bluuebunny/crossref_metadata_2025 huggingface dataset:
Lenvatinib als effektive Systemtherapie
Authors: Arnheim Katharina
Published: March 2018

Über 10 Jahre lang war Sorafenib beim fortgeschrittenen hepatozellulären Karzinom (HCC) die einzige effektive Systemtherapie. Jetzt hat sich Lenvatinib in der globalen Phase-III-Studie REFLECT beim Gesamtüberleben (OS) als zumindest gleich effektiv, beim progressionsfreien Überleben (PFS) als überlegen erwiesen.
„Das heißt, ich muss sterben?!” Training kommunikativer Fertig keiten in der Onkologie und Palliativmedizin
Authors: Neuderth S. , Thierolf A. , Wolf H.-D. , van Oorschot B. , Lukasczik M.
Published: March 2018

Das Überbringen schlechter Nachrichten wird von Ärzten oft als Herausforderung empfunden. Hinweise zum kompetenten Umgang mit solchen Gesprächssituationen sind daher zunehmend in die ärztliche Aus- und Weiterbildung implementiert worden, die entsprechenden Fertigkeiten nehmen im Nationalen Kompetenzbasierten Lernzielkatalog Medizin (NKLM) einen wichtigen Stellenwert ein. Das in diesem Beitrag vorgestellte Praxisbeispiel ermöglicht es Medizinstudierenden, das überbringen schlechter Nachrichten am übergang zu einem palliativen Behandlungsansatz im Rollenspiel mit einer Simulationspatientin zu üben. Aufgabe der Studierenden in der Arztrolle ist es, den Befund (metastasierter Brustkrebs, palliative Situation) und - sofern möglich - die Behandlungsoptionen zu besprechen. Am Universitätsklinikum Würzburg wird das Szenario im Querschnittsbereich „Interdisziplinäre Onkologie” im 7. Semester verwendet. Die besonderen Herausforderungen dieser Fallvignette sind die emotionalen Reaktionen der Patientin und ihre Situation als junge Mutter, die das Aufwachsen ihres Kindes mit hoher Wahrscheinlichkeit nicht mehr erleben wird. Die Evaluationsergebnisse der Veranstaltung sprechen für einen hohen Realitätsgehalt der Rollenspiele und eine breite Akzeptanz bei den Studierenden.
Prädiktoren für eine maligne Transformation
Authors: Krome Susanne
Published: March 2018

Goldstandard für das Grading und die Klassifikation von Gliomen ist die Biopsie. Dabei bestehen interventionelle Risiken, und der optimale Biopsieort kann verfehlt werden. Die Integration multiparametrischer Modelle ist bei Rezidiven und der Frage einer malignen Transformation hilfreich.
Active Immunisation with Partner Lymphocytes in Female Patients Who Want to Become Pregnant – Current Status
Authors: Günther Veronika , Alkatout Ibrahim , Junkers Wiebe , Maass Nicolai , Ziemann Malte , Görg Siegfried , von Otte Sören
Published: March 2018

Around 1 – 3% of all couples who try to have a child are affected by recurrent miscarriage. According to the WHO, recurrent miscarriage is defined as the occurrence of three or more consecutive miscarriages up to the 20th week of pregnancy. There are various causes of recurrent miscarriage; in many cases, the causes remain unclear, with the result that immunological factors are one of the possible causes discussed. For the motherʼs immune system, the embryo represents a semi-allogeneic transplant, as half of the embryoʼs genes are of paternal origin. In place of a conventional immune response, the embryo induces a secondary protection mechanism, which contributes to the successful implantation. When performing immunisation with partner lymphocytes, the patient receives an intradermal injection of her partnerʼs prepared lymphocytes into the volar side of the forearm in order to induce immunomodulation with a consequently increased rate of pregnancy and live birth. A prerequisite for this procedure is that all other possible causes of sterility have been ruled out in advance. Due to the highly heterogeneous nature of the data, a significant benefit as a result of the immunisation cannot yet be clearly proven. However, there are signs that the therapy may be effective when using lymphocytes that have been extracted as short a time beforehand as possible. Overall, the treatment represents a safe, low-risk procedure. Following a detailed informative discussion with the couple regarding the chances of success and following a detailed review of the indication and contraindications, immunisation with partner lymphocytes can be discussed with the couple on a case-by-case basis – provided that all other possible causes of sterility have been ruled out in advance.
Measurement of surface tension by sessile drop tensiometer with superoleophobic surface
Authors: Kwak Wonshik , Park Jun Kwon , Yoon Jinsung , Lee Sanghyun , Hwang Woonbong
Published: March 2018

A sessile drop tensiometer provides a simple and efficient method of determining the surface tension of various liquids. The technique involves obtaining the shape of an axisymmetric liquid droplet and iterative fitting of the Young–Laplace equation, which balances the gravitational deformation of the drop. Since the advent of high quality digital cameras and desktop computers, this process has been automated with precision. However, despite its appealing simplicity, there are complications and limitations in a sessile drop tensiometer, i.e., it must dispense spherical droplets with low surface tension. We propose a method of measuring surface tension using a sessile drop tensiometer with a superoleophobic surface fabricated by acidic etching and anodization for liquids with low surface tension and investigate the accuracy of the measurement by changing the wettability of the measuring plate surface.
Bandgap profiling in CIGS solar cells via valence electron energy-loss spectroscopy
Authors: Deitz Julia I. , Karki Shankar , Marsillac Sylvain X. , Grassman Tyler J. , McComb David W.
Published: March 2018

