bluuebunny/crossref_metadata_2025 huggingface dataset:
Women in the United States, 1830-1945
Authors: Kleinberg S. J.
Published: December 2015

This book examines the history of US foreign policy since the Vietnam War. It focuses on four themes: the legacy of Vietnam; the ending and aftermath of the Cold War; the debate over American international decline; and the frequently undemocratic conduct of US foreign policy. The book considers alternative explanations for the Cold War's end. It evaluates the foreign policy leadership of Presidents Carter, Reagan, Bush and Clinton and assesses prospects for US foreign policy after the Cold War.
Cinnarizine and dimenhydrinate in the treatment of vertigo in medical practice
Authors: Scholtz Arne-Wulf , Ilgner Justus , Loader Benjamin , Pritschow Bernd W. , Weisshaar Gerhard
Published: December 2015

The efficacy and safety of the fixed combination of cinnarizine 20 mg and dimenhydrinate 40 mg in the treatment of vertigo of various origins have been investigated in a prospective, noninterventional study involving private practices throughout Germany. A total of 1275 patients with an average age of 61.2 years participated in the study. The vertigo symptoms, measured by a validated mean vertigo score (primary efficacy endpoint) improved by 61 % in the course of the observational period (median: 6 weeks). Concomitant symptoms frequently associated with vertigo such as nausea, vomiting and tinnitus were also markedly reduced by 84, 85 and 51 %, respectively. Overall efficacy has been rated by the physicians as ‘very much improved’ or ‘much improved’ in 95 % of the patients. A total of 47 patients (3.7 %) reported 51 adverse drug reactions (all nonserious). The results indicate a good tolerability and efficacy of the fixed combination of cinnarizine and dimenhydrinate in the treatment of vertigo in daily medical practice, which is in line with previous findings of numerous interventional, randomised, double-blind, controlled clinical trials.
Subcutaneous Port Malfunction: A Retrospective Comparison Between Internal Jugular and Subclavian Vein Access
Authors: Samman Mahmoud , Mujo Tomas , Harris John J. , Coldwell Douglas M. , Hite-Potts Melissa , Vyleta Martin
Published: December 2015

Purpose: To evaluate malfunction rates of subcutaneous chest ports placed via the internal jugular and subclavian veins. Analysis and preventive measures to reduce the risk of complication between the 2 sites of venous access will be discussed.

Methodology: Retrospective review of 114 patients with malfunctioning subcutaneous port-a-catheters was performed. Of those 114 patients, 77 had venous access via a subclavian approach, whereas the remaining 37 had internal jugular vein access. Port insertion placement was evaluated and analysis of the malfunction rate was performed.

Results: There were 36 patients with 38 subcutaneous port malfunctions from internal jugular vein access. Thirty-four of 38 complications (89%) were not related to insertion and 4 out of 38 (11%) were related to vascular access approach. Seventy-seven patients with malfunctioning subcutaneous ports placed via the subclavian vein had a total of 127 complications. Twenty-eight of 127 complications (22%) were not related to insertion and 99 out of 127 (78%) of the complications were directly related to venous access approach.

Conclusions: Subcutaneous port placement complications can be avoided by measuring the length of the port catheter under fluoroscopic guidance and positioning the tip within 2 cm of the cavoatrial junction. Also, the jugular vein should be the first site for access unless patient circumstances do not permit this approach.
Rates of Hospitalization for Dehydration Following Hurricane Sandy in New Jersey
Authors: Swerdel Joel N. , Rhoads George G. , Cosgrove Nora M. , Kostis John B. ,   for the Myocardial Infarction Data Acquisition System (MIDAS 25) Study Group
Published: December 2015

Objective

Hurricane Sandy, one of the most destructive natural disasters in New Jersey history, made landfall on October 29, 2012. Prolonged loss of electrical power and extensive infrastructure damage restricted access for many to food and water. We examined the rate of dehydration in New Jersey residents after Hurricane Sandy.

Methods

We obtained data from 2008 to 2012 from the Myocardial Infarction Data Acquisition System (MIDAS), a repository of in-patient records from nonfederal New Jersey hospitals (N=517,355). Patients with dehydration had ICD-9-CM discharge diagnosis codes for dehydration, volume depletion, and/or hypovolemia. We used log-linear modeling to estimate the change in in-patient hospitalizations for dehydration comparing 2 weeks after Sandy with the same period in the previous 4 years (2008–2011).

Results

In-patient hospitalizations for dehydration were 66% higher after Sandy than in 2008–2011 (rate ratio [RR]: 1.66; 95% confidence interval [CI]: 1.50, 1.84). Hospitalizations for dehydration in patients over 65 years of age increased by nearly 80% after Sandy compared with 2008–2011 (RR: 1.79; 95% CI: 1.58, 2.02).

Conclusion

Sandy was associated with a marked increase in hospitalizations for dehydration. Reducing the rate of dehydration following extreme weather events is an important public health concern that needs to be addressed, especially in those over 65 years of age. (Disaster Med Public Health Preparedness. 2016;10:188–192)
Tipping Points: Teachers’ Reported Reasons for Referring Primary School Children for Excessive Anxiety
Authors: Hinchliffe Kaitlin J. , Campbell Marilyn A.
Published: December 2015

The current study explored the reasons that primary school teachers reported were tipping points for them in deciding whether or not and when to refer a child to the school student support team for excessive anxiety. Twenty teachers in two Queensland primary schools were interviewed. Content analysis of interview transcripts revealed six themes reflecting teachers’ perceived reasons for deciding to refer anxious children: (1) impact on learning; (2) atypical child behaviour; (3) repeated difficulties that do not improve over time; (4) poor response to strategies; (5) teachers’ need for support; and (6) information from parents/carers. Teachers considered different combinations of reasons and had many different tipping points for making a referral. Both teacher- and system-level influences impacted referral decisions. Implications and future research are discussed.
‘No “Sane” Person Would Have Any Idea’: Patients’ Involvement in Late Nineteenth-century British Asylum Psychiatry
Authors: Chaney Sarah
Published: December 2015

