PURPOSE: New strategies for developing inhibitors of Mycobacterium tuberculosis (Mtb) are required in order to identify the next generation of tuberculosis (TB) drugs. Our approach leverages the integration of intensive data mining and curation and computational approaches, including cheminformatics combined with bioinformatics, to suggest biological targets and their small molecule ...

Mycobacterium tuberculosis (MTB) is the principal pathogen which causes tuberculosis (TB), a disease that remains as one of the most alarming health problems worldwide. An active area for the search of new anti-TB therapies is concerned with the use computational approaches based on Chemoinformatics and/or Bioinformatics toward the discovery of ...

Although annual data are commonly used to model linear trends and changes in trends of disease incidence, monthly data could provide additional resolution for statistical inferences. Because monthly data may exhibit seasonal patterns, we need to consider seasonally adjusted models, which can be theoretically complex and computationally intensive. We propose ...

This paper formulates a set of rules to classify genotypes of the Mycobacterium tuberculosis complex (MTBC) into major lineages using spoligotypes and MIRU-VNTR results. The rules synthesize prior literature that characterizes lineages by spacer deletions and variations in the number of repeats seen at locus MIRU24 (alias VNTR2687). A tool ...

The remarkable advances in TB vaccinology over the last decade have been driven by a pragmatic approach to moving candidates along the development pipeline to clinical trials, fuelled by encouraging data on protection in animal models. Efficacy data from Phase IIb trials of the first generation of new candidates are ...

The resurgence of tuberculosis in the 1990s and the emergence of drug-resistant tuberculosis in the first decade of the 21st century increased the importance of epidemiological models for the disease. Due to slow progression of tuberculosis, the transmission dynamics and its long-term effects can often be better observed and predicted ...

De novo ligand design involves optimization of several ligand properties such as binding affinity, ligand volume, drug likeness, etc. Therefore optimization of these properties independently and simultaneously seems appropriate. In this article the ligand design problem is modeled in a multiobjective using Archived MultiObjective Simulated Annealing (AMOSA) as the underlying ...

Molecular diagnostics and genotyping of pathogens have become indispensable tools in clinical microbiology and disease surveillance. For isolates of the Mycobacterium tuberculosis complex (MTBC, causative agents of tuberculosis), multilocus variable number tandem repeat analysis (MLVA) targeting mycobacterial interspersed repetitive units (MIRU) has been internationally adopted as the new standard, portable, ...

ABSTRACT: BACKGROUND: The tuberculosis case register is the data source for the reports submitted by basic management units to the national tuberculosis program. Our objective was to measure the data entry time required to complete and double-enter one record, and to estimate the time for the correction of errors in ...

ABSTRACT: BACKGROUND: The objective of this study was to scrutinize number line estimation behaviors displayed by children in mathematics classrooms during the first three years of schooling. We extend existing research by not only mapping potential logarithmic-linear shifts but also provide a new perspective by studying in detail the estimation ...

Parkinson's disease (PD) is a disease of an aging population and its etiology is still unknown. In vivo models are attempts to capture as many of the hallmarks of PD as possible. To this end, a number of animal models are in use. These models parallel our thinking about the ...

Marijuana (Cannabis sativa) is the illicit drug most commonly used by two vulnerable populations relevant to neurodevelopment-pregnant women and teenagers. Human longitudinal studies have linked prenatal and adolescent cannabis exposure with long-term behavioral abnormalities as well as increased vulnerability to neuropsychiatric disorders in adulthood. Animal models provide a means of ...

Tuberculosis (TB) is a growing problem worldwide, especially with the emergence and high prevalence of multidrug-resistant strains. We develop a metapopulation model for TB spread, which is particularly suited to investigating transmission between areas of high and low prevalence. A case study of cross-border transmission in the Torres Strait region ...

A quantitative structure activity relationship (QSAR) study was performed on the fluroquinolones known to have anti-tuberculosis activity. The 3D-QSAR models were generated using stepwise variable selection of the four methods - multiple regression (MR), partial least square regression (PLSR), principal component regression (PCR) and artificial neural networks (kNN-MFA). The statistical ...

Protein/receptor explicit flexibility has recently become an important feature of molecular docking simulations. Taking the flexibility into account brings the docking simulation closer to the receptors' real behaviour in its natural environment. Several approaches have been developed to address this problem. Among them, modelling the full flexibility as an ensemble ...

This study tests a model of reciprocal influences between absenteeism and youth psychopathology using 3 longitudinal datasets (Ns = 20,745, 2,311, and 671). Participants in 1st through 12th grades were interviewed annually or biannually. Measures of psychopathology include self-, parent-, and teacher-report questionnaires. Structural cross-lagged regression models were tested. In a nationally ...

