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Frank Lloyd Wright's lost buildings
\"As hard as it is to imagine, about one hundred of Frank Lloyd Wright's buildings -- one of every five built -- have been demolished. Houses, apartment buildings, and recreation and business structures all succumbed to real estate pressures, changing tastes, or sheer neglect. 'Frank Lloyd Wright's Lost Buildings' is the first book to trace some of these major losses. Poignant illustrations document Wright's monumental achievements that are no longer around: the world-renowned Imperial Hotel, the festive Midway Gardens, the awe-inspiring Larkin Building. Formative, early designs by the young architect -- a boathouse, a golf club, a courtyard apartment building -- briefly come back to life, along with the architect's own desert camp and houses that helped Wright gain worldwide fame.\"--Front flap of book jacket.
Book
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
Endocrine-disrupting chemicals and risk of diabetes: an evidence-based review
The purpose of this study was to review the epidemiological and experimental evidence linking background exposure to a selection of environmental endocrine-disrupting chemicals (EDCs) with diabetes and impaired glucose metabolism. The review summarises the literature on both cross-sectional and prospective studies in humans, as well as experimental in vivo and in vitro studies. The findings were subjected to evidence grading according to the Grading of Recommendations Assessment, Development and Evaluation (GRADE) classification. We found >40 cross-sectional and seven prospective studies regarding EDCs and risk of diabetes. Taken together, there is moderate evidence for a relationship between exposure to dichlorodiphenyldichloroethylene (p,p′-DDE), a metabolite of the pesticide dichlorodiphenyltrichloroethane, and diabetes development. Regarding polychlorinated biphenyls (PCBs), it is likely that the rodent models used are not appropriate, and therefore the evidence is poorer than for p,p′-DDE. For other EDCs, such as bisphenol A, phthalates and perfluorinated chemicals, the evidence is scarce, since very few prospective studies exist. Brominated flame retardants do not seem to be associated with a disturbed glucose tolerance. Thus, evidence is accumulating that EDCs might be involved in diabetes development. Best evidence exists for p,p′-DDE. For other chemicals, both prospective studies and supporting animal data are still lacking.
Journal Article
Big is beautiful : debunking the myth of small business
\"In public discourse in the United States, small businesses are lauded as drivers of the economy and keys to economic growth, while 'big business' is often vilified. Even in the face of evidence that larger firms are proven to be more likely to stimulate economic growth, American public policy favors small businesses through measures such as lowering taxes or regulatory requirements for firms under a certain number of employees ... Rather than simply taking the opposite view that 'bigger is better,' the authors argue that a modern capitalist society has room for businesses of all sizes and that we should not be privileging one type of business over another due to size alone\"-- Provided by publisher.
Book
A comparison of intima media thickness in the common carotid artery, the bulb and plaque area as predictions of incident atherosclerotic events
There is a debate on how to evaluate carotid artery intima-media thickness (IMT). We here compared IMT of the common carotid artery (CCA) and bulb with plaque area regarding incident atherosclerotic disease.
In the PIVUS study (age 70 at baseline, 53% women, n = 856), IMT-CCA, IMT-bulb and plaque area were measured at ages 70, 75 and 80 years and these three measurements were used in updated Cox proportional hazard analysis.
Over 15 years follow-up, 135 individuals experienced a first-time atherosclerotic disease (myocardial infarction or ischemic stroke). IMT-CCA was not significantly related to this composite endpoint (p = 0.10). IMT-bulb was significantly related to the endpoint (p = 0.003), but this relationship was attenuated following adjustment for CVD risk factors (p = 0.02). On the contrary, plaque area was consistently related to incident atherosclerotic disease also following adjustment for CVD risk factors (p<0.001). When added on top of traditional risk factors, both IMT-bulb and plaque area, but not IMT-CCA, improved the discrimination compared to the traditional risk factors (+5.2%, p = 0.0026 for IMT-bulb, +3.8%, p = 0.013 for plaque area and 0.0% for IMT-CCA).
