bluuebunny/crossref_metadata_2025 huggingface dataset:
RoboTAP: Target priorities for robotic microlensing observations
Authors: Hundertmark M. , Street R. A. , Tsapras Y. , Bachelet E. , Dominik M. , Horne K. , Bozza V. , Bramich D. M. , Cassan A. , D’Ago G. , Figuera Jaimes R. , Kains N. , Ranc C. , Schmidt R. W. , Snodgrass C. , Wambsganss J. , Steele I. A. , Mao S. , Ment K. , Menzies J. , Li Z. , Cross S. , Maoz D. , Shvartzvald Y.
Published: October 2017

Context. The ability to automatically select scientifically-important transient events from an alert stream of many such events, and to conduct follow-up observations in response, will become increasingly important in astronomy. With wide-angle time domain surveys pushing to fainter limiting magnitudes, the capability to follow-up on transient alerts far exceeds our follow-up telescope resources, and effective target prioritization becomes essential. The RoboNet-II microlensing program is a pathfinder project, which has developed an automated target selection process (RoboTAP) for gravitational microlensing events, which are observed in real time using the Las Cumbres Observatory telescope network.

Aims. Follow-up telescopes typically have a much smaller field of view compared to surveys, therefore the most promising microlensing events must be automatically selected at any given time from an annual sample exceeding 2000 events. The main challenge is to select between events with a high planet detection sensitivity, with the aim of detecting many planets and characterizing planetary anomalies.

Methods. Our target selection algorithm is a hybrid system based on estimates of the planet detection zones around a microlens. It follows automatic anomaly alerts and respects the expected survey coverage of specific events.

Results. We introduce the RoboTAP algorithm, whose purpose is to select and prioritize microlensing events with high sensitivity to planetary companions. In this work, we determine the planet sensitivity of the RoboNet follow-up program and provide a working example of how a broker can be designed for a real-life transient science program conducting follow-up observations in response to alerts; we explore the issues that will confront similar programs being developed for the Large Synoptic Survey Telescope (LSST) and other time domain surveys.
Postoperative Imaging after Impingement Surgery
Authors: Grob Karl , Kim Chan-Hi , Dietrich Tobias
Published: October 2017

In addition to the patient's medical history and clinical evaluation, conventional radiographs and magnetic resonance imaging (MRI) are important tools to indicate appropriate conservative treatment or even revision surgery in patients with symptoms after surgical management of femoroacetabular impingement (FAI). We present an overview of current evidence in postoperative imaging after impingement surgery. Undercorrection of the underlying osseous FAI configuration is the most frequent indication for revision surgery within the first 2 years after index FAI surgery. Femoral neck fractures, iatrogenic chondral injuries, early conversion to total hip arthroplasty, loose bodies, and heterotopic ossifications are rare but typical early complications after surgical treatment of FAI. Abnormal MRI findings after FAI surgery such as intra-articular adhesions, labral tears, cartilage defects, and anterior capsular defects are common findings in both asymptomatic and symptomatic postoperative patients. Avascular necrosis of the femoral head is an extremely rare complication after surgical treatment of FAI.
Intra-articular Lesions: Imaging and Surgical Correlation
Authors: Todorski Inga , Lerch Till , Schwab Joseph , Cullmann-Bastian Jennifer , Tannast Moritz , Schmaranzer Florian
Published: October 2017

The past 2 decades have seen a substantial increase in hip joint preserving procedures, primarily secondary to not only hip dysplasia, but the recognition and description of femoroacetabular impingement (FAI), and its association with chondral lesions, as a potentially pre-arthritic condition. Morphological magnetic resonance imaging (MRI) plays an essential role in the preoperative assessment of osseous deformities and in particular of the resulting joint degeneration. An accurate descriptive report of chondrolabral lesions is warranted describing the tear pattern, size, localization, and extension of the lesions. This is important because different damage patterns and localization of the lesions may determine the surgical approach. The current imaging standard is direct magnetic resonance arthrography (MRA) with a small field of view, with acquisition of radial images in addition to the classic coronal, sagittal, and axial-oblique images. Early cartilage damage detected on direct MRA obtained with or without traction can predict long-term failure after FAI surgery.
Hip Imaging: Normal Variants and Asymptomatic Findings
Authors: Vande Berg Bruno , Omoumi Patrick
Published: October 2017

With the increasing use of imaging as a diagnostic tool for hip pain, more and more anatomical variants are detected, and more findings are seen in asymptomatic populations, especially in older individuals. The radiologist must be aware of these variants and asymptomatic findings to avoid interpretative errors and overdiagnosis. In this review, we cover frequently encountered anatomical variants and asymptomatic findings that can be found in the bony structures of the hip, the joint itself, as well as in the surrounding soft tissues.
Greater Trochanteric Pain Syndrome: Abductors, External Rotators
Authors: Falkowski Anna , Kovacs Balazs , Hirschmann Anna
Published: October 2017

Chronic pain and tenderness at the greater trochanter characterizes trochanteric pain syndrome. For a long time, trochanteric bursitis was thought to be the only underlying pathology; however, investigations have shown that tendinopathy of the abductors is the main cause, followed by iliotibial band thickening and, to a lesser extent, abductor tendon tears. Trochanteric bursitis can be associated with it. On magnetic resonance imaging (MRI), peritrochanteric T2 abnormalities are evident in greater trochanteric pain syndrome. However, this is also frequently encountered in asymptomatic patients. In the postoperative setting, patients with total hip arthroplasties and transtendinous lateral or posterior surgical access are prone to tendon injury. Symptomatic patients typically present with tendon tears, whereas peritrochanteric fluid, thickening, and signal alterations of the abductors and fatty atrophy of the gluteus minimus muscle are often encountered in asymptomatic postoperative hips. MRI and ultrasound are proven and reliable imaging modalities in patients with greater trochanteric pain syndrome. Awareness of typical imaging findings, in particular in postoperative patients, are helpful in the evaluation of patients.
Purely Cystic Desmoplastic Ganglioglioma: An Incidental Finding in a Giant Cyst
Authors: Bansal Sumit , Mahapatra Ashok , Patra Susama , Gharei Radhamohan
Published: October 2017

