Giving It Another Shot: A Reexamination of the Second or Subsequent Conviction Language of the Firearm Possession Sentencing Statute

The effects of the current interpretation of the federal firearm possession sentencing statute are severe, often mandating the imposition of de facto life sentences for first-time offenders. For example, suppose a twenty-three-year-old first-time offender was found guilty in a federal district court of robbing $500 from two financial institutions in two days and carrying a single firearm during the robbery spree. Under the Federal Sentencing Guidelines, this first-time offender would be subject to a sentence ranging between forty-one and fifty-one months for each robbery. Thus, for the substantive offenses, the sentence would total eighty-two to 102 months, or six years and ten months to eight years and six months. But because the offender was found to have been carrying a firearm, he could also be convicted of two counts of possessing a firearm in furtherance of a crime of violence, and thus subject to additional, mandatory sentences. Under the current interpretation of 18 U.S.C. 924(c) ( 924(c) ), the offender would be subject to a five- year sentence for the first firearm possession count in accordance with 924(c)(1)(A) and a twenty-five-year sentence for the second firearm possession count in the same proceeding in accordance with 924(c)(1)(C). Added together and without any adjustments by the trial judge, the total sentence for this hypothetical crime spree ranges from thirty-six years and ten months to thirty-eight years and six months. Serving his full sentence, the twenty-three-year-old first-time offender would thus be in prison until he is around sixty years old. Furthermore, the Comprehensive Crime Control Act of 1984 abolished parole in the federal prison system, so federal inmates must now serve at least eighty-five percent of their sentences. As the above hypothetical scenario reveals, criminal sentencing in federal courts is shaped by both the advisory Federal Sentencing Guidelines ( Sentencing Guidelines or Guidelines ), created by the United States Sentencing Commission, and by mandatory statutory provisions, passed by Congress. In this example, 924(c)(1)(A) mandates a minimum five-year sentence for the possession of a firearm during the commission of a violent crime or drug trafficking offense, and 924(c)(1)(C) mandates a minimum twenty-five-year sentence for possession of a firearm in the case of a a second or subsequent conviction

Organic thermal maturity as a proxy for frictional fault heating: Experimental constraints on methylphenanthrene kinetics at earthquake timescales

Biomarker thermal maturity is widely used to study burial heating of sediments over millions of years. Heating over short timescales such as during earthquakes should also result in measurable increases in biomarker thermal maturity. However, the sensitivity of biomarker thermal maturity reactions to short, higher-temperature heating has not been established. We report on hydrous pyrolysis experiments that determine the kinetic parameters of methylphenanthrene maturation at timescales and temperatures relevant to earthquake heating. Samples of Woodford Shale were heated at temperatures up to 343 °C over 15–150 min. The thermal maturity of the samples as measured by the methylphenanthrene index-1 (MPI-1) increased with heating time and temperature. We find that MPI-1 increases with time and temperature consistent with a first-order kinetic model and Arrhenius temperature relationship. Over the timescales tested here, MPI-1 is strongly affected by maximum temperature and less sensitive to heating duration. Production of new phenanthrene isomers and expulsion of a liquid pyrolyzate also occurred. Differential expulsion of methylphenanthrene isomers affected the apparent maturity of the rock at lower temperatures and may need to be considered for organic-rich fault rocks. Our results demonstrate that the overall MPI-1 reaction extent in both the rock and pyrolyzate are a useful measure of thermal maturity and reflect temperature history during rapid heating

Beta cell extracellular vesicle miR-21-5p cargo is increased in response to inflammatory cytokines and serves as a biomarker of type 1 diabetes

AIMS/HYPOTHESIS: Improved biomarkers are acutely needed for the detection of developing type 1 diabetes, prior to critical loss of beta cell mass. We previously demonstrated that elevated beta cell microRNA 21-5p (miR-21-5p) in rodent and human models of type 1 diabetes increased beta cell apoptosis. We hypothesised that the inflammatory milieu of developing diabetes may also increase miR-21-5p in beta cell extracellular vesicle (EV) cargo and that circulating EV miR-21-5p would be increased during type 1 diabetes development. METHODS: MIN6 and EndoC-βH1 beta cell lines and human islets were treated with IL-1β, IFN-γ and TNF-α to mimic the inflammatory milieu of early type 1 diabetes. Serum was collected weekly from 8-week-old female NOD mice until diabetes onset. Sera from a cross-section of 19 children at the time of type 1 diabetes diagnosis and 16 healthy children were also analysed. EVs were isolated from cell culture media or serum using sequential ultracentrifugation or ExoQuick precipitation and EV miRNAs were assayed. RESULTS: Cytokine treatment in beta cell lines and human islets resulted in a 1.5- to threefold increase in miR-21-5p. However, corresponding EVs were further enriched for this miRNA, with a three- to sixfold EV miR-21-5p increase in response to cytokine treatment. This difference was only partially reduced by pre-treatment of beta cells with Z-VAD-FMK to inhibit cytokine-induced caspase activity. Nanoparticle tracking analysis showed cytokines to have no effect on the number of EVs, implicating specific changes within EV cargo as being responsible for the increase in beta cell EV miR-21-5p. Sequential ultracentrifugation to separate EVs by size suggested that this effect was mostly due to cytokine-induced increases in exosome miR-21-5p. Longitudinal serum collections from NOD mice showed that EVs displayed progressive increases in miR-21-5p beginning 3 weeks prior to diabetes onset. To validate the relevance to human diabetes, we assayed serum from children with new-onset type 1 diabetes compared with healthy children. While total serum miR-21-5p and total serum EVs were reduced in diabetic participants, serum EV miR-21-5p was increased threefold compared with non-diabetic individuals. By contrast, both serum and EV miR-375-5p were increased in parallel among diabetic participants. CONCLUSIONS/INTERPRETATION: We propose that circulating EV miR-21-5p may be a promising marker of developing type 1 diabetes. Additionally, our findings highlight that, for certain miRNAs, total circulating miRNA levels are distinct from circulating EV miRNA content

