bluuebunny/crossref_metadata_2025 huggingface dataset:
Brain volume and white matter in youth with type 2 diabetes compared to obese and normal weight, non‐diabetic peers: A pilot study
Authors: Rofey Dana L. , Arslanian Silva A. , El Nokali Nermeen E. , Verstynen Timothy , Watt Jennifer C. , Black Jessica J. , Sax Rebecca , Krall Jodi S. , Proulx Chelsea , Dillon Meredith , Erickson Kirk I.
Published: August 2015

Type 2 Diabetes Mellitus (T2DM) and obesity are linked to specific patterns of subcortical brain atrophy and decreased microstructural integrity of white matter. Fifteen adolescents (12–21‐years‐old, 80% Caucasian, 15% African American, mean BMI = 32)–five with T2DM confirmed by oral glucose tolerance test, five matched obese adolescent controls without diabetes (OBCN), and five matched (race, sex) normal‐weight controls (NWCN)–underwent Magnetic Resonance Imaging (MRI) for the collection of gray matter volume and white matter integrity. Analyses of Variance (ANOVAs) of the neuroimaging data revealed significant differences in caudate nucleus volume [F(2,12) = 7.79, p < 0.05] such that the normal‐weight group had significantly greater volume than the obese and T2DM groups (NWCN>OBCN, p = 0.020; OBCN > T2DM, p = 0.042; and NWCN > T2DM; p = 0.003) after controlling for participant Body Mass Index (BMI). Similarly, there was a main effect for the volume of the thalamus [F(2,12) = 4.39, p < 0.05] with greater volume for both the NWC and the OBC groups in comparison to the T2DM group (NWC > T2DM, p = 0.020; OBC > T2DM; p = 0.040). Finally, an examination of white matter integrity among the three groups illustrated a pattern of white matter integrity reduction between normal‐weight participants and both obese controls and T2DM participants, with T2DM demonstrating the greatest deficit in functional anisotropy (FA) volume, but these results were not significant after further controlling for BMI. Results from the current pilot study illuminate a host of brain morphology differences between youth with T2DM, obese youth, and normal‐weight controls; future research with a larger sample size is critical.
Phase 3 solanezumab trials: Secondary outcomes in mild Alzheimer's disease patients
Authors: Siemers Eric R. , Sundell Karen L. , Carlson Christopher , Case Michael , Sethuraman Gopalan , Liu‐Seifert Hong , Dowsett Sherie A. , Pontecorvo Michael J. , Dean Robert A. , Demattos Ronald
Published: August 2015

Introduction

EXPEDITION and EXPEDITION2 were identically designed placebo‐controlled phase 3 studies assessing effects of solanezumab, an antiamyloid monoclonal antibody binding soluble amyloid‐β peptide, on cognitive and functional decline over 80 weeks in patients with mild‐to‐moderate Alzheimer's disease (AD). Primary findings for both studies have been published.

Methods

Secondary analyses of efficacy, biomarker, and safety endpoints in the pooled (EXPEDTION + EXPEDITION2) mild AD population were performed.

Results

In the mild AD population, less cognitive and functional decline was observed with solanezumab (n = 659) versus placebo (n = 663), measured by Alzheimer's Disease Assessment Scale Cognitive subscale, Mini‐Mental State Examination, and Alzheimer's Disease Cooperative Study–Activities of Daily Living functional scale Instrumental ADLs. Baseline‐to‐endpoint changes did not differ between treatment groups for Alzheimer's Disease Cooperative Study–Activities of Daily Living functional scale, basic items of the ADCS‐ADL, and Clinical Dementia Rating Sum of Boxes. Plasma/cerebrospinal fluid biomarker findings indicated target engagement by solanezumab. Solanezumab demonstrated acceptable safety. Efficacy findings for the moderate AD population are also provided.

Discussion

These findings describe solanezumab effects on efficacy/safety measures in a mild AD population. Another phase 3 study, EXPEDITION3, will investigate solanezumab's effects in a mild AD population.
Execution quality: An analysis of fulfillment errors at a retail distribution center
Authors: Craig Nathan , DeHoratius Nicole , Jiang Yan , Klabjan Diego
Published: August 2015

Purchase orders specify many aspects of a fulfillment process, including item quantity, delivery time, carton labeling, bar coding, electronic data interchange, retail ticketing, and others. These fulfillment terms are instrumental for highly optimized retail supply chains employing automation and techniques such as pack‐by‐store. When fulfilling a purchase order, a supplier may commit a fulfillment error, i.e., the supplier may fail to adhere to the terms specified by the retailer. The retailer may then penalize the supplier for the fulfillment error via a chargeback deduction, which reduces the supplier's revenue. We present a study of the fulfillment errors and chargebacks that occur in practice using data collected from a major retailer's distribution center. While fulfillment errors involving incorrect product quantities and delivery times have received the most attention in the literature, we find that the majority of fulfillment errors in the context we study involve documentation, bar coding, and retail ticketing. We refer to these as correctable fulfillment errors, since they are amended at the retailer's distribution center through rework. We develop a model of inventory management with correctable fulfillment errors and use the retailer's data to assess the cost of these correctable fulfillment errors to the retailer's inventory system. Our research provides guidance to managers in identifying products and suppliers that impose large fulfillment error costs as well as in setting appropriate chargebacks for fulfillment errors.
El reconocimiento de conceptos básico-clínicos bajo la terminología anatómica internacional hacia la formación médica
Authors: Parra Gámez Leticia , Ibarra Ramírez Víctor Hugo , González Ríos Jacquelina , García Hidalgo A. Alejandro
Published: August 2015

