Gaussian Processes for Big Data

We introduce stochastic variational inference for Gaussian process models. This enables the application of Gaussian process (GP) models to data sets containing millions of data points. We show how GPs can be vari- ationally decomposed to depend on a set of globally relevant inducing variables which factorize the model in the necessary manner to perform variational inference. Our ap- proach is readily extended to models with non-Gaussian likelihoods and latent variable models based around Gaussian processes. We demonstrate the approach on a simple toy problem and two real world data sets.Comment: Appears in Proceedings of the Twenty-Ninth Conference on Uncertainty in Artificial Intelligence (UAI2013

Warped linear mixed models for the genetic analysis of transformed phenotypes.

Linear mixed models (LMMs) are a powerful and established tool for studying genotype-phenotype relationships. A limitation of the LMM is that the model assumes Gaussian distributed residuals, a requirement that rarely holds in practice. Violations of this assumption can lead to false conclusions and loss in power. To mitigate this problem, it is common practice to pre-process the phenotypic values to make them as Gaussian as possible, for instance by applying logarithmic or other nonlinear transformations. Unfortunately, different phenotypes require different transformations, and choosing an appropriate transformation is challenging and subjective. Here we present an extension of the LMM that estimates an optimal transformation from the observed data. In simulations and applications to real data from human, mouse and yeast, we show that using transformations inferred by our model increases power in genome-wide association studies and increases the accuracy of heritability estimation and phenotype prediction

Bias-Variation Dilemma Challenges Clinical Trials: Inherent Limitations of Randomized Controlled Trials and Meta-Analyses Comparing Hernia Therapies

Purpose: Evaluation of hernia therapies according to the current rules of Evidence Based Medicine is widely reduced to results of RCTs or meta-analyses. RCTs have been accepted as a most important tool to confirm a superior effect of an intervention. Unfortunately, in hernia surgery, comparisons of RCTs and correspondingly their use in meta-analyses, are not, surprisingly often, able to confirm any significant impact of a specific procedure due to intrinsic restrictions in a multi-causal\ud setting with its web of influences. Methods: Based on our own experiences of clinical studies in surgery, the present article outlines several situations, with their respective reasons, which argue the severe limitations of RCTs and meta-analysis to define an optimum treatment. Results: Metaanalyses accumulate the variations of each trial, which then may cover any clear causal relationship. RCTs usually are dealing with subgroups of standard patients thus excluding the majority of our patients. Low statistical power of current cohort sizes restricts the analysis of subgroups or of effects with low incidences. Simple comparisons of means frequently are hampered by nonlinear relationships to outcome. The relevance of a specific variable is difficult to separate from other influences. The limited surveillance period of studies ignores a delayed change in outcome. Randomization cannot guarantee a standardized patient’s condition. All the arguments have to be considered as a crucial and fundamental consequence of the bias-variance dilemma or principle of uncertainty in medicine, and underline the many limitations of RCTs to evaluate any specific impact of hernia therapies on e.g. infection, pain or recurrence. Conclusions: Many surgical issues\ud cannot be and should not be investigated by RCTs, in particular, if a marked patients’ heterogeneity\ud has to be considered or the low incidences of the outcome readout cannot be addressed with sufficient statistical power without getting lost in the variation mire. Registries with their non-restricted data-acquisition should be regarded as reliable alternatives for postoperative outcome quality surveillance studies

Transcatheter aortic valve implantation in 2015

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Convergence acceleration aspects in the solution of the PN neutron transport eigenvalue problem

The solution of the eigenvalue problem for neutron transport is of utmost importance in the field of reactor physics, and represents a challenging problem for numerical models. Different eigenvalue formulations can be identified, each with its own physical significance. The numerical solution of these problems by deterministic methods requires the introduction of approximations, such as the spherical harmonics expansion in PN models, leading to results that depend on the approximations introduced (spatial mesh size, N order, ...). All these results represent, in principle, sequences that can easily profit from acceleration techniques to approach convergence towards the correct value. Such a reference value is estimated, in this work, by the Monte Carlo technique. The Wynn- acceleration method is applied to the various sequences of eigenvalues emerging when tackling the solution of the PN models with different orders and increasing spatial accuracy, in order to obtain more accurate, benchmark-quality results. It is shown that the acceleration can be successfully applied and that the analysis of the results of different acceleration approaches sheds some light on the physical meaning of the numerical approximations

