The Structure and Limits of Criminal Law

The book The Structure and Limits of Criminal Law (Ashgate) collects and reprints classic articles on three topics: the conceptual structure of criminal law doctrine, the conduct necessary and that sufficient for criminal liability, and the offender culpability and blameworthiness necessary and that sufficient for criminal liability. The collection includes articles by H.L.A. Hart, Sanford Kadish, George Fletcher, Herbert Packer, Norval Morris, Gordon Hawkins, Andrew von Hirsch, Bernard Harcourt, Richard Wasserstrom, Andrew Simester, John Darley, Kent Greenawalt, and Paul Robinson. This essay serves as an introduction to the collection, explaining how each article fits into the larger debate and giving a brief summary of each that will orient the (primarily student) reader. Part I considers how best to construct a conceptual framework for criminal law. Under existing law, criminal law doctrine tends to operate in one of three ways: defining an offense, or defining a general defense that operates independent of the offense requirements to bar liability, or defining a doctrine of imputation that treats the actor as if he satisfies an offense requirement that he does not in fact satisfy. However, one could organize criminal law doctrines differently, around the different function that each performs: articulating ex ante the rules of conduct or adjudicating ex post the violation of those rules of conduct, to assess liability and the grade of the liability. Part II examines the debate over what conduct should be necessary for criminal liability, and what conduct should be sufficient. Harm to another is surely necessary but probably insufficient. And the harm principle has been stretched so far that it cannot now, by itself, serve as a meaningful limitation in the modern criminalization debate. On the other hand, immorality or at least condemnability of conduct is surely insufficient but probably necessary: on both philosophical and empirical grounds, there is reason to think that conduct should not be criminalized unless society regards it as morally blameworthy. Part III considers the debate over what offender culpability and blameworthiness should be necessary for criminal liability, and what should be sufficient. Despite calls by some to ignore blameworthiness in the name of prevention, the increasingly more accepted view is that criminal liability should be imposed only on the blameworthy. Indeed, many go further, arguing that also the extent of the offender\u27s liability and punishment should depend upon the extent of his blameworthiness. This means retaining the mens rea requirement, offering a full array of excuse defenses, and, in its strongest form, adopting desert as an inviolable distributive principle

The Structure and Limits of Criminal Law

The book The Structure and Limits of Criminal Law (Ashgate) collects and reprints classic articles on three topics: the conceptual structure of criminal law doctrine, the conduct necessary and that sufficient for criminal liability, and the offender culpability and blameworthiness necessary and that sufficient for criminal liability. The collection includes articles by H.L.A. Hart, Sanford Kadish, George Fletcher, Herbert Packer, Norval Morris, Gordon Hawkins, Andrew von Hirsch, Bernard Harcourt, Richard Wasserstrom, Andrew Simester, John Darley, Kent Greenawalt, and Paul Robinson. This essay serves as an introduction to the collection, explaining how each article fits into the larger debate and giving a brief summary of each that will orient the (primarily student) reader. Part I considers how best to construct a conceptual framework for criminal law. Under existing law, criminal law doctrine tends to operate in one of three ways: defining an offense, or defining a general defense that operates independent of the offense requirements to bar liability, or defining a doctrine of imputation that treats the actor as if he satisfies an offense requirement that he does not in fact satisfy. However, one could organize criminal law doctrines differently, around the different function that each performs: articulating ex ante the rules of conduct or adjudicating ex post the violation of those rules of conduct, to assess liability and the grade of the liability. Part II examines the debate over what conduct should be necessary for criminal liability, and what conduct should be sufficient. Harm to another is surely necessary but probably insufficient. And the harm principle has been stretched so far that it cannot now, by itself, serve as a meaningful limitation in the modern criminalization debate. On the other hand, immorality or at least condemnability of conduct is surely insufficient but probably necessary: on both philosophical and empirical grounds, there is reason to think that conduct should not be criminalized unless society regards it as morally blameworthy. Part III considers the debate over what offender culpability and blameworthiness should be necessary for criminal liability, and what should be sufficient. Despite calls by some to ignore blameworthiness in the name of prevention, the increasingly more accepted view is that criminal liability should be imposed only on the blameworthy. Indeed, many go further, arguing that also the extent of the offender\u27s liability and punishment should depend upon the extent of his blameworthiness. This means retaining the mens rea requirement, offering a full array of excuse defenses, and, in its strongest form, adopting desert as an inviolable distributive principle

