In “Neither Ethical nor Prudent: Why Not to Choose Normothermic Regional Perfusion” Omelianchuk and colleagues offer an exceptionally clear and methodical critique of the ethical and legal permissibility of in situ normothermic regional perfusion (NRP). NRP involves, in part, the reperfusion of organs via extracorporeal membrane oxygenation (ECMO) after a declaration of death and the occlusion of the arteries supplying blood to the brain. The authors’ main conclusion is that NRP invalidates the declaration of (...) death via the standards set by the Uniform Determination of Death Act (which requires either permanent cessation of circulatory and respiratory functions or irreversible cessation of all brain functions for a determination of death) and thereby violates the Dead Donor Rule (DDR) (which, minimally, requires that organ recovery not be the cause of death). Their arguments for these points, however, are flawed. Most notably, this conclusion rests on mistaken assumptions about the role of circulation in both the UDDA and DDR. A close examination of the role of circulation in sustaining life shows that NRP is consistent with both the UDDA and the DDR. (shrink)

This letter responds to the article “Neither Ethical nor Prudent: Why Not to Choose Normothermic Regional Perfusion,” by Adam Omelianchuk et al., in the July‐August 2024 issue of the Hastings Center Report.

The interpretation of the dead donor rule (DDR) has been central to recent debates regarding normothermic regional perfusion with controlled donation after circulatory death (NRP-cDCD). Proponents...

Normothermic regional perfusion (NRP) is a relatively new approach to procuring organs for transplantation. After circulatory death is declared, perfusion is restored to either the thoracoabdominal organs (in TA-NRP) or abdominal organs alone (in A-NRP) using extracorporeal membrane oxygenation. Simultaneously, surgeons clamp the cerebral arteries, causing a fatal brain injury. Critics claim that clamping the arteries is the proximate cause of death in violation of the dead donor rule and that the procedure is therefore unethical. We (...) disagree. This account does not consider the myriad other factors that contribute to the death of the donor, including the presence of a fatal medical condition, the decision to withdraw life support, and the physician's actions in withdrawing life support and administering medication that may hasten death. Instead, we claim that physicians play a causative role in many of the events that lead to a patient's death and that these actions are often ethically and legally justified. We advance an “all things considered” view according to which TA-NRP may be considered ethically acceptable insofar as it avoids suffering and respects the wishes of the patient to improve the lives of others through organ donation. We conclude with a series of critical questions related to the practice of NRP and call for the development of national consensus on this issue in the United States. (shrink)

Thoracoabdominal normothermic regional perfusion (TA-NRP), a new method of controlled donation after circulatory death, seems to provide more and better organs for patients on organ transplant waiting lists compared to standard controlled donation after circulatory death. Despite its benefits, the ethical permissibility of TA-NRP is currently a highly debated issue. The recent statement published by the American College of Physicians (ACP) highlights the reasons for these debates. Critics’ main concern is that TA-NRP violates the Dead Donor Rule. (...) This paper presents an ethical analysis of the objections raised by the ACP against TA-NRP and argues that TA-NRP is not only morally permissible but also morally required where it is financially and technically feasible. To support this conclusion, the concepts of ‘resuscitation,’ ‘intention,’ ‘irreversibility,’ ‘permanence,’ ‘impossibility,’ and ‘respect’ in the context of TA-NRP are explored. Additionally, the ethical permissibility of this procedure is evaluated through the lenses of Utilitarianism, Kantianism, the core principles of bioethics, and the Doctrine of Double Effect. This ethical analysis demonstrates why the ACP’s objection lacks a solid moral foundation and conflates moral and legal considerations. This paper also argues that extra measures are needed to ensure the moral permissibility of TA-NRP, emphasizing the importance of informed consent, additional brain blood flow and activity monitoring, and a contingency plan to abort the organ procurement process if a sign of morally relevant brain activity is detected. (shrink)

Two of the lead articles in this issue examine the emerging practice of organ procurement by normothermic regional perfusion (NRP) in terms of whether or not these patients are “dead” at the time t...

