bluuebunny/crossref_metadata_2025 huggingface dataset:
Effective interprofessional simulation training for medical and midwifery students
Authors: Edwards S E , Platt S , Lenguerrand E , Winter C , Mears J , Davis S , Lucas G , Hotton E , Fox R , Draycott T , Siassakos D
Published: October 2015

Introduction

Good interprofessional teamworking is essential for high quality, efficient and safe clinical care. Undergraduate interprofessional training has been advocated for many years to improve interprofessional working. However, few successful initiatives have been reported and even fewer have formally assessed their educational impact.

Methods

This was a prospective observational study of medical and midwifery students at a tertiary-level maternity unit. An interprofessional training module was developed and delivered by a multiprofessional faculty to medical and midwifery students, including short lectures, team-building exercises and practical simulation-based training for one obstetric (shoulder dystocia) and three generic emergencies (sepsis, haemorrhage, collapse). Outcome measures were interprofessional attitudes, assessed with a validated questionnaire (UWE Interprofessional Questionnaire) and clinical knowledge, measured with validated multiple-choice questions.

Results

Seventy-two students participated (34 medical, 38 midwifery). Following training median interprofessional attitude scores improved in all domains (p<0.0001), and more students responded in positive categories for communication and teamwork (69–89%, p=0.004), interprofessional interaction (3–16%, p=0.012) and interprofessional relationships (74–89%, p=0.006). Scores for knowledge improved following training for medical students (65.5% (61.8–70%) to 82.3% (79.1–84.5%) (median (IQR)) p<0.0001) and student midwives (70% (64.1–76.4%) to 81.8% (79.1–86.4%) p<0.0001), and in all subject areas (p<0.0001).

Conclusions

This training was associated with meaningful improvements in students’ attitudes to teamwork, and knowledge acquisition. Integrating practical tasks and teamwork training, in authentic clinical settings, with matched numbers of medical and non-medical students can facilitate learning of both why and how to work together. This type of training could be adopted widely in undergraduate healthcare education.
Validation of the Modified Raymond–Roy classification for intracranial aneurysms treated with coil embolization
Authors: Stapleton Christopher J , Torok Collin M , Rabinov James D , Walcott Brian P , Mascitelli Justin R , Leslie-Mazwi Thabele M , Hirsch Joshua A , Yoo Albert J , Ogilvy Christopher S , Patel Aman B
Published: October 2015

Background

The Raymond–Roy Occlusion Classification (RROC) qualitatively assesses intracranial aneurysm occlusion following endovascular coil embolization. The Modified Raymond–Roy Classification (MRRC) was developed as a refinement of this classification scheme, and dichotomizes RROC III occlusions into IIIa (opacification within the interstices of the coil mass) and IIIb (opacification between the coil mass and aneurysm wall) closures.

Methods

To demonstrate in an external cohort the predictive accuracy of the MRRC, the records of 326 patients with 345 intracranial aneurysms treated with endovascular coil embolization from January 2007 to December 2013 were retrospectively analyzed.

Results

Within this cohort, 84 (24.3%) and 83 aneurysms (24.1%) had MRRC IIIa and IIIb closures, respectively, during initial coil embolization. Progression to complete occlusion was more likely with IIIa than IIIb closures (53.6% vs 19.2%, p≤0.01), while recanalization was more likely with IIIb than IIIa closures (65.1% vs 27.4%, p<0.01). Kaplan–Meier estimates demonstrated a significant difference in the test of equality for progression to complete occlusion (p=0.02) and recurrence (p<0.01) between class IIIa and IIIb distributions. For the entire cohort, male gender (p<0.01), ruptured aneurysm (p=0.04), intraluminal thrombus (p<0.01), and MRRC IIIb closure (p<0.01) were identified as predictors of recanalization. For aneurysms with an initial RROC III occlusion, MRRC IIIa closure was found to be an independent predictor of progression to complete occlusion (p=0.02).

Conclusions

This study confirms that the MRRC enhances the predictive accuracy of the RROC.
Acute consumption of p-synephrine does not enhance performance in sprint athletes
Authors: Gutiérrez-Hellín Jorge , Salinero Juan José , Abían-Vicen Javier , Areces Francisco , Lara Beatriz , Gallo Cesar , Puente Carlos , Del Coso Juan
Published: October 2015

P-Synephrine is a protoalkaloid widely used as an ergogenic aid in sports. This substance has been included in the World Anti-Doping Agency monitoring program, although scientific information about its effects on performance and athletes’ well-being is scarce. The purpose of this investigation was to determine the effectiveness of p-synephrine to increase performance in sprint athletes. In a randomized and counterbalanced order, 13 experienced sprinters performed 2 acute experimental trials after the ingestion of p-synephrine (3 mg·kg−1) or after the ingestion of a placebo (control trial). Forty-five minutes after the ingestion of the substances, the sprinters performed a squat jump, a countermovement jump, a 15-s repeated jump test, and subsequently performed 60-m and 100-m simulated sprint competitions. Self-reported questionnaires were used to assess side-effect prevalence. In comparison with the control trial, the ingestion of p-synephrine did not change countermovement jump height (37.4 ± 4.2 vs 36.7 ± 3.3 cm, respectively; P = 0.52), squat jump height (34.4 ± 3.6 vs 33.9 ± 3.7 cm; P = 0.34), or average 15-s repeated jumps height (31.8 ± 4.1 vs 32.2 ± 3.6 cm; P = 0.18). P-Synephrine did not modify maximal running speed during the 60-m (9.0 ± 0.5 vs 9.0 ± 0.4 m·s−1, respectively; P = 0.55) and 100-m sprint competitions (8.8 ± 0.5 vs 8.8 ± 0.5 m·s−1, respectively; P = 0.92). The ingestion of p-synephrine did not alter the prevalence of headache, gastrointestinal discomforts, muscle pain, or insomnia during the hours following the tests. Acute consumption of 3 mg·kg−1 of p-synephrine was ineffective to increase performance in competitive sprint athletes. Moreover, p-synephrine did not increase the occurrence of side effects after the competition.
Roles of spatial scale in quantifying stock–recruitment relationships for American lobsters in the inshore Gulf of Maine
Authors: Chang Jui-Han , Chen Yong , Halteman William , Wilson Carl
Published: October 2015

