bluuebunny/crossref_metadata_2025 huggingface dataset:
Blood Coagulation Activation in Cancer: Challenges for Cancer Treatment
Authors: Costantini V. , Zacharski L. R.
Published: July 2018

It has been known for over a century that blood coagulation and fibrinolysis pathways are activated systemically in patients with malignancy. Recent studies have revealed evidence for two distinct pathways of interaction between tumor cells and the host coagulation mechanism that include production of either initiators of thrombin formation or expression of plasminogen activators by the tumor cells in situ within intact tumor tissue. Studies in specific in vitro and animal models of malignancy have implicated either tumor cell procoagulants or urokinase in mechanisms of tumor cell proliferation, invasion, and metastasis. We have formulated a classification of human tumor types based on detection of components of either of these pathways in situ. Type I tumors are those in which the tumor cells are associated with an intact coagulation pathway that leads to thrombin formation at the tumor periphery but in which the tumor cells lack urokinase. Type II tumors are those in which the tumor cells express urokinase but lack an associated coagulation pathway leading to thrombin formation. Type III tumors are those that express neither of these pathways, or exhibit some other pattern of interaction. Evidence suggests that anticoagulant therapy is capable of ameliorating the clinical course of a procoagulant tumor type namely, small cell carcinoma of the lung. This approach may be effective in other type I tumors. Clinical trials of agents capable of inhibiting urokinase-initiated proteolysis are required to clarify cause/effect relationships in urokinase-expressing tumors. Exploration of the coagulation-cancer interaction holds considerable promise for imaginative new approaches to cancer treatment that are not only relatively nontoxic and low cost, but also effective because they may interrupt fundamental mechanisms of malignant growth control.
Ätiologie und Pathophysiologie der disseminierten intravasalen Gerinnung
Authors: Kirchmaier C. M.
Published: July 2018

Die disseminierte intravasale Gerinnung (disseminated intravascular coagulation, DIC) tritt bei einer Reihe von Krankheitsbildern auf. Es treten sowohl eine hämorrhagische Diathese mit teilweise dramatischen Blutungskomplikationen als auch Thrombosen in der Mikrozirkulation und in sehr seltenen Fällen in größeren Gefäßen auf. Klinisch steht die Blutung im Vordergrund, entscheidend für Morbidität und Mortalität ist jedoch ein Organversagen aufgrund der thrombotischen Mikrozirkulationsstörungen. Ursache für die DIC können sowohl eine Gewebstrauma als auch eine Schädigung des Gefäßendothels sein. Traumata unterschiedlicher Genese führen zur Freisetzung von Gewebsfaktor (Tissue-Faktor, TF) in die Zirkulation. Eine Schädigung des Gefäßendothels, die zur DIC führt, wird in dem größten Teil der Fälle von einer Sepsis verursacht. Auslöser ist die Einschwemmung von Endotoxin oder ähnlichen Substanzen in den Blutstrom. Dies führt zur Freisetzung einer ganzen Reihe von Mediatoren. So führen über die Stimulierung unterschiedlicher Systeme der Tumornekrosefaktor-a (TNF-a) und andere Zytokine zu einer Aktivierung des Gerinnungssystems. Die weitere Pathophysiologie einer DIC ist bei allen Grundkrankheiten ähnlich. In der Zirkulation befindliches Thrombin führt zur Ablagerung von Fibrinmonomeren und quervernetztem Fibrin in der Mikrozirkulation. Die gleichzeitige Zirkulation von Plasmin ist verantwortlich für die Bildung von Fibrinspaltprodukten, die die Polymerisation von Fibrinmonomeren und die Thrombozytenfunktion beeinflussen. Die Zerstörung von Gerinnungsfaktoren durch Plasmin verstärkt die Blutungsneigung.
Heparin-assoziierte Thrombozytopenie
Authors: Bruhn H. D.
Published: July 2018

Zur Zeit gilt die Heparin-assoziierte Thrombozytopenie als die häufigste Form einer Medikamenten-induzierten Thrombozytopenie. Sie tritt in einer klinisch harmlosen Form (Typ I) der Thrombozytopenie auf, wobei die Thrombozytenwerte hierbei selten unter 100000/jjil fallen und sich unter weiterer Heparingabe sogar normalisieren. Klinische Komplikationen sind bei diesem Typ I der Heparinassoziierten Thrombozytopenie nicht zu erwarten. Die Häufigkeit dieser Form der Heparin-assoziierten Thrombozytopenie wird mit etwa 10% angegeben. Besondere diagnostische und therapeutische Maßnahmen sind nicht erforderlich.

Die Heparin-assoziierte Thrombozytopenie Typ II unterscheidet sich auch klinisch deutlich von dem harmlosen Typ I. Sie tritt im allgemeinen 7 bis 10 Tage nach Beginn der Heparintherapie auf. Bei Patienten, die früher schon einmal Heparin erhalten hatten, kann sie jedoch bereits innerhalb weniger Stunden nach Reexposition in Erscheinung treten. Die Thrombozytenwerte fallen oft bis unter 50000 Thrombozyten/|jil Blut und normalisieren sich erst nach Absetzen des Heparins. Die Patienten sind vor allem durch arterielle Gefäßverschlüsse (White-clot-Syndrom), seltener durch venöse Gefäßverschlüsse gefährdet. Bei diesem Typ II der Heparin-assoziierten Thrombozytopenie werden immunologische Mechanismen der Plättchenaktivierung und des dann folgenden Plättchenverbrauchs diskutiert. Das Risiko, eine Thrombozytopenie zu entwickeln, ist bei Patienten, die prophylaktische Dosierungen des Heparins (niedrigdosiertes Heparin) erhalten, lediglich mit 1/10 der Häufigkeit im Vergleich zu therapeutischen Heparindosierungen zu veranschlagen: niedrigdosiertes Heparin führt im Durchschnitt in ca. 0,3% der Fälle zu einer Heparin-assoziierten Thrombozytopenie, therapeutische Heparindosierungen dagegen führen zu einer Häufigkeit der HAT zwischen 1,5 und 3% der Behandelten. Die Häufigkeit der Heparin-assoziierten Thrombozytopenie wird deutlich vom klinischen Umfeld beeinflußt: Im Bereich der kardiovaskulären Chirurgie (koronarer Bypass, Gefäßchirurgie) kommt es besonders häufig zu Heparin-assoziierten Thrombozytopenien, möglicherweise als Ausdruck der Plättchenaktivierung an extrakorporalen Oberflächen.