Reversible Optogenetic Control of Subcellular Protein Localization in a Live Vertebrate Embryo.

We demonstrate the utility of the phytochrome system to rapidly and reversibly recruit proteins to specific subcellular regions within specific cells in a living vertebrate embryo. Light-induced heterodimerization using the phytochrome system has previously been used as a powerful tool to dissect signaling pathways for single cells in culture but has not previously been used to reversibly manipulate the precise subcellular location of proteins in multicellular organisms. Here we report the experimental conditions necessary to use this system to manipulate proteins in vivo. As proof of principle, we demonstrate that we can manipulate the localization of the apical polarity protein Pard3 with high temporal and spatial precision in both the neural tube and the embryo's enveloping layer epithelium. Our optimizations of optogenetic component expression and chromophore purification and delivery should significantly lower the barrier for establishing this powerful optogenetic system in other multicellular organisms

Synthesising the existing evidence for non-pharmacological interventions targeting outcomes relevant to young people with ADHD in the school setting: systematic review protocol.

BACKGROUND: Children and adolescents with attention-deficit/hyperactivity disorder (ADHD) have impairing levels of difficulty paying attention, impulsive behaviour and/or hyperactivity. ADHD causes extensive difficulties for young people at school, and as a result these children are at high risk for a wide range of poor outcomes. We ultimately aim to develop a flexible, modular 'toolkit' of evidence-based strategies that can be delivered by primary school staff to improve the school environment and experience for children with ADHD; the purpose of this review is to identify and quantify the evidence-base for potential intervention components. This protocol sets out our plans to systematically identify non-pharmacological interventions that target outcomes that have been reported to be of importance to key stakeholders (ADHD symptoms, organisation skills, executive-global- and classroom-functioning, quality of life, self-esteem and conflict with teachers and peers). We plan to link promising individual intervention components to measured outcomes, and synthesise the evidence of effectiveness for each outcome. METHODS: A systematic search for studies published from the year 2000 that target the outcomes of interest in children and young people aged 3-12 will be conducted. Titles and abstracts will be screened using prioritisation software, and then full texts of potentially eligible studies will be screened. Systematic reviews, RCTs, non-randomised and case-series studies are eligible designs. Synthesis will vary by the type of evidence available, potentially including a review of reviews, meta-analysis and narrative synthesis. Heterogeneity of studies meta-analysed will be assessed, along with publication bias. Intervention mapping will be applied to understand potential behaviour change mechanisms for promising intervention components. DISCUSSION: This review will highlight interventions that appear to effectively ameliorate negative outcomes that are of importance for people with ADHD, parents, school staff and experts. Components of intervention design and features that are associated with effective change in the outcome will be delineated and used to inform the development of a 'toolkit' of non-pharmacological strategies that school staff can use to improve the primary school experience for children with ADHD. TRIAL REGISTRATION: PROSPERO number CRD42021233924

Synthesising the existing evidence for non-pharmacological interventions targeting outcomes relevant to young people with ADHD in the school setting: systematic review protocol.

