In a Temporally Segmented Experience Hippocampal Neurons Represent Temporally Drifting Context But Not Discrete Segments.

There is widespread agreement that episodic memory is organized into a timeline of past experiences. Recent work suggests that the hippocampus may parse the flow of experience into discrete episodes separated by event boundaries. A complementary body of work suggests that context changes gradually as experience unfolds. We recorded from hippocampal neurons as male Long-Evans rats performed 6 blocks of an object discrimination task in sets of 15 trials. Each block was separated by removal from the testing chamber for a delay to enable segmentation. The reward contingency reversed from one block to the next to incentivize segmentation. We expected animals to hold two distinct, recurring representations of context to match the two distinct rule contingencies. Instead, we found that overtrained rats began each block neither above nor below chance but by guessing randomly. While many units had clear firing fields selective to the conjunction of objects in places, a significant population also reflected a continuously drifting code both within block and across blocks. Despite clear boundaries between blocks, we saw no neural evidence for event segmentation in this experiment. Rather, the hippocampal ensemble drifted continuously across time. This continuous drift in the neural representation was consistent with the lack of segmentation observed in behavior.SIGNIFICANCE STATEMENT The neuroscience literature yet to reach consensus on how the hippocampus supports the organization of events across time in episodic memory. Initial studies reported stable hippocampal maps segmented by remapping events. However, it remains unclear whether segmentation is an artifact of cue responsivity. Recently, research has shown that the hippocampal code exhibits continuous drift. Drift may represent a continually evolving context; however, it is unclear whether this is an artifact of changing experiences. We recorded dCA1 in rats performing an object discrimination task designed to segment time. Overtrained rats could not anticipate upcoming context switches but used context boundaries to their advantage. Hippocampal ensembles showed neither evidence of alternating between stable contexts nor sensitivity to boundaries, but showed robust temporal drift.

A packaged mindset: How elongated packages induce healthy mindsets.

Product packaging is an important instrument for marketers to draw consumer attention to specific product information and influence product perceptions. The purpose of this research is to investigate whether exposure to a product's packaging can also activate specific mindsets that, once activated, alter consumers' food perceptions. The results of three experiments demonstrate that elongated containers activate a health mindset that influences both consumers' perception of the packaged food product but also their health perceptions of subsequently encountered food. Specifically, foods in elongated containers lead consumers to think of concepts related to healthiness, which have differentiable effects on subsequent healthy and unhealthy food products.

Neighborhood Recreation Facilities and Facility Membership Are Jointly Associated with Objectively Measured Physical Activity.

Efforts to increase physical activity have traditionally included either individual-level interventions (e.g., educational campaigns) or neighborhood-level interventions (e.g., additional recreational facilities). Little work has addressed the interaction between spatial proximity and individual characteristics related to facility use. We aimed to better understand the synergistic impact of both physical activity environments and recreational facility membership on objectively measured physical activity. Using the New York City Physical Activity and Transit (PAT) survey (n = 644), we evaluated associations between counts of commercial physical activity facilities within 1 km of participants' home addresses with both facility membership and accelerometry-measured physical activity. Individuals living near more facilities were more likely to report membership (adjusted odds ratio for top versus bottom quartile of facility count: 3.77 (95% CI 1.54-9.20). Additionally, while amount of facilities within a neighborhood was associated with more physical activity, this association was stronger for individuals reporting gym membership. Interventions aiming to increase physical activity should consider both neighborhood amenities and potential barriers, including the financial and social barriers of membership. Evaluation of neighborhood opportunities must expand beyond physical presence to consider multiple dimensions of accessibility.

A Local View of Informal Urban Environments: a Mobile Phone-Based Neighborhood Audit of Street-Level Factors in a Brazilian Informal Community.

