Research papers

Grand challenges in global mental health

Pamela Y. Collins, Vikram Patel, Sarah S. Joestl, Dana March, Thomas R. Insel, Abdallah S. Daar, Isabel A. Bordin, E. Jane C…

An assessment of the use of partial least squares structural equation modeling in marketing research

Joe F. Hair, Marko Sarstedt, Christian M. Ringle, Jeannette A. Mena

Biology and novel treatment options for XLA, the most common monogenetic immunodeficiency in man

Rudi W. Hendriks, Robbert G. M. Bredius, Karin Pike‐Overzet, Frank J. T. Staal

INTRODUCTION: X-linked agammaglobulinemia (XLA) is the most common primary immunodeficiency in man, and is caused by a single genetic defect. Inactivating mutations in the Bruton's tyrosine kinase (BTK) gene are invariably the cause of XLA,. XLA is characterized by a differentiation arrest at the pre-B cell stage, the absence of immunoglobulins and recurrent bacterial infections, making it an insidious disease that gradually disables the patient, and can result in death due to chronic lung disease. Current treatment involves prophylactic antibiotics and immunoglobulin infusions, which are non-curative. This disease is a good candidate for curative hematopoietic stem cell (HSC)-based gene therapy, which could correct the B cell and myeloid deficiencies. AREAS COVERED: This paper reviews the basic biology of BTK in B cell development, the clinical features of XLA, and the possibilities of gene therapy for XLA, covering the literature from 1995 to 2010. EXPERT OPINION: Work from various laboratories demonstrates the feasibility of using gene-corrected HSCs to complement the immune defects of Btk-deficiency in mice. We propose that it is timely to start clinical programs to develop stem cell based therapy for XLA, using gene-corrected autologous HSC.

MEGA5: Molecular Evolutionary Genetics Analysis Using Maximum Likelihood, Evolutionary Distance, and Maximum Parsimony Methods

Koichiro Tamura, Daniel G. Peterson, Nora Peterson, Glen Stecher, M Nei, Sudhir Kumar

Comparative analysis of molecular sequence data is essential for reconstructing the evolutionary histories of species and inferring the nature and extent of selective forces shaping the evolution of genes and species. Here, we announce the release of Molecular Evolutionary Genetics Analysis version 5 (MEGA5), which is a user-friendly software for mining online databases, building sequence alignments and phylogenetic trees, and using methods of evolutionary bioinformatics in basic biology, biomedicine, and evolution. The newest addition in MEGA5 is a collection of maximum likelihood (ML) analyses for inferring evolutionary trees, selecting best-fit substitution models (nucleotide or amino acid), inferring ancestral states and sequences (along with probabilities), and estimating evolutionary rates site-by-site. In computer simulation analyses, ML tree inference algorithms in MEGA5 compared favorably with other software packages in terms of computational efficiency and the accuracy of the estimates of phylogenetic trees, substitution parameters, and rate variation among sites. The MEGA user interface has now been enhanced to be activity driven to make it easier for the use of both beginners and experienced scientists. This version of MEGA is intended for the Windows platform, and it has been configured for effective use on Mac OS X and Linux desktops. It is available free of charge from http://www.megasoftware.net.

Helicopter Downwash/Frigate Airwake Interaction Flowfield PIV Surveys in a Low Speed Wind Tunnel

Yavuz Nacaklı, Drew Landman

The work presented was performed at Old Dominion University and is part of a larger research program aimed at identifying interactions between rotor downwash and ship airwakes. The ODU Low-Speed Wind Tunnel was used with a simplified 1/50 scale frigate waterline model and traverse mounted powered rotor. Particle Image Velocimetry (PIV) velocity surveys were compared with rotor thrust coefficient measurements at locations of identified interaction to help understand the underlying flow physics. Initially, PIV surveys of the frigate model landing deck in isolation and the rotor in isolation were performed to provide a baseline flow understanding. A PIV flowfield survey was conducted with the ship in isolation, rotor in isolation and then the combined ship/rotor cases in order to compare superposed individual velocity fields to a combined measurement. Tests were performed with and without the presence of a rotary wing downwash influence on the landing deck centerline (y=0) for a wind-over-deck angle (WOD) of zero.