In der Behandlung der Heparin-assoziierten Thrombozytopenie ist neben sofortigem Absetzen des Heparinpräparates ein Ausweichen auf andere antithrombotische Maßnahmen empfehlenswert (Hirudin, Orgaran, Cumarin, Dextran). Dem Patienten sollte auf jeden Fall zur Vermeidung späterer Komplikationen ein entsprechender Ausweis ausgehändigt werden, der auf das Problem der Heparinassoziierten Thrombozytopenie hinweist. Trotz der sicherlich damit verbundenen Schwierigkeiten sollte in der ambulanten Medizin in der Phase der Heparinapplikation zur Thromboseprophylaxe in der sogenannten Posthospitalphase versucht werden, die Plättchenzahlen im Zeitraum vom 5. bis 20.Tag der Heparintherapie zweimal zu zählen, weil die Heparin-assoziierte Thrombozytopenie Typ II in diesem Zeitraum am häufigsten auftritt.
Aktivierung des Gerinnungs-, Fibrinolyse- und Endothelzellsystems bei vier Patienten mit Heparin-assoziierter Thrombozytopenie (HAT II)
Authors: Peters U. , Fuchs G. , Funck R. , Greinacher A. , Rohner I. , Kröniger A. , Seitz M. , Egbring R.
Published: July 2018

Nur wenige Autoren berichteten bislang von einer disseminierten intravasalen Gerinnung (DIC) als Komplikation einer Heparin-assoziierten Thrombozytopenie (HAT). In der Literatur werden bis 1990 nur 14 Patienten beschrieben, die meisten von ihnen verstarben. Die HAT II und ihre Komplikationen entstehen nur bei Patienten, die einen Antikörper gegen Plättchenfaktor 4 oder den Plättchenfaktor-4-Heparin-Komplex entwickeln. Während sich der Fc-Anteil des Antikörpers oder der Antikörper-Plättchenfaktor-4-Komplex an die Plättchen bindet, kann der Plättchenfaktor 4 oder der Plättchenfaktor-4-Antikörper-Komplex auch mit Heparansulfat auf der Oberfläche von Endothelzellen reagieren. Eine solche Bindung auf der Endothelzelle kann eine generalisierte Endothelzellschädigung auslösen, die die Freisetzung von von-Willebrand-Faktor (Ristocetin-Kofaktor), Gewebeplasminogenaktivator (t-PA) und Gewebsaktivator zur Folge hätte. Letzterer kann FVII aktivieren, eine intravasale Thrombinbildung auslösen und so zu einer DIC als Komplikation einer HAT führen.

Deshalb wurden bei vier Patienten mit HAT Typ II Parameter einer EndothelzellAktivierung (t-PA; Ristofact.), einer Gerinnungsaktivierung (Thrombin-Antithrombin-lll-Komplex, TAT; Prothrombinfragment F1+2, Prf F1+2) und einer Aktivierung des Fibrinolysesystems (Plasmin-α2-Antiplasmin, PAP) gemessen, zusätzlich auch der Antithrombin-Illund der Plasminogen-Wert zu Beginn der Thrombozytopenie. Zu Beginn und während der Thrombozytopenie waren t-PA, Ristofact., TAT, Prf F1+2 und PAP erhöht, während Plasminogen erniedrigt war und AT III sich im unteren Normalbereich bewegte. Im Gegensatz dazu war der ElastaseProteinaseinhibitor-Komplex, mit einer Ausnahme, niedrig. Diese Ergebnisse verdeutlichen, daß der zirkulierende Antikörper gegen Plättchenfaktor 4 nicht nur einen erhöhten Plättchenumsatz bewirkt, sondern auch noch die Endothelzellen sowie das Gerinnungsund Fibrinolysesystem aktiviert.
Die Zeit nach der Europäischen Konsensus-Erklärung
Authors: Haas Sylvia
Published: July 2018

Im November 1991 fand in Windsor eine Europäische Konsensus-Konferenz zur Frage des derzeitigen Standes der Prävention von venösen Thromboembolien statt. Insbesondere wurde der aktuelle Stellenwert einer Prophylaxe mit unfraktioniertem Heparin (UFH) und niedermolekularen Heparinen (NMH) diskutiert. Die Konsensus-Erklärung enthält eine Reihe noch offener Fragen, welche durch zukünftige Forschungsergebnisse beantwortet werden sollten. Die vorliegende Arbeit beschäftigt sich mit den für eine Heparinprophylaxe relevanten Fragestellungen, die in der Vergangenheit bearbeitet worden sind. Zusammenfassend kann gesagt werden, daß die Zeit nach der Europäischen Konsensus-Erklärung 1991 wesentlich geprägt war von der Bestimmung der Inzidenz von unerwünschten Nebenwirkungen einer Prophylaxe und Therapie mit UFH und NMH und der Einführung einer Therapie von thromboembolischen Komplikationen mit niedermolekularen Heparinen in verschiedenen Ländern. Als wesentlicher Fortschritt beim Einsatz von niedermolekularen Heparinen kann die große therapeutische Breite und das im Vergleich zu herkömmlichem Heparin günstigere Nebenwirkungsprofil genannt werden. Prinzipiell müssen zwar die gleichen Kontraindikationen und das gleiche Nebenwirkungsrisiko wie für UFH beachtet werden, quantitativ zeichnen sich aber klinisch relevante Unterschiede ab. Insbesondere Osteoporose und Heparin-induzierte Thrombozytopenie Typ II (HIT II) scheinen seltener aufzutreten.
Nebenwirkungen der Therapie mit Blut und Blutprodukten
Authors: Riggert J. , Wagner Beate
Published: July 2018

