Feature weighting as a tool for unsupervised feature selection

Feature selection is a popular data pre-processing step. The aim is to remove some of the features in a data set with minimum information loss, leading to a number of benefits including faster running time and easier data visualisation. In this paper we introduce two unsupervised feature selection algorithms. These make use of a cluster-dependent feature-weighting mechanism reflecting the within-cluster degree of relevance of a given feature. Those features with a relatively low weight are removed from the data set. We compare our algorithms to two other popular alternatives using a number of experiments on both synthetic and real-world data sets, with and without added noisy features. These experiments demonstrate our algorithms clearly outperform the alternatives

The diagnosis of mental disorders: the problem of reification

A pressing need for interrater reliability in the diagnosis of mental disorders emerged during the mid-twentieth century, prompted in part by the development of diverse new treatments. The Diagnostic and Statistical Manual of Mental Disorders (DSM), third edition answered this need by introducing operationalized diagnostic criteria that were field-tested for interrater reliability. Unfortunately, the focus on reliability came at a time when the scientific understanding of mental disorders was embryonic and could not yield valid disease definitions. Based on accreting problems with the current DSM-fourth edition (DSM-IV) classification, it is apparent that validity will not be achieved simply by refining criteria for existing disorders or by the addition of new disorders. Yet DSM-IV diagnostic criteria dominate thinking about mental disorders in clinical practice, research, treatment development, and law. As a result, the modernDSMsystem, intended to create a shared language, also creates epistemic blinders that impede progress toward valid diagnoses. Insights that are beginning to emerge from psychology, neuroscience, and genetics suggest possible strategies for moving forward

Microbial catabolic activities are naturally selected by metabolic energy harvest rate

The fundamental trade-off between yield and rate of energy harvest per unit of substrate has been largely discussed as a main characteristic for microbial established cooperation or competition. In this study, this point is addressed by developing a generalized model that simulates competition between existing and not experimentally reported microbial catabolic activities defined only based on well-known biochemical pathways. No specific microbial physiological adaptations are considered, growth yield is calculated coupled to catabolism energetics and a common maximum biomass-specific catabolism rate (expressed as electron transfer rate) is assumed for all microbial groups. Under this approach, successful microbial metabolisms are predicted in line with experimental observations under the hypothesis of maximum energy harvest rate. Two microbial ecosystems, typically found in wastewater treatment plants, are simulated, namely: (i) the anaerobic fermentation of glucose and (ii) the oxidation and reduction of nitrogen under aerobic autotrophic (nitrification) and anoxic heterotrophic and autotrophic (denitrification) conditions. The experimentally observed cross feeding in glucose fermentation, through multiple intermediate fermentation pathways, towards ultimately methane and carbon dioxide is predicted. Analogously, two-stage nitrification (by ammonium and nitrite oxidizers) is predicted as prevailing over nitrification in one stage. Conversely, denitrification is predicted in one stage (by denitrifiers) as well as anammox (anaerobic ammonium oxidation). The model results suggest that these observations are a direct consequence of the different energy yields per electron transferred at the different steps of the pathways. Overall, our results theoretically support the hypothesis that successful microbial catabolic activities are selected by an overall maximum energy harvest rate

Methylome of human skeletal muscle after acute & chronic resistance exercise training, detraining & retraining

DNA methylation is an important epigenetic modification that can regulate gene expression following environmental encounters without changes to the genetic code. Using Infinium MethylationEPIC BeadChip Arrays (850,000 CpG sites) we analysed for the first time, DNA isolated from untrained human skeletal muscle biopsies (vastus lateralis) at baseline (rest) and immediately following an acute (single) bout of resistance exercise. In the same participants, we also analysed the methylome following a period of muscle growth (hypertrophy) evoked via chronic (repeated bouts-3 sessions/wk) resistance exercise (RE) (training) over 7-weeks, followed by complete exercise cessation for 7-weeks returning muscle back to baseline levels (detraining), and finally followed by a subsequent 7-week period of RE-induced hypertrophy (retraining). These valuable methylome data sets described in the present manuscript and deposited in an open-access repository can now be shared and re-used to enable the identification of epigenetically regulated genes/ networks that are modified after acute anabolic stimuli and hypertrophy, and further investigate the phenomenon of epigenetic memory in skeletal muscle

Conserved presence of G-quadruplex forming sequences in the Long Terminal Repeat Promoter of Lentiviruses

G-quadruplexes (G4s) are secondary structures of nucleic acids that epigenetically regulate cellular processes. In the human immunodeficiency lentivirus 1 (HIV-1), dynamic G4s are located in the unique viral LTR promoter. Folding of HIV-1 LTR G4s inhibits viral transcription; stabilization by G4 ligands intensifies this effect. Cellular proteins modulate viral transcription by inducing/unfolding LTR G4s. We here expanded our investigation on the presence of LTR G4s to all lentiviruses. G4s in the 5'-LTR U3 region were completely conserved in primate lentiviruses. A G4 was also present in a cattle-infecting lentivirus. All other non-primate lentiviruses displayed hints of less stable G4s. In primate lentiviruses, the possibility to fold into G4s was highly conserved among strains. LTR G4 sequences were very similar among phylogenetically related primate viruses, while they increasingly differed in viruses that diverged early from a common ancestor. A strong correlation between primate lentivirus LTR G4s and Sp1/NF\u3baB binding sites was found. All LTR G4s folded: their complexity was assessed by polymerase stop assay. Our data support a role of the lentiviruses 5'-LTR G4 region as control centre of viral transcription, where folding/unfolding of G4s and multiple recruitment of factors based on both sequence and structure may take place