Preliminary study on the aspects of the biology of snakehead fish parachanna obscura (günther) in a Nigerian wetland

BB Bolaji, TU Mfon, DI Utibe

Between October 2000 and March 2001, a preliminary study on the aspects of the biology of Parachanna obscura, was carried out. Sex ratio revealed female preponderance (÷2 = 4.733, df = 1, P < 0.05). There was no variation in sex ratio during the wet season but there were more females than males in the dry season (÷2=4.735, df = 1, p =

Cutadapt removes adapter sequences from high-throughput sequencing reads

Marcel Martin

When small RNA is sequenced on current sequencing machines, the resulting reads are usually longer than the RNA and therefore contain parts of the 3' adapter. That adapter must be found and removed error-tolerantly from each read before read mapping. Previous solutions are either hard to use or do not offer required features, in particular support for color space data. As an easy to use alternative, we developed the command-line tool cutadapt, which supports 454, Illumina and SOLiD (color space) data, offers two adapter trimming algorithms, and has other useful features. Cutadapt, including its MIT-licensed source code, is available for download at http://code.google.com/p/cutadapt/

Progress and challenges in translating the biology of atherosclerosis

Peter Libby, Paul M. Ridker, Göran K. Hansson

The biology of fracture healing

Richard Marsell, Thomas A. Einhorn

Hallmarks of Cancer: The Next Generation

Douglas Hanahan, Robert A. Weinberg

The hallmarks of cancer comprise six biological capabilities acquired during the multistep development of human tumors. The hallmarks constitute an organizing principle for rationalizing the complexities of neoplastic disease. They include sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, and activating invasion and metastasis. Underlying these hallmarks are genome instability, which generates the genetic diversity that expedites their acquisition, and inflammation, which fosters multiple hallmark functions. Conceptual progress in the last decade has added two emerging hallmarks of potential generality to this list-reprogramming of energy metabolism and evading immune destruction. In addition to cancer cells, tumors exhibit another dimension of complexity: they contain a repertoire of recruited, ostensibly normal cells that contribute to the acquisition of hallmark traits by creating the "tumor microenvironment." Recognition of the widespread applicability of these concepts will increasingly affect the development of new means to treat human cancer.

Global cancer statistics

Ahmedin Jemal, Freddie Bray, Jacques Ferlay, Elizabeth Ward, David Forman

The global burden of cancer continues to increase largely because of the aging and growth of the world population alongside an increasing adoption of cancer-causing behaviors, particularly smoking, in economically developing countries. Based on the GLOBOCAN 2008 estimates, about 12.7 million cancer cases and 7.6 million cancer deaths are estimated to have occurred in 2008; of these, 56% of the cases and 64% of the deaths occurred in the economically developing world. Breast cancer is the most frequently diagnosed cancer and the leading cause of cancer death among females, accounting for 23% of the total cancer cases and 14% of the cancer deaths. Lung cancer is the leading cancer site in males, comprising 17% of the total new cancer cases and 23% of the total cancer deaths. Breast cancer is now also the leading cause of cancer death among females in economically developing countries, a shift from the previous decade during which the most common cause of cancer death was cervical cancer. Further, the mortality burden for lung cancer among females in developing countries is as high as the burden for cervical cancer, with each accounting for 11% of the total female cancer deaths. Although overall cancer incidence rates in the developing world are half those seen in the developed world in both sexes, the overall cancer mortality rates are generally similar. Cancer survival tends to be poorer in developing countries, most likely because of a combination of a late stage at diagnosis and limited access to timely and standard treatment. A substantial proportion of the worldwide burden of cancer could be prevented through the application of existing cancer control knowledge and by implementing programs for tobacco control, vaccination (for liver and cervical cancers), and early detection and treatment, as well as public health campaigns promoting physical activity and a healthier dietary intake. Clinicians, public health professionals, and policy makers can play an active role in accelerating the application of such interventions globally.

An integrated approach for fusion of environmental and human health data for disease surveillance

Howard Burkom, Liane Ramac-Thomas, Steven M. Babin, Rekha Holtry, Zaruhi R. Mnatsakanyan, Cynthia Yund

This paper describes the problem of public health monitoring for waterborne disease outbreaks using disparate evidence from health surveillance data streams and environmental sensors. We present a combined monitoring approach along with examples from a recent project at the Johns Hopkins University Applied Physics Laboratory in collaboration with the U.S. Environmental Protection Agency. The project objective was to build a module for the Electronic Surveillance System for the Early Notification of Community-based Epidemics (ESSENCE) to include water quality data with health indicator data for the early detection of waterborne disease outbreaks. The basic question in the fused surveillance application is 'What is the likelihood of the public health threat of interest given recent information from available sources of evidence?' For a scientific perspective, we formulate this question in terms of the estimation of positive predictive value customary in classical epidemiology, and we present a solution framework using Bayesian Networks (BN). An overview of the BN approach presents advantages, disadvantages, and required adaptations needed for a fused surveillance capability that is scalable and robust relative to the practical data environment. In the BN project, we built a top-level health/water-quality fusion BN informed by separate waterborne-disease-related networks for the detection of water contamination and human health effects. Elements of the art of developing networks appropriate to this environment are discussed with examples. Results of applying these networks to a simulated contamination scenario are presented.