Die Posttransfusionshepatitis (PTH) ist dank erheblicher Fortschritte in der Virusdiagnostik seltener geworden. Jedoch bleibt sie als eine der häufigsten Todesursachen bei der Therapie mit Blut und Blutprodukten Gegenstand der Diskussion. In der Übersicht wird die Abhängigkeit des PTH-Risikos von der Art des applizierten Präparats und der Prävalenz an Virusträgern bei den Blutspendern sowie die Effektivität verschiedener Parameter bei der Spenderauswahl dargestellt. Künftig lassen eine verbesserte Virusdetektion mittels molekularbiologischer Methoden sowie eine Virusinaktivierung zellhaltiger Produkte eine erhöhte Infektionssicherheit der Hämotherapie erwarten.
Physiologische und pathophysiologische Grundlagen der Kohlenhydrathomöostase
Authors: Bratusch-Marrain P. R.
Published: July 2018

Die Kontrolle der Blutglukosekonzentration erfolgt durch eine Vielzahl von Regulationsmechanismen, deren Effizienz sich beim gesunden Organismus in einer nur sehr schmalen Bandbreite der Schwankungen der Blutglukosekonzentration manifestiert. Neben Insulin sind nicht nur eine Vielzahl anderer Hormone, wie Glukagon, Katecholamine, Glukokortikoide und Wachstumshormon, sondern auch zentralnervöse Steuerungsmechanismen an der Aufrechterhaltung der Glukosehomöostase beteiligt. Aufgabe dieser Kontrollsysteme ist es, trotz intermittierender Nahrungszufuhr und zeitlich davon unabhängigem, aber ebenfalls intermittierendem Energiebedarf, Hypo- und Hyperglykämien zu verhindern. Die Kenntnis dieser integrativen Steuerung des Metabolismus der Einzelorgane im Rahmen des Gesamtorganismus stellt die Voraussetzung für diagnostische und therapeutische Überlegungen bei mit Störungen der Stoffwechselhomöostase einhergehenden pathologischen Zuständen dar.
Veränderungen der Blutviskosität bei Diabetes mellitus
Authors: Kenner Th. , Hinghofer-Szalkay H.
Published: July 2018

Viskosität oder Zähigkeit einer Flüssigkeit ist definiert als das Verhältnis der zwischen den fließenden Schichten herrschenden Scherspannung zu der verformenden Scherung. Unter sonst gleichbleibenden Bedingungen ist die Scherung in Wandnähe eines Rohres proportional der Strö-mungsgeschwindigkeit der darin strömenden Flüssigkeit. Blut ist eine sogenannte nichtnewtonische Flüssigkeit, da die (»scheinbare«) Viskosität von der Scherung abhängt. Bei hoher Scherung ist die Blutviskosität wegen der normalerweise sehr beachtlichen Verformbarkeit der Erythrozyten niedrig – und kommt fast jener des Plasma nahe. Bei niedriger Scherung, das heißt also bei sehr langsamer Strömung, wird die Viskosität des Blutes wegen der Tendenz der Erythrozyten zu aggregieren und sogenannte Rouleaux (= Geldrollen) zu bilden, hoch. Alle Erkrankungen, die auf irgendeine Weise die Zusammensetzung der Plasmaeiweiße beeinflussen, verändern auch die Aggregationsneigung der Erythrozyten, die übrigens parallel mit der Blutsenkungsgeschwindigkeit geht. Die wichtigsten Änderungen der Blutviskosität bei Diabetes betreffen die beiden genannten Faktoren. Mangel an Insulin führt über eine direkte Beeinflussung der Zellmembran zu einer Abnahme der Erythro-zytenverformbarkeit – die Erythrozyten werden rigider. Sekundäre Plasmaveränderungen und Komplikationen steigern die Aggregationsneigung der Erythrozyten.

Die Komplexität der vielfachen Stoffwechselfaktoren, die bei Diabetes eine Rolle spielen, bedingen die manchmal etwas widersprüchlichen Befunde hinsichtlich Viskositätsänderung des Blutes. Die direkte Rolle, die das Insulin für die Beeinflussung, vielleicht sogar Steuerung der Verformbarkeit der Zellmembran spielt, mißt der Frage der Viskositätsänderung des Blutes bei Diabetes besondere Bedeutung zu.
Monitoring the Effects of Glycoprotein IIb/IIIa Antagonists using a Whole Blood Assay of Platelet Microaggregation
Authors: May Jane , Wilcox R. G. , Heptinstall S. , Storey R. F.
Published: July 2018

We have used a whole blood single-platelet counting assay (WBSPC) that is sensitive to microaggregation for monitoring GPIIb/IIIa antagonists and have compared this with other methodologies. In vitro effects of the GPIIb/IIIa antagonist fradafiban on ADP-induced platelet aggregation were determined using WBSPC and PRP turbidimetry, comparing citrate and hirudin anticoagulation. Fradafiban was a more potent inhibitor of aggregation assessed by PRP turbidimetry compared to WBSPC. Citrate showed only a trend towards enhancing fradafiban potency (p = 0.087). Citrated blood from 8 patients with unstable angina, randomised to receive oral lefradafiban or placebo, was studied before and during treatment using WBSPC, PRP turbidimetry, impedance aggregometry and Rapid Platelet Function Assay (RPFA, Accumetrics). RPFA, PRP turbidimetry and WBSPC measurements correlated well. Impedance aggregometry responses were oversensitive to GPIIb/IIIa blockade. WBSPC was most discriminating at high levels of inhibition and offered a rapid means of monitoring GPIIb/IIIa antagonist effect within the therapeutic range of inhibition.
A Simple and Rapid Method to Determine GPIIb/IIIa-Receptor Inhibitor Activity in Whole Blood
Authors: Kühnel Gitta , Matzdorff A. C.
Published: July 2018