A robust, reproducible method for the extraction of relative bandgap trends from scanning transmission electron microscopy (STEM) based electron energy-loss spectroscopy (EELS) is described. The effectiveness of the approach is demonstrated by profiling the bandgap through a CuIn1-xGaxSe2 solar cell that possesses intentional Ga/(In + Ga) composition variation. The EELS-determined bandgap profile is compared to the nominal profile calculated from compositional data collected via STEM-based energy dispersive X-ray spectroscopy. The EELS based profile is found to closely track the calculated bandgap trends, with only a small, fixed offset difference. This method, which is particularly advantageous for relatively narrow bandgap materials and/or STEM systems with modest resolution capabilities (i.e., >100 meV), compromises absolute accuracy to provide a straightforward route for the correlation of local electronic structure trends with nanoscale chemical and physical structure/microstructure within semiconductor materials and devices.
On the quantization of the massless Bateman system
Authors: Takahashi K.
Published: March 2018

The so-called Bateman system for the damped harmonic oscillator is reduced to a genuine dual dissipation system (DDS) by setting the mass to zero. We explore herein the condition under which the canonical quantization of the DDS is consistently performed. The roles of the observable and auxiliary coordinates are discriminated. The results show that the complete and orthogonal Fock space of states can be constructed on the stable vacuum if an anti-Hermite representation of the canonical Hamiltonian is adopted. The amplitude of the one-particle wavefunction is consistent with the classical solution. The fields can be quantized as bosonic or fermionic. For bosonic systems, the quantum fluctuation of the field is directly associated with the dissipation rate.
Electric-field induced surface instabilities of soft dielectrics and their effects on optical transmittance and scattering
Authors: Shian Samuel , Kjeer Peter , Clarke David R.
Published: March 2018

When a voltage is applied to a percolative, mechanically compliant mat of carbon nanotubes (CNTs) on a smooth elastomer bilayer attached to an ITO coated glass substrate, the in-line optical transmittance decreases with increasing voltage. Two regimes of behavior have been identified based on optical scattering, bright field optical microscopy, and confocal optical microscopy. In the low field regime, the electric field produces a spatially inhomogeneous surface deformation of the elastomer that causes local variations in optical refraction and modulates the light transmittance. The spatial variation is associated with the distribution of the CNTs over the surface. At higher fields, above a threshold voltage, an array of pits in the surface form by a nucleation and growth mechanism and these also scatter light. The formation of pits, and creases, in the thickness of the elastomer, is due to a previously identified electro-mechanical surface instability. When the applied voltage is decreased from its maximum, the transmittance returns to its original value although there is a transmittance hysteresis and a complicated time response. When the applied voltage exceeds the threshold voltage, there can be remnant optical contrast associated with creasing of the elastomer and the recovery time appears to be dependent on local jamming of CNTs in areas where the pits formed. A potential application of this work as an electrically tunable privacy window or camouflaging devices is demonstrated.
Spinning and tumbling of micron-sized triangles in a micro-channel shear flow
Authors: Fries J. , Kumar M. Vijay , Mihiretie B. Mekonnen , Hanstorp D. , Mehlig B.
Published: March 2018

We report on measurements of the angular dynamics of micron-sized equilaterally triangular platelets suspended in a micro-channel shear flow. Our measurements confirm that such particles spin and tumble like a spheroid in a simple shear. Since the triangle has corners, we can observe the spinning directly. In general, the spinning frequency is different from the tumbling frequency and the spinning is affected by tumbling. This gives rise to doubly periodic angular dynamics.
Non-parametric correlative uncertainty quantification and sensitivity analysis: Application to a Langmuir bimolecular adsorption model
Authors: Feng Jinchao , Lansford Joshua , Mironenko Alexander , Pourkargar Davood Babaei , Vlachos Dionisios G. , Katsoulakis Markos A.
Published: March 2018

We propose non-parametric methods for both local and global sensitivity analysis of chemical reaction models with correlated parameter dependencies. The developed mathematical and statistical tools are applied to a benchmark Langmuir competitive adsorption model on a close packed platinum surface, whose parameters, estimated from quantum-scale computations, are correlated and are limited in size (small data). The proposed mathematical methodology employs gradient-based methods to compute sensitivity indices. We observe that ranking influential parameters depends critically on whether or not correlations between parameters are taken into account. The impact of uncertainty in the correlation and the necessity of the proposed non-parametric perspective are demonstrated.
Temperature-dependent magnetic properties of a magnetoactive elastomer: Immobilization of the soft-magnetic filler
Authors: Bodnaruk Andrii V. , Brunhuber Alexander , Kalita Viktor M. , Kulyk Mykola M. , Snarskii Andrei A. , Lozenko Albert F. , Ryabchenko Sergey M. , Shamonin Mikhail
Published: March 2018

The magnetic properties of a magnetoactive elastomer (MAE) filled with μm-sized soft-magnetic iron particles have been experimentally studied in the temperature range between 150 K and 310 K. By changing the temperature, the elastic modulus of the elastomer matrix was modified, and it was possible to obtain magnetization curves for an invariable arrangement of particles in the sample and in the case when the particles were able to change their position within the MAE under the influence of magnetic forces. At low (less than 220 K) temperatures, when the matrix becomes rigid, the magnetization of the MAE does not show a hysteresis behavior, and it is characterized by a negative value of the Rayleigh constant. At room temperature, when the polymer matrix is compliant, a magnetic hysteresis exists where the dependence of the differential magnetic susceptibility on the magnetic field exhibits local maxima. The appearance of these maxima is explained by the elastic resistance of the matrix to the displacement of particles under the action of magnetic forces.
Static strain tuning of quantum dots embedded in a photonic wire
Authors: Tumanov D. , Vaish N. , Nguyen H. A. , Curé Y. , Gérard J.-M. , Claudon J. , Donatini F. , Poizat J.-Ph.
Published: March 2018