Introducción: La importancia del conocimiento y dominio de la anatomía en la formación del estudiante de medicina se inicia desde el primer año de la carrera de médico cirujano, por lo que el fomentar el uso de la terminología anatómica internacional (TAI) en el aprendizaje de dicha asignatura coadyuva a la integración de conocimientos que garantizan al estudiante el satisfactorio cumplimiento de las tareas y responsabilidades de su ejercicio profesional (competencias profesionales) aunado al reforzamiento de su uso y aplicación a lo largo de los ciclos clínicos. Objetivo: Mostrar el reconocimiento de conceptos médicos básico-clínicos en TAI en dos diferentes años de la formación del estudiante de medicina. Método: Se elaboró un instrumento a manera de cuestionario que demandó la asociación de conocimientos básicos de anatomía en función del reconocimiento con la TAI que se comparó en dos poblaciones de estudiantes de medicina (primer año y alumnos de ciclos clínicos). Resultados: Encontramos que en ambos grupos existe un mejor reconocimiento con epónimos. Asimismo, existe mayor frecuencia de aciertos en el grupo de alumnos de ciclos clínicos que de los alumnos de primer año así como un mejor valor de evaluación en el cuestionario. Conclusiones: El conocimiento de la anatomía en los estudiantes de medicina no se obtiene bajo los propósitos de la TAI debido a que existe mayor reconocimiento de conceptos médicos básico-clínicos de anatomía que utilizan epónimos, lo que resulta antagónico con el propósito fundamental del programa de estudios. Consideramos que el conocimiento anatómico debe facilitar la integración del conocimiento médico universal mediante el manejo y aplicación de un lenguaje anatómico internacional coherente tanto con el contexto actual del plan de estudios como con el perfil del egresado.
Alcances de una estrategia educativa participativa en el desarrollo de aptitud clínica en Geriatría
Authors: Díaz-Torres Yaneth , García-Chávez Erika , Oseguera-Rodríguez Jorge Francisco , Figueroa-García Raúl
Published: August 2015

Introducción: Las prácticas educativas tradicionales privilegian la función del profesor y la actitud receptiva  del alumno (enfoque pasivo). De manera diferente, para la corriente educativa participativa, el centro del  quehacer educativo es el aprendizaje, el protagonista es el alumno, y la labor docente debe estar  encaminada a lograr en él una educación de tipo autónomo. El objetivo de este trabajo fue estimar los  alcances de una estrategia educativa participativa para desarrollar la aptitud clínica en Geriatría en médicos  familiares.
Método: Para ello, se realizó un diseño longitudinal, prospectivo, para el cual se construyó un instrumento de evaluación en el que se incluyeron: 5 casos clínicos de importancia en Geriatría con 153 ítems que exploran 6 diferentes temas: 1) valoración geriátrica integral; 2) identificación de síndromes geriátricos; 3) integración de diagnósticos; 4) uso de recursos diagnósticos; 5) adecuación del tratamiento, y 6) medidas de geroprofilaxis. El instrumento fue validado por 2 rondas de expertos, que estimaron en un 0.95 la confiabilidad interna mediante la fórmula de Kuder-Richardson. Se incluyeron 10 médicos familiares con quienes se realizó una estrategia educativa participativa con tendencia hacia el aprendizaje autónomo, durante 60 h efectivas; la evaluación se aplicó al inicio y al final de la estrategia.
Resultados: La mediana de la puntuación obtenida por los alumnos al inicio de la estrategia fue de 56 (21-82), mientras que la mediana al final de la estrategia fue de 72 (29-100). La prueba de Wilcoxon para comparar las puntuaciones antes y después de la estrategia dio una p = 0.015.
Conclusiones: Por lo tanto, la estrategia educativa participativa es eficaz en el desarrollo de la aptitud clínica en la atención del paciente geriátrico.
Construcción de un instrumento para evaluar competencias profesionales durante la formación preclínica en Medicina
Authors: Córdova Alfredo , Moreno Julia , Stegaru Mihaela , Staff Carlos
Published: August 2015

Introducción: Los graduados universitarios buscan adquirir competencias necesarias para resolver problemas específicos a los que se enfrentan en el trabajo diario asistencial médico. También buscan tener el potencial para cambiar y adaptar su actuación y organización de manera que esta satisfaga mejor los retos y oportunidades que se les presentan. Puede que las competencias requeridas para estos desarrollos científicos a largo plazo (como profesionales) sean muy diferentes a las requeridas para desarrollos a corto plazo (como estudiantes).
Objetivo: Este estudio propone una encuesta realizada en universidades de Panamá para la carrera de Medicina. Se utilizó un muestreo probabilístico y estratificado en todas sus etapas. El objetivo de la encuesta fue conocer la opinión de los estudiantes de la carrera de Medicina respecto a asignaturas preclínicas y sobre las competencias que deben promoverse mediante la enseñanza de las mismas.
Método: Creemos que la encuesta propuesta es un instrumento adecuado para conocer cómo se desarrolla el proceso de la enseñanza por competencias. Ello ayudará a mejorar la calidad de la docencia.Resultados: La encuesta tiene varias fortalezas: a) poco onerosa y de aplicación fácil; b) naturaleza impersonal; c) el anonimato de la misma, junto con la ausencia de los docentes implicados en la asignatura evaluada, garantiza la libertad de respuesta, y d) no está ajustada a realizar en un tiempo determinado, lo que facilita las respuestas del estudiante.
Conclusión: Facilita el conocimiento del proceso de enseñanza-aprendizaje de los estudiantes de Medicina.
Desarrollo e implementación de un curso de investigación para estudiantes de ciencias de la salud: una propuesta para estimular la producción científica
Authors: Chávez Caraza Karla Lorena , Rodríguez de Ita Julieta , Lozano Ramírez Juan Francisco , Vargas Duarte Gabriel Martín , Lozano Lee Francisco Gerardo
Published: August 2015