We studied the effect of GPIIb/IIIa-inhibitors on platelet activation with flow cytometry in vitro. Citrated whole blood was incubated with increasing concentrations of three different GPIIb/IIIa-inhibitors (c7E3, DMP728, XJ757), then thrombin or ADP were added and after 1 min the sample was fixed. Samples without c7E3 but with 0.1 U/ml thrombin had a decrease in platelet count. Samples with increasing concentrations of c7E3 had a lesser or no decrease in platelet count. The two other inhibitors (DMP 725, XJ757) gave similar results. GPIIb/IIIa-inhibitors prevent aggregate formation and more single platelets remain in the blood sample. The agonist-induced decrease in platelet count correlates closely with the concentration of the GPIIb/IIIa inhibitor and receptor occupancy. This correlation may be used as a simple measure for inhibitor activity in whole blood.
Differentialdiagnostik zur Beurteilung des Thromboserisikos mit ProC® Global
Authors: Matzdorff A. , Niemann F. , Kemkes-Matthes Bettina
Published: July 2018

Im Rahmen der Thrombophilie-Diagnostik ist das Protein-C-System in den Mittelpunkt des Interesses gerückt. 80% aller heute im Labor nachweisbaren throm-bophilen Diathesen betreffen dieses System, mit Abstand häufigste Störung ist die Resistenz gegen aktiviertes Protein C bzw. die Faktor-V-Leiden-Mutation. Der ProC® Global-Test ermöglicht es nun, die wesentlichen Defekte des Protein-C-Systems zu erfassen, so daß ca. 60% der Patienten keiner weiterführenden Diagnostik mehr zugeführt werden müssen. Darüber hinaus gibt der Test Information über das Ausmaß der Störung im Protein-C-System. Inwieweit dies auch mit der klinischen Thromboseneigung korreliert, müssen prospektive Studien zeigen.
A Comparative Study Using Immunological and Biological Assays of the Haemostatic Responses to DDAVP Infusion Venous Occlusion and Exercise in Normal Men
Authors: Prowse C V , Farrugia A , Boulton F E , Tucker J , Ludlam C A , McLaren M , Belch J J F , Prentice C R M , Dawes J , MacGregor I R
Published: July 2018

In a group of six normal male volunteers, infusion of DDAVP, venous occlusion and exercise were shown to increase plasma levels of factor VIII and plasminogen activator, activity and antigen, to different extents and at differing rates. Any mechanisms suggested to explain release of these proteins by various stimuli should account for such differences.

All three stimuli could also increase plasma levels of prostacyclin metabolites, although this was only significant for high doses of DDAVP. Other potential endothelial markers, such as fibronectin and thrombospondin, showed no specific increase after any of the stimuli.
Acute Hyponasality (Closed Rhinolalia) and Craniomaxillofacial Fracture Suggest the Coexistence of Retropharyngeal Emphysema and Pneumomediastinum
Authors: Papadiochos Ioannis , Sarivalasis Stavros-Evangelos , Papadogeorgakis Nickolaos
Published: July 2018

Pneumomediastinum (PM) implies an abnormal condition where a collection of free air or gas is entrapped within the fascial planes of mediastinal cavity. It is considered as benign entity, but an uncommonly seen complication of craniofacial injuries. We report a case of a 63-year-old male patient with the presenting sign of closed rhinolalia who was diagnosed with retropharyngeal emphysema and PM due to a linear and nondisplaced fracture of midface. The patient cited multiple efforts of intense nasal blowing shortly after a facial injury by virtue of a motorcycle accident. He was admitted in our clinic for closer observation and further treatment. The use of a face mask for continuous positive airway pressure was temporarily interrupted, and high concentrations of oxygen were delivered via non-rebreather mask. Patient's course was uncomplicated and he was discharged few days later, with almost complete resolution of cervicofacial emphysema and absence of residual PM in follow-up imaging tests. Closed rhinolalia (or any acute alteration of voice) in maxillofacial trauma patients should be recognized, assessed, and considered within the algorithm for PM and retropharyngeal emphysema diagnosis and management. For every single case of cervicofacial emphysema secondary to facial injury, clinicians should maintain suspicion for retropharyngeal emphysema or PM development.
Determinanten für die Diagnosestellung einer ADHS – Eine Analyse anhand von GKV-Routinedaten –
Authors: Klora Mike , Zeidler Jan , Linder Roland , Kis Bernhard , Heßmann Philipp , Verheyen Frank , Graf von der Schulenburg J.-Matthias
Published: July 2018

Hintergrund und Ziel der Studie Bisher gibt es in Deutschland nur wenige Untersuchungen zu den soziodemographischen Einflussgrößen auf die Diagnosestellung einer ADHS-Erkrankung, obwohl die Kenntnis dieser Merkmale bedeutend für das diagnostische Prozedere und die Ausgestaltung von Präventionsprogrammen sein kann. Unser Ziel war es daher, die Evidenz zu den Einflussgrößen einer ADHS-Diagnose zu erweitern und Hinweise dafür zu geben, welchen Einfluss die familiäre Vorbelastung mit psychiatrischen Diagnosen und soziodemographischen Faktoren haben.

Material und Methoden Durch ein 3:1 Kontrollgruppendesign mit Daten der Techniker Krankenkasse wurden psychosoziale, regionale und demographische Einflussfaktoren deskriptiv und anhand einer logistischen Regression untersucht. Die unabhängigen Variablen bestanden aus Alter, Geschlecht, Region und Komorbiditäten der Patienten, dem sozioökonomischen Berufsstatus und dem Bildungsniveau der Mitglieder, den psychiatrischen Diagnosen der Eltern sowie dem Alter der Eltern bei der Geburt der Kinder (Variablen des Familienhintergrunds).

