, die die beiden Gebäudekomplexe miteinander verbindet. Eine filigrane unterspannte Stahlkonstruktion bildet zugleich die Unterkonstruktion für die äußere Glashülle. Auch die Gehfläche und die Brüstungen bestehen aus Glaselementen und verleihen der Gesamtkonstruktion das geforderte Maß an Eleganz und Transparenz. Der Aufsatz geht auf die unterschiedlichen Anforderungen dieser ungewöhnlichen Brücke ein und zeichnet dabei den Entwurfsprozess bis hin zur Fertigstellung nach (Bild 1).

Light‐weight and transparent – a glass bridge in Lisbon. The “Centre of the Unknown”, a recently completed biomedical research facility of the Champalimaud Foundation in Lisbon, Portugal, was designed by Charles Correa Associates from Mumbai, India. It comprises two building complexes set in a large public area that accommodate treatment units, research laboratories, an auditorium and exhibition area, as well as the offices of the Champalimaud Foundation itself. The ‘Champalimaud Centre for the Unknown’ is located in the Belém district of Lisbon, where the Tagus River flows into the Atlantic Ocean. Its location is of particular historical significance, as it is the place from where Portuguese pioneers set sail to discover the ‘unknown’ in the 15th and 16th centuries.

A visual highlight is the light‐weight steel and glass bridge that connects the two buildings. The glass envelope encasing the bridge consists of curved panels of laminated glass. A filigree cable supported steel structure also forms the substructure of the glass envelope. The walkway and the railing also consist of laminated safety glass and thereby confer upon the entire structure the desired sense of elegance and transparency. The technical report addresses the various requirements of this out of the ordinary bridge and outlines the bridge design from conceptual design to completion (Fig. 1).
Verwendung von Glas zur Aussteifung von Gebäuden
Authors: Freitag Claudia , Wörner Johann‐Dietrich
Published: March 2011

Der Trend in der modernen Architektur zu Stahl‐Glas‐Gebäuden entspricht dem allgemeinen Zeitgeist nach Klarheit und Funktionalität einer Gebäudestruktur. Dies weckt den Wunsch, Glasscheiben neben der bisherigen Einhausungsfunktion auch zur Tragfähigkeit, insbesondere zur Schubaussteifung der Gebäude heranzuziehen, um somit auf Aussteifungsverbände verzichten zu können.

In vorliegender Studie soll dies über Lagermechanismen erfolgen, die eine definierte Vorspannung ermöglichen, wodurch bis zu einem gewissen Grad Zugspannungen in der Scheibe durch den vorhandenen Druck‐Vorspannungszustand aufgenommen werden können.

Es werden zwei Systeme mit mechanisch aufgebrachter Vorspannung betrachtet, ein System mit diskreter Ausklotzung in den Ecken, ein System mit kontinuierlicher Linienlagerung.

Utilisation of glass panes as structural bracings. The trend in modern architecture to steel and glass buildings corresponds to the general spirit of the time for clarity and functionality of a building structure. Thereof arouses the inspiration to utilise windowpanes in addition to their common function as façade material for structural bracing by application of a defined compression pre‐stress state in the window plane, which provides for taking over shear load contingent tensile stresses to a certain degree.

The present study observes two bearing systems for mechanical application of before‐mentioned compression pre‐stress state; one system with discrete block clamping in the window corners, and one system with continuous line bearing.
Relationship between characteristic parameters of impact test for safety glasses
Authors: Pacios Álvarez Antonia , Postigo Pozo Sergio , Huerta Gómez de Merodio Maria Consuelo
Published: March 2011

This paper presents results from experiments on soft impact testing of glass plates. In the experiments, a 50‐kg twin‐tire pendulum was used to strike different glass plates at speeds of up to 4.85 m/s. The impact parameters that were defined and measured include the micro‐strain in the glass plates, pendulum acceleration, duration of contact, pendulum height, and maximum tire track values. A total of 240 impacts on 17 specimens were carried out for different glass thicknesses (5, 6, 8, and 10 mm) and boundary conditions (four sides, two sides and four pin points supported). Tempered monolithic and toughened bi‐layered laminated plates were tested. To find out if the selected parameters represent the phenomena, multiple regression analysis was carried out.

