BACKGROUND: Privately made firearms (PMFs) or ghost guns are homemade, unserialized, untraceable firearms that have been increasingly used in violent crime in the United States. Very little is known about the types of PMFs recovered by law enforcement agencies and the crimes associated with these recoveries. This lack of information limits effective violence prevention policies and practices. Comparative analysis of PMF recoveries in specific cities helps clarify whether local PMF patterns and characteristics vary or reflect more general trends. This research advances epidemiological understanding of emergent violent gun injury prevention challenges by identifying variations in recovered PMF types and use in violent, drug, and weapon-related offenses in Los Angeles and San Diego, California. METHODS: Conjunctive analysis of case configurations (CACC) identifies patterns among observations (i.e., case configurations) and calculates their probability associated with a given outcome. CACC was used to identify the most common types of PMFs recovered by the Los Angeles (LAPD) and San Diego (SDPD) police departments. For each department and offense type, case configurations with above-average probabilities of offense involvement were determined. Comparisons across departments were made to identify similarities and differences in PMF characteristics and usage. RESULTS: PMFs were more likely to be involved in violent and weapon-related offenses in Los Angles but more likely to be involved in drug-related offenses in San Diego. In both cities, the 9 mm Polymer 80 handgun was the dominant PMF. However, 9 mm handguns were most likely to be involved in weapon-related offenses in Los Angeles compared to 0.40 handguns in San Diego. Furthermore, large-caliber handguns tended to display above-average probabilities of involvement in violent and drug offenses in Los Angeles. Long guns were represented in case configurations with above-average probabilities of involvement in substantive crimes, including violence. CONCLUSIONS: Comparative analyses of PMF recovery patterns in Los Angeles and San Diego reveal meaningful contextual variations in PMF characteristics and suggest intentional firearm type selections by offenders. The results support increased regulation of PMFs and highlight the importance of efforts to identify and disrupt the illicit supply of large-caliber PMF handguns and PMF long guns.

Background

Co-transcriptional R-loops are abundant non-B DNA structures in mammalian genomes. DNA Topoisomerase I (Top1) is often thought to regulate R-loop formation owing to its ability to resolve both positive and negative supercoils. How Top1 regulates R-loop structures at a global level is unknown.

Results

Here, we perform high-resolution strand-specific R-loop mapping in human cells depleted for Top1 and find that Top1 depletion results in both R-loop gains and losses at thousands of transcribed loci, delineating two distinct gene classes. R-loop gains are characteristic for long, highly transcribed, genes located in gene-poor regions anchored to Lamin B1 domains and in proximity to H3K9me3-marked heterochromatic patches. R-loop losses, by contrast, occur in gene-rich regions overlapping H3K27me3-marked active replication initiation regions. Interestingly, Top1 depletion coincides with a block of the cell cycle in G0/G1 phase and a trend towards replication delay.

Conclusions

Our findings reveal new properties of Top1 in regulating R-loop homeostasis in a context-dependent manner and suggest a potential role for Top1 in modulating the replication process via R-loop formation.

Unemployment and violence both increased during the coronavirus pandemic in the United States (US), but no studies to our knowledge have examined their association. Using data for 16 US cities from January 2018 to July 2020, we estimated the association between acute changes in unemployment during the coronavirus pandemic and violent and acquisitive crime. We used negative binomial regression models and parametric g-computation to estimate average differences in crime incidents if the highest and lowest levels of unemployment observed in each city had been sustained across the exposure period (March-July 2020), compared with observed unemployment in each city-month. During the pandemic, the percentage of the adult population who were unemployed was 8.1 percentage points higher than expected, on average. Increases in unemployment were associated with increases in firearm violence and homicide. For example, we estimated an average increase of 3.3 firearm violence incidents (95% CI: - 0.2, 6.7) and 2.0 homicides (95% CI: - 0.2, 3.9) per city-month from March to July 2020 if all cities experienced their highest versus observed level of unemployment. There was no association between unemployment and aggravated assault or any acquisitive crime. Findings suggest that the sharp rise in unemployment during the pandemic may have contributed to increases in firearm violence and homicide, but not other crime. Additional research is needed on mechanisms of association, generalizability, and modifying factors.