Ergebnisse Es wurden 9.881 ADHS-Patienten mit einem Durchschnittsalter von 14,9 Jahren [SD: 12,6] identifiziert. Anhand dieser umfassenden Stichprobe konnte bestätigt werden, dass das ADHS-Risiko bei männlichen Patienten höher liegt als bei weiblichen Patientinnen (OR: 2,3 [95%-KI: 2,2–2,5]). Ein mittlerer oder höherer Bildungsabschluss eines Mitglieds war mit niedrigerem Risiko einer ADHS-Diagnose im Vergleich zur Referenzkategorie niedriger Bildungsstatus verbunden (OR: 0,78 [95%-KI: 0,70–0,89] bzw. OR: 0,55 [95%-KI: 0,47–0,63]). Zudem erhöhte sich das ADHS-Risiko mit höherem Alter der Eltern sowie bei Vorliegen von psychiatrischen Diagnosen dieser (OR: 1,02 [95%-KI: 1,01–1,03] bzw. OR: 2,09 [95%-KI: 1,95–2,25]). Für den sozioökonomischen Beschäftigungsstatus konnte kein eindeutiger Zusammenhang nachgewiesen werden.

Diskussion Das Wissen um soziodemographische Einflussfaktoren kann die Diagnosestellung unterstützen und Hinweise zur Entwicklung individueller Präventions- und Therapiekonzepte geben.
Oscillatory instability in a weakly non-Boussinesq fluid layer with a deformable surface
Authors: Lyubimov D. V. , Lyubimova T. P. , Lobov N. I. , Samoilova A. E.
Published: July 2018

We investigate the oscillatory convective instability in a liquid layer with a deformable free surface. We provide linear stability analysis within a non-Boussinesq approach as our aim is to examine the influence of deformability of the free surface on the Rayleigh–Bénard–Marangoni instability. Within this approach, fluid is assumed to be isothermally incompressible; the density variations are accounted for in the continuity equation and in the buoyancy and inertial terms of the momentum equations. The numerical results show significant differences in stability behavior as compared to results obtained using the Boussinesq approach. Moreover, a novel oscillatory mode of instability is revealed for the zero Marangoni number and zero gravity. This result could not be obtained within the framework of the conventional Boussinesq approximation. Thorough investigation of the novel oscillatory mode let us propose the mechanism of this mode. It is connected with the capillary wave that enforced with thermal expansion of fluid. Weakly nonlinear analysis shows that supercritical branching of standing rolls is possible.
Invited Article: Heterodyne dual-polarization epi-detected CARS microscopy for chemical and topographic imaging of interfaces
Authors: Langbein Wolfgang , Regan David , Pope Iestyn , Borri Paola
Published: July 2018

Coherent Raman Scattering (CRS) has emerged in the last decade as a powerful multiphoton microscopy technique offering chemically specific label-free imaging in real time with high three-dimensional spatial resolution. Many technical realizations of CRS microscopy have been proposed to remove, suppress, or account for the non-resonant background in the nonlinear susceptibility which complicates spectral analysis and reduces image contrast. Here, we demonstrate coherent anti-Stokes Raman scattering microscopy using a dual-polarization balanced heterodyne detection in epi-geometry (eH-CARS), providing background-free chemically specific image contrast for nanoparticles and interfaces, shot-noise limited detection, and phase sensitivity. We show the sensitivity and selectivity of eH-CARS in comparison with forward CARS and stimulated Raman scattering on polystyrene beads in agarose gel. As an important biologically relevant application, we demonstrate eH-CARS imaging of individual lipid bilayers with high contrast and topographic sensitivity.
Fourier Transform Controlled Stress Parallel Superposition (FT-CSPS): Validation and application in processing printable functional materials
Authors: Holder A. J. , Claypole J. , Claypole T. , Cooper P. G. , Williams P. R. , Curtis D. J.
Published: July 2018

In this paper, the development of a multifrequency form of controlled stress parallel superposition rheometry is reported, along with the technique’s validation and use in model gelling systems and high-value particulate suspensions. The novel technique reported herein, termed Fourier transform controlled stress parallel superposition (FT-CSPS), facilitates measurements of the superposition shear moduli and their response to an imposed unidirectional shear stress. FT-CSPS measurements are reported in applications involving (i) the determination of the relaxation properties of incipient gel networks formed in rapidly gelling samples under bulk flow conditions and (ii) measurements of the parallel dynamic moduli of non-gelling samples that experience high rates of solvent loss. By probing the rheological properties of these rapidly evolving materials using a composite waveform comprising multiple harmonic frequencies, sample mutation artefacts (which limit the use of CSPS for such materials) have been minimised. Validation of FT-CSPS has been achieved by (i) showing coincidence of data obtained using CSPS and FT-CSPS for slowly gelling systems and (ii) continuation of the expected relation between gel strength and stress relaxation exponent beyond the range of data accessible to CSPS (limited by sample mutation considerations). This work demonstrates that the rapid acquisition of parallel superposition shear moduli is feasible and facilitates the use of CSPS-based techniques for tests involving rapidly changing materials (such as those undergoing rapid gelation or relatively rapid solvent loss).
AsH3 gas-phase ex situ doping 3D silicon structures
Authors: Duffy Ray , Thomas Kevin , Galluccio Emmanuele , Mirabelli Gioele , Sultan Maeva , Kennedy Noel , Petkov Nikolay , Maxwell Graeme , Hydes Alan , O'Connell Dan , Lyons Colin , Sheehan Brendan , Schmidt Michael , Holmes Justin D. , Hurley Paul K. , Pelucchi Emanuele , Connolly James , Hatem Chris , Long Brenda
Published: July 2018