Abhängigkeit der charakteristischen Kenngrößen bei Stoßbelastung an VSG. Dieser Beitrag zeigt Ergebnisse von experimentellen Untersuchungen des weichen Stoßes auf Glasplatten. In diesen Versuchen wurde ein 50‐kg‐Doppelreifenpendel genutzt, um verschiedene Glasplatten mit Geschwindigkeiten des Pendels bis zu 4,85 m/s zu pendeln. Die definierten und gemessenen Eigenschaften des Stoßes beinhalteten die Dehnungen in der Scheibe, die Pendelbeschleunigung, die Dauer des Pendelkontakts, die Fallhöhe und die maximale Kontaktfläche. Eine Gesamtzahl von 240 Pendelschlagversuchen an 17 Probekörpern wurde für verschiedene Glasdicken (5, 6, 8 und 10 mm) und Randbedingungen (allseitig und zweiseitig sowie vierfach punktförmig gelagert) durchgeführt. Thermisch vorgespanntes, monolithisches und vorgespanntes Zweifach‐Verbundglas wurden untersucht. Zur Ermittlung, ob die ausgewählten Parameter die Realität korrekt wiedergeben, wurde eine multiple Regressionsanalyse durchgeführt.
DIN 18008 – Teil 1 und Teil 2 – Was ändert sich gegenüber der TRLV?
Authors: Kasper Ruth , Pieplow Kirsten
Published: March 2011

Die bauaufsichtliche Einführung der ersten beiden Normteile der Bemessungs‐ und Konstruktionsregeln für Glas im Bauwesen steht kurz bevor. Für den Anwender bedeutet dies, dass bald für Glasbauteile die wesentlich aufwendigeren Nachweise entsprechend dem Teilsicherheitskonzept zu führen sind. Insbesondere für Mehrscheiben‐Isolierverglasungen aus Floatglas erhöht sich der Mehraufwand, da die Einwirkungen mit unterschiedlichen Wirkungsdauern belegt sind und auf der Widerstandsseite in Form einer lasteinwirkungsdauerabhängigen Biegezugfestigkeit Berücksichtigung finden. Dieses Nachweiskonzept wird der Materialeigenschaft von Glas gerecht, jedoch erhöht sich auch der Rechenaufwand. An Beispielen werden die wesentlichen Änderungen verdeutlicht.

What changes with respect to TRLV? The implementation of the first two parts of the design and construction regulations for glass in structural engineering by the responsible building authorities is imminent. For the user this implies that for glass components soon much more time consuming structural design calculations according to the partial safety concept have to be carried out. Especially for multi‐layered insulating float glass this leads to an increasing effort, because the loads are assigned to different duration which are taken into account on the resistance side in the form of a load duration dependent tensile strength.

This structural design calculation approach satisfies the material properties of glass but also increases the computational effort. By means of examples the major changes in the new design and construction regulations are illustrated.
Zwei Verfahren zum rechnerischen Nachweis der dynamischen Beanspruchung von Verglasungen durch weichen Stoß
Authors: Weller Bernhard , Reich Stefan , Krampe Philipp
Published: March 2011

Im Entwurf der DIN 18008‐4 wird ein Berechnungsverfahren für eine dynamisch‐transiente Berechnung von durch weichen Stoß beanspruchten Glasscheiben vorgeschlagen, welches in Teil 1 dieser Veröffentlichung grundlegend erläutert wird. Mit Hilfe universell einsetzbarer FE‐Bausoftware wird dieser Vorschlag auf seine praktische Umsetzbarkeit überprüft. Dies umfasst die Modellierung von Verglasungssituationen zur Verifizierung des Modells anhand berechneter Beschleunigungen des Doppelreifenpendels und den in der Verglasung entstehenden Zeit‐Hauptzugspannungs‐ Verläufen. Die Einflüsse der Modelldetaillierung auf die berechneten Hauptzugspannungen und Beschleunigungen werden dargelegt. Ein ausgewähltes Scheibenformat wird durch experimentelle und numerische Untersuchungen mit den Lösungen des Bemessungsvorschlages für weichen Stoß verglichen.