BACKGROUND: Children and adolescents with attention-deficit/hyperactivity disorder (ADHD) have impairing levels of difficulty paying attention, impulsive behaviour and/or hyperactivity. ADHD causes extensive difficulties for young people at school, and as a result these children are at high risk for a wide range of poor outcomes. We ultimately aim to develop a flexible, modular 'toolkit' of evidence-based strategies that can be delivered by primary school staff to improve the school environment and experience for children with ADHD; the purpose of this review is to identify and quantify the evidence-base for potential intervention components. This protocol sets out our plans to systematically identify non-pharmacological interventions that target outcomes that have been reported to be of importance to key stakeholders (ADHD symptoms, organisation skills, executive-global- and classroom-functioning, quality of life, self-esteem and conflict with teachers and peers). We plan to link promising individual intervention components to measured outcomes, and synthesise the evidence of effectiveness for each outcome. METHODS: A systematic search for studies published from the year 2000 that target the outcomes of interest in children and young people aged 3-12 will be conducted. Titles and abstracts will be screened using prioritisation software, and then full texts of potentially eligible studies will be screened. Systematic reviews, RCTs, non-randomised and case-series studies are eligible designs. Synthesis will vary by the type of evidence available, potentially including a review of reviews, meta-analysis and narrative synthesis. Heterogeneity of studies meta-analysed will be assessed, along with publication bias. Intervention mapping will be applied to understand potential behaviour change mechanisms for promising intervention components. DISCUSSION: This review will highlight interventions that appear to effectively ameliorate negative outcomes that are of importance for people with ADHD, parents, school staff and experts. Components of intervention design and features that are associated with effective change in the outcome will be delineated and used to inform the development of a 'toolkit' of non-pharmacological strategies that school staff can use to improve the primary school experience for children with ADHD. TRIAL REGISTRATION: PROSPERO number CRD42021233924

Informed consent for research in Borderline Personality Disorder

<p>Abstract</p> <p>Background</p> <p>Previous research on informed consent for research in psychiatric patients has centered on disorders that affect comprehension and appreciation of risks. Little has been written about consent to research in those subjects with Borderline Personality Disorder, a prevalent and disabling condition.</p> <p>Discussion</p> <p>Despite apparently intact cognition and comprehension of risks, a borderline subject may deliberately choose self-harm in order to fulfill abnormal psychological needs, or due to suicidality. Alternatively, such a subject may refuse enrollment due to transference or the desire to harm him or herself. Such phenomena could be precipitated or prevented by the interpersonal dynamics of the informed consent encounter.</p> <p>Summary</p> <p>Caution should be exercised in obtaining informed consent for research from subjects with Borderline Personality Disorder. A literature review and recommendations for future research are discussed.</p

Developing a Reduced Gravity Testbed for the Nanoparticle Field Extraction Thruster

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/77095/1/AIAA-2009-5194-670.pd

Adrenergic and mesenchymal signatures are identifiable in cell-free DNA and correlate with metastatic disease burden in children with neuroblastoma

Background: Cell-free DNA (cfDNA) profiles of 5-hydroxymethylcytosine (5-hmC), an epigenetic marker of open chromatin and active gene expression, are correlated with metastatic disease burden in patients with neuroblastoma. Neuroblastoma tumors are comprised of adrenergic (ADRN) and mesenchymal (MES) cells, and the relative abundance of each in tumor biopsies has prognostic implications. We hypothesized that ADRN and MES-specific signatures could be quantified in cfDNA 5-hmC profiles and would augment the detection of metastatic burden in patients with neuroblastoma. Methods: We previously performed an integrative analysis to identify ADRN and MES-specific genes (n = 373 and n = 159, respectively). Purified DNA from cell lines was serial diluted with healthy donor cfDNA. Using Gene Set Variation Analysis (GSVA), ADRN and MES signatures were optimized. We then quantified signature scores, and our prior neuroblastoma signature, in cfDNA from 84 samples from 46 high-risk patients including 21 patients with serial samples. Results: Samples from patients with higher metastatic burden had increased GSVA scores for both ADRN and MES gene signatures (p Conclusions: While it is feasible to identify ADRN and MES signatures using 5-hmC profiles of cfDNA from neuroblastoma patients and correlate these signatures to metastatic burden, additional data are needed to determine the optimal strategies for clinical implementation. Prospective evaluation in larger cohorts is ongoing.</p

Biomarkers heat up during earthquakes: New evidence of seismic slip in the rock record

During earthquakes, faults heat up due to frictional work. However, evidence of heating from paleoearthquakes along exhumed faults remains scarce. Here we describe a method using thermal maturation of organic molecules in sedimentary rock to determine whether a fault has experienced differential heating compared to surrounding rocks. We demonstrate the utility of this method on an ancient, pseudotachylyte-hosting megathrust at Pasagshak Point, Alaska. Measurements of the ratio of thermally stable to thermally unstable compounds (diamondoids/n-alkanes) show that the melt-bearing rocks have higher thermal maturity than surrounding rocks. Furthermore, the mineralogy of the survivor grains and the presence of any organic molecules allow us to constrain the temperature rise during the ancient earthquakes to 840–1170 °C above ambient temperatures of ∼260 °C. From this temperature rise, we estimate that the frictional work of the earthquake was ∼105–228 MJ/m2. Using experimental friction measurements as a constraint, we estimate that the minimum slip necessary for heating was ∼1–8 m. This paper demonstrates that biomarkers will be a useful tool to identify seismic slip along faults without frictional melt