Multivariate and functional classification using depth and distance

We construct classifiers for multivariate and functional data. Our approach is based on a kind of distance between data points and classes. The distance measure needs to be robust to outliers and invariant to linear transformations of the data. For this purpose we can use the bagdistance which is based on halfspace depth. It satisfies most of the properties of a norm but is able to reflect asymmetry when the class is skewed. Alternatively we can compute a measure of outlyingness based on the skew-adjusted projection depth. In either case we propose the DistSpace transform which maps each data point to the vector of its distances to all classes, followed by k-nearest neighbor (kNN) classification of the transformed data points. This combines invariance and robustness with the simplicity and wide applicability of kNN. The proposal is compared with other methods in experiments with real and simulated data

Robust bootstrap procedures for the chain-ladder method

Insurers are faced with the challenge of estimating the future reserves needed to handle historic and outstanding claims that are not fully settled. A well-known and widely used technique is the chain-ladder method, which is a deterministic algorithm. To include a stochastic component one may apply generalized linear models to the run-off triangles based on past claims data. Analytical expressions for the standard deviation of the resulting reserve estimates are typically difficult to derive. A popular alternative approach to obtain inference is to use the bootstrap technique. However, the standard procedures are very sensitive to the possible presence of outliers. These atypical observations, deviating from the pattern of the majority of the data, may both inflate or deflate traditional reserve estimates and corresponding inference such as their standard errors. Even when paired with a robust chain-ladder method, classical bootstrap inference may break down. Therefore, we discuss and implement several robust bootstrap procedures in the claims reserving framework and we investigate and compare their performance on both simulated and real data. We also illustrate their use for obtaining the distribution of one year risk measures

Higher physical fitness levels are associated with less language decline in healthy ageing

Healthy ageing is associated with decline in cognitive abilities such as language. Aerobic fitness has been shown to ameliorate decline in some cognitive domains, but the potential benefits for language have not been examined. In a cross-sectional sample, we investigated the relationship between aerobic fitness and tip-of-the-tongue states. These are among the most frequent cognitive failures in healthy older adults and occur when a speaker knows a word but is unable to produce it. We found that healthy older adults indeed experience more tip-of-the-tongue states than young adults. Importantly, higher aerobic fitness levels decrease the probability of experiencing tip-of-the-tongue states in healthy older adults. Fitness-related differences in word finding abilities are observed over and above effects of age. This is the first demonstration of a link between aerobic fitness and language functioning in healthy older adults

Robust Identification of Target Genes and Outliers in Triple-negative Breast Cancer Data

Correct classification of breast cancer sub-types is of high importance as it directly affects the therapeutic options. We focus on triple-negative breast cancer (TNBC) which has the worst prognosis among breast cancer types. Using cutting edge methods from the field of robust statistics, we analyze Breast Invasive Carcinoma (BRCA) transcriptomic data publicly available from The Cancer Genome Atlas (TCGA) data portal. Our analysis identifies statistical outliers that may correspond to misdiagnosed patients. Furthermore, it is illustrated that classical statistical methods may fail in the presence of these outliers, prompting the need for robust statistics. Using robust sparse logistic regression we obtain 36 relevant genes, of which ca. 60\% have been previously reported as biologically relevant to TNBC, reinforcing the validity of the method. The remaining 14 genes identified are new potential biomarkers for TNBC. Out of these, JAM3, SFT2D2 and PAPSS1 were previously associated to breast tumors or other types of cancer. The relevance of these genes is confirmed by the new DetectDeviatingCells (DDC) outlier detection technique. A comparison of gene networks on the selected genes showed significant differences between TNBC and non-TNBC data. The individual role of FOXA1 in TNBC and non-TNBC, and the strong FOXA1-AGR2 connection in TNBC stand out. Not only will our results contribute to the breast cancer/TNBC understanding and ultimately its management, they also show that robust regression and outlier detection constitute key strategies to cope with high-dimensional clinical data such as omics data

Finding Outliers in Surface Data and Video

Surface, image and video data can be considered as functional data with a bivariate domain. To detect outlying surfaces or images, a new method is proposed based on the mean and the variability of the degree of outlyingness at each grid point. A rule is constructed to flag the outliers in the resulting functional outlier map. Heatmaps of their outlyingness indicate the regions which are most deviating from the regular surfaces. The method is applied to fluorescence excitation-emission spectra after fitting a PARAFAC model, to MRI image data which are augmented with their gradients, and to video surveillance data