Physical illness in patients with severe mental disorders. I. Prevalence, impact of medications and disparities in health care

MARC DE HERT, Christoph U. Correll, Julio Bobes, Marcelo Cetkovich, Dan Cohen, Itsuo Asai, Johan Detraux, Shiv Gautam, Hans‐…

The lifespan of people with severe mental illness (SMI) is shorter compared to the general population. This excess mortality is mainly due to physical illness. We report prevalence rates of different physical illnesses as well as important individual lifestyle choices, side effects of psychotropic treatment and disparities in health care access, utilization and provision that contribute to these poor physical health outcomes. We searched MEDLINE (1966 - August 2010) combining the MeSH terms of schizophrenia, bipolar disorder and major depressive disorder with the different MeSH terms of general physical disease categories to select pertinent reviews and additional relevant studies through cross-referencing to identify prevalence figures and factors contributing to the excess morbidity and mortality rates. Nutritional and metabolic diseases, cardiovascular diseases, viral diseases, respiratory tract diseases, musculoskeletal diseases, sexual dysfunction, pregnancy complications, stomatognathic diseases, and possibly obesity-related cancers are, compared to the general population, more prevalent among people with SMI. It seems that lifestyle as well as treatment specific factors account for much of the increased risk for most of these physical diseases. Moreover, there is sufficient evidence that people with SMI are less likely to receive standard levels of care for most of these diseases. Lifestyle factors, relatively easy to measure, are barely considered for screening; baseline testing of numerous important physical parameters is insufficiently performed. Besides modifiable lifestyle factors and side effects of psychotropic medications, access to and quality of health care remains to be improved for individuals with SMI.

Asymptotic formulae for likelihood-based tests of new physics

Glen Cowan, Kyle Cranmer, Eilam Gross, Ofer Vitells

We describe likelihood-based statistical tests for use in high energy physics for the discovery of new phenomena and for construction of confidence intervals on model parameters. We focus on the properties of the test procedures that allow one to account for systematic uncertainties. Explicit formulae for the asymptotic distributions of test statistics are derived using results of Wilks and Wald. We motivate and justify the use of a representative data set, called the “Asimov data set”, which provides a simple method to obtain the median experimental sensitivity of a search or measurement as well as fluctuations about this expectation.

The Ecology, Biology and Pathogenesis of Acinetobacter spp.: An Overview

James Hamuel Doughari, Patrick Alois Ndakidemi, Izanne Susan Human, Spinney Benade

Acinetobacter are a major concern because of their rapid development of resistance to a wide range of antimicrobials, and rapid profundity in transformation, surviving desiccation and persisting in the environment for a very long time. The organisms are associated with bacteraemia, pulmonary infections, meningitis, diarrhea and notorious nosocomial infections with mortality rates of 20 to 60%. Transmission is via person-to-person contact, water and food contamination, and contaminated hospital equipment. The increasing virulence and rapid development of multidrug resistance by these organisms highlights the need to search for alternatives for chemotherapy. A poor understanding of the organisms and dearth of information about their occurrence especially in developing countries informed the need for this review paper.

Microwave Engineering

K. T. Mathew

Lecture Notes in Mathematics

Stéphane Crépey, Olivier Guéant, David Hobson, Monique Jeanblanc, Jean‐Michel Lasry, Pierre Louis Lions

Childhood adversities and adult psychopathology in the WHO World Mental Health Surveys

Ronald C. Kessler, Katie A. McLaughlin, Jennifer Green, Michael J. Gruber, Nancy A. Sampson, Alan M. Zaslavsky, Sergio Aguil…

BACKGROUND: Although significant associations of childhood adversities with adult mental disorders are widely documented, most studies focus on single childhood adversities predicting single disorders. AIMS: To examine joint associations of 12 childhood adversities with first onset of 20 DSM-IV disorders in World Mental Health (WMH) Surveys in 21 countries. METHOD: Nationally or regionally representative surveys of 51 945 adults assessed childhood adversities and lifetime DSM-IV disorders with the WHO Composite International Diagnostic Interview (CIDI). RESULTS: Childhood adversities were highly prevalent and interrelated. Childhood adversities associated with maladaptive family functioning (e.g. parental mental illness, child abuse, neglect) were the strongest predictors of disorders. Co-occurring childhood adversities associated with maladaptive family functioning had significant subadditive predictive associations and little specificity across disorders. Childhood adversities account for 29.8% of all disorders across countries. CONCLUSIONS: Childhood adversities have strong associations with all classes of disorders at all life-course stages in all groups of WMH countries. Long-term associations imply the existence of as-yet undetermined mediators.