Street-level environment characteristics influence the health behaviors and safety of urban residents, and may particularly threaten health within informal communities. However, available data on how such characteristics vary within and among informal communities is limited. We sought to adapt street audit strategies designed to characterize the physical environment for use in a large informal community, Rio das Pedras (RdP) located in Rio de Janeiro, Brazil. A smartphone-based systematic observation protocol was used to gather street-level information for a high-density convenience sample of street segments (N = 630, estimated as 86% of all street segments in the community). We adapted items related to physical disorder and physical deterioration. Measures selected to illustrate the approach include the presence of the following: (1) low-hanging or tangled wires, (2) litter, (3) structural evidence of sinking, and (4) an unpleasant odor. Intercept-only spatial generalized additive models (GAM) were used to evaluate and visualize spatial variation within the RdP community. We also examined how our estimates and conclusions about spatial variation might have been affected by lower-density sampling from random subsets street observations. Random subsets were selected to determine the robustness of study results in scenarios with sparser street sampling. Selected characteristics were estimated to be present for between 18% (unpleasant odor) to 59% (low-hanging or tangled wires) of the street segments in RdP; estimates remain similar (± 6%) when relying on a random subset created to simulate lower-density spatial sampling. Spatial patterns of variation based on predicted probabilities across RdP differed by indicator. Structural sinking and low-hanging or tangled wires demonstrated relatively consistent spatial distribution patterns across full and random subset sample sizes. Smartphone-based systematic observations represent an efficient and potentially feasible approach to systematically studying neighborhood environments within informal communities. Future deployment of such tools will benefit from incorporating data collection across multiple time points to explore reliability and quantify neighborhood change. These tools can prove useful means to assess street-level exposures that can be modifiable health determinants across a wide range of informal urban settings. Findings can contribute to improved urban planning and provide useful information for identifying potential locations for neighborhood-scaled interventions that can improve living conditions for residents in Rio das Pedras.

Associations of Residential Socioeconomic, Food, and Built Environments With Glycemic Control in Persons With Diabetes in New York City From 2007-2013.

In the present study, we examined the longitudinal associations between residential environmental factors and glycemic control in 182,756 adults with diabetes in New York City from 2007 to 2013. Glycemic control was defined as a hemoglobin A1c (HbA1c) level less than 7%. We constructed residential-level measures and performed principle component analysis to formulate a residential composite score. On the basis of this score, we divided residential areas into quintiles, with the lowest and highest quintiles reflecting the least and most advantaged residential environments, respectively. Several residential-level environmental characteristics, including more advantaged socioeconomic conditions, greater ratio of healthy food outlets to unhealthy food outlets, and residential walkability were associated with increased glycemic control. Individuals who lived continuously in the most advantaged residential areas took less time to achieve glycemic control compared with the individuals who lived continuously in the least advantaged residential areas (9.9 vs. 11.5 months). Moving from less advantaged residential areas to more advantaged residential areas was related to improved diabetes control (decrease in HbA1c = 0.40%, 95% confidence interval: 0.22, 0.55), whereas moving from more advantaged residential areas to less advantaged residential areas was related to worsening diabetes control (increase in HbA1c = 0.33%, 95% confidence interval: 0.24, 0.44). These results show that residential areas with greater resources to support healthy food and residential walkability are associated with improved glycemic control in persons with diabetes.

Pulmonary Endpoints in Duchenne Muscular Dystrophy. A Workshop Summary.

Development of novel therapeutics for treatment of Duchenne muscular dystrophy (DMD) has led to clinical trials that include pulmonary endpoints that allow assessment of respiratory muscle status, especially in nonambulatory subjects. Parent Project Muscular Dystrophy (PPMD) convened a workshop in Bethesda, Maryland, on April 14 and 15, 2016, to summarize published respiratory data in DMD and give guidance to clinical researchers assessing the effect of interventions on pulmonary outcomes in DMD.

Time Cells in Hippocampal Area CA3.

UNLABELLED: Studies on time cells in the hippocampus have so far focused on area CA1 in animals performing memory tasks. Some studies have suggested that temporal processing within the hippocampus may be exclusive to CA1 and CA2, but not CA3, and may occur only under strong demands for memory. Here we examined the temporal and spatial coding properties of CA3 and CA1 neurons in rats performing a maze task that demanded working memory and a control task with no explicit working memory demand. In the memory demanding task, CA3 cells exhibited robust temporal modulation similar to the pattern of time cell activity in CA1, and the same populations of cells also exhibited typical place coding patterns in the same task. Furthermore, the temporal and spatial coding patterns of CA1 and CA3 were equivalently robust when animals performed a simplified version of the task that made no demands on working memory. However, time and place coding did differ in that the resolution of temporal coding decreased over time within the delay interval, whereas the resolution of place coding was not systematically affected by distance along the track. These findings support the view that CA1 and CA3 both participate in encoding the temporal and spatial organization of ongoing experience. SIGNIFICANCE STATEMENT: Hippocampal "time cells" that fire at specific moments in a temporally structured memory task have so far been observed only in area CA1, and some studies have suggested that temporal coding within the hippocampus is exclusive to CA1. Here we describe time cells also in CA3, and time cells in both areas are observed even without working memory demands, similar to place cells in these areas. However, unlike equivalent spatial coding along a path, temporal coding is nonlinear, with greater temporal resolution earlier than later in temporally structured experiences. These observations reveal both similarities and differences in temporal and spatial coding within the hippocampus of importance to understanding how these features of memory are represented in the hippocampus.

