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International audience; Kidney transplant survival is shortened by chronic rejection and side effects of standard immunosuppressive drugs. Cell-based immunotherapy with tolerogenic dendritic cells has long been recognized as a promising approach to reduce general immunosuppression. Published trials report the safety and the absence of therapy-related adverse reactions in patients treated with tolerogenic dendritic cells suffering from several inflammatory diseases. Here, we present the first phase I clinical trial results using human autologous tolerogenic dendritic cells (ATDC) in kidney transplantation. Eight patients received ATDC the day before transplantation in conjunction with standard steroids, mycophenolate mofetil and tacrolimus immunosuppression with an option to taper mycophenolate mofetil. ATDC preparations were manufactured in a Good Manufacturing Practice-compliant facility and fulfilled cell count, viability, purity and identity criteria for release. A control group of nine patients received the same standard immunosuppression, except basiliximab induction replaced ATDC therapy and mycophenolate tapering was not allowed. During the three-year follow-up, no deaths occurred and there was 100% graft survival. No significant increase of adverse events was associated with ATDC infusion. Episodes of rejection were observed in two patients from the ATDC group and one patient from the control group. However, all rejections were successfully treated by glucocorticoids. Mycophenolate was successfully reduced/stopped in five patients from the ATDC group, allowing tacrolimus monotherapy for two of them. Regarding immune monitoring, reduced CD8 T cell activation markers and increased Foxp3 expression were observed in the ATDC group. Thus, our results demonstrate ATDC administration safety in kidney-transplant recipients.

Purpose This paper argues for the benefits to international business (IB) of taking a much longer view at the engagement by multinational enterprises (MNEs) with host locations. Design/methodology/approach The authors showcase a project tracking the engagement by MNEs with Australia over the past two centuries. Extensive archival work has been undertaken to identify and document modes of entry, home countries, industries, operational modes and company types among the MNEs operating in Australia. The authors also describe the shifting nature of Australia as a host location. Findings The authors demonstrate the historical and ongoing diversity of ways in which MNEs interact with a host. They show that different organisational forms have prevailed over time, and that considerable operational mode changes can best be observed when a long lens is adopted. The authors show how these mode changes interact with host country dynamics, and also the broader context of the MNE and its altering strategies. Research limitations/implications The authors urge IB scholars to embrace longer timeframes to capture the complexity of MNEs’ growth and adaptation more meaningfully. Originality/value By taking such a long-run perspective, the authors shed new light on the importance of moving beyond simple snapshots to analyse key IB constructs and phenomenon.

Foreign multinational enterprises (MNEs) operating in China, especially during the nineteenth century, have attracted less interest from historians than Chinese firms and expatriate merchant houses. However, in this period, MNEs shaped advertising inShenbao, China’s most vital modern Chinese-language newspaper. Through our examination of the advertisements they placed during the newspaper’s first phase of publication, 1872–1889, we argue that MNEs were more significant to the history of business in China than heretofore recognized. We contend that they influenced Chinese print media advertising by pioneering product differentiation and branding in this newspaper. They did so, we suggest, because this approach to marketing, which differed from those used by most other foreign and Chinese domestic advertisers, provided a competitive advantage to overcome their liability of foreignness, and was facilitated by their global reach in the form of knowledge flows from offshore bases to onshore branches.

Chronic hypomagnesemia is commonly due to diarrhea, alcoholism, and drugs. More rarely, it is caused by genetic defects in the effectors of renal magnesium reabsorption.In an adult patient with acquired severe hypomagnesemia, hypocalcemia, tubulointerstitial nephropathy, and rapidly progressing kidney injury, similarities between the patient's presentation and features of genetic disorders of renal magnesium transport prompted us to investigate whether the patient had an acquired autoimmune cause of renal magnesium wasting. To determine if the patient's condition might be explained by autoantibodies directed against claudin-16 or claudin-19, transmembrane paracellular proteins involved in renal magnesium absorption, we conducted experiments with claudin knockout mice and transfected mouse kidney cells expressing human claudin-16 or claudin-19. We also examined effects on renal magnesium handling in rats given intravenous injections of IgG purified from sera from the patient or controls.Experiments with the knockout mice andPathogenic claudin-16 autoantibodies represent a novel autoimmune cause of specific renal tubular transport disturbances and tubulointerstitial nephropathy. Screening for autoantibodies targeting claudin-16, and potentially other magnesium transporters or channels in the kidney, may be warranted in patients with acquired unexplained hypomagnesemia.