Desmoplastic infantile ganglioglioma (DIG) is a rare supratentorial brain tumor occurring mostly before the age of 2 years. It has a good prognosis and total excision of the tumor is curative, necessitating no further treatment. An accurate pathologic diagnosis is crucial. Until now, approximately 70 cases of this tumor type have been reported. Solid-cystic variety is mostly described with occasional purely solid type lesion also. We are presenting a 12-month-old male infant with developmental delay and a giant cyst on the right side of supratentorial compartment, which showed histological features of desmoplastic ganglioglioma. Hence, the current case is reporting the rare histologic finding of cystic change in desmoplastic ganglioglioma. Cystic form of desmoplastic ganglioglioma should be considered in differential diagnosis of supratentorial cystic lesion in an infant. Prognosis is excellent after complete excision.
Blepharoplasty in Graves’ Ophthalmopathy
Authors: Bocchialini Gabriele , Castellani Andrea , Zanetti Umberto
Published: October 2017

Graves’ ophthalmopathy (GO) is the main extrathyroidal manifestation of Graves’ disease. Many patients require rehabilitative surgery, such as orbital decompression and lipectomy, to restore function and appearance. Graves’ lower eyelid retraction is a common, controversial sign and is resolved in most cases by eyelid surgery, which is very effective and incredibly simple compared with other kinds of surgeries in terms of comorbidity, surgical time, complications, and esthetic results. Here, we describe blepharoplasty in a patient with Graves’ ophthalmopathy.
Rekonstruktive Chirurgie der Harnröhre
Authors: Zugor Vahudin , Porres Daniel , Karapanos Leonidas , Heidenreich Axel , Akbarov Ilgar
Published: October 2017

Urethrastrikturen können in jedem Lebensalter auftreten. Häufig entstehen sie iatrogen nach traumatischen Kathetereinlagen und transurethralen Eingriffen. Die endoskopische Schlitzung ist der einfachste, aber auch der mit den häufigsten Rezidiven behaftete operative Eingriff. Die retrograde Urethrografie bzw. Zysturethrografie spielt weiterhin eine zentrale Rolle in der Diagnostik und Therapieplanung. Eine einheitliche Vorgehensweise bzgl. der Operationstechnik, des perioperativen Managements und der postoperativen Verlaufskontrollen fehlt. Die genaue Kenntnis der Harnröhre und der urogenitalen Anatomie sind Voraussetzung für eine erfolgreiche urethrale Chirurgie. Die dauerhafte Beseitigung einer Striktur kann häufig nur durch offene rekonstruktive Eingriffe erreicht werden. Die End-zu-End-Harnröhrenplastik wird hierbei für kurze bulbäre Harnröhrenstrikturen angewendet, während die Harnröhrenplastik mit Mundschleimhaut im Fall von längeren bulbären und penilen Strikturen zum Einsatz kommt. Die Harnröhren-Rekonstruktion mit dem autologen patienteneigenen Zelltransplantat MukoCell® ist eine schonende und vielversprechende Alternative zur herkömmlichen Transplantation mit nativer Mundschleimhaut. Die komplexen urethralen Rekonstruktionen sollten in Zentren mit entsprechender Expertise durchgeführt werden.
Die motorische Entwicklung von Kindern mit frühkindlichem Innenschielen
Authors: Dillmann Julia , Freitag Claudia , Holve Kerstin , Schweinfurth Silke , Lorenz Birgit , Schwarzer Gudrun
Published: October 2017

Hintergrund Im frühen bis mittleren Kindesalter ist der Zusammenhang zwischen der motorischen Entwicklung und den kindlichen visuell-räumlichen Fähigkeiten bereits vielfach nachgewiesen worden. Bisher wurden diese Zusammenhänge jedoch meist bei gesunden Kindern oder bei Kindern mit motorischen Einschränkungen untersucht. Wenig erforscht ist jedoch, inwieweit die motorische Entwicklung bei Kindern mit beeinträchtigter visuell-räumlicher Verarbeitung aufgrund von frühkindlichem Innenschielen verändert ist und welche Auswirkungen eine erste korrigierende Schieloperation auf die motorische Leistungsfähigkeit der Kinder hat. Zudem liefern die wenigen durchgeführten Studien teilweise widersprüchliche Ergebnisse.

Patienten und Methoden In der vorliegenden Studie untersuchten wir 3- bis 7-jährige Kinder, die über kein Binokularsehen aufgrund von ausgeprägtem Innenschielen (Esotropie) (Schielwinkel ≥ 12°) verfügten. Die motorische Entwicklung der Kinder mit Esotropie wurde kurz vor und 12 bis 16 Monate nach einer ersten korrigierenden Schieloperation mit der Movement Assessment Battery for Children (Movement ABC-2) beurteilt und jeweils mit den Werten einer gesunden Kontrollstichprobe verglichen.

