State of Arizona v. Guy James Goodman: On Petition for a Writ of Certiorari to the Arizona Supreme Court

Arizona’s pending certiorari petition in Arizona v. Goodman provides the Supreme Court with an opportunity to review the important issue of the circumstances under which the Constitution permits an accused sex offender to be denied bail pending trial. In 2002, Arizona voters amended their state constitution, rendering a defendant categorically ineligible for bail if “the proof is evident or the presumption great” that he committed sexual assault. In a narrowly divided opinion, the Arizona Supreme Court found that this measure unconstitutional. And yet the Court’s opinion makes clear that the Constitution does not prohibit denying bail to defendants who present (1) “a continuing danger to the community” or (2) “a risk of flight.” Nor does the Constitution prohibit categorically denying bail based on the nature of the charged offense. Indeed, thirty-four states categorically deny bail to persons charged with capital offenses, murder, specified sex offenses, or offenses punishable by life imprisonment. Review of the Arizona Supreme Court’s decision is needed to resolve the conflict between it and the Court’s precedent on an important issue of constitutional law that affects the criminal justice system, crime victims, and community safety in States across the Nation. The Court’s review is especially needed because of the serious implications for victims and their communities if the judgment below is permitted to stand. Given sex offenders’ high recidivism rates, and the life-altering harm suffered by their victims, Arizona’s legislature was entirely reasonable when it opted to categorically deny bail to sexual-assault defendants on the ground that sexual assault is an adequate proxy for future dangerousness - and to build in procedural protections that go above and beyond in ensuring due process. The Constitution does not prohibit States like Arizona and others from taking these steps to ensure sex offenders are brought to justice, victims are protected, and communities are safeguarded

<i>CYP2D6</i>, <i>SULT1A1</i> and <i>UGT2B17</i> copy number variation: quantitative detection by multiplex PCR

Aim: Among the genes of drug-metabolizing enzymes, CYP2D6 is notoriously difficult to characterize owing to the complexity of gene deletions, duplications, multiplications and the presence of hybrid genes composed of CYP2D6 and CYP2D7. For SULT1A1 up to five gene copies have been reported, while UGT2B17 is known for gene deletions only. Different platforms exist for copy number variation (CNV) detection; however, there are no gold standards. Robust methods are required that address specific challenges to accurately determine gene CNVs in complex gene loci. Materials &amp; methods: Quantitative multiplex PCR amplification (MPA) was performed on a diverse set of genomic DNA samples. Resulting PCR fragments were separated on an ABI 3730 instrument and analyzed with GeneMapper. CYP2D6 was targeted at four different gene regions and either normalized against CYP2D8 or UGT2B15 and SULT1A2. Inconsistent observations and CNVs contrasting genotype data were further characterized by long-range PCR and/or DNA sequence analysis. UGT2B17 and SULT1A1 were normalized against UGT2B15 and SULT1A2, respectively. Results: MPA detected 0–5, 1–5 and 0–2 copies for CYP2D6, SULT1A1 and UGT2B17, respectively. The interrogation of four CYP2D6 regions resulted in robust copy number assignments that were in agreement with genotype, sequencing and extra long PCR-based data. Gene deletions, duplication, and multiplications among known and novel hybrid genes were reliably identified. Novel findings regarding allelic variation include nonfunctional CYP2D6/2D7 hybrids such as CYP2D6*4N and *68, which were consistently identified on a subset of CYP2D6*4 alleles. In addition, a novel variant, designated CYP2D6*83, was discovered. For SULT1A1, we report the first six-copy case and for UGT2B15 and UGT2B17 we have evidence for rare deletion and duplication events, respectively. Conclusion: This MPA-based copy number platform not only allowed us to determine CNVs, but also served as a tool for allele discovery and characterization in a diverse panel of samples in a fast and reliable manner. Original submitted 6 July 2011; Revision submitted 24 August 2011 </jats:p

High-resolution melt analysis to detect sequence variations in highly homologous gene regions: application to <i>CYP2B6</i>