International audience; No abstract available

Transport networks can play an important role in responses to extreme climate events, especially when governments own the network and intervene directly. Railways occupied a central place in Australian rural development by the late nineteenth century, a topic that has been discussed widely by scholars of economic history. Much less is known about their contribution during the severe drought crises faced by rural communities. We investigate the role railways played during the Federation Drought of 1895-1903 in sustaining Australia's largest export industry, pastoralism. Government ownership of the railways enabled subsidies to be offered for the movement of livestock from drought areas and fodder to those areas. These policies assisted the rapid recovery of pastoral output and contributed to longer-term industry improvements. The intervention, however, came at significant financial cost to the railways, which was borne for the public good as part of an economic developmental purpose. The costs and benefits of drought relief policies continue to be debated today; our study demonstrates the major role transport networks can play in response to extreme climate events, both for immediate relief and in shaping subsequent behaviours.

Circulating immune cells are critical mediators of the response to inflammation upon recruitment to the tissue but how gene expression state influences recruitment is not well known. Here we report the longitudinal single-cell transcriptome profiling of blood mononuclear cells in patients undergoing kidney transplantation rejection. We identify a gene expression module which is associated to transcriptional regulation, homing and early activation in multiple cell types. The circulating cells expressing this module are reduced in patients undergoing graft rejection. This reduction was confirmed in a pig model of acute kidney transplantation rejection. In connection with this, the module expression drastically increased in the kidney grafts undergoing rejection indicating a preferential recruitment of cells highly expressing this module. We identify the receptor CXCR4 within the module and its ligand CXCL12 expressed in the graft as a likely recruitment mechanism between circulating cells and the tissue. We then explore publicly available transcriptomics data in circulating cells and show that this module is generally expressed in healthy individuals and more importantly is associated with the response to infection, including SARS Covid-19. Moreover, we find that module expression is predictive of immune mediated diseases. In summary, we find a gene expression module in circulating immune cells which enables preferential recruitment to inflamed tissues to mediate effector function.

International audience; Background and objectives The fact that metabolism and immune function are regulated by an endogenous molecular clock that generates circadian rhythms suggests that the magnitude of ischemia reperfusion, and subsequent inflammation on kidney transplantation, could be affected by the time of the day. Design, setting, participants, & measurements We evaluated 5026 individuals who received their first kidney transplant from deceased heart-beating donors. In a cause-specific multivariable analysis, we compared delayed graft function and graft survival according to the time of kidney clamping and declamping. Participants were divided into those clamped between midnight and noon ( ante meridiem [ am ] clamping group; 65%) or clamped between noon and midnight ( post meridiem [ pm ] clamping group; 35%), and, similarly, those who underwent am declamping (25%) or pm declamping (75%). Results Delayed graft function occurred among 550 participants (27%) with am clamping and 339 (34%) with pm clamping (adjusted odds ratio, 0.81; 95% confidence interval, 0.67 to 0.98; P =0.03). No significant association was observed between clamping time and overall death-censored graft survival (hazard ratio, 0.92; 95% confidence interval, 0.77 to 1.10; P =0.37). No significant association of declamping time with delayed graft function or graft survival was observed. Conclusions Clamping between midnight and noon was associated with a lower incidence of delayed graft function, whereas declamping time was not associated with kidney graft outcomes.

