Theta and gamma rhythmic coding through two spike output modes in the hippocampus during spatial navigation.

Hippocampal CA1 neurons generate single spikes and stereotyped bursts of spikes. However, it is unclear how individual neurons dynamically switch between these output modes and whether these two spiking outputs relay distinct information. We performed extracellular recordings in spatially navigating rats and cellular voltage imaging and optogenetics in awake mice. We found that spike bursts are preferentially linked to cellular and network theta rhythms (3-12 Hz) and encode an animal's position via theta phase precession, particularly as animals are entering a place field. In contrast, single spikes exhibit additional coupling to gamma rhythms (30-100 Hz), particularly as animals leave a place field. Biophysical modeling suggests that intracellular properties alone are sufficient to explain the observed input frequency-dependent spike coding. Thus, hippocampal neurons regulate the generation of bursts and single spikes according to frequency-specific network and intracellular dynamics, suggesting that these spiking modes perform distinct computations to support spatial behavior.

The Cornell COVID-19 Testing Laboratory: A Model to High-Capacity Testing Hubs for Infectious Disease Emergency Response and Preparedness.

The unprecedented COVID-19 pandemic posed major challenges to local, regional, and global economies and health systems, and fast clinical diagnostic workflows were urgently needed to contain the spread of SARS-CoV-2. Here, we describe the platform and workflow established at the Cornell COVID-19 Testing Laboratory (CCTL) for the high-throughput testing of clinical samples from the university and the surrounding community. This workflow enabled efficient and rapid detection and the successful control of SARS-CoV-2 infection on campus and its surrounding communities. Our cost-effective and fully automated workflow enabled the testing of over 8000 pooled samples per day and provided results for over 2 million samples. The automation of time- and effort-intensive sample processing steps such as accessioning and pooling increased laboratory efficiency. Customized software applications were developed to track and store samples, deconvolute positive pools, track and report results, and for workflow integration from sample receipt to result reporting. Additionally, quality control dashboards and turnaround-time tracking applications were built to monitor assay and laboratory performance. As infectious disease outbreaks pose a constant threat to both human and animal health, the highly effective workflow implemented at CCTL could be modeled to establish regional high-capacity testing hubs for infectious disease preparedness and emergency response.

Pulmonological issues.

Pediatric leukodystrophies are rare neurodegenerative diseases involving multiple systems. Each form has unique neurologic features but are characterized by encephalopathy with accompanying impairments evidenced in reflexes, muscle tone and movement control. Weakness of expiratory, inspiratory, and upper airway muscles may lead to impaired airway secretion clearance resulting in recurrent respiratory infections, dysphagia, sleep-disordered breathing, restrictive lung disease, and ultimately chronic respiratory insufficiency.

Locations of Adolescent Physical Activity in an Urban Environment and Their Associations with Air Pollution and Lung Function.

