Additional File Research Articles

Relationship of cardiometabolic parameters in non-smokers, current smokers, and quitters in diabetes: a systematic review and meta-analysis.

BackgroundSmoking is associated with increased macrovascular and microvascular complications in people with diabetes. In addition to other concomitant vascular perturbations, it also seems to influence the cardiometabolic parameters, which may partly explain the accelerated rate of vascular complications in smokers with diabetes. While smoking cessation is advocated as a universal component of the management of diabetes, there is some anecdotal evidence that HbA1c could increase following smoking cessation. The aim of this review is to explore the relationship between smoking and its cessation on cardiometabolic parameters in diabetes.MethodsSearches were conducted on Medline, EMBASE and CINAHL up to March 2016. After screening 6866 studies (Additional file 1), 14 observational studies with a total of 98,978 participants’ with either type 1 or type 2 diabetes were selected for review. Narrative synthesis and meta-analyses were carried out to explore the relationship between smoking and its cessation.ResultsMeta-analysis showed that the pooled mean difference of HbA1c between non-smokers and smokers was −0.61% (95% CI −0.88 to −0.33, p < 0.0001). The difference in LDL cholesterol between non-smokers and smokers was −0.11 mmol/l (95% CI −0.21 to −0.01, p = 0.04). The difference in HDL cholesterol between non-smokers and smokers was 0.12 mmol/l (95% CI 0.08–0.15, p < 0.001). However, there was no statistically significant difference in blood pressure between the two groups. The difference in HbA1c between quitters and continued smokers was not statistically significant −0.10% (95% CI −0.42 to 0.21, p = 0.53). However, a narrative synthesis revealed that over a period of 10 years, the HbA1c was comparable between non-smokers and quitters.ConclusionNon-smokers have a statistically significant lower HbA1c and more favourable lipid profile compared to smokers. Smoking cessation does not lead to an increase in HbA1c in long-term and may reduce vascular complications in diabetes by its favourable impact on lipid profile.Electronic supplementary materialThe online version of this article (doi:10.1186/s12933-016-0475-5) contains supplementary material, which is available to authorized users.

Erratum to: Illuminating uveitis: metagenomic deep sequencing identifies common and rare pathogens.

Doan et al. Genome Medicine (2016) 8:123 DOI 10.1186/s13073-016-0377-x ERRATUM Open Access Erratum to: Illuminating uveitis: metagenomic deep sequencing identifies common and rare pathogens Thuy Doan 1,2† , Michael R. Wilson 3,4† , Emily D. Crawford 3,5 , Eric D. Chow 3 , Lillian M. Khan 3 , Kristeene A. Knopp 3 , Brian D. O’Donovan 3 , Dongxiang Xia 6 , Jill K. Hacker 6 , Jay M. Stewart 2 , John A. Gonzales 1,2 , Nisha R. Acharya 1,2 and Joseph L. DeRisi 3* Erratum It has come to our attention that there is an error in Fig. 3a for this article [1]. The correct version of Fig. 3a can be found below. The red markers now reflect the se- quence differences. The text is correct. There was also a row omitted in Additional file 1: Table S1. The revised version can be found below. Additional file Additional file 1: Table S1. List of nucleotide substitutions identified in subject 6’s RV genome. The patient’s RV genome was aligned with the Stuttgart strain (GenBank DQ388280.1). A nucleotide change was considered a substitution only if the change was present in ≥ 4 reads or in 80% of the total reads at that nucleotide position. (PDF 120 kb) Author details Francis I. Proctor Foundation, University of California San Francisco, San Francisco, CA, USA. 2 Department of Ophthalmology, University of California San Francisco, San Francisco, CA, USA. 3 Department of Biochemistry and Biophysics, University of California San Francisco, San Francisco, CA, USA. Department of Neurology, University of California San Francisco, San Francisco, CA, USA. 5 Howard Hughes Medical Institute, Chevy Chase, MD, USA. 6 California Department of Public Health, Richmond, CA, USA. Received: 7 November 2016 Accepted: 7 November 2016 Reference 1. Doan T, Wilson MR, Crawford ED, Chow ED, Khan LM, Knopp KA, O’Donovan BD, Xia D, Hacker JK, Stewart JM, Gonzales JA, Archarya NR, DeRisi JL. Illuminating uveitis: metagenomic deep sequencing identifies common and rare pathogens. Genome Med. 2016;8:106. * Correspondence: joe@derisilab.ucsf.edu Equal contributors Department of Biochemistry and Biophysics, University of California San Francisco, San Francisco, CA, USA © The Author(s). 2016 Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