High-resolution melt (HRM) analysis using ‘release-on-demand’ dyes, such as EvaGreen® has the potential to resolve complex genotypes in situations where genotype interpretation is complicated by the presence of pseudogenes or allelic variants in close proximity to the locus of interest. We explored the utility of HRM to genotype a SNP (785A&gt;G, K262R, rs2279343) that is located within exon 5 of the CYP2B6 gene, which contributes to the metabolism of a number of clinically used drugs. Testing of 785A&gt;G is challenging, but crucial for accurate genotype determination. This SNP is part of multiple known CYP2B6 haplotypes and located in a region that is identical to CYP2B7, a nonfunctional pseudogene. Because small CYP2B6-specific PCR amplicons bracketing 785A&gt;G cannot be generated, we simultaneously amplified both genes. A panel of 235 liver tissue DNAs and five Coriell samples were assessed. Eight CYP2B6/CYP2B7 diplotype combinations were found and a novel variant 769G&gt;A (D257N) was discovered. The frequency of 785G corresponded to those reported for Caucasians and African–Americans. Assay performance was confirmed by CYP2B6 and/or CYP2B7 sequence analysis in a subset of samples, using a preamplified CYP2B6-specific long-range-PCR amplicon as HRM template. Inclusion rather than exclusion of a homologous pseudogene allowed us to devise a sensitive, reliable and affordable assay to test this CYP2B6 SNP. This assay design may be utilized to overcome the challenges and limitations of other methods. Owing to the flexibility of HRM, this assay design can easily be adapted to other gene loci of interest. </jats:p

Victims in Criminal Procedure

In this revised fourth edition, the authors have updated the casebook in light of dramatic changes that have taken place in crime victims rights since the last edition. This book includes substantial revisions, including a new separate chapter on crime victim privacy issues. It also examines a new wave of expansive state constitutional amendments, known collectively as Marsy\u27s Law, that expand victims rights and enforcement procedures in states such as California, Ohio, Illinois, and others.https://lawcommons.lclark.edu/faculty_books/1005/thumbnail.jp

Mature Results of a Prospective Trial of Rituximab in Patients (Pt) with Post Transplant Lymphoproliferative Disorder (PTLD) Unresponsive or Ineligible for Reduced Immunosuppression (RIS).

Abstract Background: PTLDs are typically B-cell neoplasms occurring as uncommon but serious complications of reduced T-cell immune surveillance associated with organ transplantation. RIS benefits only a subset of PTLD patients and cytotoxic therapy may be poorly tolerated. Therefore, in October 1998 we initiated a prospective study of rituximab in patients who failed or were unable to receive RIS and now report mature results. Methods: Patients with CD20+ PTLD were eligible if they had failed to completely respond to RIS or RIS was contraindicated and had Karnofsky performance status &gt;60, age 3–70 years (y), measurable disease, and no change in immunosuppression for at least 2 weeks and no cytotoxic therapy within 4 weeks. Rituximab was given as 375 mg/m2 weekly x 4 with disease evaluation at 1, 3, 6, 9, 12 and 18 months. Response data, survival curves, and the impact of clinical and pathological factors were evaluated. Results: 24 of 26 enrolled pt were eligible and evaluable. Median age was 42y with 5 &lt;17 y, 18 were male, and 14 progressed on RIS. Median time to PTLD from transplant was 47 months (m) (8 &lt;24 m). 17/22 were EBV+, 17 were large cell or Burkitt histology, and 10 PTLD occurred in the allograft site. Response rate was 63% (46 %CR, 17% PR) and CRs were durable (1/11 progressed). With median follow-up of 65 m (range 44–82), outcomes at 5 y are: overall survival 48%, freedom from progression 41% and failure-free survival 21%. 7 pt died without progression, yielding 5 y cause-specific survival of 69%. Nine of 13 pt with disease progression were successfully salvaged with second-line therapy. In univariate analysis PTLD characteristics did not significantly correlate with outcome but 2/2 Burkitt pt quickly progressed. Conclusions: Rituximab provided effective, durable treatment for ~40% of pt failing RIS in this series of mainly late PTLD and a majority of pt progressing after rituximab could be treated successfully. However, overall and failure-free survival reflect significant co-morbidity in this population.</jats:p