In transplant medicine, the use of normothermic regional perfusion (NRP) in donation after circulatory determination of death raises ethical difficulties. NRP is objectionable because it restores the donor's circulation, thus invalidating a death declaration based on the permanent cessation of circulation. NRP's defenders respond with arguments that are tortuous and factually inaccurate and depend on introducing extraneous concepts into the law. However, results comparable to NRP's—more and higher‐quality organs and more efficient allocation—can be achieved by removing organs (...) from deceased donors and using normothermic machine perfusion (NMP) to support the organs outside the body, without jeopardizing confidence in transplantation's legal and ethical foundations. Given the controversy that NRP generates and the convoluted justifications made for it, we recommend a prudential approach we call “ethical parsimony,” which holds that, in the choice between competing means of achieving a result, the ethically simpler one is to be preferred. This approach makes clear that policy‐makers should favor NMP over NRP. (shrink)

The current issue of the American Journal of Bioethics illustrates the scope of disagreement among professionals about normothermic regional perfusion (NRP). A similar range of opinions has been de...

Normothermic Regional Perfusion, or NRP, is a method of donated organ reperfusion using cardiopulmonary bypass or a modified extracorporeal membrane oxygenation (ECMO) circuit after circulatory death while leaving organs in the dead donor’s corpse. Despite its potential, several key ethical issues remain unaddressed by this technology.

Donation after circulatory determination of death (DCDD) is an accepted practice in the United States, but heart procurement under these circumstances has been debated. Although the practice is experiencing a resurgence due to the recently completed trials using ex vivo perfusion systems, interest in thoracoabdominal normothermic regional perfusion (TA-NRP), wherein the organs are reanimated in situ prior to procurement, has raised many ethical questions. We outline practical, ethical, and equity considerations to ensure transplant programs make well-informed (...) decisions about TA-NRP. We present a multidisciplinary analysis of the relevant ethical issues arising from DCDD-NRP heart procurement, including application of the Dead Donor Rule and the Uniform Definition of Death Act, and provide recommendations to facilitate ethical analysis and input from all interested parties. We also recommend informed consent, as distinct from typical “authorization,” for cadaveric organ donation using TA-NRP. (shrink)

The implementation of the thoracoabdominal normothermic regional perfusion in organ donation after circulatory determination of death (TANRP-DCDD) protocol is garnering increasing attention and pre...

An adult university hospital ethics committee evaluated a proposed TA-NRP protocol in the fall of 2018. The protocol raised ethical concerns about violation of the Uniform Determination of Death Act and the prohibition known as the Dead Donor Rule, with potential resultant legal consequences. An additional concern was the potential for increased mistrust by the community of organ donation and transplantation. The ethics committee evaluated the responses to these concerns as unable to surmount the ethical and legal boundaries and the (...) ethics committee declined to endorse the procedure. These concerns endure. (shrink)

At the conclusion of their 1968 report, the Harvard Ad Hoc Committee argued that “responsible medical opinion” was ready to accept severe and permanent neurologic injury as a new criterion for deat...

Why is there still debate about definitions of death in medicine and bioethics? Is it because of existential uncertainty and philosophical curiosity about when a person has died so the person’s dea...

Old habits die hard; so, it seems, do old arguments. Proponents of thoracoabdominal normothermic regional perfusion (TA-NRP, but more commonly referred to as NRP) continue to proffer arguments and...

The introduction of normothermic regional perfusion (NRP) in controlled donation after circulatory determination of death (cDCDD) protocols is by some regarded as controversial and ethically troublesome. One of the main concerns that opponents have about introducing NRP in cDCDD protocols is that reestablishing circulation will negate the determination of death by circulatory criteria, potentially resuscitating the donor. In this article, I argue that this is not the case. If we take a closer look at the concept of (...) death underlying the circulatory criterion for determination of death, we find that the purpose of the criterion is to show whether the organism as a whole has died. I argue that this purpose is fulfilled by the circulatory criterion in cDCDD protocols, and that applying NRP does not negate the determination of death or resuscitate the donor. (shrink)

Normothermic Regional Perfusion (NRP) is increasingly being adopted as an intervention designed to improve organ utilization from donors after circulatory death because of the efficiency with which...

Does normothermic regional perfusion (NRP) resurrect the dead? That was the question I asked in one of the target articles published in the special issue of The American Journal of Bioethics (AJOB)...