Introducción: En México, la producción de artículos científicos en medicina es baja. Además la experiencia en investigación es limitada durante los primeros años de la carrera de medicina. De esto surge la necesidad de formar investigadores desde etapas tempranas dentro de su preparación profesional.
Método: Se instituyó un curso de investigación teórico-práctico durante el verano académico (6 semanas) en 3 ocasiones. Participaron un total de 38 alumnos (11 en 2012, 16 en 2013 y 11 en 2014). El objetivo fue proporcionar los conocimientos teóricos y prácticos para elaborar y desarrollar un proyecto de investigación hasta llevarlo a su publicación. El curso consistió en dar soporte teórico con clases presenciales y en línea donde el alumno aprendió los fundamentos en investigación y cómo diseñar un protocolo aplicando el pensamiento crítico. Simultáneamente, mediante tutoreo estrecho, se guió a los equipos de trabajo sobre cómo desarrollar el protocolo diseñado y su implementación en el trabajo de campo, la interpretación de resultados hasta la redacción del artículo científico. 
Resultados: Se produjeron 8 trabajos de investigación dentro del área clínica. Todos los trabajos han sido presentados en congresos, otros están en proceso de envío a revistas para su publicación y uno ha sido publicado.
Conclusiones: Con este curso sembramos en el alumno el interés por la investigación para que sea capaz de desarrollar sus propios proyectos en el futuro. Por lo que este curso puede implementarse en otras carreras con el fin de crear más investigadores e incrementar la producción científica en México.
La libertad de cátedra: ¿una libertad malentendida?
Authors: Aguilar-Tamayo Raúl , Sánchez-Mendiola Melchor , Fortoul van der Goes Teresa I.
Published: August 2015

El concepto de «libertad de cátedra» existe desde hace varias décadas, y en tiempos recientes ha habido controversia por el uso que en ocasiones se hace del mismo. El presente ensayo pretende revisar aspectos de la libertad de cátedra en educación superior, utilizando algunas definiciones y la normatividad que existe al respecto en México y en la Universidad Nacional Autónoma de México. Lo anterior con la finalidad de propiciar la reflexión y el debate sobre la vigencia de la libertad de cátedra en educación en ciencias de la salud, y sus implicaciones educativas.
Ética y profesionalismo en un mundo cambiante
Authors: Worthington Roger P.
Published: August 2015

La medicina se encuentra en un estado constante de cambio, y lo mismo podría decirse de la organización y la prestación de servicios de salud, lo que puede dar lugar a obligaciones contradictorias en cuanto a la ética, el profesionalismo y las normas a las que los clínicos generalmente se enfrentan. La complejidad aumenta si hay confusión en cuanto a lo que comprenden estos 2 dominios, y si bien hay mucha literatura sobre la ética y el profesionalismo en la medicina, menos se ha escrito acerca de la relación entre ellos. Un observador lego podría ser perdonado por tener poco conocimiento sobre dónde termina uno y empieza el otro; también es posible que pocos profesionales hayan reflexionado específicamente sobre estos temas, y no solo puede ayudar en el caso de los educadores (cuya tarea es diseñar, implementar y evaluar los programas y planes de estudios) para tener mayor claridad sobre estos temas, sino que potencialmente podría también beneficiar a los pacientes.
La ética y el profesionalismo no son lo mismo, a pesar de que tienen una conexión íntima, y si la ética y el profesionalismo se convertirán en parte del ADN de la práctica de los médicos, debe ser claro para todos los dominios que comprenden y lo que significa la terminología. Esto podría hacer una diferencia en cómo los médicos se comportan el uno hacia el otro, y más importante aún, para con sus pacientes; las actitudes definen el comportamiento, el comportamiento influye la forma en que se dan los episodios individuales de atención, así que esto es mucho más que simplemente una cuestión de semántica.
¿Dicotomía artificial en la formación científica y emocional? Réplica
Authors: Sánchez-Mendiola Melchor
Published: August 2015

Muchas gracias por su carta y el interés en el material publicado en la revista.
¿Dicotomía artificial en la formación científica y emocional?
Authors: Lemus Alcántara Sergio
Published: August 2015

Tenemos el beneficio de recibir la revista Investigación en Educación Médica, en la cual encontramos tópicos de suma importancia para la necesaria reflexión y análisis sobre los procesos formativos de médicos de pregrado y posgrado.
Comet Lander Makes a Hard Discovery
Authors: Wendel JoAnna
Published: August 2015

The Philae probe, dropped onto a comet by the Rosetta spacecraft, has made contact with a surface thought too hard to be on a comet and has detected a few organic molecules new to comet exploration.
Unliganded EphA3 dimerization promoted by the SAM domain
Authors: Singh Deo R. , Cao QingQing , King Christopher , Salotto Matt , Ahmed Fozia , Zhou Xiang Yang , Pasquale Elena B. , Hristova Kalina
Published: August 2015