We use strain to statically tune the semiconductor band gap of individual InAs quantum dots (QDs) embedded in a GaAs photonic wire featuring very efficient single photon collection. Thanks to the geometry of the structure, we are able to shift the QD excitonic transition by more than 25 meV by using nano-manipulators to apply the stress. Moreover, owing to the strong transverse strain gradient generated in the structure, we can relatively tune two QDs located in the wire waveguide and bring them in resonance, opening the way to the observation of collective effects such as superradiance.
Movement of small mammals through a road-underpass is facilitated by a wildlife railing
Authors: Goldingay Ross L. , Taylor Brendan D. , Parkyn Jonathan L.
Published: March 2018

Wildlife underpasses in Australia are commonly fitted with timber railings to facilitate the passage of arboreal and scansorial mammals but there are no published accounts of railing use. We compared detections of such mammals on railings in two underpasses to detections on the ground in these and other underpasses. The brown antechinus (Antechinus stuartii) and the black rat (Rattus rattus) were detected on a closely monitored railing on 12–14% of nights over three years. These species were detected on the ground of underpasses on <1% of nights. Koalas (Phascolarctos cinereus) and brushtail possums (Trichosurus spp.) were infrequently detected, koalas only on the ground and brushtail possums mostly on the ground. These observations suggest that road crossings by small scansorial mammals can be facilitated by timber railings.
Determination of Young's Modulus in the Circumferential Direction of Corn Stalks
Authors: Murawski K , Kukielka J
Published: March 2018

A corn stalk is assumed to be a tube with strong anisotropic properties. For this model a set of four fundamental equations is written which describes the behaviour of one-dimensional pressure waves of small amplitude and long wavelength in an infinite thin-walled compliant tube with walls of elastic rings. The reductive Taniuti-Wei (1968) method is developed in order to reduce this set to Burgers' equation. Finally, formulae which describe the velocity of pressure shocks are derived. The analysis of these formulae along with associated measurements allows calculation of Young's modulus in the circumferential direction for corn stalks.
Nonlinear Shift of Wave Parameters of Whistlers in the Ionosphere in the Presence of Negative Ions
Authors: Sur AK , Kashyapi PK , Paul SN , Chakraborty B
Published: March 2018

In this paper the nonlinear shift of the wave number of ion-cyclotron whistlers propagating through the ionosphere in the presence of negative ions is estimated. The results are discussed both numerically and graphically for the proton whistler. It is seen that under some physical situations the nonlinear shift of the wave number of the proton whistler is very significant. Furthermore, the nonlinear shift of the wave number depends significantly on the variation of negative ion concentration when the wave frequency is very close to an ion-cyclotron frequency.
Anova Health Institute's harm reduction initiatives for people who use drugs
Authors: Hugo Johannes M. , Rebe Kevin B. , Tsouroulis Evan , Manion Anthony , de Swart Glenn , Struthers Helen , McIntyre James A.
Published: March 2018

Chemsex is the colloquial term used for a specific pattern of drug use that is increasingly common among men who have sex with men (MSM) globally. The recreational substances employed are used specifically in a sexualized context. The reasons for chemsex among MSM are complex. The Anova Health Institute (Anova) provided harm-reduction services in Cape Town, South Africa in 2013 and 2014. This project, known as Tikking the Boxes had two objectives: first to provide direct harm-reduction services to drug-using MSM in Cape Town, South Africa, and second, to reduce HIV and hepatitis B and C transmission among this population. This was done by identifying drug-using behaviour among MSM and linking them to harm-reduction services. Employing people who were currently using drugs was a novel aspect of this program, and successfully facilitated access to MSM drug-using networks. At the launch of the project, the concept of harm reduction was easily misunderstood by MSM. Another challenge was that the harm-reduction service, encompassing needle exchange, excluded opioid substitution therapy. People who use drugs were employed as outreach workers, requiring the project to be very flexible and adaptable to sometimes complex lives and difficult-to-reach peers. JAB SMART is Anova’s new harm-reduction initiative and started in May 2017, with support from the City of Johannesburg Health Department, and is the first project of its kind in the city to provide harm-reduction services to people who inject drugs (PWID) and their sexual partners.
Effect of grain refinement on strain hardening and fracture in austenitic stainless steel
Authors: Xu D. M. , Wan X. L. , Yu J. X. , Xu G. , Li G. Q.
Published: March 2018

The present study aims to investigate the effect of grain refinement on strain hardening behaviour and fracture surface characteristics in 316LN austenitic stainless steel (ASS). The ASSs with varying grain sizes were obtained through 90% cold rolled reduction and subsequently phase reversion annealing treatment. The results showed that the grain refinement from coarse-grained (CG) structure to ultrafine-grained (UFG) structure increased the yield strength whilst maintaining a reasonable ductility. The strain hardening curves in all the samples were divided into three stages. The fractures in all the samples were ductile fracture with dimples. The subtle differences in the strain hardening behaviour and fracture surface characteristics among the samples with various grain sizes from CG structure to UFG structure were influenced by the deformation mechanisms of austenite.
Kinesins relocalize the chromosomal passenger complex to the midzone for spindle disassembly
Authors: Ibarlucea-Benitez Itziar , Ferro Luke S. , Drubin David G. , Barnes Georjana
Published: March 2018