New parton distributions for collider physics

Hung-Liang Lai, Marco Guzzi, J. Huston, Li Zhao, Pavel Nadolsky, Jon Pumplin, C.–P. Yuan

We extract new parton distribution functions (PDFs) of the proton by global analysis of hard scattering data in the general-mass framework of perturbative quantum chromodynamics. Our analysis includes new theoretical developments together with the most recent collider data from deep-inelastic scattering, vector boson production, and single-inclusive jet production. Because of the difficulty in fitting both the D0 Run-II $W$ lepton asymmetry data and some fixed-target DIS data, we present two families of PDFs, CT10 and CT10W, without and with these high-luminosity $W$ lepton asymmetry data included in the global analysis. With both sets of PDFs, we study theoretical predictions and uncertainties for a diverse selection of processes at the Fermilab Tevatron and the CERN Large Hadron Collider.

Human papillomavirus genotype attribution in invasive cervical cancer: a retrospective cross-sectional worldwide study

Silvia de Sanjosé, Wim Quint, Laia Alemany, D.T. Geraets, Jo Ellen Klaustermeier, Belén Lloveras, Sara Tous, Ana Félix, Luis…

Recurrent neural network based language model

Tomáš Mikolov, Martin Karafiát, Lukáš Burget, Jaň Černocký, Sanjeev Khudanpur

A new recurrent neural network based language model (RNN LM) with applications to speech recognition is presented. Results indicate that it is possible to obtain around 50% reduction of perplexity by using mixture of several RNN LMs, compared to a state of the art backoff language model. Speech recognition experiments show around 18% reduction of word error rate on the Wall Street Journal task when comparing models trained on the same amount of data, and around 5% on the much harder NIST RT05 task, even when the backoff model is trained on much more data than the RNN LM. We provide ample empirical evidence to suggest that connectionist language models are superior to standard n-gram techniques, except their high computational (training) complexity. Index Terms: language modeling, recurrent neural networks, speech recognition

Effects of Field Studies on Learning Outcome in Biology

Ajaja O. Patrick

The major purpose of this study was to determine the effects of field experiences on students’ knowledge of process of science and biology achievement. The design of the study was experimental, 2 x 2, pre-test, post-test control group design. The sample of the study consisted of 100 biology students in two intact classes. Four research questions were raised and collapsed to four hypotheses. The first three hypotheses were tested with t-test statistic at 0.05 level of significance. The fourth hypothesis was tested with Pearson Product Moment Correlation Statistic. The major findings of this study included: a significance difference in process of science scores between pre-test and posttest of field trip students; a significant difference in process of science test scores between students exposed to field trip experiences and those who were not exposed; a significant difference in biology achievement test scores between students exposed to field trip experiences and those who were not; and a strong correlation between process of science score and biology achievement score. It was concluded that field trip experiences enhanced students’ understanding of process of science, improved students’ attitude towards biology and significantly influenced their biology achievement.

How wide is the “knowing-doing” gap in invasion biology?

Karen J. Esler, Heidi Prozesky, Gyan Prakash Sharma, Mélodie A. McGeoch

Screening for serious mental illness in the general population with the K6 screening scale: results from the WHO World Mental Health (WMH) survey initiative

Ronald C. Kessler, Jennifer Green, Michael J. Gruber, Nancy A. Sampson, Evelyn J. Bromet, Marius Cuitan, Toshi A. Furukawa, …

Data are reported on the background and performance of the K6 screening scale for serious mental illness (SMI) in the World Health Organization (WHO) World Mental Health (WMH) surveys. The K6 is a six-item scale developed to provide a brief valid screen for Diagnostic and Statistical Manual of Mental Disorders 4th edition (DSM-IV) SMI based on the criteria in the US ADAMHA Reorganization Act. Although methodological studies have documented good K6 validity in a number of countries, optimal scoring rules have never been proposed. Such rules are presented here based on analysis of K6 data in nationally or regionally representative WMH surveys in 14 countries (combined N = 41,770 respondents). Twelve-month prevalence of DSM-IV SMI was assessed with the fully-structured WHO Composite International Diagnostic Interview. Nested logistic regression analysis was used to generate estimates of the predicted probability of SMI for each respondent from K6 scores, taking into consideration the possibility of variable concordance as a function of respondent age, gender, education, and country. Concordance, assessed by calculating the area under the receiver operating characteristic curve, was generally substantial (median 0.83; range 0.76-0.89; inter-quartile range 0.81-0.85). Based on this result, optimal scaling rules are presented for use by investigators working with the K6 scale in the countries studied.