Two mechanical design concepts for simulating the soft body impact at glazings – Part 2: Numerical comparison and experimental verification. The draft of DIN 18808‐4 contains a novel design concept of a dynamic calculation for a glazing against soft impact. Part 1 of this contribution explains the ideas of the concept. By means of universally applicable FE structural analysis software this recommendation is verified for its practical handling. This includes the modelling of the glazing for verification by means of calculated pendulum accelerations and the principle tensile stresses in the glazing. The influence of the detailing of the FE‐model on calculated principle tensile stresses and pendulum accelerations is explained. The calculated results are compared to experimental results obtained on a single glazing.
FKG Fachverband Konstruktiver Glasbau – Arbeitskreis Kantenfestigkeit
Authors: Ensslen Frank
Published: March 2011

Der Arbeitskreis Kantenfestigkeit beim Fachverband Konstruktiver Glasbau e.V. wurde im Oktober 2009 gegründet und setzt sich aus Vertretern von Universitäten, Prüfstellen, Glasveredlern und Ingenieurbüros zusammen. Er hat sich zur Aufgabe gesetzt, die Kantenfestigkeit bzw. Kantenqualität in Abhängigkeit von der Kantenbearbeitungsart zuerst experimentell und im späteren Projektverlauf numerisch zu untersuchen. Ein Ziel ist die Formulierung eines Empfehlungspapiers für die zweckmäßigste Kantenausführung in Abhängigkeit von der Scheibenanwendung bzw. Kantenbeanspruchung.
Concise Review: Human Pluripotent Stem Cell-Based Models for Cardiac and Hepatic Toxicity Assessment
Authors: Sartipy Peter , Björquist Petter
Published: March 2011

Considering the costs associated with drug development, there are billions of dollars to be saved by reducing late-stage attrition in the pharmaceutical industries. Reports on the use of human pluripotent stem cells (hPSCs) and their functional derivatives in applications for safety assessment of drugs have begun to appear in the scientific literature. These reports are encouraging and fuel further developments of improved human cellular models that may increase the clinical relevance and reduce the need of experimental animals in preclinical drug discovery. However, a few factors still limit the general and wide-spread industry implementation of these new stem cell-based models, including cost of manufacture, level of functionality of the differentiated cells, assay validation, verification of human relevance, and benchmarking to conventional models. This review discusses the emerging field of hPSC-based models for drug discovery and development with a focus on cardiac and hepatic toxicity testing and how these approaches may improve current applications used in the pharmaceutical industry. Although much research remains to make hPSC-based models mainstream tools in the industry, importantly, this review highlights currently available opportunities. In addition, a forward looking discussion on novel applications using tissue preparations generated from hPSCs illustrates the opportunities to create complex models in vitro with the aim of simulating the systemic response of a drug in vivo.
Influence of fetal and parental factors on intrauterine growth measurements: results of the EDEN mother–child cohort
Authors: Albouy‐Llaty M. , Thiebaugeorges O. , Goua V. , Magnin G. , Schweitzer M. , Forhan A. , Lelong N. , Slama R. , Charles M. A. , Kaminski M. ,   and the ‘EDEN Mother–Child Cohort Study Group’
Published: March 2011

Objective

In small‐for‐gestational‐age neonates, parental and fetal characteristics can be used to distinguish between constitutionally small size and growth restriction, which is associated with a higher risk of morbidity and mortality. The aim of this study was to quantify relationships of parental and fetal characteristics with fetal ultrasound measurements.

Methods

The EDEN mother–child cohort included 2002 pregnant women with singleton pregnancies attending one of two university hospitals. Data from two routine ultrasound examinations for fetal biometry were recorded, at 20–25 and 30–35 weeks of gestation. Biparietal diameter (BPD), head circumference (HC), femur length (FL), abdominal circumference (AC) and estimated fetal weight (EFW) were studied as a function of prepregnancy maternal body mass index (BMI), maternal height, paternal height, fetal sex and gestational age.

Results

Data were obtained at the first scan from 1833 women and at the second scan from 1752 women. Parental anthropometric characteristics were significantly associated with ultrasound measurements at both scans. Maternal BMI was more strongly associated with AC and EFW, whereas both maternal and paternal height were more strongly associated with FL. An association was also found between fetal sex and all ultrasound measurements other than FL.

Conclusion

Maternal and paternal anthropometric characteristics are significantly associated with ultrasound measurements in mid to late pregnancy. These relationships provide support for the use of these characteristics in ultrasound fetal size reference charts. Copyright © 2011 ISUOG. Published by John Wiley & Sons, Ltd.
Cadmium(II) Complexes with Mixed cis‐Epoxysuccinate and 2,2′‐Bipyridyl‐Like Ligands: Syntheses, Crystal Structures, and Luminescent Properties
Authors: Liu Chun‐Sen , Wang Cong , Hu Min , Fang Shao‐Ming
Published: March 2011