Ergebnisse Hinsichtlich der motorischen Gesamtleistung zeigten die Kinder mit frühkindlicher Esotropie sowohl vor als auch nach dem operativen Eingriff eine geringere Leistung als die augengesunden Kontrollkinder. Präoperativ waren bei den Kindern mit Esotropie insbesondere die Subskalen Handgeschicklichkeit und Balance beeinträchtigt, postoperativ die Subskalen Handgeschicklichkeit und Ballfertigkeiten. In keinem Bereich verbesserten sich die Kinder mit frühkindlicher Esotropie signifikant nach OP im Vergleich zu vor OP. Jedoch schnitten die Patienten, die den Bagolini-Test positiv erkannten, signifikant besser im Bereich der Balance ab als die Patienten, die den Bagolini-Test nicht erkannten.

Schlussfolgerung Die Kinder mit frühkindlichem Innenschielen zeigten deutliche motorische Defizite, sowohl vor als auch nach einer ersten korrigierenden Schieloperation. Zudem wirkte sich messbares Simultansehen positiv auf die Balance der Kinder aus. Mögliche Erklärungen und praktische Implikationen werden diskutiert.
Myelin-Oligodendrozyten-Glykoprotein-Antikörper bei Neuritis nervi optici im Kindesalter
Authors: Tegetmeyer Helmut , Merkenschlager Andreas
Published: October 2017

Hintergrund Myelin-Oligodendrozyten-Glykoprotein (MOG) ist an der Oberfläche der Myelinscheiden und der Oligodendrozyten im Zentralnervensystem lokalisiert. Im Kindes- und Erwachsenenalter zeigt sich eine Assoziation von MOG-AK im Serum mit rezidivierender und bilateraler Neuritis nervi optici (NNO), mit akuter disseminierter Enzephalitis (ADEM) und mit transverser Myelitis (TM). Die Kombination von NNO mit TM oder anderen entzündlichen Hirnläsionen ist typisch für eine Neuromyelitis-optica-Spektrum-Erkrankung (NMO-SD), die mit hochspezifischen pathogenen Aquaporin-4-IgG-Autoantikörpern (AQP4-AK) im Serum assoziiert ist. Kinder mit NMO-SD sind häufig seronegativ für AQP4-AK, aber seropositiv für MOG-AK. Krankheitsverlauf und Therapie der NNO bei Kindern mit NNO-positiven MOG-AK sind deshalb von besonderem Interesse.

Patienten Die Krankheitsverläufe von 2 8-jährigen Jungen mit akuter NNO werden dargestellt (bilaterale NNO, AQP4-AK negativ, MOG-AK positiv). Patient 1 erlitt trotz immunsuppressiver Therapie mehrere Rezidive bei persistierenden MOG-AK mit zunehmender Optikusatrophie, erheblicher einseitiger Visusminderung und passagerer Hirnstammbeteiligung. Bei Patient 2 liegt ein bisher monophasischer Verlauf mit raschem Abfall der MOG-AK und nur geringer asymmetrischer Optikusatrophie vor.

Diskussion MOG-AK sind im Kindesalter mit rezidivierender NNO und Hirnläsionen assoziiert, die typisch für eine ADEM oder eine NMO-SD sind. In der akuten Phase der klinischen Symptomatik werden hohe MOG-AK-Titer beobachtet. Rezidive der NNO führen zu einem zunehmenden Verlust der retinalen Nervenfaserschicht. Diagnostisch sind die Antikörperbestimmung (AQP4-AK, MOG-AK) sowie eine MRT-Bildgebung obligat. Als therapeutische Schlussfolgerung ergibt sich daraus die Notwendigkeit einer konsequenten Behandlung mit initial Kortikosteroiden und nachfolgender Immunsuppression (z. B. Azathioprin, Mycophenolat, bei refraktären Fällen auch Rituximab) sowie der Kontrolle der MOG-AK-Titer.
A high-saturation Fe-27Co material with microalloying additions
Authors: Fohr Frederik , Volbers Niklas
Published: October 2017

This paper reports work on a new variant of the high saturation Fe-27Co alloy. Ternary additions of niobium or tantalum are found to impart ductility to the hot formed material by means of grain refinement. The magnetic and tensile properties of the new alloy with the trade name VACOFLUX® 27 are compared to the standard chromium-type alloy. While the electrical resistivity is reduced, the saturation magnetization of VACOFLUX® 27 is superior.
Silicon-doped hafnium oxide anti-ferroelectric thin films for energy storage
Authors: Ali Faizan , Liu Xiaohua , Zhou Dayu , Yang Xirui , Xu Jin , Schenk Tony , Müller Johannes , Schroeder Uwe , Cao Fei , Dong Xianlin
Published: October 2017

Motivated by the development of ultracompact electronic devices as miniaturized energy autonomous systems, great research efforts have been expended in recent years to develop various types of nano-structural energy storage components. The electrostatic capacitors characterized by high power density are competitive; however, their implementation in practical devices is limited by the low intrinsic energy storage density (ESD) of linear dielectrics like Al2O3. In this work, a detailed experimental investigation of energy storage properties is presented for 10 nm thick silicon-doped hafnium oxide anti-ferroelectric thin films. Owing to high field induced polarization and slim double hysteresis, an extremely large ESD value of 61.2 J/cm3 is achieved at 4.5 MV/cm with a high efficiency of ∼65%. In addition, the ESD and the efficiency exhibit robust thermal stability in 210–400 K temperature range and an excellent endurance up to 109 times of charge/discharge cycling at a very high electric field of 4.0 MV/cm. The superior energy storage performance together with mature technology of integration into 3-D arrays suggests great promise for this recently discovered anti-ferroelectric material to replace the currently adopted Al2O3 in fabrication of nano-structural supercapacitors.
Thermal behavior of a PV panel integrated with PCM-filled metallic tubes: An experimental study
Authors: Waqas Adeel , Jie Ji , Xu Lijie
Published: October 2017