The erythropoietin-producing hepatocellular carcinoma A3 (EphA3) receptor tyrosine kinase (RTK) regulates morphogenesis during development and is overexpressed and mutated in a variety of cancers. EphA3 activation is believed to follow a ‘seeding mechanism’ model, in which ligand binding to the monomeric receptor acts as a trigger for signal-productive receptor clustering. We study EphA3 lateral interactions on the surface of live cells and we demonstrate that EphA3 forms dimers in the absence of ligand binding. We further show that these dimers are stabilized by interactions involving the EphA3 sterile α-motif (SAM) domain. The discovery of unliganded EphA3 dimers challenges the current understanding of the chain of EphA3 activation events and suggests that EphA3 may follow the ‘pre-formed dimer’ model of activation known to be relevant for other receptor tyrosine kinases. The present work also establishes a new role for the SAM domain in promoting Eph receptor lateral interactions and signalling on the cell surface.
Microscopic bubbles sap seismic waves’ strength
Authors: Smart Ashley G.
Published: August 2015

The effect, long theorized but only now observed, suggests that gas-rich subterranean reservoirs might reveal themselves in the echoes of earthquakes.
Comets born of cosmic splats
Authors: Chang Sung
Published: August 2015

Simulations reveal how some cometary nuclei got their shapes and structures.
A femtosecond laser pulse makes molecular bonds
Authors: Wilson R. Mark
Published: August 2015

The shape of the pulse determines the quantum state and stability of the newly formed molecules.
Physics is a casualty of Ukrainian turmoil
Authors: Kramer David
Published: August 2015

Help is needed for physicists and students who were uprooted from rebel-controlled eastern Ukraine. But the particulars are just being fleshed out.
A beachhead on the island of stability
Authors: Oganessian Yuri Ts. , Rykaczewski Krzysztof P.
Published: August 2015

Recent experiments to synthesize the heaviest elements have dramatically expanded the periodic table and the Segrè chart of nuclides.
Single-molecule sensing with nanopores
Authors: Muthukumar Murugappan , Plesa Calin , Dekker Cees
Published: August 2015

A 70-year-old idea for measuring blood cells has evolved into a powerful, versatile tool for studying DNA, proteins, and other biomolecules.
The new wave of pilot-wave theory
Authors: Bush John W. M.
Published: August 2015

Small drops bouncing across a vibrating liquid bath display many features reminiscent of quantum systems.
Mesmerizing magnetic fields
Authors: Martin James E. , Solis Kyle J.
Published: August 2015

The behavior displayed by a suspension of magnetic particles exposed to a rapidly varying multiaxial magnetic field is both dazzling and practically applicable.
Repeatability of Central and Peripheral Pulse Wave Velocity Measures: The Atherosclerosis Risk in Communities (ARIC) Study
Authors: Meyer Michelle L. , Tanaka Hirofumi , Palta Priya , Patel Mehul D. , Camplain Ricky , Couper David , Cheng Susan , Al Qunaibet Ada , Poon Anna K. , Heiss Gerardo
Published: August 2015

BACKGROUND

Arterial stiffness measures are emerging tools for risk assessment and stratification for hypertension and cardiovascular disease (CVD). Carotid-femoral pulse wave velocity (cfPWV) is an established measure of central arterial stiffness. Other measures of PWV include femoral-ankle (faPWV), a measure of peripheral stiffness, and brachial-ankle PWV (baPWV), a composite measure of central and peripheral stiffness. Repeatability of central, peripheral, and composite PWV measures has not been adequately examined or compared.

METHODS

Participants ( n = 79; mean age 75.7 years; USA) from a repeatability study nested within the Atherosclerosis Risk in Communities (ARIC) Study visit 5 (2011–2013) underwent 2 standardized visits, 4–8 weeks apart. Trained technicians obtained 2 PWV measurements at each visit using the VP-1000 Plus system. We calculated the intraclass correlation coefficient (ICC), SE of measurement, and minimal detectable change (MDC 95 ; 95% confidence interval) and difference (MDD).

RESULTS

The ICCs and 95% confidence intervals (95% CIs) were 0.70 (0.59, 0.81) for cfPWV, 0.84 (0.78, 0.90) for baPWV, and 0.69 (0.59, 0.79) for faPWV. The MDC 95 between repeat measures within an individual was 411.0cm/s for cfPWV, 370.6cm/s for baPWV, and 301.4cm/s for faPWV. The MDD for 2 independent samples of 100 per group was 139.3cm/s for cfPWV, 172.3cm/s for baPWV, and 100.4cm/s for faPWV.

CONCLUSIONS

Repeatability was acceptable for all PWV measures in a multicenter, population-based study of older adults and supports its use in epidemiologic studies. Quantifying PWV measurement variation is critical for applications to risk assessment and stratification and eventual translation to clinical practice.
HHalign-Kbest: exploring sub-optimal alignments for remote homology comparative modeling
Authors: Yu Jinchao , Picord Geraldine , Tuffery Pierre , Guerois Raphael
Published: August 2015

Motivation: The HHsearch algorithm, implementing a hidden Markov model (HMM)-HMM alignment method, has shown excellent alignment performance in the so-called twilight zone (target-template sequence identity with ∼20%). However, an optimal alignment by HHsearch may contain small to large errors, leading to poor structure prediction if these errors are located in important structural elements.

Results: HHalign-Kbest server runs a full pipeline, from the generation of suboptimal HMM-HMM alignments to the evaluation of the best structural models. In the HHsearch framework, it implements a novel algorithm capable of generating k-best HMM-HMM suboptimal alignments rather than only the optimal one. For large proteins, a directed acyclic graph-based implementation reduces drastically the memory usage. Improved alignments were systematically generated among the top k suboptimal alignments. To recognize them, corresponding structural models were systematically generated and evaluated with Qmean score. The method was benchmarked over 420 targets from the SCOP30 database. In the range of HHsearch probability of 20–99%, average quality of the models (TM-score) raised by 4.1–16.3% and 8.0–21.0% considering the top 1 and top 10 best models, respectively.

