Defining Spatial Epidemiology: A Systematic Review and Re-orientation.

BACKGROUND: Spatial epidemiology has emerged as an important subfield of epidemiology over the past quarter century. We trace the origins of spatial epidemiology and note that its emergence coincided with technological developments in spatial statistics and geography. We hypothesize that spatial epidemiology makes important contributions to descriptive epidemiology and analytic risk-factor studies but is not yet aligned with epidemiology's current focus on causal inference and intervention. METHODS: We conducted a systematic review of studies indexed in PubMed that used the term "spatial epidemiolog*" in the title, abstract, or keywords. Excluded articles were not written in English, examined disease in animals, or reported biologic pathogen distribution only. We coded the included papers into five categories (review, demonstration of method, descriptive, analytic, and intervention) and recorded the unit of analysis (i.e., individual vs. ecological). We additionally examined articles coded as analytic ecologic studies using scales for lexical content. RESULTS: A total of 482 articles met the inclusion criteria, including 76 reviews, 117 demonstrations of methods, 122 descriptive studies, 167 analytic studies, and 0 intervention studies. Demonstration studies were most common from 2006 to 2014, and analytic studies were most common after 2015. Among the analytic ecologic studies, those published in later years used more terms relevant to spatial statistics (incidence rate ratio =1.3; 95% confidence interval [CI] = 1.1, 1.5) and causal inference (incidence rate ratio =1.1; 95% CI = 1.1, 1.2). CONCLUSIONS: Spatial epidemiology is an important and growing subfield of epidemiology. We suggest a re-orientation to help align its practice with the goals of contemporary epidemiology.

Temperature and firearm violence in four US cities: testing competing hypotheses.

INTRODUCTION: Firearm violence is a major public health issue in the USA. There is growing evidence that firearm violence is associated with higher ambient temperatures. The aim of this study was to test competing hypotheses that could explain associations between temperature and firearm violence: temperature-aggression theory and routine activities theory. METHODS: We examined associations between elevated daily temperatures and shooting incidents in four US cities: Chicago, Illinois; Cincinnati, Ohio; New York, New York and Philadelphia, Pennsylvania. Temperature was operationalised using two different measures: daily maximum temperature and deviations of the daily maximum temperature from 30-year averages. Generalised linear autoregressive moving average models related temperature to shooting incidence while controlling for seasonal effects. RESULTS: As maximum daily temperature deviates from the expected, there was an association with increased shooting incidents in all four cities (eg, New York: b=0.014, 95% CI=0.011 to 0.017). An interaction term created by multiplying daily maximum temperature by the daily difference of maximum temperature from a 30-year average was also found to have a positive association in all four cities (eg, New York: b=0.020, 95% CI=0.016 to 0.025). DISCUSSION: These findings accord with previous studies demonstrating a positive relationship between temperature and firearm violence and further support temperature-aggression theory as the primary causal mechanism.

Physical environmental roadway interventions and injury and death for vulnerable road users: a natural experiment in New York City.

INTRODUCTION: This study examined the effectiveness of three physical environmental roadway interventions (enhanced crossings, speed humps, and turn traffic calming) in preventing crashes involving pedestrian and cyclist injury and mortality in New York City. METHODS: We examined crashes that occurred within a 100-foot radius of intervention and control sites from 2015 to 2019. We used a staggered difference-in-difference design to estimate the association between each intervention type and pedestrian and cyclist crash outcomes. RESULTS: Estimates for enhanced crossings and speed humps included the possibility of no association with crashes, but estimates for turn traffic calming interventions showed reduced odds of crashes involving pedestrian injury by 16% (OR 0.84, 95% CI 0.74 to 0.95) and crashes involving pedestrian fatality by 80% (OR 0.20, 95% CI 0.08 to 0.47). When stratifying by street segment length as a proxy for areas with high speeding risk, turn traffic calming treatments appeared to be most effective at intersections connected to long street segments. DISCUSSION: Turn traffic calming may substantially reduce crash risks for pedestrians. Municipalities can prioritise this physical environmental intervention, especially at turns near long street segments, as a low-cost intervention with substantial public health impact.

Gene Expression Patterns Associated with Survival in Glioblastoma.