Two new CdII complexes, [Cd(ces)(phen)]∞ (1) and {[Cd(ces)(bpy)(H2O)](H2O)}2 (2), were prepared by slow solvent evaporation methods from mixtures of cis‐epoxysuccinic acid and Cd(ClO4)2·6H2O in the presence of phen or bpy co‐ligand (ces = cis‐epoxysuccinate, phen = 1,10‐phenanthroline, and bpy = 2,2′‐bipyridine). Single‐crystal X‐ray diffraction analyses show that complex 1 has a one‐dimensional (1D) helical chain that is further assembled into a two‐dimensional (2D) sheet, and then an overall three‐dimensional (3D) network by the interchain C–H···O hydrogen bonds. Complex 2 features a dinuclear structure, which is further interlinked into a 3D supramolecular network by the co‐effects of intermolecular C–H···O and C–H···π hydrogen bonds as well as π···π stacking interactions. The structural differences between 1 and 2 are attributable to the intervention of different 2,2′‐bipyridyl‐like co‐ligands. Moreover, 1 and 2 exhibit intense solid‐state luminescence at room temperature, which mainly originates from the intraligand π→π* transitions of aromatic co‐ligands.
Functionalised Silver Chalcogenide Clusters
Authors: Langer Robert , Breitung Ben , Wünsche Linda , Fenske Dieter , Fuhr Olaf
Published: March 2011

Eight new silver chalcogenide clusters with different functional groups in the ligand shell were synthesised and characterised by single‐crystal X‐ray diffraction. The optical properties of the isostructural clusters [Ag6(S‐C6H4‐CN)6(PPh3)6] (1) and [Ag6(S‐C6H4‐NO2)6(PPh3)6] (2) are described and compared. In addition, the reactivity of 1 towards metal salts and Lewis acids was investigated, which led to the compounds [Ag6(S‐C6H4‐CN)6(PPh3)5] (3) and [Ag14S(S‐C6H4‐CN)12(PPh3)8][FeCl2(thf)4]3 (4). The sulfur‐functionalised cluster [Ag14S(S‐C6H4‐NCS)12(PPh3)8] (5) has prospects for further reactions and for the immobilisation on gold surfaces. The reactions of silver carboxylates with O,S‐bis(trimethylsilyl)‐4‐hydroxythiophenol and bis(trimethylsilyl) chalcogenides in the presence of tertiary phosphanes lead to the formation of the clusters [Ag23S2(S‐C6H4‐OSiMe3)15(S‐C6H4‐OH)3(PPh3)8] (6) and [Ag40Se4(S‐C6H4‐OSiMe3)32(PPh3)8] (7). Compound 6 can be regarded as a dimer of the described Ag14‐clusters in 4 and 5, whereas the inorganic core of cluster 7 has an unusual curved structural motif. The reaction of AgOAc with 4‐hydroxothiophenol in the presence of triethylphosphane leads to the assembly of a three dimensional network of [Ag8(S‐C6H4‐OH)6(PEt3)8](OAc)2 (8) in the crystal structure. A solution of 8 was investigated by ESI mass spectrometry, which resulted in the detection of a series of polynuclear silver thiolates with the general composition [Agn(S‐C6H4‐OH)n–1(PEt3)2]+.
Dimensions of Support Among Abused Women in the Workplace
Authors: Yragui Nanette L. , Mankowski Eric S. , Perrin Nancy A. , Glass Nancy E.
Published: March 2011

The authors draw on social support theory to examine supervisor support match (support wanted and received), support mismatch (support not wanted and received) and work outcomes for abused low‐wage working women, and to determine if supervisor support match and mismatch are more strongly associated with work outcomes than global supervisor support Face‐to‐face interviews were conducted with a community sample of abused, employed women who have experienced intimate partner violence (IPV) in the past year (N = 163). Using hierarchical regression, we found, after accounting for global supervisor support; a higher level of supervisor support match was associated with greater job satisfaction, fewer job reprimands and less job termination. Findings from the study inform theories of social support and have practical implications for workplace interventions for IPV.
Gaucher disease: when molecular testing and clinical presentation disagree ‐the novel c.1226A>G(p.N370S)‐‐RecNcil allele
Authors: Balwani Manisha , Grace Marie E. , Desnick Robert J.
Published: March 2011