Transparently Exploiting Device-Reserved Memory for Application Performance in Mobile Systems

Most embedded systems require contiguous memory space to be reserved for devices, which may lead to memory under-utilization. Although several approaches have been proposed to address this issue, they have limitations of either inefficient memory usage or long latency for switching the reserved memory space between a device and general-purpose uses. Our scheme, on the other hand, utilizes reserved memory as an eviction-based file cache. It guarantees contiguous memory allocation to devices while providing idle device memory as an additional file cache called eCache for general-purpose usage. Because eCache stores only evicted data from the in-kernel page cache, the memory efficiency is preserved and the allocation time for devices is minimized. Cost-based region selection also minimizes additional read I/O operations by carefully discarding cached data from eCache. The additional indexing cost incurred by adding eCache is minimized by integrating its index structure with the kernel page cache. The prototype is implemented on the Nexus S smartphone and is evaluated using popular Android applications. The evaluation results show that our scheme outperforms previous approaches in terms of the application launch performance. The device memory reallocation time is also limited to a few milliseconds, which is sufficiently small to make our scheme transparent.

Erratum to: Simple steps to develop trial follow-up procedures.

Unfortunately, the original version of this article [1] contained an error. There were errors in the reference numbers in Additional file 1. This has now been corrected and Additional file 1 is included here with the correct reference numbers.

A comprehensive open package format for preservation and distribution of geospatial data and metadata

The complexities of the intricate geospatial resources and formats make preservation and distribution of GIS data difficult even among experts. The proliferation of, for instance, KML, Internet map services, etc, reflects the need for sharing geodata but a comprehensive solution when having to deal with data and metadata of a certain complexity is not currently provided. Original geospatial data is usually divided into several parts to record its different aspects (spatial and thematic features, etc), plus additional files containing, metadata, symbolization specifications and tables, etc; these parts are encoded in different formats, both standard and proprietary. To simplify data access, software providers encourage the use of an additional element that we call generically “map project”, and this contains links to other parts (local or remote). Consequently, in order to distribute the data and metadata refereed by the map in a complete way, or to apply the Open Archival Information System (OAIS) standard to preserve it for the future, we need to face the multipart problem. This paper proposes a package allowing the distribution of real (comprehensive although diverse and complex) GIS data over the Internet and for data preservation. This proposal, complemented with the right tools, hides but keeps the multipart structure, so providing a simpler but professional user experience. Several packaging strategies are reviewed in the paper, and a solution based on ISO 29500-2 standard is chosen. The solution also considers the adoption of the recent Open Geospatial Consortium Web Services common standard (OGC OWS) context document as map part, and as a way for also combining data files with geospatial services. Finally, and by using adequate strategies, different GIS implementations can use several parts of the package and ignore the rest: a philosophy that has proven useful (e.g. in TIFF).

Comparing groups versus individuals in decision making: a systematic review protocol

Biodiversity management requires effective decision making at various stages. However decision making in the real world is complex, driven by multiple factors and involves a range of stakeholders. Understanding the factors that influence decision making is crucial to addressing the conflicts that arise in conservation. Decisions can be made either by individuals or by groups. This precise context has been studied extensively for several decades by behavioural economists, social psychologists and intelligence analysts. The observations from these disciplines can offer useful insights for biodiversity conservation. A systematic review on group versus individual decision making is currently lacking. This systematic review would enable us to synthesize the key insights from these disciplines for a range of scenarios useful for conservation. The review will document studies that have investigated differences between group and individual decision making. The focus will be on empirical studies; the comparators in this case are decisions made by individuals while the intervention is group decision making. Outcomes include level of bias in decision outcomes or group performance. The search terms will include various combinations of the words “group”, “individual” and “decision-making”. The searches will be conducted in major publication databases, google scholar and specialist databases. Articles will be screened at the title and abstract and full text level by two reviewers. After checking for internal validity, the articles will be synthesized into subsets of decision contexts in which decision making by groups and individuals have been compared. The review process, all extracted data, original studies identified in the systematic review process and inclusion and exclusion decisions will be freely available as Additional file 1 in the final review.

