Classification Using Generalized Partial Least Squares

The advances in computational biology have made simultaneous monitoring of thousands of features possible. The high throughput technologies not only bring about a much richer information context in which to study various aspects of gene functions but they also present challenge of analyzing data with large number of covariates and few samples. As an integral part of machine learning, classification of samples into two or more categories is almost always of interest to scientists. In this paper, we address the question of classification in this setting by extending partial least squares (PLS), a popular dimension reduction tool in chemometrics, in the context of generalized linear regression based on a previous approach, Iteratively ReWeighted Partial Least Squares, i.e. IRWPLS (Marx, 1996). We compare our results with two-stage PLS (Nguyen and Rocke, 2002A; Nguyen and Rocke, 2002B) and other classifiers. We show that by phrasing the problem in a generalized linear model setting and by applying bias correction to the likelihood to avoid (quasi)separation, we often get lower classification error rates.

Cancer, meta-analysis and reporting biases: the case of erythropoiesis-stimulating agents.

Reporting and publication bias is a well-known problem in meta-analysis and healthcare research. In 2002 we conducted a meta-analysis on the effects of erythropoiesis-stimulating agents (ESAs) on overall survival in cancer patients, which suggested some evidence for improved survival in patients receiving ESAs compared with controls. However, a meta-analysis of individual patient data conducted several years later showed the opposite of our first meta-analysis, that is, evidence for increased on-study mortality and reduced overall survival in cancer patients receiving ESAs. We aimed to determine whether the results of our first meta-analysis could have been affected by publication and reporting biases and, if so, whether timely access to clinical study reports and individual patient data could have prevented this. We conducted a hypothetical meta-analysis for overall survival including all studies and study data that could have been available in 2002, at the time when we conducted our first meta-analysis. Compared with our original meta-analysis, which suggested an overall survival benefit for cancer patients receiving ESAs [hazard ratio (HR) 0.81, 95% confidence interval (CI) 0.67‒0.99], our hypothetical meta-analysis based on the results of all studies conducted at the time of the first analysis did not show evidence for a beneficial effect of ESAs on overall survival (HR 0.97, 95% CI 0.83‒1.12). Thus we have to conclude that our first meta-analysis showed misleading overall survival benefits due to publication and reporting biases, which could have been prevented by timely access to clinical study reports and individual patient data. Unrestricted access to clinical study protocols including amendments, clinical study reports and individual patient data is needed to ensure timely detection of both beneficial and harmful effects of healthcare interventions.

A new tool based on two micromanipulators facilitates the handling of ultrathin cryosection ribbons

A close to native structure of bulk biological specimens can be imaged by cryo-electron microscopy of vitreous sections (CEMOVIS). In some cases structural information can be combined with X-ray data leading to atomic resolution in situ. However, CEMOVIS is not routinely used. The two critical steps consist of producing a frozen section ribbon of a few millimeters in length and transferring the ribbon onto an electron microscopy grid. During these steps, the first sections of the ribbon are wrapped around an eyelash (unwrapping is frequent). When a ribbon is sufficiently attached to the eyelash, the operator must guide the nascent ribbon. Steady hands are required. Shaking or overstretching may break the ribbon. In turn, the ribbon immediately wraps around itself or flies away and thereby becomes unusable. Micromanipulators for eyelashes and grids as well as ionizers to attach section ribbons to grids were proposed. The rate of successful ribbon collection, however, remained low for most operators. Here we present a setup composed of two micromanipulators. One of the micromanipulators guides an electrically conductive fiber to which the ribbon sticks with unprecedented efficiency in comparison to a not conductive eyelash. The second micromanipulator positions the grid beneath the newly formed section ribbon and with the help of an ionizer the ribbon is attached to the grid. Although manipulations are greatly facilitated, sectioning artifacts remain but the likelihood to investigate high quality sections is significantly increased due to the large number of sections that can be produced with the reported tool.

Assessing the reporting quality in abstracts of randomized controlled trials in leading journals of oral implantology.

AIM Abstracts of randomized clinical trials are extremely important as trial appraisal is often based on the information included here. The objective of this study was to assess the quality of the reporting of RCT abstracts in journals of Oral Implantology. MATERIAL AND METHODS Six leading Implantology journals were screened for RCTs between years 2008 and 2012. A 21-item modified CONSORT for abstracts checklist was used to examine the completeness of abstract reporting. Descriptive statistics and linear regression modeling were employed for data analysis. RESULTS One hundred and sixty three RCT abstracts were included in this study. The majority of the RCTs were published in the Clinical Oral Implants Research (42.9%). The mean overall reporting quality score was 58.6% (95% CI: 57.6-59.7). The highest score was noted in the European Journal of Oral Implantology (63.8%; 95% CI: 61.8-65.8). Multivariate analysis demonstrated that abstract quality score was related to publication journal and number of research centers involved. Most abstracts adequately reported interventions (89.0%), objectives (77.9%) and conclusions (74.8%) while failed to report randomization procedures, allocation concealment, effect estimate, confidence intervals, and funding. Registration of RCTs was not reported in any of the abstracts. CONCLUSIONS The reporting quality in abstracts of RCTs published in Oral Implantology journals needs to be improved. Editors and authors should be encouraged to endorse the CONSORT for abstracts guidelines in order to achieve optimal quality in abstract reporting.

