Nearly 9 million Americans live in extreme-poverty neighborhoods, places that also tend to be racially segregated and dangerous. Yet, the effects on the well-being of residents of moving out of such ...communities into less distressed areas remain uncertain. Using data from Moving to Opportunity, a unique randomized housing mobility experiment, we found that moving from a high-poverty to lower-poverty neighborhood leads to long-term (10- to 15-year) improvements in adult physical and mental health and subjective well-being, despite not affecting economic self-sufficiency. A 1—standard deviation decline in neighborhood poverty (13 percentage points) increases subjective well-being by an amount equal to the gap in subjective well-being between people whose annual incomes differ by $13,000—a large amount given that the average control group income is $20,000. Subjective well-being is more strongly affected by changes in neighborhood economic disadvantage than racial segregation, which is important because racial segregation has been declining since 1970, but income segregation has been increasing.
We examine long-term neighborhood effects on low-income families using data from the Moving to Opportunity (MTO) randomized housing-mobility experiment. This experiment offered to some public-housing ...families but not to others the chance to move to less-disadvantaged neighborhoods. We show that ten to 15 years after baseline, MTO: (i) improves adult physical and mental health; (ii) has no detectable effect on economic outcomes or youth schooling or physical health; and (iii) has mixed results by gender on other youth outcomes, with girls doing better on some measures and boys doing worse. Despite the somewhat mixed pattern of impacts on traditional behavioral outcomes, MTO moves substantially improve adult subjective well-being. PUBLICATION ABSTRACT
Margaret McGregor and colleagues consider Bradford Hill's framework for examining causation in observational research for the association between nursing home care quality and for-profit ownership.
The sea urchin embryo development toxicity test was used to investigate toxicity of the benthic substrate in Biscayne National Park (BISC). Twenty-five sites were selected based upon a high potential ...for anthropogenic stressor input (e. g., hydrocarbons, personal care products, nutrients, etc.) or proximity to coral reef habitats. We found that sediment interstitial water (porewater) was toxic to urchin embryos at 22 of 25 sites. Healthy sites included two coral reefs (Anniversary Reef and Marker 14 Reef) and Turkey Point Channel. Discrete areas of BISC have highly toxic sediments and the presence of sediment contaminants could negatively impact reproduction, growth and population density of benthic invertebrates, such as corals. Results of the sea urchin embryo development toxicity test can be used as a baseline assessment for monitoring improvements or degradation in ecosystem health and could be a valuable tool to investigate the suitability of degraded habitats for future reef restoration. Since the last comprehensive environmental assessment of BISC was performed in 1999, further investigation into the sources of toxicity at BISC is needed.
Objectives This study sought to develop a model that predicts bleeding complications using an expanded bleeding definition among patients undergoing percutaneous coronary intervention (PCI) in ...contemporary clinical practice. Background New knowledge about the importance of periprocedural bleeding combined with techniques to mitigate its occurrence and the inclusion of new data in the updated CathPCI Registry data collection forms encouraged us to develop a new bleeding definition and risk model to improve the monitoring and safety of PCI. Methods Detailed clinical data from 1,043,759 PCI procedures at 1,142 centers from February 2008 through April 2011 participating in the CathPCI Registry were used to identify factors associated with major bleeding complications occurring within 72 h post-PCI. Risk models (full and simplified risk scores) were developed in 80% of the cohort and validated in the remaining 20%. Model discrimination and calibration were assessed in the overall population and among the following pre-specified patient subgroups: females, those older than 70 years of age, those with diabetes mellitus, those with ST-segment elevation myocardial infarction, and those who did not undergo in-hospital coronary artery bypass grafting. Results Using the updated definition, the rate of bleeding was 5.8%. The full model included 31 variables, and the risk score had 10. The full model had similar discriminatory value across pre-specified subgroups and was well calibrated across the PCI risk spectrum. Conclusions The updated bleeding definition identifies important post-PCI bleeding events. Risk models that use this expanded definition provide accurate estimates of post-PCI bleeding risk, thereby better informing clinical decision making and facilitating risk-adjusted provider feedback to support quality improvement.