The aim of this study was to investigate gene expression alterations associated with overall survival (OS) in glioblastoma (GBM). Using the Nanostring nCounter platform, we identified four genes (COL1A2, IGFBP3, NGFR, and WIF1) that achieved statistical significance when comparing GBM with non-neoplastic brain tissue. The four genes were included in a multivariate Cox Proportional Hazard model, along with age, extent of resection, and O6-methylguanine-DNA methyltransferase (MGMT) promotor methylation, to create a unique glioblastoma prognostic index (GPI). The GPI score inversely correlated with survival: patient with a high GPI had a median OS of 7.5 months (18-month OS = 9.7%) whereas patients with a low GPI had a median OS of 20.1 months (18-month OS = 54.5%; log rank p-value = 0.004). The GPI score was then validated in 188 GBM patients from The Cancer Genome Atlas (TCGA) from a national data base; similarly, patients with a high GPI had a median OS of 10.5 months (18-month OS = 12.4%) versus 16.9 months (18-month OS = 41.5%) for low GPI (log rank p-value = 0.0003). We conclude that this novel mRNA-based prognostic index could be useful in classifying GBM patients into risk groups and refine prognosis estimates to better inform treatment decisions or stratification into clinical trials.

Neighborhood Built Environment and Sleep Health: A Longitudinal Study in Low-Income and Predominantly African-American Neighborhoods.

In the present study, we examined the associations between physical characteristics of neighborhoods and sleep health outcomes and assessed the mediating role of physical activity in these associations. A longitudinal study (the Pittsburgh Hill/Homewood Research on Eating, Shopping, and Health (PHRESH) Zzz Study; n = 1,051) was conducted in 2 low-income, predominately African-American neighborhoods in Pittsburgh, Pennsylvania, with repeated measures of neighborhood characteristics and sleep health outcomes from 2013 to 2018. Built environment measures of walkability, urban design, and neighborhood disorder were captured from systematic field observations. Sleep health outcomes included insufficient sleep, sleep duration, wakefulness after sleep onset, and sleep efficiency measured from 7-day actigraphy data. G-computations based on structural nested mean models were used to examine the total effects of each built environment feature, and causal mediation analyses were used to evaluate direct and indirect effects operating through physical activity. Urban design features were associated with decreased wakefulness after sleep onset (risk difference (RD) = -1.26, 95% confidence interval (CI): -4.31, -0.33). Neighborhood disorder (RD = -0.46, 95% CI: -0.86, -0.07) and crime rate (RD = -0.54, 95% CI: -0.93, -0.08) were negatively associated with sleep efficiency. Neighborhood walkability was not associated with sleep outcomes. We did not find a strong and consistent mediating role of physical activity. Interventions to improve sleep should target modifiable factors, including urban design and neighborhood disorder.

Hyper-entanglement between pulse modes and frequency bins.

Hyper-entanglement between two or more photonic degrees of freedom (DOF) can enhance and enable new quantum protocols by allowing each DOF to perform the task it is optimally suited for. Here we demonstrate the generation of photon pairs hyper-entangled between pulse modes and frequency bins. The pulse modes are generated via parametric downconversion in a domain-engineered crystal and subsequently entangled to two frequency bins via a spectral mapping technique. The resulting hyper-entangled state is characterized and verified via measurement of its joint spectral intensity and non-classical two-photon interference patterns from which we infer its spectral phase. The protocol combines the robustness to loss, intrinsic high dimensionality and compatibility with standard fiber-optic networks of the energy-time DOF with the ability of hyper-entanglement to increase the capacity and efficiency of the quantum channel, already exploited in recent experimental applications in both quantum information and quantum computation.

Current State and Opportunities with Long-acting Injectables: Industry Perspectives from the Innovation and Quality Consortium "Long-Acting Injectables" Working Group.

Long-acting injectable (LAI) formulations can provide several advantages over the more traditional oral formulation as drug product opportunities. LAI formulations can achieve sustained drug release for extended periods of time, which results in less frequent dosing requirements leading to higher patient adherence and more optimal therapeutic outcomes. This review article will provide an industry perspective on the development and associated challenges of long-acting injectable formulations. The LAIs described herein include polymer-based formulations, oil-based formulations, and crystalline drug suspensions. The review discusses manufacturing processes, including quality controls, considerations of the Active Pharmaceutical Ingredient (API), biopharmaceutical properties and clinical requirements pertaining to LAI technology selection, and characterization of LAIs through in vitro, in vivo and in silico approaches. Lastly, the article includes a discussion around the current lack of suitable compendial and biorelevant in vitro models for the evaluation of LAIs and its subsequent impact on LAI product development and approval.