Use of normothermic regional perfusion (NRP) for organ recovery in donation after circulatory death (DCD) raises two crucial, and intertwined, ethical questions. The first is whether the use of NRP...

The articles by Bernat, Busch, Dudzinski et al., and Derse illustrate the difficulties with reconciling normothermic regional perfusion (NRP) with the dead donor rule (DDR) (Bernat forthcoming; Busch forthcoming; Dudzinski et al. forthcoming; Derse forthcoming). I appreciate their arguments because they help illuminate the issues that generate a dilemma: either reject NRP or the DDR. I am convinced that the dilemma is unavoidable because the procurement team is involved with determining and securing the death of the donor (...) when circulation restarts. Evidence for this is found in the reasons and recommendations given for blocking blood flow to the brain, both of which betray a lack of certainty over the donor’s vital status. The surgical activity in NRP therefore conflicts with the values the DDR protects: respect for the donor’s life and avoidance of conflict of interest. (shrink)

While much of the debate around the practice of normothermic regional perfusion (NRP) is focused on the potential violation of the dead donor rule (DDR), another concern is whether allowing this pr...

Other than the ligation of the aortic arch vessels, extracorporeal cardiopulmonary resuscitation (ECPR) and thoraco-abdominal normothermic regional ­perfusion (TA-NRP) in donation after circulatory...

Nielsen Busch and Mjaaland argue that controlled donation after circulatory death (DCD), and normothermic regional perfusion (NRP) do not violate the dead donor rule (DDR) (Nielsen Busch and Mjaala...

Organ donation after the circulatory determination of death requires the permanent cessation of circulation while organ donation after the brain determination of death requires the irreversible cessation of brain functions. The unified brain-based determination of death connects the brain and circulatory death criteria for circulatory death determination in organ donation as follows: permanent cessation of systemic circulation causes permanent cessation of brain circulation which causes permanent cessation of brain perfusion which causes permanent cessation of brain function. The relevant circulation (...) that must cease in circulatory death determination is that to the brain. Eliminating brain circulation from the donor ECMO organ perfusion circuit in thoracoabdominal NRP protocols satisfies the unified brain-based determination of death but only if the complete cessation of brain circulation can be proved. Despite its medical and physiologic rationale, the unified brain-based determination of death remains inconsistent with the Uniform Determination of Death Act. (shrink)

Background: Ethical frameworks for organ donation following circulatory death (DCD) were established >20 years ago. However, considerable variation exists among these, indicating consensus has not been reached on all issues. Additionally, advances such as cardiac DCD transplants and normothermic regional perfusion (NRP) may have reignited old debates.Methods: We reviewed the English-language literature addressing ethical issues in DCD from 1993 to 2022, examining changes in frequency with which ethical principles and their sub-themes identified within each, were addressed.Results: Non-maleficence (...) was the most frequently addressed principle (192 of 199 articles), as well as the most varied, with 9 subthemes (versus 2-4 within each of the other bioethical principles).Conclusions: There were several changes in the terminology used to refer to DCD over time, and substantial interest in cardiac DCD and NRP in recent publications, arising in 11 and 19 of the 30 publications from 2018 to 2022. (shrink)

This letter responds to letters by Garson Leder and by Harrison Lee in the same issue, September‐October 2024, of the Hastings Center Report.

The present study examined deep gray matter perfusion in neonates with congenital heart disease (CHD) with arterial spin labeling magnetic resonance imaging preoperatively. We found that neonates with cyanotic CHD showed lower right thalamus compared with controls and lower right basal ganglia perfusion compared with acyanotic CHD. When the CHD group was assessed as a whole, it showed slightly decreased left thalamus perfusion compared with controls. The results suggest that cardiac physiology plays a crucial part in changes (...) in regional cerebral perfusion. Perfusion with arterial spin labeling may be a useful marker of high risk for impaired cerebral blood flow auto-regulation and cerebral hypoperfusion in neonates with CHD. (shrink)