Anesthesie met α2-agonisten bij de lama: een literatuuroverzicht aangevuld met eigen onderzoek

Many articles on anesthesia in llamas have been published Xylazme, combined with ketamine is the most frequently used injectable anesthetic protocol and it warrants an effective and reliable anesthesia to perform short procedures The use of other (alpha(2)-agonists is far less documented in the literature A study was carried out to evaluate and compare the anesthetic and cardiorespiratory effects of intramuscular medetomidine-ketamine and dexmedetomidine-ketamine in llamas The induction of anesthesia, cardiorespiratory parameters and the recovery time were similar in both groups However, during recovery, significantly more ataxia was observed in the llamas that received medetomidine than in the llamas that received dexmedetomidin

A paradox of syntactic priming: why response tendencies show priming for passives, and response latencies show priming for actives

Speakers tend to repeat syntactic structures across sentences, a phenomenon called syntactic priming. Although it has been suggested that repeating syntactic structures should result in speeded responses, previous research has focused on effects in response tendencies. We investigated syntactic priming effects simultaneously in response tendencies and response latencies for active and passive transitive sentences in a picture description task. In Experiment 1, there were priming effects in response tendencies for passives and in response latencies for actives. However, when participants' pre-existing preference for actives was altered in Experiment 2, syntactic priming occurred for both actives and passives in response tendencies as well as in response latencies. This is the first investigation of the effects of structure frequency on both response tendencies and latencies in syntactic priming. We discuss the implications of these data for current theories of syntactic processing

Etanercept, improved dosage schedules and combinations in the treatment of psoriasis: an update

Etanercept, a subcutaneously administered fully human soluble tumor necrosis factor (TNF) receptor, was initially approved for the treatment of psoriasis at a dose of 25 mg twice weekly in repeated 24-week cycles with the possibility to double the dose in the first 12 weeks of the first cycle. During intermittent treatment, patients retain their ability to respond to etanercept. Recently, a new dosing schedule of etanercept 50 mg once weekly was approved, based on a study in which PASI-75 (75% improvement of Psoriasis Area and Severity Index) was achieved by 37% and 71% of patients at week 12 and 24. Another study demonstrated a PASI-75 of 57% and 69% in pediatric psoriasis patients receiving etanercept 0.8 mg/kg (up to 50 mg) once weekly for 12 and 24 weeks respectively, resulting in European approval from age 8. Based on recent clinical trials, the antipsoriatic effect of etanercept can be markedly increased in combination with acitretin, methotrexate or UVB. The combination with acitretin appears attractive because of its non-immunosuppressive and chemopreventive properties. Etanercept–methotrexate combination therapy is well established in rheumatologic patients. From a long-term perspective, the combination of TNF-inhibitors with phototherapy (photocarcinogenesis) or cyclosporine (carcinogenesis, infections) warrants great caution however. Finally, combination with topical calcipotriol–betamethasone ointment may increase the speed of response to TNF-inhibitors in the first 4 weeks of treatment

Consensus guidelines for the management of radiation dermatitis and coexisting acne-like rash in patients receiving radiotherapy plus EGFR inhibitors for the treatment of squamous cell carcinoma of the head and neck

Background: Radiation dermatitis occurs to some degree in most patients receiving radiotherapy, with or without chemotherapy. Patients with squamous cell carcinoma of the head and neck (SCCHN) who receive radiotherapy in combination with epidermal growth factor receptor (EGFR) inhibitors, such as cetuximab, may develop a characteristic acne-like rash in addition to dermatitis. Design: An advisory board of 11 experienced radiation oncologists, medical oncologists and dermatologists discussed the management options for skin reactions in patients receiving EGFR inhibitors and radiotherapy for SCCHN. Skin toxicity was categorised according to the National Cancer Institute—Common Terminology Criteria for Adverse Events (version 3) grading. Results: Both general and grade-specific approaches for the management of dermatitis in this patient group are presented. It was concluded that where EGFR inhibitor-related acne-like rash and dermatitis coexist within irradiated fields, management should be based on the grade of dermatitis: for grade 1 (or no dermatitis), treatment recommendations for EGFR-related acne-like rash outside irradiated fields should be followed; for grades 2 and above, treatment recommendations for dermatitis were proposed. Conclusions: This paper presents comprehensive consensus guidelines for the treatment of dermatitis in patients with SCCHN receiving EGFR inhibitors in combination with radiotherap