The current research work aims to maintain high photovoltaic (PV) efficiency by keeping them at low operating temperature. For this purpose, commercially available phase change material (PCM) RT24 encapsulated in copper tubes was attached at the back side of a PV panel as a heat sink. The main concept of using the copper tube as PCM encapsulation is to produce a fin effect on the back of the PV panel to enhance the rate of heat transfer from the PV panel to ambient air. The experimental results showed that a maximum temperature reduction of 8.5 °C can be achieved at the front surface of the PV panel with 2.5 kg of PCM per square meter of the PV panel area. The PV back surface was also cooled down from 62 °C to 56 °C by the PCM. Enhancement in efficiency up to 3% was observed. The fin effect for the PV panel cooling was observed as the PV panel was maintained at a lower temperature, even after the PCM was completely utilized. The total cost incurred for the current PCM-based thermal regulation of the PV panel was $93/m2 of the PV area or $0.60/W of the PV power.
Thermal instability in rotating shallow water with horizontal temperature/density gradients
Authors: Gouzien É. , Lahaye N. , Zeitlin V. , Dubos T.
Published: October 2017

A specific instability of vortices is found in rotating shallow water equations with horizontal density/temperature gradients, which is used for modelling atmospheric and oceanic mixed layers. The model is re-interpreted as dynamics of rotating non-isentropic two-dimensional gas. The instability, which was not reported previously, develops in a way suggesting its convective character. It appears when anomaly of buoyancy at the center of the vortex and the vorticity have opposite signs (for positive Coriolis parameters), and coexists with the standard barotropic instability, having higher growth rates in a wide range of parameters and leading to efficient mixing at a nonlinear stage.
Blood-borne virus transmission in an urban, culturally diverse neighbourhood: results from a cross-sectional bio-behavioural survey using innovative outreach methods in a hard-to-reach population
Authors: Peach Elizabeth , Cogger Shelley , Byron Kat , Francis Penny , O'Keefe Daniel , Higgs Peter , Stoove Mark , Elmore Kasey , Dietze Paul , Hellard Margaret
Published: October 2017

Background
Following a HIV outbreak among Aboriginal people in a culturally diverse inner-city suburb of Melbourne, a blood-borne virus (BBV) screening program was conducted to inform public health interventions to prevent transmission and facilitate timely diagnosis and linkage to care. Methods: In August–September 2014, community health workers recruited people who inject drugs (PWID) from a local needle and syringe program. Participants were tested for hepatitis C virus (HCV), hepatitis B virus (HBV), HIV and syphilis and completed a bio-behavioural questionnaire. Results: In total, 128 PWID participated in the study. Serological evidence of exposure to HCV and HBV was detected among 118 (93%) and 57 participants (45%) respectively. Five participants were HIV positive. Independent risk factors for needle sharing were Aboriginality (AOR = 6.21, P < 0.001), attending health care for mental health problems (AOR = 2.79, P = 0.023) and inability to access drug treatment in the previous 6 months (AOR = 4.34, P = 0.023). Conclusions: BBV prevalence in this sample was much higher than reported in other recent Australian studies. This local population is at high risk of further BBV transmission, particularly Aboriginal PWID. Individual and service-related factors associated with risk in the context of a dynamic urban drug culture and HIV outbreak suggest an urgent need for tailored harm-reduction measures.
Modelling the drivers of natural fire activity: the bias created by cropland fires
Authors: Bekar İsmail , Tavşanoğlu Çağatay
Published: October 2017

Wildland and cropland fires, which differ considerably in fire regime characteristics, have often been evaluated jointly to estimate regional or global fire regimes using satellite-based fire activity data. We hypothesised that excluding cropland fires will change the output of the models regarding the drivers of natural fire activity. We modelled MODIS fire activity data of western and southern Turkey for the years 2000–2015 using binomial generalised linear models in which many climatic, anthropogenic and geographic factors were included as predictor variables. For modelling, we used different datasets created by the exclusion of various cropland and vegetation land cover classes. More fire activity was observed as the number of cropland-dominated cells increased in a dataset. The explained deviance (%) of the binomial GLM differed substantially in the separate datasets for most of the variables. Moreover, excluding croplands gradually from the overall dataset resulted in a substantial decrease in the explained deviance (%) in the models for all variables. The results suggest that cropland fires have a significant effect on the output of fire regime models. Therefore, a clear distinction should be drawn between wildland and cropland fires in such models for a better understanding of natural fire activity.
Assessment of Early Migration Dynamics of River‐Specific Hatchery Atlantic Salmon Smolts
Authors: Hawkes James P. , Sheehan Timothy F. , Stich Daniel S.
Published: October 2017