Mitotic spindle disassembly after chromosome separation is as important as spindle assembly, yet the molecular mechanisms for spindle disassembly are unclear. In this study, we investigated how the chromosomal passenger complex (CPC), which contains the Aurora B kinase Ipl1, swiftly concentrates at the spindle midzone in late anaphase, and we researched the role of this dramatic relocalization during spindle disassembly. We showed that the kinesins Kip1 and Kip3 are essential for CPC relocalization. In cells lacking Kip1 and Kip3, spindle disassembly is severely delayed until after contraction of the cytokinetic ring. Purified Kip1 and Kip3 interact directly with the CPC and recruit it to microtubules in vitro, and single-molecule experiments showed that the CPC diffuses dynamically on microtubules but that diffusion stops when the CPC encounters a Kip1 molecule. We propose that Kip1 and Kip3 trap the CPC at the spindle midzone in late anaphase to ensure timely spindle disassembly.
Portfolio return using Black-litterman single view model with ARMA-GARCH and Treynor Black model
Authors: Arisena Adri , Noviyanti Lienda , Achmad Zanbar S
Published: March 2018

Abstrack

Establishing an optimal portfolio is a method that can help investors to minimize risk and optimize profits. Some models for optimal portfolio include Black-litterman Model and Treynor Black Model. The Black-litterman Model combines the elements of historical data and views of investors to form a new prediction of the portfolio as the basis for the preparation of weighted asset models. Predicted views in this study using time series ARMA-GARCH. The stock return data mostly have high volatility causing heteroscedasticity problems, so the GARCH model is chosen to overcome the problem. Treynor Black Model is active and passive portfolio. An active portfolio is that investors allocate their investment funds to individual securities in the capital market, while passive portfolios are investors allocating their investment funds to the stock market indices. In this research we will use Treynor-Black Model with active portfolio, so that investors can choose stock according to their allocation of funds. The purpose of this research is to form the weight of Black-litterman model portfolio with a single view investor using ARMA-GARCH and compare the profit result obtained from the formation of portfolio Black-litterman Model and Treynor-Black Model. The selected shares are PT. Bank BCA (BBCA), PT. Gudang Garam (GGRM), and PT. Waskita Karya (WSKT).
The influence of steaming and a ratio of grated coconut to water on the yield and quality of virgin coconut oil
Authors: Rahmah N L , Istikoma R , Kumalaningsih S
Published: March 2018

The quality of Virgin Coconut Oil (VCO) is determined by the quality of coconut milk. High quality of coconut milk can be obtained by proper handling of grated coconut as raw material. When coconut was shredded, the lipases are exposed which can hydrolyse the oil resulting free fatty acid (FFA).Steaming is a technique to inactivate lipases. In addition, a ratio of grated coconut to water and steaming duration are important factor to the VCO extraction. Therefore, this study aimed to obtain the best combination of steaming duration and suitable ratio of grated coconut to water in order to produce high quality VCO. The research design was Factorial Randomized Block Design consisted of 2 factors: steaming duration (5; 10; and 15 minutes) and grated coconut to water ratio (1:0; 1:1; 1:2; 1:3; and 1:4 w/v),each treatment was repeated twice. Parameters analyzed were FFA, moisture content, and yield values. The result showed that the best treatment was a treatment with 15 minutes steaming of grated coconut and 1:4 ratio of grated coconut to water. The best treatment VCO had characteristic as follows: FFA 0.054 %, moisture content 0.129 % and yield 17.563 %.
Assessment of good manufacturing practice for small scale food industry in Malang region, East Java, Indonesia
Authors: Purwantiningrum I , Widyhastuty W , Christian J , Sari N
Published: March 2018

Enhancing food safety in developing countries, such as Indonesia, poses more challenges, especially those of the small- and medium-scale. Various food safety systems are available and readily implemented in the food industry. However, to ensure the effectiveness of such systems, pre-requisite programs should be applied prior to the implementation of food safety system. One of the most acknowledged pre-requisite program is Good Manufacturing Practices (GMP). The aim of this study is to assess the GMP compliance of some small-scale food companies in East Java. Three types of traditional food product were selected, include tempe chips, palm sugar, and instant herbal drink. A survey involving three companies for each type of traditional food was conducted. Data was obtained through observation and assessment based on tabulated criteria in GMP criteria. In essential, the result revealed the compliment level of the food companies being surveyed. There was different level of compliment between each type of the food industry, where the palm sugar industry had the lowest level of compliment compared to the other two. This difference is due to the food safety awareness, social and cultural influences, and also knowledge on food safety and hygiene practice.
An Information-Driven 2-Pathway Characterization of Occipitotemporal and Posterior Parietal Visual Object Representations
Authors: Vaziri-Pashkam Maryam , Xu Yaoda
Published: March 2018

