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A multimodal program focused on preventing nosocomial respiratory viral infections. Definite cases per 1,000 discharges increased 1.3-fold in hospital units screening visitors for respiratory viral symptoms during the 2017–2018 respiratory virus season but not during the 2016–2017 season. Definite cases per 1,000 discharges increased 3.1-fold in hospital units that did not screen visitors either season.
OBJECTIVES/SPECIFIC AIMS: Triple-negative breast cancer (TNBC) accounts for one-fifth of the breast cancer patient population. The heterogeneous nature of TNBC and lack of options for targeted therapy make its treatment a constant adventure. The deficiency of tumor suppressors p53 and ARF is one of the known genetic signatures enriched in TNBC. Crucial questions remain about how TNBC is regulated by these genetic alterations. METHODS/STUDY POPULATION: In order to address this issue, we established p53/ARF-defective murine embryonic fibroblast and mammary epithelial cell to study the molecular and phenotypic consequences. Moreover, transgenic mice were generated to investigate the effect of p53/ARF deficiency on mammary tumor development in vivo. RESULTS/ANTICIPATED RESULTS: Increased proliferation and transformation capability were observed in p53/ARF-defective cells, and an aggressive form of mammary tumor was also seen in p53−/−ARF−/− mice. Gene expression profiling and knock-down experiments using shRNAs were conducted to identify inflammatory marker ISG15 and RNA-editing enzyme ADAR1 as potential culprits for the elevated oncogenic potential. Interestingly, we found that the overexpression of ISG15 and ADAR1 is also prevalent in human TNBC cell lines. Reducing ADAR1 expression abrogated the oncogenic potential of human TNBC cell lines, while non-TNBC cells are less susceptible. DISCUSSION/SIGNIFICANCE OF IMPACT: These results indicate critical roles played by the tumor suppressors p53 and ARF in the pathogenesis of TNBC, likely through regulating ADAR1-mediated RNA modifications. Further understanding of this pathway promises to shed light on genetics-driven vulnerabilities of TNBC and inform development of more effective therapeutic strategies.
Every nuclear weapons program for decades has relied extensively on illicit imports of nuclear-related technologies. This book offers the most detailed public account of how states procure what they need to build nuclear weapons, what is currently being done to stop them, and how global efforts to prevent such trade could be strengthened. While illicit nuclear trade can never be stopped completely, effective steps to block illicit purchases of nuclear technology have sometimes succeeded in slowing nuclear weapons programs and increasing their costs, giving diplomacy more chance to work. Hence, this book argues, preventing illicit transfers wherever possible is a key element of an effective global non-proliferation strategy.
Network analysis is an emerging approach in the study of psychopathology, yet few applications have been seen in eating disorders (EDs). Furthermore, little research exists regarding changes in network strength after interventions. Therefore the present study examined the network structures of ED and co-occurring depression and anxiety symptoms before and after treatment for EDs.
Participants from residential or partial hospital ED treatment programs (N = 446) completed assessments upon admission and discharge. Networks were estimated using regularized Graphical Gaussian Models using 38 items from the Eating Disorders Examination-Questionnaire, Quick Inventory of Depressive Symptomatology, and State-Trait Anxiety Inventory.
ED symptoms with high centrality indices included a desire to lose weight, guilt about eating, shape overvaluation, and wanting an empty stomach, while restlessness, self-esteem, lack of energy, and feeling overwhelmed bridged ED to depression and anxiety symptoms. Comparisons between admission and discharge networks indicated the global network strength did not change significantly, though symptom severity decreased. Participants with denser networks at admission evidenced less change in ED symptomatology during treatment.
Findings suggest that symptoms related to shape and weight concerns and guilt are central ED symptoms, while physical symptoms, self-esteem, and feeling overwhelmed are links that may underlie comorbidities in EDs. Results provided some support for the validity of network approaches, in that admission networks conveyed prognostic information. However, the lack of correspondence between symptom reduction and change in network strength indicates that future research is needed to examine network dynamics in the context of intervention and relapse prevention.
Depression and metabolic syndrome (MetS) are frequently comorbid disorders that are independently associated with premature mortality. Conversely, cardiorespiratory fitness (CRF) is associated with reduced mortality risk. These factors may interact to impact mortality; however, their effects have not been assessed concurrently. This analysis assessed the mortality risk of comorbid depression/MetS and the effect of CRF on mortality in those with depression/MetS.
Prospective study of 47 702 adults in the Cooper Center Longitudinal Study. Mortality status was attained from the National Death Index. History of depression was determined by patient response (yes or no) to a standardized medical history questionnaire. MetS was categorized using the American Heart Association/National Heart, Lung, and Blood Institute criteria. CRF was estimated from the final speed/grade of a treadmill graded exercise test.
13.9% reported a history of depression, 21.4% met criteria for MetS, and 3.0% met criteria for both MetS and history of depression. History of depression (HR = 1.24, p = 0.003) and MetS (HR = 1.28, p < 0.001) were independently associated with an increased mortality risk, with the greatest mortality risk among individuals with both a history of depression and MetS (HR = 1.59, p < 0.001). Higher CRF was associated with a significantly lower risk of mortality (p < 0.001) in all individuals, including those with MetS and/or a history of depression.
Those with higher levels CRF had reduced mortality risk in the context of depression/MetS. Interventions that improve CRF could have substantial impact on the health of persons with depression/MetS.