Dopant incorporation in Si can be done in situ during epitaxial growth, or ex situ for localised material modification from a variety of sources including ion, solid, liquid, or gas. Gas-phase doping has the advantage that it does not require a thin film deposition, it is more effective at entering tight spaces than a liquid, and it is less damaging and more conformal than a beam-line ion implant. In this work, we apply arsine (AsH3) gas at approximately atmospheric pressures in order to n-type dope three-dimensional (3D) Si device structures. It was observed that the gas-phase doping can be either corrosive or gentle to thin-body Si depending on the process conditions. Initial doping processes caused damage to the Si due to etching, but after process optimisation, the structural integrity of the Si nanostructures could be maintained successfully. Moreover, it was noted that evaluating doping processes entirely on planar Si surfaces can be misleading: processes which appear promising initially may not be transferrable to non-planar thin-body structures like fins or nanowires, due to unwanted Si etching. Overall, we found that gas-phase doping with AsH3 could provide >1020 cm−3 electrically active As concentrations. This high As incorporation makes gas-phase doping very attractive for future gate-all-around devices, where the space between features will decline with continued transistor scaling.
Sustainable thermal interface materials from recycled cotton textiles and graphene nanoplatelets
Authors: Zahid Muhammad , Masood Muhammad Tamoor , Athanassiou Athanassia , Bayer Ilker S.
Published: July 2018

Fabrication of thermal interface materials (TIMs) from sustainable resources is a very challenging task but at the same time of great importance due to the continuously growing problem of electronic waste management. A variety of TIMs comprising synthetic polymers loaded with metallic wires or ceramic nanofillers are commercially available; however, they are usually frail and difficult to recycle. In this letter, we report a simple fabrication process for sustainable bio-based TIMs using regenerated cellulose and graphene nanoplatelets (GnPs). The process relies on forming conductive inks by dissolving post-consumer cotton fabrics and dispersing GnPs in a common solvent, followed by solution casting/drying. The TIM pads become electrically conductive (30 S/m) at 25 wt. % GnP concentrations. Their cross-plane thermal conductivity (k) was estimated to be 5.50 W/mK using infrared thermal measurements on a chip-stack setup. Additionally, the surface or in-plane 2D thermal conductivity was found to be approximately 800 W/mK. In the case of damage, the TIMs can be recycled by re-dispersing in the solvent.
Searching for meaning in the interface between research and management
Authors: Legge Sarah
Published: July 2018

A key goal in conservation science is to generate information that helps to improve the effectiveness of management, and thus benefit threatened and declining species. I have worked on this issue at the interface of science and management, in both the non-profit and academic sectors. I present examples of some of this research, focussing on research into the causes of, and remedial management for, northern faunal declines. In particular, I present the values of research at large, realistic scales, of considering interactions between threats, and of pairing large-scale work with focal studies on the responses of individual animals to threats and their management. I reflect on the common gap between conservation science and management, and provide thoughts about how this might be bridged. Throughout the article, I try to infuse some of the personal and human elements that are the backstory to any conservation work.
Conservation genetics of eastern Australian herpetofauna in a rapidly changing landscape: a perspective on conservation management and policy implementation
Authors: Melville Jane
Published: July 2018

Over the last 200 years Australia has seen wide-scale habitat losses and land-clearing but in the last two decades the rate of loss has been accelerating dramatically, with intensification of land clearing and unprecedented urban growth around most of our major cities. It is within this framework of such rapid change that I have been undertaking conservation genetic research of lizards and frogs over the last 15 years. Here I reflect on the impacts of two rapidly changing landscapes that I have documented through my research. First, the profound impact of land clearing and shifting agricultural practices from mixed-cropping farms to vast broadacre monocultures on the grassland earless dragons of the Condamine River floodplains in south-eastern Queensland. Second, the rapid expansion of the Melbourne urban growth boundaries and how planning processes can impact the future survival of lizard and frog species within an urban environment. Both these cases highlight the impacts of rapid landscape change and emphasise the need for appropriate regulation and planning. Recommendations to slow the detrimental decline and potential extinction of these species include tighter land-clearing regulations and compliance monitoring, plus funding and integration of high-quality research into planning policy at early strategic stages. However, it is also vital that as conservation researchers we effectively communicate to the wider community our knowledge of the impacts that these landscape changes are having on our native flora and fauna.
Low endemic bee diversity and very wide host range in lowland Fiji: support for the pollinator super-generalist hypothesis in island biogeography
Authors: Crichton Arthur , Francis Nikki , Doherty Seamus , Tuiwawa Marika , Hayes Sarah , Stevens Mark I. , Schwarz Michael P.
Published: July 2018

The success of invading plants in island ecosystems has often been inferred to result from ‘invader complexes’, where cointroduced plants and their specialist pollinators can reciprocally enhance each other’s spread. However, it has also been suggested that in islands with low pollinator diversity, those pollinators should evolve into super-generalists that may be able to pollinate a wide range of exotic plants, enabling the spread of exotic weeds. Fiji has a very depauperate endemic bee fauna and previous studies have suggested that its only lowland bee species, Homalictus fijiensis (Apoidea: Halictidae), has a very wide range of host plants. However, those studies only included a small number of endemic flowering plants. Our study expands observations of bee–flower interactions to explore host plant ranges of H. fijiensis and introduced bee species to include a wider variety of native and introduced plant species. We show that H. fijiensis does have a wider host range than introduced bees, including Apis mellifera (Apoidea: Apidae), and an ability to exploit extrafloral nectaries and poricidal anthers that are not utilised by the introduced bee species. Our results support the hypothesis that super-generalism can evolve in islands where pollinator diversity is low, and that this may make those islands susceptible to weed invasions.
Cognitive resource allocation determines the organization of personal networks
Authors: Tamarit Ignacio , Cuesta José A. , Dunbar Robin I. M. , Sánchez Angel
Published: July 2018

Significance

The way we organize our social relationships is key to understanding the structure of our society. We propose a quantitative theory to tackle this issue, assuming that our capacity to maintain relationships is limited and that different types of relationships require different investments. The theory accounts for well-documented empirical evidence on personal networks, such that connections are typically arranged in layers of increasing size and decreasing emotional content. More interestingly, it predicts that when the number of available relationships is small, this structure is inverted, having more close relationships than acquaintances. We provide evidence of the existence of both regimes in real communities and analyze the consequences of these findings in our understanding of social groups.
Automated workflow composition in mass spectrometry-based proteomics
Authors: Palmblad Magnus , Lamprecht Anna-Lena , Ison Jon , Schwämmle Veit
Published: July 2018

Motivation

Numerous software utilities operating on mass spectrometry (MS) data are described in the literature and provide specific operations as building blocks for the assembly of on-purpose workflows. Working out which tools and combinations are applicable or optimal in practice is often hard. Thus researchers face difficulties in selecting practical and effective data analysis pipelines for a specific experimental design.