In his 1895 textbook,Mental Physiology, Bethlem Royal Hospital physician Theo Hyslop acknowledged the assistance of three fellow hospital residents. One was a junior colleague. The other two were both patients: Walter Abraham Haigh and Henry Francis Harding. Haigh was also thanked in former superintendent George Savage’s bookInsanity and Allied Neuroses(1884). In neither instance were the patients identified as such. This begs the question: what role did Haigh and Harding play in asylum theory and practice? And how did these two men interpret their experiences, both within and outside the asylum? By focusing on Haigh and Harding’s unusual status, this paper argues that the notion of nineteenth-century ‘asylum patient’ needs to be investigated by paying close attention to specific national and institutional circumstances. Exploring Haigh and Harding’s active engagement with their physicians provides insight into this lesser-known aspect of psychiatry’s history. Their experience suggests that, in some instances, representations of madness at that period were the product of a two-way process of negotiation between alienist and patient. Patients, in other words, were not always mere victims of ‘psychiatric power’; they participated in the construction and circulation of medical notions by serving as active intermediaries between medical and lay perceptions of madness.
Making Sense of the ‘Chemical Revolution’. Patients’ Voices on the Introduction of Neuroleptics in the 1950s
Authors: Majerus Benoît
Published: December 2015

The so-called chemical revolution has produced a vast historiographical corpus. Yet the patient’s voice remains surprisingly absent from these stories. Based on the archives of theInstitut de Psychiatrie (Brussels), this paper traces the introduction of Largactil as recounted in patient letters, physician records and nurse notes. The paper thus contributes to the history of therapies from below, but also participates in the historiographical debate about whether the introduction of neuroleptics can indeed be considered a revolution.
Introduction: Jewish Studies and Postcolonialism
Authors: Goetschel Willi , Quayson Ato
Published: December 2015

The introduction to this special issue makes the case for seeing Jewish studies and postcolonialism as part of a historical constellation that has mutual filiations and genealogies in the two fields. It calls for the imperative to see the world’s problems historically but also through the mutually illuminating perspectives of the two fields.
Two bronze age cargoes in British waters
Authors: Muckelroy Keith
Published: December 2015

Since the mid-1960s, significant advances have been made in the techniques and organization of archaeological research in British waters. However, the sites discovered and explored during the first decade of such work have dated without exception to the centuries after 1500 AD. The results from investigations such as those on the Mary Rose of 1545 (Rule, 1978) or the wrecks of the Spanish Armada (Martin, 1975) have clearly demonstrated the potential of such sites to shed light on periods and topics for which documentary sources are also available; nevertheless, the full archaeological significance of this new area of research remained unrealized through being limited to the post-medieval period. The discovery and study of two underwater bronze age sites in the past few years have thus changed the whole complexion of British maritime archaeology. The purpose of this note is to provide a brief interim account of the sites involved, and indicate a few of their implications for Bronze Age studies.
Archaeological retrospect I
Authors: Phillips Charles
Published: December 2015

Looking back over a concern with archaeology which has lasted for half a century I am grateful to have been present through a crucial period in its development.

There were few advantages in my earliest days. On my father’s side I come from a line of farmers, land appraisers, bailiffs and the like which I can trace back in some detail for nearly three hundred years, living for the most part in Northwest Essex; on my mother’s side my ancestors were North Wessex peasants and inn-keepers, with a probable admixture of Welsh cattle-drover blood at the end of the eighteenth century. Wantage and Abingdon were their local centres. All with the exception of one or two backsliders were strict Evangelicals, often wavering on the verge of Dissent, and none ever aspired to any higher standard of education than one who entered the Congregational ministry in 1827. Any known interest in learning or antiquity showed itself more among the Wessex peasants than the clod-hoppers of Essex. My maternal grandfather, who was a native of the Vale of White Horse, was personally known to me and was interested in the many relics of the past observable about him, an intelligent man but with little formal instruction.
The late Hallstatt chieftain's grave at Hochdorf
Authors: Biel J.
Published: December 2015

The roots of Celtic civilization can be seen to lie in the hill strongholds of late Hallstatt period in Eastern France, Switzerland and Southern Germany, distinguished by their Mediterranean contacts: these have been classed as the residences of chieftains, Fürstensitze, by Kimmig (1968). Three of these Fürstensitze have particularly attracted archaeological attention in the last 30 years, in Southern Germany, the Heuneburg on the Upper Danube (Kimmig, 1968; Kimmig/Gersbach, 1971), and the Hohenasperg near Ludwigsburg (Zürn, 1970), and in Burgundy Mt Lassois near Châtillonsur-Seine (Joffroy, 1960). The excavation of the Heuneburg was mainly confined to the settlement site itself, whereas we know the Hohenasperg only from the graves surrounding the site. The excavation of the Grafenbühl tumulus by Hartwig Zürn in 1964/65 (Zürn, 1970) has shown, however, that the importance of the Hohenasperg must have been at least equal to that of the Heuneburg.
The two Indian epics vis-à-vis archaeology
Authors: Lal B. B.
Published: December 2015

The historicity of the two Indian epics, viz., the Mahābhārata and the Rāmāyana, has been the subject of heated debate ever since these epics attracted the attention of scholars, both in India and abroad. Thus, while there are some who hold that every event mentioned in these epics is historically true, there are others who regard them as mere figments of the imagination. Apart from the possibility that ‘orthodoxy’ and ‘reactionary attitude’ may respectively be partly responsible for such extremely divergent views, the confusion seems to arise from the fact that these epics are neither contemporary documentation of the episodes concerned nor have their texts remained immune from large-scale interpolations.
The first ‘Woodhenge’ in Middle Europe
Authors: Behrens Hermann
Published: December 2015