OBJECTIVES To assess the impact of expanded criteria donors (ECD) on urinary complications in kidney transplantation. PATIENTS AND METHODS The UriNary Complications Of Renal Transplant (UNyCORT) is a cohort study based on the French prospective Donnees Informatisees et VAlidees en Transplantation/Computerized and VAlidated Data in Transplantation (DIVAT) cohort. Data were extracted between 1 January 2002 and 1 January 2018 with 1-year minimum follow-up, in relation to 44 pre- and postoperative variables. ECD status was included according to United Network for Organ Sharing (UNOS) definition. The primary outcome of the UNyCORT study was the association between the donor's ECD/standard criteria donors (SCD) status and urinary complications at 1 year in uni- and multivariate analysis. Sub-group analysis, stratified analysis on ECD/SCD donor's status and transplant failure analysis were then conducted. RESULTS Between 1 January 2002 and 1 January 2018, 10 279 kidney transplants in adult recipients were recorded within the DIVAT network. A total of 8559 (83.4%) donors were deceased donors and 1699 (16.6%) were living donors (LD). Among donation after circulatory death (DCD) donors, 224 (2.85%) were uncontrolled DCD and 93 (1.09%) were controlled DCD donors. A total of 3617 (43.9%) deceased donors were ECD. The overall urological complication rate was 16.26%. The donor's ECD status was significantly associated with an increased risk of urological complications at 1 year in multivariate analysis (odds ratio: 1.50, 95% CI 1.31-1.71; P

Resume Introduction La penurie de transplants renaux incite au quotidien a repousser les limites d’eligibilite au don. De nombreux donneurs en etat de mort encephalique presentent une insuffisance renale aigue lors de leur deces. Est-ce une reelle contre-indication au prelevement et a une transplantation renale ? Cette etude a pour objectif d’evaluer la survie des transplants issus de donneurs en mort encephalique ayant une mauvaise fonction renale lors du prelevement. Materiels et methodes L’ensemble des 2385 transplantations realisees sur deux centres hospitaliers universitaires entre 2010 et 2017, ont ete analyses de facon retrospective. L’ensemble des patients ayant eu une mono transplantation renale issue d’un donneur en etat de mort encephalique presentant une insuffisance renale aigue (IRA) ont ete inclus dans l’analyse. L’IRA a ete definie ici par une modification de plus de 50 % du debit de filtration glomerulaire (DFG) entre l’entree en reanimation et le prelevement, jusqu’a un seuil inferieur a 45 mL/min/1,73m2 au moment du prelevement. La survie des transplants a 12 mois, la reprise retardee de la fonction (RRF) des transplants et le DFG a 12 mois ont ete analyses. Une analyse de la survie en fonction des resultats de la biopsie preimplantatoire a egalement ete realisee lorsque celle-ci etait disponible. Resultats Un total de164 patients ont ete inclus ainsi durant cette periode. A l’arrivee en reanimation le DFG moyen etait 67,7 ± 19 mL/min/1,73m2. Lors du prelevement l’âge moyen des donneurs etait de 56,4 ± 17,7 ans, le DFG etait de 33,7 ± 8,0 mL/min, 16 %(n = 26) des donneurs etaient anuriques. L’ischemie froide (IF) etait de 16,8 ± 5,0 heures. L’âge moyen des receveurs etait de 55,6 ± 14,1 ans. Il s’agissait d’une premiere transplantation dans 81 % des cas. La reprise de la fonction renale a eu lieu dans les 7,8 ± 9,4 jours apres transplantation. Il y a eu deux non fonctions primaires « primary non function » (PNF). 152 patients (93 %) avaient un transplant fonctionnel a 12 mois. Le DFG moyen a 12 mois etait de 46,8 ± 20,1 mL/min/1,73 m2 et 122 patients (73 %) avaient un DFG superieur a 30 mL/min1,73 m2. Soixante et onze pour cent des biopsies preimplantatoires objectivaient de la necrose tubulaire aigue (NTA), la survie de ces transplants etait de 85 %, comparable a la population totale (p = 0,21). Aucune necrose corticale n’a ete observee. Conclusion L’insuffisance renale aigue du donneur en etat de mort encephalique ne doit pas a elle seule etre une contre-indication au prelevement renal.