Many Atlantic Salmon Salmo salar populations within the southern extent of the species’ range are at critically low abundances, while others have been extirpated. The focus of many ongoing recovery efforts is on maximizing the number of smolts that reach the ocean, where marine survival is low, primarily through hatchery supplementation and improvement of in‐river hydropower system management. However, estuaries also are known to be sites of high mortality, although in many cases the correlates of this mortality are poorly characterized. We acoustically tagged hatchery smolts (n = 666) during 2001–2005 to evaluate migration performance through freshwater, estuarine, and bay reaches of the small but tidally dynamic Dennys River, Maine, USA, to investigate potential drivers contributing to low returns within the system. Migration behaviors (e.g., migration timing and tidal use) were typical for Atlantic Salmon smolts, but reversals during migration were observed upon entry into the estuary environment more frequently in this system than in regional rivers. We used Cormack–Jolly–Seber mark–recapture models to estimate apparent survival within the study environment during this period. We found two distinct periods of survival, with much lower survival in 2003–2005 than in 2001 and 2002 (more than a 40% decrease). Among the variables considered, temperature and migratory behavior had the largest effects on survival. We found that survival increased by about 28% across the range of temperatures observed during these years; additionally, survival increased by about 15% for fish that reversed direction during migration compared to fish that did not. These results indicate that extreme environmental changes during the transition through this coastal system constitute a significant obstacle to Atlantic Salmon restoration stocking efforts.
Enhancement of AZ80 joints using ultrasonic vibration-assisted welding process
Authors: Li Hui , Zhang Jiansheng , Xiong Yibo
Published: October 2017

Ultrasonic vibration-assisted welding process was developed to improve the microstructures and mechanical properties of AZ80 Mg alloy joints. Results show that the ultrasonic vibration-assisted welding process has a significant effect on the morphology and size of both β-Mg17Al12 precipitated phases and α-Mg grains. With ultrasonic vibration treatment, the primary α-Mg grains are transformed from coarse dendrites to nearly fine equiaxed grains, and the β-Mg17Al12 phases at α-Mg boundaries are refined and become discontinuous, owing to the cavitation effects and acoustic streaming effects induced by ultrasonic vibration. The mechanical properties of AZ80 Mg alloy joints under the ultrasonic vibration-assisted process are obviously improved. And the influence mechanisms of the ultrasonic vibration-assisted welding process on joints are discussed in detail.
Responses of low and high compression during recovery after repeated sprint training in well‐trained handball players
Authors: Zinner Christoph , Pelka Maximilian , Ferrauti Alexander , Meyer Tim , Pfeiffer Mark , Sperlich Billy
Published: October 2017

The aim of the study was to investigate the effects of wearing various levels of compression following repeated and exhausting sprint exercise on variables related to recovery. Twelve well‐trained handball players performed three sessions of repeated and exhausting sprint exercise (30 × 30m). Directly after each session the participants wore tights extending from below the hip to the foot with either 0, 10, or 25 mm Hg of compression onto the thigh and calf muscles. 48 h after the training session all participants performed 5 × 30m sprints and counter movement jumps. Before, directly after, 24 h, and 48 h after the training session venous blood samples were drawn for the determination of creatine kinase (CK), urea, C‐reactive protein (CRP). At the same time points, subjective ratings of the Acute Recovery and Stress Scale (ARSS) questionnaires were obtained. The results for plasma concentrations of CK and urea showed ‘likely’ to ‘very, very likely’ beneficial effects for compression garments exerting 10 mm Hg of compression (p = 0.06–1.0). With regard to sprint and jump performance no differences were evident between 0, 10, and 25 mm Hg (p = 0.07–1.0). In addition, subjective scores from the ARSS did not differ between conditions over time (p > 0.05). We conclude that the application of 10 mm Hg leg compression compared to 0 and 25 mm Hg of compression during 48 h of recovery from repeated and exhausting sprints lowered the plasma concentrations of CK and urea with no improvements in recovery for performance.
A Daple-Akt feed-forward loop enhances noncanonical Wnt signals by compartmentalizing β-catenin
Authors: Aznar Nicolas , Sun Nina , Dunkel Ying , Ear Jason , Buschman Matthew D. , Ghosh Pradipta
Published: October 2017

Cellular proliferation is antagonistically regulated by canonical and noncanonical Wnt signals; their dysbalance triggers cancers. We previously showed that a multimodular signal transducer, Daple, enhances PI3-K→Akt signals within the noncanonical Wnt signaling pathway and antagonistically inhibits canonical Wnt responses. Here we demonstrate that the PI3-K→Akt pathway serves as a positive feedback loop that further enhances noncanonical Wnt signals by compartmentalizing β-catenin. By phosphorylating the phosphoinositide- (PI) binding domain of Daple, Akt abolishes Daple’s ability to bind PI3-P-enriched endosomes that engage dynein motor complex for long-distance trafficking of β-catenin/E-cadherin complexes to pericentriolar recycling endosomes (PCREs). Phosphorylation compartmentalizes Daple/β-catenin/E-cadherin complexes to cell–cell contact sites, enhances noncanonical Wnt signals, and thereby suppresses colony growth. Dephosphorylation compartmentalizes β-catenin on PCREs, a specialized compartment for prolonged unopposed canonical Wnt signaling, and enhances colony growth. Cancer-associated Daple mutants that are insensitive to Akt mimic a constitutively dephosphorylated state. This work not only identifies Daple as a platform for cross-talk between Akt and the noncanonical Wnt pathway but also reveals the impact of such cross-talk on tumor cell phenotypes that are critical for cancer initiation and progression.
A microtubule polymerase cooperates with the kinesin-6 motor and a microtubule cross-linker to promote bipolar spindle assembly in the absence of kinesin-5 and kinesin-14 in fission yeast
Authors: Yukawa Masashi , Kawakami Tomoki , Okazaki Masaki , Kume Kazunori , Tang Ngang Heok , Toda Takashi
Published: October 2017

