Cross-validated stepwise regression for identification of novel non-nucleoside reverse transcriptase inhibitor resistance associated mutations

<p>Abstract</p> <p>Background</p> <p>Linear regression models are used to quantitatively predict drug resistance, the phenotype, from the HIV-1 viral genotype. As new antiretroviral drugs become available, new resistance pathways emerge and the number of resistance associated mutations continues to increase. To accurately identify which drug options are left, the main goal of the modeling has been to maximize predictivity and not interpretability. However, we originally selected linear regression as the preferred method for its transparency as opposed to other techniques such as neural networks. Here, we apply a method to lower the complexity of these phenotype prediction models using a 3-fold cross-validated selection of mutations.</p> <p>Results</p> <p>Compared to standard stepwise regression we were able to reduce the number of mutations in the reverse transcriptase (RT) inhibitor models as well as the number of interaction terms accounting for synergistic and antagonistic effects. This reduction in complexity was most significant for the non-nucleoside reverse transcriptase inhibitor (NNRTI) models, while maintaining prediction accuracy and retaining virtually all known resistance associated mutations as first order terms in the models. Furthermore, for etravirine (ETR) a better performance was seen on two years of unseen data. By analyzing the phenotype prediction models we identified a list of forty novel NNRTI mutations, putatively associated with resistance. The resistance association of novel variants at known NNRTI resistance positions: 100, 101, 181, 190, 221 and of mutations at positions not previously linked with NNRTI resistance: 102, 139, 219, 241, 376 and 382 was confirmed by phenotyping site-directed mutants.</p> <p>Conclusions</p> <p>We successfully identified and validated novel NNRTI resistance associated mutations by developing parsimonious resistance prediction models in which repeated cross-validation within the stepwise regression was applied. Our model selection technique is computationally feasible for large data sets and provides an approach to the continued identification of resistance-causing mutations.</p

Happiness Through Vacationing: Just a Temporary Boost or Long-Term Benefits?

Does vacationing add to our happiness in the long run? This question was addressed in a study of 3,650 Dutch citizens who reported their leisure travel every 3 months during 2 years and rated their happiness at the end of each year. Participants who had been on vacation appeared to be marginally happier, in terms of hedonic level of affect, than those who had not. This difference in Affect balance between vacationers and non-vacationers is probably due to a very minor causal effect of vacationing on hedonic level of affect. Possibly, vacationing is positively reminisced and these memories allow for the prevalence of more positive affect in people's lives. Happiness did not predict vacationing. The effect of holiday trips on vacationers' happiness is mostly short-lived; among vacationers, happiness was unrelated to the number of trips and days spent on vacation. A separate analysis of vacationers, who value vacationing most, yielded the same results. Implications for future research are discussed

Vacationers Happier, but Most not Happier After a Holiday

The aim of this study was to obtain a greater insight into the association between vacations and happiness. We examined whether vacationers differ in happiness, compared to those not going on holiday, and if a holiday trip boosts post-trip happiness. These questions were addressed in a pre-test/post-test design study among 1,530 Dutch individuals. 974 vacationers answered questions about their happiness before and after a holiday trip. Vacationers reported a higher degree of pre-trip happiness, compared to non-vacationers, possibly because they are anticipating their holiday. Only a very relaxed holiday trip boosts vacationers’ happiness further after return. Generally, there is no difference between vacationers’ and non-vacationers’ post-trip happiness. The findings are explained in the light of set-point theory, need theory and comparison theory

Improvement of psychometric properties of a scale measuring inpatient satisfaction with care: a better response rate and a reduction of the ceiling effect