Street Audits to Measure Neighborhood Disorder: Virtual or In-Person?

Neighborhood conditions may influence a broad range of health indicators, including obesity, injury, and psychopathology. In particular, neighborhood physical disorder-a measure of urban deterioration-is thought to encourage crime and high-risk behaviors, leading to poor mental and physical health. In studies to assess neighborhood physical disorder, investigators typically rely on time-consuming and expensive in-person systematic neighborhood audits. We compared 2 audit-based measures of neighborhood physical disorder in the city of Detroit, Michigan: One used Google Street View imagery from 2009 and the other used an in-person survey conducted in 2008. Each measure used spatial interpolation to estimate disorder at unobserved locations. In total, the virtual audit required approximately 3% of the time required by the in-person audit. However, the final physical disorder measures were significantly positively correlated at census block centroids (r = 0.52), identified the same regions as highly disordered, and displayed comparable leave-one-out cross-validation accuracy. The measures resulted in very similar convergent validity characteristics (correlation coefficients within 0.03 of each other). The virtual audit-based physical disorder measure could substitute for the in-person one with little to no loss of precision. Virtual audits appear to be a viable and much less expensive alternative to in-person audits for assessing neighborhood conditions.

Associations Among Neighborhood Characteristics and Sexual Risk Behavior Among Black and White MSM Living in a Major Urban Area.

Identifying neighborhood characteristics associated with sexual HIV risk behavior among gay, bisexual and other men who have sex with men (MSM) living in urban areas may inform the development of policies and programs to reduce risk and subsequently HIV prevalence in urban areas. New York City M2M was a cross-sectional study designed to identify neighborhood-level characteristics associated with sexual risk behaviors among MSM living in New York City. This paper presents results of an analysis of neighborhood-level indicators of three distinct social theories of influence of the neighborhood environment on human behavior: physical disorder, social disorganization and social norms theories. Using multilevel modeling on a sample of 766 MSM stratified by race/ethnicity, we found little support for the role of social disorganization on the sexual risk behavior of MSM, whereas different indicators of physical disorder exerted negative effects across race groups. Our results suggest that the beneficial effects of housing stock maintenance and general neighborhood physical orderliness and cleanliness may have positive effects beyond those traditionally studied for African American MSM and that the field needs novel theorizing regarding whether and how neighborhood or virtual community-level factors relate to sexual behavior among MSM.

Blepharochalasis: something to cry about.

Blepharochalasis is a rare disorder of unknown etiology defined by loose, atrophic periorbital skin following recurrent episodes of eyelid edema. Characteristic histopathology shows complete absence of elastic fibers. The current case progressed after multiple episodes of crying, which may be related to matrix metalloproteinase dysregulation. This case offers further insights into the possible pathogenesis of blepharochalasis, paving the way for more targeted, disease-modifying therapies.

Neighborhood determinants of mood and anxiety disorders among men who have sex with men in New York City.

PURPOSE: We examined the relationship between economic, physical, and social characteristics of neighborhoods, where men who have sex with men (MSM) lived and socialized, and symptom scores of depression and generalized anxiety disorder (GAD). METHODS: Participants came from a cross-sectional study of a population-based sample of New York City MSM recruited in 2010-2012 (n = 1126). Archival and survey-based data were obtained on neighborhoods, where the men lived and where they socialized most often. RESULTS: MSM who socialized in neighborhoods with more economic deprivation and greater general neighborhood attachment experienced higher GAD symptoms. The relationship between general attachment to neighborhoods where MSM socialized and mental health depended on the level of gay community attachment: in neighborhoods characterized by greater gay community attachment, general neighborhood attachment was negatively associated with GAD symptoms, while in low gay community attachment neighborhoods, general neighborhood attachment had a positive association with GAD symptoms. CONCLUSIONS: This study illustrates the downsides of having deep ties to social neighborhoods when they occur in the absence of broader access to ties with the community of one's sexual identity. Interventions that help MSM cross the spatial boundaries of their social neighborhoods and promote integration of MSM into the broader gay community may contribute to the reduction of elevated rates of depression and anxiety in this population.

Quantifying Distance Overestimation From Global Positioning System in Urban Spaces.

