Futility Analysis in the Cross-Validation of Machine Learning Models

Many machine learning models have important structural tuning parameters that cannot be directly estimated from the data. The common tactic for setting these parameters is to use resampling methods, such as cross--validation or the bootstrap, to evaluate a candidate set of values and choose the best based on some pre--defined criterion. Unfortunately, this process can be time consuming. However, the model tuning process can be streamlined by adaptively resampling candidate values so that settings that are clearly sub-optimal can be discarded. The notion of futility analysis is introduced in this context. An example is shown that illustrates how adaptive resampling can be used to reduce training time. Simulation studies are used to understand how the potential speed--up is affected by parallel processing techniques.Comment: 22 pages, 5 figure

Building Predictive Models in R Using the caret Package

The caret package, short for classification and regression training, contains numerous tools for developing predictive models using the rich set of models available in R. The package focuses on simplifying model training and tuning across a wide variety of modeling techniques. It also includes methods for pre-processing training data, calculating variable importance, and model visualizations. An example from computational chemistry is used to illustrate the functionality on a real data set and to benchmark the benefits of parallel processing with several types of models.

Breastfeeding and the 2015 South African guidelines for prevention of mother-to-child transmission of HIV

No abstract availabl

More than just hormones: H295R cells as predictors of reproductive toxicity

AbstractMany of the commonly observed reproductive toxicities associated with therapeutic compounds can be traced to a disruption of the steroidogenic pathway. We sought to develop an in vitro assay that would predict reproductive toxicity and be high throughput in nature. H295R cells, previously validated as having an intact and functional steroidogenic pathway, were treated with 83 known-positive and 79 known-negative proprietary and public-domain compounds. The assay measured the expression of the key enzymes STAR, 3βHSD2, CYP17A1, CYP11B2, CYP19A1, CYP21A2, and CYP11A1 and the hormones DHEA, progesterone, testosterone, and cortisol. We found that a Random Forest model yielded a receiver operating characteristic area under the curve (ROC AUC) of 0.845, with sensitivity of 0.724 and specificity of 0.758 for predicting in vivo reproductive toxicity with this in vitro assay system

A Functional ABCC11 Allele Is Essential in the Biochemical Formation of Human Axillary Odor

The characteristic human axillary odor is formed by bacterial action on odor precursors that originate from apocrine sweat glands. Caucasians and Africans possess a strong axillary odor ,whereas many Asians have only a faint acidic odor. In this study, we provide evidence that the gene ABCC11 (MRP8), which encodes an apical efflux pump, is crucial for the formation of the characteristic axillary odor and that a single-nucleotide polymorphism (SNP) 538G → A, which is prominent among Asian people, leads to a nearly complete loss of the typical odor components in axillary sweat. The secretion of amino-acid conjugates of human-specific odorants is abolished in homozygotic carriers of the SNP, and steroidal odorants and their putative precursors are significantly reduced. Moreover, we show that ABCC11 is expressed and localized in apocrine sweat glands. These data point to a key function of ABCC11 in the secretion of odorants and their precursors from apocrine sweat glands. SNP 538G → A, which also determines human earwax type, is present on an extended haplotype, which has reached >95% frequency in certain populations in recent human evolution. A strong positive selection in mate choice for low-odorant partners with a dysfunctional ABCC11 gene seems a plausible explanation for this striking frequency of a loss-of-function allele

Adherence and virologic suppression during the first 24 weeks on antiretroviral therapy among women in Johannesburg, South Africa - a prospective cohort study

