Inequality aversion predicts support for public and private redistribution.

Rising inequality has brought redistribution back on the political agenda. In theory, inequality aversion drives people's support for redistribution. People can dislike both advantageous inequality (comparison relative to those worse off) and disadvantageous inequality (comparison relative to those better off). Existing experimental evidence reveals substantial variation across people in these preferences. However, evidence is scarce on the broader role of these two distinct forms of inequality aversion for redistribution in society. We provide evidence by exploiting a unique combination of data. We use an incentivized experiment to measure inequality aversion in a large population sample (≈9,000 among 20- to 64-y-old Danes). We link the elicited inequality aversion to survey information on individuals' support for public redistribution (policies that reduce income differences) and administrative records revealing their private redistribution (real-life donations to charity). In addition, the link to administrative data enables us to include a large battery of controls in the empirical analysis. Theory predicts that support for public redistribution increases with both types of inequality aversion, while private redistribution should increase with advantageous inequality aversion, but decrease with disadvantageous inequality aversion. A strong dislike for disadvantageous inequality makes people willing to sacrifice own income to reduce the income of people who are better off, thereby reducing the distance to people with more income than themselves. Public redistribution schemes achieve this but private donations to charity do not. Our empirical results provide strong support for these predictions and with quantitatively large effects compared to other predictors.

Mutation enhances cooperation in direct reciprocity.

Direct reciprocity is a powerful mechanism for the evolution of cooperation based on repeated interactions between the same individuals. But high levels of cooperation evolve only if the benefit-to-cost ratio exceeds a certain threshold that depends on memory length. For the best-explored case of one-round memory, that threshold is two. Here, we report that intermediate mutation rates lead to high levels of cooperation, even if the benefit-to-cost ratio is only marginally above one, and even if individuals only use a minimum of past information. This surprising observation is caused by two effects. First, mutation generates diversity which undermines the evolutionary stability of defectors. Second, mutation leads to diverse communities of cooperators that are more resilient than homogeneous ones. This finding is relevant because many real-world opportunities for cooperation have small benefit-to-cost ratios, which are between one and two, and we describe how direct reciprocity can attain cooperation in such settings. Our result can be interpreted as showing that diversity, rather than uniformity, promotes evolution of cooperation.

Air-ventilated normothermic mechanical perfusion improves susceptibility to donation after circulatory death and cold preservation-induced cholestatic liver injury through PPAR-γ/UGT1A1 axis.

End-ischemic normothermic mechanical perfusion (NMP) could provide a curative treatment to reduce cholestatic liver injury from donation after circulatory death (DCD) in donors. However, the underlying mechanism remains elusive. Our previous study demonstrated that air-ventilated NMP could improve functional recovery of DCD in a preclinical NMP rat model. Here, metabolomics analysis revealed that air-ventilated NMP alleviated DCD- and cold preservation-induced cholestatic liver injury, as shown by the elevated release of alanine aminotransferase (ALT), aspartate aminotransferase (AST), bilirubin, and γ-glutamyl transferase (GGT) in the perfusate (p < .05) and the reduction in the levels of bile acid metabolites, including ω-muricholic acid, glycohyodeoxycholic acid, glycocholic acid, and glycochenodeoxycholate (GCDC) in the perfused livers (p < .05). In addition, the expression of the key bile acid metabolism enzyme UDP-glucuronosyltransferase 1A1 (UGT1A1), which is predominantly expressed in hepatocytes, was substantially elevated in the DCD rat liver, followed by air-ventilated NMP (p < .05), and in vitro, this increase was induced by decreased GCDC and hypoxia-reoxygenation in the hepatic cells HepG2 and L02 (p < .05). Knockdown of UGT1A1 in hepatic cells by siRNA aggravated hepatic injury caused by GCDC and hypoxia-reoxygenation, as indicated by the ALT and AST levels in the supernatant. Mechanistically, UGT1A1 is transcriptionally regulated by peroxisome proliferator-activator receptor-γ (PPAR-γ) under hypoxia-physoxia. Taken together, our data revealed that air-ventilated NMP could alleviate DCD- and cold preservation-induced cholestatic liver injury through PPAR-γ/UGT1A1 axis. Based on the results from this study, air-ventilated NMP confers a promising approach for predicting and alleviating cholestatic liver injury through PPAR-γ/UGT1A1 axis.