Accurate chromosome segregation relies on the bipolar mitotic spindle. In many eukaryotes, spindle formation is driven by the plus-end–directed motor kinesin-5 that generates outward force to establish spindle bipolarity. Its inhibition leads to the emergence of monopolar spindles with mitotic arrest. Intriguingly, simultaneous inactivation of the minus-end–directed motor kinesin-14 restores spindle bipolarity in many systems. Here we show that in fission yeast, three independent pathways contribute to spindle bipolarity in the absence of kinesin-5/Cut7 and kinesin-14/Pkl1. One is kinesin-6/Klp9 that engages with spindle elongation once short bipolar spindles assemble. Klp9 also ensures the medial positioning of anaphase spindles to prevent unequal chromosome segregation. Another is the Alp7/TACC-Alp14/TOG microtubule polymerase complex. Temperature-sensitive alp7cut7pkl1 mutants are arrested with either monopolar or very short spindles. Forced targeting of Alp14 to the spindle pole body is sufficient to render alp7cut7pkl1 triply deleted cells viable and promote spindle assembly, indicating that Alp14-mediated microtubule polymerization from the nuclear face of the spindle pole body could generate outward force in place of Cut7 during early mitosis. The third pathway involves the Ase1/PRC1 microtubule cross-linker that stabilizes antiparallel microtubules. Our study, therefore, unveils multifaceted interplay among kinesin-dependent and -independent pathways leading to mitotic bipolar spindle assembly.
Generalized correlation measure using count statistics for gene expression data with ordered samples
Authors: Wang Y X Rachel , Liu Ke , Theusch Elizabeth , Rotter Jerome I , Medina Marisa W , Waterman Michael S , Huang Haiyan
Published: October 2017

Motivation

Capturing association patterns in gene expression levels under different conditions or time points is important for inferring gene regulatory interactions. In practice, temporal changes in gene expression may result in complex association patterns that require more sophisticated detection methods than simple correlation measures. For instance, the effect of regulation may lead to time-lagged associations and interactions local to a subset of samples. Furthermore, expression profiles of interest may not be aligned or directly comparable (e.g. gene expression profiles from two species).

Results

We propose a count statistic for measuring association between pairs of gene expression profiles consisting of ordered samples (e.g. time-course), where correlation may only exist locally in subsequences separated by a position shift. The statistic is simple and fast to compute, and we illustrate its use in two applications. In a cross-species comparison of developmental gene expression levels, we show our method not only measures association of gene expressions between the two species, but also provides alignment between different developmental stages. In the second application, we applied our statistic to expression profiles from two distinct phenotypic conditions, where the samples in each profile are ordered by the associated phenotypic values. The detected associations can be useful in building correspondence between gene association networks under different phenotypes. On the theoretical side, we provide asymptotic distributions of the statistic for different regions of the parameter space and test its power on simulated data.

Availability and implementation

The code used to perform the analysis is available as part of the Supplementary Material.

Supplementary information

Supplementary data are available at Bioinformatics online.
Effector Biology in Focus: A Primer for Computational Prediction and Functional Characterization
Authors: Dalio Ronaldo J. D. , Herlihy John , Oliveira Tiago S. , McDowell John M. , Machado Marcos
Published: October 2017

Plant–pathogen interactions are controlled by a multilayered immune system, which is activated by pathogen recognition in the host. Pathogens secrete effector molecules to interfere with the immune recognition or signaling network and reprogram cell structure or metabolism. Understanding the effector repertoires of diverse pathogens will contribute to unraveling the molecular mechanism of virulence and developing sustainable disease-control strategies for crops and natural ecosystems. Effector functionality has been investigated extensively in only a small number of pathogen species. However, many more pathogen genomes are becoming available, and much can be learned from a broader view of effector biology in diverse pathosystems. The purpose of this review is to summarize methodology for computational prediction of protein effectors, functional characterization of effector proteins and their targets, and the use of effectors as probes to screen for new sources of host resistance. Although these techniques were generally developed in model pathosystems, many of the approaches are directly applicable for exploration and exploitation of effector biology in pathosystems that are less well studied. We hope to facilitate such exploration, which will broaden understanding of the mechanisms that underpin the biological diversity of plant–pathogen interactions, and maximize the impact of new approaches that leverage effector biology for disease control.
Computer-assisted Surgery in Revision Total Knee Replacement: A Description of the Technique
Authors: Perret Michael C. , Khan Riaz J.K. , Fick Daniel P. , Haebich Samantha
Published: October 2017

Revision total knee replacement is an increasing problem worldwide. The technical challenges involved in revision surgery, especially with component placement, have drawn attention to computer navigation techniques which have been shown to improve outcomes in the primary setting. We present a detailed description of our preoperative planning and operative technique, and results of our prospective case series.
ALL-PROBE VITRECTOMY DISSECTION TECHNIQUES FOR DIABETIC TRACTIONAL RETINAL DETACHMENTS
Authors: Berrocal María H.
Published: October 2017

Purpose:

To describe the all-probe lift and shave technique to remove fibrovascular tissue and repair diabetic retinal detachments. Anatomical and visual acuity outcomes with this technique are presented.

Methods:

In this single surgeon, retrospective review of a consecutive series of eyes with tractional retinal detachment associated with diabetic retinopathy repaired with probe-only dissection techniques. The technique of alternating aspiration with blunt dissection and shaving with the vitrectomy probe is described and shown in video.

Results:

Forty-two eyes with tractional retinal detachment were successfully repaired and achieved anatomical attachment with the lift and shave technique. Twenty eyes were repaired with 27 g vitrectomy and 22 eyes with 25 g. Ninety percent of eyes improved two or more Snellen lines. Minimum follow-up was 6 months. Complications included iatrogenic breaks in one eye (5%), nonclearing vitreous hemorrhage in four eyes (9%), and reoperation in three eyes (7%) for epiretinal membranes.