In recent years, the concept of entropy stabilization of crystal structures in oxide systems has led to an increased research activity in the field of "high entropy oxides". These compounds comprise the incorporation of multiple metal cations into single-phase crystal structures and interactions among the various metal cations leading to interesting novel and unexpected properties. Here, we report on the reversible lithium storage properties of the high entropy oxides, the underlying mechanisms governing these properties, and the influence of entropy stabilization on the electrochemical behavior. It is found that the stabilization effect of entropy brings significant benefits for the storage capacity retention of high entropy oxides and greatly improves the cycling stability. Additionally, it is observed that the electrochemical behavior of the high entropy oxides depends on each of the metal cations present, thus providing the opportunity to tailor the electrochemical properties by simply changing the elemental composition.

Several molecules present in the diet, including flavonoids, can inhibit the growth of cancer cells with an ability to act as "chemopreventers". Their cancer-preventive effects have been attributed to various mechanisms, including the induction of cell-cycle arrest and/or apoptosis as well as the antioxidant functions. The antioxidant activity of chemopreventers has recently received a great interest, essentially because oxidative stress participates in the initiation and progression of different pathological conditions, including cancer. Since antioxidants are capable of preventing oxidative damage, the wide use of natural food-derived antioxidants is receiving greater attention as potential anti-carcinogens. Among flavonoids, quercetin (Qu) is considered an excellent free-radical scavenging antioxidant, even if such an activity strongly depends on the intracellular availability of reduced glutathione. Apart from antioxidant activity, Qu also exerts a direct, pro-apoptotic effect in tumor cells, and can indeed block the growth of several human cancer cell lines at different phases of the cell cycle. Both these effects have been documented in a wide variety of cellular models as well as in animal models. The high toxicity exerted by Qu on cancer cells perfectly matches with the almost total absence of any damages for normal, non-transformed cells. In this review we discuss the molecular mechanisms that are based on the biological effects of Qu, and their relevance for human health.

Violent crime increased and most property crime decreased in many United States (US) cities during the coronavirus pandemic. Using negative binomial regressions, we examined the association between physical distancing (a central coronavirus containment strategy) and crime within 16 large cities (in 12 US states and the District of Columbia) through July 2020. Physical distancing was measured with aggregated smartphone data and defined as the average change in the percentage of the population staying completely at home. Outcome data were obtained from the Gun Violence Archive and city open data portals. In multivariable models, increases in the percentage of the population staying home were associated with decreases in reported incidents of aggravated assault, interpersonal firearm violence, theft, rape, and robbery, and increases in arson, burglary, and motor vehicle theft. Results suggest that changes in the frequency of interpersonal interactions affected crime during the coronavirus pandemic. More research is needed on the specificity of these assocations and their underlying mechanisms.

Background

Firearm violence is a significant public health problem in the United States. A surge in firearm purchasing following the onset of the coronavirus pandemic may have contributed to an increase in firearm violence. We sought to estimate the state-level association between firearm purchasing and interpersonal firearm violence during the pandemic.

Methods

Cross-sectional study of the 48 contiguous states and the District of Columbia from January 2018 through July 2020. Data were obtained from the National Instant Criminal Background Check System (a proxy for firearm purchasing) and the Gun Violence Archive. Using negative binomial regression models, we estimated the association between cumulative excess firearm purchases in March through July 2020 (measured as the difference between observed rates and those expected from autoregressive integrated moving average models) and injuries (including nonfatal and fatal) from intentional, interpersonal firearm violence (non-domestic and domestic violence).

Results

We estimated that there were 4.3 million excess firearm purchases nationally from March through July 2020 and a total of 4075 more firearm injuries than expected from April through July. We found no relationship between state-level excess purchasing and non-domestic firearm violence, e.g., each excess purchase per 100 population was associated with a rate ratio (RR) of firearm injury from non-domestic violence of 0.76 (95% CI: 0.50-1.02) in April; 0.99 (95% CI: 0.72-1.25) in May; 1.10 (95% CI: 0.93-1.32) in June; and 0.98 (95% CI: 0.85-1.12) in July. Excess firearm purchasing within states was associated with an increase in firearm injuries from domestic violence in April (RR: 2.60; 95% CI: 1.32-5.93) and May (RR: 1.79; 95% CI: 1.19-2.91), though estimates were sensitive to model specification.