It is well known in ecological studies that the choice of spatial scale can influence the possibility of detecting ecological patterns and the type of patterns observed. However, this has rarely been evaluated for fish stock–recruitment (SR) dynamics. Inappropriate scales may result in failure to identify possible SR relationships, especially for species with complicated life history and stock structure and locally generated recruitment. Using American lobster (Homarus americanus) in the Gulf of Maine (GOM) as an example, we tested the hypotheses that the SR relationship is detectable only at certain spatial scales and the functional SR relationships vary with spatial scales. We estimated the SR relationship separately for American lobster in the eastern and western GOM, which have strongly differing oceanographic conditions that may result in different suitable spatial scale and SR dynamics for lobster. We analyzed data of 11 different spatial scales using a Bayesian method. The model fit and performances in the posterior predictive assessment for the SR models were convexly related to the spatial scales. The functional SR relationships differed for different spatial scale. The SR parameter estimates are negatively or concavely related to the spatial scale. The best model was found at medium spatial scale for both the eastern and western GOM, and the scale differed between the eastern and western GOM, suggesting that optimal spatial scale might be process-related. We demonstrated that the choice of spatial scale directly affected the possibility of identifying the SR relationship, the estimation of SR parameters, the type of SR relationships, and the predictive abilities of the SR models.
Measurement and prediction of bark thickness in Picea abies: assessment of accuracy, precision, and sample size requirements
Authors: Stängle Stefan M. , Weiskittel Aaron R. , Dormann Carsten F. , Brüchert Franka
Published: October 2015

Tree and log diameters are usually measured outside bark, but inside-bark diameters are of greater economic interest and are often derived with local or regional bark thickness equations. To date, the influence of measurement method, sampling design, and sample size on bark thickness equation accuracy and precision has received limited attention. The objectives of this study were to use an extensive regional bark thickness dataset for Norway spruce (Picea abies (L.) Karst) in southwestern Germany to (1) quantify the accuracy and precision of bark thickness measurements with a Swedish bark gauge, (2) determine the required number of measurements to assess the within-tree variation, and (3) estimate the required sample sizes per plot and per region to develop an accurate bark thickness prediction equation. Bark gauge readings were validated with measurements derived from X-ray computed tomography (CT) and indicate that Swedish bark gauges generally overestimated bark thickness by 13.6% ± 28.4% (mean ± standard deviation). Results suggested having at least one measurement location every 2 m along a tree bole and at least five bark thickness measurements per each of these locations to achieve an allowable error of <15%. For the study area, Monte Carlo simulations indicated that a total sample size of 50–250 trees was needed, depending on the complexity of the desired bark thickness model. Overall, this analysis indicated that there was relatively high within- and between-tree variation in bark thickness, but adequate sampling methods and sample sizes produced highly accurate bark thickness equations.
Continuous and high-frequency measurements in limnology: history, applications, and future challenges
Authors: Meinson Pille , Idrizaj Agron , Nõges Peeter , Nõges Tiina , Laas Alo
Published: October 2015

Over the past 15 years, an increasing number of studies in limnology have been using data from high-frequency measurements (HFM). This new technology offers scientists a chance to investigate lakes at time scales that were not possible earlier and in places where regular sampling would be complicated or even dangerous. This has allowed capturing the effects of episodic or extreme events, such as typhoons on lakes. In the present paper we review the various fields of limnology, such as monitoring, studying highly dynamic processes, lake metabolism studies, and budget calculations, where HFM has been applied, and which have benefitted most from the application. Our meta-analysis showed that more than half of the high-frequency studies from lakes were made in North America and Europe. The main field of application has been lake ecology (monitoring, lake metabolism) followed by physical limnology. Water temperature and dissolved oxygen have been the most universal and commonly measured parameters and we review the various study purposes for which these measurements have been used. Although a considerable challenge for the future, our review highlights that broadening the spatial scale of HFM would substantially broaden the applicability of these data across a spectrum of different fields.
A Study on Regression Analysis by Expanded RBF Network Based on Copula with Linear Correlation and Rank Correlation
Authors: Ota Shuhei , Kimura Mitsuhiro
Published: October 2015

We extend the traditional RBF network to be a more powerful tool in terms of considering dependence among explanatory variables. For this purpose, we propose two kernel functions of RBF network, i.e., FGM-Gauss kernel and ρ-Gauss kernel based on a copula. A copula is another expression of a joint probability distribution function. After proposing the new models, we compare the regression performances between RBF network with the traditional Gauss kernel, FGM-Gauss kernel, ρ-Gauss kernel, and the multiple linear regression analysis by numerical experimentations. We show that new models have better regression performances than RBF network with Gauss kernel and multiple regression analysis if the explanatory variables depend on each other.
Dielectric behavior of a flexible three-phase polyimide/BaTiO3/multi-walled carbon nanotube composite film
Authors: Wang Junli , Qi Shengli , Sun Yiyi , Tian Guofeng , Wu Dezhen
Published: October 2015