State of Arizona v. Guy James Goodman: On Petition for a Writ of Certiorari to the Arizona Supreme Court

Arizona’s pending certiorari petition in Arizona v. Goodman provides the Supreme Court with an opportunity to review the important issue of the circumstances under which the Constitution permits an accused sex offender to be denied bail pending trial. In 2002, Arizona voters amended their state constitution, rendering a defendant categorically ineligible for bail if “the proof is evident or the presumption great” that he committed sexual assault. In a narrowly divided opinion, the Arizona Supreme Court found that this measure unconstitutional. And yet the Court’s opinion makes clear that the Constitution does not prohibit denying bail to defendants who present (1) “a continuing danger to the community” or (2) “a risk of flight.” Nor does the Constitution prohibit categorically denying bail based on the nature of the charged offense. Indeed, thirty-four states categorically deny bail to persons charged with capital offenses, murder, specified sex offenses, or offenses punishable by life imprisonment. Review of the Arizona Supreme Court’s decision is needed to resolve the conflict between it and the Court’s precedent on an important issue of constitutional law that affects the criminal justice system, crime victims, and community safety in States across the Nation. The Court’s review is especially needed because of the serious implications for victims and their communities if the judgment below is permitted to stand. Given sex offenders’ high recidivism rates, and the life-altering harm suffered by their victims, Arizona’s legislature was entirely reasonable when it opted to categorically deny bail to sexual-assault defendants on the ground that sexual assault is an adequate proxy for future dangerousness - and to build in procedural protections that go above and beyond in ensuring due process. The Constitution does not prohibit States like Arizona and others from taking these steps to ensure sex offenders are brought to justice, victims are protected, and communities are safeguarded

Impact of Whole‐Body Radiation Dose on Response and Toxicity in Patients With Neuroblastoma After Therapy With 131I‐Metaiodobenzylguanidine (MIBG)

BACKGROUND:(131) I-metaiodobenzylguanidine ((131) I-MIBG) is a targeted radiopharmaceutical for patients with neuroblastoma. Despite its tumor-specific uptake, the treatment with (131) I-MIBG results in whole-body radiation exposure. Our aim was to correlate whole-body radiation dose (WBD) from (131) I-MIBG with tumor response, toxicities, and other clinical factors. METHODS:This retrospective cohort analysis included 213 patients with high-risk neuroblastoma treated with (131) I-MIBG at UCSF Benioff Children's Hospital between 1996 and 2015. WBD was determined from radiation exposure rate measurements. The relationship between WBD ordered tertiles and variables were analyzed using Cochran-Mantel-Haenszel test of trend, Kruskal-Wallis test, and one-way analysis of variance. Correlation between WBD and continuous variables was analyzed using Pearson correlation and Spearman rank correlation. RESULTS:WBD correlated with (131) I-MIBG administered activity, particularly with (131) I-MIBG per kilogram (P &lt; 0.001). Overall response rate did not differ significantly among the three tertiles of WBD. Correlation between response by relative Curie score and WBD was of borderline significance, with patients receiving a lower WBD showing greater reduction in osteomedullary metastases by Curie score (rs = 0.16, P = 0.049). There were no significant ordered trends among tertiles in any toxicity measures (grade 4 neutropenia, thrombocytopenia &lt; 20,000/μl, and grade &gt; 1 hypothyroidism). CONCLUSIONS:This study showed that (131) I-MIBG activity per kilogram correlates with WBD and suggests that activity per kilogram will predict WBD in most patients. Within the range of activities prescribed, there was no correlation between WBD and either response or toxicity. Future studies should evaluate tumor dosimetry, rather than just WBD, as a tool for predicting response following therapy with (131) I-MIBG