Research papers

The PRISMA Statement for Reporting Systematic Reviews and Meta-Analyses of Studies That Evaluate Health Care Interventions: Explanation and Elaboration

Alessandro Liberati, Douglas G. Altman, Jennifer Tetzlaff, Cynthia D. Mulrow, Peter C Gøtzsche, John P. A. Ioannidis, Mike C…

Systematic reviews and meta-analyses are essential to summarize evidence relating to efficacy and safety of health care interventions accurately and reliably. The clarity and transparency of these reports, however, is not optimal. Poor reporting of systematic reviews diminishes their value to clinicians, policy makers, and other users.Since the development of the QUOROM (QUality Of Reporting Of Meta-analysis) Statement--a reporting guideline published in 1999--there have been several conceptual, methodological, and practical advances regarding the conduct and reporting of systematic reviews and meta-analyses. Also, reviews of published systematic reviews have found that key information about these studies is often poorly reported. Realizing these issues, an international group that included experienced authors and methodologists developed PRISMA (Preferred Reporting Items for Systematic reviews and Meta-Analyses) as an evolution of the original QUOROM guideline for systematic reviews and meta-analyses of evaluations of health care interventions.The PRISMA Statement consists of a 27-item checklist and a four-phase flow diagram. The checklist includes items deemed essential for transparent reporting of a systematic review. In this Explanation and Elaboration document, we explain the meaning and rationale for each checklist item. For each item, we include an example of good reporting and, where possible, references to relevant empirical studies and methodological literature. The PRISMA Statement, this document, and the associated Web site (http://www.prisma-statement.org/) should be helpful resources to improve reporting of systematic reviews and meta-analyses.

Classification and Developmental Biology of Congenital Anomalies of the Hand and Upper Extremity

Paul R. Manske, Kerby C. Oberg

1Washington University School of Medicine, Campus Box 8233, 660 South Euclid Avenue, St. Louis, MO 63110. E-mail address: [email protected] 2Divisions of Pediatric Pathology and Human Anatomy, Department of Surgery, Loma Linda University, 24785 Stewart Street, Room B09c, Loma Linda, CA 92350

The Sequence Alignment/Map format and SAMtools

Heng Li, Bob Handsaker, Alec Wysoker, Tim Fennell, Jue Ruan, Nils Homer, Gábor Marth, Gonçalo R. Abecasis, Richard Durbin, 1…

SUMMARY: The Sequence Alignment/Map (SAM) format is a generic alignment format for storing read alignments against reference sequences, supporting short and long reads (up to 128 Mbp) produced by different sequencing platforms. It is flexible in style, compact in size, efficient in random access and is the format in which alignments from the 1000 Genomes Project are released. SAMtools implements various utilities for post-processing alignments in the SAM format, such as indexing, variant caller and alignment viewer, and thus provides universal tools for processing read alignments. AVAILABILITY: http://samtools.sourceforge.net.

AutoDock Vina: Improving the speed and accuracy of docking with a new scoring function, efficient optimization, and multithreading

Oleg Trott, Arthur J. Olson

AutoDock Vina, a new program for molecular docking and virtual screening, is presented. AutoDock Vina achieves an approximately two orders of magnitude speed-up compared with the molecular docking software previously developed in our lab (AutoDock 4), while also significantly improving the accuracy of the binding mode predictions, judging by our tests on the training set used in AutoDock 4 development. Further speed-up is achieved from parallelism, by using multithreading on multicore machines. AutoDock Vina automatically calculates the grid maps and clusters the results in a way transparent to the user.

ImageNet: A large-scale hierarchical image database

Jia Deng, Wei Dong, Richard Socher, Li-Jia Li, Kai Li, Li Fei-Fei

The explosion of image data on the Internet has the potential to foster more sophisticated and robust models and algorithms to index, retrieve, organize and interact with images and multimedia data. But exactly how such data can be harnessed and organized remains a critical problem. We introduce here a new database called “ImageNet”, a large-scale ontology of images built upon the backbone of the WordNet structure. ImageNet aims to populate the majority of the 80,000 synsets of WordNet with an average of 500–1000 clean and full resolution images. This will result in tens of millions of annotated images organized by the semantic hierarchy of WordNet. This paper offers a detailed analysis of ImageNet in its current state: 12 subtrees with 5247 synsets and 3.2 million images in total. We show that ImageNet is much larger in scale and diversity and much more accurate than the current image datasets. Constructing such a large-scale database is a challenging task. We describe the data collection scheme with Amazon Mechanical Turk. Lastly, we illustrate the usefulness of ImageNet through three simple applications in object recognition, image classification and automatic object clustering. We hope that the scale, accuracy, diversity and hierarchical structure of ImageNet can offer unparalleled opportunities to researchers in the computer vision community and beyond.