In 1967 the regional museum for prehistory at Halle (Saale) began an excavation in the field known as the Schalkenburg, near Quenstedt, which lies in Hettstedt district, on the eastern edge of the Harz mountains, about 50 km north-west of Halle, in the south-west of the German Democratic Republic (PL. xxva). The excavations were carried out annually in the months of July and August (Behrens & Schröter 1980), and their aim was to investigate a settlement of the neolithic Bernburg culture.
Schliemann's discovery of ‘Priam's Treasure’: two enigmas
Authors: Easton Donald F.
Published: December 2015

There has always been an enigma over the precise date during the Troy excavations of 1873 when Schliemann found the collection of metalwork which he dignified as ‘Priam's Treasure’ . His only published indication of the date appears to be his statement in 1884 that the discovery was made ‘at the end of May 1873’ (Schliemann 1884, 57). Biographers, even those who have studied Schliemann' s unpublished diaries and letters, have proposed a variety of dates, Ludwig places it ‘on a morning in the middle of June, one day before the termination of the work’ , in other words on the 14th June (Ludwig, 1931, 179). Payne prefers 30th May, ‘or a few days earlier’ (Payne, 1958, 116). Stone seems to settle for Saturday 31st May (Stone, 1976, 318f). Poole and Deuel place the discovery simply in late May or early June (Poole, 1967, 133; Deuel, 1978, 194). Brackman suggests 17th June or several days earlier, but suspends judgement on the matter (Brackman, 1974, 157). Ernst Meyer, who, because of his extensive work on the Schliemann papers in the late 1930s, has some claim to be regarded as the definitive biographer, at first gave the date as lying between 7th and 10th June (Meyer, 1953, I, 342, n. 335). Later, however, he narrowed this to 7th June on the authority of an otherwise unpublished entry in Schliemann's diary (Meyer, 1969, 273). Thus there is not only disagreement in the secondary sources, but in Schliemann's own writings; for this date, which is indeed explicitly named in the diary, conflicts with Schliemann's published statement referring to ‘the end of May 1873’.
The first Welshman: excavations at Pontnewydd
Authors: Green H. Stephen
Published: December 2015

Pontnewydd Cave lies in the Elwy Valley, near the western edge of the Vale of Clywd (FIG. 1), six km north-west of the modern town of Denbigh. The site first became well-known through the successive investigations of the nineteenth-century geologists Professors William Boyd Dawkins and T. H. McKenny Hughes, the latter working with the Reverend D. R. Thomas, then Vicar of Cefn. Boyd Dawkins' s excavations at the site (1874, 286–7; 1880, 192) yielded a fauna which included hippopotamus, but no artifacts were observed. The work of Hughes & Thomas (1874; Hughes, 1887) seems to have been confined principally to scouring Boyd Dawkins' s dumps, and yielded not only fauna but also evidence of the presence of man in the form both of artifacts and of a human molar tooth, since lost. This molar has long excited interest on account of its description by Busk (in Hughes & Thomas, 1874, 390) as being ‘of very large size’ and looking ‘quite as ancient as the rest [of the fauna]’. One of the many research aims of the current investigation was, therefore, to examine the possibility that the cave was a site where human remains might be found in association with an archaeological industry.
Testing a back-arc ‘aulacogen’ model for the Central Metasedimentary Belt of the Grenville Province
Authors: DICKIN ALAN , HYNES EDEN , STRONG JACOB , WISBORG MARK
Published: December 2015

Nearly 70 new Nd isotope analyses are presented for plutonic orthogneisses from the Grenvillian Central Metasedimentary Belt (CMB) in order to test a back-arc aulacogen model for its origin. Nd isotope signatures of metaplutonic rocks are used as probes of the formation age of the crust at depth, revealing sharp boundaries between old crustal blocks and juvenile (1.2–1.35 Ga) Elzevirian-age crust. Firstly, a hidden block of old crustal basement is revealed between areas of juvenile crust south of Douglas, Ontario. Secondly, TDM ages refine the boundary between juvenile crust and old basement (1.35–1.55 Ga) within the Weslemkoon batholith, showing this pluton to be a polygenetic stitching pluton that straddles a hidden crustal boundary. Finally, the CMB boundary zone is shown to form a sharp age boundary between juvenile and old crustal domains, and is interpreted as a reactivated rift-bounding normal fault. When the distribution of rift-related alkaline rocks is compared with these crustal boundaries, the Bancroft nepheline syenite suite is centrally located in a juvenile ensimatic zone between blocks of old basement. Such a location, near the axis of a juvenile crustal segment, implies emplacement late in the rifting process. Similarly, the Blue Mountain nepheline syenite appears to post-date an earlier rifting event to the southeast. Hence, a multi-stage model is proposed for the evolution of a back-arc aulacogen, which is consistent with the distribution of marble and volcanic/plutonic units in the CMB. The model places the Bancroft nepheline syenites in a precise plate tectonic context for the first time.
Multi-symplectic magnetohydrodynamics: II, addendum and erratum
Authors: Webb G. M. , McKenzie J. F. , Zank G. P.
Published: December 2015