Recent studies have demonstrated the existence of rich visual representations in both occipitotemporal cortex (OTC) and posterior parietal cortex (PPC). Using fMRI decoding and a bottom-up data-driven approach, we showed that although robust object category representations exist in both OTC and PPC, there is an information-driven 2-pathway separation among these regions in the representational space, with occipitotemporal regions arranging hierarchically along 1 pathway and posterior parietal regions along another pathway. We obtained 10 independent replications of this 2-pathway distinction, accounting for 58–81% of the total variance of the region-wise differences in visual representation. The separation of the PPC regions from higher occipitotemporal regions was not driven by a difference in tolerance to changes in low-level visual features, did not rely on the presence of special object categories, and was present whether or not object category was task relevant. Our information-driven 2-pathway structure differs from the well-known ventral-what and dorsal-where/how characterization of posterior brain regions. Here both pathways contain rich nonspatial visual representations. The separation we see likely reflects a difference in neural coding scheme used by PPC to represent visual information compared with that of OTC.
Parameter estimation in stock assessment modelling: caveats with gradient-based algorithms
Authors: Subbey Sam
Published: March 2018

Using simple illustrative examples, this note highlights some of the caveats with gradient-based algorithms. This class of algorithms underpins the state-of-the-art modelling platform in fisheries science. The goal is to sound a cautionary note about an increasing trend in fisheries science, where blind faith is being invested in results obtained from algorithms that are fast, and proven to have machine precision.
Pre-discovery transits of the exoplanets WASP-18b and WASP-33b from Hipparcos
Authors: McDonald I , Kerins E
Published: March 2018

We recover transits of WASP-18b and WASP-33b from Hipparcos (1989–1993) photometry. Marginal detections of HAT-P-56b and HAT-P-2b may be also present in the data. New ephemerides are fitted to WASP-18b and WASP-33b. A tentative (∼1.3σ) orbital decay is measured for WASP-18b, but the implied tidal quality factor (Q΄ ∼ 5 × 105) is small and survival time (<106 yr) is too short to be likely. No orbital decay is measured for WASP-33b, and a limit of Q΄ > 2 × 105 is placed. For both planets, the uncertainties in published ephemerides appear underestimated: the uncertainty in the period derivative of WASP-18b would be greatly reduced if its current ephemeris could be better determined.
Asymmetric ejecta of cool supergiants and hypergiants in the massive cluster Westerlund 1
Authors: Andrews H , Fenech D , Prinja R K , Clark J S , Hindson L
Published: March 2018

We report new 5.5 GHz radio observations of the massive star cluster Westerlund 1, taken by the Australia Telescope Compact Array, detecting nine of the ten yellow hypergiants (YHGs) and red supergiants (RSGs) within the cluster. Eight of nine sources are spatially resolved. The nebulae associated with the YHGs Wd1-4a, -12a, and -265 demonstrate a cometary morphology – the first time this phenomenon has been observed for such stars. This structure is also echoed in the ejecta of the RSGs Wd1-20 and -26; in each case the cometary tails are directed away from the cluster core. The nebular emission around the RSG Wd1-237 is less collimated than these systems but once again appears more prominent in the hemisphere facing the cluster. Considered as a whole, the nebular morphologies provide compelling evidence for sculpting via a physical agent associated with Westerlund 1, such as a cluster wind.
Low thyroid function is not associated with an accelerated deterioration in renal function
Authors: Meuwese Christiaan L , van Diepen Merel , Cappola Anne R , Sarnak Mark J , Shlipak Michael G , Bauer Douglas C , Fried Linda P , Iacoviello Massimo , Vaes Bert , Degryse Jean , Khaw Kay-Tee , Luben Robert N , Åsvold Bjørn O , Bjøro Trine , Vatten Lars J , de Craen Anton J M , Trompet Stella , Iervasi Giorgio , Molinaro Sabrina , Ceresini Graziano , Ferrucci Luigi , Dullaart Robin P F , Bakker Stephan J L , Jukema J Wouter , Kearney Patricia M , Stott David J , Peeters Robin P , Franco Oscar H , Völzke Henry , Walsh John P , Bremner Alexandra , Sgarbi José A , Maciel Rui M B , Imaizumi Misa , Ohishi Waka , Dekker Friedo W , Rodondi Nicolas , Gussekloo Jacobijn , den Elzen Wendy P J ,   Thyroid Studies Collaboration
Published: March 2018

Background

Chronic kidney disease (CKD) is frequently accompanied by thyroid hormone dysfunction. It is currently unclear whether these alterations are the cause or consequence of CKD. This study aimed at studying the effect of thyroid hormone alterations on renal function in cross-sectional and longitudinal analyses in individuals from all adult age groups.

Methods

Individual participant data (IPD) from 16 independent cohorts having measured thyroid stimulating hormone, free thyroxine levels and creatinine levels were included. Thyroid hormone status was defined using clinical cut-off values. Estimated glomerular filtration rates (eGFR) were calculated by means of the four-variable Modification of Diet in Renal Disease (MDRD) formula. For this IPD meta-analysis, eGFR at baseline and eGFR change during follow-up were computed by fitting linear regression models and linear mixed models in each cohort separately. Effect estimates were pooled using random effects models.

Results

A total of 72 856 individuals from 16 different cohorts were included. At baseline, individuals with overt hypothyroidism (n = 704) and subclinical hypothyroidism (n = 3356) had a average (95% confidence interval) −4.07 (−6.37 to −1.78) and −2.40 (−3.78 to −1.02) mL/min/1.73 m2 lower eGFR as compared with euthyroid subjects (n = 66 542). In (subclinical) hyperthyroid subjects (n = 2254), average eGFR was 3.01 (1.50–4.52) mL/min/1.73 m2 higher. During 329 713 patient years of follow-up, eGFR did not decline more rapidly in individuals with low thyroid function compared with individuals with normal thyroid function.