Who gets the high quality jobs ten years after compulsory school?

Good work quality is crucial for employee well-being and health. Indicators of work quality are, among others, aspects of one’s work organization and learning opportunities. Based on the Job-Demands Control model we investigate if a) young employees are confronted with different combinations of job characteristics, b) cluster membership is predicted through socio-demographic and educational factors as well as positive self-evaluations and health, and c) cluster membership leads to different associations with job-related and general well-being. Based on TREE (Transition from Education to Employment) data we found three clusters of job characteristics, i.e. high resources – low demands, medium resources – medium demands, and low resources – high demands. Likelihood to be in a more favourable group was higher for females and young employees who reported more positive self-evaluations and higher learning efforts after compulsory school. Young employees in more favourable groups also reported higher levels of job-related and general well-being.

Time relevance, citation of reporting guidelines, and breadth of literature search in systematic reviews in orthodontics

INTRODUCTION As the importance of systematic review (SR) conclusions relies upon the scientific rigor of methods and the currency of evidence, we aimed to investigate the currency of orthodontic SRs using as proxy the time from the initial search to publication. Additionally, SR information regarding reporting guidelines, registration, and literature searches were recorded when available. MATERIALS AND METHODS A systematic PubMed search was carried out using the Clinical Queries page to identify orthodontic SRs cited between 1 January 2008 and 7 November 2013. Data related to reporting guidelines, review registration, dates of review processing, literature search, and abstract reporting were retrieved and classified by journal type. Survival analysis was used to assess the time to reach predefined manuscript stages for orthodontic and non-orthodontic journals. RESULTS One hundred twenty seven of the originally identified 585 SRs were considered eligible. The median interval from search until publication was 13.2 months (interquartile range: IQR = 9.7 months) irrespective of the journal type. There was evidence (P = 0.05) that SRs published by non-orthodontic journals appeared in PubMed faster than in orthodontic journals (non-orthodontic: median = 6.5 months; IQR = 5.7 months; orthodontic: median = 10.2 months; IQR = 5.6 months) from submission to publication and from acceptance to publication (non-orthodontic: median = 1.5 months; IQR = 2.4 months; orthodontic: median = 6.0 months; IQR = 6.2 months; P < 0.001). More than half of these SRs did not cite adherence to any reporting guidelines, whereas all but five studies were not prospectively registered. Search of unpublished research was undertaken in approximately 21 per cent and 29 per cent of the SRs published in non-orthodontic and orthodontic periodicals, respectively. CONCLUSIONS This study indicates that SR users should be aware that median time for orthodontic SRs from search to publication is 13.2 months. SRs published in non-orthodontic journals are likely to be more current in terms of submission until time to publication and acceptance until time to publication compared with those published in orthodontic journals.

Splitsville: A Study of Income Inequality and Political Polarization in the United States House of Representatives

The study compares a measure of income inequality with polarization scores of U.S. Representatives from the 104th to the 109th Congresses. It attempts to explain the link, on the abstract level, between high inequality and high polarization. The end findings indicate that inequality increases a Representative's likelihood to act liberally.

Is family medicine meeting the HIV/AIDS challenge? A national survey of family physicians' beliefs, clinical competence, and experience regarding HIV disease