Two new methods to fit models for network meta-analysis with random inconsistency effects

BackgroundMeta-analysis is a valuable tool for combining evidence from multiple studies. Network meta-analysis is becoming more widely used as a means to compare multiple treatments in the same analysis. However, a network meta-analysis may exhibit inconsistency, whereby the treatment effect estimates do not agree across all trial designs, even after taking between-study heterogeneity into account. We propose two new estimation methods for network meta-analysis models with random inconsistency effects.MethodsThe model we consider is an extension of the conventional random-effects model for meta-analysis to the network meta-analysis setting and allows for potential inconsistency using random inconsistency effects. Our first new estimation method uses a Bayesian framework with empirically-based prior distributions for both the heterogeneity and the inconsistency variances. We fit the model using importance sampling and thereby avoid some of the difficulties that might be associated with using Markov Chain Monte Carlo (MCMC). However, we confirm the accuracy of our importance sampling method by comparing the results to those obtained using MCMC as the gold standard. The second new estimation method we describe uses a likelihood-based approach, implemented in the metafor package, which can be used to obtain (restricted) maximum-likelihood estimates of the model parameters and profile likelihood confidence intervals of the variance components.ResultsWe illustrate the application of the methods using two contrasting examples. The first uses all-cause mortality as an outcome, and shows little evidence of between-study heterogeneity or inconsistency. The second uses “ear discharge" as an outcome, and exhibits substantial between-study heterogeneity and inconsistency. Both new estimation methods give results similar to those obtained using MCMC.ConclusionsThe extent of heterogeneity and inconsistency should be assessed and reported in any network meta-analysis. Our two new methods can be used to fit models for network meta-analysis with random inconsistency effects. They are easily implemented using the accompanying R code in the Additional file 1. Using these estimation methods, the extent of inconsistency can be assessed and reported.Electronic supplementary materialThe online version of this article (doi:10.1186/s12874-016-0184-5) contains supplementary material, which is available to authorized users.

Erratum to: Transmission of α-synucleinopathy from olfactory structures deep into the temporal lobe.

* C E D Pi “Please download the high-resolution supplemental versions of these files at the link at the end of this article (Additional file 3) or email the corresponding author at leakr@duq.edu for access to the files and zoom in and out of the stitched montages in order to appreciate the density of the pathology, distinguish it from background, and judge the precise anatomical location.” In the Fig. 2 legend, the article [1] should have had the additional line: “For a high-resolution version of this figure, please download the image at the link at the end of this article (Additional file 3) or email the corresponding author at leakr@duq.edu for access to the files.” In the Fig. 3 legend, the article [1] should have had the additional line: “To view the pSer129 pathology in the entorhinal cortex and transentorhinal region in panel c, please

The changing graduate labour market: analysis using a new indicator of graduate jobs

Abstract This paper examines differentiation in the recent evolving graduate labour market in Britain. Using a novel statistically derived indicator of graduate jobs, based on job skill requirements in three-digit occupations obtained from the British Skills and Employment Survey series, we analyse trends in the labour market between 1997/2001 and 2006/2012. The indicator performs better than other indicators in validation tests, could be applied flexibly in other contexts, and is available in the Additional file 1. We find that the massive influx of graduates into the labour force has been absorbed with no increase in overeducation. However, the returns to graduation have become more dispersed, with those at the upper quartile of the residual distribution increasing, while those at the lowest quartile have fallen. The wage gap between matched and overeducated graduates increased by 11 log points. Using the British Household Panel Study, we find that the persistence of overeducation status did not change but for non-employed male graduates moving into employment, the chances of entering a graduate job decreased. JEL Classification: J21, J24, J3