Empirical Desert, Individual Prevention, and Limiting Retributivism: A Reply

A number of articles and empirical studies over the past decade, most by Paul Robinson and co-authors, have suggested a relationship between the extent of the criminal law\u27s reputation for being just in its distribution of criminal liability and punishment in the eyes of the community – its moral credibility – and its ability to gain that community\u27s deference and compliance through a variety of mechanisms that enhance its crime-control effectiveness. This has led to proposals to have criminal liability and punishment rules reflect lay intuitions of justice – empirical desert – as a means of enhancing the system\u27s moral credibility. In a recent article, Christopher Slobogin and Lauren Brinkley-Rubinstein (SBR) report seven sets of studies that they argue undermine these claims of empirical desert and moral credibility and instead support SBR\u27s proposed distributive principle of individual prevention, a view that focuses on an offender\u27s future dangerousness rather than on his perceived desert. The idea that there is a relationship between the criminal law\u27s reputation for justness and its crime-control effectiveness did not originate with Robinson and his co-authors. Rather, it has been a common theme among a wide range of punishment theory scholars for many decades. A particularly important conclusion of recent Robinson studies, however, is their confirmation that this relationship is a continuous one: even small nudges in moral credibility can produce corresponding changes in the community\u27s deference to the criminal law. This is important because it shows that even piecemeal changes or changes at the margin – as in reforming even one unjust doctrine or procedure – can have real implications for crime-control. SBR\u27s studies, rather than contradicting the crime-control power of empirical desert, in fact confirm it. Further, SBR\u27s studies do not provide support for their proposed individual prevention distributive principle, contrary to what they claim. While SBR try to associate their principle with the popular limiting retributivism adopted by the American Law Institute in its 2007 amendment of the Model Penal Code, in fact it is, in many respects, just the reverse of that principle. With limiting retributivism, the Model Code\u27s new provision sets desert as dominant, never allowing punishment to conflict with it. SBR would have punishment essentially always set according to future dangerousness; it is to be constrained by desert only when the extent of the resulting injustices or failures of justice is so egregious as to significantly delegitimize the government and its law. This ignores the fact that even minor departures from justice may have an important cumulative effect on the system as a whole. What SBR propose – essentially substituting preventive detention for criminal justice – promotes the worst of the failed policies of the 1960s, where detention decisions were made at the back-end by experts, and conflicts with the trend of the past several decades of encouraging more community involvement in criminal punishment, not less

Empirical Desert, Individual Prevention, and Limiting Retributivism: A Reply

A number of articles and empirical studies over the past decade, most by Paul Robinson and co-authors, have suggested a relationship between the extent of the criminal law\u27s reputation for being just in its distribution of criminal liability and punishment in the eyes of the community – its moral credibility – and its ability to gain that community\u27s deference and compliance through a variety of mechanisms that enhance its crime-control effectiveness. This has led to proposals to have criminal liability and punishment rules reflect lay intuitions of justice – empirical desert – as a means of enhancing the system\u27s moral credibility. In a recent article, Christopher Slobogin and Lauren Brinkley-Rubinstein (SBR) report seven sets of studies that they argue undermine these claims of empirical desert and moral credibility and instead support SBR\u27s proposed distributive principle of individual prevention, a view that focuses on an offender\u27s future dangerousness rather than on his perceived desert. The idea that there is a relationship between the criminal law\u27s reputation for justness and its crime-control effectiveness did not originate with Robinson and his co-authors. Rather, it has been a common theme among a wide range of punishment theory scholars for many decades. A particularly important conclusion of recent Robinson studies, however, is their confirmation that this relationship is a continuous one: even small nudges in moral credibility can produce corresponding changes in the community\u27s deference to the criminal law. This is important because it shows that even piecemeal changes or changes at the margin – as in reforming even one unjust doctrine or procedure – can have real implications for crime-control. SBR\u27s studies, rather than contradicting the crime-control power of empirical desert, in fact confirm it. Further, SBR\u27s studies do not provide support for their proposed individual prevention distributive principle, contrary to what they claim. While SBR try to associate their principle with the popular limiting retributivism adopted by the American Law Institute in its 2007 amendment of the Model Penal Code, in fact it is, in many respects, just the reverse of that principle. With limiting retributivism, the Model Code\u27s new provision sets desert as dominant, never allowing punishment to conflict with it. SBR would have punishment essentially always set according to future dangerousness; it is to be constrained by desert only when the extent of the resulting injustices or failures of justice is so egregious as to significantly delegitimize the government and its law. This ignores the fact that even minor departures from justice may have an important cumulative effect on the system as a whole. What SBR propose – essentially substituting preventive detention for criminal justice – promotes the worst of the failed policies of the 1960s, where detention decisions were made at the back-end by experts, and conflicts with the trend of the past several decades of encouraging more community involvement in criminal punishment, not less