A three-phase composite film was produced by inserting multi-walled carbon nanotubes (MWCNTs) and BaTiO3 nanoparticles into polyimide (PI). The combination of in-situ polymerization and water-based preparation involved in the experiment ensured fillers’ homogeneous dispersion in the matrix, which led to flexible shape of the composite films. The dielectric properties of composite films as a function of the frequency and the volume fraction of MWCNTs were studied. Such composite film displayed a high dielectric constant (314.07), low dielectric loss and excellent flexibility at 100[Formula: see text]Hz in the neighborhood of percolation threshold (9.02 vol%) owing to the special microcapacitor structure. The experimental results were highly consistent with the power law of percolation theory.
Finite N corrections to the limiting distribution of the smallest eigenvalue of Wishart complex matrices
Authors: Perret Anthony , Schehr Grégory
Published: October 2015

We study the probability density function (PDF) of the smallest eigenvalue of Laguerre–Wishart matrices [Formula: see text] where [Formula: see text] is a random [Formula: see text] ([Formula: see text]) matrix, with complex Gaussian independent entries. We compute this PDF in terms of semi-classical orthogonal polynomials, which are deformations of Laguerre polynomials. By analyzing these polynomials, and their associated recurrence relations, in the limit of large [Formula: see text], large [Formula: see text] with [Formula: see text] — i.e. for quasi-square large matrices [Formula: see text] — we show that this PDF, in the hard edge limit, can be expressed in terms of the solution of a Painlevé III equation, as found by Tracy and Widom, using Fredholm operator techniques. Furthermore, our method allows us to compute explicitly the first [Formula: see text] corrections to this limiting distribution at the hard edge. Our computations confirm a recent conjecture by Edelman, Guionnet and Péché. We also study the soft edge limit, when [Formula: see text], for which we conjecture the form of the first correction to the limiting distribution of the smallest eigenvalue.
An Alternative Paradigm for Food Production, Distribution, and Consumption: A Noneconomist’s Perspective
Authors: Rausser Gordon , Zilberman David , Kahn Gabriel
Published: October 2015

The Industrial Food and Agricultural (IFA) industry has become increasingly excoriated by proponents of the Naturalization Food and Agricultural (NFA) paradigm over the past decade. Thought leaders of this alternative movement have been calling for economic and policy overhauls of the food system—touching upon human health, labor rights, the environment, climate change, and animal welfare. Although the majority of these thought leaders are not economists or scientists, their arguments are structured to shape consumer choices and farmers’ production decisions, influence food and agricultural policy, and ultimately affect the economics of the industry. In this article, we survey publications at the forefront of the NFA paradigm, touching upon the work of Pollan, Schlosser, Petrini, Bittman, Nestle, and Kremen, among others, as well as the earlier contributions of Carson, Sinclair, Steinbeck, Buck, and even Jefferson. Their solutions, although short on quantitative analysis and long on prescriptions, address the real concerns of the general public and lay the foundation for economists to advance public discourse through analytical research on the NFA paradigm.
Multiple Myeloma Impairs Bone Marrow Localization of Effector Natural Killer Cells by Altering the Chemokine Microenvironment
Authors: Ponzetta Andrea , Benigni Giorgia , Antonangeli Fabrizio , Sciumè Giuseppe , Sanseviero Emilio , Zingoni Alessandra , Ricciardi Maria Rosaria , Petrucci Maria Teresa , Santoni Angela , Bernardini Giovanni
Published: October 2015

Natural killer (NK) cells are key innate immune effectors against multiple myeloma, their activity declining in multiple myeloma patients with disease progression. To identify the mechanisms underlying NK cell functional impairment, we characterized the distribution of functionally distinct NK cell subsets in the bone marrow of multiple myeloma-bearing mice. Herein we report that the number of KLRG1− NK cells endowed with potent effector function rapidly and selectively decreases in bone marrow during multiple myeloma growth, this correlating with decreased bone marrow NK cell degranulation in vivo. Altered NK cell subset distribution was dependent on skewed chemokine/chemokine receptor axes in the multiple myeloma microenvironment, with rapid downmodulation of the chemokine receptor CXCR3 on NK cells, increased CXCL9 and CXCL10, and decreased CXCL12 expression in bone marrow. Similar alterations in chemokine receptor/chemokine axes were observed in patients with multiple myeloma. Adoptive transfer experiments demonstrated that KLRG1− NK cell migration to the bone marrow was more efficient in healthy than multiple myeloma–bearing mice. Furthermore, bone marrow localization of transferred CXCR3-deficient NK cells with respect to wild type was enhanced in healthy and multiple myeloma-bearing mice, suggesting that CXCR3 restrains bone marrow NK cell trafficking. Our results indicate that multiple myeloma–promoted CXCR3 ligand upregulation together with CXCL12 downmodulation act as exit signals driving effector NK cells outside the bone marrow, thus weakening the antitumor immune response at the primary site of tumor growth. Cancer Res; 75(22); 4766–77. ©2015 AACR.
Systemic Administration and Targeted Radiosensitization via Chemically Synthetic Aptamer–siRNA Chimeras in Human Tumor Xenografts
Authors: Ni Xiaohua , Zhang Yonggang , Zennami Kenji , Castanares Mark , Mukherjee Amarnath , Raval Raju R. , Zhou Haoming , DeWeese Theodore L. , Lupold Shawn E.
Published: October 2015

