Experimental Execution

On July 23, 2014, an execution in Arizona lasted nearly two hours, with the inmate struggling to breathe and gasping over 600 times, according to a local reporter witnessing the execution. This was the third example of a botched execution in seven months. The Supreme Court last evaluated the constitutionality of execution by lethal injection in 2008, but did not provide a clear standard for evaluating risks. Since that time, the lethal injection landscape has transformed. States are using entirely new drugs and drug combinations, and sometimes obtain these drugs from questionable sources, making it hard to predict what will happen in any given execution. The Court has now granted certiorari to examine the constitutionality of Oklahoma’s lethal injection protocol in the case of Glossip v. Gross. Although it is increasingly common to refer to lethal injection executions as experimental, this Article is the first to conduct a rigorous analysis of whether and to what extent executions by lethal injection involve the conduct of research and therefore should be analyzed under the ethical and regulatory framework that governs biomedical research. I argue that an important factor driving this high error rate is that the use of novel drugs, drug combinations, and dosages in lethal injection executions is a type of research. More specifically, it is poorly designed experimentation that is not based on evidence. If the death penalty is justified, individual inmates are being exposed to uncertain (and sometimes unnecessary) risks in order to obtain benefits for others by furthering the underlying aims of capital punishment. This insight suggests three important conclusions. First, states should draw from existing scholarship on ethics and regulations that apply to biomedical research with captive and vulnerable populations. Prisoners are considered a vulnerable population, and experimental executions involving prisoners should abide by the general principles that are applicable to research: respect for autonomy, non-maleficence, and justice. Second, legal safeguards that follow from these principles should be applied to executions—in particular, states should ask for informed consent from prisoners to modifications of lethal injection protocols, obtain independent review by a regulatory body like the Food and Drug Administration, and apply a standard requiring risk minimization in the choice of drugs and procedures. Finally, states should systematically gather data as they engage in experimental execution

Piercing the Veil: The Limits of Brain Death as a Legal Fiction

Brain death is different from the traditional, biological conception of death. Although there is no possibility of a meaningful recovery, considerable scientific evidence shows that neurological and other functions persist in patients accurately diagnosed as brain dead. Elsewhere with others, I have argued that brain death should be understood as an unacknowledged status legal fiction. A legal fiction arises when the law treats something as true, though it is known to be false or not known to be true, for a particular legal purpose (like the fiction that corporations are persons). Moving towards greater transparency, it is legally and ethically justifiable to use this fiction to determine when to permit treatment withdrawal and organ transplantation. However, persistent controversy and recent conflicts between hospitals and families over the treatment of brain-dead patients demonstrate the need for clearer limits on the legal fiction of brain death. This Article argues that more people should recognize that brain death is a legal fiction and further contends that existing scholarship has inadequately addressed the appropriate use of the legal fiction of brain death in legal conflicts. For instance, as in Jahi McMath’s case (in which a mother wanted to keep her daughter on a ventilator after she was determined brain dead), families may distrust physicians and hospitals who fail to acknowledge that brain death is a legal fiction. Legislators in most states have ignored the need to permit statutory exceptions for individuals with strong sanctity of life views. When hospitals treat braindead pregnant women, as in Marlise Mu˜ noz’s case, courts have failed to weigh the fundamental constitutional rights of pregnant women against the state’s interests. Finally, judges and legislators should sometimes “pierce the veil” of brain death and should not use the legal fiction in cases involving: (1) religious and moral objections, (2) insurance reimbursement for extended care of brain-dead patients, (3) maintenance of pregnant, brain-dead women, and (4) biomedical research. The Article concludes with general guidance for judges, legislators, and other legal actors to use regarding legal fictions

From a Constitutional Right to a Policy of Exceptions: Abigail Alliance and the Future of Access to Experimental Therapy

Although there has been considerable attention to the plight of terminally ill patients with highly sympathetic constitutional and contractual claims that they should be permitted access to unapproved drugs, courts have been appropriately reluctant to grant such claims. Congress and administrative agencies have the requisite institutional competence to decide complex policy issues related to science and health care such as those involved in establishing an expanded access program. Congress and FDA should allow only limited access to unapproved therapies because there are significant concerns about the safety and efficacy of unapproved drugs. Moreover, many of the proposals to widen access may cause delays to the approval process and increased health care costs that are unlikely to be borne in our current climate. Accordingly, we propose limiting access outside of clinical trials, but expanding eligibility for clinical trials in order to ensure that people receive access in a controlled and systematic manner

Diffuse neonatal hemangiomatosis presenting as congestive cardiac failure - A case report