Research autopsy programmes in oncology: shared experience from 14 centres across the world.

While there is a great clinical need to understand the biology of metastatic cancer in order to treat it more effectively, research is hampered by limited sample availability. Research autopsy programmes can crucially advance the field through synchronous, extensive, and high-volume sample collection. However, it remains an underused strategy in translational research. Via an extensive questionnaire, we collected information on the study design, enrolment strategy, study conduct, sample and data management, and challenges and opportunities of research autopsy programmes in oncology worldwide. Fourteen programmes participated in this study. Eight programmes operated 24 h/7 days, resulting in a lower median postmortem interval (time between death and start of the autopsy, 4 h) compared with those operating during working hours (9 h). Most programmes (n = 10) succeeded in collecting all samples within a median of 12 h after death. A large number of tumour sites were sampled during each autopsy (median 15.5 per patient). The median number of samples collected per patient was 58, including different processing methods for tumour samples but also non-tumour tissues and liquid biopsies. Unique biological insights derived from these samples included metastatic progression, treatment resistance, disease heterogeneity, tumour dormancy, interactions with the tumour micro-environment, and tumour representation in liquid biopsies. Tumour patient-derived xenograft (PDX) or organoid (PDO) models were additionally established, allowing for drug discovery and treatment sensitivity assays. Apart from the opportunities and achievements, we also present the challenges related with postmortem sample collections and strategies to overcome them, based on the shared experience of these 14 programmes. Through this work, we hope to increase the transparency of postmortem tissue donation, to encourage and aid the creation of new programmes, and to foster collaborations on these unique sample collections. © 2024 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.

Dual electronic effects achieving a high-performance Ni(II) pincer catalyst for CO2 photoreduction in a noble-metal-free system.

A carbazolide-bis(NHC) NiII catalyst (1; NHC, N-heterocyclic carbene) for selective CO2 photoreduction was designed herein by a one-stone-two-birds strategy. The extended π-conjugation and the strong σ/π electron-donation characteristics (two birds) of the carbazolide fragment (one stone) lead to significantly enhanced activity for photoreduction of CO2 to CO. The turnover number (TON) and turnover frequency (TOF) of 1 were ninefold and eightfold higher than those of the reported pyridinol-bis(NHC) NiII complex at the same catalyst concentration using an identical Ir photosensitizer, respectively, with a selectivity of ∼100%. More importantly, an organic dye was applied to displace the Ir photosensitizer to develop a noble-metal-free photocatalytic system, which maintained excellent performance and obtained an outstanding quantum yield of 11.2%. Detailed investigations combining experimental and computational studies revealed the catalytic mechanism, which highlights the potential of the one-stone-two-birds effect.

Angiogenic activity of mitochondria; beyond the sole bioenergetic organelle.

Angiogenesis is a complex process that involves the expansion of the pre-existing vascular plexus to enhance oxygen and nutrient delivery and is stimulated by various factors, including hypoxia. Since the process of angiogenesis requires a lot of energy, mitochondria play an important role in regulating and promoting this phenomenon. Besides their roles as an oxidative metabolism base, mitochondria are potential bioenergetics organelles to maintain cellular homeostasis via sensing alteration in oxygen levels. Under hypoxic conditions, mitochondria can regulate angiogenesis through different factors. It has been indicated that unidirectional and bidirectional exchange of mitochondria or their related byproducts between the cells is orchestrated via different intercellular mechanisms such as tunneling nanotubes, extracellular vesicles, and gap junctions to maintain the cell homeostasis. Even though, the transfer of mitochondria is one possible mechanism by which cells can promote and regulate the process of angiogenesis under reperfusion/ischemia injury. Despite the existence of a close relationship between mitochondrial donation and angiogenic response in different cell types, the precise molecular mechanisms associated with this phenomenon remain unclear. Here, we aimed to highlight the possible role of mitochondria concerning angiogenesis, especially the role of mitochondrial transport and the possible relation of this transfer with autophagy, the housekeeping phenomenon of cells, and angiogenesis.

Inadvertent Platelet Transfusion from Monkeypox Virus-Infected Donor to Recipient, Thailand, 2023.