A recent paper by Webb et al. (J. Plasma Phys., vol. 80, 2014, pp. 707–743) on multi-symplectic magnetohydrodynamics (MHD) using Clebsch variables in an Eulerian action principle with constraints is further extended. We relate a class of symplecticity conservation laws to a vorticity conservation law, and provide a corrected form of the Cartan–Poincaré differential form formulation of the system. We also correct some typographical errors (omissions) in Webb et al. (J. Plasma Phys., vol. 80, 2014, pp. 707–743). We show that the vorticity–symplecticity conservation law, that arises as a compatibility condition on the system, expressed in terms of the Clebsch variables is equivalent to taking the curl of the conservation form of the MHD momentum equation. We use the Cartan–Poincaré form to obtain a class of differential forms that represent the system using Cartan’s geometric theory of partial differential equations
Reading Publicity Photographs through the Elizabeth Robins Archive: How Images of the Actress and the Queen Constructed a New Sexual Ideal
Authors: Bonapfel Elizabeth M.
Published: December 2015

In this article, I trace the origins of the normalization of pornographic tropes as the new sexual ideal in contemporary visual culture to late nineteenth- and early twentieth-century publicity photos of actresses and monarchs by examining one prominent transatlantic actress's collection of publicity photos, the Elizabeth Robins Papers at the Fales Library at New York University. As I show, around the turn of the twentieth century, a new standard of idealized feminine beauty was produced by the combination of two contradictory images of celebrity: the distant decorum of the monarch and the perceived erotic sexuality of the actress. The mass production of publicity photographs, which took the form of cartes-de-visite in the 1860s and cabinet photos in the 1870s, broadened the spectrum of sexuality by positioning these two quintessential celebrity types—the actress and the monarch—in relation to the tableau vivant and to existing and emerging tropes of portraiture. The image of the actress existed in relation to several mutually dependent discourses in the late nineteenth and early twentieth centuries: the rise of photography in relation to other art forms; the rise of theatrical spectacle in relation to advertising, consumerism, and fashion; the rise of women's public role in relation to sexuality, the body, and beauty culture; and the paradoxical democratization of celebrity culture as related to the monarchy. All of these factors center on a figure who lived so vividly in the public imaginary that she could be found in multiple spaces: on the stage, in stationers’ shops, on postcards, in newspapers, in photograph albums.
Life History and Risk of Death after 50: A Survival Analysis for Europe
Authors: Nicińska Anna , Kalbarczyk-Stęclik Małgorzata
Published: December 2015

Dans notre étude nous avons examiné l’influence des événements du passé des individus sur le risque de décès des Européens âgés de plus de 50 ans, en contrôlant autres variables pertinentes. Notre analyse était basée sur les données d’entretiens biographiques rétrospectifs, les données d’entretiens réguliers au suivi longitudinal et celles d’entretiens de fin de vie de l’Enquête européenne SHARE sur la santé, le vieillissement et la retraite en Europe. En particulier, nous relevons l’état de santé auto-déclaré pendant l’enfance; les périodes de pauvreté, de faim et de mauvaise santé éprouvées dans le passé; et aussi l’histoire des soins de santé, y compris les soins dentaires, les analyses de sang et les mesures de pression artérielle. Ces informations, avec l’age, le sexe, l’état de santé subjectif et objectif, et d’autres facteurs socio-démographiques, permettent d’expliquer le risque de décès. L’analyse de survie, en contrôlant des variables pertinentes, montre que les événements du passé ont un impact significatif sur le risque de décès des Européens âgés de plus de 50 ans.
Comparative efficacy of four candidate DNA barcode regions for identification of Vicia species
Authors: Raveendar Sebastin , Lee Jung-Ro , Shim Donghwan , Lee Gi-An , Jeon Young-Ah , Cho Gyu-Taek , Ma Kyung-Ho , Lee Sok-Young , Sung Gi-Ho , Chung Jong-Wook
Published: December 2015

The genus Vicia L., one of the earliest domesticated plant genera, is a member of the legume tribe Fabeae of the subfamily Papilionoideae (Fabaceae). The taxonomic history of this genus is extensive and controversial, which has hindered the development of taxonomic procedures and made it difficult to identify and share these economically important crop resources. Species identification through DNA barcoding is a valuable taxonomic classification tool. In this study, four DNA barcodes (ITS2, matK, rbcL and psbA-trnH) were evaluated on 110 samples that represented 34 taxonomically best-known species in the Vicia genus. Topologies of the phylogenetic trees based on an individual locus were similar. Individual locus-based analyses could not discriminate closely related Vicia species. We proposed a concatenated data approach to increase the resolving power of ITS2. The DNA barcodes matK, psbA-trnH and rbcL were used as an additional tool for phylogenetic analysis. Among the four barcodes, three-barcode combinations that included psbA-trnH with any two of the other barcodes (ITS2, matK or rbcL) provided the best discrimination among Vicia species. Species discrimination was assessed with bootstrap values and considered successful only when all the conspecific individuals formed a single clade. Through sequencing of these barcodes from additional Vicia accessions, 17 of the 34 known Vicia species could be identified with varying levels of confidence. From our analyses, the combined barcoding markers are useful in the early diagnosis of targeted Vicia species and can provide essential baseline data for conservation strategies, as well as guidance in assembling germplasm collections.
Nebenwirkungen bei Kindern besser verstehen und vermeiden
Authors: Gotta Verena , van den Anker Johannes , Pfister Marc
Published: December 2015