Rationale: Physical activity while being exposed to high concentrations of air pollution may lead to greater inhalation of pollutant particles and gases. Thus, owing to features of the built city environment, specific locations where physical activity take place may put individuals at increased risk for harmful inhaled exposures leading to decrements in lung function.Objectives: The objectives were to determine locations throughout an urban landscape where children engage in moderate to vigorous activity (MVA). We hypothesized that outdoor activity would be associated with increased exposure to air pollution and reduced lung function.Methods: Children aged 9-14 years living in New York City (NYC) (n = 151) wore global positioning system devices and wrist accelerometers for two 24-hour periods. Time-stamped global positioning system points and accelerometer data were aggregated and mapped using ArcGIS to determine locations where children engaged in MVA. Location-specific particulate matter <2.5 microns and nitrogen dioxide (NO2) was determined based on land use regression models of street-level pollution. Temporal air pollution exposure was determined based on daily concentrations collected at one central site in NYC. Forced expiratory volume in 1 second (FEV1), forced vital capacity (FVC), and forced expiratory flow, midexpiratory phase (FEF25-75) were collected following each 24-hour period. Data were analyzed using multivariable linear regression models to examine associations between MVA time and both lung function and air pollution in separate models. Additionally, a multiplicative interaction term (MVA time × season) was included to test whether the association between MVA time and lung function outcomes varied by warmer versus colder months.Results: On average, children spent less MVA time outdoors (38.2 ± 39.6 min/d) compared with indoors (71.9 ± 74.7 min/d, P < 0.01), regardless of season. The majority of outdoor MVA occurred along sidewalks and roadbeds (30.2 ± 33.3 min/d, 76.9% of outdoor) where annual average concentrations of NO2 were relatively high. Interquartile range (IQR) increase in outdoor MVA time (44 min) was associated with higher levels of annual average NO2 (P < 0.01) but not particulate matter <2.5 microns. In warmer months, for IQR increase in outdoor MVA time, children had 1.41% lower FEV1/FVC (95% confidence interval [95% CI], -2.46 to -0.36) and 4.40% lower percent predicted FEF25-75 (95% CI, -8.02 to -0.78). These results persisted even after adjustment for location-specific annual average concentrations of NO2. No association was observed between MVA time and lung function in colder months (P > 0.05), and a formal test for interaction (MVA time × season) was significant (P value for interaction = 0.01 and 0.03 for FEV1/FVC and FEF25-75, respectively).Conclusions: Children in NYC spent less time active outdoors compared with indoors. Outdoor activity was greatest near traffic sources and associated with higher annual average concentrations of NO2. In warmer months, outdoor activity was associated with lower lung function, but this association did not appear to be mediated by higher exposure to outdoor pollution during exercise.

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.

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.

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.

RNA sequencing data from neutrophils of patients with cystic fibrosis reveals potential for developing biomarkers for pulmonary exacerbations.

BACKGROUND: There is no effective way to predict cystic fibrosis (CF) pulmonary exacerbations (CFPE) before they become symptomatic or to assess satisfactory treatment responses. METHODS: RNA sequencing of peripheral blood neutrophils from CF patients before and after therapy for CFPE was used to create transcriptome profiles. Transcripts with an average transcripts per million (TPM) level > 1.0 and a false discovery rate (FDR) < 0.05 were used in a cosine K-nearest neighbor (KNN) model. Real time PCR was used to corroborate RNA sequencing expression differences in both neutrophils and whole blood samples from an independent cohort of CF patients. Furthermore, sandwich ELISA was conducted to assess plasma levels of MRP8/14 complexes in CF patients before and after therapy. RESULTS: We found differential expression of 136 transcripts and 83 isoforms when we compared neutrophils from CF patients before and after therapy (>1.5 fold change, FDR-adjusted P < 0.05). The model was able to successfully separate CF flare samples from those taken from the same patients in convalescence with an accuracy of 0.75 in both the training and testing cohorts. Six differently expressed genes were confirmed by real time PCR using both isolated neutrophils and whole blood from an independent cohort of CF patients before and after therapy, even though levels of myeloid related protein MRP8/14 dimers in plasma of CF patients were essentially unchanged by therapy. CONCLUSIONS: Our findings demonstrate the potential of machine learning approaches for classifying disease states and thus developing sensitive biomarkers that can be used to monitor pulmonary disease activity in CF.

Cardiopulmonary phenotypic discordance is common in Duchenne muscular dystrophy.

OBJECTIVE: To determine the prevalence of discordant cardiopulmonary function among patients with Duchenne muscular dystrophy (DMD) in our clinic. METHODS: Retrospective chart review from 1999 to 2017. INCLUSION CRITERIA: DMD patients age ≥ 18 years, alive, with discordant cardiopulmonary function. No patients received glucocorticoid therapy. Discordant cardiopulmonary function was defined as either: good heart function (EF ≥ 40%) and bad lung function (FVC < 1 L) (Group A); or, bad heart function (EF < 40%) and good lung function (FVC ≥ 1 L) (Group B). RESULTS: Among 74 eligible patients, 25 patients (34%) had discordant cardiopulmonary function (21 patients in Group A and 4 patients in Group B). Three dystrophin mutations were shared by >2 patients (nine patients with deletion of exon 44; three patients with deletion of exon 51; three patients with duplication of exon 2). Among the 15 patients with a shared genotype, eight patients (53%) had discordant cardiopulmonary function (five patients in group A, three patients in group B). Twenty-six patients had a deletion involving or distal to exon 45. Ten of these patients (38%) had discordant cardiopulmonary function (eight patients in Group A, two patients in Group B). CONCLUSION: In our cohort of DMD patients, discordant cardiopulmonary function was common (present in one-third of our patients), and the dystrophin genotype did not reliably predict a patient's cardiopulmonary phenotype. If confirmed by larger, multi-center studies, our findings have significant implications for predicting patient prognosis, evaluating DMD therapies, and designing new DMD therapies.

