Project description:Approximately 7% of women with breast cancer are diagnosed before the age of 40 years, and this disease accounts for more than 40% of all cancer in women in this age group. Survival rates are worse when compared to those in older women, and multivariate analysis has shown younger age to be an independent predictor of adverse outcome. Inherited syndromes, specifically BRCA1 and BRCA2, must be considered when developing treatment algorithms for younger women. Chemotherapy, endocrine, and local therapies have the potential to significantly impact both the physiologic health-including future fertility, premature menopause, and bone health-and the psychological health of young women as they face a diagnosis of breast cancer.
Project description:In November 1973, my colleagues A. C. Y. Chang, H. W. Boyer, R. B. Helling, and I reported in PNAS that individual genes can be cloned and isolated by enzymatically cleaving DNA molecules into fragments, linking the fragments to an autonomously replicating plasmid, and introducing the resulting recombinant DNA molecules into bacteria. A few months later, Chang and I reported that genes from unrelated bacterial species can be combined and propagated using the same approach and that interspecies recombinant DNA molecules can produce a biologically functional protein in a foreign host. Soon afterward, Boyer's laboratory and mine published our collaborative discovery that even genes from animal cells can be cloned in bacteria. These three PNAS papers quickly led to the use of DNA cloning methods in multiple areas of the biological and chemical sciences. They also resulted in a highly public controversy about the potential hazards of laboratory manipulation of genetic material, a decision by Stanford University and the University of California to seek patents on the technology that Boyer and I had invented, and the application of DNA cloning methods for commercial purposes. In the 40 years that have passed since publication of our findings, use of DNA cloning has produced insights about the workings of genes and cells in health and disease and has altered the nature of the biotechnology and biopharmaceutical industries. Here, I provide a personal perspective of the events that led to, and followed, our report of DNA cloning.
Project description:Abundance-occupancy (A-O) relationships are widely documented for many organismal groups and regions, and have been used to gain an understanding of regional population and community trends. Monitoring changes in abundance and occupancy over time may be what is required to document changes in conservation status and needs for some species, communities, or areas.We hypothesize that if there is a higher proportion of declining species in one group of species compared with another (e.g., migratory species vs. permanent residents), then a consequence of that difference will be vastly different abundance-occupancy relationships. If this difference persists through time, then the resulting A-O relationships between the groups will continue to diverge.For neotropical migrants, short-distance migrants, and permanent resident birds of North America, we assess the numbers of declining species over 1969-2009. We further test for differences in the A-O relationship across these three groups, and in rates of change in abundance and occupancy separately.We find significant differences in numbers of declining species across the migratory groups, a significant decline in the A-O relationship for permanent residents, a significant increase for Neotropical migrants, and a nonsignificant decline for short-distance migrants over the 40 years. Further, abundances are not changing at different rates but occupancies are consistently greater over time for neotropical migrants versus permanent residents, likely driving the changes in A-O relationships observed.In these analyses, we documented changing A-O trends for different groups of species, over a relatively long time period for ecological studies, one of only a few studies to examine A-O relationships over time. Further, we have shown that a temporally unvarying abundance-occupancy relationship is not universal, and we posit that variability in A-O relationships is due to human impacts on habitats, coupled with variation in species' abilities to respond to human impacts.
Project description:Liver problems caused by infection, cholestasis and sinusoidal liver injury in the months following HCT have become less frequent because of preventive and pre-emptive strategies. When patients develop jaundice after transplant, the time to search for treatable causes is early in the course of jaundice, as the risk of mortality rises steeply with small increments of serum bilirubin above normal. Chronic hepatitis C, persistent GVHD, cirrhosis and hepatocellular carcinoma are significant liver problems in the longest-lived survivors of HCT.
Project description:We aimed to determine which discipline had the greater performance improvements in the history of Ironman triathlon in Hawaii and also which discipline had the greater influence in overall race time. Data from 1983 to 2018 of the top three women and men of each year who competed in the Ironman World Championship were included. In addition to exploratory data analyses, linear regressions between split times and years of achievement were performed. Further, a stepwise multiple linear regression was applied using total race time as the dependent variable and split times as the independent variables. Both women and men significantly improved their performances from 1983 to 2018 in the Ironman World Championship. Swimming had the largest difference in improvements between men and women (3.0% versus 12.1%, respectively). A negative and significant decrease in each discipline was identified for both women and men, with cycling being the discipline with the greatest reduction. The results from the stepwise multiple regression indicated that cycling was the discipline with the highest influence on overall race time for both sexes. Based on the findings of this study, cycling seems to be the Ironman triathlon discipline that most improved overall race times and is also the discipline with the greatest influence on the overall race time of elite men and women in the Ironman World Championship.
Project description:The underlying causes of migraine headache remained enigmatic for most of the 20th century. In 1979, The Lancet published a novel hypothesis proposing an integral role for the neuropeptide-containing trigeminal nerve. This hypothesis led to a transformation in the migraine field and understanding of key concepts surrounding migraine, including the role of neuropeptides and their release from meningeal trigeminal nerve endings in the mechanism of migraine, blockade of neuropeptide release by anti-migraine drugs, and activation and sensitisation of trigeminal afferents by meningeal inflammatory stimuli and upstream role of intense brain activity. The study of neuropeptides provided the first evidence that antisera directed against calcitonin gene-related peptide (CGRP) and substance P could neutralise their actions. Successful therapeutic strategies using humanised monoclonal antibodies directed against CGRP and its receptor followed from these findings. Nowadays, 40 years after the initial proposal, the trigeminovascular system is widely accepted as having a fundamental role in this highly complex neurological disorder and provides a road map for future migraine therapies.