Zusammenfassung. Entwicklungsbedingte physiologisch-pharmakologische Faktoren beeinflussen das Nebenwirkungsprofil von Arzneimitteln (unerwünschte Arzneimittelwirkungen, UAW) in der Kindheit. Eine erhöhte Empfindlichkeit gegenüber UAW wird vor allem bei Säuglingen und Neugeborenen beobachtet, verursacht durch eine grössere Arzneimittel-Exposition (aufgrund veränderter Pharmakokinetik) oder eine grössere Empfindlichkeit gegenüber dem Arzneimittel (aufgrund veränderter Pharmakodynamik). Das Wirkungs- und Nebenwirkungsprofil der meisten erhältlichen Arzneimittel wurde bei Kindern nicht formell in klinischen Studien evaluiert. Daher ist die optimale Dosierung bei dieser Patientengruppe selten bekannt. Zudem erschweren kinderunfreundliche Arzneiformen eine exakte Dosierung, was das Risiko von UAW aufgrund eines Dosierungsfehlers erhöht. Dieser Artikel gibt einen Überblick über pädiatrische UAW und zeigt neue Entwicklungen im regulatorischen und pharmakologisch-klinischen Bereich auf, die zukünftig helfen könnten, unerwünschte Nebenwirkungen bei Kindern besser zu verstehen und vermeiden.
Arzneimittelallergien: klinische Präsentation und Warnzeichen
Authors: Scherer Hofmeier Kathrin , Bircher Andreas J.
Published: December 2015

Zusammenfassung. Prinzipiell können alle Medikamente allergische Reaktionen auslösen, allerdings gibt es erhebliche Unterschiede in der Häufigkeit und klinischen Präsentation. Antibiotika, Antiepileptika und NSAIDs gehören zu den häufigsten Auslösern. Das Risiko für Sensibilisierungen und für schwere Verläufe hängt vom Aussmass der Immunaktivierung des Einzelnen ab, von Dosis, Dauer der Behandlung, Verabreichungsart, Geschlecht und bei einigen Substanzen auch von HLA-Merkmalen. Im vorliegenden Artikel werden die häufigsten immunmediierten Hypersensitivitätsreaktionen gegen Arzneimittel vorgestellt und auf klinische Warnzeichen für schwere Verläufe hingewiesen.
Evidenzbasierte Psychotherapie bei Zwangsstörungen
Authors: Kathmann Norbert
Published: December 2015

Zusammenfassung. Theoretischer Hintergrund: Leitlinien im Bereich der Medizin und Psychotherapie basieren auf systematischen Zusammenstellungen der verfügbaren Evidenz und dienen der Entscheidungshilfe für Praktiker. Für die Zwangsstörung wurde 2013 eine S3-Leitlinie publiziert. Fragestellung und Methode: Hier werden deren wichtigste Empfehlungen zur psychotherapeutischen Behandlung zusammengefasst und verbleibende Forschungslücken bezüglich praxisrelevanter Fragen aufgezeigt. Ergebnisse: Die Kognitive Verhaltenstherapie (KVT) wird als Verfahren der ersten Wahl empfohlen, während für andere, auch sehr verbreitete Verfahren kaum Evidenz vorliegt. Einige wichtige prozedurale Aspekte der KVT sind jedoch nicht genügend untersucht. Schlussfolgerungen: Angesichts der klinischen Bedeutung der Zwangsstörung besteht erheblicher Forschungsbedarf. Es wird auf die Bedeutung von Praxisbewährungsstudien hingewiesen. Schließlich wird diskutiert, wie aus aktueller psychologischer und neurobiologischer Grundlagenforschung zur Zwangsstörung, hier ausgeführt am Beispiel der Endophänotypenforschung, innovative Interventionen entwickelt werden können. Diese zielen darauf ab, den Anteil klinisch signifikant gebesserter Patienten zu erhöhen und die Nachhaltigkeit der Besserung zu sichern.
Dysfunktionale Attributionen von Eltern und ihre Bedeutung für ihr Erziehungsverhalten und für expansives Problemverhalten von Kindern
Authors: Katzmann Josepha , Hautmann Christopher , Greimel Lisa , Imort Stephanie , Pinior Julia , Scholz Kristin , Döpfner Manfred
Published: December 2015

Zusammenfassung. Theoretischer Hintergrund: Dysfunktionale elterliche Attributionen bei kindlichem Fehlverhalten werden als wichtiger Einflussfaktor für ungünstiges Erziehungsverhalten und assoziierte kindliche expansive Verhaltensauffälligkeiten diskutiert. Fragestellung: In einer Stichprobe von Kindern mit externalisierenden Verhaltensstörungen wurden nach einer psychometrischen Überprüfung des Fragebogens zur Erfassung dysfunktionaler elterlicher Attributionen (FDEA) die Zusammenhänge der elterlichen Attributionen mit expansiven Verhaltensproblemen und erziehungsbezogenen Maßen analysiert. Methode: Neben internen Konsistenzanalysen erfolgten eine Überprüfung der Faktorenstruktur sowie korrelative Analysen. Ergebnisse: Das angenommene 2-Faktoren-Modell konnte mit einer guten bis befriedigenden internen Konsistenz bestätigt werden. Dysfunktionale Attributionen zeigten Zusammenhänge mit der expansiven Symptomatik sowie mit erziehungsbezogenen Variablen. Schlussfolgerung: Bei der Erforschung expansiver Verhaltensauffälligkeiten und ungünstigen Erziehungsverhaltens sollten dysfunktionale elterliche Attributionen stärker berücksichtigt werden. Sie können mittels des FDEA reliabel und valide erhoben werden.
Acceptorless dehydrogenation of small molecules through cooperative base metal catalysis
Authors: West Julian G. , Huang David , Sorensen Erik J.
Published: December 2015

