Paradigm of tunable clustering using binarization of consensus partition matrices (Bi-CoPaM) for gene discovery

Copyright @ 2013 Abu-Jamous et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.Clustering analysis has a growing role in the study of co-expressed genes for gene discovery. Conventional binary and fuzzy clustering do not embrace the biological reality that some genes may be irrelevant for a problem and not be assigned to a cluster, while other genes may participate in several biological functions and should simultaneously belong to multiple clusters. Also, these algorithms cannot generate tight clusters that focus on their cores or wide clusters that overlap and contain all possibly relevant genes. In this paper, a new clustering paradigm is proposed. In this paradigm, all three eventualities of a gene being exclusively assigned to a single cluster, being assigned to multiple clusters, and being not assigned to any cluster are possible. These possibilities are realised through the primary novelty of the introduction of tunable binarization techniques. Results from multiple clustering experiments are aggregated to generate one fuzzy consensus partition matrix (CoPaM), which is then binarized to obtain the final binary partitions. This is referred to as Binarization of Consensus Partition Matrices (Bi-CoPaM). The method has been tested with a set of synthetic datasets and a set of five real yeast cell-cycle datasets. The results demonstrate its validity in generating relevant tight, wide, and complementary clusters that can meet requirements of different gene discovery studies.National Institute for Health Researc

UNCLES: Method for the identification of genes differentially consistently co-expressed in a specific subset of datasets

Background: Collective analysis of the increasingly emerging gene expression datasets are required. The recently proposed binarisation of consensus partition matrices (Bi-CoPaM) method can combine clustering results from multiple datasets to identify the subsets of genes which are consistently co-expressed in all of the provided datasets in a tuneable manner. However, results validation and parameter setting are issues that complicate the design of such methods. Moreover, although it is a common practice to test methods by application to synthetic datasets, the mathematical models used to synthesise such datasets are usually based on approximations which may not always be sufficiently representative of real datasets. Results: Here, we propose an unsupervised method for the unification of clustering results from multiple datasets using external specifications (UNCLES). This method has the ability to identify the subsets of genes consistently co-expressed in a subset of datasets while being poorly co-expressed in another subset of datasets, and to identify the subsets of genes consistently co-expressed in all given datasets. We also propose the M-N scatter plots validation technique and adopt it to set the parameters of UNCLES, such as the number of clusters, automatically. Additionally, we propose an approach for the synthesis of gene expression datasets using real data profiles in a way which combines the ground-truth-knowledge of synthetic data and the realistic expression values of real data, and therefore overcomes the problem of faithfulness of synthetic expression data modelling. By application to those datasets, we validate UNCLES while comparing it with other conventional clustering methods, and of particular relevance, biclustering methods. We further validate UNCLES by application to a set of 14 real genome-wide yeast datasets as it produces focused clusters that conform well to known biological facts. Furthermore, in-silico-based hypotheses regarding the function of a few previously unknown genes in those focused clusters are drawn. Conclusions: The UNCLES method, the M-N scatter plots technique, and the expression data synthesis approach will have wide application for the comprehensive analysis of genomic and other sources of multiple complex biological datasets. Moreover, the derived in-silico-based biological hypotheses represent subjects for future functional studies.The National Institute for Health Research (NIHR) under its Programme Grants for Applied Research Programme (Grant Reference Number RP-PG-0310-1004)

Antibiotic use among 8-month-old children in Malmö, Sweden – in relation to child characteristics and parental sociodemographic, psychosocial and lifestyle factors