Since the beginning of our pancreas transplant programme, plasma C-peptide was routinely measured daily during the postoperative period. We aimed to evaluate the clinical interest of the C-peptide in the follow-up of pancreas transplantation with a particular look on early graft failure. From 2000 to 2016, 384 pancreas transplantations were evaluated. We collected and compared C-peptide, glycaemia and adjusted C-peptide (aCP; calculated based on C-peptide, glycaemia and creatininaemia) in patients with and without pancreas failure within 30 days after surgery. Variations of glycaemia, C-peptide and aCP between the day before and the day of failure were also recorded. The difference of aCP was significant during the first week after transplantation between patients with thrombosis and those with functional allograft: 63.2 vs. 26.7 on day 1, P = 0.0003; 61.4 vs. 26.7 on day 3, P

Introduction: In kidney transplant recipients, belatacept is usually pursued indefinitely after it has been started. In the setting of the belatacept shortage and after having evaluated the benefit–risk ratio, we established a strategy consisting of time-limited belatacept therapy/transient calcineurin inhibitor withdrawal, whose results are analyzed in that study. Methods: We considered all the kidney transplant recipients that had been switched from conventional immunosuppressive therapy to belatacept and then for whom belatacept has been withdrawn intentionally. Furthermore, in the first 8 patients, we assessed changes in peripheral blood mononuclear cells (PBMC) transcriptome using RNAseq before and 3 months after belatacept withdrawal. Results: Over the study period, 28 out of 94 patients had belatacept intentionally withdrawn including 25 (89%) switched to low-dose CNI. One rejection due to poor compliance occurred. The eGFR after 12 months remained stable from 48 ± 19 mL.1.73 m−2 to 46 ± 17 mL.1.73 m−2 (p = 0.68). However, patients that resumed belatacept/withdrew CNIs (n = 10) had a trend towards a better eGFR comparing with the others (n = 15): 54 ± 20 mL.1.73 m−2 vs. eGFR 43 ± 16 mL.1.73 m−2, respectively (p = 0.15). The only factor associated with belatacept resumption was when the withdrawal took place during the COVID-19 outbreak. Transcriptome analysis of PBMCs, did not support rebound in alloimmune response. Conclusions: These findings underpin the use of belatacept as part of a time-limited therapy, in selected kidney transplant recipients, possibly as an approach to allow efficient vaccination against SARS-CoV-2.

Capitalism is back. Three decades ago, when all alternatives to liberal democracy and free markets appeared discredited, talk of capitalism seemed passé. Now, after a decade of political and economic turmoil, capitalism and its temporal critique of progress and decline again seems an indispensable category to understanding a world in flux. Among the social sciences, historians have led both the embrace and critique of this ‘re-emergent’ concept. This roundtable discussion between leading and emerging Australian scholars working across histories of economy, work, policy, geography and political economy, extends this agenda. Representing the outcome of a workshop convened at La Trobe University in November 2018 and responding to questions posed by conveners Huf and Rees, five participants debate the nature, utility and future of the new constellation of ‘economic’ historical scholarship. While conducted well before the outbreak of COVID-19, the ensuring discussion nevertheless speaks saliently to the crises of our times.

Much of our knowledge about the nineteenth-century natural history boom resides with the collectors themselves and their collections. We know much less about the conduct of the global trade that made collecting possible. That such a trade occurred in the face of significant obstacles of distance, variable prices, inadequate information, and diverse agents makes our knowledge deficit the more significant. William John Macleay, based in Sydney, built his significant natural history collection by trading locally as well as across the globe. Our study of Macleay measures his complete set of trading transactions at a time of rapid expansion of his collection. It analyses how he chose between different forms of exchange and agreed fair value in order to complete long-distance specimen trading.

The practices of ecologically-minded alternative communities illuminate differing perspectives on what might constitute an economy. This paper explores the extant literature and presents a framework for considering four spheres of confluence between the modern market economy and diverse economies: economic production practices, attitudes towards growth, environmental responsiveness and the socialrelational context of transactions. Drawing on evidence from an Australian ecovillage, the paper adopts the framework presented as a means of understanding the experiences of cooperatively negotiating various practices necessary to establish an intentionally sustainable community economy. Through this analysis, the paper provides insights into ways ecovillages may operate in the context of the modern market economy without adopting all of its practices. Ecovillages may indeed be places where convergence between economic approaches may be incubated, experienced and experimented, and through closer trading with the local external communities opportunities for the diffusion of such practices may ensue.

