New FPT algorithms for finding the temporal hybridization number for sets of phylogenetic trees

We study the problem of finding a temporal hybridization network for a set of phylogenetic trees that minimizes the number of reticulations. First, we introduce an FPT algorithm for this problem on an arbitrary set of $m$ binary trees with $n$ leaves each with a running time of $O(5^k\cdot n\cdot m)$, where $k$ is the minimum temporal hybridization number. We also present the concept of temporal distance, which is a measure for how close a tree-child network is to being temporal. Then we introduce an algorithm for computing a tree-child network with temporal distance at most $d$ and at most $k$ reticulations in $O((8k)^d5^ k\cdot n\cdot m)$ time. Lastly, we introduce a $O(6^kk!\cdot k\cdot n^2)$ time algorithm for computing a minimum temporal hybridization network for a set of two nonbinary trees. We also provide an implementation of all algorithms and an experimental analysis on their performance

New FPT algorithms for finding the temporal hybridization number for sets of phylogenetic trees

We study the problem of finding a temporal hybridization network containing at most k reticulations, for an input consisting of a set of phylogenetic trees. First, we introduce an FPT algorithm for the problem on an arbitrary set of m binary trees with n leaves each with a running time of O(5 k· n· m). We also present the concept of temporal distance, which is a measure for how close a tree-child network is to being temporal. Then we introduce an algorithm for computing a tree-child network with temporal distance at most d and at most k reticulations in O((8 k) d5 k· k· n· m) time. Lastly, we introduce an O(6 kk! · k· n2) time algorithm for computing a temporal hybridization network for a set of two nonbinary trees. We also provide an implementation of all algorithms and an experimental analysis on their performance

External validation of NTCP-models for radiation pneumonitis in lung cancer patients treated with chemoradiotherapy

PURPOSE: Normal tissue complication probability (NTCP) models can be used to estimate the risk of radiation pneumonitis (RP). The aim of this study was to externally validate the most frequently used prediction models for RP, i.e., the QUANTEC and APPELT models, in a large cohort of lung cancer patients treated with IMRT or VMAT. [1-2] METHODS AND MATERIALS: This prospective cohort study, included lung cancer patients treated between 2013 and 2018. A closed testing procedure was performed to test the need for model updating. To improve model performance, modification or removal of variables was considered. Performance measures included tests for goodness of fit, discrimination, and calibration.RESULTS: In this cohort of 612 patients, the incidence of RP ≥ grade 2 was 14.5%. For the QUANTEC-model, recalibration was recommended which resulted in a revised intercept and adjusted regression coefficient (from 0.126 to 0.224) of the mean lung dose (MLD),. The APPELT-model needed revision including model updating with modification and elimination of variables. After revision, the New RP-model included the following predictors (and regression coefficients): MLD (B = 0.250), age (B = 0.049, and smoking status (B = 0.902). The discrimination of the updated APPELT-model was higher compared to the recalibrated QUANTEC-model (AUC: 0.79 vs. 0.73).CONCLUSIONS: This study demonstrated that both the QUANTEC- and APPELT-model needed revision. Next to changes of the intercept and regression coefficients, the APPELT model improved further by model updating and performed better than the recalibrated QUANTEC model. This New RP-model is widely applicable containing non-tumour site specific variables, which can easily be collected.</p

The BioPAX community standard for pathway data sharing

Biological Pathway Exchange (BioPAX) is a standard language to represent biological pathways at the molecular and cellular level and to facilitate the exchange of pathway data. The rapid growth of the volume of pathway data has spurred the development of databases and computational tools to aid interpretation; however, use of these data is hampered by the current fragmentation of pathway information across many databases with incompatible formats. BioPAX, which was created through a community process, solves this problem by making pathway data substantially easier to collect, index, interpret and share. BioPAX can represent metabolic and signaling pathways, molecular and genetic interactions and gene regulation networks. Using BioPAX, millions of interactions, organized into thousands of pathways, from many organisms are available from a growing number of databases. This large amount of pathway data in a computable form will support visualization, analysis and biological discovery. © 2010 Nature America, Inc. All rights reserved

Effect of Male Accessory Gland Products on Egg Laying in Gastropod Molluscs

van Iersel S, Swart EM, Nakadera Y, van Straalen NM, Koene JM. Effect of Male Accessory Gland Products on Egg Laying in Gastropod Molluscs. Journal of Visualized Experiments. 2014;(88): e51698.In internally fertilizing animals, seminal fluid is usually added to the spermatozoa, together forming the semen or ejaculate. Besides nourishing and activating sperm, the components in the seminal fluid can also influence female physiology to augment fertilization success of the sperm donor. While many studies have reported such effects in species with separate sexes, few studies have addressed this in simultaneously hermaphroditic animals. This video protocol presents a method to study effects of seminal fluid in gastropods, using a simultaneously hermaphroditic freshwater snail, the great pond snail Lymnaea stagnalis, as model organism. While the procedure is shown using complete prostate gland extracts, individual components (i.e., proteins, peptides, and other compounds) of the seminal fluid can be tested in the same way. Effects of the receipt of ejaculate components on egg laying can be quantified in terms of frequency of egg laying and more subtle estimates of female reproductive performance such as egg numbers within each egg masses. Results show that seminal fluid proteins affect female reproductive output in this simultaneous hermaphrodite, highlighting their importance for sexual selection