In the county of Scania, Sweden, antibiotic use among small children is among the highest in the country. The aim of this study was to investigate the associations between antibiotic use among 8-month-old children in Malmö and characteristics of the child as well as parental sociodemographic characteristics, lifestyle factors, and psychosocial support. The study was a population-based cross-sectional survey. The study population consisted of children who visited the Child Health Care (CHC) centres in Malmö for their 8-month health checkup during 2003–2006 and whose parents answered a self-administered questionnaire (n = 7266 children). The questionnaire was distributed to parents of children registered with the CHC and invited for an 8-month checkup during the study period. The odds of using antibiotics increased as parental educational level decreased. Using high educational level as a reference group, low maternal educational level was associated with an increased antibiotic use for the child, odds ratio (OR) = 1.61 (95% CI: 1.34–1.93). Furthermore, children whose parents were born outside Sweden showed higher antibiotic use, OR = 1.43 (95% CI: 1.24–1.65), in comparison with children whose parents were born in Sweden. Exposure to environmental smoking, parental experience of economic stress, and a low level of emotional support increased the odds for antibiotic use. Boys had higher odds of use of antibiotics than girls, OR = 1.40 (95% CI: 1.25–1.57). Having a low birth weight, having an allergy and having siblings also increased the odds for early antibiotic use, while breastfeeding seemed to have a protective role. Conclusion There were clear associations between parental factors such as sociodemographic, psychosocial and lifestyle factors and antibiotic use at this early stage of life. Several characteristics of the child also affected the use of antibiotics

Specialized ommatidia of the polarization-sensitive dorsal rim area in the eye of monarch butterflies have non-functional reflecting tapeta

Many insects exploit sky light polarization for navigation or cruising-course control. The detection of polarized sky light is mediated by the ommatidia of a small specialized part of the compound eye: the dorsal rim area (DRA). We describe the morphology and fine structure of the DRA in monarch butterflies (Danaus plexippus). The DRA consists of approximately 100 ommatidia forming a narrow ribbon along the dorsal eye margin. Each ommatidium contains two types of photoreceptor with mutually orthogonal microvilli orientations occurring in a 2:6 ratio. Within each rhabdomere, the microvilli are well aligned. Rhabdom structure and orientation remain constant at all retinal levels, but the rhabdom profiles, as seen in tangential sections through the DRA, change their orientations in a fan-like fashion from the frontal to the caudal end of the DRA. Whereas these properties (two microvillar orientations per rhabdom, microvillar alignment along rhabdomeres, ommatidial fan array) are typical for insect DRAs in general, we also report and discuss here a novel feature. The ommatidia of monarch butterflies are equipped with reflecting tapeta, which are directly connected to the proximal ends of the rhabdoms. Although tapeta are also present in the DRA, they are separated from the rhabdoms by a space of approximately 55 μm effectively inactivating them. This reduces self-screening effects, keeping polarization sensitivity of all photoreceptors of the DRA ommatidia both high and approximately equal

The Problem of Signal and Symbol Integration: A Study of Cooperative Mobile Autonomous Agent Behaviors

This paper explores and reasons about the interplay between symbolic and continuous representations. We first provide some historical perspective on signal and symbol integration as viewed by the Artificial Intelligence (AI), Robotics and Computer Vision communities. The domain of autonomous robotic agents residing in dynamically changing environments anchors well different aspects of this integration and allows us to look at the problem in its entirety. Models of reasoning, sensing and control actions of such agents determine three different dimensions for discretization of the agent-world behavioral state space. The design and modeling of robotic agents, where these three aspects have to be closely tied together, provide a good experimental platform for addressing the signal-to-symbol transformation problem. We present some experimental results from the domain of cooperating mobile agents involved in tasks of navigation and manipulation

Polymorphism in NEDD4L Is Associated with Increased Salt Sensitivity, Reduced Levels of P-renin and Increased Levels of Nt-proANP