Computerized relaxation training has been suggested as an effective and easily accessible intervention for individuals with psychological distress. To better elucidate the neural mechanism that underpins the effects of relaxation training, we investigated whether a 10-session computerized relaxation training program changed prefrontal gamma-aminobutyric acid levels and cerebral blood flow in women with psychological distress. We specifically focused on women since they were reported to be more vulnerable to develop stress-related disorders than men. Nineteen women with psychological distress but without a (...) diagnosis of psychiatric disorders received the 10-day computerized relaxation training program that consisted of 30-min cognitive-relaxation training and 10-min breathing-relaxation training per day. At baseline and post-intervention, perceived stress levels, anxiety, fatigue, and sleep quality were assessed by self-report questionnaires. Brain magnetic resonance spectroscopy and arterial spin labeling scans were also performed before and after the intervention to evaluate GABA levels and relative CBF in the prefrontal region. Levels of perceived stress, anxiety, fatigue, and sleep quality improved following 10 sessions of computerized relaxation training, resulting in a significant relief in composite scores of stress-related symptoms. The prefrontal GABA levels decreased, while relative CBF increased after the intervention. In addition, a greater increase in relative prefrontal CBF was associated with better composite scores of stress-related symptoms following the intervention. The current findings suggest that computerized relaxation training may improve stress-related symptoms through modulating the prefrontal GABA levels and CBF in women with psychological distress. (shrink)

Background: There is increasing evidence to support the efficacy of transcranial direct current stimulation applications in cognitive augmentation and rehabilitation. Neuromodulation achieved with tDCS may further regulate regional cerebral perfusion affiliated through the neurovascular unit; however, components of cerebral perfusion decrease across aging. A novel neuroimaging approach, functional near-infrared spectroscopy, can aid in quantifying these regional perfusional changes. To date, the interaction of the effects of tDCS on cognitive performance across the lifespan and obtained fNIRS hemodynamic (...) responses remain unknown.Objective: This review aims to examine the effects of tDCS on cognitive performance and fNIRS hemodynamic responses within the context of cognitive aging.Methods: Six databases were searched for studies. Quality appraisal and data extraction were conducted by two independent reviewers. Meta-analysis was carried out to determine overall and subgroup effect sizes.Results: Eight studies met inclusion criteria. The overall effect size demonstrates that tDCS can alter cognitive performance and fNIRS signals, with aging being a potential intermediary in tDCS efficacy.Conclusion: From the studies included, the effects of tDCS on cognitive performance and fNIRS metrics are most prominent in young healthy adults and appear to become less robust with increasing age. Given the small number of studies included in this review further investigation is recommended. (shrink)

In this paper we discuss the interaction between science policies (and particularly in the area of scientific research) and higher education policies in Gulf and Mediterranean Arab countries. Our analysis reveals a discrepancy between the two sub-regions with respect to integration in the global market, cooperation in scientific research and international mobility of students. The paper discusses the implications of the analysis of reform policies and higher education restructuring.

Some patients who have been diagnosed as “dead by neurologic criteria” continue to exhibit certain brain functions, most commonly, neuroendocrine functions. This preservation of neurologic function after the diagnosis of “brain death” or “brainstem death” is an ongoing source of controversy and concern in the medical, bioethics, and legal literatures. Most obviously, if some brain function persists, then it is not the case that all functions of the entire brain have ceased and hence, declaring such a patient to be “dead” (...) would be a false positive, in any nation with so-called “whole brain death” laws. Furthermore, and perhaps more concerning, the preservation of any brain function necessarily entails the preservation of some amount of brain perfusion, thereby raising the concern as to whether additional areas of neural tissue may remain viable, including areas in the brainstem. These and other considerations cast significant doubt on the reliability of diagnosing either “brain death” or “brainstem death.”. (shrink)