OBJECTIVES: To investigate accuracy of distance measures computed from Global Positioning System (GPS) points in New York City. METHODS: We performed structured walks along urban streets carrying Globalsat DG-100 GPS Data Logger devices in highest and lowest quartiles of building height and tree canopy cover. We used ArcGIS version 10.1 to select walks and compute the straight-line distance (Geographic Information System-measured) and sum of distances between consecutive GPS waypoints (GPS-measured) for each walk. RESULTS: GPS distance overestimates were associated with building height (median overestimate = 97% for high vs 14% for low building height) and to a lesser extent tree canopy (43% for high vs 28% for low tree canopy). CONCLUSIONS: Algorithms using distances between successive GPS points to infer speed or travel mode may misclassify trips differentially by context. Researchers studying urban spaces may prefer alternative mode identification techniques.

Use of Google Street View to Assess Environmental Contributions to Pedestrian Injury.

OBJECTIVES: To demonstrate an information technology-based approach to assess characteristics of streets and intersections associated with injuries that is less costly and time-consuming than location-based studies of pedestrian injury. METHODS: We used imagery captured by Google Street View from 2007 to 2011 to assess 9 characteristics of 532 intersections within New York City. We controlled for estimated pedestrian count and estimated the relation between intersections' characteristics and frequency of injurious collisions. RESULTS: The count of pedestrian injuries at intersections was associated with the presence of marked crosswalks (80% increase; 95% confidence interval [CI] = 2%, 218%), pedestrian signals (156% increase; 95% CI = 69%, 259%), nearby billboards (42% increase; 95% CI = 7%, 90%), and bus stops (120% increase; 95% CI = 51%, 220%). Injury incidence per pedestrian was lower at intersections with higher estimated pedestrian volumes. CONCLUSIONS: Consistent with in-person study observations, the information-technology approach found traffic islands, visual advertising, bus stops, and crosswalk infrastructures to be associated with elevated counts of pedestrian injury in New York City. Virtual site visits for pedestrian injury control studies are a viable and informative methodology.

Altered Morphology and Immunohistochemical Characteristics in Metastatic Malignant Melanoma After Therapy With Vemurafenib.

Metastatic melanoma is traditionally diagnosed using classic morphologic features in addition to immunohistochemical studies. The authors report a case of metastatic malignant melanoma where both morphology and immunohistochemistry were altered after treatment. This 51-year-old patient presented with metastatic melanoma to the brain and axilla. Initially, both metastases showed classic morphology and diffuse staining with the pan-melanoma antibody cocktail. This cocktail is a combination of 3 antibodies commonly used to diagnose melanocytic neoplasms: Melan-A (MART-1), tyrosinase, and HMB-45. In combination, the cocktail is highly sensitive for detecting melanocytic neoplasms and is commonly used to diagnose metastatic melanoma. Her tumor was positive for the BRAF 1799T>A (V600E) mutation, and she was treated with BRAF inhibitor therapy (vemurafenib). However, the axillary tumor recurred after treatment with vemurafenib. The recurrent tumor showed a markedly different morphology and complete loss of staining with the pan-melanoma antibody cocktail. This loss of staining accompanied by the change in morphology was an observation not previously documented after therapy with vemurafenib. This case demonstrates a potential pitfall in the diagnosis of metastatic or recurrent malignant melanoma.

Mosaic tetrasomy 13q and phylloid hypomelanosis: a case report and review of the literature.

A 6-year-old girl presented for evaluation of skin discoloration. Examination revealed oval and oblong hypopigmented macules on her trunk and extremities. Cytogenetic studies and immunohistochemistry of biopsies from normally pigmented and hypopigmented skin revealed mosaicism for partial tetrasomy for 13q with low melanocyte levels in lesional skin. The patient was diagnosed with phylloid hypomelanosis (PH), a distinct clinical entity linked to abnormalities in chromosome 13. This article reviews the literature regarding PH and supports the notion that mosaicism of the melanocyte region of chromosome 13q is responsible for PH.

Sibling concordance for clinical features of Duchenne and Becker muscular dystrophies.

