Not So Civil Commitment: A Proposal for Statutory Reform Grounded in Procedural Justice

Every year, millions of Americans struggle with serious mental illness. Of them, thousands experience civil, or involuntary, commitment—that is, hospitals invoke the coercive power of the state to force these individuals into psychiatric hospitals against their will. Whether someone requires hospitalization is a complex question of psychology, medicine, and substantive law. But the process of civil commitment itself is troubling. Across the board, states fail to afford those facing civil commitment meaningful procedural protections. Current state laws subject individuals facing commitment to extended periods of confinement with little to no judicial intervention. Indeed, individuals facing commitment may wait weeks or more for a judicial hearing. And when hearings do occur, they start and end in a matter of minutes. Within those few minutes, little advocacy occurs: lawyers are often passive, judges are often impatient, and respondents rarely have the chance to speak. Worse, some states fail to provide hearings at all. In sum, civil commitment occurs in “pitch darkness.” Civil commitment procedure should limit, not compound, these harms. Applying fundamentals of procedural justice, this Note proposes three statutory reforms to increase fairness to those experiencing civil commitment. First, this Note calls for states to hold probable cause hearings within seventy-two hours of confinement. Second, states should explicitly define the duties and role of counsel within commitment proceedings. Third, states should task community mental health boards with monitoring the commitment process to increase compliance with the law and bring visibility to these proceedings. Ultimately, this Note aims to promote procedural justice for those facing civil commitment and rekindle a conversation about how states treat those experiencing serious mental illness

Genome-Wide Association Study of Susceptibility to Idiopathic Pulmonary Fibrosis

Rationale: Idiopathic pulmonary fibrosis (IPF) is a complex lung disease characterised by scarring of the lung that is believed to result from an atypical response to injury of the epithelium. Genome-wide association studies have reported signals of association implicating multiple pathways including host defence, telomere maintenance, signalling and cell-cell adhesion. Objectives: To improve our understanding of factors that increase IPF susceptibility by identifying previously unreported genetic associations. Methods and measurements: We conducted genome-wide analyses across three independent studies and meta-analysed these results to generate the largest genome-wide association study of IPF to date (2,668 IPF cases and 8,591 controls). We performed replication in two independent studies (1,456 IPF cases and 11,874 controls) and functional analyses (including statistical fine-mapping, investigations into gene expression and testing for enrichment of IPF susceptibility signals in regulatory regions) to determine putatively causal genes. Polygenic risk scores were used to assess the collective effect of variants not reported as associated with IPF. Main results: We identified and replicated three new genome-wide significant (P<5×10−8) signals of association with IPF susceptibility (associated with altered gene expression of KIF15, MAD1L1 and DEPTOR) and confirmed associations at 11 previously reported loci. Polygenic risk score analyses showed that the combined effect of many thousands of as-yet unreported IPF susceptibility variants contribute to IPF susceptibility. Conclusions: The observation that decreased DEPTOR expression associates with increased susceptibility to IPF, supports recent studies demonstrating the importance of mTOR signalling in lung fibrosis. New signals of association implicating KIF15 and MAD1L1 suggest a possible role of mitotic spindle-assembly genes in IPF susceptibility

<i>GRIN2A</i>-related disorders:genotype and functional consequence predict phenotype

Alterations of the N-methyl-d-aspartate receptor (NMDAR) subunit GluN2A, encoded by GRIN2A, have been associated with a spectrum of neurodevelopmental disorders with prominent speech-related features, and epilepsy. We performed a comprehensive assessment of phenotypes with a standardized questionnaire in 92 previously unreported individuals with GRIN2A-related disorders. Applying the criteria of the American College of Medical Genetics and Genomics to all published variants yielded 156 additional cases with pathogenic or likely pathogenic variants in GRIN2A, resulting in a total of 248 individuals. The phenotypic spectrum ranged from normal or near-normal development with mild epilepsy and speech delay/apraxia to severe developmental and epileptic encephalopathy, often within the epilepsy-aphasia spectrum. We found that pathogenic missense variants in transmembrane and linker domains (misTMD+Linker) were associated with severe developmental phenotypes, whereas missense variants within amino terminal or ligand-binding domains (misATD+LBD) and null variants led to less severe developmental phenotypes, which we confirmed in a discovery (P = 10-6) as well as validation cohort (P = 0.0003). Other phenotypes such as MRI abnormalities and epilepsy types were also significantly different between the two groups. Notably, this was paralleled by electrophysiology data, where misTMD+Linker predominantly led to NMDAR gain-of-function, while misATD+LBD exclusively caused NMDAR loss-of-function. With respect to null variants, we show that Grin2a+/- cortical rat neurons also had reduced NMDAR function and there was no evidence of previously postulated compensatory overexpression of GluN2B. We demonstrate that null variants and misATD+LBD of GRIN2A do not only share the same clinical spectrum (i.e. milder phenotypes), but also result in similar electrophysiological consequences (loss-of-function) opposing those of misTMD+Linker (severe phenotypes; predominantly gain-of-function). This new pathomechanistic model may ultimately help in predicting phenotype severity as well as eligibility for potential precision medicine approaches in GRIN2A-related disorders

Not So Civil Commitment: A Proposal for Statutory Reform Grounded in Procedural Justice