Conclusions

Low thyroid function is not associated with a deterioration of renal function. The cross-sectional association may be explained by renal dysfunction causing thyroid hormone alterations.
How Cervical Reconstruction Surgery Affects Global Spinal Alignment
Authors: Mizutani Jun , Strom Russell , Abumi Kuniyoshi , Endo Kenji , Ishii Ken , Yagi Mitsuru , Tay Bobby , Deviren Vedat , Ames Christopher
Published: March 2018

BACKGROUND

There have been no reports describing how cervical reconstruction surgery affects global spinal alignment (GSA).

OBJECTIVE

To elucidate the effects of cervical reconstruction for GSA through a retrospective multicenter study.

METHODS

Seventy-eight patients who underwent cervical reconstruction surgery for cervical kyphosis were divided into a Head-balanced group (n = 42) and a Trunk-balanced group (n = 36) according to the values of the C7 plumb line (PL). We also divided the patients into a cervical sagittal balanced group (CSB group, n = 18) and a cervical sagittal imbalanced group (CSI group, n = 60) based on the C2 PL-C7 PL distance. Various sagittal Cobb angles and the sagittal vertical axes were measured before and after surgery.

RESULTS

Cervical alignment was improved to achieve occiput-trunk concordance (the distance between the center of gravity [COG] PL, which is considered the virtual gravity line of the entire body, and C7 PL < 30 mm) despite the location of COG PL and C7PL. A subsequent significant change in thoracolumbar alignment was observed in Head-balanced and CSI groups. However, no such significant change was observed in Trunk-balanced and CSB groups. We observed 1 case of transient and 1 case of residual neurological worsening.

CONCLUSION

The primary goal of cervical reconstruction surgery is to achieve occiput-trunk concordance. Once it is achieved, subsequent thoracolumbar alignment changes occur as needed to harmonize GSA. Cervical reconstruction can restore both cervical deformity and GSA. However, surgeons must consider the risks and benefits in such challenging cases.
Molecular Mapping of Fusarium Head Blight Resistance in the Spring Wheat Line ND2710
Authors: Zhao Mingxia , Wang Guomei , Leng Yueqiang , Wanjugi Humphrey , Xi Pinggen , Grosz Michael D. , Mergoum Mohamed , Zhong Shaobin
Published: March 2018

ND2710 is a hard red spring wheat line with a very high level of resistance to Fusarium head blight (FHB). It was selected from the progeny of a cross between ND2603 (an advanced breeding line derived from the Sumai 3/Wheaton cross) and Grandin (a spring wheat cultivar). The FHB resistance of ND2710 is presumably derived from Sumai 3 because the other parents (Grandin and Wheaton) are very susceptible to FHB. To identify and map the quantitative trait loci (QTL) for FHB resistance in ND2710, we developed a mapping population consisting of 233 recombinant inbred lines (RILs) from the cross between ND2710 and the spring wheat cultivar Bobwhite. These RILs along with their parents and checks were evaluated for reactions to FHB in three greenhouse experiments and one field experiment during 2013 to 2014. The population was also genotyped with the wheat 90K iSelect single-nucleotide polymorphism (SNP) assay, and a genetic linkage map was developed with 1,373 non-cosegregating SNP markers, which were distributed on all 21 wheat chromosomes spanning 914.98 centimorgans of genetic distance. Genetic analyses using both phenotypic and genotypic data identified one major QTL (Qfhb.ndwp-3B) on the short arm of chromosome 3B, and three minor QTL (Qfhb.ndwp-6B, Qfhb.ndwp-2A, and Qfhb.ndwp-6A) on 6B, 2A, and 6A, respectively. The major QTL on 3B was detected in all experiments and explained 5 to 20% of the phenotypic variation, while the three minor QTL on 6B, 2A, and 6A explained 5 to 12% phenotypic variation in at least two experiments, except for Qfhb.ndwp-2A, which was only detected in the field experiment. Qfhb.ndwp-3B and Qfhb.ndwp-6B were mapped to the genomic regions containing Fhb1 and Fhb2, respectively, confirming that they originated from Sumai 3. The additive effect of the major and minor QTL may contribute to the high level of FHB resistance in ND2710. The SNP markers closely linked to the FHB resistance QTL will be useful for marker-assisted selection of FHB resistance in wheat breeding programs.
Validation of the Healthy Foot Screen: A Novel Assessment Tool for Common Clinical Abnormalities
Authors: Persaud Reneeka , Coutts Patricia M. , Brandon Alisa , Verma Luvneet , Elliott James A. , Sibbald R. Gary
Published: March 2018

GENERAL PURPOSE:

The purpose of this learning activity is to provide information about the Healthy Foot Screen, a new tool for assessment of common foot abnormalities.

TARGET AUDIENCE:

This continuing education activity is intended for physicians, physician assistants, nurse practitioners, and nurses with an interest in skin and wound care.

LEARNING OBJECTIVES/OUTCOMES:

After completing this continuing education activity, you should be able to:

1. Recognize prevalence, causes, risk factors, signs, and types of common foot problems.

2. Identify the results of this study about the new foot screening tool and its implications in primary care.

BACKGROUND:

Foot health is a key component of general health and well-being. Nevertheless, feet are often overlooked by healthcare providers and patients. Common foot problems include infections or inflammatory conditions, abnormal nail disorders (eg, onychomycosis), structural bony abnormalities, circulation disorders, and other conditions. The development of an easy-to-use, rapid, clinical tool to assess foot health can facilitate primary care provider recognition and treatment of common foot problems. This study ascertained interrater item reliability and validity from the preliminary version of one such tool called the Healthy Foot Screen.