Ngravs: Distinct gravitational interactions in gadget-2

We discuss an extension of the massively parallel cosmological simulation code gadget-2, which now enables investigation of multiple and distinct gravitational force laws, provided they are dominated by a constant scaling of the Newtonian force. In addition to simplifying investigations of a universally modified force law, the ngravs extension provides a foundation for state-of-the-art collisionless cosmological simulations of exotic gravitational scenarios. We briefly review the algorithms used by gadget-2, and present our extension to multiple gravities, highlighting additional features that facilitate consideration of exotic force laws. We discuss the accuracy and performance of the ngravs extension, both internally and with an unaltered gadget-2, in the relevant operational modes. The ngravs extension is publicly released to the research community. Program summaryProgram title: Gadget-2.0.7-ngravsCatalogue identifier: AFAV_v1_0Program summary URL:http://cpc.cs.qub.ac.uk/summaries/AFAV_v1_0.htmlProgram obtainable from: CPC Program Library, Queen’s University, Belfast, N. IrelandLicensing provisions: GNU GPL v2No. of lines in distributed program, including test data, etc.: 36504No. of bytes in distributed program, including test data, etc.: 3919508Distribution format: tar.gzProgramming language: C.Computer: Commodity.Operating system: Unix.RAM: 256MB+Classification: 1.9, 4.12.External routines: GSL, FFTW3, HDF5 (optional)Nature of problem:N-body cosmological codes are traditionally designed to investigate a single gravitating species interacting via the Newtonian force law. There exist viable extensions to General Relativity [1], however, which predict weakfield, slow-motion limits featuring distinct gravitational force laws between distinct particle species. To enable investigation and constraint of these theories with available astrophysical data, a necessary first step is to extend an N-body simulator to handle distinct gravitating species.Solution method:The massively parallel Barnes–Hut tree, Fast Fourier Transform, and sorting routines of the versatile and well-vetted N-body simulator [2] gadget-2 were extended to support D distinct gravitationally interacting species. The tree implementation now vectorizes over each species’ monopole masses and positions, the Fourier routines now handle active and passive gravitational masses separately, and the sorting routines now group all particle data by type. An additional file was introduced allowing the user to specify all D2 gravitational interactions: real space, Fourier space, and lattice summation corrections. To improve monopole approximations in scenarios where the scale of the gravitational interaction depends on the mass itself, an optional tracking of the number of bodies contributing to any particular monopole approximation has been written.Restrictions:Force laws with mass-dependent scale lengths are not amenable to the implemented Fourier methods (or even the traditional [3] Fourier approach). Nodes containing highly heterogeneous collections of particles with different mass-dependent scale lengths may not be well-approximated, even with the additional tracking introduced. The collisional “gas” species can only interact via a single gravitational force law.Unusual features:The extension allows consideration of quite general and exotic interactions between bodies, and will serve as a common platform for model-dependent adjustments to the cosmological background evolution.Additional comments:Data file format is identical to that of gadget-2. Configuration file format is unchanged, save for the addition of required bindings between particle species and gravitational type.Running time:Typical running times are ≤2Dx those of gadget-2, where D is an integer between 1 and 6.

The treatment of multidirectional instability of the shoulder with a rehabilitation programme: Part 2.

The most commonly recommended initial treatment for multidirectional instability is a rehabilitation program. Although there is evidence to support the effect of conservative management on this condition, the published literature provides little information on the exercise parameters of such programs. This paper is the second part of a two-part series that outlines a six-stage rehabilitation program for multidirectional instability with a focus on scapula control and exercise drills into functional positions. This paper outlines stages 3 to 6 of this rehabilitation program. This clinical protocol is currently being tested for efficacy as part of a randomized controlled trial (Australian New Zealand Clinical Trials Registry #ACTRN12613001240730). The information in this paper and additional online supplementary files will provide therapists with adequate detail to replicate the rehabilitation program in the clinical setting.

The treatment of multidirectional instability of the shoulder with a rehabilitation program: Part 1.