The merging of community ecology and phylogenetic biology

Jeannine Cavender‐Bares, Kenneth H. Kozak, Paul V. A. Fine, Steven W. Kembel

The increasing availability of phylogenetic data, computing power and informatics tools has facilitated a rapid expansion of studies that apply phylogenetic data and methods to community ecology. Several key areas are reviewed in which phylogenetic information helps to resolve long-standing controversies in community ecology, challenges previous assumptions, and opens new areas of investigation. In particular, studies in phylogenetic community ecology have helped to reveal the multitude of processes driving community assembly and have demonstrated the importance of evolution in the assembly process. Phylogenetic approaches have also increased understanding of the consequences of community interactions for speciation, adaptation and extinction. Finally, phylogenetic community structure and composition holds promise for predicting ecosystem processes and impacts of global change. Major challenges to advancing these areas remain. In particular, determining the extent to which ecologically relevant traits are phylogenetically conserved or convergent, and over what temporal scale, is critical to understanding the causes of community phylogenetic structure and its evolutionary and ecosystem consequences. Harnessing phylogenetic information to understand and forecast changes in diversity and dynamics of communities is a critical step in managing and restoring the Earth's biota in a time of rapid global change.

A New Equation to Estimate Glomerular Filtration Rate

Andrew S. Levey, Lesley A. Stevens, Christopher H. Schmid, Yaping Zhang, Alejandro Castro, Harold I. Feldman, John W. Kusek,…

BACKGROUND: Equations to estimate glomerular filtration rate (GFR) are routinely used to assess kidney function. Current equations have limited precision and systematically underestimate measured GFR at higher values. OBJECTIVE: To develop a new estimating equation for GFR: the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation. DESIGN: Cross-sectional analysis with separate pooled data sets for equation development and validation and a representative sample of the U.S. population for prevalence estimates. SETTING: Research studies and clinical populations ("studies") with measured GFR and NHANES (National Health and Nutrition Examination Survey), 1999 to 2006. PARTICIPANTS: 8254 participants in 10 studies (equation development data set) and 3896 participants in 16 studies (validation data set). Prevalence estimates were based on 16,032 participants in NHANES. MEASUREMENTS: GFR, measured as the clearance of exogenous filtration markers (iothalamate in the development data set; iothalamate and other markers in the validation data set), and linear regression to estimate the logarithm of measured GFR from standardized creatinine levels, sex, race, and age. RESULTS: In the validation data set, the CKD-EPI equation performed better than the Modification of Diet in Renal Disease Study equation, especially at higher GFR (P < 0.001 for all subsequent comparisons), with less bias (median difference between measured and estimated GFR, 2.5 vs. 5.5 mL/min per 1.73 m(2)), improved precision (interquartile range [IQR] of the differences, 16.6 vs. 18.3 mL/min per 1.73 m(2)), and greater accuracy (percentage of estimated GFR within 30% of measured GFR, 84.1% vs. 80.6%). In NHANES, the median estimated GFR was 94.5 mL/min per 1.73 m(2) (IQR, 79.7 to 108.1) vs. 85.0 (IQR, 72.9 to 98.5) mL/min per 1.73 m(2), and the prevalence of chronic kidney disease was 11.5% (95% CI, 10.6% to 12.4%) versus 13.1% (CI, 12.1% to 14.0%). LIMITATION: The sample contained a limited number of elderly people and racial and ethnic minorities with measured GFR. CONCLUSION: The CKD-EPI creatinine equation is more accurate than the Modification of Diet in Renal Disease Study equation and could replace it for routine clinical use. PRIMARY FUNDING SOURCE: National Institute of Diabetes and Digestive and Kidney Diseases.