METHODS:

A total of 18 patients from a community dermatology clinic were individually screened by 11 interprofessional healthcare assessors using the preliminary tool. The assessors included a dermatologist/internist, family physicians, nurses, and podiatrists. The initial draft of the Healthy Foot Screen was created through an extensive literature review, complemented by the clinical judgment of the study team. Cronbach α was calculated for each item to determine interrater reliability. A minimum value of 0.6 was set for an item to be included in the final tool. Where applicable, scores for each item on the screen were calculated for right and left lower limbs and then averaged. Assessors were asked to complete a short survey.

RESULTS:

Interrater reliability scores for items on the screen were as follows: diabetes and smoking, 1.0; neuropathy, 0.988; palpable foot pulse, 0.916; abnormal fourth to fifth toe web space, 0.905; previous ulcer/amputation, 0.869; pitting edema, 0.872; bony abnormality, 0.804; dry bottom of foot, 0.799; toenail infection, 0.793; other spots/lesions,0.688; and red areas/blisters/pustules, 0.659. Generally, assessors found the tool easy to use, although some areas for improvement were noted.

CONCLUSIONS:

The Healthy Foot Screen can facilitate primary care provider diagnosis and treatment of common foot problems.
Potential clinical and immunotherapeutic utility of talimogene laherparepvec for patients with melanoma after disease progression on immune checkpoint inhibitors and BRAF inhibitors
Authors: Chesney Jason , Imbert-Fernandez Yoannis , Telang Sucheta , Baum Mary , Ranjan Smita , Fraig Mostafa , Batty Nicolas
Published: March 2018

Talimogene laherparepvec is a genetically modified herpes simplex virus type 1–based oncolytic immunotherapy for the local treatment of unresectable subcutaneous and nodal tumors in patients with melanoma recurrent after initial surgery. We report on two patients with melanoma who, after progression on numerous systemic therapies, derived clinical benefit from talimogene laherparepvec in an expanded-access protocol (ClinicalTrials.gov, NCT02147951). Intralesional talimogene laherparepvec (day 1, ≤4 ml 106 PFU/ml; after 3 weeks, ≤4 ml 108 PFU/ml every 2 weeks) was administered until complete response, no injectable tumors, progressive disease, or intolerance occurred. Patient 1 was 71 years old, had stage IIIB disease, and had previously received granulocyte–macrophage colony-stimulating factor, vemurafenib, metformin, ipilimumab, dabrafenib, trametinib, and pembrolizumab. Patient 2 was 45 years old, had stage IIIC disease, and had previously received nivolumab/ipilimumab combination therapy. There were marked reductions in the number and size of melanoma lesions during treatment with talimogene laherparepvec. Both patients experienced mild-to-moderate nausea and vomiting, which were managed using ondansetron, metoclopramide, and pantoprazole. Both patients completed treatment with talimogene laherparepvec in the expanded-access protocol on 24 November 2015, but received talimogene laherparepvec in clinical practice. Patient 1 continues to receive therapy (>60 weeks); patient 2 experienced a complete response at 23 weeks. Immunohistochemistry of a biopsied dermal metastasis from patient 1 showed a marked infiltration of CD4+ and CD8+ T cells after 1 year of treatment. Talimogene laherparepvec was active in patients with advanced melanoma with disease progression following multiple previous systemic therapies; no new safety signals were identified.
Fatty acid receptor GPR120: a novel marker for human melanoma
Authors: Kleemann Johannes , Hrgovic Igor , Ter-Nedden Jan , Kleimann Pia , Steinhorst Katja , Härle Katja , Müller Jutta , Kaufmann Roland , Meissner Markus , Kippenberger Stefan
Published: March 2018

The correlation between ultraviolet radiation of the skin and melanoma incidence in humans is well established. Interestingly, epidemiologic data suggest also a correlation to an increased BMI pointing to metabolic trigger factors in melanoma pathogenesis. To substantiate this connection, we studied the expression of G-protein-coupled receptor 120 (GPR120), a receptor sensitive to unsaturated long-chain free fatty acids in melanoma tissues. One-hundred fourteen tissue sections histologically confirmed as nevi (n=32), primary melanoma (n=39), and melanoma metastasis (n=43) were immunohistochemically stained against GPR120. The staining was evaluated by three trained dermatopathologists and independently scored. Compared with nevi, primary melanoma and melanoma metastasis showed significantly higher levels of GPR120 staining. Only three out of 32 nevi showed strong GPR120 expression [median immunoreactivity-scoring system (IRS) score: 1, range: 0–10], whereas in primary melanomas 14 out of 39 were highly GPR120-positive (median IRS score: 7, range: 0–12) and in melanoma metastasis 27 out of 43 were highly GPR120-positive (median IRS score: 9, range: 0–12). GPR120 expression and tumor thickness (mm) show a statistically significant correlation in primary melanoma (P=0.011). Moreover, GPR120-positive staining was found throughout the epidermis and in sebaceous and sweat glands, which is yet not described. This study identified GPR120 as a novel marker for melanoma, indicating that melanoma cells are sensitive to free fatty acids. It is tempting to speculate that pharmacologically interfering with GPR120 signaling might improve melanoma therapy.
Exploring the Use of C-Reactive Protein to Estimate the Pharmacodynamics of Vancomycin
Authors: Rawson Timothy M. , Charani Esmita , Moore Luke S. P. , Gilchrist Mark , Georgiou Pantelis , Hope William , Holmes Alison H.
Published: March 2018

Background:

C-reactive protein (CRP) pharmacodynamic (PD) models have the potential to provide adjunctive methods for predicting the individual exposure response to antimicrobial therapy. We investigated CRP PD linked to a vancomycin pharmacokinetic (PK) model using routinely collected data from noncritical care adults in secondary care.