The dehydrogenation of unactivated alkanes is an important transformation both in industrial and biological systems. Recent efforts towards this reaction have revolved around high temperature, organometallic C–H activation by noble metal catalysts that produce alkenes and hydrogen gas as the sole products. Conversely, natural desaturase systems proceed through stepwise hydrogen atom transfer at physiological temperature; however, these transformations require a terminal oxidant. Here we show combining tetra-n-butylammonium decatungstate (TBADT) and cobaloxime pyridine chloride (COPC) can catalytically dehydrogenate unactivated alkanes and alcohols under near-UV irradiation at room temperature with hydrogen as the sole by-product. This noble metal-free process follows a nature-inspired pathway of high- and low-energy hydrogen atom abstractions. The hydrogen evolution ability of cobaloximes is leveraged to render the system catalytic, with cooperative turnover numbers up to 48 and yields up to 83%. Our results demonstrate how cooperative base metal catalysis can achieve transformations previously restricted to precious metal catalysts.
Interneuronal DISC1 regulates NRG1-ErbB4 signalling and excitatory–inhibitory synapse formation in the mature cortex
Authors: Seshadri Saurav , Faust Travis , Ishizuka Koko , Delevich Kristen , Chung Youjin , Kim Sun-Hong , Cowles Martis , Niwa Minae , Jaaro-Peled Hanna , Tomoda Toshifumi , Lai Cary , Anton E. S. , Li Bo , Sawa Akira
Published: December 2015

Neuregulin-1 (NRG1) and its receptor ErbB4 influence several processes of neurodevelopment, but the mechanisms regulating this signalling in the mature brain are not well known. DISC1 is a multifunctional scaffold protein that mediates many cellular processes. Here we present a functional relationship between DISC1 and NRG1-ErbB4 signalling in mature cortical interneurons. By cell type-specific gene modulation in vitro and in vivo including in a mutant DISC1 mouse model, we demonstrate that DISC1 inhibits NRG1-induced ErbB4 activation and signalling. This effect is likely mediated by competitive inhibition of binding of ErbB4 to PSD95. Finally, we show that interneuronal DISC1 affects NRG1-ErbB4-mediated phenotypes in the fast spiking interneuron-pyramidal neuron circuit. Post-mortem brain analyses and some genetic studies have reported interneuronal deficits and involvement of the DISC1, NRG1 and ErbB4 genes in schizophrenia, respectively. Our results suggest a mechanism by which cross-talk between DISC1 and NRG1-ErbB4 signalling may contribute to these deficits.
A new tool called DISSECT for analysing large genomic data sets using a Big Data approach
Authors: Canela-Xandri Oriol , Law Andy , Gray Alan , Woolliams John A. , Tenesa Albert
Published: December 2015

Large-scale genetic and genomic data are increasingly available and the major bottleneck in their analysis is a lack of sufficiently scalable computational tools. To address this problem in the context of complex traits analysis, we present DISSECT. DISSECT is a new and freely available software that is able to exploit the distributed-memory parallel computational architectures of compute clusters, to perform a wide range of genomic and epidemiologic analyses, which currently can only be carried out on reduced sample sizes or under restricted conditions. We demonstrate the usefulness of our new tool by addressing the challenge of predicting phenotypes from genotype data in human populations using mixed-linear model analysis. We analyse simulated traits from 470,000 individuals genotyped for 590,004 SNPs in ∼4 h using the combined computational power of 8,400 processor cores. We find that prediction accuracies in excess of 80% of the theoretical maximum could be achieved with large sample sizes.
Systematic investigation and microbial community profile of indole degradation processes in two aerobic activated sludge systems
Authors: Ma Qiao , Qu Yuanyuan , Zhang Xuwang , Liu Ziyan , Li Huijie , Zhang Zhaojing , Wang Jingwei , Shen Wenli , Zhou Jiti
Published: December 2015

Indole is widely spread in various environmental matrices. Indole degradation by bacteria has been reported previously, whereas its degradation processes driven by aerobic microbial community were as-yet unexplored. Herein, eight sequencing batch bioreactors fed with municipal and coking activated sludges were constructed for aerobic treatment of indole. The whole operation processes contained three stages, i.e. stage I, glucose and indole as carbon sources; stage II, indole as carbon source; and stage III, indole as carbon and nitrogen source. Indole could be completely removed in both systems. Illumina sequencing revealed that alpha diversity was reduced after indole treatment and microbial communities were significantly distinct among the three stages. At genus level, Azorcus and Thauera were dominant species in stage I in both systems, while Alcaligenes, Comamonas and Pseudomonas were the core genera in stage II and III in municipal sludge system, Alcaligenes and Burkholderia in coking sludge system. In addition, four strains belonged to genera Comamonas, Burkholderia and Xenophilus were isolated using indole as sole carbon source. Burkholderia sp. IDO3 could remove 100 mg/L indole completely within 14 h, the highest degradation rate to date. These findings provide novel information and enrich our understanding of indole aerobic degradation processes.
The ratio of FoxA1 to FoxA2 in lung adenocarcinoma is regulated by LncRNA HOTAIR and chromatin remodeling factor LSH
Authors: Wang Ranran , Shi Ying , Chen Ling , Jiang Yiqun , Mao Chao , Yan Bin , Liu Shuang , Shan Bin , Tao Yongguang , Wang Xiang
Published: December 2015

The lncRNA HOTAIR is a critical regulator of cancer progression. Chromatin remodeling factor LSH is critical for normal development of plants and mammals. However, the underlying mechanisms causing this in cancer are not entirely clear. The functional diversification of the FOXA1 and FOXA2 contributes to the target genes during evolution and carcinogenesis. Little is known about the ratio of FOXA1 to FOXA2 in cancer. We here found that both HOTAIR and LSH overexpression was significantly correlated with poor survival in patients with lung adenocarcinoma cancer (ADC). Also, the ratio of FOXA1 and FOXA2 is linked with poor survival in patients with lung ADC. HOTAIR regulates the ratio of FOXA1 to FOXA2 and migration and invasion. HOTAIR and the ratio of FOXA1 to FOXA2 are negatively correlated. HOTAIR knockdown inhibits migration and invasion. HOTAIR is associated with LSH and this association linked with the binding of LSH in the promoter of FOXA1, not FOXA2. Targeted inhibition of HOTAIR suppresses the migratory and invasive properties. These data suggest that HOTAIR is an important mediator of the ratio of FOXA1 and FOXA2 and LSH involves in and suggest that HOTAIR inhibition may represent a promising therapeutic option for suppressing lung ADC progression.
A novel, native-format bispecific antibody triggering T-cell killing of B-cells is robustly active in mouse tumor models and cynomolgus monkeys
Authors: Smith Eric J. , Olson Kara , Haber Lauric J. , Varghese Bindu , Duramad Paurene , Tustian Andrew D. , Oyejide Adelekan , Kirshner Jessica R. , Canova Lauren , Menon Jayanthi , Principio Jennifer , MacDonald Douglas , Kantrowitz Joel , Papadopoulos Nicholas , Stahl Neil , Yancopoulos George D. , Thurston Gavin , Davis Samuel
Published: December 2015

