The Association Between Neighborhood Environment and Mortality: Results from a National Study of Veterans.

BACKGROUND: As the largest integrated US health system, the Veterans Health Administration (VHA) provides unique national data to expand knowledge about the association between neighborhood socioeconomic status (NSES) and health. Although living in areas of lower NSES has been associated with higher mortality, previous studies have been limited to higher-income, less diverse populations than those who receive VHA care. OBJECTIVE: To describe the association between NSES and all-cause mortality in a national sample of veterans enrolled in VHA primary care. DESIGN: One-year observational cohort of veterans who were alive on December 31, 2011. Data on individual veterans (vital status, and clinical and demographic characteristics) were abstracted from the VHA Corporate Data Warehouse. Census tract information was obtained from the US Census Bureau American Community Survey. Logistic regression was used to model the association between NSES deciles and all-cause mortality during 2012, adjusting for individual-level income and demographics, and accounting for spatial autocorrelation. PARTICIPANTS: Veterans who had vital status, demographic, and NSES data, and who were both assigned a primary care physician and alive on December 31, 2011 (n = 4,814,631). MAIN MEASURES: Census tracts were used as proxies for neighborhoods. A summary score based on census tract data characterized NSES. Veteran addresses were geocoded and linked to census tract NSES scores. Census tracts were divided into NSES deciles. KEY RESULTS: In adjusted analysis, veterans living in the lowest-decile NSES tract were 10 % (OR 1.10, 95 % CI 1.07, 1.14) more likely to die than those living in the highest-decile NSES tract. CONCLUSIONS: Lower neighborhood SES is associated with all-cause mortality among veterans after adjusting for individual-level socioeconomic characteristics. NSES should be considered in risk adjustment models for veteran mortality, and may need to be incorporated into strategies aimed at improving veteran health.

The neural circuit mechanisms underlying the retinal response to motion reversal.

To make up for delays in visual processing, retinal circuitry effectively predicts that a moving object will continue moving in a straight line, allowing retinal ganglion cells to anticipate the object's position. However, a sudden reversal of motion triggers a synchronous burst of firing from a large group of ganglion cells, possibly signaling a violation of the retina's motion prediction. To investigate the neural circuitry underlying this response, we used a combination of multielectrode array and whole-cell patch recordings to measure the responses of individual retinal ganglion cells in the tiger salamander to reversing stimuli. We found that different populations of ganglion cells were responsible for responding to the reversal of different kinds of objects, such as bright versus dark objects. Using pharmacology and designed stimuli, we concluded that ON and OFF bipolar cells both contributed to the reversal response, but that amacrine cells had, at best, a minor role. This allowed us to formulate an adaptive cascade model (ACM), similar to the one previously used to describe ganglion cell responses to motion onset. By incorporating the ON pathway into the ACM, we were able to reproduce the time-varying firing rate of fast OFF ganglion cells for all experimentally tested stimuli. Analysis of the ACM demonstrates that bipolar cell gain control is primarily responsible for generating the synchronized retinal response, as individual bipolar cells require a constant time delay before recovering from gain control.

Alert response to motion onset in the retina.

Previous studies have shown that motion onset is very effective at capturing attention and is more salient than smooth motion. Here, we find that this salience ranking is present already in the firing rate of retinal ganglion cells. By stimulating the retina with a bar that appears, stays still, and then starts moving, we demonstrate that a subset of salamander retinal ganglion cells, fast OFF cells, responds significantly more strongly to motion onset than to smooth motion. We refer to this phenomenon as an alert response to motion onset. We develop a computational model that predicts the time-varying firing rate of ganglion cells responding to the appearance, onset, and smooth motion of a bar. This model, termed the adaptive cascade model, consists of a ganglion cell that receives input from a layer of bipolar cells, represented by individual rectified subunits. Additionally, both the bipolar and ganglion cells have separate contrast gain control mechanisms. This model captured the responses to our different motion stimuli over a wide range of contrasts, speeds, and locations. The alert response to motion onset, together with its computational model, introduces a new mechanism of sophisticated motion processing that occurs early in the visual system.

Association of the neighborhood retail food environment with sodium and potassium intake among US adults.

INTRODUCTION: High sodium intake and low potassium intake, which can contribute to hypertension and risk of cardiovascular disease, may be related to the availability of healthful food in neighborhood stores. Despite evidence linking food environment with diet quality, this relationship has not been evaluated in the United States. The modified retail food environment index (mRFEI) provides a composite measure of the retail food environment and represents the percentage of healthful-food vendors within a 0.5 mile buffer of a census tract. METHODS: We analyzed data from 8,779 participants in the National Health and Nutrition Examination Survey, 2005-2008. By using linear regression, we assessed the relationship between mRFEI and sodium intake, potassium intake, and the sodium-potassium ratio. Models were stratified by region (South and non-South) and included participant and neighborhood characteristics. RESULTS: In the non-South region, higher mRFEI scores (indicating a more healthful food environment) were not associated with sodium intake, were positively associated with potassium intake (P [trend] = .005), and were negatively associated with the sodium-potassium ratio (P [trend] = .02); these associations diminished when neighborhood characteristics were included, but remained close to statistical significance for potassium intake (P [trend] = .05) and sodium-potassium ratio (P [trend] = .07). In the South, mRFEI scores were not associated with sodium intake, were negatively associated with potassium intake (P [trend] = < .001), and were positively associated with sodium-potassium ratio (P [trend] = .01). These associations also diminished after controlling for neighborhood characteristics for both potassium intake (P [trend] = .03) and sodium-potassium ratio (P [trend] = .40). CONCLUSION: We found no association between mRFEI and sodium intake. The association between mRFEI and potassium intake and the sodium-potassium ratio varied by region. National strategies to reduce sodium in the food supply may be most effective to reduce sodium intake. Strategies aimed at the local level should consider regional context and neighborhood characteristics.