The Effect of Gun-Free School Zones on Crimes Committed with a Firearm in Saint Louis, Missouri.

There have been no peer-reviewed, quantitative research studies on the effectiveness of gun-free school zones. The objective of this study was to use a cross-sectional, multi-group controlled ecological study design in St. Louis, MO city that compared the counts of crimes committed with a firearm occurring in gun-free school zones compared to a contiguous area immediately surrounding the gun-free school zone (i.e., gun-allowing zones) in 2019. Gun-free school zones were measured and analyzed in two ways. In the primary analysis, boundaries of the tax parcels were used for each school as the beginning of the gun-free school zone. Results from this analysis, after adjustment for pair-matching and confounding, were null. In the secondary analysis, gun-free school zones were measured as beginning at the geographic centroid of the school's address. After adjusting for the pair-matching and confounding, this analysis showed 13.7% significantly fewer crimes committed with a firearm in gun-free school zones compared to gun-allowing zones. These results suggest that gun-free school zones are not being targeted for firearm crime in St. Louis, MO.

Suicide Following the COVID-19 Pandemic Outbreak: Variation Across Place, Over Time, and Across Sociodemographic Groups. A Systematic Integrative Review.

PURPOSE OF REVIEW: To systematically examine changes in suicide trends following the initial COVID-19 outbreak, focusing on geographical and temporal heterogeneity and on differences across sociodemographic subgroups. RECENT FINDINGS: Of 46 studies, 26 had low risk of bias. In general, suicides remained stable or decreased following the initial outbreak - however, suicide increases were detected during spring 2020 in Mexico, Nepal, India, Spain, and Hungary; and after summer 2020 in Japan. Trends were heterogeneous across sociodemographic groups (i.e., there were increases among racially minoritized individuals in the US, young adults and females across ages in Japan, older males in Brazil and Germany, and older adults across sex in China and Taiwan). Variations may be explained by differences in risk of COVID-19 contagion and death and in socioeconomic vulnerability. Monitoring geographical, temporal, and sociodemographic differences in suicide trends during the COVID-19 pandemic is critical to guide suicide prevention efforts.

Ride-Hailing and Road Traffic Crashes: A Critical Review.

Ride-hailing businesses, including Uber and Lyft, have reshaped road traffic since they first began operating in the United States approximately a decade ago. It follows that ride-hailing may also alter the incidence and distribution of road traffic crash injuries and deaths. The available evidence relating ride-hailing to crashes is critically reviewed in this article. We present a theoretical model that synthesizes the hypothesized mechanisms, and we identify common methodological challenges and suggest priorities for future research. Mixed results have been reported for the overall incidence of road traffic crash injuries and deaths, likely due to heterogeneous impacts on vehicular traffic flow (e.g., increasing the volume of vehicles); on vehicle-, person-, and event-level characteristics (e.g., reducing alcohol-impaired driver crashes); on road-user types (e.g., increasing pedestrian crashes); and on environmental conditions (e.g., reducing crashes most substantially where public transit access is poorest). The lack of a well-developed theory of human mobility and methodological challenges that are common to many ecological studies impede exploration of these sources of moderation. Innovative solutions are required to explicate ride-hailing's heterogeneous impacts, to guide policy that can take advantage of the public health benefits of ride-hailing, and to ensure that research keeps pace with technological advances that continue to reshape road traffic use.

Gun shows and universal background check laws across state lines.

States with more gun laws have fewer gun assaults, and associations are strongest for background check laws. However, sales between private buyers and sellers (i.e., gun shows) are exempt from some background check requirements according to federal and most state laws. The aim of this study was to determine whether gun shows are more likely to take place in counties that are near states with universal background check laws. This cross-sectional study used gun show data from a 2018 public online listing aggregated within 3107 counties in the contiguous 48 states. The main independent variable was the presence of a universal background check law in neighboring states. We controlled for potential drivers of demand for gun shows, including the total number of gun laws within-state and in neighboring states, local and in-flowing population size, and proportion of the local and in-flowing population who were gun owners. Bayesian conditional autoregressive Poisson models estimated associations between neighboring-state universal background check law and the presence of a gun show in each county while accounting for spatial dependencies and nesting of counties within states. Of the 1869 identified gun shows, nine of the states in which they occurred had a universal background check law. The presence of excess gun shows in counties near states with universal background check laws is consistent with the hypothesis that gun shows service demand from people seeking to circumvent prohibitions against gun purchases.