The most commonly recommended initial treatment for multidirectional instability is a rehabilitation program. Although there is evidence to support the effect of conservative management on this condition, the published literature provides little information on the exercise parameters of such programs. In addition, current published rehabilitation programs for multidirectional instability do not focus on scapula stability or exercise drills into functional and sports-specific positions, which are often important aspects to consider in this patient population. The aim of this paper (Part 1) is to outline the first two stages of a six-stage rehabilitation program for the conservative management of multidirectional instability with a focus on scapula control and exercise drills into functional positions. This clinical protocol is currently being tested for efficacy as part of a randomized controlled trial (Australian New Zealand Clinical Trials Registry #ACTRN12613001240730). The information in this paper and additional online supplementary files will provide therapists with adequate detail to replicate the rehabilitation program in the clinical setting.

Erik Beek and Rick R. van Rijn (Eds): Diagnostic Pediatric Ultrasound

This is an interesting book designed to underline the crucial role of ultrasonography in paediatric imaging. The editors are two prominent Dutch authorities in the field, Erik Beek (Consulting Radiologist at the University Medical Center, Utrecht) and Rick R. van Rijn (Professor at the Emma Children’s Hospital, Academic Medical Center, Amsterdam), and the contributors includemany European experts in paediatric diagnostic imaging. The book consists of 660 pages in 18 chapters. The first chapter is dedicated to the importance of correct child examination and a child-friendly environment in a hospital ward, while the second chapter provides a concise overview of the basic principles of ultrasonography. In the following 15 chapters the approach to paediatric pathology is by single organs and systems, starting from neonatal ultrasonography. Before considering pathology, the authors always provide a description of embryology, normal anatomy and the most common anatomical variants. The last chapter focuses on a brief overview of the most common ultrasound-guided interventional procedures used by paediatric radiologists. The volume contains 2,025 illustrations, including diagnostic images, diagrammatic representations and panels illustrated with pictures, that make the correct interpretation of the imaging easier for both radiologists and nonradiologists. In addition, many chapters are accompanied by CD video material that enriches the information contained in the book; additional teaching files and videos on ultrasonography are available from the website MediaCenter.thieme.com. It is immediately clear that the main goal of this text is to emphasize the centrality of sonography in paediatric diagnostic imaging in daily practice. It explains in detail why ultrasonography must always be the first-line imaging modality in the approach to paediatric patients because it offers a safe and noninvasive method for obtaining data. According to the aim of the authors, the discussion leaves little room for consideration of other diagnostic methods, such as CTandMRI. Thus, it offers a wide range of information about ultrasonography, especially for the first time for paediatricians and paediatric surgeons, but provides only a partial view of paediatric diagnostic imaging for radiology specialists. However, this aspect probably goes beyond the intentions of the volume and such supplementary information can readily be obtained from other texts. The main strength of this book is the huge variety of highquality images used, particularly normal reference images that complement and provide a means of comparison with pathological findings, which make the text easier to understand and consult. Moreover, for less expert operators, the video content offers a specific reference model to use in daily practice. The only deficiency of the text is attributable to the brief and incomplete description of ultrasound-guided interventional procedures, that are not discussed in sufficient detail. In conclusion, the book can be considered a valid tool for specialists such as radiologists, paediatricians and paediatric surgeons. On the one hand, it is necessary to appreciate the intention to combine clinical evaluation and ultrasonography protocols to optimize diagnostic performance, by adapting technical methods of examination to the individual patient. On the other hand, for a complete development of the argument, it would have been desirable to complete the final part of the text by adding a more detailed description of ultrasound-guided interventional procedures, that are increasingly common in clinical practice. Overall, the book is clear, user-friendly and easy to read; with a large number of didactic tables and images; it provides a complete compendium of the key points of diagnostic paediatric ultrasonography. * Gianfranco Vallone gianfranco.vallone2@unina.it

Vaccination with endosomal unknown epitopes produces therapeutic response in rheumatoid arthritis patients and modulates adjuvant arthritis of rats

