Optimal Piecewise Linear Regression Algorithm for QSAR Modelling

Quantitative Structure‐Activity Relationship (QSAR) models have been successfully applied to lead optimisation, virtual screening and other areas of drug discovery over the years. Recent studies, however, have focused on the development of models that are predictive but often not interpretable. In this article, we propose the application of a piecewise linear regression algorithm, OPLRAreg, to develop both predictive and interpretable QSAR models. The algorithm determines a feature to best separate the data into regions and identifies linear equations to predict the outcome variable in each region. A regularisation term is introduced to prevent overfitting problems and implicitly selects the most informative features. As OPLRAreg is based on mathematical programming, a flexible and transparent representation for optimisation problems, the algorithm also permits customised constraints to be easily added to the model. The proposed algorithm is presented as a more interpretable alternative to other commonly used machine learning algorithms and has shown comparable predictive accuracy to Random Forest, Support Vector Machine and Random Generalised Linear Model on tests with five QSAR data sets compiled from the ChEMBL database

Outcomes of ethnic minority groups with node-positive, non-metastatic breast cancer in two tertiary referral centers in Sydney, Australia

Purpose: There is a lack of information in ethnic minority groups with regard to presentation and treatment of early node-positive breast cancer. We carried out a retrospective study of patients referred to two tertiary cancer centers in South Western Sydney, both of which serve a high proportion of this ethnic minority population. Patients and methods: Women who had pathologically node-positive non-metastatic breast cancer (T1-3, N1-3, M0) diagnosed between 2003 and 2006 were studied, with variables of interest being tumor size, number of positive nodes, histological grade, hormone receptor status, age at diagnosis, country of birth and treatment. We compared the Asian and Western subgroups with regard to tumor characteristics, treatment and clinical outcomes. Results: A total of 652 eligible patients were identified, with a median follow-up of 6.1 years. Women with Asian backgrounds (n = 125, 20%) were significantly younger at presentation (48 years versus 55 years, p-value <0.0001) and more likely to undergo mastectomy (53% versus 39%, p-value 0.0009) and chemotherapy (86% versus 72%, p-value 0.0063) than their non-Asian counterparts. Tumor stage, grade and receptor status were not statistically different between these two groups. There were also no differences in disease-free survival and overall survival, with medians of 12.7 and 14.8 years respectively. Conclusion: Women of Asian background are younger at diagnosis, which may reflect population epidemiology and likely results in higher uptake of chemotherapy. Higher mastectomy rates may be influenced by cultural factors. Future research is warranted to investigate potential differences in tumor biology, psychosocial, economic and cultural factors

Contemporary role of cardiac magnetic resonance in the management of patients with suspected or known coronary artery disease

Cardiac magnetic resonance imaging (CMR) is a useful non-invasive radiation-free imaging modality for the management of patients with coronary artery disease (CAD). CMR cine imaging provides the “gold standard” assessment of ventricular function, late gadolinium enhancement (LGE) provides useful data for the diagnosis and extent of myocardial scar and viability, while stress imaging is an established technique for the detection of myocardial perfusion defects indicating ischemia. Beyond its role in the diagnosis of CAD, CMR allows accurate risk stratification of patients with established CAD. This review aims to summarize the data regarding the role of CMR in the contemporary management of patients with suspected or known coronary artery disease

Comparison of magnetic resonance imaging and computed tomography for breast target volume delineation in prone and supine positions

Purpose To\ua0determine whether T2-weighted MRI improves seroma cavity (SC) and whole breast (WB) interobserver conformity for radiation therapy purposes, compared with the gold standard of CT, both in the prone and supine positions. Methods and Materials Eleven observers (2 radiologists and 9 radiation oncologists) delineated SC and WB clinical target volumes (CTVs) on T2-weighted MRI and CT supine and prone scans (4 scans per patient) for 33 patient datasets. Individual observer's volumes were compared using the Dice similarity coefficient, volume overlap index, center of mass shift, and Hausdorff distances. An average cavity visualization score was also determined. Results Imaging modality did not affect interobserver variation for WB CTVs. Prone WB CTVs were larger in volume and more conformal than supine CTVs (on both MRI and CT). Seroma cavity volumes were larger on CT than on MRI. Seroma cavity volumes proved to be comparable in interobserver conformity in both modalities (volume overlap index of 0.57\ua0(95% Confidence Interval (CI) 0.54-0.60) for CT supine and 0.52\ua0(95% CI 0.48-0.56) for MRI supine, 0.56\ua0(95% CI 0.53-0.59) for CT prone and 0.55\ua0(95% CI 0.51-0.59) for MRI prone); however, after registering modalities together the intermodality variation (Dice similarity coefficient of 0.41\ua0(95% CI 0.36-0.46) for supine and 0.38\ua0(0.34-0.42) for prone) was larger than the interobserver variability for SC, despite the location typically remaining constant. Conclusions Magnetic resonance imaging interobserver variation was comparable to CT for the WB CTV and SC delineation, in both prone and supine positions. Although the cavity visualization score and interobserver concordance was not significantly higher for MRI than for CT, the SCs were smaller on MRI, potentially owing to clearer SC definition, especially on T2-weighted MR images