Bispecific antibodies, while showing great therapeutic potential, pose formidable challenges with respect to their assembly, stability, immunogenicity and pharmacodynamics. Here we describe a novel class of bispecific antibodies with native human immunoglobulin format. The design exploits differences in the affinities of the immunoglobulin isotypes for Protein A, allowing efficient large-scale purification. Using this format, we generated a bispecific antibody, REGN1979, targeting the B cell marker, CD20 and the CD3 component of the T cell receptor, which triggers redirected killing of B cells. In mice, this antibody prevented growth of B cell tumors and also caused regression of large established tumors. In cynomolgus monkeys, low doses of REGN1979 caused prolonged depletion of B cells in peripheral blood with a serum half-life of approximately 14 days. Further, the antibody induced a deeper depletion of B cells in lymphoid organs than rituximab. This format has broad applicability for development of clinical bispecific antibodies.
Uncovering MicroRNA Regulatory Hubs that Modulate Plasma Cell Differentiation
Authors: Tsai Dong-Yan , Hung Kuo-Hsuan , Lin I-Ying , Su Shin-Tang , Wu Shih-Ying , Chung Cheng-Han , Wang Tong-Cheng , Li Wen-Hsiung , Shih Arthur Chun-Chieh , Lin Kuo-I
Published: December 2015

Using genome-wide approaches, we studied the microRNA (miRNA) expression profile during human plasma cell (PC) differentiation induced by stimulation of human blood B cells with T follicular helper cell–dependent signals. Combining the profiles of differentially expressed genes in PC differentiation with gene ontology (GO) analysis revealed that a significant group of genes involved in the transcription factor (TF) activity was preferentially changed. We thus focused on studying the effects of differentially expressed miRNAs on several key TFs in PC differentiation. Cohorts of differentially expressed miRNAs cooperating as miRNA hubs were predicted and validated to modulate key TFs, including a down-regulated miRNA hub containing miR-101-3p, -125b-5p and -223-3p contributing to induction of PRDM1 as well as an up-regulated miRNA hub containing miR-34a-5p, -148a-3p and -183-5p suppressing BCL6, BACH2 and FOXP1. Induced expression of NF-κB and PRDM1 during PC differentiation controlled the expression of up- and down-regulated miRNA hubs, respectively. Co-expression of miR-101-3p, -125b-5p and -223-3p in stimulated B cells showed synergistic effects on inhibition of PC formation, which can be rescued by re-introduction of PRDM1. Together, we catalogue the complex roadmap of miRNAs and their functional interplay in collaboratively directing PC differentiation.
Microspectrometric insights on the uptake of antibiotics at the single bacterial cell level
Authors: Cinquin Bertrand , Maigre Laure , Pinet Elizabeth , Chevalier Jacqueline , Stavenger Robert A. , Mills Scott , Réfrégiers Matthieu , Pagès Jean-Marie
Published: December 2015

Bacterial multidrug resistance is a significant health issue. A key challenge, particularly in Gram-negative antibacterial research, is to better understand membrane permeation of antibiotics in clinically relevant bacterial pathogens. Passing through the membrane barrier to reach the required concentration inside the bacterium is a pivotal step for most antibacterials. Spectrometric methodology has been developed to detect drugs inside bacteria and recent studies have focused on bacterial cell imaging. Ultimately, we seek to use this method to identify pharmacophoric groups which improve penetration and therefore accumulation, of small-molecule antibiotics inside bacteria. We developed a method to quantify the time scale of antibiotic accumulation in living bacterial cells. Tunable ultraviolet excitation provided by DISCO beamline (synchrotron Soleil) combined with microscopy allows spectroscopic analysis of the antibiotic signal in individual bacterial cells. Robust controls and measurement of the crosstalk between fluorescence channels can provide real time quantification of drug. This technique represents a new method to assay drug translocation inside the cell and therefore incorporate rational drug design to impact antibiotic uptake.
The transcription factor ccaat/enhancer binding protein β (C/EBPβ) and miR-27a regulate the expression of porcine Dickkopf2 (DKK2)
Authors: Tao Hu , Wang Lei , Zhou Jiawei , Pang Panfei , Cai Shanzhi , Li Jialian , Mei Shuqi , Li Fenge
Published: December 2015