Methods:

Patients receiving intermittent intravenous vancomycin therapy in secondary care were identified. A 2-compartment vancomycin PK model was linked to a previously described PD model describing CRP response. PK and PD parameters were estimated using a Non-Parametric Adaptive Grid technique. Exposure–response relationships were explored with vancomycin area-under-the-concentration-time-curve (AUC) and EC50 (concentration of drug that causes a half maximal effect) using the index, AUC:EC50, fitted to CRP data using a sigmoidal Emax model.

Results:

Twenty-nine individuals were included. Median age was 62 (21–97) years. Fifteen (52%) patients were microbiology confirmed. PK and PD models were adequately fitted (r2 0.83 and 0.82, respectively). There was a wide variation observed in individual Bayesian posterior EC50 estimates (6.95–48.55 mg/L), with mean (SD) AUC:EC50 of 31.46 (29.22). AUC:EC50 was fitted to terminal CRP with AUC:EC50 >19 associated with lower CRP value at 96–120 hours of therapy (100 mg/L versus 44 mg/L; P < 0.01).

Conclusions:

The use of AUC:EC50 has the potential to provide in vivo organism and host response data as an adjunct for in vitro minimum inhibitory concentration data, which is currently used as the gold standard PD index for vancomycin therapy. This index can be estimated using routinely collected clinical data. Future work must investigate the role of AUC:EC50 in a prospective cohort and explore linkage with direct patient outcomes.
Quantifying Soft Tissue Shape and Symmetry: Patients with Cleft Lip/Palate and Facial Paralysis
Authors: Trotman Carroll Ann , Faraway Julian , Hadlock Tessa , Banks Caroline , Jowett Nathan , Regan Daniel
Published: March 2018

Background:

The objective of this study was to demonstrate simple three-dimensional analyses of facial soft tissue shape and asymmetry.

Methods:

There were 2 study samples: one retrospective comprised patients with repaired cleft lip and palate (CL/P) and control subjects; and the other prospective comprised patients with unilateral facial paralysis (FP) and control subjects. The data collected were digitized three-dimensional facial landmarks. Scores for shape and asymmetry of subjects’ faces and for different facial regions were generated using Procrustes methods. Pivotal bootstrap methods and analysis of variance were used to test for significant differences in the scores between the patients and controls, and plots of the scores were generated to compare differences among the subjects.

Results:

(1) Shape scores: The CL/P patients demonstrated significant overall and regional facial differences (P ≤ 0.01). The patients were further from the control mean, especially those with unilateral CL/P. Patients with FP demonstrated significant differences (P ≤ 0.05) for the lower face only. (2) Asymmetry scores: CL/P and FP patients demonstrated significant overall and regional facial differences (CL/P, P ≤ 0.0001; FP, P ≤ 0.01). CL/P and FP patients were more asymmetric and were further from the control mean, and patients with unilateral CL/P were more asymmetric than the bilateral CL/P patients.

Conclusion:

Clinicians can use the analyses to isolate differences and/or changes in the face due to shape or asymmetry, or a combination of both; based on the score plots, the extent of the shape and asymmetry differences can be compared among subjects and the extent of changes due to surgery measured.
SENSITIVITY AND SPECIFICITY OF DETECTING POLYPOIDAL CHOROIDAL VASCULOPATHY WITH EN FACE OPTICAL COHERENCE TOMOGRAPHY AND OPTICAL COHERENCE TOMOGRAPHY ANGIOGRAPHY
Authors: de Carlo Talisa E. , Kokame Gregg T. , Kaneko Kyle N. , Lian Rebecca , Lai James C. , Wee Raymond
Published: March 2018

Purpose:

Determine sensitivity and specificity of polypoidal choroidal vasculopathy (PCV) diagnosis with structural en face optical coherence tomography (OCT) and OCT angiography (OCTA).

Methods:

Retrospective review of the medical records of eyes diagnosed with PCV by indocyanine green angiography with review of diagnostic testing with structural en face OCT and OCTA by a trained reader. Structural en face OCT, cross-sectional OCT angiograms alone, and OCTA in its entirety were reviewed blinded to the findings of indocyanine green angiography and each other to determine if they could demonstrate the PCV complex. Sensitivity and specificity of PCV diagnosis was determined for each imaging technique using indocyanine green angiography as the ground truth.

Results:

Sensitivity and specificity of structural en face OCT were 30.0% and 85.7%, of OCT angiograms alone were 26.8% and 96.8%, and of the entire OCTA were 43.9% and 87.1%, respectively. Sensitivity and specificity were improved for OCT angiograms and OCTA when looking at images taken within 1 month of PCV diagnosis.

Conclusion:

Sensitivity of detecting PCV was low using structural en face OCT and OCTA but specificity was high. Indocyanine green angiography remains the gold standard for PCV detection.