D-optimal plans for variable selection in data bases

This paper is based on an article of Pumplün et al. (2005a) that investigates the use of Design of Experiments in data bases in order to select variables that are relevant for classification in situations where a sufficient number of measurements of the explanatory variables is available, but measuring the class label is hard, e. g. expensive or time-consuming. Pumplün et al. searched for D-optimal designs in existing data sets by means of a genetic algorithm and assessed variable importance based on the found plans. If the design matrix is standardized these D-optimal plans are almost orthogonal and the explanatory variables are nearly uncorrelated. Thus Pumplün et al. expected that their importance for discrimination can be judged independently of each other. In a simulation study Pumplün et al. applied this approach in combination with five classification methods to eight data sets and the obtained error rates were compared with those resulting from variable selection on the basis of the complete data sets. Based on the D-optimal plans in some cases considerably lower error rates were achieved. Although Pumplün et al. (2005a) obtained some promising results, it was not clear for different reasons if D-optimality actually is beneficial for variable selection. For example, D-efficiency and orthogonality of the resulting plans were not investigated and a comparison with variable selection based on random samples of observations of the same size as the D-optimal plans was missing. In this paper we extend the simulation study of Pumplün et al. (2005a) in order to verify their results and as basis for further research in this field. Moreover, in Pumplün et al. D-optimal plans are only used for data preprocessing, that is variable selection. The classification models are estimated on the whole data set in order to assess the effects of D-optimality on variable selection separately. Since the number of measurements of the class label in fact is limited one would normally employ the same observations that were used for variable selection for learning, too. For this reason in our simulation study the appropriateness of D-optimal plans for training classification methods is additionally investigated. It turned out that in general in terms of the error rate there is no difference between variable selection on the basis of D-optimal plans and variable selection on random samples. However, for training of linear classification methods D-optimal plans seem to be beneficial. --

Comparison of classical and sequential design of experiments in note onset detection

Design of experiments is an established approach to parameter optimization of industrial processes. In many computer applications however it is usual to optimize the parameters via genetic algorithms. The main idea of this work is to apply design of experiment’s techniques to the optimization of computer processes. The major problem here is finding a compromise between model validity and costs, which increase with the number of experiments. The second relevant problem is choosing an appropriate model, which describes the relationship between parameters and target values. One of the recent approaches here is model combination, which can be used in sequential designs in order to improve automatic prediction of the next trial point. In this paper a musical note onset detection algorithm will be optimized using sequential parameter optimization with model combination. It will be shown that parameter optimization via design of experiments leads to better values of the target variable than usual parameter optimization via grid search or genetic optimization algorithms. Furthermore, the results of this application study reveal, whether the combination of many models brings improvements in finding the optimal parameter setting

Examining patient preferences in the treatment of rheumatoid arthritis using a discrete-choice approach

Background: Biological disease-modifying antirheumatic drugs (bDMARDs) used in second-line treatment of rheumatoid arthritis (RA) are administered parenterally. However, so-called targeted synthetic DMARDs (tsDMARDs) – developed more recently – offer alternative (ie, oral) administration forms in second-line treatment. Since bDMARDs and tsDMARDs can be regarded as equal in terms of efficacy, the present study examines whether such characteristics as route of administration drive RA patients’ treatment choice. This may ultimately suggest superiority of some second-line DMARDs over equally effective options, at least according to RA-patient preferences. Objective: The current study assessed the importance of oral administration among other treatment characteristics differing between available second-line DMARDs for RA patients’ preferences using a discrete-choice experiment (DCE). Materials and methods: The DCE involved scenarios of three hypothetical treatment options in a d-efficient design with varying levels of key attributes (route and frequency of administration, time till onset of drug effect, combination therapy, possible side effects), as defined by focus groups. Further patient characteristics were recorded by an accompanying questionnaire. In the DCE, patients were asked to choose best and worst options (best–worst scaling). Results were analyzed by count analysis and adjusted regression analysis. Results: A total of 1,588 subjects completed the DCE and were eligible for final analyses. Across all characteristics included in the DCE, “oral administration” was most desired and “intravenous infusion” was most strongly rejected. This was followed by “no combination with methotrexate” being strongly preferred and “intake every 1–2 weeks” being strongly rejected. On average, levels of route of administration showed strongest influences on patients’ decisions in post hoc bootstrapping analysis. Conclusion: According to the results, an oral DMARD that does not have to be combined with methotrexate and is not administered (only) every 1–2 weeks appears a highly favorable treatment option for patients with RA. DMARDs meeting these preferences may increase compliance and adherence in RA treatment

Large-scale, prospective, observational studies in patients with psoriasis and psoriatic arthritis: A systematic and critical review