Results

We provide a toolkit to support researchers in identifying, comparing and benchmarking multiple workflows from individual bioinformatics tools. Automated workflow composition is enabled by the tools’ semantic annotation in terms of the EDAM ontology. To demonstrate the practical use of our framework, we created and evaluated a number of logically and semantically equivalent workflows for four use cases representing frequent tasks in MS-based proteomics. Indeed we found that the results computed by the workflows could vary considerably, emphasizing the benefits of a framework that facilitates their systematic exploration.

Availability and implementation

The project files and workflows are available from https://github.com/bio-tools/biotoolsCompose/tree/master/Automatic-Workflow-Composition.

Supplementary information

Supplementary data are available at Bioinformatics online.
On the Inner Products of Some Deligne–Lusztig-type Representations
Authors: Chen Zhe
Published: July 2018

In this paper we introduce a family of Deligne–Lusztig-type varieties attached to connected reductive groups over quotients of discrete valuation rings, naturally generalising the higher Deligne–Lusztig varieties and some constructions related to the algebraisation problem raised by Lusztig. We establish the inner product formula between the representations associated to these varieties and the higherDeligne–Lusztig representations.
Equity and Gender Issues Among Members of the Canadian Association of Gastroenterology
Authors: Perera Sheron , Bistritz Lana , Beaton Melanie D
Published: July 2018

Background

Gender equity has historically been a challenge within gastroenterology.

Aims

The Canadian Association of Gastroenterology (CAG) developed a survey to identify issues pertaining to equity and gender faced by its membership and to determine areas of action.

Methods

In 2014, the survey was emailed to all 1155 CAG members, and the data were analyzed using statistical methods.

Results

One hundred eleven CAG members responded to the survey. Of those, 52% were male, 75% were between 26 and 45 years of age, and 55% were in their first decade of practice. More males held the status of full professor (21% versus 0%; P=0.022). Male CAG members reported working more hours per week than their female counterparts (58.3 ± 15.4 versus 52.3 ± 11.8, P=0.025). Regarding commitments outside the workplace, 81% of respondents had a spouse/partner, and 52% had children under 18 years of age, both of which did not significantly differ based on gender. Overall, 70% were satisfied or very satisfied with their career path. However, significantly more females felt their age/ethnicity/gender/marital status hindered career advancement (36% versus 14%; P=0.008). Furthermore, more females reported difficulties attaining work-life balance (45% versus 22%; P=0.015).

Conclusions

This survey highlights that gender and equity challenges continue to exist within gastroenterology. The needs assessment highlights that work-life balance, physician well-being, negotiation skills and mentorship are areas of importance to many CAG members.
Prolactin-Secreting Lung Adenocarcinoma Metastatic to the Pituitary Mimicking a Prolactinoma: A Case Report
Authors: Yao Hong , Rui Weiwei , Zhang Yong , Liu Yanting , Lin Shaojian , Tang Hao , Zhao Weiguo , Wu Zhebao
Published: July 2018

BACKGROUND AND IMPORTANCE

Metastasis to the pituitary gland is uncommon in patients with systemic disseminated cancer. Individual articles have reported cases of pituitary metastasis mimicking a prolactinoma, but no case of a prolactin-secreting tumor metastasizing to the pituitary mimicking a prolactinoma has been reported so far.

CLINICAL PRESENTATION

This article reports a 67-yr-old man with a recent onset of headaches, ophthalmoplegia, hypopituitarism, and hyperprolactinemia who was initially diagnosed with prolactinoma and given bromocriptine in the local hospital. Because of vomiting after taking drugs, he was transferred to our hospital for further diagnosis and treatment. Serum prolactin was elevated up to 1022 ng/mL, and pituitary magnetic resonance imaging revealed a 2.9 × 2.8 × 2.3 cm sellar mass with pituitary apoplexy, for which endoscopic transsphenoidal surgery was performed. Postoperative pathology and western blotting disclosed a prolactin-positive metastatic lung adenocarcinoma. Whole exome sequencing revealed a number of gene mutations including KRAS, PIK3CA, ALK, and CTNNB1. The patient died of deterioration of the lung disease 3 mo after the initial diagnosis.