Radiation therapy is a highly effective tool for treating all stages of prostate cancer, from curative approaches in localized disease to palliative care and enhanced survival for patients with distant bone metastases. The therapeutic index of these approaches may be enhanced with targeted radiation-sensitizing agents. Aptamers are promising nucleic acid delivery agents for short interfering RNAs (siRNA) and short hairpin RNAs (shRNA). We have previously developed a radiation-sensitizing RNA aptamer–shRNA chimera that selectively delivers DNA-PK targeting shRNAs to prostate-specific membrane antigen (PSMA) positive cells in the absence of transfection reagents. Although these chimera are effective, their synthesis requires in vitro transcription and their evaluation was limited to intratumoral administration. Here, we have developed a second-generation aptamer–siRNA chimera that can be assembled through the annealing of three separate chemically synthesized components. The resulting chimera knocked down DNA-PK in PSMA-positive prostate cancer cells, without the need of additional transfection reagents, and enhanced the efficacy of radiation-mediated cell death. Following intravenous injection, the chimera effectively knocked down DNA-PK in established subcutaneous PSMA-positive tumors. Systemic treatment with these radiation-sensitizing agents selectively enhanced the potency of external beam radiation therapy for established PSMA-positive tumors. Mol Cancer Ther; 14(12); 2797–804. ©2015 AACR.
A TORC2–Akt Feed-Forward Topology Underlies HER3 Resiliency in HER2-Amplified Cancers
Authors: Amin Dhara N. , Ahuja Deepika , Yaswen Paul , Moasser Mark M.
Published: October 2015

The requisite role of HER3 in HER2-amplified cancers is beyond what would be expected as a dimerization partner or effector substrate and it exhibits a substantial degree of resiliency that mitigates the effects of HER2-inhibitor therapies. To better understand the roots of this resiliency, we conducted an in-depth chemical-genetic interrogation of the signaling network downstream of HER3. A unique attribute of these tumors is the deregulation of TORC2. The upstream signals that ordinarily maintain TORC2 signaling are lost in these tumors, and instead TORC2 is driven by Akt. We find that in these cancers HER3 functions as a buffering arm of an Akt–TORC2 feed-forward loop that functions as a self-perpetuating module. This network topology alters the role of HER3 from a conditionally engaged ligand-driven upstream physiologic signaling input to an essential component of a concentric signaling throughput highly competent at preservation of homeostasis. The competence of this signaling topology is evident in its response to perturbation at any of its nodes. Thus, a critical pathophysiologic event in the evolution of HER2-amplified cancers is the loss of the input signals that normally drive TORC2 signaling, repositioning it under Akt dependency, and fundamentally altering the role of HER3. This reprogramming of the downstream network topology is a key aspect in the pathogenesis of HER2-amplified cancers and constitutes a formidable barrier in the targeted therapy of these cancers. Mol Cancer Ther; 14(12); 2805–17. ©2015 AACR.
ERK Signal Suppression and Sensitivity to CH5183284/Debio 1347, a Selective FGFR Inhibitor
Authors: Nakanishi Yoshito , Mizuno Hideaki , Sase Hitoshi , Fujii Toshihiko , Sakata Kiyoaki , Akiyama Nukinori , Aoki Yuko , Aoki Masahiro , Ishii Nobuya
Published: October 2015

Drugs that target specific gene alterations have proven beneficial in the treatment of cancer. Because cancer cells have multiple resistance mechanisms, it is important to understand the downstream pathways of the target genes and monitor the pharmacodynamic markers associated with therapeutic efficacy. We performed a transcriptome analysis to characterize the response of various cancer cell lines to a selective fibroblast growth factor receptor (FGFR) inhibitor (CH5183284/Debio 1347), a mitogen-activated protein kinase kinase (MEK) inhibitor, or a phosphoinositide 3-kinase (PI3K) inhibitor. FGFR and MEK inhibition produced similar expression patterns, and the extracellular signal–regulated kinase (ERK) gene signature was altered in several FGFR inhibitor–sensitive cell lines. Consistent with these findings, CH5183284/Debio 1347 suppressed phospho-ERK in every tested FGFR inhibitor–sensitive cell line. Because the mitogen-activated protein kinase (MAPK) pathway functions downstream of FGFR, we searched for a pharmacodynamic marker of FGFR inhibitor efficacy in a collection of cell lines with the ERK signature and identified dual-specificity phosphatase 6 (DUSP6) as a candidate marker. Although a MEK inhibitor suppressed the MAPK pathway, most FGFR inhibitor–sensitive cell lines are insensitive to MEK inhibitors and we found potent feedback activation of several pathways via FGFR. We therefore suggest that FGFR inhibitors exert their effect by suppressing ERK signaling without feedback activation. In addition, DUSP6 may be a pharmacodynamic marker of FGFR inhibitor efficacy in FGFR-addicted cancers. Mol Cancer Ther; 14(12); 2831–9. ©2015 AACR.
BI 885578, a Novel IGF1R/INSR Tyrosine Kinase Inhibitor with Pharmacokinetic Properties That Dissociate Antitumor Efficacy and Perturbation of Glucose Homeostasis
Authors: Sanderson Michael P. , Apgar Joshua , Garin-Chesa Pilar , Hofmann Marco H. , Kessler Dirk , Quant Jens , Savchenko Alexander , Schaaf Otmar , Treu Matthias , Tye Heather , Zahn Stephan K. , Zoephel Andreas , Haaksma Eric , Adolf Günther R. , Kraut Norbert
Published: October 2015