We report a 31 year old woman who had prenatal carrier screening for Ashkenazi Jewish (AJ) genetic diseases and was found to have two acid ß‐glucosidase (GBA) mutations, c.1226A>G(p.N370S) and c.1448T>C(p.L444P), consistent with the diagnosis of Type 1 Gaucher disease (GD1). This genotype typically manifests in late‐adolescence with hepatosplenomegaly and early‐onset bone involvement. The Proband had a normal physical examination, no organomegaly, and normal blood counts, skeletal survey, and bone density. Leukocyte acid ß‐glucosidase and plasma chitotriosidase activities were normal. To investigate these unexpected results, her GBA alleles were RT‐PCR amplified and sequenced. Five RT‐PCR clones were negative for both mutations, while five clones had the c.1226A>G(p.N370S) and c.1448T>C(p.L444P) mutations, along with c.1483G>C(p.A456P), and c.1497G>C(p.V460V) mutations, the latter three lesions composing the rare GBA pseudogene‐derived RecNcil allele. Genetic testing misdiagnosed the asymptomatic Proband as affected with Type 1 Gaucher disease; however, molecular studies revealed a novel allele with the two common GBA mutations on the RecNcil background. This allele presumably arose by crossing‐over between a c.1226A>G allele and the pseudogene, gene conversion, or a new c.1226A>G mutation on the RecNcil background. This novel complex allele highlights a limitation of carrier screening for GD.
Transferrin mutations at the glycosylation site complicate diagnosis of congenital disorders of glycosylation type I
Authors: Guillard Mailys , Wada Yoshinao , Hansikova Hana , Yuasa Isao , Vesela Katerina , Ondruskova Nina , Kadoya Machiko , Janssen Alice , Van den Heuvel Lambertus P. W. J. , Morava Eva , Zeman Jiri , Wevers Ron A. , Lefeber Dirk J.
Published: March 2011

Congenital disorders of glycosylation (CDG) form a group of metabolic disorders caused by deficient glycosylation of proteins and/or lipids. Isoelectric focusing (IEF) of serum transferrin is the most common screening method to detect abnormalities of protein N‐glycosylation. On the basis of the IEF profile, patients can be grouped into CDG type I or CDG type II. Several protein variants of transferrin are known that result in a shift in isoelectric point (pI). In some cases, these protein variants co‐migrate with transferrin glycoforms, which complicates interpretation. In two patients with abnormal serum transferrin IEF profiles, neuraminidase digestion and subsequent IEF showed profiles suggestive of the diagnosis of CDG type I. Mass spectrometry of tryptic peptides of immunopurified transferrin, however, revealed a novel mutation at the N‐glycan attachment site. In case 1, a peptide with mutation p.Asn630Thr in the 2nd glycosylation site was identified, resulting in an additional band at disialotransferrin position on IEF. After neuraminidase digestion, a single band was found at the asialotransferrin position, indistinguishable from CDG type I patients. In case 2, a peptide with mutation p.Asn432His was found. These results show the use of mass spectrometry of transferrin peptides in the diagnostic track of CDG type I.
Clifford modules and invariants of quadratic forms
Authors: Karoubi Max , Serre Jean-Pierre
Published: March 2011

We construct new invariants of quadratic forms over commutative rings, using ideas from Topology. More precisely, we define a hermitian analog of the Bott class with target algebraic K-theory, based on the classification of Clifford modules. These invariants of quadratic forms go beyond the classical invariants defined via the Clifford algebra. An appendix by J.-P. Serre, of independent interest, describes the “square root” of the Bott class in the general framework of lambda rings.
Prevention and reversal of diet-induced leptin resistance with a sugar-free diet despite high fat content
Authors: Shapiro Alexandra , Tümer Nihal , Gao Yongxin , Cheng Kit-Yan , Scarpace Philip J.
Published: March 2011

Chronic consumption of a Western-type diet, containing both elevated sugar and fat, results in leptin resistance. We hypothesised that fructose, as part of the sugar component of Western-type diets, is one causative ingredient in the development of leptin resistance and that removal of this component will prevent leptin resistance despite high fat (HF) content. We fed rats a sugar-free (SF), 30 % HF (SF/HF) diet or a 40 % high-fructose (HFr), 30 % HF (HFr/HF) diet for 134 d. The HFr/HF diet resulted in impaired anorexic and body-weight responses to both peripherally (0·6 mg/kg, assessed on day 65 of the diet) and centrally (1·5 μg/d, assessed on days 129–134) administered leptin, whereas SF/HF-fed rats were fully leptin responsive. At day 70, half the HFr/HF-fed animals were switched to the SF/HF diet, reversing the leptin resistance (assessed 18 d after the diet switch). The HFr/HF diet elevated serum leptin and reduced adiponectin, and levels were restored abruptly at day 3 after switching to the SF/HF diet. These data demonstrate that a diet containing both HFr and fat leads to leptin resistance, while an isoenergetic SF/HF diet does not. Moreover, removal of fructose from this diet reverses the leptin resistance and the elevated leptin, suggesting a cause-and-effect relationship. These data suggest that fructose is the bioactive component of a HF/high-sugar diet that is essential for the induction of leptin resistance.
Making scents of behavioural genetics: lessons fromDrosophila
Authors: ANHOLT ROBERT R. H.
Published: March 2011