OBJECTIVE: Neuronal precursor cell expressed developmentally down-regulated 4-like (NEDD4L) is a regulator of the amiloride-sensitive epithelial sodium channel (ENaC), thus a candidate gene for salt sensitivity. Carriers of an intact NEDD4L C2-domain, encoded by the NEDD4L rs4149601 (G/A) GG genotype, together with the C-allele of the NEDD4L rs2288774 (C/T) polymorphism have previously been shown to have increased blood pressure. Our aim was to test if genetic variation in NEDD4L is associated with increased salt sensitivity. METHODS: 39 normotensive subjects were studied. The difference in 24-hour systolic blood pressure after four weeks on 150 mmol/day NaCl intake and four weeks on 50 mmol/day NaCl was defined as salt sensitivity. The rs4149601 and rs2288774 polymorphisms were genotyped using PCR-based techniques. RESULTS: Carriers of the rs4149601 GG-genotype together with the rs2288774 CC-genotype had significantly higher salt sensitivity (median, IQR) (18.0, 7.5–20.0 mmHg vs 6.0, 0.0–10.0 mmHg, P = 0.007) and lower plasma renin concentration (P-renin) (6.0, 2.0–9.5 mU/L vs 15.0, 9.0–24.0 mU/L, P = 0.005) as compared to non-carriers of these genotypes. In carriers of the rs4149601 GG-genotype together with the rs2288774 CC- or CT-genotype, as compared to non-carriers, salt sensitivity was (8.0, 6.0–18.0 mmHg vs 5.0, 0.0–10.0 mmHg, P = 0.07) and P-renin (9.0, 6.0–16.0 mU/L vs 15.0, 9.0–28.0 mU/L, P = 0.03). CONCLUSION: Genetic NEDD4L variation seems to affect salt sensitivity and P-renin in normotensive subjects, suggesting that genotyping of NEDD4L may be clinically useful in order to identify subjects who benefit from dietary salt restriction in the prevention of hypertension

Effects of music therapy in the treatment of children with delayed speech development - results of a pilot study

<p>Abstract</p> <p>Background</p> <p>Language development is one of the most significant processes of early childhood development. Children with delayed speech development are more at risk of acquiring other cognitive, social-emotional, and school-related problems. Music therapy appears to facilitate speech development in children, even within a short period of time. The aim of this pilot study is to explore the effects of music therapy in children with delayed speech development.</p> <p>Methods</p> <p>A total of 18 children aged 3.5 to 6 years with delayed speech development took part in this observational study in which music therapy and no treatment were compared to demonstrate effectiveness. Individual music therapy was provided on an outpatient basis. An ABAB reversal design with alternations between music therapy and no treatment with an interval of approximately eight weeks between the blocks was chosen. Before and after each study period, a speech development test, a non-verbal intelligence test for children, and music therapy assessment scales were used to evaluate the speech development of the children.</p> <p>Results</p> <p>Compared to the baseline, we found a positive development in the study group after receiving music therapy. Both phonological capacity and the children's understanding of speech increased under treatment, as well as their cognitive structures, action patterns, and level of intelligence. Throughout the study period, developmental age converged with their biological age. Ratings according to the Nordoff-Robbins scales showed clinically significant changes in the children, namely in the areas of client-therapist relationship and communication.</p> <p>Conclusions</p> <p>This study suggests that music therapy may have a measurable effect on the speech development of children through the treatment's interactions with fundamental aspects of speech development, including the ability to form and maintain relationships and prosodic abilities. Thus, music therapy may provide a basic and supportive therapy for children with delayed speech development. Further studies should be conducted to investigate the mechanisms of these interactions in greater depth.</p> <p>Trial registration</p> <p>The trial is registered in the German clinical trials register; Trial-No.: DRKS00000343</p

Physiological and Biomechanical Responses of Highly Trained Distance Runners to Lower-Body Positive Pressure Treadmill Running