Thrombospondin-1 proteomimetic polymers exhibit anti-angiogenic activity in a neovascular age-related macular degeneration mouse model.

Neovascular age-related macular degeneration (nAMD) is the leading cause of blindness in the developed world. Current therapy includes monthly intraocular injections of anti-VEGF antibodies, which are ineffective in up to one third of patients. Thrombospondin-1 (TSP1) inhibits angiogenesis via CD36 binding, and its down-regulated expression is negatively associated with the onset of nAMD. Here, we describe TSP1 mimetic protein-like polymers (TSP1 PLPs). TSP1 PLPs bind CD36 with high affinity, resist degradation, show prolonged intraocular half-lives (13.1 hours), have no toxicity at relevant concentrations in vivo (40 µM), and are more efficacious in ex vivo choroidal sprouting assays compared to the peptide sequence and Eylea (aflibercept), the current standard of care anti-VEGF treatment. Furthermore, PLPs exhibit superior in vivo efficacy in a mouse model for nAMD compared to control PLPs consisting of scrambled peptide sequences, using fluorescein angiography and immunofluorescence. Since TSP-1 inhibits angiogenesis by VEGF-dependent and independent mechanisms, TSP1 PLPs are a potential therapeutic for patients with anti-VEGF treatment-resistant nAMD.

Low error discrimination using a correlated population code.

We explored the manner in which spatial information is encoded by retinal ganglion cell populations. We flashed a set of 36 shape stimuli onto the tiger salamander retina and used different decoding algorithms to read out information from a population of 162 ganglion cells. We compared the discrimination performance of linear decoders, which ignore correlation induced by common stimulation, with nonlinear decoders, which can accurately model these correlations. Similar to previous studies, decoders that ignored correlation suffered only a modest drop in discrimination performance for groups of up to ∼30 cells. However, for more realistic groups of 100+ cells, we found order-of-magnitude differences in the error rate. We also compared decoders that used only the presence of a single spike from each cell with more complex decoders that included information from multiple spike counts and multiple time bins. More complex decoders substantially outperformed simpler decoders, showing the importance of spike timing information. Particularly effective was the first spike latency representation, which allowed zero discrimination errors for the majority of shape stimuli. Furthermore, the performance of nonlinear decoders showed even greater enhancement compared with linear decoders for these complex representations. Finally, decoders that approximated the correlation structure in the population by matching all pairwise correlations with a maximum entropy model fit to all 162 neurons were quite successful, especially for the spike latency representation. Together, these results suggest a picture in which linear decoders allow a coarse categorization of shape stimuli, whereas nonlinear decoders, which take advantage of both correlation and spike timing, are needed to achieve high-fidelity discrimination.

Poisson cluster analysis of cardiac arrest incidence in Columbus, Ohio.

BACKGROUND: Scarce resources in disease prevention and emergency medical services (EMS) need to be focused on high-risk areas of out-of-hospital cardiac arrest (OHCA). OBJECTIVE: Cluster analysis using geographic information systems (GISs) was used to find these high-risk areas and test potential predictive variables. METHODS: This was a retrospective cohort analysis of EMS-treated adults with OHCAs occurring in Columbus, Ohio, from April 1, 2004, through March 31, 2009. The OHCAs were aggregated to census tracts and incidence rates were calculated based on their adult populations. Poisson cluster analysis determined significant clusters of high-risk census tracts. Both census tract-level and case-level characteristics were tested for association with high-risk areas by multivariate logistic regression. RESULTS: A total of 2,037 eligible OHCAs occurred within the city limits during the study period. The mean incidence rate was 0.85 OHCAs/1,000 population/year. There were five significant geographic clusters with 76 high-risk census tracts out of the total of 245 census tracts. In the case-level analysis, being in a high-risk cluster was associated with a slightly younger age (-3 years, adjusted odds ratio [OR] 0.99, 95% confidence interval [CI] 0.99-1.00), not being white, non-Hispanic (OR 0.54, 95% CI 0.45-0.64), cardiac arrest occurring at home (OR 1.53, 95% CI 1.23-1.71), and not receiving bystander cardiopulmonary resuscitation (CPR) (OR 0.77, 95% CI 0.62-0.96), but with higher survival to hospital discharge (OR 1.78, 95% CI 1.30-2.46). In the census tract-level analysis, high-risk census tracts were also associated with a slightly lower average age (-0.1 years, OR 1.14, 95% CI 1.06-1.22) and a lower proportion of white, non-Hispanic patients (-0.298, OR 0.04, 95% CI 0.01-0.19), but also a lower proportion of high-school graduates (-0.184, OR 0.00, 95% CI 0.00-0.00). CONCLUSIONS: This analysis identified high-risk census tracts and associated census tract-level and case-level characteristics that can be used to target public education efforts to prevent OHCA and to mitigate its occurrence with CPR and automated external defibrillator training. In addition, EMS resources can be redeployed to minimize response times to these census tracts.