The Rock Physics Handbook

Gary Mavko, Tapan Mukerji, Jack Dvorkin

The Rock Physics Handbook addresses the relationships between geophysical observations and the underlying physical properties of rocks. It distills a vast quantity of background theory and laboratory results into a series of concise chapters that provide practical solutions to problems in geophysical data interpretation. This expanded second edition presents major new chapters on statistical rock physics and velocity-porosity-clay models for clastic sediments. Other new and expanded topics include anisotropic seismic signatures, borehole waves, models for fractured media, poroelastic models, and attenuation models. This new edition also provides an enhanced set of appendices with key empirical results, data tables, and an atlas of reservoir rock properties – extended to include carbonates, clays, gas hydrates, and heavy oils. Supported by a website hosting MATLAB routines for implementing the various rock physics formulas, this book is a vital resource for advanced students and university faculty, as well as petroleum industry geophysicists and engineers.

AutoDock4 and AutoDockTools4: Automated docking with selective receptor flexibility

Garrett M. Morris, Ruth Huey, William Lindstrom, Michel F. Sanner, Richard K. Belew, David S. Goodsell, Arthur J. Olson

We describe the testing and release of AutoDock4 and the accompanying graphical user interface AutoDockTools. AutoDock4 incorporates limited flexibility in the receptor. Several tests are reported here, including a redocking experiment with 188 diverse ligand-protein complexes and a cross-docking experiment using flexible sidechains in 87 HIV protease complexes. We also report its utility in analysis of covalently bound ligands, using both a grid-based docking method and a modification of the flexible sidechain technique.

Universal Solvation Model Based on Solute Electron Density and on a Continuum Model of the Solvent Defined by the Bulk Dielectric Constant and Atomic Surface Tensions

Aleksandr V. Marenich, Christopher J. Cramer, Donald G. Truhlar

We present a new continuum solvation model based on the quantum mechanical charge density of a solute molecule interacting with a continuum description of the solvent. The model is called SMD, where the "D" stands for "density" to denote that the full solute electron density is used without defining partial atomic charges. "Continuum" denotes that the solvent is not represented explicitly but rather as a dielectric medium with surface tension at the solute-solvent boundary. SMD is a universal solvation model, where "universal" denotes its applicability to any charged or uncharged solute in any solvent or liquid medium for which a few key descriptors are known (in particular, dielectric constant, refractive index, bulk surface tension, and acidity and basicity parameters). The model separates the observable solvation free energy into two main components. The first component is the bulk electrostatic contribution arising from a self-consistent reaction field treatment that involves the solution of the nonhomogeneous Poisson equation for electrostatics in terms of the integral-equation-formalism polarizable continuum model (IEF-PCM). The cavities for the bulk electrostatic calculation are defined by superpositions of nuclear-centered spheres. The second component is called the cavity-dispersion-solvent-structure term and is the contribution arising from short-range interactions between the solute and solvent molecules in the first solvation shell. This contribution is a sum of terms that are proportional (with geometry-dependent proportionality constants called atomic surface tensions) to the solvent-accessible surface areas of the individual atoms of the solute. The SMD model has been parametrized with a training set of 2821 solvation data including 112 aqueous ionic solvation free energies, 220 solvation free energies for 166 ions in acetonitrile, methanol, and dimethyl sulfoxide, 2346 solvation free energies for 318 neutral solutes in 91 solvents (90 nonaqueous organic solvents and water), and 143 transfer free energies for 93 neutral solutes between water and 15 organic solvents. The elements present in the solutes are H, C, N, O, F, Si, P, S, Cl, and Br. The SMD model employs a single set of parameters (intrinsic atomic Coulomb radii and atomic surface tension coefficients) optimized over six electronic structure methods: M05-2X/MIDI!6D, M05-2X/6-31G, M05-2X/6-31+G, M05-2X/cc-pVTZ, B3LYP/6-31G, and HF/6-31G. Although the SMD model has been parametrized using the IEF-PCM protocol for bulk electrostatics, it may also be employed with other algorithms for solving the nonhomogeneous Poisson equation for continuum solvation calculations in which the solute is represented by its electron density in real space. This includes, for example, the conductor-like screening algorithm. With the 6-31G basis set, the SMD model achieves mean unsigned errors of 0.6-1.0 kcal/mol in the solvation free energies of tested neutrals and mean unsigned errors of 4 kcal/mol on average for ions with either Gaussian03 or GAMESS.

The Biology of Chromatin Remodeling Complexes

Cedric R. Clapier, Bradley R. Cairns

The packaging of chromosomal DNA by nucleosomes condenses and organizes the genome, but occludes many regulatory DNA elements. However, this constraint also allows nucleosomes and other chromatin components to actively participate in the regulation of transcription, chromosome segregation, DNA replication, and DNA repair. To enable dynamic access to packaged DNA and to tailor nucleosome composition in chromosomal regions, cells have evolved a set of specialized chromatin remodeling complexes (remodelers). Remodelers use the energy of ATP hydrolysis to move, destabilize, eject, or restructure nucleosomes. Here, we address many aspects of remodeler biology: their targeting, mechanism, regulation, shared and unique properties, and specialization for particular biological processes. We also address roles for remodelers in development, cancer, and human syndromes.

