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"Anderson, Peter"
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Predicting drug activity against cancer cells by random forest models based on minimal genomic information and chemical properties
A key goal of precision medicine is predicting the best drug therapy for a specific patient from genomic information. In oncology, cancers that appear similar pathologically can vary greatly in how they respond to the same drug. Fortunately, data from high-throughput screening programs often reveal important relationships between genomic variability of cancer cells and their response to drugs. Nevertheless, many current computational methods to predict compound activity against cancer cells require large quantities of genomic, epigenomic, and additional cellular data to develop and to apply. Here we integrate recent screening data and machine learning to train classification models that predict the activity/inactivity of compounds against cancer cells based on the mutational status of only 145 oncogenes and a set of compound structural descriptors. Using IC50 values of 1 μM as activity cutoffs, our predictive models have sensitivities of 87%, specificities of 87%, and yield an area under the receiver operating characteristic curve equal to 0.94. We also develop regression models to predict log(IC50) values of compounds for cancer cells; the models achieve a Pearson correlation coefficient of 0.86 for cross-validation and up to 0.65-0.73 against blind test sets. Predictive performance remains strong when as few as 50 oncogenes are included. Finally, even when 40% of experimental IC50 values are missing from screening data, they can be imputed with sufficient reliability that classification accuracy is not diminished. The presented models are fast to generate and may serve as easily implemented screening tools for personalized oncology medicine, drug repurposing, and drug discovery.
Journal Article
Defining the Neurologic Consequences of Preterm Birth
The authors outline the three major forms of brain injury in very preterm infants and the role of injury in subsequent brain development, noting mediating factors and their neurodevelopmental consequences.
Journal Article
Happy orchid : help it flower, watch it flourish
\"Make the flowers on your exquisite new orchid last, and help it rebloom after dormancy. Featuring care profiles for more than 125 varieties, Happy Orchid makes it easy to care for your plant with advice on where to position it, how to keep it flowering, when to water and fertilize it, and how often to repot it. With step-by-step instructions and tips for creating attractive displays, you will soon be an expert grower, inspired to fill your home with these exotic and beautiful flowers.\"--Back cover.
Book
Glutamine for Amelioration of Radiation and Chemotherapy Associated Mucositis during Cancer Therapy
Glutamine is a major dietary amino acid that is both a fuel and nitrogen donor for healing tissues damaged by chemotherapy and radiation. Evidence supports the benefit of oral (enteral) glutamine to reduce symptoms and improve and/or maintain quality of life of cancer patients. Benefits include not only better nutrition, but also decreased mucosal damage (mucositis, stomatitis, pharyngitis, esophagitis, and enteritis). Glutamine supplementation in a high protein diet (10 grams/day) + disaccharides, such as sucrose and/or trehalose, is a combination that increases glutamine uptake by mucosal cells. This increased topical effect can reduce painful mucosal symptoms and ulceration associated with chemotherapy and radiation in the head and neck region, esophagus, stomach and small intestine. Topical and oral glutamine seem to be the preferred routes for this amino acid to promote mucosal healing during and after cancer treatment.
Journal Article
Applied theatre : research : radical departures
\"Applied Theatre: Research is the first book to consolidate thinking about applied theatre as research through a thorough investigation of ATAR as a research methodology. It will be an indispensable resource for teachers and researchers in the area. The first section of the book details the history of the relationship between applied theatre and research, especially in the area of evaluation and impact assessment, and offering an examination of the literature surrounding applied theatre and research. The book then explores how applied theatre as research (ATAR) works as a democratic and pro-social adjunct to community based research and explains its complex relationship to arts informed inquiry, Indigenous research methods and other research epistemologies. The book provides a rationale for this approach focusing on its capacity for reciprocity within communities. The second part of the book provides a series of international case studies of effective practice which detail some of the key approaches in the method and based on work conducted in Australia, New Zealand, Singapore and the South Pacific. The case studies provide a range of cultural contexts for the playing out of various forms of ATAR, and a concluding chapter considers the tensions and the possibilities inherent in ATAR. This is a groundbreaking book for all researchers who are working with communities who require a method that moves beyond current research practice\"-- Provided by publisher.
Book
PrEP uptake, persistence, adherence, and effect of retrospective drug level feedback on PrEP adherence among young women in southern Africa: Results from HPTN 082, a randomized controlled trial
Pre-exposure prophylaxis (PrEP) is highly effective and an important prevention tool for African adolescent girls and young women (AGYW), but adherence and persistence are challenging. PrEP adherence support strategies for African AGYW were studied in an implementation study.
HIV Prevention Trials Network (HPTN) 082 was conducted in Cape Town, Johannesburg (South Africa) and Harare (Zimbabwe) from October 2016 to October 2018 to evaluate PrEP uptake, persistence, and the effect of drug level feedback on adherence. Sexually active HIV-negative women ages 16-25 were offered PrEP and followed for 12 months; women who accepted PrEP were randomized to standard adherence support (counseling, 2-way SMS, and adherence clubs) or enhanced adherence support with adherence feedback from intracellular tenofovir-diphosphate (TFV-DP) levels in dried blood spots (DBS). PrEP uptake, persistence through 12 months (no PrEP hold or missed visits), and adherence were assessed. The primary outcome was high adherence (TFV-DP ≥700 fmol/punch) at 6 months, compared by study arm. Of 451 women enrolled, median age was 21 years, and 39% had curable sexually transmitted infections (STIs). Most (95%) started PrEP, of whom 55% had uninterrupted PrEP refills through 12 months. Of those with DBS, 84% had detectable TFV-DP levels at month 3, 57% at month 6, and 31% at month 12. At 6 months, 36/179 (21%) of AGYW in the enhanced arm had high adherence and 40/184 (22%) in the standard adherence support arm (adjusted odds ratio [OR] of 0.92; 95% confidence interval [CI] 0.55, 1.34; p = 0.76). Four women acquired HIV (incidence 1.0/100 person-years), with low or undetectable TFV-DP levels at or prior to seroconversion, and none of whom had tenofovir or emtricitabine resistance mutations. The study had limited power to detect a modest effect of drug level feedback on adherence, and there was limited awareness of PrEP at the time the study was conducted.
In this study, PrEP initiation was high, over half of study participants persisted with PrEP through month 12, and the majority of young African women had detectable TFV-DP levels through month 6 with one-fifth having high adherence. Drug level feedback in the first 3 months of PrEP use did not increase the proportion with high adherence at month 6. HIV incidence was 1% in this cohort with 39% prevalence of curable STIs and moderate PrEP adherence. Strategies to support PrEP use and less adherence-dependent formulations are needed for this population.
ClinicalTrials.gov NCT02732730.
Journal Article