In Thailand, platelet product from a blood donor was transfused to a recipient who had dengue. Two days later, the donor was confirmed to have monkeypox virus infection. Monkeypox virus DNA was undetectable in recipient specimens up to 2 weeks after transfusion. The recipient remained asymptomatic at 4 weeks of monitoring.

Effects of Trehalose Preconditioning on H9C2 Cell Viability and Autophagy Activation in a Model of Donation after Circulatory Death for Heart Transplantation.

Donation after circulatory death (DCD) is a promising strategy for alleviating donor shortage in heart transplantation. Trehalose, an autophagy inducer, has been shown to be cardioprotective in an ischemia-reperfusion (IR) model; however, its role in IR injury in DCD remains unknown. In the present study, we evaluated the effects of trehalose on cardiomyocyte viability and autophagy activation in a DCD model. In the DCD model, cardiomyocytes (H9C2) were exposed to 1 h warm ischemia, 1 h cold ischemia, and 1 h reperfusion. Trehalose was administered before cold ischemia (preconditioning), during cold ischemia, or during reperfusion. Cell viability was measured using the Cell Counting Kit-8 after treatment with trehalose. Autophagy activation was evaluated by measuring autophagy flux using an autophagy inhibitor, chloroquine, and microtubule-associated protein 1A/1B light chain 3 B (LC3)-II by western blotting. Trehalose administered before the ischemic period (trehalose preconditioning) increased cell viability. The protective effects of trehalose preconditioning on cell viability were negated by chloroquine treatment. Furthermore, trehalose preconditioning increased autophagy flux. Trehalose preconditioning increased cardiomyocyte viability through the activation of autophagy in a DCD model, which could be a promising strategy for the prevention of cardiomyocyte damage in DCD transplantation.

Salvaging donated kidneys from prolonged warm ischemia during ex vivo hypothermic oxygenated perfusion.

Prolonged warm ischemic is the main cause discarding donated organs after cardiac death. Here, we identified that prolonged warm ischemic time induced disseminated intravascular coagulation and severe capillary vasospasm after cardiac death of rat kidneys. Additionally, we found a significant accumulation of fibrinogen in a hypoxic cell culture of human umbilical vein epithelial cells and in isolated kidneys exposed to prolonged warm ischemic following flushing out of blood. However, pre-flushing the kidney with snake venom plasmin in a 90-minute warm ischemic model maximized removal of micro thrombi and facilitated the delivery of oxygen and therapeutic agents. Application of carbon monoxide-releasing CORM-401 during ex vivo hypothermic oxygenated perfusion achieved multipath protective effects in prolonged warm ischemic kidneys. This led to significant improvements in perfusion parameters, restoration of the microcirculation, amelioration of mitochondrial injury, oxidative stress, and apoptosis. This benefit resulted in significantly prolonged warm ischemic kidney recipient survival rates of 70%, compared with none in those receiving ex vivo hypothermic oxygenated perfusion alone. Significantly, ex vivo hypothermic oxygenated perfusion combined with cytoprotective carbon monoxide releasing CORM-401 treatment meaningfully protected the donated kidney after cardiac death from ischemia-reperfusion injury by reducing inflammation, oxidative stress, apoptosis, and pathological damage. Thus, our study suggests a new combination treatment strategy to potentially expand the donor pool by increasing use of organs after cardiac death and salvaging prolonged warm ischemic kidneys.

Antiobesity pharmacotherapy to facilitate living kidney donation.

Obesity is a chronic, relapsing disease that increases the risks of living kidney donation; at the same time, transplant centers have liberalized body mass index constraints for donors. With the increasing number of antiobesity medications available, the treatment of obesity with antiobesity medications may increase the pool of potential donors and enhance donor safety. Antiobesity medications are intended for long-term use given the chronic nature of obesity. Cessation of treatment can be expected to lead to weight regain and increase the risk of comorbidity rebound/development. In addition, antiobesity medications are meant to be used in conjunction with-rather than in replacement of-diet and physical activity optimization. Antiobesity medication management includes selecting medications that may ameliorate any coexisting medical conditions, avoiding those that are contraindicated in such conditions, and being sensitive to any out-of-pocket expenses that may be incurred by the potential donor. A number of questions remain regarding who will and should shoulder the costs of long-term obesity treatment for donors. In addition, future studies are needed to quantify the degree of weight loss and duration of weight loss maintenance needed to normalize the risk of adverse kidney outcomes relative to comparable nondonors and lower-weight donors.