This paper describes the research carried out into small and medium enterprises (SMEs) and corporate responsibility (CR) in the Northwest of England during Phase I of Responsibility Northwest, a partnership programme designed to significantly increase the CR of the region. By engaging with significant numbers of SMEs and SME support providers across the region, key insights were gained in three key areas: • The current attitudes to, understanding of, and management of CR issues in the SME sector.• The barriers to (...) greater implementation of CR management.• The opportunities for overcoming the barriers and improving regional CR. The research revealed a large diversity both in terms of understanding of the issues and their management. Seven key barriers to improve CR performance were identified which centred round the inappropriateness and inaccessibility of current CR approaches and support services on CR, certain characteristics of SMEs which tend to reduce their interest and opportunities for engaging in CR activities and supply-chain barriers. Fortunately there was significant agreement on the mechanisms which should be used to overcome these barriers, in particular the importance of delivering CR support through existing business networks that are valued and trusted by SMEs. These results have been used to create the partnership programme, Responsibility Northwest Phase II that runs until 2008 and aims to significantly increase the overall CR of Northwest England. (shrink)

The Region Connection Calculus (RCC) is a qualitative spatial reasoning formalism, developed in knowledge representation and geographical information systems. We argue that RCC can be viewed as a more fine-grained approach to the use of Euler diagrams to visualize categorical statements like ‘all A are B’. We present RCC using the syntax of first-order modal logic and a topological semantics. We compare the Gergonne relations (a well-known set of 5 jointly exhaustive and pairwise disjoint relations between two non-empty sets, visualized (...) using Euler-type diagrams) with RCC8 (a similar set of 8 relations for regions). (shrink)

There are at least two passages in the jamesian corpus where he seems to establish a topology of "regional ontologies", or to set up multiple "language games". the first of these is "the principles of psychology" when he talks about "the many worlds", or "...sub-universes commonly discriminated from each other...", the second is in "pragmatism", where he notes that there "are...at least three well-characterized levels, stages, or types of thought about the world we live in..." two questions immediately come (...) to mind about these levels. first, is each of these areas of equal importance, epistemologically and ontologically speaking? second, how, if at all, are these regional areas related to each other? each of these questions has a seemingly obvious answer. to wit, the world of perception is more important than any of the other areas; and second, the regional areas are related in terms of the disjunctive and conjunctive transitions which james so strenuously upholds, resulting in an overall "concatenated" picture. i argue that both of these responses are insufficient, and that the issue is more complicated than it first appears. (edited). (shrink)

A topological description of space is given, based on the relation of connection among regions and the property of being limited. A minimal set of 10 constraints is shown to permit definitions of points and of open and closed sets of points and to be characteristic of locally compact T2 spaces. The effect of adding further constraints is investigated, especially those that characterise continua. Finally, the properties of mappings in region-based topology are studied. Not all such mappings correspond to point (...) functions and those that do correspond to continuous functions. (shrink)

The paper considers the role of universities as actors in regional development, and the implications for approaches to knowledge, including knowledge construction. The new role for universities requires the production of knowledge, which relates to the needs of the region. Particular attention was given to the Agder region of Norway, and Agder University College.

In-vivo phenotyping of genetically engineered mouse models for amyotrophic lateral sclerosis is established by combining BT-MRI and CASL G. Vanhoutte1, E. Storkebaum2, P. Carmeliet2, A. Van der Linden1.

Se realizó una revisión bibliográfica con el objetivo de sistematizar los principales postulados existentes respecto a la Historia Regional como disciplina y su relación con la asignatura Historia de Cuba. La información aportada se procesó según los métodos científicos de análisis y síntesis e histórico lógico. Ello incluyó la interpretación de los criterios vertidos por especialistas que permiten considerar a Camagüey como una región histórica, en estrecho vínculo con las condiciones en las que se imparte la Historia de Cuba (...) en la Universidad de Ciencias Médicas de Camagüey, en la que la escasez de bibliografía sobre este tópico en particular influye sobre el estudio de la asignatura. Ello recalca la necesidad de desarrollar investigaciones de este tipo, con el propósito de que dichos estudios puedan ser empleados como materiales de apoyo a la docencia. A literature review was made in order to systematize the existing main postulates regarding Regional History as a discipline and its relationship with the subject History of Cuba. The information provided was processed according to scientific methods of analysis. synthesis and historico-logical. This included the interpretation of the criteria stated by specialists that allow to consider Camag|ey as a historical region, in close liaison with the conditions in which the history of Cuba is taught at the University of Medical Sciences in Camaguey, where the lack of literature on this topic particularly influences on the study of the subject. This underscores the need to develop research of this type, so these studies can be used as support for teaching materials. (shrink)