The expression of behaviours is influenced by many segregating genes. Behaviours are, therefore, complex traits. They have, however, unique characteristics that set them apart from physiological and morphological quantitative traits. First, behaviours are the ultimate expression of the nervous system. This means that understanding the genetic underpinnings of behaviours requires a neurobiological context, i.e. an understanding of the genes–brain–behaviour axis. In other words, how do ensembles of genes empower specific neural circuits to drive behaviours? Second, behaviours represent the interface between an organism and its environment. Thus, environmental effects are likely to make substantial contributions to determining behavioural outputs and genotype-by-environment interactions are expected to be prominent. It is important to differentiate between genes that contribute to the manifestation of the behavioural phenotype and genes that contribute to phenotypic variation in behaviour. The former are identified by classical mutagenesis experiments, whereas the latter can be detected through quantitative genetic approaches. Genes that contribute to phenotypic variation in behaviour harbour polymorphisms that provide the substrates for evolution. This review focuses on olfactory behaviour inDrosophilawith the goal to illustrate how fundamental insights derived from studies on chemosensation can be applied to a wide range of behavioural phenotypes.
From Galton to GWAS: quantitative genetics of human height
Authors: VISSCHER PETER M. , McEVOY BRIAN , YANG JIAN
Published: March 2011

Height has been studied in human genetics since the late 1800s. We review what we have learned about the genetic architecture of this trait from the resemblance between relatives and from genetic marker data. All empirical evidence points towards height being highly polygenic, with many loci contributing to variation in the population and most effect sizes appear to be small. Nevertheless, combining new genetic and genomic technologies with phenotypic measures on height on large samples facilitates new answers to old questions, including the basis of assortative mating in humans, estimation of non-additive genetic variation and partitioning between-cohort phenotypic differences into genetic and non-genetic underlying causes.
Caenorhabditis elegansas a platform for molecular quantitative genetics and the systems biology of natural variation
Authors: GAERTNER BRYN E. , PHILLIPS PATRICK C.
Published: March 2011

Over the past 30 years, the characteristics that have made the nematodeCaenorhabditis elegansone of the premier animal model systems have also allowed it to emerge as a powerful model system for determining the genetic basis of quantitative traits, particularly for the identification of naturally segregating and/or lab-adapted alleles with large phenotypic effects. To better understand the genetic underpinnings of natural variation in other complex phenotypes,C. elegansis uniquely poised in the emerging field of quantitative systems biology because of the extensive knowledge of cellular and neural bases to such traits. However, perturbations in standing genetic variation and patterns of linkage disequilibrium among loci are likely to limit our ability to tie understanding of molecular function to a broader evolutionary context. Coupling the experimental strengths of theC. eleganssystem with the ecological advantages of closely related nematodes should provide a powerful means of understanding both the molecular and evolutionary genetics of quantitative traits.
Ellen McDonald Gumperz (1936–1972): An Obituary
Authors: Zelliot Eleanor , Conlon Frank
Published: March 2011

The death of Ellen McDonald Gumperz in the midst of her period of mature scholarship and professional recognition was a loss not only to John Gumperz, her family, children and friends, but to those working in the many areas her studies probed. Her last research touched two of her basic interests: the area of Maharashtra in India and the structure of nineteenth century modernization. A planned study of communications systems was frustrated by her illness and by the paucity of local records. However, she left a number of studies which reveal a fine analytical mind and a lucid writing style and which break new ground in examining structures and in using modern quantitative methods in Indian history.
SOCIOECONOMIC, DEMOGRAPHIC AND LEGAL INFLUENCES ON CONSANGUINITY AND KINSHIP IN NORTHERN COASTAL SWEDEN 1780–1899
Authors: EGERBLADH I. , BITTLES A. H.
Published: March 2011