OPTN/SRTR 2022 Annual Data Report: Deceased Organ Donation.

The Scientific Registry of Transplant Recipients uses data collected by the Organ Procurement and Transplantation Network to calculate metrics such as organs recovered per donor, organs transplanted per donor, and organs recovered for transplant but not transplanted (ie, nonuse). In 2022, there were 14,905 deceased donors, a 7.5% increase from 13,863 in 2021, and this number has been increasing since 2010. The number of deceased donor organs used for transplant increased to 37,334 in 2022, a 4.6% increase from 35,687 in 2021; this number has been increasing since 2012. The increase may be due in part to the rising number of deaths of young people amid the ongoing opioid epidemic. The number of organs transplanted included 10,130 left kidneys, 10,039 right kidneys, 298 en bloc kidneys, 922 pancreata, 8,847 livers, 83 intestines, 4,169 hearts, and 2,633 lungs. Compared with 2021, transplants of all organs except pancreata and intestines increased in 2022. In 2022, 3,563 left kidneys, 3,673 right kidneys, 156 en bloc kidneys, 366 pancreata, 965 livers, 4 intestines, 54 hearts, and 219 lungs were not used. These data suggest an opportunity to increase the number of transplants by reducing the number of unused organs. Despite the COVID-19 pandemic, there was no dramatic increase in the number of unused organs and there was an increase in the total numbers of donors and transplants.

An ethical analysis of conditional and partially directed live kidney donation among strangers-The Israeli experience.

Living donor kidney transplantation (LDKT) is one of the most effective treatment options for people with end-stage renal disease. Traditionally, LDKT can be either "directed" or "nondirected," based on whether the recipient is specified by the donor. Recently, there has been an increase in conditional and semidirected live kidney donation among strangers, where the donor specifies the characteristics of the recipient whom they wish to donate to. This practice has both gained popularity and sparked controversy in the state of Israel through the nonprofit organization Matnat Chaim. We analyze the ethical implications of this practice by applying traditional principles of medical ethics to conditional LDKT. Although semidirected and conditional LDKT presents some ethical challenges, overall, its practice effectively aligns with core ethical principles. The donors' right to make stipulations respects the donor's autonomy, the practice avoids harm and benefits both donor and recipient, and justice and utility are upheld as the practice specifically benefits marginalized patients and optimizes resource utilization. Finally, we present data from our institution demonstrating how conditional LDKT increased transplantation for all ethnic groups; Jewish recipients of LDKT increased by 151.32% (P = .034) Arab recipients of LDKT increased by 111.11% (P = .036).

Impact of simultaneous heart procurement on outcomes of donation after circulatory death lung transplantation.

Donation after circulatory death (DCD) heart procurement is done using either direct procurement (DP) or thoracoabdominal normothermic machine perfusion (TA-NRP). Both approaches could impact lung transplant outcomes with combined heart and lung procurements from the same donor. The impact of such practice on DCD lung transplant remains unstudied. We performed a retrospective analysis using the United Network for Organ Sharing (UNOS) dataset, identifying DCD lung transplants where the donor also donated the heart (cardia lung donor [CD]). A cohort of noncardiac DCD lung donors (noncardiac lung donor [NCD]) from the same era, matched for donor and recipient characteristics, was used as a comparison group. Both immediate and long-term outcomes were examined. A subanalysis was performed comparing the distinct impact of DP or TA-NRP on DCD lung transplant outcomes. Overall graft survival did not significantly differ between CD and NCD. However, recipients in the CD group trended toward a lower P/F ratio at 72 hours (CD vs NCD: 284 vs 3190; P = .054). In the subanalysis, we identified 40 DP donors and 22 TA-NRP donors. We found the both cohorts had lower P/F ratio at 72 hours than the NCD control (P = .04). Overall, 1-year graft survival was equivalent among the TA-NRP, DP, and NCD cohorts.

Financial toxicity in living donor liver transplantation: A call to action for financial neutrality.