Availability and implementation:  http://bioserv.rpbs.univ-paris-diderot.fr/services/HHalign-Kbest/ (source code and server).

Contact:  guerois@cea.fr

Supplementary information: Supplementary data are available at Bioinformatics online.
An efficient algorithm for the extraction of HGVS variant descriptions from sequences
Authors: Vis Jonathan K. , Vermaat Martijn , Taschner Peter E. M. , Kok Joost N. , Laros Jeroen F. J.
Published: August 2015

Motivation: Unambiguous sequence variant descriptions are important in reporting the outcome of clinical diagnostic DNA tests. The standard nomenclature of the Human Genome Variation Society (HGVS) describes the observed variant sequence relative to a given reference sequence. We propose an efficient algorithm for the extraction of HGVS descriptions from two sequences with three main requirements in mind: minimizing the length of the resulting descriptions, minimizing the computation time and keeping the unambiguous descriptions biologically meaningful.

Results: Our algorithm is able to compute the HGVS descriptions of complete chromosomes or other large DNA strings in a reasonable amount of computation time and its resulting descriptions are relatively small. Additional applications include updating of gene variant database contents and reference sequence liftovers.

Availability: The algorithm is accessible as an experimental service in the Mutalyzer program suite (https://mutalyzer.nl). The C++ source code and Python interface are accessible at: https://github.com/mutalyzer/description-extractor.

Contact:  j.k.vis@lumc.nl
MICC: an R package for identifying chromatin interactions from ChIA-PET data
Authors: He Chao , Zhang Michael Q. , Wang Xiaowo
Published: August 2015

Summary: ChIA-PET is rapidly emerging as an important experimental approach to detect chromatin long-range interactions at high resolution. Here, we present Model based Interaction Calling from ChIA-PET data (MICC), an easy-to-use R package to detect chromatin interactions from ChIA-PET sequencing data. By applying a Bayesian mixture model to systematically remove random ligation and random collision noise, MICC could identify chromatin interactions with a significantly higher sensitivity than existing methods at the same false discovery rate.

Availability and implementation:  http://bioinfo.au.tsinghua.edu.cn/member/xwwang/MICCusage

Contact:  michael.zhang@utdallas.edu or xwwang@tsinghua.edu.cn

Supplementary information:  Supplementary data are available at Bioinformatics online.
stringgaussnet: from differentially expressed genes to semantic and Gaussian networks generation
Authors: Chaplais Emmanuel , Garchon Henri-Jean
Published: August 2015

Motivation: Knowledge-based and co-expression networks are two kinds of gene networks that can be currently implemented by sophisticated but distinct tools. We developed stringgaussnet, an R package that integrates both approaches, starting from a list of differentially expressed genes.

Contact:  henri-jean.garchon@inserm.fr

Availability and implementation: Freely available on the web at http://cran.r-project.org/web/packages/stringgaussnet.
MEPSA: minimum energy pathway analysis for energy landscapes
Authors: Marcos-Alcalde Iñigo , Setoain Javier , Mendieta-Moreno Jesús I. , Mendieta Jesús , Gómez-Puertas Paulino
Published: August 2015

Summary: From conformational studies to atomistic descriptions of enzymatic reactions, potential and free energy landscapes can be used to describe biomolecular systems in detail. However, extracting the relevant data of complex 3D energy surfaces can sometimes be laborious. In this article, we present MEPSA (Minimum Energy Path Surface Analysis), a cross-platform user friendly tool for the analysis of energy landscapes from a transition state theory perspective. Some of its most relevant features are: identification of all the barriers and minima of the landscape at once, description of maxima edge profiles, detection of the lowest energy path connecting two minima and generation of transition state theory diagrams along these paths. In addition to a built-in plotting system, MEPSA can save most of the generated data into easily parseable text files, allowing more versatile uses of MEPSA’s output such as the generation of molecular dynamics restraints from a calculated path.

Availability and implementation: MEPSA is freely available (under GPLv3 license) at: http://bioweb.cbm.uam.es/software/MEPSA/

Contact: pagomez@cbm.csic.es

Supplementary information:  Supplementary data are available at Bioinformatics online.
Climbing back up what slippery slope? Dynamics of the European eel stock and its management in historical perspective
Authors: Dekker Willem , Beaulaton Laurent
Published: August 2015

Few fish stocks are as influenced by (intentional and inadvertent) human impacts as the European eel, all across the continent. The dynamics of this stock, however, are poorly understood—neither the causes of the historically low abundance, nor minimal protection levels, are beyond discussion. Rather than analysing contemporary processes, this article turns back in time—two centuries or more—unravelling historical abundances and distribution patterns; reviewing historical actions and objectives; and discussing technical developments and scientific advice—picturing the slippery slope the eel stock has come down from. The first claim, that the continental stock was in decline, dates from the early 1800s; stock-enhancement actions were initiated shortly after. Diffuse objectives, technical innovations, eternal optimism, and—above all—no quantification impede the exact evaluation of historical reports. After 1950, when quantification improved, a slow but consistent decline was observed, but it is only two decades after the crash in glass eel recruitment (in 1980), that protection plans addressed the bad status of the stock. A slippery slope, full of pitfalls—yet, we now observe several years of increasing recruitment.
Normalizing clinical terms using learned edit distance patterns
Authors: Kate Rohit J
Published: August 2015

Background Variations of clinical terms are very commonly encountered in clinical texts. Normalization methods that use similarity measures or hand-coded approximation rules for matching clinical terms to standard terminologies have limited accuracy and coverage.