In elderly subjects, both IMT-bulb and plaque area improved the discrimination regarding incident atherosclerotic disease when added to traditional risk factors. This was not seen for IMT-CCA. IMT-CCA was therefore inferior compared to the other two carotid artery ultrasonographic measurements in this sample of elderly subjects.
Journal Article
A Development of the Human Development Index
This paper presents a variant human development index H. It resembles the human development index HDI, published annually since 1990 by the United Nations Development Programme, but it is calibrated to reflect ‘development’ as evident in the actual progression of life expectancy, education and income shown over 1990–2017 by the people of the world as a whole. Index H uses the same dimensions and country statistics as the HDI but has no arbitrary parameters; all its parameters are derived from the statistics. The fundamental assumption is that humans overall choose how much education and work serves them best to improve health and income. Index H also facilitates comparison of a country's progress over time, allowing for both ordinal and cardinal interpretations, with the world in year 2000 used as unit of development. Moreover, H provides explicit quantified valuation of health, safety and education policy. Just as the HDI has properly downplayed the importance of income in comparison with health and education, H discounts the income variable (Gross National Income), but even further.
Journal Article
Reading achievement and motivation in boys and girls : field studies and methodological approaches
This volume links theoretical and instructional approaches on how reading is motivated and assessed, and examines the interrelationship between reading motivation and achievement among boys and girls in culturally and geographically different settings. Much of the research on children's reading has focused on cognitive processes; however, reading is an activity that also requires interest and motivation. These attitudes are generally defined as readers' affect toward reading and their consequence is that children with more positive attitudes are more motivated to read. Taking into account the variability that exists within the notion of gender and age, this volume aims to examine and scrutinize previous research on the topic, as well as test theories on how the different dimensions of reading motivation vary with gender, in relation to cultural issues, motivational constructs, such as engagement and classroom climate, the role of emotions, interests and attitudes towards reading, among others. The book will be of interest to researchers, educators, graduate students, and other professionals working in the area of literacy, reading motivation, reading achievement and gender differences.
Book
Circulating levels of perfluoroalkyl substances and prevalent diabetes in the elderly
Aims/hypothesis
Several environmental contaminants, such as polychlorinated biphenyls, dioxins, bisphenol A and phthalates, have been linked to diabetes. We therefore investigated whether other kinds of contaminants, perfluoroalkyl substances (PFAS), also called perfluorinated compounds (PFCs), are also associated with diabetes.
Methods
The Prospective Investigation of the Vasculature in Uppsala Seniors (PIVUS) study investigated 1,016 men and women aged 70 years. Seven PFAS were detected in almost all participant sera by ultra-high performance liquid chromatograph/tandem mass spectrometry. Diabetes was defined as use of hypoglycaemic agents or fasting glucose >7.0 mmol/l.
Results
114 people had diabetes. In the linear analysis, no significant relationships were seen between the seven PFAS and prevalent diabetes. However, inclusion of the quadratic terms of the PFAS revealed a significant non-linear relationship between perfluorononanoic acid (PFNA) and diabetes, even after adjusting for multiple confounders (OR 1.96, 95% CI 1.19, 3.22,
p
= 0.008 for the linear term and OR 1.25, 95% CI 1.08, 1.44,
p
= 0.002 for the quadratic term). Perfluorooctanoic acid (PFOA) also showed such a relationship (
p
= 0.01). PFOA was related to the proinsulin/insulin ratio (a marker of insulin secretion), but none of the PFAS was related to the HOMA-IR (a marker of insulin resistance) following adjustment for multiple confounders.
Conclusions/interpretation
PFNA was related to prevalent diabetes in a non-monotonic fashion in this cross-sectional study, supporting the view that this perfluoroalkyl substance might influence glucose metabolism in humans at the level of exposure seen in the general elderly population.
Journal Article