Contemporary Homozygous Familial Hypercholesterolemia in the United States: Insights From the CASCADE FH Registry

Erratum in: J Am Heart Assoc. 2023 Jun 6;12(11):e027706. doi: 10.1161/JAHA.122.027706. Epub 2023 Jun 1.Free PMC article: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10227232/Background: Homozygous familial hypercholesterolemia (HoFH) is a rare, treatment-resistant disorder characterized by earlyonset atherosclerotic and aortic valvular cardiovascular disease if left untreated. Contemporary information on HoFH in the United States is lacking, and the extent of underdiagnosis and undertreatment is uncertain. Methods and Results: Data were analyzed from 67 children and adults with clinically diagnosed HoFH from the CASCADE (Cascade Screening for Awareness and Detection) FH Registry. Genetic diagnosis was confirmed in 43 patients. We used the clinical characteristics of genetically confirmed patients with HoFH to query the Family Heart Database, a US anonymized payer health database, to estimate the number of patients with similar lipid profiles in a “real-world” setting. Untreated lowdensity lipoprotein cholesterol levels were lower in adults than children (533 versus 776mg/dL; P=0.001). At enrollment, atherosclerotic cardiovascular disease and supravalvular and aortic valve stenosis were present in 78.4% and 43.8% and 25.5% and 18.8% of adults and children, respectively. At most recent follow-up, despite multiple lipid-lowering treatment, low-density lipoprotein cholesterol goals were achieved in only a minority of adults and children. Query of the Family Heart Database identified 277 individuals with profiles similar to patients with genetically confirmed HoFH. Advanced lipid-lowering treatments were prescribed for 18%; 40% were on no lipid-lowering treatment; atherosclerotic cardiovascular disease was reported in 20%; familial hypercholesterolemia diagnosis was uncommon. Conclusions: Only patients with the most severe HoFH phenotypes are diagnosed early. HoFH remains challenging to treat. Results from the Family Heart Database indicate HoFH is systemically underdiagnosed and undertreated. Earlier screening, aggressive lipid-lowering treatments, and guideline implementation are required to reduce disease burden in HoFH.Dr Martin is supported by grants/contracts from the American Heart Association (20SFRN35380046, 20SFRN35490003, 878924, and 882415), Patient‐Centered Outcomes Research Institute (PCORI) (ME‐2019C1‐15328), National Institutes of Health (NIH) (R01AG071032 and P01 HL108800), the David and June Trone Family Foundation, Pollin Digital Health Innovation Fund, and Sandra and Larry Small; Dr Knowles is supported by the NIH through grants P30 DK116074 (to the Stanford Diabetes Research Center), R01 DK116750, R01 DK120565, and R01 DK106236; and by a grant from the Bilateral Science Foundation. Dr Linton is supported by NIH grants P01HL116263, HL148137, HL159487, and HL146134.info:eu-repo/semantics/publishedVersio

The Characterization of Twenty Sequenced Human Genomes

We present the analysis of twenty human genomes to evaluate the prospects for identifying rare functional variants that contribute to a phenotype of interest. We sequenced at high coverage ten “case” genomes from individuals with severe hemophilia A and ten “control” genomes. We summarize the number of genetic variants emerging from a study of this magnitude, and provide a proof of concept for the identification of rare and highly-penetrant functional variants by confirming that the cause of hemophilia A is easily recognizable in this data set. We also show that the number of novel single nucleotide variants (SNVs) discovered per genome seems to stabilize at about 144,000 new variants per genome, after the first 15 individuals have been sequenced. Finally, we find that, on average, each genome carries 165 homozygous protein-truncating or stop loss variants in genes representing a diverse set of pathways

Cardiomyocyte BRAF and type 1 RAF inhibitors promote cardiomyocyte and cardiac hypertrophy in mice in vivo