Every year, millions of Americans struggle with serious mental illness. Of them, thousands experience civil, or involuntary, commitment—that is, hospitals invoke the coercive power of the state to force these individuals into psychiatric hospitals against their will. Whether someone requires hospitalization is a complex question of psychology, medicine, and substantive law. But the process of civil commitment itself is troubling. Across the board, states fail to afford those facing civil commitment meaningful procedural protections. Current state laws subject individuals facing commitment to extended periods of confinement with little to no judicial intervention. Indeed, individuals facing commitment may wait weeks or more for a judicial hearing. And when hearings do occur, they start and end in a matter of minutes. Within those few minutes, little advocacy occurs: lawyers are often passive, judges are often impatient, and respondents rarely have the chance to speak. Worse, some states fail to provide hearings at all. In sum, civil commitment occurs in “pitch darkness.” Civil commitment procedure should limit, not compound, these harms. Applying fundamentals of procedural justice, this Note proposes three statutory reforms to increase fairness to those experiencing civil commitment. First, this Note calls for states to hold probable cause hearings within seventy-two hours of confinement. Second, states should explicitly define the duties and role of counsel within commitment proceedings. Third, states should task community mental health boards with monitoring the commitment process to increase compliance with the law and bring visibility to these proceedings. Ultimately, this Note aims to promote procedural justice for those facing civil commitment and rekindle a conversation about how states treat those experiencing serious mental illness

Passive Mode Locking of a Self-frequency-doubling Yb:Yal 3 (BO 3 ) 4 Laser

We report passive mode-locking experiments with a novel self-doubling laser crystal Yb:YAl3(BO3)4 (Yb:YAB). The diode-pumped laser was mode locked by an ion-implanted semiconductor saturable absorber mirror. Far off phase matching, soliton mode locking produced pulse widths of 198 fs to 1.4 ps, with up to 660-mW output and optical efficiency of 24% at 1040 nm. The shortest pulses had a peak power of 28 kW with 440-mW average power and 16% efficiency. A few degrees off phase matching, a total of 60 mW of green femtosecond pulses was generated simultaneously. Close to phase matching, the laser produced picosecond pulses and, without infrared output, a total of 270 mW of green output, corresponding to 10% conversion efficiency (absorbed pump to green output)

Diagnostic Likelihood Thresholds That Define a Working Diagnosis of Idiopathic Pulmonary Fibrosis

Rationale: The level of diagnostic likelihood at which physicians prescribe antifibrotic therapy without requesting surgical lung biopsy (SLB) in patients suspected of idiopathic pulmonary fibrosis (IPF) is unknown.Objectives: To determine how often physicians advocate SLB in patient subgroups defined by IPF likelihood and risk associated with SLB, and to identify the level of diagnostic likelihood at which physicians prescribe antifibrotic therapy with requesting SLB.Methods: An international cohort of respiratory physicians evaluated 60 cases of interstitial lung disease, giving: 1) differential diagnoses with diagnostic likelihood; 2) a decision on the need for SLB; and 3) initial management. Diagnoses were stratified according to diagnostic likelihood bands described by Ryerson and colleagues.Measurements and Main Results: A total of 404 physicians evaluated the 60 cases (24,240 physician-patient evaluations). IPF was part of the differential diagnosis in 9,958/24,240 (41.1%) of all physician-patient evaluations. SLB was requested in 8.1%, 29.6%, and 48.4% of definite, provisional high-confidence and provisional low-confidence diagnoses of IPF, respectively. In 63.0% of provisional high-confidence IPF diagnoses, antifibrotic therapy was prescribed without requesting SLB. No significant mortality difference was observed between cases given a definite diagnosis of IPF (90-100% diagnostic likelihood) and cases given a provisional high-confidence IPF diagnosis (hazard ratio, 0.97; P = 0.65; 95% confidence interval, 0.90-1.04).Conclusions: Most respiratory physicians prescribe antifibrotic therapy without requesting an SLB if a provisional high-confidence diagnosis or "working diagnosis" of IPF can be made (likelihood ≥ 70%). SLB is recommended in only a minority of patients with suspected, but not definite, IPF.status: publishe

AN OPTIMIZATION PROBLEM FOR A PRODUCTION SYSTEM WITH REAL OPTION APPROACH (Nonlinear Analysis and Convex Analysis)

Arhinia, or absence of the nose, is a rare malformation of unknown etiology that is often accompanied by ocular and reproductive defects. Sequencing of 40 people with arhinia revealed that 84% of probands harbor a missense mutation localized to a constrained region of SMCHD1 encompassing the ATPase domain. SMCHD1 mutations cause facioscapulohumeral muscular dystrophy type 2 (FSHD2) via a trans-acting loss-of-function epigenetic mechanism. We discovered shared mutations and comparable DNA hypomethylation patterning between these distinct disorders. CRISPR/Cas9-mediated alteration of smchd1 in zebrafish yielded arhinia-relevant phenotypes. Transcriptome and protein analyses in arhinia probands and controls showed no differences in SMCHD1 mRNA or protein abundance but revealed regulatory changes in genes and pathways associated with craniofacial patterning. Mutations in SMCHD1 thus contribute to distinct phenotypic spectra, from craniofacial malformation and reproductive disorders to muscular dystrophy, which we speculate to be consistent with oligogenic mechanisms resulting in pleiotropic outcomes