Inhibition of the IGF1R, INSRA, and INSRB receptor tyrosine kinases represents an attractive approach of pharmacologic intervention in cancer, owing to the roles of the IGF1R and INSRA in promoting cell proliferation and survival. However, the central role of the INSRB isoform in glucose homeostasis suggests that prolonged inhibition of this kinase could result in metabolic toxicity. We describe here the profile of the novel compound BI 885578, a potent and selective ATP-competitive IGF1R/INSR tyrosine kinase inhibitor distinguished by rapid intestinal absorption and a short in vivo half-life as a result of rapid metabolic clearance. BI 885578, administered daily per os, displayed an acceptable tolerability profile in mice at doses that significantly reduced the growth of xenografted human GEO and CL-14 colon carcinoma tumors. We found that treatment with BI 885578 is accompanied by increases in circulating glucose and insulin levels, which in turn leads to compensatory hyperphosphorylation of muscle INSRs and subsequent normalization of blood glucose within a few hours. In contrast, the normalization of IGF1R and INSR phosphorylation in GEO tumors occurs at a much slower rate. In accordance with this, BI 885578 led to a prolonged inhibition of cell proliferation and induction of apoptosis in GEO tumors. We propose that the remarkable therapeutic window observed for BI 885578 is achieved by virtue of the distinctive pharmacokinetic properties of the compound, capitalizing on the physiologic mechanisms of glucose homeostasis and differential levels of IGF1R and INSR expression in tumors and normal tissues. Mol Cancer Ther; 14(12); 2762–72. ©2015 AACR.
Quantifying the Ototoxicity of Mitomycin: Before versus after Myringotomy
Authors: Roskies Michael , Citra Dan , Daniel Sam J.
Published: October 2015

Objectives: Recent research has focused on mitomycin C (MMC) application as a means to circumvent complications that arise when using ventilation tubes during myringotomy. This study has two aims: (1) to synergize the current literature to create a standardized clinical approach for using MMC, and (2) to determine at which point during the myringotomy the application of MMC proves the safest (i.e., before or after incision). Methods: We measured the auditory brainstem response (ABR) and distortion product otoacoustic emissions (DPOAE) in 9 female chinchillas to determine whether applying MMC before or after incision was also the safest. The tests were then repeated on days 3, 10 and 17. Results: The change in the ABR thresholds from baseline was greater in the experimental than in the control group; however, after stratification, the ‘after' group experienced a statistically significant change (19.38 ± 8.26) on day 17, whereas the ‘before' group did not (2.00 ± 3.26; p = 0.003). No such changes were seen with DPOAE testing. Conclusions: Mitomycin is less ototoxic to the middle ear when applied before myringotomy is done. We recommend future studies to apply the clinical approach we have designed to standardize its use in selected cases.
Versorgung von Riesenrissen der Netzhaut mittels Mikroinzisions-Vitrektomie
Authors: Kunikata Hiroshi
Published: October 2015

Riesenrisse der Netzhaut (RRN; ≥90°) sind selten und selbst für erfahrene vitreoretinale Chirurgen schwer erfolgreich zu behandeln. Die Mikroinzisions-Vitrektomie (microincision vitrectomy surgery; MIVS) stellt einen großen Fortschritt in der Behandlung von RRN dar. Wir beschreiben hier die Operationstechnik und die damit verbundenen Komplikationen. Operationstechnik: Zunächst wird das Auge mittels MIVS gründlich vitrektomiert; hierbei wird ein modernes Weitwinkel-Beobachtungssystem mit Chandelier-Lichtquelle verwendet. Dann wird behutsam flüssiges Perfluorocarbon (perfluorocarbon liquid; PFCL) injiziert. Nach einer Endofotokoagulation wird das PFCL für eine 2-wöchige intraokulare Tamponade durch Silikonöl (SÖ) ersetzt. Nach Entfernung des SÖ wird die vollständige Refixation der Netzhaut und Erholung des Sehvermögens erreicht. Komplikationen: Zu den möglichen postoperativen retinalen Komplikationen zählen epiretinale Gliose, subretinales PFCL, Netzhaut-Falten, zystoides Makulaödem und erneute Netzhaut-Ablösung infolge proliferativer Vitreoretinopathie. Alle Komplikationen sind medikamentös oder chirurgisch behandelbar. Schlussfolgerungen: Die Techniken der MIVS eröffnen einen gangbaren neuen Weg für die Behandlung von Augen mit RRN. In Kombination mit der intraoperativen Anwendung von PFCL und einer 2-wöchigen Tamponade mit SÖ kann die MIVS allen vitreoretinalen Chirurgen, die nach exzellenten Refixationsraten streben, nachdrücklich empfohlen werden.
Perioperative and Palliative Chemotherapy for Esophageal Cancer
Authors: Behrens Angelika , Ell Christian , Lordick Florian
Published: October 2015

Perioperative and palliative chemotherapy for esophageal carcinoma has undergone substantial changes in recent years. The implementation of trastuzumab in the treatment of HER2-positive advanced adenocarcinoma is a milestone as it marked the introduction of the first molecularly targeted treatment of gastric cancer. Current studies are investigating whether anti-HER2-directed treatment also proves effective in the perioperative setting. Data from the CROSS study on neoadjuvant radio-/chemotherapy with paclitaxel and carboplatin have helped to establish a new standard of care for the treatment of localized esophageal cancer. Finally, preliminary experience in potentially curative treatment approaches for oligometastatic tumor stages may offer new treatment options for patients with stage IV gastric cancer. However, some of these innovative approaches urgently require validation in larger, prospective, and controlled multicenter studies. Highly active forms of radiotherapy, radio-/chemotherapy, or chemoimmunotherapy can achieve complete tumor remissions in some patients. Despite these advances, life expectancy unfortunately continues to be very limited in the majority of patients with locally advanced or metastatic esophageal carcinoma.
Fallbericht von schwerer Hornhaut-Toxizität nach topischer Anwendung von 0,5%igem Moxifloxacin
Authors: Vignesh A.P. , Srinivasan Renuka , Karanth Swathi
Published: October 2015