Infantile hepatic hemangioma has substantial arteriovenous shunting which may lead to cardiovascular compromise and hydrops fetalis. It may present as hepatomegaly since the entire liver is involved in most cases. As mortality is very high, a high index of suspicion is required to make a diagnosis and common complications arising out it, especially in the presence of cutaneous hemangioma. We present a 2-month-old baby born at term presented with features suggestive of sepsis with multiple cutaneous hemangiomas, and on evaluation, there was congestive cardiac failure, which was initially thought of cardiac origin but subsequently came out to be arteriovenous shunting of blood in liver

High density linkage mapping of genomic and transcriptomic SNPs for synteny analysis and anchoring the genome sequence of chickpea

This study presents genome-wide discovery of SNPs through next generation sequencing of the genome of Cicer reticulatum. Mapping of the C. reticulatum sequenced reads onto the draft genome assembly of C. arietinum (desi chickpea) resulted in identification of 842,104 genomic SNPs which were utilized along with an additional 36,446 genic SNPs identified from transcriptome sequences of the aforementioned varieties. Two new chickpea Oligo Pool All (OPAs) each having 3,072 SNPs were designed and utilized for SNP genotyping of 129 Recombinant Inbred Lines (RILs). Using Illumina GoldenGate Technology genotyping data of 5,041 SNPs were generated and combined with the 1,673 marker data from previously published studies, to generate a high resolution linkage map. The map comprised of 6698 markers distributed on eight linkage groups spanning 1083.93 cM with an average inter-marker distance of 0.16 cM. Utility of the present map was demonstrated for improving the anchoring of the earlier reported draft genome sequence of desi chickpea by ~30% and that of kabuli chickpea by 18%. The genetic map reported in this study represents the most dense linkage map of chickpea , with the potential to facilitate efficient anchoring of the draft genome sequences of desi as well as kabuli chickpea varieties

How penalizing substance use in pregnancy affects treatment and research: A qualitative examination of researchers\u27 perspectives

INTRODUCTION: Laws regulating substance use in pregnancy are changing and may have unintended consequences on scientific efforts to address the opioid epidemic. Yet, how these laws affect care and research is poorly understood. METHODS: We conducted semi-structured qualitative interviews using purposive and snowball sampling of researchers who have engaged pregnant people experiencing substance use. We explored views on laws governing substance use in pregnancy and legal reform possibilities. Interviews were double coded. Data were examined using thematic analysis. RESULTS: We interviewed 22 researchers (response rate: 71 per cent) and identified four themes: (i) harms of punitive laws, (ii) negative legal impacts on research, (iii) proposals for legal reform, and (iv) activism over time. DISCUSSION: Researchers view laws penalizing substance use during pregnancy as failing to treat addiction as a disease and harming pregnant people and families. Respondents routinely made scientific compromises to protect participants. While some have successfully advocated for legal reform, ongoing advocacy is needed. CONCLUSION: Adverse impacts from criminalizing substance use during pregnancy extend to research on this common and stigmatized problem. Rather than penalizing substance use in pregnancy, laws should approach addiction as a medical issue and support scientific efforts to improve outcomes for affected families

Parental Factors Associated With the Decision to Participate in a Neonatal Clinical Trial

Importance: It remains poorly understood how parents decide whether to enroll a child in a neonatal clinical trial. This is particularly true for parents from racial or ethnic minority populations. Understanding factors associated with enrollment decisions may improve recruitment processes for families, increase enrollment rates, and decrease disparities in research participation. Objective: To assess differences in parental factors between parents who enrolled their infant and those who declined enrollment for a neonatal randomized clinical trial. Design, setting, and participants: This survey study conducted from July 2017 to October 2019 in 12 US level 3 and 4 neonatal intensive care units included parents of infants who enrolled in the High-dose Erythropoietin for Asphyxia and Encephalopathy (HEAL) trial or who were eligible but declined enrollment. Data were analyzed October 2019 through July 2020. Exposure: Parental choice of enrollment in neonatal clinical trial. Main outcomes and measures: Percentages and odds ratios (ORs) of parent participation as categorized by demographic characteristics, self-assessment of child's medical condition, study comprehension, and trust in medical researchers. Survey questions were based on the hypothesis that parents who enrolled their infant in HEAL differ from those who declined enrollment across 4 categories: (1) infant characteristics and parental demographic characteristics, (2) perception of infant's illness, (3) study comprehension, and (4) trust in clinicians and researchers. Results: Of a total 387 eligible parents, 269 (69.5%) completed the survey and were included in analysis. This included 183 of 242 (75.6%) of HEAL-enrolled and 86 of 145 (59.3%) of HEAL-declined parents. Parents who enrolled their infant had lower rates of Medicaid participation (74 [41.1%] vs 47 [55.3%]; P = .04) and higher rates of annual income greater than $55 000 (94 [52.8%] vs 30 [37.5%]; P = .03) compared with those who declined. Black parents had lower enrollment rates compared with White parents (OR, 0.35; 95% CI, 0.17-0.73). Parents who reported their infant's medical condition as more serious had higher enrollment rates (OR, 5.7; 95% CI, 2.0-16.3). Parents who enrolled their infant reported higher trust in medical researchers compared with parents who declined (mean [SD] difference, 5.3 [0.3-10.3]). There was no association between study comprehension and enrollment. Conclusions and relevance: In this study, the following factors were associated with neonatal clinical trial enrollment: demographic characteristics (ie, race/ethnicity, Medicaid status, and reported income), perception of illness, and trust in medical researchers. Future work to confirm these findings and explore the reasons behind them may lead to strategies for better engaging underrepresented groups in neonatal clinical research to reduce enrollment disparities