Materials and Methods In this paper, a novel method is presented that automatically learns patterns of variations of clinical terms from known variations from a resource such as the Unified Medical Language System (UMLS). The patterns are first learned by computing edit distances between the known variations, which are then appropriately generalized for normalizing previously unseen terms. The method was applied and evaluated on the disease and disorder mention normalization task using the dataset of SemEval 2014 and compared with the normalization ability of the MetaMap system and a method based on cosine similarity.

Results Excluding the mentions that already exactly match in UMLS and the training dataset, the proposed method obtained 64.7% accuracy on the rest of the test dataset. The accuracy was calculated as the number of mentions that correctly matched the gold-standard concept unique identifiers (CUIs) or correctly matched to be without a CUI. In comparison, MetaMap’s accuracy was 41.9% and cosine similarity’s accuracy was 44.6%. When only the output CUIs were evaluated, the proposed method obtained 54.4% best F -measure (at 92.1% precision and 38.6% recall) while MetaMap obtained 19.4% best F -measure (at 38.0% precision and 13.0% recall) and cosine similarity obtained 38.1% best F -measure (at 70.3% precision and 26.1% recall).

Conclusions The novel method was found to perform much better than the MetaMap system and the cosine similarity based method in normalizing disease mentions in clinical text that did not exactly match in UMLS. The method is also general and can be used for normalizing clinical terms of other semantic types as well.
Wrong to be Right
Authors: Kang Jung J. , Reiter Robert E. , Kummer Nicolas , DeKernion Jean , Steinberg Michael L. , King Christopher R.
Published: August 2015

Objectives:

To examine the impact of positive surgical margin (PSM) laterality on failure after radical prostatectomy (RP). A PSM can influence local recurrence and outcomes after salvage radiation. Unlike intrinsic risk factors, a PSM is caused by intervention and thus iatrogenic failures may be elucidated by analyzing margin laterality as surgical approach is itself lateralized.

Patients and Methods:

We reviewed 226 RP patients between 1991 and 2013 with PSM. Data includes operation type, pre/postoperative PSA, surgical pathology, and margin type (location, focality, laterality). The median follow-up was 47 months. Biochemical recurrence after RP was defined as PSA≥0.1 ng/mL or 2 consecutive rises above nadir. Ninety-two patients received salvage radiation therapy (SRT). Failure after SRT was defined as any PSA≥0.2 ng/mL or greater than presalvage. Kaplan-Meier and Cox multivariate analyses compared relapse rates.

Results:

The majority of PSM were iatrogenic (58%). Laterality was associated with differences in median relapse: right 20 versus left 51 versus bilateral 14 months (P<0.01). Preoperative PSA, T-stage, Gleason grade, and laterality were associated with biochemical progression on univariate and multivariate analyses. Right-sided margins were more likely to progress than left (hazard ratio, 1.67; P=0.04). More right-sided margins were referred for SRT (55% right vs. 23% left vs. 22% bilateral), but were equally salvaged. Only T-stage and pre-SRT PSA independently influenced SRT success.

Conclusions:

Most PSM are iatrogenic, with right-sided more likely to progress (and sooner) than left sided. Margin laterality is a heretofore unrecognized independent predictor of biochemical relapse and hints at the need to modify the traditional unilateral surgical technique.
Predicting the Surgical Margin of Resection in Periocular Cutaneous Neoplasms and the Significance of Reconstruction Following Mohs Micrographic Surgery
Authors: Sines Daniel T. , Polomsky Matej , Dutton Jonathan J.
Published: August 2015

Purpose:

To evaluate the features of periocular cutaneous malignancies that may contribute to larger surgical defects or require more complex reconstructive procedures.

Methods:

A retrospective review of 181 patients with biopsy proven periocular cutaneous malignancies seen between April 2005 and September 2010, and undergoing Mohs micrographic surgery was performed. The longest horizontal and vertical diameters of the tumor and the post-Mohs surgical defect were measured in each patient. These measurements were used to calculate the relative margin of resection (MOR) required for tumor eradication as well as the size of the surgical defect. The date of surgery, histologic diagnosis and location of the tumor, type of reconstruction, and the presence of recurrence were also recorded.

Results:

The average MOR for all tumor subtypes taken together was 3.4 mm horizontally and 2.6 mm vertically for basal cell carcinomas (BCCA). The post-Mohs defect area was 3.2 times greater than the preoperative tumor area for all BCCA subtypes, and 3.9 times greater for morphea type (p = 0.8083). The average MOR for squamous cell carcinomas (SCCA) was 5.1 mm horizontally and 3.7 mm vertically. The post-Mohs defect area was 3.8 times greater than the preoperative tumor area for SCCAs. When comparing the preoperative horizontal tumor diameter to the horizontal MOR of BCCAs and SCCAs, the correlation was 0.23 (p < 0.0001) and 0.31 (p < 0.0001), respectively. While the average MOR was within standard limits, a significant number of tumors required a greater MOR. On review of the data, 30.6% of patients with BCCA required a MOR greater than 3 mm, 17.3% of patients with BCCA required a MOR greater than 4 mm, and 29.1% of patients with SCCA required a MOR of greater than 5 mm. Tumors located at the lateral canthus required the largest MOR (p < 0.01), while those on the lower eyelid were associated with the smallest MOR in BCCAs. As expected from anatomical considerations, tumors at the medial canthus required significantly more complex reconstruction procedures (p < 0.01). An ordered logistic regression model demonstrated that BCCA preoperative clinical tumor surface area was a significant indicator for the degree of reconstruction required (p < 0.01).