Background
The benefits of moderate to vigorous physical activity (MVPA) for breast cancer survivors are well established. However, most are insufficiently active. Fit2Thrive used the Multiphase ...Optimization Strategy methodology to determine the effect of 5 intervention components on MVPA in this population.
Methods
Two hundred sixty‐nine participants (mean age, 52.5 years; SD, 9.9 years) received a core intervention (the Fit2Thrive self‐monitoring app and Fitbit) and were randomly assigned to 5 intervention components set to on/off in a full factorial experiment: support calls, deluxe app, buddy, online gym, and text messages. The intervention was delivered over 12 weeks with a 12‐week follow‐up. MVPA was measured via accelerometry at the baseline (T1), at 12 weeks (T2), and at 24 weeks (T3). The main effects and interaction effects at each time point were examined for all components.
Results
Trial retention was high: 91.8% had valid accelerometer data at T2 or T3. Across all conditions, there were significant increases in MVPA (+53.6 min/wk; P < .001) and in the proportion of survivors meeting MVPA guidelines (+22.3%; P < .001) at T2 that were maintained but attenuated at T3 (MVPA, +24.6 min/wk; P < .001; meeting guidelines, +12.6%; P < .001). No individual components significantly improved MVPA, although increases were greater for the on level versus the off level for support calls, buddy, and text messages at T2 and T3.
Conclusions
The Fit2Thrive core intervention (the self‐monitoring app and Fitbit) is promising for increasing MVPA in breast cancer survivors, but the components provided no additional increases in MVPA. Future research should evaluate the core intervention in a randomized trial and determine what components optimize MVPA behaviors in breast cancer survivors.
Systematically testing 5 technology‐supported physical activity promotion intervention components alongside the Fit2Thrive core intervention (Fit2Thrive self‐monitoring app and Fitbit) results in an increase in physical activity after the intervention and at a 12‐week follow‐up in breast cancer survivors. However, increases are not significantly greater with any component turned on versus off. This indicates that the Fit2Thrive core is a promising scalable strategy for increasing moderate to vigorous physical activity.
A mechanistic model is formulated to account for the high reactivity of chelating azides (organic azides capable of chelation-assisted metal coordination at the alkylated azido nitrogen position) and ...copper(II) acetate (Cu(OAc)2) in copper(II)-mediated azide–alkyne cycloaddition (AAC) reactions. Fluorescence and 1H NMR assays are developed for monitoring the reaction progress in two different solvents, methanol and acetonitrile. Solvent kinetic isotopic effect and premixing experiments give credence to the proposed different induction reactions for converting copper(II) to catalytic copper(I) species in methanol (methanol oxidation) and acetonitrile (alkyne oxidative homocoupling), respectively. The kinetic orders of individual components in a chelation-assisted, copper(II)-accelerated AAC reaction are determined in both methanol and acetonitrile. Key conclusions resulting from the kinetic studies include (1) the interaction between copper ion (either in +1 or +2 oxidation state) and a chelating azide occurs in a fast, pre-equilibrium step prior to the formation of the in-cycle copper(I)-acetylide, (2) alkyne deprotonation is involved in several kinetically significant steps, and (3) consistent with prior experimental and computational results by other groups, two copper centers are involved in the catalysis. The X-ray crystal structures of chelating azides with Cu(OAc)2 suggest a mechanistic synergy between alkyne oxidative homocoupling and copper(II)-accelerated AAC reactions, in which both a bimetallic catalytic pathway and a base are involved. The different roles of the two copper centers (a Lewis acid to enhance the electrophilicity of the azido group and a two-electron reducing agent in oxidative metallacycle formation, respectively) in the proposed catalytic cycle suggest that a mixed valency (+2 and +1) dinuclear copper species be a highly efficient catalyst. This proposition is supported by the higher activity of the partially reduced Cu(OAc)2 in mediating a 2-picolylazide-involved AAC reaction than the fully reduced Cu(OAc)2. Finally, the discontinuous kinetic behavior that has been observed by us and others in copper(I/II)-mediated AAC reactions is explained by the likely catalyst disintegration during the course of a relatively slow reaction. Complementing the prior mechanistic conclusions drawn by other investigators, which primarily focus on the copper(I)/alkyne interactions, we emphasize the kinetic significance of copper(I/II)/azide interaction. This work not only provides a mechanism accounting for the fast Cu(OAc)2-mediated AAC reactions involving chelating azides, which has apparent practical implications, but suggests the significance of mixed-valency dinuclear copper species in catalytic reactions where two copper centers carry different functions.