A national sample of family physicians was surveyed to (1) assess family physicians' beliefs about the human immunodeficiency virus (HIV) and individuals at risk for infection, their clinical competence regarding HIV-related issues, and their experiences with HIV disease; (2) present conclusions to the American Academy of Family Physicians (AAFP) to effect the development of an early clinical care protocol and a continuing medical education curriculum; and (3) collect base-line data for use in the evaluation of an early clinical care protocol and a continuing medical education curriculum, in the case that such programs are developed and disseminated. After considering retired or deceased respondents, of the 2,660 physicians surveyed, 1,678 (63.7%) responded. The resulting sample was representative of the active members of the AAFP. About 77% of the respondents were unable to accurately identify the universal precautions for blood and body fluids to prevent occupational transmission of HIV or hepatitis B virus (HBV). Residency trained and board certified physicians expressed fewer "external constraints," such as fear of losing patients, obviating them from providing treatment to individuals with HIV disease (p =.004 and p $<$.001, respectively). These physicians also manifested fewer "internal constraints" to the provision of HIV treatment, such as fear of becoming infected (p $<$.001 and p =.012, respectively). Residency trained physicians also expressed a greater comfort with discussing sexually-related topics with their patients than did non-residency trained physicians (p $<$.001). There were 67.1% of the physicians surveyed who reported never providing treatment to an individual with HIV disease. Residency trained and board certified physicians expressed a greater likelihood to provide treatment to HIV-infected patients (p $<$.001) than non-residency trained and non-board certified physicians.^ Among the various primary care specialties, family medicine is especially vulnerable to the current challenges of HIV/AIDS. These challenges are augmented by the epidemiologic pattern that characterizes AIDS. For the past several years, we have seen AIDS in this country assume a similar pattern to that seen in most other countries; HIV is becoming increasingly prevalent in the heterosexual population as well as in locations removed from metropolitan centers. This current phase of the epidemic generates greater pressures upon primary care physicians, particularly family physicians, to become better acquainted with the means to provide early care to HIV/AIDS patients and to prevent HIV/AIDS among their patients. Family medicine is especially appropriate for providing care to HIV patients because family medicine involves treatment to all age groups and conditions; other primary care specialties focus on limited patient populations or specific conditions. Family physicians should be armed with the expertise to confront HIV/AIDS. However, family physicians' clinical competence and experience with HIV is not known. The data collected in this survey describes their competencies, attitudes, and experiences. ^

Renal Cryoablation: Investigation of Periprocedural Visualization Tools and Treatment Response Quantification

Cryoablation for small renal tumors has demonstrated sufficient clinical efficacy over the past decade as a non-surgical nephron-sparing approach for treating renal masses for patients who are not surgical candidates. Minimally invasive percutaneous cryoablations have been performed with image guidance from CT, ultrasound, and MRI. During the MRI-guided cryoablation procedure, the interventional radiologist visually compares the iceball size on monitoring images with respect to the original tumor on separate planning images. The comparisons made during the monitoring step are time consuming, inefficient and sometimes lack the precision needed for decision making, requiring the radiologist to make further changes later in the procedure. This study sought to mitigate uncertainty in these visual comparisons by quantifying tissue response to cryoablation and providing visualization of the response during the procedure. Based on retrospective analysis of MR-guided cryoablation patient data, registration and segmentation algorithms were investigated and implemented for periprocedural visualization to deliver iceball position/size with respect to planning images registered within 3.3mm with at least 70% overlap and a quantitative logit model was developed to relate perfusion deficit in renal parenchyma visualized in verification images as a result of iceball size visualized in monitoring images. Through retrospective study of 20 patient cases, the relationship between likelihood of perfusion loss in renal parenchyma and distance within iceball was quantified and iteratively fit to a logit curve. Using the parameters from the logit fit, the margin for 95% perfusion loss likelihood was found to be 4.28 mm within the iceball. The observed margin corresponds well with the clinically accepted margin of 3-5mm within the iceball. In order to display the iceball position and perfusion loss likelihood to the radiologist, algorithms were implemented to create a fast segmentation and registration module which executed in under 2 minutes, within the clinically-relevant 3 minute monitoring period. Using 16 patient cases, the average Hausdorff distance was reduced from 10.1mm to 3.21 mm with average DSC increased from 46.6% to 82.6% before and after registration.

Detection histories for eight species of Amazona parrots in Venezuela during the NeoMaps bird surveys in 2010

Documenting changes in distribution is necessary for understanding species' response to environmental changes, but data on species distributions are heterogeneous in accuracy and resolution. Combining different data sources and methodological approaches can fill gaps in knowledge about the dynamic processes driving changes in species-rich, but data-poor regions. We combined recent bird survey data from the Neotropical Biodiversity Mapping Initiative (NeoMaps) with historical distribution records to estimate potential changes in the distribution of eight species of Amazon parrots in Venezuela. Using environmental covariates and presence-only data from museum collections and the literature, we first used maximum likelihood to fit a species distribution model (SDM) estimating a historical maximum probability of occurrence for each species. We then used recent, NeoMaps survey data to build single-season occupancy models (OM) with the same environmental covariates, as well as with time- and effort-dependent detectability, resulting in estimates of the current probability of occurrence. We finally calculated the disagreement between predictions as a matrix of probability of change in the state of occurrence. Our results suggested negative changes for the only restricted, threatened species, Amazona barbadensis, which has been independently confirmed with field studies. Two of the three remaining widespread species that were detected, Amazona amazonica, Amazona ochrocephala, also had a high probability of negative changes in northern Venezuela, but results were not conclusive for Amazona farinosa. The four remaining species were undetected in recent field surveys; three of these were most probably absent from the survey locations (Amazona autumnalis, Amazona mercenaria and Amazona festiva), while a fourth (Amazona dufresniana) requires more intensive targeted sampling to estimate its current status. Our approach is unique in taking full advantage of available, but limited data, and in detecting a high probability of change even for rare and patchily-distributed species. However, it is presently limited to species meeting the strong assumptions required for maximum-likelihood estimation with presence-only data, including very high detectability and representative sampling of its historical distribution.