Background: As a way to train at faster running speeds, add training volume, prevent injury, or rehabilitate after an injury, lower-body positive pressure treadmills (LBPPT) have become increasingly commonplace among athletes. However, there are conflicting evidence and a paucity of data describing the physiological and biomechanical responses to LBPPT running in highly trained or elite caliber runners at the running speeds they habitually train at, which are considerably faster than those of recreational runners. Furthermore, data is lacking regarding female runners’ responses to LBPPT running. Therefore, this study was designed to evaluate the physiological and biomechanical responses to LBPPT running in highly trained male and female distance runners. Methods: Fifteen highly trained distance runners (seven male; eight female) completed a single running test composed of 4 × 9-min interval series at fixed percentages of body weight ranging from 0 to 30% body weight support (BWS) in 10% increments on LBPPT. The first interval was always conducted at 0% BWS; thereafter, intervals at 10, 20, and 30% BWS were conducted in random order. Each interval consisted of three stages of 3 min each, at velocities of 14.5, 16.1, and 17.7 km·h−1 for men and 12.9, 14.5, and 16.1 km·h−1 for women. Expired gases, ventilation, breathing frequency, heart rate (HR), rating of perceived exertion (RPE), and stride characteristics were measured during each running speed and BWS. Results: Male and female runners had similar physiological and biomechanical responses to running on LBPPT. Increasing BWS increased stride length (p \u3c 0.02) and flight duration (p \u3c 0.01) and decreased stride rate (p \u3c 0.01) and contact time (p \u3c 0.01) in small-large magnitudes. There was a large attenuation of oxygen consumption (VO2) relative to BWS (p \u3c 0.001), while there were trivial-moderate reductions in respiratory exchange ratio, minute ventilation, and respiratory frequency (p \u3e 0.05), and small-large effects on HR and RPE (p \u3c 0.01). There were trivial-small differences in VE, respiratory frequency, HR, and RPE for a given VO2 across various BWS (p \u3e 0.05). Conclusions: The results indicate the male and female distance runners have similar physiological and biomechanical responses to LBPPT running. Overall, the biomechanical changes during LBPPT running all contributed to less metabolic cost and corresponding physiological changes. Keywords: AlterG, Lower-body positive pressure, Body weight support, Anti-gravity, Running, Stride characteristics, Physiological characteristics, Metabolic demand, Oxygen demand, Oxygen cos

Gender differences in presentation and diagnosis of chest pain in primary care

<p>Abstract</p> <p>Background</p> <p>Chest pain is a common complaint and reason for consultation in primary care. Research related to gender differences in regard to Coronary Heart Disease (CHD) has been mainly conducted in hospital but not in primary care settings. We aimed to analyse gender differences in aetiology and clinical characteristics of chest pain and to provide gender related symptoms and signs associated with CHD.</p> <p>Methods</p> <p>We included 1212 consecutive patients with chest pain aged 35 years and older attending 74 general practitioners (GPs). GPs recorded symptoms and findings of each patient and provided follow up information. An independent interdisciplinary reference panel reviewed clinical data of every patient and decided about the aetiology of chest pain at the time of patient recruitment. Multivariable regression analysis was performed to identify clinical predictors that help to rule in or out CHD in women and men.</p> <p>Results</p> <p>Women showed more psychogenic disorders (women 11,2%, men 7.3%, p = 0.02), men suffered more from CHD (women 13.0%, men 17.2%, p = 0.04), trauma (women 1.8%, men 5.1%, p < 0.001) and pneumonia/pleurisy (women 1.3%, men 3.0%, p = 0.04) Men showed significantly more often chest pain localised on the right side of the chest (women 9.1%, men 25.0%, p = 0.01). For both genders known clinical vascular disease, pain worse with exercise and age were associated positively with CHD. In women pain duration above one hour was associated positively with CHD, while shorter pain durations showed an association with CHD in men. In women negative associations were found for stinging pain and in men for pain depending on inspiration and localised muscle tension.</p> <p>Conclusions</p> <p>We found gender differences in regard to aetiology, selected clinical characteristics and association of symptoms and signs with CHD in patients presenting with chest pain in a primary care setting. Further research is necessary to elucidate whether these differences would support recommendations for different diagnostic approaches for CHD according to a patient's gender.</p