Conclusions

Nationwide, firearm purchasing and firearm violence increased substantially during the first months of the coronavirus pandemic. At the state level, the magnitude of the increase in purchasing was not associated with the magnitude of the increase in firearm violence. Increases in purchasing may have contributed to additional firearm injuries from domestic violence in April and May. Results suggest much of the rise in firearm violence during our study period was attributable to other factors, indicating a need for additional research.

Introduction

Scientific discoveries over the past few decades have provided significant insight into the abuse liability and negative health consequences associated with tobacco and nicotine-containing products. While many of these advances have led to the development of policies and laws that regulate access to and formulations of these products, further research is critical to guide future regulatory efforts, especially as novel nicotine-containing products are introduced and selectively marketed to vulnerable populations.

Discussion

In this narrative review, we provide an overview of the scientific findings that have impacted regulatory policy and discuss considerations for further translation of science into policy decisions. We propose that open, bidirectional communication between scientists and policy makers is essential to develop transformative preventive- and intervention-focused policies and programs to reduce appeal, abuse liability, and toxicity of the products.

Conclusions

Through these types of interactions, collaborative efforts to inform and modify policy have the potential to significantly decrease the use of tobacco and alternative nicotine products and thus enhance health outcomes for individuals.

Implications

This work addresses current topics in the nicotine and tobacco research field to emphasize the importance of basic science research and provide examples of how it can be utilized to inform public policy. In addition to relaying current thoughts on the topic from experts in the field, the article encourages continued efforts and communication between basic scientists and policy officials.

Cell-to-cell communication is essential for the organization, coordination, and development of cellular networks and multi-cellular systems. Intercellular communication is mediated by soluble factors (including growth factors, neurotransmitters, and cytokines/chemokines), gap junctions, exosomes and recently described tunneling nanotubes (TNTs). It is unknown whether a combination of these communication mechanisms such as TNTs and gap junctions may be important, but further research is required. TNTs are long cytoplasmic bridges that enable long-range, directed communication between connected cells. The proposed functions of TNTs are diverse and not well understood but have been shown to include the cell-to-cell transfer of vesicles, organelles, electrical stimuli and small molecules. However, the exact role of TNTs and gap junctions for intercellular communication and their impact on disease is still uncertain and thus, the subject of much debate. The combined data from numerous laboratories indicate that some TNT mediate a long-range gap junctional communication to coordinate metabolism and signaling, in relation to infectious, genetic, metabolic, cancer, and age-related diseases. This review aims to describe the current knowledge, challenges and future perspectives to characterize and explore this new intercellular communication system and to design TNT-based therapeutic strategies.

Cell-to-cell communication is essential for the organization, coordination, and development of cellular networks and multi-cellular systems. Intercellular communication is mediated by soluble factors (including growth factors, neurotransmitters, and cytokines/chemokines), gap junctions, exosomes and recently described tunneling nanotubes (TNTs). It is unknown whether a combination of these communication mechanisms such as TNTs and gap junctions may be important, but further research is required. TNTs are long cytoplasmic bridges that enable long-range, directed communication between connected cells. The proposed functions of TNTs are diverse and not well understood but have been shown to include the cell-to-cell transfer of vesicles, organelles, electrical stimuli and small molecules. However, the exact role of TNTs and gap junctions for intercellular communication and their impact on disease is still uncertain and thus, the subject of much debate. The combined data from numerous laboratories indicate that some TNT mediate a long-range gap junctional communication to coordinate metabolism and signaling, in relation to infectious, genetic, metabolic, cancer, and age-related diseases. This review aims to describe the current knowledge, challenges and future perspectives to characterize and explore this new intercellular communication system and to design TNT-based therapeutic strategies.