Most studies on consanguinity have been conducted on contemporary populations and have focused on the prevalence and types of preferred intra-familial marriage. With its comprehensive birth, marriage and deaths records dating back to the late 17th century, and the legal bar on first cousin marriage removed in the mid-19th century, Sweden offers unique opportunities to examine the factors that determine by whom, where and why consanguineous marriages were contracted. The present study covers the period 1780–1899 and presents a detailed portrait of cousin and sibling exchange marriages in the Skellefteå region of northern coastal Sweden. The combined prevalence of first, second and third cousin marriage increased from 2.3% in 1790–1810 to 8.8% in 1880–1899, and multi-generation consanguinity also increased significantly over the study period. The distribution and prevalence of first cousin marriages was strikingly non-random, with a significantly greater propensity for consanguinity among land-owning families, especially involving first-born sons, within specific pedigrees, and in a number of more remote inland communities. Additional factors associated with a greater likelihood of consanguineous marriage included physical or mental disability among males, and among females the prior birth of an illegitimate child. Besides the inherent interest in the social and demographic structure of this region of northern Sweden during the course of the 19th century, in future studies it will be important to determine the degree to which the observed patterns of consanguineous and sibling exchange marriages in these past generations could have influenced present-day genetic structure.
INTRA- AND INTERGENERATIONAL SOCIAL MOBILITY IN RELATION TO HEIGHT, WEIGHT AND BODY MASS INDEX IN A BRITISH NATIONAL COHORT
Authors: KRZYŻANOWSKA MONIKA , MASCIE-TAYLOR C. G. NICHOLAS
Published: March 2011

Using a sample of 2090 father and son pairs, the extent of intra- and inter-generational social mobility (migration between social classes) was examined over a 42-year period in a British cohort in relation to height, weight and body mass index (BMI). The mean height difference between the highest and lowest social class decreased from about 4 cm in the fathers' generation to about 3 cm in the sons' generation, indicating a decline in heterogeneity in height between classes. For fathers downward intra-generational social mobility ranged between 11% and 18% while between 16% and 26% were upwardly mobile; for sons 15% were downwardly mobile and 21% upwardly mobile. On average downwardly mobile fathers were shorter by between 0.1 cm and 0.7 cm while upwardly mobile fathers were taller by, on average, 0.6 cm to 1.7 cm. For sons, the downwardly mobile were on average 0.7 cm shorter and the upwardly mobile 0.8 cm taller. For weight and BMI there were no consistent relationships with intra-generational mobility in either the fathers' or sons' generations. Inter-generationally, between 18% and 19% of sons were downwardly mobile and between 39% and 40% were upwardly mobile; the downwardly mobile were shorter by about 0.9 cm and the upwardly taller by between 0.6 cm and 1.2 cm. Sons with higher BMI were more likely to be inter-generationally downwardly mobile.
Oscillatory Kelvin–Helmholtz instability. Part 2. An experiment in fluids with a large viscosity contrast
Authors: YOSHIKAWA HARUNORI N. , WESFREID JOSÉ EDUARDO
Published: March 2011

The stability of two-layer oscillatory flows was studied experimentally in a cylindrical container with a vertical axis. Two superposed immiscible liquids, differing greatly in viscosity, were set in relative oscillatory motion by alternating container rotation. Waves arising beyond a threshold were observed in detail for small oscillation frequencies ranging from 0.1 to 6 Hz. Measurements were performed on the growth rate and the wavenumber of these waves. The instability threshold was determined from the growth rate data. It was found that the threshold and the wavenumber varied with the frequency. In particular, significantly lower thresholds and longer waves were found than those predicted by the inviscid theory of the oscillatory Kelvin–Helmholtz instability. Favourable agreement with the predictions of an existing viscous theory for small oscillation amplitude flows indicates the important role of viscosity, even at the highest frequency, and suggests a similar mechanism behind the instability as that for the short wave instability in steady Couette flows. A semi-numerical stability determination for finite amplitude flows was also performed to improve the prediction in experiments with a frequency lower than 1 Hz.
Three-dimensional flow instability in a lid-driven isosceles triangular cavity
Authors: GONZÁLEZ L. M. , AHMED M. , KÜHNEN J. , KUHLMANN H. C. , THEOFILIS V.
Published: March 2011

Linear three-dimensional modal instability of steady laminar two-dimensional states developing in a lid-driven cavity of isosceles triangular cross-section is investigated theoretically and experimentally for the case in which the equal sides form a rectangular corner. An asymmetric steady two-dimensional motion is driven by the steady motion of one of the equal sides. If the side moves away from the rectangular corner, a stationary three-dimensional instability is found. If the motion is directed towards the corner, the instability is oscillatory. The respective critical Reynolds numbers are identified both theoretically and experimentally. The neutral curves pertinent to the two configurations and the properties of the respective leading eigenmodes are documented and analogies to instabilities in rectangular lid-driven cavities are discussed.
Synchronization of flexible sheets
Authors: ELFRING GWYNN J. , LAUGA ERIC
Published: March 2011