BackgroundOur previous results showed that intrasynovial Rifamycin SV caused the lysis of synoviocites and freed the autoantigens which in turn stimulated the immunoregulatory rather than autoreactive T cell response in rheumatoid patients. Here, we hypothesize that disruption in vitro of peripheral blood mononuclear cells, by freeze/thawing or by lytic action of Rifamycin SV, would induce the release of endosomal pathogenic autoantigens from APCs present in the circulation, which could then be isolated from degrading enzymes by ultrafiltration.MethodsThe preparation of the ultrafiltrates are based on the rupture of PBMCs (5 × 106 cells/mL) by the addition of Rifamycin SV in culture (250 μg/mL), which causes the lysis of 90 % of the cells in 3 h, or by three cycles of freeze/thawing of the PBMC, from −80 °C to room temperature. The lysate and the fragmented cells were then centrifuged and ultrafiltered by passage through a filtration device with a cut-off of 10 kDa. Also the synovial fluid was subjected to ultrafiltration.Results and conclusionsAt clinical monitoring of the 30th day, 22/58 (38 %) patients subcutaneously treated with the autologous ultrafiltrate prepared by the freeze/thawing of PBMCs reached an ACR20. Comparable results were obtained with the other two ultrafiltrates.Cell cultures The addition of ultrafiltrates to rheumatoid PBMCs cultures led to the upregulation of a marker for T-regulatory cells, and downregulation of a cell proliferation marker; changes that together have the meaning of a global immunomodulatory response and that only a specific antigen (ultrafiltrate UF-f/t) might induce in the rheumatoid patient, probably by activating pre-existing protective network.Experimental arthritis All the ultrafiltrates except that prepared by Rifamycin SV were able to modulate the adjuvant arthritis in rats. In particular, longlasting synovial fluid induced a significant reduction of the severity of subsequent arthritis (p < 0.01) while SF from recent RA effusion (5–10 days after a previous complete extraction) and knee osteoarthrosis were ineffective. It is reasonable to assume there are at least two unknown endosomal immunoactive epitopes; one developing its immunotherapeutic property in RA, and the other, related to the molecule of HSP60, reduces the severity of oncoming arthritis. Both epitopes are present in humans, have a molecular weight of ≤10 kDa and do not appear to be bystander antigens. Please see Additional file 1 for the abstract in Italian.Electronic supplementary materialThe online version of this article (doi:10.1186/s12967-016-0908-7) contains supplementary material, which is available to authorized users.

Erratum to: ‘Justice at Sea: Fishers’ politics and marine conservation in coastal Odisha, India’

© L p i Unfortunately, the original version of this article [1] contained errors. The author has made several edits to be included in the text as shown below. Section: ‘Introduction’, middle of paragraph 5: Drop ‘additional’ in ‘additional case work’ Section: ‘Territory, nature, people, state’, second sentence paragraph 6: Change ‘Indeed, state creation itself...’ to ‘State creation in turn...’ Section: ‘State policy, turtle conservation and marine fishing’, last sentence of paragraph 3: Drop ‘usage’ in ‘popular usage meaning of a mechanized boat’ so that is reads as ‘popular meaning of a mechanized boat’ Section: ‘The Indian state, refugees and the 2005 controversy’, last sentence of paragraph 4: Drop ‘had’ ‘The Act had was partly meant to prevent....’ So that it reads as ‘The Act was partly meant to prevent...’ The additional files (1 and 2) currently placed at the bottom of the text, need to be embedded in the text and function as figures. Additional File 1 should be Figure 1 and be placed at the end of the 5 paragraph of the Introduction. This also means that “(additional file 1)” at the end of the last sentence of paragraph 5 needs to be deleted. Additional File 2 should be Figure 2 and be placed at the end of the 7 paragraph of the section entitled, “State policy, turtle conservation and marine fishing”. This also means that “(additional file 2)” at the end of the last sentence of paragraph 7 needs to be deleted. There are further changes to the Bibliography. Mahesh should be corrected to Mukul in the following references: Gupta, Charu and Mukul Sharma. 2008. Contested coastlines: Fisherfolk, nations and borders in South Asia. New Delhi: Routledge. Sharma, Mukul. 2012. Green and saffron: Hindu nationalism and Indian environmental politics. Ranikhet: Permanent Black. The following is an unpublished reference that needs to be changed in the bibliography. Chhotray, Vasudha. 2016. Nullification of citizenship: Negotiating authority without identity documents in coastal Odisha. Forthcoming. The following is a missing reference in the bibliography which is to be inserted between Forsyth and Gupta in the bibliography

A valid assessment of students’ skill in determining relationships on evolutionary trees