Publishing Linked Data - There is no One-Size-Fits-All Formula

Publishing Linked Data is a process that involves several design decisions and technologies. Although some initial guidelines have been already provided by Linked Data publishers, these are still far from covering all the steps that are necessary (from data source selection to publication) or giving enough details about all these steps, technologies, intermediate products, etc. Furthermore, given the variety of data sources from which Linked Data can be generated, we believe that it is possible to have a single and uni�ed method for publishing Linked Data, but we should rely on di�erent techniques, technologies and tools for particular datasets of a given domain. In this paper we present a general method for publishing Linked Data and the application of the method to cover di�erent sources from di�erent domains.

Análise exômica em pacientes portadores de cardiomiopatia hipertrófica

A cardiomiopatia hipertrófica (CMH) é uma doença geneticamente determinada, caracterizada por hipertrofia ventricular primária, com prevalência estimada de 0.2% na população geral. Qualquer portador tem 50% de chance de transmitir esta doença para seus filhos, o que torna cada vez mais relevante a importância do estudo genético dos indivíduos acometidos e de seus familiares. Já foram descritas diversas mutações genéticas causadoras de CMH, a maioria em genes que codificam proteínas do sarcômero, e algumas mutações mais raras em genes não sarcoméricos. O objetivo desse estudo é sequenciar as regiões exônicas de genes candidatos, incluindo os principais envolvidos na hipertrofia miocárdica, utilizando o sequenciamento de nova geração (Generation Sequencing); testar a aplicabilidade e viabilidade deste sistema para identificar mutações já confirmadas e propor as prováveis novas mutações causadoras de CMH. Métodos e resultados: 66 pacientes não aparentados portadores de CMH foram estudados e submetidos à coleta de sangue para obtenção do DNA para analisar as regiões exômicas de 82 genes candidatos, utilizando a plataforma MiSeq (Illumina). Identificou-se 99 mutações provavelmente patogênicas em 54 pacientes incluídos no estudo (81,8%) relacionadas ou não a CMH, e distribuídas em 42 genes diferentes. Destas mutações 27 já haviam sido publicadas, sendo que 17 delas descritas como causadoras de CMH. Em 28 pacientes (42,4%) identificou-se mutação nos três principais genes sarcoméricos relacionados à CMH (MYH7, MYBPC3, TNNT2). Encontrou-se também um grande número de variantes não sonôminas de efeito clínico incerto e algumas mutações relacionadas a outras enfermidades. Conclusão: a análise da sequencia dos exônos de genes candidatos, demonstrou ser uma técnica promissora para o diagnóstico genético de CMH de forma mais rápida e sensível. A quantidade de dados gerados é o um fator limitante até o momento, principalmente em doenças geneticamente complexas com envolvimento de diversos genes e com sistema de bioinformática limitado.

Moral Opinion Polarization and the Erosion of Trust

Since Puntam's seminal work on declining levels of social capital, the question of how social trust is formed has reached unprecedented heights of critical enquiry. While most of the current research concentrates on ethnic diversity and income inequality as the main influences driving down generalized trust, we focus on opinion polarization as another potential impact factor on trust. In more detail, we investigate the extent to which polarization over morally charged issues such as homsexuality, abortion and euthanasia affects individuals' likelihood to trust others. We hypothesize that moral issues have a natural tendency to divide societies' opinions into opposing poles and, thus, to challenge social cohesion in modern civil societies. Based on hierarchical analyses of the fifth wave of the World Values Survey (WVS) — comprising a sample of 39 countries — our results reveal that individuals living in countries characterized by more opinion polarization tend to have less trust in other people.

Correspondence concerning a decision in the suit between the Kansas Pacific and Union Pacific Railroads /

With: Acts of Congress relating to the Union Pacific railroad and branches. Washington : J.L. Pearson, Printer, 1877. Bound together subsequent to publication.

Pacific railroad lines : speech of Hon. J.B. Chaffee, of Colorado, in the United States Senate, November 13, 1877.

Cover title.