When swimming in close proximity, some microorganisms such as spermatozoa synchronize their flagella. Previous work on swimming sheets showed that such synchronization requires a geometrical asymmetry in the flagellar waveforms. Here we inquire about a physical mechanism responsible for such symmetry breaking in nature. Using a two-dimensional model, we demonstrate that flexible sheets with symmetric internal forcing deform when interacting with each other via a thin fluid layer in such a way as to systematically break the overall waveform symmetry, thereby always evolving to an in-phase conformation where energy dissipation is minimized. This dynamics is shown to be mathematically equivalent to that obtained for prescribed waveforms in viscoelastic fluids, emphasizing the crucial role of elasticity in symmetry breaking and synchronization.
A neurocognitive comparison of cognitive flexibility and response inhibition in gamblers with varying degrees of clinical severity
Authors: Odlaug B. L. , Chamberlain S. R. , Kim S. W. , Schreiber L. R. N. , Grant J. E.
Published: March 2011

Background

As a behavioral addiction with clinical and phenomenological similarities to substance addiction, recreational and pathological gambling represent models for studying the neurobiology of addiction, without the confounding deleterious brain effects which may occur from chronic substance abuse.

Method

A community sample of individuals aged 18–65 years who gamble was solicited through newspaper advertising. Subjects were grouped a priori into three groups (no-risk, at-risk, and pathological gamblers) based on a diagnostic interview. All subjects underwent a psychiatric clinical interview and neurocognitive tests assessing motor impulsivity and cognitive flexibility. Subjects with a current axis I disorder, history of brain injury/trauma, or implementation or dose changes of psychoactive medication within 6 weeks of study enrollment were excluded.

Results

A total of 135 no-risk, 69 at-risk and 46 pathological gambling subjects were assessed. Pathological gamblers were significantly older, and exhibited significant deficiencies in motor impulse control (stop-signal reaction times), response speed (median ‘go’ trial response latency) and cognitive flexibility [total intra-dimensional/extra-dimensional (IDED) errors] versus controls. The finding of impaired impulse control and cognitive flexibility was robust in an age-matched subgroup analysis of pathological gamblers. The no-risk and at-risk gambling groups did not significantly differ from each other on task performance.

Conclusions

Impaired response inhibition and cognitive flexibility exist in people with pathological gambling compared with no-risk and at-risk gamblers. The early identification of such illness in adolescence or young adulthood may aid in the prevention of addiction onset of such disabling disorders.
Symptomatic remission and neurocognitive functioning in patients with schizophrenia
Authors: Hofer A. , Bodner T. , Kaufmann A. , Kemmler G. , Mattarei U. , Pfaffenberger N. M. , Rettenbacher M. A. , Trebo E. , Yalcin N. , Fleischhacker W. W.
Published: March 2011

Background

A cross-sectional study was conducted in participants with schizophrenia to explore a potential association between the patients' remission status and neurocognitive functioning and to examine whether these factors have an impact on functional outcome.

Method

Psychopathological symptoms were rated by means of the Positive and Negative Syndrome Scale with symptom remission being assessed by applying the severity component of the recently proposed remission criteria. Tests for the cognitive battery were selected to cover domains known to be impaired in patients with schizophrenia. Next to pre-morbid intelligence, attention performance, executive functioning, verbal fluency, verbal learning and memory, working memory and visual memory were assessed. The joint effect of remission status and neurocognitive functioning on treatment outcome was investigated by logistic regression analysis.

Results

Out of 140 patients included in the study, 62 were symptomatically remitted. Mean age, education and sex distribution were comparable in remitted and non-remitted patients. Remitted patients showed significantly higher values on tests of verbal fluency, alertness and optical vigilance. Both symptomatic remission as well as performance on tests of working memory and verbal memory had a significant effect on the patients' employment status.

Conclusions

In the present study neuropsychological measures of frontal lobe functioning were associated with symptomatic remission from schizophrenia. In addition, both symptomatic remission and performance on tests of working memory and verbal memory had a significant effect on the patients' employment status. Longitudinal follow-up data are needed to determine how the associations of these determinants of functional outcome interact and change over time.