<p>Abstract</p> <p>Background</p> <p>Observational studies, if conducted appropriately, play an important role in the decision-making process providing invaluable information on effectiveness, patient-reported outcomes and costs in a real-world environment. We conducted a systematic review of large-scale, prospective, cohort studies with the aim of (a) summarising design characteristics, the interventions or aspects of the disease studied and the outcomes measured and (b) investigating methodological quality.</p> <p>Methods</p> <p>We included prospective, cohort studies which included at least 100 adults with psoriasis or psoriatic arthritis. Studies were identified through searches in electronic databases (Pubmed, Medline, Cochrane library, Centre for Reviews and Dissemination). Information on study characteristics were extracted and tabulated and quality assessment, using a checklist of 18 questions, was conducted.</p> <p>Results</p> <p>Thirty five papers covering 16 cohorts met the inclusion criteria. There were ten treatment-related studies, only two of which provided a comparison between treatments, and six non-treatment studies which examined a number of characteristics of the disease including mortality, morbidity, cost of illness and health-related quality of life. All studies included a clinical outcome measure and 11 included patient-reported outcomes, however only two studies reported information on patient utilities and two on costs. The quality of the assessed studies varied widely. Studies did well on a number of quality assessment questions including having clear objectives, documenting selection criteria, providing a representative sample, defining interventions/characteristics under study, defining and using appropriate outcomes, describing results clearly and using appropriate statistical tests. The quality assessment criteria least adhered to involved questions regarding sample size calculations, describing potential selection bias, defining and adjusting for confounders and losses to follow-up, and defining and describing a comparison group.</p> <p>Conclusion</p> <p>The review highlights the need for well designed prospective observational studies on the effectiveness, patient-reported outcomes and economic impact of treatment regimes for patients with psoriasis and psoriatic arthritis in a real-world environment.</p

Treatment of Atopic Dermatitis and Impact on Quality of Life: A Review with Emphasis on Topical Non-Corticosteroids

Atopic dermatitis (AD) is a chronic skin disease with increasing prevalence and rising costs. Stigmatisation and pruritus are only some aspects of potential quality-of-life (QOL) impairments. AD is not curable and repeated treatments are often necessary. At present, treatment with topically-applied corticosteroids is state-of-the-art for mild to moderate flare-ups. However, many patients are worried about the use of corticosteroids due to the widespread fear of adverse effects. In this review the present literature is analysed concerning impact on quality of life for topically-applicable alternatives to the state-of-the-art treatment. For comparison reasons, data from other treatment modalities are additionally given. Characteristics of studies were analysed using `general' (year and mode of publication, type and aim of study, number of patients, and clinical measurement) and `QOL specific' criteria (type and number of QOL measurements including relevance for study aim and age group, validation in used language, sensitivity to change, and improvement at end of study). QOL data are published only in the minority of studies evaluating treatment efficacy and do not cover the variety of possible therapies. Data are available for tacrolimus, pimecrolimus, UVA/UVB combination and UVB narrowband (topical non-corticosteroidal treatments), as well as for topical corticosteroids, cyclosporin, and inpatient treatment. All studies provided a marked improvement in quality of life after therapy. One study assessed quality of life after a treatment-free follow-up period obtaining a clear increase in impact on quality of life. Since studies used different QOL measurements and vary in inclusion criteria, treatment schedules and presentation of results, a comparison of QOL improvement is not recommended. A single randomised study compared topically applied non-corticosteroidal treatment (UVA/UVB combination) with another treatment modality (cyclosporin) and found no difference in QOL improvement. At present, there is a clear lack of controlled randomised studies evaluating different active treatment modalities and their impact on quality of life. Consensus meetings are desirable to formulate guidelines for the selection and correct use of QOL measurements. Patients' fear of side effects (e.g. concerning corticosteroids) should be integrated in QOL questionnaires for evaluation of possible compliance problems and real costs. Since relapse after treatment is frequent in AD, QOL measurements should also be performed after a treatment-free follow-up period. At present, we can not answer the question `which treatment best improves quality of life in AD?'.Antihistamines, Atopic dermatitis, Azathioprine, Corticosteroids, Cyclosporin, Herbal medicines, Interferon gamma, Methotrexate, Pharmacoeconomics, Phototherapy, Psoralens, Quality of life