<p>Abstract</p> <p>Background</p> <p>Adherence is a necessary part of successful antiretroviral treatment (ART). We assessed risk factors for incomplete adherence among a cohort of HIV-infected women initiating ART and examined associations between adherence and virologic response to ART.</p> <p>Methods</p> <p>A secondary data analysis was conducted on a cohort of 154 women initiating non-nucleoside reverse transcriptase inhibitor (NNRTI)-based ART at a single site in Johannesburg, South Africa. Ninety women had been enrolled in a prevention of mother-to-child transmission (pMTCT) program and were exposed to single-dose nevirapine (sdNVP) >18 months earlier. Women were interviewed pre-treatment and clinical, virologic and adherence data were collected during follow-up to 24 weeks. Incomplete adherence to ART was defined as returning >5% of medications, estimated by pill counts at scheduled visits. Multivariable logistic regression analysis and unadjusted odds ratio (95%CI) were performed, using STATA/SE (ver 10.1).</p> <p>Results</p> <p>About half of the women (53%) were <30 years of age, 63% had <11 years of schooling, 69% were unemployed and 37% lived in a shack. Seven percent of women had a viral load >400 copies/ml at 24 weeks and 37% had incomplete adherence at one or more visits. Incomplete adherence was associated with less education (p = 0.01) and lack of financial support from a partner (p = 0.02) after adjustment for confounders. Only when adherence levels dropped below 80% was there a significant association with viremia in the group overall (p = 0.02) although adherence <95% was associated with viremia in the sdNVP-exposed group (p = 0.03). The main reasons for incomplete adherence were being away from home, busy with other things and forgetting to take their medication.</p> <p>Conclusion</p> <p>Virologic response to NNRTI-treatment in the cohort was excellent. However, women who received sdNVP were at greater risk of virologic failure when adherence was <95%. Women exposed to sdNVP, and those with less education and less social support may benefit from additional adherence counseling to ensure the long-term success of ART. More than 80% adherence may be sufficient to maintain virologic suppression on NNRTI-based regimens in the short-term, however complete adherence should be encouraged.</p

Videogame: mais que um entretenimento, um agente estimulador da criatividade

This article aims to highlight that videogame is more than an entertainment, and acts as a stimulating agent of creativity. To base the reasoning, theoretical concepts on creativity, games and videogames are presented; (2000), and Gregory D. Clemenson and Craig EL Stark (2015), are also analyzed in the field of Psychology and Neuroscience by Stošić and Stošić (2014), Sabrina Schenk, Robert K. Lech, Boris Suchan ), Daphne Bavelier (2015-2016) and C. Shawn Green (2015-2016), published from 2014 to 2016, where, through research, aimed to identify and analyze the benefits of video games related to creativity through motor and cognitive skills . It has been observed that video games stimulate cognitive processes, including spatial, emotional and motivational vision, as well as critical thinking, fast decision making, problem solving and memory enhancement.Este artigo objetiva evidenciar que o videogame é mais que um entretenimento, e atua como um agente estimulador da criatividade. Para embasar o raciocínio, são apresentadas conceituações teóricas sobre criatividade, jogos e videogames; na sequência, realiza-se a análise dos estudos ligados às áreas da Psicologia e Neurociência, de Stošić e Stošić (2014), Sabrina Schenk, Robert K. Lech, Boris Suchan (2015) e Gregory D. Clemenson and Craig E.L. Stark (2015), Daphne Bavelier (2015-2016) e C. Shawn Green (2015-2016), publicados de 2014 a 2016, onde, através de pesquisas, visavam identificar e analisar os benefícios dos videogames relacionados à criatividade, através das habilidades motoras e cognitivas. Observou-se que os videogames estimulam os processos cognitivos, incluindo a visão espacial, emocional e motivacional, além do pensamento crítico, rapidez na tomada de decisão, e também a resolução de problemas e o aumento da memória

Ratification vote on taxonomic proposals to the International Committee on Taxonomy of Viruses (2016)

This article lists the changes to virus taxonomy approved and ratified by the International Committee on Taxonomy of Viruses (ICTV) in April 2016. Changes to virus taxonomy (the Universal Scheme of Virus Classification of the International Committee on Taxonomy of Viruses [ICTV]) now take place annually and are the result of a multi-stage process. In accordance with the ICTV Statutes (http://​www.​ictvonline.​org/​statutes.​asp), proposals submitted to the ICTV Executive Committee (EC) undergo a review process that involves input from the ICTV Study Groups (SGs) and Subcommittees (SCs), other interested virologists, and the EC. After final approval by the EC, proposals are then presented for ratification to the full ICTV membership by publication on an ICTV web site (http://​www.​ictvonline.​org/​) followed by an electronic vote. The latest set of proposals approved by the EC was made available on the ICTV website by January 2016 (https://​talk.​ictvonline.​org/​files/​proposals/​). A list of these proposals was then emailed on 28 March 2016 to the 148 members of ICTV, namely the EC Members, Life Members, ICTV Subcommittee Members (including the SG chairs) and ICTV National Representatives. Members were then requested to vote on whether to ratify the taxonomic proposals (voting closed on 29 April 2016)