Historical redlining and the epidemiology of present-day firearm violence in the United States: A multi-city analysis.

Firearm violence is a major cause of morbidity, mortality, and racial health disparities in the United States. Previous studies have identified associations between historically racist housing discrimination (i.e., redlining practices) and firearm violence; however, these studies generally have been limited to a single city and have yet to provide sufficient evidence through which to determine the extent and dynamics of the impact of this relationship across the country. The aim of our study was (1) to estimate the association of historical redlining on both violent and firearm death across the country in nested models; and (2) to examine spatial non-stationarity to determine whether the impact of historical redlining on violent and firearm death was the same across the U.S. We used multilevel Bayesian conditional autoregressive Poisson models to determine the relationship between redlining as illustrated through Home Owners' Loan Corporation maps and 2019 violent and firearm deaths at the ZIP code-level nested within 21 cities across the U.S. We found that at the ZIP code level, there was a dose-responsive relationship between HOLC grading and the incidence of present-day firearm deaths. In general, redlined ZIP codes had higher relative incidence of firearm deaths. Associations were not stable across cities. For example, associations were relatively stronger in Baltimore, MD and weaker in Los Angeles, CA. This research reinforces the findings of previous studies examining the impact of redlining on firearm death across the extent of the entire country in 21 cities and claim that HOLC grades are associated with present-day violence.

The changing epidemiology of interpersonal firearm violence during the COVID-19 pandemic in Philadelphia, PA.

Recent increases in firearm violence in U.S. cities are well-documented, however dynamic changes in the people, places and intensity of this public health threat during the COVID-19 pandemic are relatively unexplored. This descriptive epidemiologic study spanning from January 1, 2015 - March 31, 2021 utilizes the Philadelphia Police Department's registry of shooting victims, a database which includes all individuals shot and/or killed due to interpersonal firearm violence in the city of Philadelphia. We compared victim and event characteristics prior to the pandemic with those following implementation of pandemic containment measures. In this study, containment began on March 16, 2020, when non-essential businesses were ordered to close in Philadelphia. There were 331 (SE = 13.9) individuals shot/quarter pre-containment vs. 545 (SE = 66.4) individuals shot/quarter post-containment (p = 0.031). Post-containment, the proportion of women shot increased by 39% (95% CI: 1.21, 1.59), and the proportion of children shot increased by 17% (95% CI: 1.00, 1.35). Black women and children were more likely to be shot post-containment (RR 1.11, 95% CI: 1.02, 1.20 and RR 1.08, 95% CI: 1.03, 1.14, respectively). The proportion of mass shootings (≥4 individuals shot within 100 m within 1 h) increased by 53% post-containment (95% CI: 1.25, 1.88). Geographic analysis revealed relative increases in all shootings and mass shootings in specific city locations post-containment. The observed changes in firearm injury epidemiology following COVID-19 containment in Philadelphia demonstrate an intensification in firearm violence, which is increasingly impacting people who are likely made more vulnerable by existing social and structural disadvantage. These findings support existing knowledge about structural causes of interpersonal firearm violence and suggest structural solutions are required to address this public health threat.

Isocaloric low protein diet in a mouse model for vanishing white matter does not impact ISR deregulation in brain, but reveals ISR deregulation in liver.