Respiratory Management of the Patient With Duchenne Muscular Dystrophy.

In 2010, Care Considerations for Duchenne Muscular Dystrophy, sponsored by the Centers for Disease Control and Prevention, was published in Lancet Neurology, and in 2018, these guidelines were updated. Since the publication of the first set of guidelines, survival of individuals with Duchenne muscular dystrophy has increased. With contemporary medical management, survival often extends into the fourth decade of life and beyond. Effective transition of respiratory care from pediatric to adult medicine is vital to optimize patient safety, prognosis, and quality of life. With genetic and other emerging drug therapies in development, standardization of care is necessary to accurately assess treatment effects in clinical trials. This revision of respiratory recommendations preserves a fundamental strength of the original guidelines: namely, reliance on a limited number of respiratory tests to guide patient assessment and management. A progressive therapeutic strategy is presented that includes lung volume recruitment, assisted coughing, and assisted ventilation (initially nocturnally, with the subsequent addition of daytime ventilation for progressive respiratory failure). This revision also stresses the need for serial monitoring of respiratory muscle strength to characterize an individual's respiratory phenotype of severity as well as provide baseline assessments for clinical trials. Clinical controversies and emerging areas are included.

Health Care Transition Experiences of Males with Childhood-onset Duchenne and Becker Muscular Dystrophy: Findings from the Muscular Dystrophy Surveillance Tracking and Research Network (MD STARnet) Health Care Transitions and Other Life Experiences Survey.

Introduction: As the proportion of males with Duchenne muscular dystrophy (DMD) surviving into adulthood increases, more information is needed regarding their health care transition planning, an essential process for adolescents and young adults with DMD. The objective of this study was to describe the health care transition experiences of a population of males living with Duchenne or Becker muscular dystrophy (DBMD). Methods: The eligible participants, identified through the Muscular Dystrophy Surveillance Tracking and Research Network (MD STARnet) surveillance project, were 16-31 years old and lived in Arizona, Colorado, Georgia, Iowa, or western New York (n=258). The MD STARnet Health Care Transitions and Other Life Experiences Survey was conducted in 2013 and administered online or in a telephone interview. Sixty-five males (25%) completed the survey. Among non-ambulatory males, response differences were compared by age group. Statistical comparisons were conducted using Fisher's exact test, or when appropriate, the Chisquare test. Results: Twenty-one percent of non-ambulatory males aged 16-18 years, 28% of non-ambulatory males aged 19-23 years, 25% of non-ambulatory males aged 24-30 years, and 18 ambulatory males had a written transition plan. Nineteen percent of non-ambulatory males aged 24-30 years had delayed or gone without needed health care in the past 12 months. Among non-ambulatory males aged 24-30 years, 75% had cardiology providers and 69% had pulmonology providers involved in their care in the past 12 months. Twentyeight percent of non-ambulatory males aged 19-23 years and 25% of non-ambulatory males aged 24-30 years reported that they did not receive health care or other services at least once because they were unable to leave their home. Non-ambulatory males aged 16-18 years (29%) were less likely to have ever discussed how to obtain or keep health insurance as they get older compared to non-ambulatory males aged 24-30 years (69%) (p <0.01). Discussion: This study identified potential barriers to the successful health care transition of males with DBMD. The results of this study may indicate a lack of targeted informational resources and education focused on supporting the transition of young men with DBMD as they age from adolescence into adulthood within the healthcare system. Future studies could determine the reasons for the potential barriers to health care and identify the optimal transition programs for males with DBMD. There are a few online resources on transition available to adolescents and young adults with special health care needs.

Neighborhood food environment, dietary fatty acid biomarkers, and cardiac arrest risk.