Luteinising hormone profiles in conception and non-conception natural cycles

Objective: The aim of this study was to assess whether luteinising hormone (LH) surge characteristics influenced the likelihood of conceiving naturally.Methods: This was a single-cycle, home-based, observational, case-controlled study. Volunteers collected daily urine samples for one menstrual cycle. LH was measured and the basal levels, surge day, peak day, peak concentration and magnitude of LH surges were examined. Predictive models using sociodemographic data, LH surge characteristics, and sociodemographic data combined with LH profile properties, were evaluated.Results: The surge profile did not differ between cycles with early or late ovulation and was not affected by age or body mass index (BMI). The mean LH surge day was day 16 for both groups. Mean LH surge and concentrations did not differ between groups (surge concentration 54.8IU/l vs. 58.2IU/l and peak concentration 82.0IU/l vs. 81.6IU/l for pregnant vs. non-pregnant volunteers, respectively). Non-pregnant volunteers were more likely, however, to have a raised or a reduced basal LH on day 6 or have an atypical LH profile. Sociodemographic characteristics were significant predictors of pregnancy, and sociodemographic variable-based models had the greatest predictive ability for conception, providing up to 65% predictive accuracy.Conclusions: Sociodemographic variables can be used to predict the likelihood of a woman conceiving naturally. Provided an LH surge is present, its profile does not relate to the likelihood of spontaneous pregnancy. The conception rate was significantly lower, however, in women with elevated or reduced basal levels of LH, suggesting that follicular maturation needs an optimal basal level of LH in natural conception cycles

Budgerigars adopt robust, but idiosyncratic flight paths

We have investigated the paths taken by Budgerigars while flying in a tunnel. The flight trajectories of nine Budgerigars (Melopsittacus undulatus) were reconstructed in 3D from high speed stereo videography of their flights in an obstacle-free tunnel. Individual birds displayed highly idiosyncratic flight trajectories that were consistent from flight to flight over the course of several months. We then investigated the robustness of each bird's trajectory by interposing a disk-shaped obstacle in its preferred flight path. We found that each bird continued to fly along its preferred trajectory up to a point very close to the obstacle before veering over the obstacle rapidly, making a minimal deviation to avoid a collision, and subsequently returning to its original path. Thus, Budgerigars show a high propensity to stick to their individual, preferred flight paths even when confronted with a clearly visible obstacle, and do not adopt a substantially different, unobstructed route. The robust preference for idiosyncratic flight paths, and the tendency to pass obstacles by flying above them, provide new insights into the strategies that underpin obstacle avoidance in birds. We believe that this is the first carefully controlled study of the behaviour of birds in response to a newly introduced obstacle in their flight path. The insights from the study could also have implications for conservation efforts to mitigate collisions of birds with man-made obstacles

Monitoring the menstrual cycle: Comparison of urinary and serum reproductive hormones referenced to true ovulation

Objective The aim of the study was to examine relationships and interindividual variations in urinary and serum reproductive hormone levels relative to ultrasound-observed ovulation in menstrual cycles of apparently normally menstruating women.Methods This was a prospective study of normally menstruating women (no known subfertility), aged 18-40 years (n = 40), who collected daily urine samples and attended the study centre for blood samples and transvaginal ultrasound during one complete menstrual cycle. Serum luteinising hormone (LH), progesterone, estradiol, urinary LH, pregnanediol-3- glucuronide (P3G) and estrone-3-glucuronide were measured. Ultrasound was conducted by two physicians and interpreted by central expert review.Results Menstrual cycle length varied from 22 to 37 days (median 27 days). Ovulation by ultrasound ranged from day 8 to day 26 (median day 15). Serum and urinary hormone profiles showed excellent agreement. Estrogen and LH hormone peaks in urine and serum showed a range of signal characteristics across the study group before and after ovulation. The rise in estrogen and LH always occurred before ovulation; the progesterone rise from baseline always occurred after ovulation.Conclusions Urinary and serum reproductive hormones showed excellent agreement and may be used interchangeably. The beginning of the surge in serum and urinary LH was an excellent predictor of ovulation. The rise in progesterone and P3G above baseline was a consistent marker of luteinisation confirming ovulation. Both LH and progesterone surges delivered clear, sharp signals in all volunteers, allowing reliable detection and confirmation of ovulation

Transcriptome sequencing of melanocytic nevi and melanomas from Grm1 transgenic mice to determine melanoma driver mutations

Malignant melanoma is thought to exhibit a high base mutation rate compared with other solid tumors. Therefore, there is a strong interest in discovering new mutations and understanding their impact on melanoma pathogenesis. Mutations in several genes such as BRAF, NRAS or KIT are associated with melanoma development and progression. The most common BRAF mutation, BRAF V600E, results in the constitutive activation of MAPK/ERK signaling in the tumor cells affecting cell division and differentiation. Moreover, previous studies have shown that allele variations of the CDKN2A gene and OCA2 gene are associated with melanoma susceptibility