Moxifloxacin ist ein sehr gebräuchliches topisches Antibiotikum zur Behandlung verschiedener bakterieller Infektionen des Auges. Seine Sicherheit und Wirksamkeit sind durch zahlreiche Studien belegt. Wir berichten über einen Fall einer seltenen Nebenwirkung seiner Anwendung. Ein 10-jähriges Mädchen, das sich mit akuter bakterieller Konjunktivitis ohne Hornhaut-Beteiligung in beiden Augen vorgestellt hatte, wurde mit Konservierungsmittel-freiem, 0,5%igem, topischem Moxifloxacin 4-mal täglich behandelt. In beiden Augen entwickelte sich nach Beginn der Behandlung eine schwere Hornhaut-Toxizität mit perikornealer Stauung und Hornhaut-Ödem. Die Sehschärfe des Mädchens fiel in beiden Augen von 20/20 auf 20/400 ab. Das topische Moxifloxacin wurde abgesetzt, woraufhin die Hornhaut sich drastisch erholte und die Sehschärfe sich normalisierte. Dieser Fall zeigt, dass topisches Moxifloxacin - wenngleich selten - schwere Keratitis verursachen kann und dass weitere Studien erforderlich sind, um die Sicherheit zu beurteilen.
Maternal Telomere Length and Risk of Down Syndrome: Epidemiological Impact of Smokeless Chewing Tobacco and Oral Contraceptive on Segregation of Chromosome 21
Authors: Ray Anirban , Hong Chang-Sook , Feingold Eleanor , Ghosh Papiya , Ghosh Priyanka , Bhaumik Pranami , Dey Subratakumar , Ghosh Sujay
Published: October 2015

Background: We have previously demonstrated a relationship between children born with Down syndrome and maternal telomere length. Similarly, exposure to tobacco and oral contraceptives has been explored in one of our earlier studies as a risk factor for Down syndrome. Objective: In the present study, we consider the interactions among these risk factors associated with Down syndrome in a population from Kolkata, India, using analyses stratified by maternal age. Methods: We estimated the telomere length of women with children with Down syndrome by restriction enzyme/Southern blot methods. Linear regression was employed to estimate telomere shortening as an indicator of the maternal age of conception. Interactions among the various factors were analyzed by logistic regression. Result: We found an association between the use of smokeless chewing tobacco and shorter telomere length among women who experienced meiosis I nondisjunction at gametogenesis; the effect is seen across all maternal age groups. In contrast, oral contraceptive use alone did not exhibit a statistically significant association with maternal telomere length, but there was an interaction with the use of smokeless chewing tobacco in the older mothers who experienced meiotic II nondisjunction. Conclusion: Environmental/habitual factors interact with molecular components of the oocyte, which ultimately increases the risk of chromosome 21 nondisjunction and subsequently of giving birth to a child with Down syndrome.
Aryl Hydrocarbon Receptor Activation in Acne Vulgaris Skin: A Case Series from the Region of Naples, Italy
Authors: Fabbrocini Gabriella , Kaya Gürkan , Caseiro Silverio Patricia , De Vita Valerio , Kaya Aysin , Fontao Fabienne , Sorg Olivier , Saurat Jean-Hilaire
Published: October 2015

Background: Dioxins are persistent organic pollutants present in the environment. They exert their biological effects by binding to an intracellular receptor, the aryl hydrocarbon receptor (AhR). Activation of AhR leads to the induction of cytochrome p450 1A1 (CYP1A1). Expression of CYP1A1 in human skin is a key marker for AhR activation, and it may induce comedogenesis resulting in acne-like lesions known as chloracne/metabolising acquired dioxin-induced skin hamartomas (MADISH). The contribution of this pathway in patients seen in a busy acne clinic is unknown. Materials and Methods: We explored the expression of CYP1A1 by immunohistochemistry in the acne lesions of 16 patients living in the region of Naples, Italy, where epidemiological studies have suggested a possibly increased exposure to environmental dioxins. A composite score to outline potential components of the chloracne/MADISH histological pattern was used. Results: CYP1A1 expression was observed in 11 lesions (69%) and was distributed in sebaceous glands, follicular epithelium, cystic wall and endothelial cells. The histological score for chloracne/MADISH was ‘likely' in 3 cases and ‘possible' in 11 cases. Compared to current data on CYP1A1 expression in the skin of 67 patients with proven exposure to AhR agonists, these data indicate a high incidence of AhR activation in this series. Conclusion: This is the first study analysing AhR activation in skin in a series of patients from a hospital-based acne clinic. It provides information for future controlled prospective studies. The significance of CYP1A1 expression in terms of AhR ligand exposure is discussed.
Novel KIF7 Mutation in a Tunisian Boy with Acrocallosal Syndrome: Case Report and Review of the Literature
Authors: Ibisler Aysegül , Hehr Ute , Barth Andre , Koch Margarete , Epplen Jörg T. , Hoffjan Sabine
Published: October 2015