After 2 decades of limited growth, living donor liver transplant (LDLT) has been increasingly accepted as a promising solution to the growing organ shortage in the US. With experience, LDLT offers superior graft and patient survival with low rates of rejection. However, not all waitlisted patients have equal access to LDLT, with financial toxicity representing a substantial barrier. Potential living liver donors face indirect, direct, and opportunity costs associated with donation as well as insurance-based discrimination and variable employer leave policies. There are multiple potential national, local, and patient-centered solutions to address some of the cost-related issues associated with living LDLT. These include standardization of employer leave policies, creation of federal and state-led tax relief programs, optimization of National Living Donor Assistance Center use, engagement of independent living donor advocates, creation of financial toolkits, and encouragement of recipient or donor-led fundraising. In this piece, members of the North American Living Liver Donation Group, a consortium of 37 LDLT programs, explore these financial challenges and discuss solutions to achieve financial neutrality, where individuals can donate free from financial constraints or gains. As a community, it is imperative that we confront factors driving financial toxicity to improve equity and access to LDLT.

The decedent model: A new paradigm for de-risking high stakes clinical trials like xenotransplantation.

The first 2 living recipients of pig hearts died unexpectedly within 2 months, despite both recipients receiving what over 30 years of nonhuman primate (NHP) research would suggest were the optimal gene edits and immunosuppression to ensure success. These results prompt us to question how faithfully data from the NHP model translate into human outcomes. Before attempting any further heart xenotransplants in living humans, it is highly advisable to gain a more comprehensive understanding of why the promising preclinical NHP data did not accurately predict outcomes in humans. It is also unlikely that additional NHP data will provide more information that would de-risk a xenoheart clinical trial because these cases were based on the best practices from the most successful NHP results to date. Although imperfect, the decedent model offers a complementary avenue to determine appropriate treatment regimens to control the human immune response to xenografts and better understand the biologic differences between humans and NHP that could lead to such starkly contrasting outcomes. Herein, we explore the potential benefits and drawbacks of the decedent model and contrast it to the advantages and disadvantages of the extensive body of data generated in the NHP xenoheart transplantation model.

Sexual and gender minority relevant policies in Canadian and United States organ and tissue donation and transplantation systems: An opportunity to improve equity and safety.

Current policies in organ and tissue donation and transplantation (OTDT) systems in Canada and the United States unnecessarily restrict access to donation for sexual and gender minorities (SGMs) and pose safety risks to transplant recipients. We compare SGM-relevant policies between the Canadian and United States systems. Policy domains include the risk assessment of living and deceased organ and tissue donors, physical examination considerations, viral testing recommendations, and informed consent and communication. Identified gaps between current evidence and existing OTDT policies along with differences in SGM-relevant policies between systems, represent an opportunity for improvement. Specific recommendations for OTDT system policy revisions to achieve these goals include the development of behavior-based, gender-neutral risk assessment criteria, a reduction in current SGM no-sexual contact period requirements pending development of inclusive criteria, and destigmatization of sexual contact with people living with human immunodeficiency virus. OTDT systems should avoid rectal examinations to screen for evidence of receptive anal sex without consent and mandate routine nucleic acid amplification test screening for all donors. Transplant recipients must receive enhanced risk-to-benefit discussions regarding decisions to accept or decline an offer of an organ classified as increased risk. These recommendations will expand the donor pool, enhance equity for SGM people, and improve safety and outcomes for transplant recipients.

The Differential Impact of Early Graft Dysfunction in Kidney Donation After Brain Death and After Circulatory Death: Insights from the Dutch National Transplant Registry.

Kidneys donated after circulatory death (DCD) perform similarly to kidneys donated after brain death (DBD). However, the respective incidences of delayed graft function (DGF) differ. This questions the donor type-specific impact of early graft function on long-term outcome. Using competing risk and cox regression analysis, we compared death-censored graft loss between types of early graft function: DGF (temporary dialysis dependency started within seven days after transplantation), slow graft function (SGF, three-day plasma creatinine decline less than 10% per day), and immediate graft function (IGF). In 1061 DBD and 1605 DCD graft recipients (January 2014 until January 2023), graft survival was similar. DGF was associated with death-censored graft loss in DBD and DCD (adjusted hazard ratios [aHR]: DGF in DBD: 1.79 [1.04- 2.91], p = 0.027, DGF in DCD: 1.84 [1.18 - 2.87], p = 0.008; Reference: no DGF). SGF was associated with death-censored graft loss in DBD, but not significantly in DCD (aHR DBD: 2.82 (1.34 - 5.93), p = 0.007, and DCD: 1.54 (0.72 - 3.35), p = 0.262; Reference: IGF). Early graft dysfunction has a differential impact on graft outcome in DBD and DCD. The differences between DBD and DCD should be accounted for in research and the clinic.