This study sought to develop a model that predicts bleeding complications using an expanded bleeding definition among patients undergoing percutaneous coronary intervention (PCI) in contemporary ...clinical practice.
New knowledge about the importance of periprocedural bleeding combined with techniques to mitigate its occurrence and the inclusion of new data in the updated CathPCI Registry data collection forms encouraged us to develop a new bleeding definition and risk model to improve the monitoring and safety of PCI.
Detailed clinical data from 1,043,759 PCI procedures at 1,142 centers from February 2008 through April 2011 participating in the CathPCI Registry were used to identify factors associated with major bleeding complications occurring within 72 h post-PCI. Risk models (full and simplified risk scores) were developed in 80% of the cohort and validated in the remaining 20%. Model discrimination and calibration were assessed in the overall population and among the following pre-specified patient subgroups: females, those older than 70 years of age, those with diabetes mellitus, those with ST-segment elevation myocardial infarction, and those who did not undergo in-hospital coronary artery bypass grafting.
Using the updated definition, the rate of bleeding was 5.8%. The full model included 31 variables, and the risk score had 10. The full model had similar discriminatory value across pre-specified subgroups and was well calibrated across the PCI risk spectrum.
The updated bleeding definition identifies important post-PCI bleeding events. Risk models that use this expanded definition provide accurate estimates of post-PCI bleeding risk, thereby better informing clinical decision making and facilitating risk-adjusted provider feedback to support quality improvement.
We have taken a genetic-based fate-mapping approach to determine the specific contributions of telencephalic progenitors to the structures that comprise the amygdalar fear circuit including the ...central (CA), lateral (LA), and basolateral (BLA) amygdala. Our data indicate that progenitors in the ventral pallium (VP) contribute projection neurons to the LA and BLA but not the CA. Rather, the CA appears to derive, at least in part, from progenitors located in the ventral lateral ganglionic eminence (vLGE). Diverse groups of interneurons populate these amygdalar nuclei, and as predicted our data support the notion that they originate from subpallial progenitors. A rather specific population of amygdalar interneurons, the intercalated cells (ITCs), is known to play a fundamental role in fear-related behaviors. However, no information on their specific origin has, as yet, been provided. Our findings suggest that the ITCs arise from the dorsal lateral ganglionic eminence (dLGE) and migrate in the lateral migratory stream to populate the paracapsular regions as well as the main intercalated mass of the amygdala (IA). Germ-line Gsx2 mutants are known to exhibit an expansion of the VP into the LGE and a concomitant reduction in the dLGE and vLGE. Accordingly, Gsx2 conditional mutants display a significantly enlarged LA and a significant reduction in ITCs both within the paracapsular regions and the IA. Additional support for a dLGE origin of the ITCs was obtained in conditional mutants of the dLGE gene Sp8. Thus, our findings indicate diverse origins for the neuronal components that comprise the amygdalar fear circuit.
Clinical and genomic evidence suggests that the metastatic potential of a primary tumor may be dictated by prometastatic events that have additional oncogenic capability. To test this “deterministic” ...hypothesis, we adopted a comparative oncogenomics-guided function-based strategy involving: (1) comparison of global transcriptomes of two genetically engineered mouse models with contrasting metastatic potential, (2) genomic and transcriptomic profiles of human melanoma, (3) functional genetic screen for enhancers of cell invasion, and (4) evidence of expression selection in human melanoma tissues. This integrated effort identified six genes that are potently proinvasive and oncogenic. Furthermore, we show that one such gene,
ACP5, confers spontaneous metastasis in vivo, engages a key pathway governing metastasis, and is prognostic in human primary melanomas.
► Integrates melanoma mouse models and human genomics data to derive cancer gene list ► Uses a function-based screening approach to identify oncogenic metastasis drivers ► Shows that ACP5 engages the FAK-signaling complex and is prognostic in melanoma ► Metastatic events present in early tumors can reflect their oncogenic capability
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