Acrocallosal syndrome (ACLS) is a rare autosomal recessive disorder characterized by agenesis of the corpus callosum, facial dysmorphism, postaxial polydactyly of the hands as well as preaxial polydactyly of the feet, and developmental delay. Mutations in the KIF7 gene, encoding a molecule within the Sonic hedgehog (SHH) pathway, have been identified as causative for ACLS but also for the fatal hydrolethalus syndrome and some cases of Joubert syndrome. We report here on a Tunisian boy who shows the clinical characteristics of ACLS and was found to have a novel homozygous KIF7 nonsense mutation. Further, we summarize the current knowledge about the clinical spectrum associated with KIF7 mutations as well as genetic and/or phenotypic overlap with ciliopathies and other mutations in the SHH pathway.
Tumor DNA Index and α-Fetoprotein Level Define Outcome following Liver Transplantation for Advanced Hepatocellular Carcinoma
Authors: Andreou Andreas , Bahra Marcus , Guel Safak , Struecker Benjamin , Sauer Igor M. , Klein Fritz , Pascher Andreas , Pratschke Johann , Seehofer Daniel
Published: October 2015

Background: Patients with hepatocellular carcinoma (HCC) beyond the Milan criteria are expected to have inferior outcome after liver transplantation (LT) and are therefore currently not considered for LT in many countries. The purpose of this study was to identify predictive factors for overall survival following LT for HCC that may support the Milan criteria in the selection of appropriate transplant candidates. Methods: Clinicopathological data on 364 patients with HCC who underwent LT between 1989 and 2010 were retrospectively evaluated. Predictors of overall survival in the entire cohort as well as in subsets of patients within (n = 214) and beyond (n = 150) the Milan criteria were analyzed. Results: Multivariate analysis in the entire cohort identified DNA index >1.5 (p < 0.0001), α-fetoprotein level (AFP) >200 ng/ml (p = 0.005), and HCC beyond the Milan criteria (p = 0.002) to be associated with worse overall survival. In patients within the Milan criteria (median survival: 170 months), DNA index >1.5 (p < 0.0001) was the only predictor of worse overall survival in multivariate analysis. In patients beyond the Milan criteria (median survival: 44 months), DNA index >1.5, AFP >200 ng/ml, microvascular invasion, patient age >60 years, and DNA index >1.5 concomitant with AFP >200 ng/ml were associated with worse overall survival in univariate analysis. Multivariate analysis identified DNA index >1.5 concomitant with AFP >200 ng/ml (p < 0.0001) as the only independent predictor of worse overall survival. Consequently, patients beyond the Milan criteria with a combined favorable DNA index ≤1.5 and AFP ≤200 ng/ml had a median survival (147 months) comparable to that of patients within the Milan criteria. Conclusions: DNA index and AFP level predict overall survival following LT in patients with advanced HCC beyond the Milan criteria. A combined assessment of these markers during the evaluation of transplant candidates can contribute to the selection of patients with HCC who may benefit from LT independently of their tumor burden.
Clinical Implication of Serine Metabolism-Associated Enzymes in Colon Cancer
Authors: Yoon Shinkyo , Kim Jong Gwang , Seo An Na , Park Soo Yeun , Kim Hye Jin , Park Jun Seok , Choi Gyu Seog , Jeong Ji Yun , Jun Do Youn , Yoon Ghil Suk , Kang Byung Woog
Published: October 2015

Purpose: Recently, enzymes of the serine synthetic pathway (SSP) have been suggested as key player in the metabolic adaptation of oncogenesis. We assessed the expression of enzymes of the SSP in colonic tumor tissue (TT) and paired normal tissue (pNT) and the prognostic implications. Methods: From 2006 to 2010, we included 486 patients with colon cancer who underwent curative surgery at Kyungpook National University Hospital. Phosphoglycerate dehydrogenase (PHGDH), pyruvate dehydrogenase kinase (PDK) 1, PDK2, pyruvate kinase M2 (PKM2), and phosphoserine aminotransferase (PSAT) expression were investigated by immunohistochemical staining (IHC) in TT and pNT. The IHC values were calculated by multiplying intensity by proportion. The final score was classified as follows: 0-2 as negative and 3-12 as positive. Results: During the median follow-up duration of 55.5 months (37.4-90.6), 78 patients experienced recurrence. The expression of PHGDH, PDK1, and PSAT was significantly higher in TT than pNT (p < 0.001 for each). The univariate analysis for relapse-free survival revealed that TT PDK2 positivity was the only positive prognostic factor (p = 0.023). However, the expression of TT PDK2 did not represent a prognostic value in multivariate analysis. Conclusions: In conclusion, PHGDH, PDK1, and PSAT were significantly increased in colonic TT compared with pNT. The prognostic implication of these enzymes needs to be further investigated.
Periprocedural Risk of Stroke Is Elevated in Patients with End-Stage Renal Disease on Hemodialysis
Authors: Cherian Laurel , Conners James , Cutting Shawna , Lee Vivien H. , Song Sarah
Published: October 2015