Conclusions:

Standard 3 mm to 4 mm MOR for BCCAs, and 5 mm MOR for SCCAs could result in an unacceptable risk of tumor recurrence if the surgical margins are not examined histologically. With increasing preoperative tumor size, there is an increase in the MOR required for BCCA and SCCA, supporting that large tumors require a greater MOR.
Histopathologic Clues in Diagnosing Oral Mucosal Grafts to the Conjunctiva
Authors: Jakobiec Frederick A. , Stagner Anna M. , Raizman Michael B. , Hatton Mark P.
Published: August 2015

Excised redundant, forniceal “conjunctival” tissue from a 67-year-old man who experienced a chemical injury to his OS 25 years earlier was evaluated histopathologically with the hematoxylin-eosin, periodic acid Schiff (PAS) with and without diastase, mucicarmine, and Alcian blue methods. Additional immunoperoxidase testing for gross cystic disease fluid protein-15 (GCDFP-15) was undertaken. Non-keratinizing squamous epithelium composed of 8 to 10 layers of swollen keratinocytes without goblet cells surmounted a variably dense and well-vascularized collagenized lamina propria deep to which, in submucosal fibroadipose tissue, was embedded an accessory gland. The acini of the gland were composed of both GCDFP-15-positive serous cells and mucicarmine-positive goblet cells, indicating they were seromucinous rather than entirely serous, as is characteristic of normal lacrimal glandular tissue. Different features of the surface epithelium, the lamina propria, and the submucosa can separate the conjunctival and oral mucous membranes. A close analysis of the cytologic composition of associated accessory glands can reinforce the correct diagnosis of an oral mucous membrane graft when the past surgical history is unclear, because only serous cells but not mucocytes comprise the lacrimal glandular units.
Prostaglandin Eyedrops Are Associated With Decreased Thicknesses of Eyelid Dermis and Orbicularis Oculi Muscle: Ultrasonographic Findings
Authors: Goh Alice S. , Nassiri Nariman , Kohn Jocelyne C. , Rootman Daniel B. , Giaconi JoAnn , Law Simon K. , Coleman Anne L. , Caprioli Joseph , Goldberg Robert A.
Published: August 2015

Purpose:

To investigate the effect of prostaglandin analog eyedrops on the periorbital soft tissue using high-resolution ultrasonography.

Methods:

In this cross-sectional study, the authors included patients with bilateral glaucoma on unilateral prostaglandin therapy for the past 12 or more contiguous months. High-resolution ultrasonography was performed bilaterally on the upper and lower eyelids of each subject to measure thicknesses of dermis, orbicularis oculi muscle, and skin to arcus marginalis distance. Comparisons were made between eyes on prostaglandin eyedrops versus those not on prostaglandin analogs.

Results:

Twenty patients (16 females, 4 males) with a mean age of 67.2 ± 6.4 years were recruited. The mean duration of prostaglandin analog therapy was 5.4 ± 3.9 years. The authors found that eyes on prostaglandin analog therapy had statistically significantly reduced thicknesses of dermis, orbicularis oculi muscle, and skin to arcus marginalis distance in the upper and lower eyelids compared with the fellow eyes (p < 0.05 for all). In univariate regression analysis, the amount of changes in thicknesses of dermis, orbicularis oculi muscle, and skin to arcus marginalis distance among eyes on prostaglandin analog therapy and the fellow eyes was not statistically significantly associated with different variables including age, gender, years of being on prostaglandin analog therapy, type of prostaglandin analog, history of glaucoma and/or cataract surgeries, intraocular pressure, and number of glaucoma medications.

Conclusions:

The findings indicate that eyes on prostaglandin analog therapy have reduced thicknesses of dermis, orbicularis oculi muscle, and skin to arcus marginalis distance compared with the fellow eyes.
A Review of Eyelid Margin Malpositions: A Unique Spectrum in a South-East Asian Tertiary Hospital
Authors: Tan Benjamin Boon Chuan , Mansurali Vanessa Naseem , Sundar Gangadhara , Amrith Shantha
Published: August 2015

Purpose:

Due to the anatomical differences between the Asian and non-Asian eyelid, the authors hypothesize a different spectrum of eyelid margin malposition conditions seen in Singapore as compared with a predominant Caucasian population. The purpose of the study is to describe the spectrum of eyelid margin malpositions that were operated in a South-East Asian Tertiary Hospital.

Methods:

Retrospective study involving all patients who required surgery for eyelid margin malpositions over a 2-year period. The etiology and ethnic spread of patients were analyzed for each eyelid margin malposition.

Results:

A total of 249 eyelids (144 patients) were analyzed. There were 127 Chinese (88.2%), 8 Malays (5.6%), 6 Indians (4.2%), 2 Indonesians (1.4%), and 1 Korean (0.7%). Epiblepharon (53.4%) was the commonest surgery performed, followed by entropion (25.7%) and ectropion (20.9%). Among patients with epiblepharon and entropion, Chinese patients formed the overwhelming majority (>95%). There were no Eurasians or Indians who presented with epiblepharon or entropion. Among patients with ectropion, there was a higher representation of Indian patients (16.7%).

Conclusions:

This study shows that the spectrum of eyelid margin malpositions in Singapore is unique and that developmental epiblepharon remains the commonest eyelid margin malposition requiring surgery. In terms of involutional eyelid margin malpositions, entropion is more common than ectropion, especially among the Chinese. The similarity in terms of eyelid involvement and ethnic distribution of both epiblepharon and involutional entropion suggests that there is a common factor in both these conditions, which the authors infer is due to the unique anatomy of the Asian eyelid.
Ambulance patients with nondocumented sepsis have a high mortality risk: a retrospective study
Authors: Roest Asselina A. , Stoffers Judith , Pijpers Evelien , Jansen Jochen , Stassen Patricia M.
Published: August 2015

Objective

Sepsis is a serious disease leading to high mortality. Early recognition is important because treatment is most effective when started quickly.