Reporting trends, practices, and resource utilization in neuroendocrine tumors of the prostate gland: a survey among thirty-nine genitourinary pathologists

Background: Neuroendocrine differentiation in the prostate gland ranges from clinically insignificant neuroendocrine differentiation detected with markers in an otherwise conventional prostatic adenocarcinoma to a lethal high-grade small/large cell neuroendocrine carcinoma. The concept of neuroendocrine differentiation in prostatic adenocarcinoma has gained considerable importance due to its prognostic and therapeutic ramifications and pathologists play a pivotal role in its recognition. However, its awareness, reporting, and resource utilization practice patterns among pathologists are largely unknown. Methods: Representative examples of different spectrums of neuroendocrine differentiation along with a detailed questionnaire were shared among 39 urologic pathologists using the survey monkey software. Participants were specifically questioned about the use and awareness of the 2016 WHO classification of neuroendocrine tumors of the prostate, understanding of the clinical significance of each entity, and use of different immunohistochemical (IHC) markers. De-identified respondent data were analyzed. Results: A vast majority (90%) of the participants utilize IHC markers to confirm the diagnosis of small cell neuroendocrine carcinoma. A majority (87%) of the respondents were in agreement regarding the utilization of type of IHC markers for small cell neuroendocrine carcinoma for which 85% of the pathologists agreed that determination of the site of origin of a high-grade neuroendocrine carcinoma is not critical, as these are treated similarly. In the setting of mixed carcinomas, 62% of respondents indicated that they provide quantification and grading of the acinar component. There were varied responses regarding the prognostic implication of focal neuroendocrine cells in an otherwise conventional acinar adenocarcinoma and for Paneth cell-like differentiation. The classification of large cell neuroendocrine carcinoma was highly varied, with only 38% agreement in the illustrated case. Finally, despite the recommendation not to perform neuroendocrine markers in the absence of morphologic evidence of neuroendocrine differentiation, 62% would routinely utilize IHC in the work-up of a Gleason score 5 + 5 = 10 acinar adenocarcinoma and its differentiation from high-grade neuroendocrine carcinoma. Conclusion: There is a disparity in the practice utilization patterns among the urologic pathologists with regard to diagnosing high-grade neuroendocrine carcinoma and in understanding the clinical significance of focal neuroendocrine cells in an otherwise conventional acinar adenocarcinoma and Paneth cell-like neuroendocrine differentiation. There seems to have a trend towards overutilization of IHC to determine neuroendocrine differentiation in the absence of neuroendocrine features on morphology. The survey results suggest a need for further refinement and development of standardized guidelines for the classification and reporting of neuroendocrine differentiation in the prostate gland

Combination of searches for heavy spin-1 resonances using 139 fb−1 of proton-proton collision data at s = 13 TeV with the ATLAS detector

A combination of searches for new heavy spin-1 resonances decaying into different pairings of W, Z, or Higgs bosons, as well as directly into leptons or quarks, is presented. The data sample used corresponds to 139 fb−1 of proton-proton collisions at = 13 TeV collected during 2015–2018 with the ATLAS detector at the CERN Large Hadron Collider. Analyses selecting quark pairs (qq, bb, , and tb) or third-generation leptons (τν and ττ) are included in this kind of combination for the first time. A simplified model predicting a spin-1 heavy vector-boson triplet is used. Cross-section limits are set at the 95% confidence level and are compared with predictions for the benchmark model. These limits are also expressed in terms of constraints on couplings of the heavy vector-boson triplet to quarks, leptons, and the Higgs boson. The complementarity of the various analyses increases the sensitivity to new physics, and the resulting constraints are stronger than those from any individual analysis considered. The data exclude a heavy vector-boson triplet with mass below 5.8 TeV in a weakly coupled scenario, below 4.4 TeV in a strongly coupled scenario, and up to 1.5 TeV in the case of production via vector-boson fusion