Walking and bicycling are important but underused modes of transportation in the United States. Road design influences how much walking and bicycling takes place along streets and roads. Currently, numerous national policy initiatives, including Safe Routes to School and Complete Streets, are attempting to improve pedestrian and bicycling infrastructure and ...

Mapping of number onto space is fundamental to mathematics and measurement. Previous research suggests that while typical adults with mathematical schooling map numbers veridically onto a linear scale, pre-school children and adults without formal mathematics training, as well as individuals with dyscalculia, show strong compressive, logarithmic-like non-linearities when mapping both ...

One of the procedures used most recently with longitudinal data is linear mixed models. In the context of health research the increasing number of studies that now use these models bears witness to the growing interest in this type of analysis. This paper describes the application of linear mixed models ...

Background. Prisons are recognised internationally as institutions with very high tuberculosis (TB) burdens where transmission is predominantly determined by contact between infectious and susceptible prisoners. A recent South African court case described the conditions under which prisoners awaiting trial were kept. With the use of these data, a mathematical model ...

Thailand's implementation of the Directly Observed Treatment, Short course (DOTS) strategy to increase tuberculosis (TB) control program efficacy has not achieved the World Health Organization (WHO) TB key targets. We defined two TB control models in the study. Patients in Model 1 were treated with a conventional DOTS strategy and ...

Recent factor analytic studies in Attention-Deficit/Hyperactivity Disorder (ADHD) have shown that hierarchical models provide a better fit of ADHD symptoms than correlated models. A hierarchical model includes a general ADHD factor and specific factors for inattention, and hyperactivity/impulsivity. The aim of this 12-month longitudinal study was to test the generalizability ...

ABSTRACT: BACKGROUND: In Uganda, malaria and lymphatic filariasis (causative agent Wuchereria bancrofti) are transmitted by the same vector species of Anopheles mosquitoes, and thus are likely to share common environmental risk factors and overlap in geographical space. In a comprehensive nationwide survey in 2000-2003 the geographical distribution of W. bancrofti ...

CONTEXT: The results of individual studies investigating the efficacy of chilling and other processing interventions on Salmonella prevalence or concentration in broiler chicken carcasses are inconsistent or contradictory. OBJECTIVE: Determine efficacy of chilling on reducing Salmonella prevalence or concentration on broiler carcasses using systematic review-meta-analysis, and explore sources of heterogeneity ...

Deriving hypotheses from I3 theory (pronounced "I-cubed theory"), the authors conducted 4 studies to clarify the circumstances under which dispositional aggressiveness predicts intimate partner violence (IPV) perpetration. Consistent with the hypothesis that this link would be stronger when inhibitory processes are weak rather than strong, Studies 1 and 2 demonstrated ...

Foa, Cascardi, Zoellner and Feeny developed two models of women's influence on intimate partner violence (IPV), which integrate victim-related variables associated with the cessation or continuation of partner violence (i.e., repeat IPV). One of the models focuses on psychological factors while the other centers on environmental factors. Central to both ...

SUMMARYIn order to characterize the association between county-level risk factors and the incidence of Cryptosporidium in the 2007 Iowa outbreak, we used generalized linear mixed models with the number of Cryptosporidium cases per county as the dependent variable. We employed a spatial power covariance structure, which assumed that the correlation ...

The Mediterranean basin is considered a hotspot of biological diversity with a long history of modification of natural ecosystems by human activities, and is one of the regions that will face extensive changes in climate. For 181 terrestrial mammals (68% of all Mediterranean mammals), we used an ensemble forecasting approach ...

Field studies evaluating the effects of multiple concurrent preharvest interventions for Escherichia coli O157 are logistically and economically challenging; however, modeling techniques may provide useful information on these effects while also identifying crucial information gaps that can guide future research. We constructed a risk assessment model with data obtained from ...

The positive youth development (PYD) perspective emphasizes that thriving occurs when individual ↔context relations involve the alignment of adolescent strengths with the resources in their contexts. The authors propose that a key component of this relational process is the strength that youth possess in the form of self-regulatory processes; these ...

Influenza pandemics in the last century were characterized by successive waves and differences in impact and timing between different regions, for reasons not clearly understood. The 2009 H1N1 pandemic showed rapid global spread, but with substantial heterogeneity in timing within each hemisphere. Even within Europe substantial variation was observed, with ...

Zhao and Running (Reports, 20 August 2010, p. 940) reported a reduction in global terrestrial net primary production (NPP) from 2000 through 2009. We argue that the small trends, regional patterns, and interannual variations that they describe are artifacts of their NPP model. Satellite observations of vegetation activity show no ...