Producing the Dutch and Belgian mortality projections: A stochastic multi-population standard

The quantification of longevity risk in a systematic way requires statistically sound forecasts of mortality rates and their corresponding uncertainty. Actuarial associations have a long history and continue to play an important role in the development, application and dispersion of mortality projections for the countries they represent. This paper gives an in depth presentation and discussion of the mortality projections as published by the Dutch (in 2014) and Belgian (in 2015) actuarial associations. The goal of these institutions was to publish a stochastic mortality projection model in line with both rigorous standards of state-of-the art academic work as well as the requirements of practical work such as robustness and transparency. Constructed by a team of authors from both academia and practice, the developed mortality projection standard is a Li & Lee type multi-population model. To project mortality, a global Western European trend and a country-specific deviation from this trend are jointly modelled with a bivariate time series model. We motivate and document all choices made in the model specification, calibration and forecasting process as well as the model selection strategy. We show the model fit and mortality projections and illustrate the use of the model in several pension-related applications.status: publishe

The Role of Intestinal Microbiota in Metastatic Colorectal Cancer Patients Treated With Capecitabine

BACKGROUND: Previous pre-clinical research has indicated that the intestinal microbiota can potentiate anti-tumour efficacy of capecitabine and that capecitabine treatment impacts intestinal microbiota composition and diversity. Using a longitudinal design, this study explores the associations between the intestinal microbiota and treatment response in patients with metastatic colorectal cancer (mCRC) during capecitabine treatment. PATIENTS AND METHODS: Patients with mCRC treated with capecitabine were prospectively enrolled in a multicentre cohort study. Patients collected a faecal sample and completed a questionnaire before, during, and after three cycles of capecitabine. Several clinical characteristics, including tumour response, toxicity and antibiotic use were recorded. Intestinal microbiota were analysed by amplicon sequencing of the 16S rRNA V4 gene-region. RESULTS: Thirty-three patients were included. After three cycles of capecitabine, six patients (18%) achieved a partial response, 25 (76%) showed stable disease, and one (3%) experienced progressive disease. Of the 90 faecal samples were collected. Microbial diversity (α-diversity), community structure (β-diversity), and bacterial abundance on phylum and genus level were not significantly different between responders and non-responders and were not significantly affected by three cycles of capecitabine. CONCLUSION: This is the first clinical study with longitudinal intestinal microbiota sampling in mCRC patients that explores the role of the intestinal microbiota during treatment with capecitabine. Intestinal microbiota composition and diversity before, during, and after three cycles of capecitabine were not associated with response in this study population. Capecitabine did not induce significant changes in the microbiota composition and diversity during the treatment period. Individual effects of antibiotics during capecitabine treatment were observed

An instrument dedicated for modelling of pulmonary radiotherapy

Background and purpose: Radiotherapy plays a pivotal role in lung cancer treatment. Selection of patients for new (radio)therapeutic options aiming at improving outcomes requires reliable and validated prediction models. We present the implementation of a prospective platform for evaluation and development of lung radiotherapy (proPED-LUNG) as an instrument enabling multidimensional predictive modelling. Materials and methods: ProPED-LUNG was designed to comprise relevant baseline and follow up data of patients receiving pulmonary radiotherapy with curative intent. Patient characteristics, diagnostic and staging information, treatment parameters including full dose-volume-histograms, tumour control, survival, and toxicity are scored. Besides physician-rated data, a range of patient-rated data regarding symptoms and health-related quality-of-life are collected. Results: After 18 months of accrual, 315 patients have been included (accrual rate, 18 per month). Of the first hundred patients included, 70 received conformal (chemo)radiotherapy and 30 underwent stereotactic radiotherapy. Compliance at 3 and 6 months follow-up was 96-100% for patient-rated, and 8194% for physician-rated assessments. For data collection, 0.4 FTE were allocated in a 183 FTE department (0.2%). Conclusions: ProPED-LUNG is feasible with high compliance rates and yields a large amount of high quality prospective disease-related, treatment-related, patient- and physician-rated data which can be used to evaluate new developments in pulmonary radiotherapy. (C) 2015 Elsevier Ireland Ltd. All rights reserved