Objective: To describe the most common clinical factors and stroke etiologies in a case series of patients with end-stage renal disease on hemodialysis (ESRD/HD) with transient ischemic attack (TIA) or ischemic stroke (IS). Background: Prior studies have shown that patients on HD are at an elevated risk of stroke, but these studies have focused on the overall stroke risk. This case series sought to determine the percentage of acute ischemic events that occur during or immediately after HD. Methods: ICD-9 codes were used to identify IS and TIA patients with ESRD/HD admitted to the stroke service from August 22, 2011, to June 21, 2014. Charts were reviewed to determine the age, sex, and race/ethnicity of the cohort. TIA/IS diagnosis was confirmed by a vascular neurologist. Clinical factors were assessed, including: onset during or shortly after HD, defined as occurring within 12 h of HD; the presence of a lesion on diffusion-weighted MRI; hypotension, hyponatremia, or hypoglycemia at symptom onset; the stroke etiology; the presence of focal neurologic deficits; whether the patient was in the window period for intravenous tissue plasminogen activator (IVtPA) upon presentation, and whether the patient received IVtPA. Results: We identified 34 ESRD/HD patients with a diagnosis of TIA/stroke in the specified time period. A majority of patients (70.6%) were African American. Patient age ranged from 32 to 84 years, with a median age of 67 years. Twenty-seven patients (79.4%) had confirmed ischemic infarcts on diffusion-weighted MRI. Seven patients (20.6%) were diagnosed with TIA. In 13 patients (38.2%), symptom onset occurred during or shortly after HD. Of these 13 patients, 8 (61.5%) had symptom onset during HD. Three patients (8.8%) had documented hypotension near the time of symptom onset, and 2 (5.9%) were hyponatremic on presentation to the emergency department. The distribution of stroke etiologies was as follows: 4 (11.8%) watershed distribution, 1 (2.9%) large artery atherosclerosis, 2 (20.6%) small vessel disease, 10 (29.4%) cardioembolic, and 9 (26.5%) cryptogenic. In 28 patients (82.4%), focal neurologic deficits were observed on presentation. Nine patients (26.5%) arrived within the window period for IVtPA, and 4 (11.8%) were eligible and received IVtPA. Conclusions: Of all patients with ESRD on HD admitted to the stroke service over the study period, over one third (38.3%) had the onset of their ischemic event during or shortly after HD, and nearly one quarter (23.5%) had the onset during HD. While clinicians may be tempted to attribute neurologic changes after HD to metabolic etiologies, they should also be aware that HD represents a period of elevated risk for acute ischemia.
Primary Vitreoretinal Lymphoma Masquerading as Refractory Retinitis
Authors: Zloto Ofira , Abd Elkader Amir E. , Fabian Ido Didi , Vishnevskia-Dai Vicktoria
Published: October 2015

Purpose: To report a case of a patient with primary vitreoretinal lymphoma masquerading as retinitis. Methods: Retrospective review of the patient's clinical, histopathological and imaging records. Results: Cytopathology was negative for malignancy, and preliminary polymerase chain reaction results supported the diagnosis of varicella zoster virus retinitis. Therefore, the patient was treated with antiviral therapy. However, under this treatment, the retinitis progressed. As a result, primary vitreoretinal lymphoma was suspected, and empirical treatment with intravitreal methotrexate injections was started. Under this treatment, the ocular features improved. Five months after initial ocular presentation and ocular resolution, the patient presented with central nervous system lymphoma. Conclusion: This case should raise the awareness of the variable clinical presentations, the challenging diagnosis and treatment of primary vitreoretinal lymphoma. All cases should be continuously systemically evaluated.
Trends in Anemia Management in Hemodialysis Patients with Cancer
Authors: Butler Anne M. , Kshirsagar Abhijit V. , Olshan Andrew F. , Nielsen Matthew E. , Wheeler Stephanie B. , Brookhart M. Alan
Published: October 2015

Background: Erythropoiesis-stimulating agents (ESAs), intravenous iron, and blood transfusion are used to treat anemia in both end-stage renal disease (ESRD) and cancer. However, anemia treatment patterns have not been described among ESRD patients undergoing hemodialysis with concurrent cancer, especially in the recent era of ESA-related safety concerns. Methods: We analyzed Medicare data from a cohort of hemodialysis patients diagnosed with incident cancer. We used multivariable generalized linear models to estimate trends and patterns in ESA use, iron use, transfusion use, epoetin alfa (EPO) dose, iron dose, and resulting hemoglobin levels (2000-2011). Results: Of 43,760 eligible patients, quarterly ESA use declined slightly from a peak of 94.1 to 90.0%. Quarterly EPO dose increased from 2000 to 2004, then declined; quarterly hemoglobin levels followed a similar pattern. Iron use increased rapidly from 46.9 to 79.3%. Iron dose increased until 2010 and then declined. There was an increase in the quarterly transfusion use (6.3-11.7%) and in the mean number of transfusion days per year (1.4-1.8). Anemia treatment patterns varied by demographic/clinical subgroups, especially among patients receiving chemotherapy, who required higher ESA use, EPO dose, and frequency of transfusions. Conclusions: Despite safety concerns about ESAs in both the ESRD and cancer populations, the proportion of hemodialysis patients with cancer who used ESAs between 2000 and 2011 remained extremely high. EPO dose and hemoglobin levels increased and then decreased. Iron use, iron dose, and transfusions increased substantially. Future research examining the risk-benefit profile of different anemia management strategies in the dialysis population with cancer is needed.
Muscle Strength, Function and Heart Autonomic Regulation System Recovery at the Sub-Acute Stage Post Stroke
Authors: Shapira-Vadler Orit , Treger Iuly , Katz-Leurer Michal
Published: October 2015

Background: To compare the rate of recovery of motor and functional ability and heart rate variability (HRV) parameters during the inpatient rehabilitation period. Summary: Twenty-three patients post first stroke at the sub-acute phase underwent motor and functional ability and HRV assessments 20 and 50 days after the event. A significant improvement was noted in motor and functional ability performance during the follow-up period, while no such change was noted in the HRV parameters. Key Messages: Patients post first-ever stroke exhibited a significant motor and functional improvement during the sub-acute phase post stroke, while no change was noted in their HRV parameters, which may imply that no significant changes in the sympatho-vagal balance took place during this period.