Conclusion:

The all-probe lift and shave technique of fibrovascular dissection is a streamlined approach for the management of tractional retinal detachments. Advantages include the need for minimal ancillary instrumentation, increased efficiency, and reduced complications.
Corneal Tissue From Dry Eye Donors Leads to Enhanced Graft Rejection
Authors: Inomata Takenori , Hua Jing , Nakao Takeshi , Shiang Tina , Chiang Homer , Amouzegar Afsaneh , Dana Reza
Published: October 2017

Purpose:

To assess the effect of dry eye disease (DED) in graft donors on dendritic cell (DC) maturation, host T-cell sensitization, and corneal allograft rejection.

Methods:

Corneas of control (healthy donor) and DED mice (C57BL/6) were transplanted onto fully allogeneic naive BALB/c recipients (n = 10 mice/group). Long-term allograft survival was evaluated for 8 weeks. Corneas and draining lymph nodes (dLNs) were harvested at posttransplantation day 14 (n = 5 mice/group). The frequencies of MHCIIhigh CD11c+ DCs in the donor corneas and host dLNs and the frequencies of interferon (IFN)-γ+ and IL-17+ CD4+ T cells and Foxp3 expression by Tregs in host dLNs were investigated using flow cytometry. The enzyme-linked immunospot assay was used to assess host T-cell allosensitization through direct and indirect pathways (n = 3/group).

Results:

Recipients of DED donor corneas showed significantly reduced graft survival (10%) compared with control mice (50% survival, P = 0.022), and had significantly increased frequencies of mature DCs in the grafted cornea (DED donor 44.0% ± 0.36% vs. healthy donor 35.4 ± 0.5%; P < 0.0001) and host dLNs (DED donor 25.1% ± 0.66% vs. healthy donor 13.7% ± 1.6%; P = 0.005). Frequencies of IFN-γ+ and IL-17+ T cells were increased in the dLNs of recipients of DED corneas, whereas the expression (mean fluorescence intensity) of Foxp3 in Tregs was decreased significantly in these mice (DED donor 6004 ± 193 vs. healthy donor 6806 ± 81; P = 0.0002). Enzyme-linked immunospot analysis showed that the direct pathway of allosensitization was significantly amplified in recipients of grafts with DED (P = 0.0146).

Conclusions:

Our results indicate that DED in the donor is a significant risk factor for subsequent corneal allograft rejection.
Pharmacokinetics, Safety and Efficacy of Maraviroc in Treatment-experienced Pediatric Patients Infected With CCR5-Tropic HIV-1
Authors: Giaquinto Carlo , Mawela Muthuhadini Patience , Chokephaibulkit Kulkanya , Negra Marinella Della , Mitha Ismail Haroon , Fourie Jan , Fang Annie , van der Ryst Elna , Valluri Srinivas Rao , Vourvahis Manoli , Zhang-Roper Rebecca Yanhui , Craig Charles , McFadyen Lynn , Clark Andrew , Heera Jayvant
Published: October 2017

Background:

Maraviroc is a CC-chemokine receptor 5 antagonist approved to treat adults infected with CC-chemokine receptor 5–tropic (R5) HIV-1. Study A4001031 was conducted to evaluate the pharmacokinetics, safety and efficacy of maraviroc in combination with optimized background therapy in treatment-experienced pediatric patients infected with R5 HIV-1 and support registration of maraviroc for pediatric use.

Methods:

This is an open-label, 2-stage, age-stratified, noncomparative multicenter study. One-hundred and three participants were enrolled into 4 age/formulation cohorts and dosed twice daily. Initial doses were determined by body surface area and optimized background therapy, based on drug interactions with maraviroc in adults. Dose adjustment and pharmacokinetic reevaluation occurred if the average concentrations (C
avg) at Week 2 were <100 ng/mL (Stage 1—dose finding).

Results:

Data from the Week 48 analysis demonstrated that 49/50 Stage 1 participants rolling over into Stage 2 (safety and efficacy) achieved C
avg ≥100 ng/mL. Doses were identified that achieved similar concentration ranges to those seen in adults. The majority (90/103) received optimized background therapy containing potent cytochrome P450 3A inhibitors. Maraviroc was well tolerated and the safety and efficacy were comparable to those of adults. All cohorts had a mean decrease from baseline in HIV-1 RNA of >1 log10. Increases from baseline in the median CD4+ cell count and percentage were seen for all age groups.

Conclusions:

The maraviroc dosing strategy resulted in participants achieving the target C
avg, with exposure ranges similar to those observed in adults on approved doses. The safety and efficacy of maraviroc in this pediatric population were comparable to those seen in adults.
The Lived Experience of Gynecologic Cancer Survivors in Taiwan
Authors: Tsai Li-Yun , Wang Kung-Liahng , Liang Shu-Yuan , Tsai Jung-Mei , Tsay Shiow-Luan
Published: October 2017

Background:

Although it is now possible to achieve permanent remission in a large percentage of gynecologic cancer (GC) cases, many GC patients in remission experience side effects or complications that influence their physical function and family relationships. Compared with other types of cancer patients, survivors of GC face greater challenges in terms of physical and psychological adaptations, and many of these do not receive sufficient assistance. An in-depth understanding of the lived experiences and demands of GC survivors is key to constructing comprehensive related healthcare services.

Purpose:

The aim of this study was to understand the lived experience of GC survivors in Taiwan to help their return to a healthy life.

Methods:

This was a phenomenological study. Twenty-three survivors of GC participated in semistructured interviews that were held in a private environment. The transcripts were based on synchronous recordings from the interviews. Giorgi’s phenomenology analysis was adopted for data analysis.