SGR 0418+5729: a low-magnetic-field magnetar

Soft gamma-ray repeaters and anomalous X-ray pulsars are a small (but growing) group of X-ray sources characterized by the emission of short bursts and by a large variability in their persistent flux. They are believed to be magnetars, i.e. neutron stars powered by extreme magnetic fields 1E14-1E15 G). We found evidence for a magnetar with a low magnetic field, SGR 0418+5729, recently detected after it emitted bursts similar to those of soft gamma-ray repeaters. New X-ray observations show that its dipolar magnetic field cannot be greater than 8E12 G, well in the range of ordinary radio pulsars, implying that a high surface dipolar magnetic field is not necessarily required for magnetar-like activity. The magnetar population may thus include objects with a wider range of magnetic-field strengths, ages and evolutionary stages than observed so far.Comment: 4 pages, 2 figures; to appear in the Proceedings of the Pulsar Conference 2010, Chia, Sardinia (Italy), 10-15 October 201

Quality of dying in hospital general wards: a cross-sectional study about the end-of-life care

Abstract Background In the last decade, access to national palliative care programs have improved, however a large proportion of patients continued to die in hospital, particularly within internal medicine wards. Objectives To describe treatments, symptoms and clinical management of adult patients at the end of their life and explore whether these differ according to expectation of death. Methods Single-centre cross-sectional study performed in the medical and surgical wards of a large tertiary-level university teaching hospital in the north of Italy. Data on nursing interventions and diagnostic procedure in proximity of death were collected after interviewing the nurse and the physician responsible for the patient. Relationship between nursing treatments delivered and patients’ characteristics, quality of dying and nurses’ expectation about death was summarized by means of multiple correspondence analysis (MCA). Results Few treatments were found statistically associated with expectation of death in the 187 patients included. In the last 48 h, routine (70.6%) and biomarkers (41.7%) blood tests were performed, at higher extent on patients whose death was not expected. Many symptoms classified as severe were reported when death was highly expected, except for agitation and respiratory fatigue which were reported when death was moderately expected. A high Norton score and absence of anti-bedsore mattress were associated with unexpected death and poor quality of dying, as summarized by MCA. Quality of dying was perceived as good by nurses when death was moderately and highly expected. Physicians rated more frequently than nurses the quality of dying as good or very good, respectively 78.6 and 57.8%, denoting a fair agreement between the two professionals (k = 0.24, P <  0.001). The palliative care consultant was requested for only two patients. Conclusion Staff in medical and surgical wards still deal inadequately with the needs of dying people. Presence of hospital-based specialist palliative care could lead to improvements in the patients’ quality of life

Gemcitabine-based doublets versus single-agent therapy for elderly patients with advanced nonsmall cell lung cancer: a Literature-based Meta-analysis.

Although platinum-based combinations are considered the best option of care for patients with advanced nonsmall cell lung cancer (NSCLC), single-agent therapy is the preferred treatment for older patients. Since the late 1990s, various combinations of third-generation agents (gemcitabine [G], vinorel- bine, docetaxel, and paclitaxel) have been tested, yielding contradictory results. The authors of this report performed a literature-based meta-analysis to assess the efficacy and tolerability of G-based doublets compared with single-agent chemotherapy for elderly patients with NSCLC. METHODS: Data from all published, randomized, phase 3 trials that compared a G-based doublet with a third-generation single agent in elderly patients were collected from electronic databases (Medline and the Cochrane Central Register of Controlled Trials), relevant reference lists, and abstract books. Pooled odds ratios (ORs) were calculated for the 1-year survival rate, the overall response rate (ORR), and grade 3 and 4 toxicities. RESULTS: Four eligible trials (1436 patients) were selected from 442 studies that initially were identified. A significant difference in ORR favoring G-based doublets over single agents was observed (OR, 0.65; 95% confidence interval [95% CI], 0.51-0.82 [P<.001]), whereas the trend toward an improved 1-year survival rate was not significant (OR, 0.78; 95% CI, 0.57-1.06 [P¼.169]). Grade 3 and 4 toxicities did not differ significantly except for thrombocytopenia (OR, 1.76; 95% CI, 1.12-2.76 [P¼.014]). CONCLUSIONS: G-based doublets appeared to be effective and feasible compared with single agents in the treatment of elderly patients with advanced NSCLC who were not suitable for full-dose, platinum-based chemotherapy. Further prospective, elderly specific, phase 3 trials will be necessary