Evolutionary trees illustrate relationships among taxa. Interpreting these relationships requires developing a set of “tree-thinking” skills that are typically included in introductory college biology courses. One of these skills is determining relationships among taxa using the most recent common ancestor, yet many students instead use one or more alternate strategies to determine relationships. Several alternate strategies have been well documented and these include using superficial similarity, proximity at the tips of a tree, or the fewest intervening nodes in the tree to group taxa. We administered interviews (n = 16) and pencil-and-paper questionnaires (n = 205), and constructed a valid and reliable assessment that measured how well students determined relationships among taxa on an evolutionary tree. Our questions asked students to consider a focal taxon and identify which of two additional taxa is most closely related to it. We paired the use of most recent common ancestor with one of three alternative strategies (i.e., similarity, proximity, or node-counting) to explicitly test students’ understanding of the relationships among the taxa on each tree. Our assessment enables us to identify students who are effectively distracted by an alternative strategy, those who use the most recent common ancestor inconsistently, or who are guessing in order to determine relationships among taxa. Our 18-question tool (see Additional file 1) can be used for formative assessment of student understanding of how to interpret relationships on evolutionary trees. Because our assessment tests for the same skill throughout, students who answer incorrectly, even once, likely have an incomplete understanding of how to determine relationships on evolutionary trees and should receive follow-up instruction.

CNV analysis in the Lithuanian population.

BackgroundAlthough copy number variation (CNV) has received much attention, knowledge about the characteristics of CNVs such as occurrence rate and distribution in the genome between populations and within the same population is still insufficient. In this study, Illumina 770 K HumanOmniExpress-12 v1.0 (and v1.1) arrays were used to examine the diversity and distribution of CNVs in 286 unrelated individuals from the two main ethnolinguistic groups of the Lithuanian population (Aukštaičiai and Žemaičiai) (see Additional file 3). For primary data analysis, the Illumina GenomeStudio™ Genotyping Module v1.9 and two algorithms, cnvPartition 3.2.0 and QuantiSNP 2.0, were used to identify high-confidence CNVs.ResultsA total of 478 autosomal CNVs were detected by both algorithms, and those were clustered in 87 copy number variation regions (CNVRs), spanning ~12.5 Mb of the genome (see Table 1). At least 8.6 % of the CNVRs were unique and had not been reported in the Database of Genomic Variants. Most CNVRs (57.5 %) were rare, with a frequency of <1 %, whereas common CNVRs with at least 5 % frequency made up only 1.1 % of all CNVRs identified. About 49 % of non-singleton CNVRs were shared between Aukštaičiai and Žemaičiai, and the remaining CNVRs were specific to each group. Many of the CNVs detected (66 %) overlapped with known UCSC gene regions.ConclusionsThe ethnolinguistic groups of the Lithuanian population could not be differentiated based on CNV profiles, which may reflect their geographical proximity and suggest the homogeneity of the Lithuanian population. In addition, putative novel CNVs unique to the Lithuanian population were identified. The results of our study enhance the CNV map of the Lithuanian population.Electronic supplementary materialThe online version of this article (doi:10.1186/s12863-016-0373-6) contains supplementary material, which is available to authorized users.

MonoPhy: a simple R package to find and visualize monophyly issues

Background.The monophyly of taxa is an important attribute of a phylogenetic tree. A lack of it may hint at shortcomings of either the tree or the current taxonomy, or can indicate cases of incomplete lineage sorting or horizontal gene transfer. Whichever is the reason, a lack of monophyly can misguide subsequent analyses. While monophyly is conceptually simple, it is manually tedious and time consuming to assess on modern phylogenies of hundreds to thousands of species.Results.The R packageMonoPhyallows assessment and exploration of monophyly of taxa in a phylogeny. It can assess the monophyly of genera using the phylogeny only, and with an additional input file any other desired higher order taxa or unranked groups can be checked as well.Conclusion.Summary tables, easily subsettable results and several visualization options allow quick and convenient exploration of monophyly issues, thus makingMonoPhya valuable tool for any researcher working with phylogenies.