ABSTRACT: BACKGROUND: Climate has a long history in organizational studies, but few theoretical models integrate the complex effects of climate during innovation implementation. In 1996, a theoretical model was proposed that organizations could develop a positive climate for implementation by making use of various policies and practices that promote organizational ...

The mounting evidence for anthropogenic changes in global climate raises many pressing questions about the potential effects on biological systems, and in particular the transmission of infectious diseases. Vector-borne diseases, such as dengue, may be particularly sensitive to both periodic fluctuations and sustained changes in global and local climates, because ...

This study compared the use of the conventional multilevel model (MM) with that of the multiple membership multilevel model (MMMM) for handling multiple membership data structures. Multiple membership data structures are commonly encountered in longitudinal educational data sets in which, for example, mobile students are members of more than one ...

Realistic, individual-based models based on detailed census data are increasingly used to study disease transmission. Whether the rich structure of such models improves predictions is debated. This is studied here for the spread of varicella, a childhood disease, in a realistic population of children where infection occurs in the household, ...

BACKGROUND. Studies that have combined accelerometers and global positioning systems (GPS) to identify walking have done so in carefully controlled conditions. This study tested algorithms for identifying walking trips from accelerometer and GPS data in free-living conditions. The study also assessed the accuracy of the locations where walking occurred compared ...

In this paper, the authors describe different instrumental variable (IV) estimators of causal risk ratios and odds ratios with particular attention to methods that can handle continuously measured exposures. The authors present this discussion in the context of a Mendelian randomization analysis of the effect of body mass index (BMI; ...

Two-compartment models provide more precise information about the contribution of the different portions of the airways to exhaled nitric oxide (NO). Airway wall concentration of NO (Caw,NO) and maximum flux of NO in the airways (J'aw,NO) reflect the tissue production rate of NO and they can be modified by corticosteroids. ...

Rhipicephalus sanguineus, the brown dog tick, has a worldwide distribution in areas with a relatively warm climate, including mild winters. This tick plays an important role as vector for various animal and human pathogens, including bacteria and protozoa. Based on precise daily meteorological data from the past 40 years, combined ...

Following the emergence of a novel strain of influenza A(H1N1) in Mexico and the United States in April 2009, its epidemiology in Europe during the summer was limited to sporadic and localised outbreaks. Only the United Kingdom experienced widespread transmission declining with school holidays in late July. Using statistical modelling ...

When novel scientific questions arise after longitudinal binary data have been collected, the subsequent selection of subjects from the cohort for whom further detailed assessment will be undertaken is often necessary to efficiently collect new information. Key examples of additional data collection include retrospective questionnaire data, novel data linkage, or ...

The current study examined the ability of the transtheoretical model (TTM) to describe and predict alcohol consumption-related behaviors. Data from 321 first-year students were collected on the first day of classes and the week before finals. Three structural models consistent with the TTM were evaluated and tested. The three models ...

The pharmaceutical industry is interested in developing new treatments for severe asthma (SA), recognising that there is a substantial unmet clinical need in this area. However, it faces a significant set of barriers in attempting to do so, including a) problems arising from the way SA is defined, b) the ...

Aim To determine whether excessive IgE production by patients with atopic allergic asthma decreases with omalizumab therapy. Methods Omalizumab, free and total IgE data were obtained from an epidemiological study and six randomised, double-blind, placebo-controlled trials in patients with allergic asthma. The binding between omalizumab and IgE together with the ...

The QT interval is regarded as an important biomarker for the assessment of arrhythmia liability, and evidence of QT prolongation has led to the withdrawal and relabeling of numerous compounds. Traditional methods of assessing QT prolongation correct the QT interval for the length of the RR interval (which varies inversely ...

The systemic inflammatory response syndrome often accompanies critical illnesses and can be an important cause of morbidity and mortality. Marked abnormalities in cardiovascular function accompany acute illnesses manifested as sustained tachyarrhythmias, which are but one component of systemic dysregulation. The realization that cardiac pacemaker activity is under control of the ...

A series of N-(pyrimidin-4-yl)-phenylalanine VLA-4 antagonists is described. Optimization of substituents at the 2 and 5 positions of the pyrimidine ring gave 14, a very potent VLA-4 inhibitor which is orally active in a sheep asthma model.

Airway remodeling in patients with chronic asthma is characterized by a thickening of the airway walls. It has been demonstrated in previous theoretical models that this change in thickness can have an important mechanical effect on the properties of the wall, in particular on the phenomenon of mucosal folding induced ...

Airway smooth muscle (ASM) cells have been shown to secrete significant amounts of immunomodulatory factors (IMFs), many of which are typically ascribed to trafficking leukocytes (e.g., GM-CSF, IL-6, IL-13, and eotaxin), and may be indicative of an immunomodulatory role for ASM in control of airway function, as well as in ...