Synchronized firing among retinal ganglion cells signals motion reversal.

We show that when a moving object suddenly reverses direction, there is a brief, synchronous burst of firing within a population of retinal ganglion cells. This burst can be driven by either the leading or trailing edge of the object. The latency is constant for movement at different speeds, objects of different size, and bright versus dark contrasts. The same ganglion cells that signal a motion reversal also respond to smooth motion. We show that the brain can build a pure reversal detector using only a linear filter that reads out synchrony from a group of ganglion cells. These results indicate that not only can the retina anticipate the location of a smoothly moving object, but that it can also signal violations in its own prediction. We show that the reversal response cannot be explained by models of the classical receptive field and suggest that nonlinear receptive field subunits may be responsible.

Racial residential segregation and stroke mortality in Atlanta.

OBJECTIVE: To assess the association between neighborhood-level racial residential segregation and stroke mortality using a spatially derived segregation index. DESIGN: Cross-sectional study SETTING: Atlanta Metropolitan Statistical Area METHODS: The study population consisted of non-Hispanic Black and White residents of the Atlanta Metropolitan Statistical Area during the time period Jan 1, 2000 to December 31, 2006. Census tract-level stroke death rates for Blacks and Whites were modeled as a function of the segregation index while controlling for two neighborhood-level chronic stressors (poverty, low education). RESULTS: Racial segregation was positively associated with stroke mortality for both Blacks and Whites aged 35-64 years. Among Blacks and Whites aged 65 or older, segregation was negatively associated with stroke mortality after controlling for the two stressors, suggesting that they were pathways between segregation and stroke death rates. CONCLUSION: Future studies are needed to identify additional pathways between residential segregation and other health outcomes, and to collect data that support a life course approach to understanding the impact of residential segregation on health.

Detection and prediction of periodic patterns by the retina.

A fundamental task of the brain is detecting patterns in the environment that enable predictions about the future. Here, we show that the salamander and mouse retinas can recognize a wide class of periodic temporal patterns, such that a subset of ganglion cells fire strongly and specifically in response to a violation of the periodicity. This sophisticated retinal processing may provide a substrate for hierarchical pattern detection in subsequent circuits.

An oscillatory circuit underlying the detection of disruptions in temporally-periodic patterns.

Neurons in diverse brain areas can respond to the interruption of a regular stimulus pattern by firing bursts of spikes. Here we describe a simple model, which permits such responses to periodic stimuli over a substantial frequency range. Focusing on the omitted stimulus response (OSR) in isolated retinas subjected to periodic patterns of dark flashes, we develop a biophysically-realistic model which accounts for resonances in ON bipolar cells. The bipolar cell terminal contains an LRC oscillator whose inductance is modulated by a transient calcium concentration, thus adjusting its resonant frequency to approximately match that of the stimulus. The model reproduces ganglion cell outputs, which sum the ON and OFF bipolar pathways, and it responds to omitted flashes with approximately constant latencies, as observed experimentally.

Sophisticated temporal pattern recognition in retinal ganglion cells.

Pattern recognition is one of the most important tasks of the visual system, and uncovering the neural mechanisms underlying recognition phenomena has been a focus of researchers for decades. Surprisingly, at the earliest stages of vision, the retina is capable of highly sophisticated temporal pattern recognition. We stimulated the retina of tiger salamander (Ambystoma tigrinum) with periodic dark flash sequences and found that retinal ganglion cells had a wide variety of different responses to a periodic flash sequence with many firing when a flash was omitted. The timing of the omitted stimulus response (OSR) depended on the period, with individual cells tracking the stimulus period down to increments of 5 ms. When flashes occurred earlier than expected, cells updated their expectation of the next flash time by as much as 50 ms. When flashes occurred later than expected, cells fired an OSR and reset their temporal expectation to the average time interval between flashes. Using pharmacology to investigate the retinal circuitry involved, we found that inhibitory transmission from amacrine cells was not required, but on bipolar cells were required. The results suggest a mechanism in which the intrinsic resonance of on bipolars leads to the OSR in ganglion cells. We discuss the implications of retinal pattern recognition on the neural code of the retina and visual processing in general.

Shadows of the past: temporal retrieval effects in recognition memory.

We examine whether temporally defined associations play a role in item recognition. The role of these associations in recall tasks is well known; we demonstrate an important role in item recognition as well. In this study, subjects were significantly more likely to recognize a test item as having been previously experienced if the preceding test item was studied in a temporally proximal list position than if the preceding test item came from a more distant list position. Further analyses showed that this associative effect was almost entirely due to cases in which the preceding test item received a highest-confidence recognition judgment.