Donor utilization in heart transplant with donation after circulatory death in the United States.

Heart transplantation using donation after circulatory death (DCD) was recently adopted in the United States. This study aimed to characterize organ yield from adult (≥18 years) DCD heart donors in the United States using the United Network for Organ Sharing registry. The registry does not identify potential donors who do not progress to circulatory death, and only those who progressed to death were included for analysis. Outcomes included organ recovery from the donor operating room and organ utilization for transplant. Multiple logistic regression was used to identify predictors of heart recovery and utilization. Among 558 DCD procurements, recovery occurred in 89.6%, and 92.5% of recovered hearts were utilized for transplant. Of 506 DCD procurements with available data, 65.0% were classified as direct procurement and perfusion and 35.0% were classified as normothermic regional perfusion (NRP). Logistic regression identified that NRP, shorter agonal time, younger donor age, and highest volume of organ procurement organizations were independently associated with increased odds for heart recovery. NRP independently predicted heart utilization after recovery. DCD heart utilization in the United States is satisfactory and consistent with international experience. NRP procurements have a higher yield for DCD heart transplantation compared with direct procurement and perfusion, which may reflect differences in donor assessment and acceptance criteria.

Temporal trends in kidney paired donation in the United States: 2006-2021 UNOS/OPTN database analysis.

Kidney paired donation (KPD) is a major innovation that is changing the landscape of kidney transplantation in the United States. We used the 2006-2021 United Network for Organ Sharing data to examine trends over time. KPD is increasing, with 1 in 5 living donor kidney transplants (LDKTs) in 2021 facilitated by KPD. The proportion of LDKT performed via KPD was comparable for non-Whites and Whites. An increasing proportion of KPD transplants are going to non-Whites. End-chain recipients are not identified in the database. To what extent these trends reflect how end-chain kidneys are allocated, as opposed to increase in living donation among minorities, remains unclear. Half the LDKT in 2021 in sensitized (panel reactive antibody ≥ 80%) and highly sensitized (panel reactive antibody ≥ 98%) groups occurred via KPD. Yet, the proportion of KPD transplants performed in sensitized recipients has declined since 2013, likely due to changes in the deceased donor allocation policies and newer KPD strategies such as compatible KPD. In 2021, 40% of the programs reported not performing any KPD transplants. Our study highlights the need for understanding barriers to pursuing and expanding KPD at the center level and the need for more detailed and accurate data collection at the national level.

Why partial heart transplantation could be regulated as organ transplantation.

Partial heart transplant (PHT) is a recent clinical innovation involving the transplantation of a segment of the heart (valves) directly from the deceased donor into the recipient patient. This procedure holds out the possibility of significant benefit, especially for pediatric patients because these grafts show growth potential after transplant, reducing or eliminating the current need for repeat procedures. The clinical process for donation and transplant of partial heart (PH) grafts generally follows an organ clinical pathway; however, the Food and Drug Administration has recently stated its intent to regulate PH as tissues, raising a host of regulatory considerations. PHT requires donor testing and eligibility determinations within a short, clinically viable timeframe and, similar to organ transplant, involves donor-recipient matching. Waitlist allocation policies that are a regulatory focus of the Organ Procurement and Transplantation Network including equity and efficiency may become relevant. Oversight of PHT by the Organ Procurement and Transplantation Network could be accomplished through interpretation of the vascular composite allograft definition or through designation by the US Department of Health and Human Services of PH grafts as organs. While some clinical questions remain unanswered, it is important to carefully address these regulatory considerations to support the emergence of this innovation and ensure the continued trust of the donating public and the patients who may benefit from PHT.