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

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

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

Fair Allocation of Scarce Therapies for Coronavirus Disease 2019 (COVID-19)

The US Food and Drug Administration (FDA) has issued emergency use authorizations (EUAs) for monoclonal antibodies (mAbs) for nonhospitalized patients with mild or moderate coronavirus disease 2019 (COVID-19) disease and for individuals exposed to COVID-19 as postexposure prophylaxis. EUAs for oral antiviral drugs have also been issued. Due to increased demand because of the Delta variant, the federal government resumed control over the supply and asked states to ration doses. As future variants (e.g., the Omicron variant) emerge, further rationing may be required. We identify relevant ethical principles (i.e., benefiting people and preventing harm, equal concern, and mitigating health inequities) and priority groups for access to therapies based on an integrated approach to population health and medical factors (eg, urgently scarce healthcare workers, persons in disadvantaged communities hard hit by COVID-19). Using priority categories to allocate scarce therapies effectively operationalizes important ethical values. This strategy is preferable to the current approach of categorical exclusion or inclusion rules based on vaccination, immunocompromised status, or older age, or the ad hoc consideration of clinical risk factors

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

Inhibition of the Phosphatidylinositol-3 Kinase Pathway Using Bimiralisib in Loss-of-Function NOTCH1-Mutant Head and Neck Cancer

BACKGROUND: PI3K/mTOR inhibition leads to apoptosis of NOTCH1-mutant head and neck squamous cell carcinoma (HNSCC) cells. We tested the efficacy of the PI3K/mTOR inhibitor bimiralisib in patients with NOTCH1-mutant HNSCC. METHODS: Patients with recurrent/metastatic NOTCH1-mutant HNSCC who had progressed during chemotherapy and immunotherapy received bimiralisib until unacceptable toxicity or progression. To assess whether NOTCH1 mutations can be detected in blood, we measured circulating tumor DNA (ctDNA). To assess activated NOTCH1 protein levels, we quantitated cleaved NOTCH1 (cl-NOTCH) by immunohistochemistry. RESULTS: Eight patients were treated, and 6 were evaluable for response. The objective response rate was 17%. For all 8 patients, median progression-free and overall survival was 5 and 7 months, respectively. Bimiralisib was well tolerated, with expected hyperglycemia. Pharmacokinetic values were consistent with published studies. NOTCH1 mutations were detected in 83.3% of ctDNA. Staining for tumor cl-NOTCH1 was negative. The trial closed early due to sponsor insolvency. CONCLUSION: Although the trial was small, outcomes with bimiralisib were better than the historical standard of care; Results will need to be confirmed in a larger trial. The lack of cl-NOTCH1 was consistent with loss-of-function mutations and validated our mutation function algorithm. The ability to detect NOTCH1 mutations in blood will help future studies

ExaFEL: extreme-scale real-time data processing for X-ray free electron laser science

ExaFEL is an HPC-capable X-ray Free Electron Laser (XFEL) data analysis software suite for both Serial Femtosecond Crystallography (SFX) and Single Particle Imaging (SPI) developed in collaboration with the Linac Coherent Lightsource (LCLS), Lawrence Berkeley National Laboratory (LBNL) and Los Alamos National Laboratory. ExaFEL supports real-time data analysis via a cross-facility workflow spanning LCLS and HPC centers such as NERSC and OLCF. Our work therefore constitutes initial path-finding for the US Department of Energy's (DOE) Integrated Research Infrastructure (IRI) program. We present the ExaFEL team's 7 years of experience in developing real-time XFEL data analysis software for the DOE's exascale supercomputers. We present our experiences and lessons learned with the Perlmutter and Frontier supercomputers. Furthermore we outline essential data center services (and the implications for institutional policy) required for real-time data analysis. Finally we summarize our software and performance engineering approaches and our experiences with NERSC's Perlmutter and OLCF's Frontier systems. This work is intended to be a practical blueprint for similar efforts in integrating exascale compute resources into other cross-facility workflows