Suitability of PSA-detected localised prostate cancers for focal therapy: Experience from the ProtecT study

This article is available through a Creative Commons Attribution-NonCommercial-Share Alike 3.0 Unported License. Copyright @ 2011 Cancer Research UK.Background: Contemporary screening for prostate cancer frequently identifies small volume, low-grade lesions. Some clinicians have advocated focal prostatic ablation as an alternative to more aggressive interventions to manage these lesions. To identify which patients might benefit from focal ablative techniques, we analysed the surgical specimens of a large sample of population-detected men undergoing radical prostatectomy as part of a randomised clinical trial. Methods: Surgical specimens from 525 men who underwent prostatectomy within the ProtecT study were analysed to determine tumour volume, location and grade. These findings were compared with information available in the biopsy specimen to examine whether focal therapy could be provided appropriately. Results: Solitary cancers were found in prostatectomy specimens from 19% (100 out of 525) of men. In addition, 73 out of 425 (17%) men had multiple cancers with a solitary significant tumour focus. Thus, 173 out of 525 (33%) men had tumours potentially suitable for focal therapy. The majority of these were small, well-differentiated lesions that appeared to be pathologically insignificant (38–66%). Criteria used to select patients for focal prostatic ablation underestimated the cancer's significance in 26% (34 out of 130) of men and resulted in overtreatment in more than half. Only 18% (24 out of 130) of men presumed eligible for focal therapy, actually had significant solitary lesions. Conclusion: Focal therapy appears inappropriate for the majority of men presenting with prostate-specific antigen-detected localised prostate cancer. Unifocal prostate cancers suitable for focal ablation are difficult to identify pre-operatively using biopsy alone. Most lesions meeting criteria for focal ablation were either more aggressive than expected or posed little threat of progression.National Institute for Health Researc

Examining the Relationship Between Genetic Counselors’ Attitudes Toward Deaf People and the Genetic Counseling Session

Given the medical and cultural perspectives on deafness it is important to determine if genetic counselors’ attitudes toward deaf people can affect counseling sessions for deafness genes. One hundred fifty-eight genetic counselors recruited through the National Society of Genetic Counselors Listserv completed an online survey assessing attitudes toward deaf people and scenario-specific comfort levels discussing and offering genetic testing for deafness. Respondents with deaf/Deaf friends or who work in prenatal or pediatric settings had more positive attitudes toward deaf people than those without deaf/Deaf friends or those working in ‘other’ settings. More positive attitudes toward deaf people correlated with higher comfort level talking about genetic testing for the two scenarios involving culturally Deaf clients; and correlated with higher comfort level offering genetic testing to culturally Deaf clients wishing to have a deaf child. Attitudes and comfort level were not correlated in the scenarios involving hearing or non-culturally deaf clients. These results suggest that genetic counselors’ attitudes could affect information provision and the decision making process of culturally Deaf clients. Cultural sensitivity workshops in genetic counseling training programs that incorporate personal interactions with culturally Deaf individuals are recommended. Additional suggestions for fostering personal interactions are provided

Of cattle, sand flies and men : a systematic review of risk factor analyses for South Asian visceral leishmaniasis and implications for elimination

Background: Studies performed over the past decade have identified fairly consistent epidemiological patterns of risk factors for visceral leishmaniasis (VL) in the Indian subcontinent. Methods and Principal Findings: To inform the current regional VL elimination effort and identify key gaps in knowledge, we performed a systematic review of the literature, with a special emphasis on data regarding the role of cattle because primary risk factor studies have yielded apparently contradictory results. Because humans form the sole infection reservoir, clustering of kala-azar cases is a prominent epidemiological feature, both at the household level and on a larger scale. Subclinical infection also tends to show clustering around kala-azar cases. Within villages, areas become saturated over a period of several years; kala-azar incidence then decreases while neighboring areas see increases. More recently, post kalaazar dermal leishmaniasis (PKDL) cases have followed kala-azar peaks. Mud walls, palpable dampness in houses, and peridomestic vegetation may increase infection risk through enhanced density and prolonged survival of the sand fly vector. Bed net use, sleeping on a cot and indoor residual spraying are generally associated with decreased risk. Poor micronutrient status increases the risk of progression to kala-azar. The presence of cattle is associated with increased risk in some studies and decreased risk in others, reflecting the complexity of the effect of bovines on sand fly abundance, aggregation, feeding behavior and leishmanial infection rates. Poverty is an overarching theme, interacting with individual risk factors on multiple levels. Conclusions: Carefully designed demonstration projects, taking into account the complex web of interconnected risk factors, are needed to provide direct proof of principle for elimination and to identify the most effective maintenance activities to prevent a rapid resurgence when interventions are scaled back. More effective, short-course treatment regimens for PKDL are urgently needed to enable the elimination initiative to succeed