We explored links between food environments, dietary intake biomarkers, and sudden cardiac arrest in a population-based longitudinal study using cases and controls accruing between 1990 and 2010 in King County, WA. Surprisingly, presence of more unhealthy food sources near home was associated with a lower 18:1 trans-fatty acid concentration (-0.05% per standard deviation higher count of unhealthy food sources, 95% Confidence Interval [CI]: 0.01, 0.09). However, presence of more unhealthy food sources was associated with higher odds of cardiac arrest (Odds Ratio [OR]: 2.29, 95% CI: 1.19, 4.41 per standard deviation in unhealthy food outlets). While unhealthy food outlets were associated with higher cardiac arrest risk, circulating 18:1 trans fats did not explain the association.

Muscular Dystrophies.

Muscular dystrophies represent a complex, varied, and important subset of neuromuscular disorders likely to require the care of a pulmonologist. The spectrum of conditions encapsulated by this subset ranges from severe and fatal congenital muscular dystrophies with onset in infancy to mild forms of limb and girdle weakness with onset in adulthood and minimal respiratory compromise. The list and classification of muscular dystrophies are undergoing near-constant revision, based largely on new insights from genetics and molecular medicine. The authors present an overview of the muscular dystrophies, including their basic features, common clinical phenotypes, and important facets of management.

Airway clearance techniques in neuromuscular disorders: A state of the art review.

This is a unique state of the art review written by a group of 21 international recognized experts in the field that gathered during a meeting organized by the European Neuromuscular Centre (ENMC) in Naarden, March 2017. It systematically reports the entire evidence base for airway clearance techniques (ACTs) in both adults and children with neuromuscular disorders (NMD). We not only report randomised controlled trials, which in other systematic reviews conclude that there is a lack of evidence base to give an opinion, but also include case series and retrospective reviews of practice. For this review, we have classified ACTs as either proximal (cough augmentation) or peripheral (secretion mobilization). The review presents descriptions; standard definitions; the supporting evidence for and limitations of proximal and peripheral ACTs that are used in patients with NMD; as well as providing recommendations for objective measurements of efficacy, specifically for proximal ACTs. This state of the art review also highlights how ACTs may be adapted or modified for specific contexts (e.g. in people with bulbar insufficiency; children and infants) and recommends when and how each technique should be applied.

Diagnosis and management of Duchenne muscular dystrophy, part 2: respiratory, cardiac, bone health, and orthopaedic management.

A coordinated, multidisciplinary approach to care is essential for optimum management of the primary manifestations and secondary complications of Duchenne muscular dystrophy (DMD). Contemporary care has been shaped by the availability of more sensitive diagnostic techniques and the earlier use of therapeutic interventions, which have the potential to improve patients' duration and quality of life. In part 2 of this update of the DMD care considerations, we present the latest recommendations for respiratory, cardiac, bone health and osteoporosis, and orthopaedic and surgical management for boys and men with DMD. Additionally, we provide guidance on cardiac management for female carriers of a disease-causing mutation. The new care considerations acknowledge the effects of long-term glucocorticoid use on the natural history of DMD, and the need for care guidance across the lifespan as patients live longer. The management of DMD looks set to change substantially as new genetic and molecular therapies become available.

Levels and determinants of tree pollen in New York City.

Exposure to allergenic tree pollen is a risk factor for multiple allergic disease outcomes. Little is known about how tree pollen levels vary within cities and whether such variation affects the development or exacerbation of allergic disease. Accordingly, we collected integrated pollen samples at uniform height at 45 sites across New York City during the 2013 pollen season. We used these monitoring results in combination with adjacent land use data to develop a land use regression model for tree pollen. We evaluated four types of land use variables for inclusion in the model: tree canopy, distributed building height (a measure of building volume density), elevation, and distance to water. When included alone in the model, percent tree canopy cover within a 0.5 km radial buffer explained 39% of the variance in tree pollen (1.9% increase in tree pollen per one-percentage point increase in tree canopy cover, P<0.0001). The inclusion of additional variables did not improve model fit. We conclude that intra-urban variation in tree canopy is an important driver of tree pollen exposure. Land use regression models can be used to incorporate spatial variation in tree pollen exposure in studies of allergic disease outcomes.

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.

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.