The primary aim of this retrospective cohort study was to assess how many sepsis patients are documented as septic by ambulance staff. The secondary aims were to investigate how many sepsis patients are transported by ambulance, to compare them with patients transported otherwise, to investigate which factors influence documentation of sepsis and to assess whether documentation influences mortality.

Methods

We retrieved all data from ambulance and emergency department charts of patients who visited the internist in the emergency department from March 2011 to July 2012.

Results

In total, 47.4% (n=363) sepsis patients were transported by ambulance. These patients were older (71.5 vs. 55.7 years, P<0.0001), admitted more frequently (97.2 vs. 85.4%, P<0.001), significantly more frequently had severe sepsis (47.4 vs. 25.8%, P<0.0001) or septic shock (12.4 vs. 4.0%, P<0.0001), and died more frequently within 28 days (17.9 vs. 7.2%, P<0.0001) than those who were transported otherwise.

In 41.9% of ambulance patients, sepsis was not documented by ambulance staff. Measurement of temperature was important for documentation of sepsis (odds ratio 11.2, 95% confidence interval 5.2–24.4). In 32.1% of ambulance patients, sepsis could have been identified by assessing vital signs. Mortality in these nondocumented patients was higher than that in documented patients (25.7 vs. 12.9%, P=0.003).

Conclusion

Ambulance patients are seriously ill, but sepsis is often not documented by ambulance staff. Nondocumentation is associated with high mortality and could be resolved by assessing vital signs, particularly the temperature.
A Nursing Survey on Nutritional Care Practices in French‐Speaking Pediatric Intensive Care Units
Authors: Valla Frédéric V. , Gaillard‐Le Roux Bénédicte , Ford‐Chessel Carole , De Monte Malorie , Tume Lyvonne , Letois Flavie , Mura Thibault , Choueiry Elie , Rooze Shancy , Moullet Clémence , Jotterand‐Chaparro Corinne , Jacquot Aurélien
Published: August 2015

Objectives:

Malnutrition in critically ill children contributes to morbidity and mortality. The French‐speaking pediatric intensive care nutrition group (NutriSIP) aims to promote optimal nutrition through education and research.

Methods:

The NutriSIP‐designed NutriRéa‐Ped study included a cross‐sectional survey. This 62‐item survey was sent to the nursing teams of all of the French‐speaking pediatric intensive care units (PICUs) to evaluate nurses’ nutrition knowledge and practices. One nurse per PICU was asked to answer and describe the practices of their team.

Results:

Of 44 PICUs, 40 responded in Algeria, Belgium, Canada, France, Lebanon, Luxemburg, and Switzerland. The majority considered nutrition as a priority care but only 12 of the 40 (30%) had a nutrition support team, 26 of the 40 (65%) had written nutrition protocols, and 19 of 39 (49%) nursing teams felt confident with the nutrition goals. Nursing staff generally did not know how to determine nutritional requirements or to interpret malnutrition indices. They were also unaware of reduced preoperative fasting times and fast‐track concepts. In 17 of 35 (49%) PICUs, the target start time for enteral feeding was within the first 24 hours; however, frequent interruptions occurred because of neuromuscular blockade, fasting for extubation or surgery, and high gastric residual volumes. Combined pediatric neonatal intensive care units were less likely to perform systematic nutritional assessment and to start enteral nutrition rapidly.

Conclusions:

We found a large variation in nursing practices around nutrition, exacerbated by the lack of nutritional guidelines but also because of the inadequate nursing knowledge around nutritional factors. These findings encourage the NutriSIP to improve nutrition through focused education programs and research.
Nutritional/Growth Status in a Large Cohort of Medically Fragile Children Receiving Long‐Term Enteral Nutrition Support
Authors: Khan Zahra , Marinschek Sabine , Pahsini Karoline , Scheer Peter , Morris Nicholas , Urlesberger Berndt , Dunitz‐Scheer Marguerite
Published: August 2015

Objective:

The aim of the present study was to assess the nutritional status and growth of medically fragile children receiving long‐term enteral nutritional support (ENS).

Methods:

A retrospective cross‐sectional survey was conducted at a tertiary‐level pediatric hospital. Growth features and nutritional intake of children (n = 287) receiving ENS were evaluated. During a period of 5 years (2009–2013), study patients in the age group of 1 to 36 months had been referred for the explicit reason of tube weaning. Data were documented with the help of ARCHIMED (version 46.2) and analyzed using SPSS for Windows version 21. Nutritional/growth status was determined by using World Health Organization growth standard tables.

Results:

Anthropometric parameters of children were compared with World Health Organization standards, and the prevalence of underweight, wasting, and stunting was very high despite being exclusively or predominantly on ENS. Results revealed that the age of a child, inadequate amount of caloric supply/day, the diagnosis of small‐for‐gestational age, and the type of tube (nasogastric tube) were significantly associated with growth/nutritional status (P < 0.05). Duration of ENS in the percentage of the cohort's lifetime and the main diagnosis were not associated with nutritional/growth outcomes.

Conclusions:

In medically fragile children, ENS does not ensure adequate growth per se. ENS requires highly specialized and individually tailored management and in many cases regular adjustments. Long‐term tube feeding plans often seem unable to ensure the required amount of nutritional support, which surely compromise the individual efficacy of ENS.