The Cologne Database for Molecular Spectroscopy, CDMS, in the Virtual Atomic and Molecular Data Centre, VAMDC

The Cologne Database for Molecular Spectroscopy, CDMS, was founded 1998 to provide in its catalog section line lists of mostly molecular species which are or may be observed in various astronomical sources (usually) by radio astronomical means. The line lists contain transition frequencies with qualified accuracies, intensities, quantum numbers, as well as further auxiliary information. They have been generated from critically evaluated experimental line lists, mostly from laboratory experiments, employing established Hamiltonian models. Separate entries exist for different isotopic species and usually also for different vibrational states. As of December 2015, the number of entries is 792. They are available online as ascii tables with additional files documenting information on the entries.The Virtual Atomic and Molecular Data Centre, VAMDC, was founded more than 5years ago as a common platform for atomic and molecular data. This platform facilitates exchange not only between spectroscopic databases related to astrophysics or astrochemistry, but also with collisional and kinetic databases. A dedicated infrastructure was developed to provide a common data format in the various databases enabling queries to a large variety of databases on atomic and molecular data at once.For CDMS, the incorporation in VAMDC was combined with several modifications on the generation of CDMS catalog entries. Here we introduce related changes to the data structure and the data content in the CDMS. The new data scheme allows us to incorporate all previous data entries but in addition allows us also to include entries based on new theoretical descriptions. Moreover, the CDMS entries have been transferred into a mySQL database format. These developments within the VAMDC framework have in part been driven by the needs of the astronomical community to be able to deal efficiently with large data sets obtained with the Herschel Space Telescope or, more recently, with the Atacama Large Millimeter Array.

Erratum to: ‘Phase II/III weekly nab-paclitaxel plus gemcitabine or carboplatin versus gemcitabine/carboplatin as first-line treatment of patients with metastatic triple-negative breast cancer (the tnAcity study): study protocol for a randomized controlled trial

Triple-negative breast cancer is an aggressive disease with unmet clinical needs. In a phase III study of patients with metastatic triple-negative breast cancer, first-line gemcitabine/carboplatin resulted in a median progression-free survival of 4.6 months. nab-Paclitaxel-based regimens (with gemcitabine or carboplatin ± bevacizumab) also demonstrated efficacy and safety in first-line phase II trials of human epidermal growth factor receptor 2-negative metastatic breast cancer. In this international, multicenter, open-label, randomized phase II/III trial, the efficacy and safety of first-line nab-paclitaxel with gemcitabine or with carboplatin will be compared with gemcitabine/carboplatin (control arm) for metastatic triple-negative breast cancer. In the phase II portion, 240 patients with measurable metastatic triple-negative breast cancer and treatment naive for metastatic disease will be randomized 1:1:1 (stratified by disease-free interval: ≤ 1 versus > 1 year) to nab-paclitaxel 125 mg/m2 plus gemcitabine 1000 mg/m2, nab-paclitaxel 125 mg/m2 plus carboplatin area under the curve 2 mg × min/mL, or gemcitabine 1000 mg/m2 plus carboplatin area under the curve 2 mg × min/mL, all given on days 1 and 8 of a 21-day cycle. Investigator-assessed progression-free survival (primary endpoint), overall response rate, overall survival, and safety will be assessed. A ranking algorithm of five efficacy and safety parameters will be used to pick the “winner” of the nab-paclitaxel regimens. In the phase III portion, 550 patients will be randomized 1:1 (stratified by disease-free interval: ≤ 1 versus > 1 year, and prior adjuvant/neoadjuvant taxane use) to the nab-paclitaxel combination arm selected from the phase II portion or to the control arm. Patients in phase II will not be part of the phase III population. The phase III primary endpoint is blinded, independently-assessed progression-free survival; secondary endpoints include blinded, independently assessed overall response rate, overall survival, disease control rate, duration of response, and safety. Biomarker and circulating tumor-cell exploratory analyses and quality-of-life assessments will also be performed. A list of approving ethical bodies was provided in Additional file 1. The tnAcity trial aims to identify a new standard cytotoxic chemotherapy regimen for first-line treatment of metastatic triple-negative breast cancer. ClinicalTrials.gov: NCT01881230 . Date of registration: 17 June 2013.