Multiplexed Immunoassay Panel Identifies Novel CSF Biomarkers for Alzheimer's Disease Diagnosis and Prognosis

Clinicopathological studies suggest that Alzheimer's disease (AD) pathology begins ∼10-15 years before the resulting cognitive impairment draws medical attention. Biomarkers that can detect AD pathology in its early stages and predict dementia onset would, therefore, be invaluable for patient care and efficient clinical trial design. We utilized a targeted proteomics approach to discover novel cerebrospinal fluid (CSF) biomarkers that can augment the diagnostic and prognostic accuracy of current leading CSF biomarkers (Aβ42, tau, p-tau181).Using a multiplexed Luminex platform, 190 analytes were measured in 333 CSF samples from cognitively normal (Clinical Dementia Rating [CDR] 0), very mildly demented (CDR 0.5), and mildly demented (CDR 1) individuals. Mean levels of 37 analytes (12 after Bonferroni correction) were found to differ between CDR 0 and CDR>0 groups. Receiver-operating characteristic curve analyses revealed that small combinations of a subset of these markers (cystatin C, VEGF, TRAIL-R3, PAI-1, PP, NT-proBNP, MMP-10, MIF, GRO-α, fibrinogen, FAS, eotaxin-3) enhanced the ability of the best-performing established CSF biomarker, the tau/Aβ42 ratio, to discriminate CDR>0 from CDR 0 individuals. Multiple machine learning algorithms likewise showed that the novel biomarker panels improved the diagnostic performance of the current leading biomarkers. Importantly, most of the markers that best discriminated CDR 0 from CDR>0 individuals in the more targeted ROC analyses were also identified as top predictors in the machine learning models, reconfirming their potential as biomarkers for early-stage AD. Cox proportional hazards models demonstrated that an optimal panel of markers for predicting risk of developing cognitive impairment (CDR 0 to CDR>0 conversion) consisted of calbindin, Aβ42, and age.Using a targeted proteomic screen, we identified novel candidate biomarkers that complement the best current CSF biomarkers for distinguishing very mildly/mildly demented from cognitively normal individuals. Additionally, we identified a novel biomarker (calbindin) with significant prognostic potential

In Search of NPY Y4R Antagonists: Incorporation of Carbamoylated Arginine, Aza-Amino Acids, or d-Amino Acids into Oligopeptides Derived from the C-Termini of the Endogenous Agonists

The cross-linked pentapeptides (2R, 7R)-diaminooctanedioyl- bis(Tyr-Arg-Leu-Arg-Tyr-amide) ((2R, 7R)BVD- 74D, (2R, 7R)-1) and octanedioyl-bis(Tyr-Arg-Leu-ArgTyr- amide) (2) as well as the pentapeptide Ac-Tyr-Arg-LeuArg- Tyr-amide (3) were previously described as neuropeptide Y Y-4 receptor (Y4R) partial agonists. Here, we report on a series of analogues of (2R, 7R)-1 and 2 in which Arg(2), Leu(3), or Arg(4) were replaced by the respective aza-amino acids. The replacement of Arg(2) in 3 with a carbamoylated arginine building block and the extension of the N-terminus by an additional arginine led to the high-affinity hexapeptide Ac-Arg-Tyr-N-omega-[(4-aminobutyl) aminocarbonyl] Arg-Leu-Arg-Tyr-amide (35), which was used as a precursor for a D-amino acid scan. The target compounds were investigated for Y4R functional activity in assays with complementary readouts: aequorin Ca2+ and beta-arrestin 1 or beta-arrestin 2 assays. In contrast to the parent compounds, which are Y4R agonists, several ligands were able to suppress the effect elicited by the endogenous ligand pancreatic polypeptide and therefore represent a novel class of peptide Y4R antagonists