Biopython: freely available Python tools for computational molecular biology and bioinformatics

Peter Cock, Tiago Antão, Jeffrey T. Chang, Brad Chapman, Cymon J. Cox, Andrew Dalke, Iddo Friedberg, Thomas Hamelryck, Frank…

Abstract Summary: The Biopython project is a mature open source international collaboration of volunteer developers, providing Python libraries for a wide range of bioinformatics problems. Biopython includes modules for reading and writing different sequence file formats and multiple sequence alignments, dealing with 3D macro molecular structures, interacting with common tools such as BLAST, ClustalW and EMBOSS, accessing key online databases, as well as providing numerical methods for statistical learning. Availability: Biopython is freely available, with documentation and source code at www.biopython.org under the Biopython license. Contact: All queries should be directed to the Biopython mailing lists, see www.biopython.org/wiki/_Mailing_listspeter.cock@scri.ac.uk.

Generalized linear mixed models: a practical guide for ecology and evolution

Benjamin M. Bolker, M. Brooks, Connie J. Clark, Shane W. Geange, John R. Poulsen, M. Henry H. Stevens, Jada-Simone S. White

Information, Physics, and Computation

Marc Mézard, Andrea Montanari

Abstract This book presents a unified approach to a rich and rapidly evolving research domain at the interface between statistical physics, theoretical computer science/discrete mathematics, and coding/information theory. The topics which have been selected, including spin glasses, error correcting codes, satisfiability, are central to each field. The approach focuses on the limit of large random instances, adopting a common formulation in terms of graphical models. It presents message passing algorithms like belief propagation and survey propagation, and their use in decoding and constraint satisfaction solving. It also explains analysis techniques like density evolution and the cavity method, and uses them to derive phase diagrams and study phase transitions.

The Expanded Biology of Serotonin

Miles Berger, J.A. Gray, Bryan L. Roth

Serotonin is perhaps best known as a neurotransmitter that modulates neural activity and a wide range of neuropsychological processes, and drugs that target serotonin receptors are used widely in psychiatry and neurology. However, most serotonin is found outside the central nervous system, and virtually all of the 15 serotonin receptors are expressed outside as well as within the brain. Serotonin regulates numerous biological processes including cardiovascular function, bowel motility, ejaculatory latency, and bladder control. Additionally, new work suggests that serotonin may regulate some processes, including platelet aggregation, by receptor-independent, transglutaminase-dependent covalent linkage to cellular proteins. We review this new "expanded serotonin biology" and discuss how drugs targeting specific serotonin receptors are beginning to help treat a wide range of diseases.

Ambient belonging: How stereotypical cues impact gender participation in computer science.

Sapna Cheryan, Victoria C. Plaut, Paul Davies, Claude M. Steele

People can make decisions to join a group based solely on exposure to that group's physical environment. Four studies demonstrate that the gender difference in interest in computer science is influenced by exposure to environments associated with computer scientists. In Study 1, simply changing the objects in a computer science classroom from those considered stereotypical of computer science (e.g., Star Trek poster, video games) to objects not considered stereotypical of computer science (e.g., nature poster, phone books) was sufficient to boost female undergraduates' interest in computer science to the level of their male peers. Further investigation revealed that the stereotypical broadcast a masculine stereotype that discouraged women's sense of ambient belonging and subsequent interest in the environment (Studies 2, 3, and 4) but had no similar effect on men (Studies 3, 4). This masculine stereotype prevented women's interest from developing even in environments entirely populated by other women (Study 2). Objects can thus come to broadcast stereotypes of a group, which in turn can deter people who do not identify with these stereotypes from joining that group.

Sperm Biology: an Evolutionary Perspective

Alan N. Hodgson

New response evaluation criteria in solid tumours: Revised RECIST guideline (version 1.1)

E. Eisenhauer, P. Therasse, Jan Bogaerts, Lawrence H. Schwartz, Daniel J. Sargent, Robert C. Ford, Janet Dancey, Susan G. Ar…

Systematic and integrative analysis of large gene lists using DAVID bioinformatics resources

Da Wei Huang, Brad T. Sherman, Richard A. Lempicki

Shape‐Controlled Synthesis of Metal Nanocrystals: Simple Chemistry Meets Complex Physics?