CONCLUSION

To the best of our knowledge, this is the first report of a prolactin-secreting tumor metastasizing to the pituitary mimicking a prolactinoma as confirmed by both immunohistochemistry and western blot. Prolactin secretion is rare and elusive, and may associate with specified gene mutations.
Speciation with gene flow via cycles of isolation and migration: insights from multiple mangrove taxa
Authors: He Ziwen , Li Xinnian , Yang Ming , Wang Xinfeng , Zhong Cairong , Duke Norman C , Wu Chung-I , Shi Suhua
Published: July 2018

Allopatric speciation requiring an unbroken period of geographical isolation has been the standard model of neo-Darwinism. While doubts have been repeatedly raised, strict allopatry without any gene flow remains a plausible mechanism in most cases. To rigorously reject strict allopatry, genomic sequences superimposed on the geological records of a well-delineated geographical barrier are necessary. The Strait of Malacca, narrowly connecting the Pacific and Indian Ocean coasts, serves at different times either as a geographical barrier or a conduit of gene flow for coastal/marine species. We surveyed 1700 plants from 29 populations of 5 common mangrove species by large-scale DNA sequencing and added several whole-genome assemblies. Speciation between the two oceans is driven by cycles of isolation and gene flow due to the fluctuations in sea level leading to the opening/closing of the Strait to ocean currents. Because the time required for speciation in mangroves is longer than the isolation phases, speciation in these mangroves has proceeded through many cycles of mixing-isolation-mixing, or MIM, cycles. The MIM mechanism, by relaxing the condition of no gene flow, can promote speciation in many more geographical features than strict allopatry can. Finally, the MIM mechanism of speciation is also efficient, potentially yielding mn (m > 1) species after n cycles.
A 100 pc-scale fast and dense outflow in the narrow-line Seyfert 1 galaxy IRAS 04576+0912
Authors: Kawaguchi Toshihiro , Ozaki Shinobu , Sugai Hajime , Matsubayashi Kazuya , Hattori Takashi , Shimono Atsushi , Aoki Kentaro , Hayano Yutaka , Minowa Yosuke , Mitsuda Kazuma , Hashiba Yasuhito
Published: July 2018

We report the initial results of an adaptive-optics-assisted, optical integral-field-unit observation of IRAS 04576+0912, the nearest (z = 0.039) active galactic nucleus with a prominent blueshift/tail in [O iii] emission from a sample of such objects that we have collected from the literature. We aim at addressing the putative quasar-mode feedback process with Subaru/Kyoto 3D II+AO188. The optical waveband (6400–7500 Å) enables us to measure the gas density via the [S ii] doublets, in contrast to earlier near-IR studies. Since the fast [O iii] outflow happens only around rapidly growing central black holes, this object is suitable for investigating the black hole–galaxy coevolution. The obtained data cube exhibits a blue tail in the [S ii] emission at many lenslets. By fitting the spectrum with the high excess flux at the [S ii] bluetail, we find a fast (∼860 km s−1), dense (>3000 cm−3), wide-angle, and offset outflow in central 100 pc scales. Although the large opening angle and the high gas outflow-to-accretion ratio may favor the feedback hypothesis, the inferred kinetic power injection rate of this ionized gas outflow seems insufficient to influence the whole host galaxy. A conventional assumption of a low density must have overestimated the feedback process.
Epidemiology and Costs of Sepsis in the United States—An Analysis Based on Timing of Diagnosis and Severity Level*
Authors: Paoli Carly J. , Reynolds Mark A. , Sinha Meenal , Gitlin Matthew , Crouser Elliott
Published: July 2018

Objectives:

To characterize the current burden, outcomes, and costs of managing sepsis patients in U.S. hospitals.

Design:

A retrospective observational study was conducted using the Premier Healthcare Database, which represents ~20% of U.S. inpatient discharges among private and academic hospitals. Hospital costs were obtained from billing records per the cost accounting method used by each hospital. Descriptive statistics were performed on patient demographics, characteristics, and clinical and economic outcomes for the index hospitalization and 30-day readmissions.

Setting:

Sepsis patient hospitalizations, including inpatient, general ward, and ICU (intermediate and/or step-down).

Patients:

Adults over 18 years old with a hospital discharge diagnosis code of sepsis from January 1, 2010, to September 30, 2016.

Interventions:

None. This was a retrospective observational study of deidentified data.

Measurements and Main Results:

The final study cohort consisted of 2,566,689 sepsis cases, representing patients with a mean age of 65 years (50.8% female). Overall mortality was 12.5% but varied greatly by severity (5.6%, 14.9%, and 34.2%) for sepsis without organ dysfunction, severe sepsis, and septic shock, respectively. Costs followed a similar pattern increasing by severity level: $16,324, $24,638, and $38,298 and varied widely by sepsis present at admission ($18,023) and not present at admission ($51,022).

Conclusions:

The highest burden of incidence and total costs occurred in the lowest severity sepsis cohort population. Sepsis cases not diagnosed until after admission, and those with increasing severity had a higher economic burden and mortality on a case-by-case basis. Methods to improve early identification of sepsis may provide opportunities for reducing the severity and economic burden of sepsis in the United States.
PATHOLOGY OF PERIMACULAR FOLDS DUE TO VITREORETINAL TRACTION IN ABUSIVE HEAD TRAUMA
Authors: Abed Alnabi Waleed , Tang Garland J. , Eagle Ralph C. , Gulino Sam , Thau Avrey , Levin Alex V.
Published: July 2018

Purpose:

To demonstrate vitreoretinal traction as a mechanism for perimacular folds in abusive head trauma.

Methods:

We performed gross and histopathologic examination of eyes of children with suspected abusive head trauma and identified those with typical perimacular folds. Information was collected regarding the incident that led to the child's death and systemic manifestations noted at autopsy. Eyes were prepared in a fashion that allowed for demonstration of the vitreoretinal interface.

Results:

Ten eyes of five patients (2–13 months) were examined. All patients had systemic manifestations of abusive trauma including intracranial injury. All cases provided evidence of vitreoretinal traction producing perimacular folds. Condensed vitreous was seen attached to the apices of the retinal folds, and the detached internal limiting membrane comprising the inner surfaces of the schisis cavity. Four cases showed severe bilateral multilayered symmetric retinal hemorrhages extending to the ora serrata. All cases showed optic nerve sheath subdural hemorrhage and subarachnoid hemorrhage. Orbital hemorrhage was unilateral in two cases and bilateral in three cases. Four cases showed orbital fat hemorrhage. One case showed extraocular muscle sheath and cranial nerve sheath hemorrhage. Two cases showed juxtapapillary intrascleral hemorrhage.

Conclusion:

Vitreoretinal traction is the likely mechanism of perimacular folds in abusive head trauma.