Results:

Three themes with six subthemes were extracted from the data, including (a) the inner struggle of living with cancer and recurrence: repeatedly exploring the causes of cancer and treatment and facing a fear of cancer recurrence, (b) the interpretation and adjustment to cancer treatment: filled with fluctuating physical and mental distress and working to adopt a different perspective, and (c) the long passage of finding a desirable lifestyle: adjusting to long-term coexistence with side effects and realizing the strength of society, body, and mind.

Conclusions/Implications for Practice:

The journey of rehabilitation for GC survivors is very long. The participants in this study faced different respective challenges during the diagnosis, treatment, and adjustment phases. Conventional disease-oriented medical care cannot satisfy the requirements of cancer patients because of patient-decentralized services. Our results indicate that GC survivors face diverse problems, both physically and mentally. Healthcare professionals should work to facilitate the psychological adjustment of cancer survivors and provide timely professional advice in combination with social resources. These results may serve as a reference for cancer care professionals who are navigating healthcare services.
Sensitivity of the Cogstate Test Battery for Detecting Prolonged Cognitive Alterations Stemming From Sport-Related Concussions
Authors: Sicard Veronik , Moore Robert D. , Ellemberg Dave
Published: October 2017

Objective:

To determine if the Cogstate test battery contains the requisite sensitivity to detect prolonged cognitive alterations.

Methods:

One hundred twenty collegiate athletes (71 with a history of concussion; 49 controls) completed the Cogstate test battery, to which we added a 2-back condition. In addition to the Cogstate clinical (transformed variables), we analyzed the raw data.

Results:

The clinical variables failed to reveal any group differences. Further, although the raw data failed to reveal group differences for tasks measuring lower-level cognition, group differences were observed for accuracy on the 1- and 2-back tasks, which require multiple aspects of higher cognition. The overall classification accuracy was higher using the raw data than the clinical variables. The combined sensitivity of the 1- and 2-back task was moderate and specificity was high.

Conclusions:

These results suggest that using the raw scores over clinical variables increases the sensitivity of the test battery. Moreover, these results add another piece of evidence suggesting that concussive injuries are associated with subtle long-term alterations in aspects of higher cognition. Importantly, these deficits would have gone unobserved if we had relied solely on automated clinical variables. The current results further our scientific understanding of concussion and may be used to advance clinical practices.
Dual-Task Tandem Gait and Average Walking Speed in Healthy Collegiate Athletes
Authors: Howell David R. , Oldham Jessie R. , Meehan William P. , DiFabio Melissa S. , Buckley Thomas A.
Published: October 2017

Objectives:

To (1) examine the association between a commonly used concussion test, tandem gait, in single/dual-task conditions with single-task and dual-task average walking speed, (2) characterize the prevalence of tandem gait false positives, and (3) develop a normative reference range of dual-task tandem gait times.

Design:

Cross-sectional study.

Setting:

Two NCAA collegiate athletic facilities.

Independent Variables:

Athletes completed the tandem gait test and a gait evaluation in single/dual-task conditions during a preseason examination.

Main Outcome Measures:

Associations between tandem gait times and average walking speeds were evaluated using multiple linear regression models. Various tandem gait test time pass/fail cutoffs were calculated to examine false-positive rates.

Results:

Among the 171 participants (103 men, 19.8 ± 1.2 years of age), dual-task tandem gait completion times were independently associated with dual-task average walking speed [β = −4.018; 95% confidence interval (CI), −7.153 to −0.883], but single-task associations were not found. Male gender was associated with faster tandem gait times in both single-task (β = −0.880, 95% CI, −1.731 to −0.029) and dual-task conditions (β = −2.225, 95% CI, −3.691 to −0.759). A pass/fail cutoff threshold of 14 seconds resulted in a 2% false-positive rate for single-task tandem gait, while it resulted in a 29% false-positive rate during dual-task tandem gait.

Conclusions:

Average walking speed and dual-task tandem gait represent objective measures that are useful in concussion management. While a single-task tandem gait cutoff of 14 seconds seems appropriate for males, adjustments may be necessary based on sex and alternate pass/fail criteria may be appropriate for dual-task tandem gait.
Patient Experience-based Value Sets
Authors: Pickard A. Simon , Hung Yu-Ting , Lin Fang-Ju , Lee Todd A.
Published: October 2017

Background:

Although societal preference weights are desirable to inform resource-allocation decision-making, patient experienced health state-based value sets can be useful for clinical decision-making, but context may matter.

Objective:

To estimate EQ-5D value sets using visual analog scale (VAS) ratings for patients undergoing knee replacement surgery and compare the estimates before and after surgery.

Methods:

We used the Patient Reported Outcome Measures data collected by the UK National Health Service on patients undergoing knee replacement from 2009 to 2012. Generalized least squares regression models were used to derive value sets based on the EQ-5D-3 level using a development sample before and after surgery, and model performance was examined using a validation sample.

Results:

A total of 90,450 preoperative and postoperative valuations were included. For preoperative valuations, the largest decrement in VAS values was associated with the dimension of anxiety/depression, followed by self-care, mobility, usual activities, and pain/discomfort. However, pain/discomfort had a greater impact on VAS value decrement in postoperative valuations. Compared with preoperative health problems, postsurgical health problems were associated with larger value decrements, with significant differences in several levels and dimensions, including level 2 of mobility, level 2/3 of usual activities, level 3 of pain/discomfort, and level 3 of anxiety/depression. Similar results were observed across subgroups stratified by age and sex.

Conclusions:

Findings suggest patient experience-based value sets are not stable (ie, context such as timing matters). However, the knowledge that lower values are assigned to health states postsurgery compared with presurgery may be useful for the patient-doctor decision-making process.