The extracellular signal-regulated kinase 1/2 (ERK1/2) cascade promotes cardiomyocyte hypertrophy and is cardioprotective, with the three RAF kinases forming a node for signal integration. Our aims were to determine if BRAF is relevant for human heart failure, whether BRAF promotes cardiomyocyte hypertrophy, and if Type 1 RAF inhibitors developed for cancer (that paradoxically activate ERK1/2 at low concentrations: the “RAF paradox”) may have the same effect. BRAF was upregulated in heart samples from patients with heart failure compared with normal controls. We assessed the effects of activated BRAF in the heart using mice with tamoxifen-activated Cre for cardiomyocyte-specific knock-in of the activating V600E mutation into the endogenous gene. We used echocardiography to measure cardiac dimensions/function. Cardiomyocyte BRAFV600E induced cardiac hypertrophy within 10 d, resulting in increased ejection fraction and fractional shortening over 6 weeks. This was associated with increased cardiomyocyte size without significant fibrosis, consistent with compensated hypertrophy. The experimental Type 1 RAF inhibitor, SB590885, and/or encorafenib (a RAF inhibitor used clinically) increased ERK1/2 phosphorylation in cardiomyocytes, and promoted hypertrophy, consistent with a “RAF paradox” effect. Both promoted cardiac hypertrophy in mouse hearts in vivo, with increased cardiomyocyte size and no overt fibrosis. In conclusion, BRAF potentially plays an important role in human failing hearts, activation of BRAF is sufficient to induce hypertrophy, and Type 1 RAF inhibitors promote hypertrophy via the “RAF paradox”. Cardiac hypertrophy resulting from these interventions was not associated with pathological features, suggesting that Type 1 RAF inhibitors may be useful to boost cardiomyocyte function

Contemporary Homozygous Familial Hypercholesterolemia in the United States: Insights From the CASCADE FH Registry

Background Homozygous familial hypercholesterolemia (HoFH) is a rare, treatment‐resistant disorder characterized by early‐onset atherosclerotic and aortic valvular cardiovascular disease if left untreated. Contemporary information on HoFH in the United States is lacking, and the extent of underdiagnosis and undertreatment is uncertain. Methods and Results Data were analyzed from 67 children and adults with clinically diagnosed HoFH from the CASCADE (Cascade Screening for Awareness and Detection) FH Registry. Genetic diagnosis was confirmed in 43 patients. We used the clinical characteristics of genetically confirmed patients with HoFH to query the Family Heart Database, a US anonymized payer health database, to estimate the number of patients with similar lipid profiles in a “real‐world” setting. Untreated low‐density lipoprotein cholesterol levels were lower in adults than children (533 versus 776 mg/dL; P=0.001). At enrollment, atherosclerotic cardiovascular disease and supravalvular and aortic valve stenosis were present in 78.4% and 43.8% and 25.5% and 18.8% of adults and children, respectively. At most recent follow‐up, despite multiple lipid‐lowering treatment, low‐density lipoprotein cholesterol goals were achieved in only a minority of adults and children. Query of the Family Heart Database identified 277 individuals with profiles similar to patients with genetically confirmed HoFH. Advanced lipid‐lowering treatments were prescribed for 18%; 40% were on no lipid‐lowering treatment; atherosclerotic cardiovascular disease was reported in 20%; familial hypercholesterolemia diagnosis was uncommon. Conclusions Only patients with the most severe HoFH phenotypes are diagnosed early. HoFH remains challenging to treat. Results from the Family Heart Database indicate HoFH is systemically underdiagnosed and undertreated. Earlier screening, aggressive lipid‐lowering treatments, and guideline implementation are required to reduce disease burden in HoFH

Evaluating the Effects of SARS-CoV-2 Spike Mutation D614G on Transmissibility and Pathogenicity.

Global dispersal and increasing frequency of the SARS-CoV-2 spike protein variant D614G are suggestive of a selective advantage but may also be due to a random founder effect. We investigate the hypothesis for positive selection of spike D614G in the United Kingdom using more than 25,000 whole genome SARS-CoV-2 sequences. Despite the availability of a large dataset, well represented by both spike 614 variants, not all approaches showed a conclusive signal of positive selection. Population genetic analysis indicates that 614G increases in frequency relative to 614D in a manner consistent with a selective advantage. We do not find any indication that patients infected with the spike 614G variant have higher COVID-19 mortality or clinical severity, but 614G is associated with higher viral load and younger age of patients. Significant differences in growth and size of 614G phylogenetic clusters indicate a need for continued study of this variant

The genetic architecture of the human cerebral cortex

The cerebral cortex underlies our complex cognitive capabilities, yet little is known about the specific genetic loci that influence human cortical structure. To identify genetic variants that affect cortical structure, we conducted a genome-wide association meta-analysis of brain magnetic resonance imaging data from 51,665 individuals. We analyzed the surface area and average thickness of the whole cortex and 34 regions with known functional specializations. We identified 199 significant loci and found significant enrichment for loci influencing total surface area within regulatory elements that are active during prenatal cortical development, supporting the radial unit hypothesis. Loci that affect regional surface area cluster near genes in Wnt signaling pathways, which influence progenitor expansion and areal identity. Variation in cortical structure is genetically correlated with cognitive function, Parkinson's disease, insomnia, depression, neuroticism, and attention deficit hyperactivity disorder