<p>Abstract</p> <p>Background</p> <p>The objective was to solve two problems of an already validated scale measuring inpatient opinion on care: 1) a high non-response rate for some items due to the "not applicable" response option and 2) a skewed score distribution with high ceiling effect.</p> <p>Methods</p> <p>The EQS-H scale ("échelle de qualité des soins en hospitalisation") comprised 26 items and 2 sub-scales of 13 items each, 'quality of medical information' (MI) and 'relationships with staff and daily routine' (RS). Three studies were conducted: a first mono-centre study (n = 552, response rate = 83.4%, self-completion of the scale the day before discharge) to construct a shorter version of the scale without the items with high non-response rate and maintaining those useful to ensure good internal validity (construct, convergent and divergent) and reliability; a second mono-centre study (n = 1246, response rate = 77.9%, self-completion of the scale before discharge) to confirm psychometric properties of the new version; a third multi-centre national study (n = 886, response rate 41.7%, self-completion at home 15 days after discharge) to test a new response pattern in order to reduce ceiling effect.</p> <p>Results</p> <p>Six items having a non-response rate >20% were deleted, increasing rates of exhaustive response to all items from 15% to 48%. Factorial analysis supported the evidence for removing 4 more items to ensure good internal validity and reliability of the new version. These good results (initial variance explained: 43%; Cronbach's α: 0.80 (MI) and 0.81 (RS)) were confirmed by the second study. The new response format produced a normalisation of the 2 scores with a large decrease in ceiling effect (25% to 4% for MI subscale and 61% to 8% for RS). Psychometric properties of the final version were excellent: the 2 subscales (8 items each) explained 66% of the variance in principal component analysis, Cronbach's α were respectively 0.92 (MI) and 0.93 (RS).</p> <p>Conclusion</p> <p>The new version of the EQS-H has better psychometric properties than the previous one. Rates of missing values are lower, and score distribution is normalized. An English version of this scale focused on quality of medical information delivered and on relationship with staff already exists, and this could be useful to conduct cross-cultural studies of health care service quality.</p

Elevated visual dependency in young adults after chemotherapy in childhood

Chemotherapy in childhood can result in long-term neurophysiological side-effects, which could extend to visual processing, specifically the degree to which a person relies on vision to determine vertical and horizontal (visual dependency). We investigated whether adults treated with chemotherapy in childhood experience elevated visual dependency compared to controls and whether any difference is associated with the age at which subjects were treated. Visual dependency was measured in 23 subjects (mean age 25.3 years) treated in childhood with chemotherapy (CTS) for malignant, solid, non-CNS tumors. We also stratified CTS into two groups: those treated before 12 years of age and those treated from 12 years of age and older. Results were compared to 25 healthy, age-matched controls. The subjective visual horizontal (SVH) and vertical (SVV) orientations was recorded by having subjects position an illuminated rod to their perceived horizontal and vertical with and without a surrounding frame tilted clockwise and counter-clockwise 20° from vertical. There was no significant difference in rod accuracy between any CTS groups and controls without a frame. However, when assessing visual dependency using a frame, CTS in general (p = 0.006) and especially CTS treated before 12 years of age (p = 0.001) tilted the rod significantly further in the direction of the frame compared to controls. Our findings suggest that chemotherapy treatment before 12 years of age is associated with elevated visual dependency compared to controls, implying a visual bias during spatial activities. Clinicians should be aware of symptoms such as visual vertigo in adults treated with chemotherapy in childhood

Does the Integration of Haptic and Visual Cues Reduce the Effect of a Biased Visual Reference Frame on the Subjective Head Orientation?

The selection of appropriate frames of reference (FOR) is a key factor in the elaboration of spatial perception and the production of robust interaction with our environment. The extent to which we perceive the head axis orientation (subjective head orientation, SHO) with both accuracy and precision likely contributes to the efficiency of these spatial interactions. A first goal of this study was to investigate the relative contribution of both the visual and egocentric FOR (centre-of-mass) in the SHO processing. A second goal was to investigate humans' ability to process SHO in various sensory response modalities (visual, haptic and visuo-haptic), and the way they modify the reliance to either the visual or egocentric FORs. A third goal was to question whether subjects combined visual and haptic cues optimally to increase SHO certainty and to decrease the FORs disruption effect.Thirteen subjects were asked to indicate their SHO while the visual and/or egocentric FORs were deviated. Four results emerged from our study. First, visual rod settings to SHO were altered by the tilted visual frame but not by the egocentric FOR alteration, whereas no haptic settings alteration was observed whether due to the egocentric FOR alteration or the tilted visual frame. These results are modulated by individual analysis. Second, visual and egocentric FOR dependency appear to be negatively correlated. Third, the response modality enrichment appears to improve SHO. Fourth, several combination rules of the visuo-haptic cues such as the Maximum Likelihood Estimation (MLE), Winner-Take-All (WTA) or Unweighted Mean (UWM) rule seem to account for SHO improvements. However, the UWM rule seems to best account for the improvement of visuo-haptic estimates, especially in situations with high FOR incongruence. Finally, the data also indicated that FOR reliance resulted from the application of UWM rule. This was observed more particularly, in the visual dependent subject. Conclusions: Taken together, these findings emphasize the importance of identifying individual spatial FOR preferences to assess the efficiency of our interaction with the environment whilst performing spatial tasks