This paper provides new accelerator mass spectrometry (AMS) radiocarbon age data for the last volcanic events in the Carpathian-Pannonian region of eastern-central Europe. The eruption ages were determined on charcoal fragments collected from pumiceous pyroclastic flow deposits at 2 localities of the Ciomadul Volcano. Two charcoal samples from the southeastern margin of the volcano (Bixad locality) set the date of the last volcanic eruption to 27,200 ± 260 yr BP (29,500 ± 260 cal BC). On the other hand, our data show that the Tusnad pyroclastic flow deposit, previously considered as representing the youngest volcanic rock of the region, erupted at ∼39,000 yr BP (∼41,300 cal BC). Thus, a period of dormancy more than 10,000 yr long might have elapsed between the 2 volcanic events. The different ages of the Tusnad and Bixad pyroclastic flow deposits are confirmed also by the geochemical data. The bulk pumices, groundmass glass, and the composition of the main mineral phases (plagioclase and amphibole) suggest eruption of slightly different magmas. Considering also the assumed long volcanic history (∼600 ka) of the Ciomadul, these data suggest that further detailed studies are necessary on this seemingly inactive volcano in order to evaluate the possible renewal of volcanic activity in the future.
This study employed a paired priming paradigm to ask whether input features influence a child's propensity to use non-nominative versus nominative case in subject position, and to use non-nominative forms even when verbs are marked for agreement. Thirty English-speaking children (ages 2;6 to 3;7) heard sentences with pronouns that had non-contrasting case forms (e.g. Dad hugs it and it hugs Tigger) and it was hypothesized that these forms would lead to more errors (e.g. Himhugs Barney) in an elicited phrase more often than if the children heard contrasting case forms (e.g. Dad hugs us and we hug the doggie). Tense/agreement features were also examined in children's elicited productions. The findings were consistent with predictions, and supported the input ambiguity hypothesis of Pelham (2011). Implications for current accounts of the optional infinitive stage are discussed.
Changes in the physical environment are major drivers of evolutionary change, either through direct effects on the distribution and abundance of species or more subtle shifts in the outcome of biological interactions. To investigate this phenomenon, we built a fossil data set of drilling gastropod predation on bivalve prey for the last 11 Myr to determine how the regional collapse in Caribbean upwelling and planktonic productivity affected predator–prey interactions. Contrary to theoretical expectations, predation increased nearly twofold after productivity declined, while the ratio of drilling predators to prey remained unchanged. This increase reflects a gradual, several-fold increase in the extent of shallow-water coral reefs and seagrass meadows in response to the drop in productivity that extended over several million years. Drilling predation is uniformly higher in biogenic habitats than in soft sediments. Thus, changes in predation intensity were driven by a shift in dominant habitats rather than a direct effect of decreased productivity. Most previous analyses of predation through time have not accounted for variations in environmental conditions, raising questions about the patterns observed. More fundamentally, however, the consequences of large-scale environmental perturbations may not be instantaneous, especially when changes in habitat and other aspects of local environmental conditions cause cascading series of effects.
We documented changes in the relative abundance of bivalve genera and functional groups in the southwest Caribbean over the past 11 Myr to determine their response to oceanographic changes associated with the closure of the Central American Seaway ca. 3.5 Ma. Quantitative bulk samples from 29 localities yielded 106,000 specimens in 145 genera. All genera were assigned to functional groups based on diet, relationship to the substrate, and mobility. Ordinations of assemblages based on quantitative data for functional groups demonstrated strong shifts in community structure, with a stark contrast between assemblages older than 5 Ma and those younger than 3.5 Ma. These changes are primarily due to an increase in the abundance of attached epifaunal bivalves (e.g., Chama, Arcopsis, and Barbatia) and a decrease in infaunal bivalves (e.g., Varicorbula and Caryocorbula). Taxa associated with seagrasses, including deposit-feeding and chemosymbiotic bivalves (e.g., Lucina), also increased in relative abundance compared to suspension feeders. The composition of bivalve assemblages is correlated with the carbonate content of sediments and the percentage of skeletal biomass that is coral. Our results strongly support the hypothesis that increases in the extent of coral reefs and Thalassia communities were important drivers of biologic turnover in Neogene Caribbean benthic communities.
Elongate canines evolved independently at least four times among mammalian carnivores, and each time skulls were modified in similar ways. We have compared the cranial morphology of sabertooths to that of their non-sabertoothed relatives, living and extinct, and applied simple biomechanical models to elucidate the functional significance of the morphological differences. Our analysis suggests that (1) sabertooth morphology represents modification for wider gape with retention of a powerful bite force at the carnassial; (2) sabertooths probably used a throat or ventral neck slash to kill prey; and (3) elongate canines and retractile claws may have facilitated the exploitation of relatively larger prey by sabertooths compared to non-sabertooth carnivores.
In the past fifteen years, the biological interpretation of vertebrate fossils has been markedly advanced by the application of experimental techniques in functional morphology, biomechanical and allometric modelling, more rigorously-derived empirical correlations between form and function in living species, and studies of modern community structure and of the taphonomic processes by which fossil assemblages are formed. Traditional paleontological methods of phylogenetic analysis are under attack by the advocates of cladistics; the resulting debate is leading to increased rigor in paleontological systematics. Paleobiogeographical studies of vertebrates has become an extremely active area of research due to the need to reanalyze past distribution patterns in the light of plate tectonics.
New information has extended the fossil record of vertebrates back to the Late Cambrian, but little more is known about the nature of the earliest vertebrates or of the pre-vertebrate ancestors. Much has been learned of the fishes antecedent to tetrapods but little of the earliest tetrapods. The early reptiles are now well known, but the nature of their amphibian ancestors is uncertain. Restudy of Archaeopteryx has suggested a dinosaurian ancestry for birds. The origin and early evolution of mammals is the subject of extensive research as a result of greatly augmented recent collecting. The most active and innovative research is on the biology of dinosaurs, especially on their physiology. Among Cenozoic mammals, the fossil record of primates has been greatly expanded and knowledge of primate history, from the basal prosimians of the Paleocene to early man, is increasing rapidly.