Objective: Vanishing white matter (VWM) is a genetic brain white matter disorder caused by mutations in eIF2B. eIF2B is central in the integrated stress response (ISR), during which its activity is inhibited by various cellular stresses. VWM is a chronic progressive disease with episodes of rapid neurological deterioration provoked by stresses. VWM patients and VWM mouse models show ISR deregulation in brain, correlating with chronic disease development. ISR inhibition ameliorates the chronic disease in VWM mice. The subacute deteriorations have not been modeled yet. We hypothesized that ISR activation could worsen disease progression in mice and model the episodic neurological deterioration.Method: We chose to activate the ISR by subjecting wild-type (wt) and VWM mice to an isocaloric low protein diet. This model would allow us to investigate the contribution of ISR activation in subacute decline in VWM.Results: We found that the low protein diet did not significantly affect amino acid levels nor ISR levels in wt and VWM mouse brain. Our study serendipitously led to the discovery of increased levels of glycine, asparagine and Fgf21 mRNA in VWM mouse brain irrespective of the dietary protein content. Strikingly, the ISR was not activated by the low protein diet in the liver of VWM in contrast to wt mice, due to a modest ISR deregulation in this organ.Discussion: A model for subacute neurological deterioration in VWM was not established. Possibly, ISR deregulation in VWM results in reduced ISR responsiveness.

FGF21 prevents low-protein diet-induced renal inflammation in aged mice.

Low-protein (LP) diets extend lifespan through a comprehensive improvement in metabolic health across multiple tissues and organs. Many of these metabolic responses to protein restriction are secondary to transcriptional activation and release of FGF21 from the liver. However, the effects of an LP diet on the kidney in the context of aging has not been examined. Therefore, the goal of the current study was to investigate the impact of chronic consumption of an LP diet on the kidney in aging mice lacking FGF21. Wild-type (WT; C57BL/6J) and FGF21 knockout (KO) mice were fed a normal protein diet (20% casein) or an LP (5% casein) diet ad libitum from 3 to 22 mo of age. The LP diet led to a decrease in kidney weight and urinary albumin-to-creatinine ratio in both WT and FGF21 KO mice. Although the LP diet produced only mild fibrosis and infiltration of leukocytes in WT kidneys, the effects were significantly exacerbated by the absence of FGF21. Accordingly, transcriptomic analysis showed that inflammation-related pathways were significantly enriched and upregulated in response to LP diet in FGF21 KO mice but not WT mice. Collectively, these data demonstrate that the LP diet negatively affected the kidney during aging, but in the absence of FGF21, the LP diet-induced renal damage and inflammation were significantly worse, indicating a protective role of FGF21 in the kidney.NEW & NOTEWORTHY Long-term protein restriction is not advantageous for an otherwise healthy, aging kidney, as it facilitates the development of renal tubular injury and inflammatory cell infiltration. We provide evidence using FGF21 knockout animals that FGF21 is essential to counteract the renal injury and inflammation during aging on a low-protein diet.

Learning of food preferences: mechanisms and implications for obesity & metabolic diseases.

Omnivores, including rodents and humans, compose their diets from a wide variety of potential foods. Beyond the guidance of a few basic orosensory biases such as attraction to sweet and avoidance of bitter, they have limited innate dietary knowledge and must learn to prefer foods based on their flavors and postoral effects. This review focuses on postoral nutrient sensing and signaling as an essential part of the reward system that shapes preferences for the associated flavors of foods. We discuss the extensive array of sensors in the gastrointestinal system and the vagal pathways conveying information about ingested nutrients to the brain. Earlier studies of vagal contributions were limited by nonselective methods that could not easily distinguish the contributions of subsets of vagal afferents. Recent advances in technique have generated substantial new details on sugar- and fat-responsive signaling pathways. We explain methods for conditioning flavor preferences and their use in evaluating gut-brain communication. The SGLT1 intestinal sugar sensor is important in sugar conditioning; the critical sensors for fat are less certain, though GPR40 and 120 fatty acid sensors have been implicated. Ongoing work points to particular vagal pathways to brain reward areas. An implication for obesity treatment is that bariatric surgery may alter vagal function.

Firearm Homicide Incidence, Within-state Firearm Laws, and Interstate Firearm Laws in US Counties.