Introduction Decreased immunosuppression has been proposed for kidney transplant recipients infected with Covid-19 but the impact on the alloreactive immune response during and after infection has been poorly investigated. We assessed the occurrence of anti HLA donor specific antibodies (post-Covid DSA) and rejection episodes following Covid-19 with particular focus on immunosuppression modulation. Methods Kidney transplant recipients from two French institutions had anti-HLA antibody screening before and after Covid-19. Management of immunosuppression, rejection episodes, Covid-19 severity, inflammatory markers and antiviral therapies were recorded. Results From 251 recruited patients, 72 were excluded because of Covid-19 related death (n= 25) and incomplete immunological follow-up (n= 47). Among the remaining 179 included patients, almost half were hospitalized (49.2%). Antimetabolites were interrupted in 47% of patients (82% in hospitalized, median time of resumption of 23 days and in 15% non-hospitalized, median time of resumption of 7 days). Calcineurin inhibitors were interrupted in 12% of patients (all hospitalized, median time of resumption of 11 days). The incidence of post-Covid DSA was 4% (8% and 0% in hospitalized and non-hospitalized, respectively). Allograft rejection occurred in 3 patients (1.7%) and all were hospitalized. Younger age, transplantation less than one year and preexisting DSA were more frequently observed in post-Covid DSA positive patients, whereas inflammatory markers, lymphopenia and use of antiviral therapies were not. Conclusion The incidence of post-Covid DSA among Covid-19 positive kidney transplant recipients was low (4%) despite a significant decrease in immunosuppression and was mainly restricted to high-risk immunological patient’s status. Covid-19 severity was not associated with post-Covid DSA and/or rejection., Graphical abstract

International audience; No abstract available

International audience; Introduction: Cyst infection is a known complication of autosomal dominant polycystic kidney disease (ADPKD). Here, we describe incidence, risk factors, clinical presentation, and outcomes of cyst infection in kidney transplant recipient.Methods: We conducted a single-center retrospective cohort study of patients with ADPKD with renal allografts between January 1, 2009, and October 31, 2020. Cyst infection diagnosis was based on previously described clinical and radiological criteria, using positron emission tomography when available.Results: A total of 296 patients with ADPKD with renal allografts were included, and 21 patients experienced 22 episodes of cyst infection over a median follow-up of 4 (2–7) years. The cumulative incidence rate was 3% at 1 year, 6 % at 5 years, and 12% at 10 years after transplantation. In multivariate analysis, history of cyst infection before transplantation was the only significant risk factor identified to predict the occurrence of cyst infection after kidney transplantation (hazard ratio [HR] 3.47, 95% CI 1.29–9.31). The clinical presentation at diagnosis of cyst infection included isolated fever in 5 (23%) episodes, acute kidney injury in 12 (55%), and severe sepsis/septic shock in 3 (14%) episodes. Among the 16 (73%) episodes with culture positivity, Escherichia coli was the most common pathogen. There was no difference between early (≤1 year after transplantation) and late (>1 year) cyst infection episodes in terms of clinical presentation and outcomes. Cyst infection was significantly associated with graft loss (HR 3.93, 95% CI 1.21–12.80), but no causal relationship could be established.Conclusion: Incidence of cyst infection in ADPKD after kidney transplantation is low, history of cyst infection representing the main risk factor.

The archives of the Australian Museum and the Macleay Museum are deployed to analyse the global trading networks of two important Australian natural history collectors in the mid-nineteenth century...

The article is a rare investigation into multinational activity in a wealthy resource-based colonial economy toward the end of the first wave of globalization. It challenges the conventional wisdom that multinationals had a limited presence in pre-1914 Australia, where government loans and portfolio investment from Britain into infrastructural and primary industries dominated. Our new database of nearly five hundred foreign firms, from various nations and spread across the host economy, shows a thriving and diverse international business community whose agency mattered for economic development in Australia. Colonial ties, natural resources, stable institutions, and high incomes all attracted foreign firms.

Cooperative corporate behavior has often been explained through the social anatomy of business leaders and structural ties among firms. Our alternative approach investigates how quotidian interactions built trust and routines among a group of major firms in the Australian wool trade—a sector that required regular interaction to be effective. Deploying extensive archives of their meetings, we use social network analysis to examine interactions among the key group of firms and individuals. Through content analysis we infer the behavior and atmosphere of meetings. Finally, an evaluation of meeting agendas and outcomes demonstrates cooperation and a shared commitment to improving the operation of the wool trade in the 1920s.