Preventable tragedies: findings from the #NotAnAccident index of unintentional shootings by children

Abstract Background Between 2015 and 2021, 3,498 Americans died from unintentional gun injuries, including 713 children 17 years and younger. Roughly 30 million American children live in homes with firearms, many of which are loaded and unlocked. This study assesses the scope of unintentional shootings by children 17 and younger in the US and the relationship between these shootings and state-level secure storage laws. Methods Demographic and injury data of both perpetrators and victims of unintentional shootings by children 17 and younger in the US from 1/1/2015–12/31/2021 were extracted from the #NotAnAccident Index. The #NotAnAccident Index contains media-report data, which is systematically flagged through Google Alerts. We describe characteristics of incidents and examine incident rates over time. The association between state-level secure storage laws and rates of unintentional shootings by children is assessed in multivariate negative binomial regression models. Results 2,448 unintentional shootings by children resulted in 926 deaths and 1,603 nonfatal gun injuries over a period of seven years. Most perpetrators (81%) and victims (76%) were male. The mean age was 10.0 (SD 5.5) for shooters and 10.9 (SD 8.1) for victims. Children were as likely to shoot themselves (49%) as they were to shoot others (47%). The majority of victims were under 18 years old (91%). Shootings most often occurred in or around homes (71%) and with handguns (53%). From March to December 2020, coinciding with the COVID-19 pandemic, incidents increased 24% over the same period in 2019, which was driven largely by an increase among shooters ages 0–5. Depending on the type of law, rates of unintentional shootings by children were 24% to 72% lower in states with secure storage laws, compared to states without such laws. Conclusions Unintentional shootings by children are on the rise, particularly among children 0–5 years old, but are preventable tragedies. Our results show that secure firearm storage policies are strongly correlated with lower rates of unintentional shootings by children. Firearm storage policies, practices, and education efforts are needed to ensure guns are kept secured and inaccessible to children

Site-Specific mTOR Phosphorylation Promotes mTORC1-Mediated Signaling and Cell Growth ▿

The mammalian target of rapamycin (mTOR) complex 1 (mTORC1) functions as a rapamycin-sensitive environmental sensor that promotes cellular biosynthetic processes in response to growth factors and nutrients. While diverse physiological stimuli modulate mTORC1 signaling, the direct biochemical mechanisms underlying mTORC1 regulation remain poorly defined. Indeed, while three mTOR phosphorylation sites have been reported, a functional role for site-specific mTOR phosphorylation has not been demonstrated. Here we identify a new site of mTOR phosphorylation (S1261) by tandem mass spectrometry and demonstrate that insulin-phosphatidylinositol 3-kinase signaling promotes mTOR S1261 phosphorylation in both mTORC1 and mTORC2. Here we focus on mTORC1 and show that TSC/Rheb signaling promotes mTOR S1261 phosphorylation in an amino acid-dependent, rapamycin-insensitive, and autophosphorylation-independent manner. Our data reveal a functional role for mTOR S1261 phosphorylation in mTORC1 action, as S1261 phosphorylation promotes mTORC1-mediated substrate phosphorylation (e.g., p70 ribosomal protein S6 kinase 1 [S6K1] and eukaryotic initiation factor 4E binding protein 1) and cell growth to increased cell size. Moreover, Rheb-driven mTOR S2481 autophosphorylation and S6K1 phosphorylation require S1261 phosphorylation. These data provide the first evidence that site-specific mTOR phosphorylation regulates mTORC1 function and suggest a model whereby insulin-stimulated mTOR S1261 phosphorylation promotes mTORC1 autokinase activity, substrate phosphorylation, and cell growth