INTRODUCTION: The correlation of markers of disease severity among brothers with Duchenne or Becker muscular dystrophy has implications for clinical guidance and clinical trials. METHODS: Sibling pairs with Duchenne or Becker muscular dystrophy (n = 60) were compared for ages when they reached clinical milestones of disease progression, including ceased ambulation, scoliosis of ≥ 20°, and development of cardiomyopathy. RESULTS: The median age at which younger brothers reached each milestone, compared with their older brothers ranged from 25 months younger for development of cardiomyopathy to 2 months older for ceased ambulation. For each additional month of ambulation by the older brother, the hazard of ceased ambulation by the younger brother decreased by 4%. CONCLUSIONS: The ages when siblings reach clinical milestones of disease vary widely between siblings. However, the time to ceased ambulation for older brothers predicts the time to ceased ambulation for their younger brothers.

A prospective study of socioeconomic status, prostate cancer screening and incidence among men at high risk for prostate cancer.

PURPOSE: Higher socioeconomic status (SES) men are at higher risk of prostate cancer (PCa) diagnosis, an association commonly interpreted as a function of higher rates of prostate screening among higher SES men. However, the extent to which screening explains this association has not been well quantified. METHODS: Within a Detroit area cohort of 6,692 men followed up after a benign prostate procedure, a case-control study was conducted of 494 PCa cases and controls matched on age, race, duration of follow-up, and date of initial benign finding; 2000 Census data were used in a principal component analysis to derive a single factor, labeled the neighborhood SES index (NSESI), representing zip code-level SES. RESULTS: Among cases, higher SES was associated with a younger age at initial biopsy: -1.48 years (95 % CI, -2.32, -0.64) per unit NSESI. After adjustment for confounders and duration of follow-up, higher SES was associated with more PSA tests and DRE during follow-up; 9 % (95 % CI, 2, 16) and 8 % (95 % CI, 1, 15) more respectively, per unit NSESI. Higher SES was associated with a higher risk of PCa diagnosis during follow-up, multivariable adjusted OR = 1.26 per unit increase in NSESI (95 % CI, 1.04, 1.49). Further adjustment for screening frequency somewhat reduced the association between SES and PCa risk (OR = 1.19 per unit NSESI, 95 % CI, 0.98, 1.44). CONCLUSIONS: Differences in screening frequency only partially explained the association between higher zip code SES and PCa risk; other health care-related factors should also be considered as explanatory factors.

Oral corticosteroids and onset of cardiomyopathy in Duchenne muscular dystrophy.

OBJECTIVE: To estimate the age when cardiomyopathy develops in boys with Duchenne muscular dystrophy (DMD) and to analyze the effect of corticosteroid treatment on the age of cardiomyopathy onset. STUDY DESIGN: We identified a population-based sample of 462 boys with DMD, born between 1982 and 2005, in 5 surveillance sites in the US. Echocardiographic and corticosteroid treatment data were collected. Cardiomyopathy was defined by a reduced fractional shortening (<28%) or ejection fraction (<55%). The age of cardiomyopathy onset was determined. Survival analysis was performed to determine the effects of corticosteroid treatment on cardiomyopathy onset. RESULTS: The mean (SD) age of cardiomyopathy onset was 14.3 (4.2) years for the entire population and 15.2 (3.4) years in corticosteroid-treated vs 13.1 (4.8) in non-treated boys. Survival analysis described a significant delay of cardiomyopathy onset for boys treated with corticosteroids (P < .02). By 14.3 years of age, 63% of non-treated boys had developed cardiomyopathy vs only 36% of those treated. Among boys treated with corticosteroids, there is a significant positive effect of duration of corticosteroid treatment on cardiomyopathy onset (P < .0001). For every year of corticosteroid treatment, the probability of developing cardiomyopathy decreased by 4%. CONCLUSIONS: Oral corticosteroid treatment was associated with delayed cardiomyopathy onset. The duration of corticosteroid treatment also correlated positively with delayed cardiomyopathy onset. Our analysis suggests that a boy with DMD treated for 5 years with corticosteroids might experience a 20% decrease in the likelihood of developing cardiomyopathy compared with untreated boys.

Poorly differentiated carcinoma arising in the setting of erythema ab igne.

Erythema ab igne (EAI) is a reticulated, erythematous, or hyperpigmented dermatosis that is caused by chronic exposure to infrared radiation. Chronic lesions of EAI have significant potential for malignant transformation. We report a case of poorly differentiated carcinoma arising within a patch of long-standing EAI on the lower extremity of a 92-year-old female. This case highlights the importance of recognizing EAI early and counseling patients to avoid further exposure to the offending infrared source to reduce the risk of malignant transformation. EAI has been associated with several different types of cutaneous neoplasms including the Merkel cell carcinoma, squamous cell carcinoma, and cutaneous marginal zone lymphoma.