Evaluation of machine-learning methods for ligand-based virtual screening

Machine-learning methods can be used for virtual screening by analysing the structural characteristics of molecules of known (in)activity, and we here discuss the use of kernel discrimination and naive Bayesian classifier (NBC) methods for this purpose. We report a kernel method that allows the processing of molecules represented by binary, integer and real-valued descriptors, and show that it is little different in screening performance from a previously described kernel that had been developed specifically for the analysis of binary fingerprint representations of molecular structure. We then evaluate the performance of an NBC when the training-set contains only a very few active molecules. In such cases, a simpler approach based on group fusion would appear to provide superior screening performance, especially when structurally heterogeneous datasets are to be processed

The development of the advanced web shop based on purchase history

The goal of thesis is to develop a typical web shop application with some additional functionality. This functionality enables web shop customers to browse products in a more efficient way and thus makes shop more profitable. For this purpose, we developed a specific mechanism that handles product presentation in customer adapted way. First we describe technologies used for development. Programing language C# is presented shortly as well as some other frameworks (ASP.net, Entity framework,), libraries (LINQ) and other web technologies (HTML, CSS, AJAX). For storing and manipulating data a database with tables in MS SQL database is created. Furthermore we take a look at requirements, idea and logic of solution. We present solution design and present how specific functionality behaves in case of different user types. We present a solution analysis where a comparison with other similar solutions and user tests are shown. Finally we discuss problems during the development and possibilities about the future improvements

Unexpected combination of acute croup and myocarditis: Case report

BACKGROUND: Lower vaccination coverage among foreign-born children is of concern because they live in households and communities characterized by more intense exposure to infectious diseases. Because of their higher prevalence rates, there is an increasing occurrence of infectious diseases imported into developed countries. This case report emphasizes the emerging necessity for new clinicians and pathologists of having competence with old infectious disease pathology. CASE PRESENTATION: A three and a half year old girl, who presented with croup history of 5 days and has been in severe respiratory distress, was admitted to the Pediatric Intensive Care Unit in shock and acute respiratory failure. The patient was immediately intubated, and a grayish nonadherent membrane extending through the glottis down into the larynx was apparent during the procedure. Echocardiographic findings, which were consistent with acute myocarditis, confirmed poor left ventricular contractility despite escalating high doses of inotropes. Autopsy showed numerous strains of toxigenic corynobacterium diphtheriae, which also grew on the Loeffler cultures of membranes received during the intubation. CONCLUSION: It is critical that new generations of clinicians and bio-pathologists not only be trained in the subspecialty of infectious disease pathology, but that they also be willing participants in the diagnosis and investigation of infectious diseases

Measurement of the cross-section and charge asymmetry of WW bosons produced in proton-proton collisions at s=8\sqrt{s}=8 TeV with the ATLAS detector

This paper presents measurements of the $W^+ \rightarrow \mu^+\nu$ and $W^- \rightarrow \mu^-\nu$ cross-sections and the associated charge asymmetry as a function of the absolute pseudorapidity of the decay muon. The data were collected in proton--proton collisions at a centre-of-mass energy of 8 TeV with the ATLAS experiment at the LHC and correspond to a total integrated luminosity of 20.2~\mbox{fb^{-1}}. The precision of the cross-section measurements varies between 0.8% to 1.5% as a function of the pseudorapidity, excluding the 1.9% uncertainty on the integrated luminosity. The charge asymmetry is measured with an uncertainty between 0.002 and 0.003. The results are compared with predictions based on next-to-next-to-leading-order calculations with various parton distribution functions and have the sensitivity to discriminate between them.Comment: 38 pages in total, author list starting page 22, 5 figures, 4 tables, submitted to EPJC. All figures including auxiliary figures are available at https://atlas.web.cern.ch/Atlas/GROUPS/PHYSICS/PAPERS/STDM-2017-13