Using Affymetrix porcine Gene-Chip analyses, we found that Dickkopf2 (DKK2), a WNT antagonist, is differentially expressed in pre-ovulatory follicles between Large White and Chinese Taihu sows. This study aims to identify the regulatory factors responsible for DKK2 expression. Deletion fragment and mutation analyses identified DKK2-D3 as the porcine DKK2 core promoter. There were four C/EBPβ binding sites within the DKK2 core promoter. The C allele that results from a spontaneous alteration (DKK2 c.−1130 T > C) in the core promoter was associated with a higher total number born (TNB) and a higher number born alive (NBA) in all parities in a synthetic pig population. This was possibly the result of a change in C/EBPβ binding ability, which was confirmed using chromatin immunoprecipitation (ChIP) and electrophoretic mobility shift assays (EMSA). Moreover, C/EBPβ specifically bound to and activated the DKK2 promoter, as revealed by mutation analysis, overexpression and RNA interference (RNAi) experiments. We also confirmed that miR-27a is a negative regulator of the DKK2 gene using miR-27a overexpression and inhibition experiments and mutation analyses. RTCA xCELLigence experiments showed that miR-27a suppressed Chinese hamster ovary (CHO) cell proliferation by down-regulating DKK2 gene expression. Taken together, our findings suggest that C/EBPβ and miR-27a control DKK2 transcription.
Radiobiological modeling analysis of the optimal fraction scheme in patients with peripheral non-small cell lung cancer undergoing stereotactic body radiotherapy
Authors: Huang Bao-Tian , Lu Jia-Yang , Lin Pei-Xian , Chen Jian-Zhou , Li De-Rui , Chen Chuang-Zhen
Published: December 2015

This study aimed to determine the optimal fraction scheme (FS) in patients with small peripheral non-small cell lung cancer (NSCLC) undergoing stereotactic body radiotherapy (SBRT) with the 4 × 12 Gy scheme as the reference. CT simulation data for sixteen patients diagnosed with primary NSCLC or metastatic tumor with a single peripheral lesion ≤3 cm were used in this study. Volumetric modulated arc therapy (VMAT) plans were designed based on ten different FS of 1 × 25 Gy, 1 × 30 Gy, 1 × 34 Gy, 3 × 15 Gy, 3 × 18 Gy, 3 × 20 Gy, 4 × 12 Gy, 5 × 12 Gy, 6 × 10 Gy and 10 × 7 Gy. Five different radiobiological models were employed to predict the tumor control probability (TCP) value. Three other models were utilized to estimate the normal tissue complication probability (NTCP) value to the lung and the modified equivalent uniform dose (mEUD) value to the chest wall (CW). The 1 × 30 Gy regimen is recommended to achieve 4.2% higher TCP and slightly higher NTCP and mEUD values to the lung and CW compared with the 4 × 12 Gy schedule, respectively. This regimen also greatly shortens the treatment duration. However, the 3 × 15 Gy schedule is suggested in patients where the lung-to-tumor volume ratio is small or where the tumor is adjacent to the CW.
Versatile microscale screening platform for improving recombinant protein productivity in Chinese hamster ovary cells
Authors: Hansen Henning Gram , Nilsson Claes Nymand , Lund Anne Mathilde , Kol Stefan , Grav Lise Marie , Lundqvist Magnus , Rockberg Johan , Lee Gyun Min , Andersen Mikael Rørdam , Kildegaard Helene Faustrup
Published: December 2015

Chinese hamster ovary (CHO) cells are widely used as cell factories for the production of biopharmaceuticals. In contrast to the highly optimized production processes for monoclonal antibody (mAb)-based biopharmaceuticals, improving productivity of non-mAb therapeutic glycoproteins is more likely to reduce production costs significantly. The aim of this study was to establish a versatile target gene screening platform for improving productivity for primarily non-mAb glycoproteins with complete interchangeability of model proteins and target genes using transient expression. The platform consists of four techniques compatible with 96-well microplates: lipid-based transient transfection, cell cultivation in microplates, cell counting and antibody-independent product titer determination based on split-GFP complementation. We were able to demonstrate growth profiles and volumetric productivity of CHO cells in 96-half-deepwell microplates comparable with those obtained in shake flasks. In addition, we demonstrate that split-GFP complementation can be used to accurately measure relative titers of therapeutic glycoproteins. Using this platform, we were able to detect target gene-specific increase in titer and specific productivity of two non-mAb glycoproteins. In conclusion, the platform provides a novel miniaturized and parallelisable solution for screening target genes and holds the potential to unravel genes that can enhance the secretory capacity of CHO cells.
Lysosomal Cholesterol Accumulation Sensitizes To Acetaminophen Hepatotoxicity by Impairing Mitophagy
Authors: Baulies Anna , Ribas Vicent , Núñez Susana , Torres Sandra , Alarcón-Vila Cristina , Martínez Laura , Suda Jo , Ybanez Maria D. , Kaplowitz Neil , García-Ruiz Carmen , Fernández-Checa Jose C.
Published: December 2015

The role of lysosomes in acetaminophen (APAP) hepatotoxicity is poorly understood. Here, we investigated the impact of genetic and drug-induced lysosomal cholesterol (LC) accumulation in APAP hepatotoxicity. Acid sphingomyelinase (ASMase)−/−mice exhibit LC accumulation and higher mortality after APAP overdose compared to ASMase+/+littermates. ASMase−/−hepatocytes display lower threshold for APAP-induced cell death and defective fusion of mitochondria-containing autophagosomes with lysosomes, which decreased mitochondrial quality control. LC accumulation in ASMase+/+hepatocytes caused by U18666A reproduces the susceptibility of ASMase−/−hepatocytes to APAP and the impairment in the formation of mitochondria-containing autolysosomes. LC extraction by 25-hydroxycholesterol increased APAP-mediated mitophagy and protected ASMase−/−mice and hepatocytes against APAP hepatotoxicity, effects that were reversed by chloroquine to disrupt autophagy. The regulation of LC by U18666A or 25-hydroxycholesterol did not affect total cellular sphingomyelin content or its lysosomal distribution. Of relevance, amitriptyline-induced ASMase inhibition in human hepatocytes caused LC accumulation, impaired mitophagy and increased susceptibility to APAP. Similar results were observed upon glucocerebrosidase inhibition by conduritol β-epoxide, a cellular model of Gaucher disease. These findings indicate that LC accumulation determines susceptibility to APAP hepatotoxicity by modulating mitophagy and imply that genetic or drug-mediated ASMase disruption sensitizes to APAP-induced liver injury.