BACKGROUND: Firearm homicides occur less frequently in US states with more firearm control laws. However, firearms are easily transported across state lines, and laws in one location may affect firearm violence in another. This study examined associations between within-state firearm laws and firearm homicide while accounting for interference from laws in other nearby states. METHODS: The units of analysis were 3,107 counties in the 48 contiguous US states, arrayed in 15 yearly panels for 2000 to 2014 (n = 46,605). The dependent measure was firearm homicides accessed from the Centers for Disease Control and Prevention (CDC) Compressed Mortality Data. The main independent measures were counts of firearm laws and the proportion of laws within categories (e.g., background checks, child access prevention laws). We calculated these measures for interstate laws using a geographic gravity function between county centroids. Bayesian conditional autoregressive Poisson models related within-state firearm laws and interstate firearm laws to firearm homicides. RESULTS: There were 172,726 firearm homicides in the included counties over the 15 years. States had between 3 and 100 firearm laws. Within-state firearm laws (incidence rate ratio [IRR] = 0.995, 95% confidence interval [CI] = 0.992, 0.997) and interstate firearm laws (IRR = 0.993, 95% CI = 0.990, 0.996) were independently associated with fewer firearm homicides, and associations for within-state laws were strongest where interstate laws were weakest. CONCLUSIONS: Additional firearm laws are associated with fewer firearm homicides both within the states where the laws are enacted and elsewhere in the United States. Interference from interstate firearm laws may bias associations for studies of within-state laws and firearm homicide.

Optimised domain-engineered crystals for pure telecom photon sources.

The ideal photon-pair source for building up multi-qubit states needs to produce indistinguishable photons with high efficiency. Indistinguishability is crucial for minimising errors in two-photon interference, central to building larger states, while high heralding rates will be needed to overcome unfavourable loss scaling. Domain engineering in parametric down-conversion sources negates the need for lossy spectral filtering allowing one to satisfy these conditions inherently within the source design. Here, we present a telecom-wavelength parametric down-conversion photon source that operates on the achievable limit of domain engineering. We generate photons from independent sources which achieve two-photon interference visibilities of up to 98.6 ± 1.1% without narrow-band filtering. As a consequence, we reach net heralding efficiencies of up to 67.5%, which corresponds to collection efficiencies exceeding 90%.

Physiologic Responses to Dietary Sulfur Amino Acid Restriction in Mice Are Influenced by Atf4 Status and Biological Sex.

BACKGROUND: Dietary sulfur amino acid restriction (SAAR) improves body composition and metabolic health across several model organisms in part through induction of the integrated stress response (ISR). OBJECTIVE: We investigate the hypothesis that activating transcription factor 4 (ATF4) acts as a converging point in the ISR during SAAR. METHODS: Using liver-specific or global gene ablation strategies, in both female and male mice, we address the role of ATF4 during dietary SAAR. RESULTS: We show that ATF4 is dispensable in the chronic induction of the hepatokine fibroblast growth factor 21 while being essential for the sustained production of endogenous hydrogen sulfide. We also affirm that biological sex, independent of ATF4 status, is a determinant of the response to dietary SAAR. CONCLUSIONS: Our results suggest that auxiliary components of the ISR, which are independent of ATF4, are critical for SAAR-mediated improvements in metabolic health in mice.

Trends in US Alcohol Consumption Frequency During the First Wave of the SARS-CoV-2 Pandemic.

BACKGROUND: The SARS-CoV-2 pandemic created disruptions and stressors which may have influenced alcohol consumption frequency trends. Varying COVID-19 health burden and alcohol policies may have contributed to different consumption trends between states. The aim of this study is to assess trends in alcohol consumption and moderation by state of residence. METHODS: We examined trends in adult drinking days, during the first wave of the pandemic (March 10 to June 8) using longitudinal data from the Understanding America Study (N = 6,172 unique participants; N = 28,059 observations). Because state mandates were responsive to disease burden, we modeled the interaction of time by COVID-19 burden, defined as whether the state had the median (or higher) daily incidence of COVID-19 cases on the survey date, and state random effects. We controlled for individual sociodemographics, perceived personal/familial COVID-19 burden, mental health symptomology, and risk avoidance. RESULTS: Drinking days increased throughout the duration (incidence risk ratio [IRR] for drinking per increase in one calendar day = 1.003, 95% CI 1.001, 1.004); trends were heterogeneous by disease burden, with individuals living in states with lower COVID-19 burden increasing (IRR = 1.005, 95% CI 1.003, 1.007) faster than those living in states with higher COVID-19 burden (IRR = 1.000, 95% CI 0.998, 1.002). Trends were heterogeneous between states, but there was no evidence of systematic geographic clustering of state trends. CONCLUSIONS: Drinking days increased during the first months of the COVID-19 pandemic, particularly among residents of states with lower disease burden.