Younan Xia, Yujie Xiong, Byungkwon Lim, Sara E. Skrabalak

Nanocrystals are fundamental to modern science and technology. Mastery over the shape of a nanocrystal enables control of its properties and enhancement of its usefulness for a given application. Our aim is to present a comprehensive review of current research activities that center on the shape-controlled synthesis of metal nanocrystals. We begin with a brief introduction to nucleation and growth within the context of metal nanocrystal synthesis, followed by a discussion of the possible shapes that a metal nanocrystal might take under different conditions. We then focus on a variety of experimental parameters that have been explored to manipulate the nucleation and growth of metal nanocrystals in solution-phase syntheses in an effort to generate specific shapes. We then elaborate on these approaches by selecting examples in which there is already reasonable understanding for the observed shape control or at least the protocols have proven to be reproducible and controllable. Finally, we highlight a number of applications that have been enabled and/or enhanced by the shape-controlled synthesis of metal nanocrystals. We conclude this article with personal perspectives on the directions toward which future research in this field might take.

WGCNA: an R package for weighted correlation network analysis

Peter Langfelder, Steve Horvath

BACKGROUND: Correlation networks are increasingly being used in bioinformatics applications. For example, weighted gene co-expression network analysis is a systems biology method for describing the correlation patterns among genes across microarray samples. Weighted correlation network analysis (WGCNA) can be used for finding clusters (modules) of highly correlated genes, for summarizing such clusters using the module eigengene or an intramodular hub gene, for relating modules to one another and to external sample traits (using eigengene network methodology), and for calculating module membership measures. Correlation networks facilitate network based gene screening methods that can be used to identify candidate biomarkers or therapeutic targets. These methods have been successfully applied in various biological contexts, e.g. cancer, mouse genetics, yeast genetics, and analysis of brain imaging data. While parts of the correlation network methodology have been described in separate publications, there is a need to provide a user-friendly, comprehensive, and consistent software implementation and an accompanying tutorial. RESULTS: The WGCNA R software package is a comprehensive collection of R functions for performing various aspects of weighted correlation network analysis. The package includes functions for network construction, module detection, gene selection, calculations of topological properties, data simulation, visualization, and interfacing with external software. Along with the R package we also present R software tutorials. While the methods development was motivated by gene expression data, the underlying data mining approach can be applied to a variety of different settings. CONCLUSION: The WGCNA package provides R functions for weighted correlation network analysis, e.g. co-expression network analysis of gene expression data. The R package along with its source code and additional material are freely available at http://www.genetics.ucla.edu/labs/horvath/CoexpressionNetwork/Rpackages/WGCNA.

Closing the gap in a generation: health equity through action on the social determinants of health

Michael Marmot, Sharon Friel, Ruth Bell, Tanja A. J. Houweling, Sebastian Taylor

Research electronic data capture (REDCap)—A metadata-driven methodology and workflow process for providing translational research informatics support

Paul A. Harris, Robert Taylor, Robert J. Thielke, Jonathon Payne, Nathaniel Gonzalez, José G. Conde

Nudge: improving decisions about health, wealth, and happiness

A groundbreaking discussion of how we can apply the new science of to nudge people toward decisions that will improve their lives by making them healthier, wealthier, and more free Every day, we make decisions on topics ranging from personal investments to schools for our children to the meals we eat to the causes we champion. Unfortunately, we often choose poorly. Nobel laureate Richard Thaler and legal scholar and bestselling author Cass Sunstein explain in this important exploration of that, being human, we all are susceptible to various biases that can lead us to blunder. Our mistakes make us poorer and less healthy; we often make bad decisions involving education, personal finance, health care, mortgages and credit cards, the family, and even the planet itself. In Nudge, Thaler and Sunstein invite us to enter an alternative world, one that takes our humanness as a given. They show that by knowing how people think, we can design environments that make it easier for people to choose what is best for themselves, their families, and their society. Using colorful examples from the most important aspects of life, Thaler and Sunstein demonstrate how thoughtful choice architecture can be established to nudge us in beneficial directions without restricting freedom of choice. Nudge offers a unique new take-from neither the left nor the right-on many hot-button issues, for individuals and governments alike. This is one of the most engaging and provocative books to come along in many years.