Rat allotransplantation of epigastric microsurgical flaps: a study of rejection and the immunosuppressive effect of cyclosporin A

The rejection of allotransplantation of epigastric microsurgical flaps and the effect of immunosuppression have been studied in 58 rats. Three sets of experiments were planned: (1) Wistar Furth isogenic donors and receptors (control set); (2) Brown Norway donors and Wistar Furth receptors (rejection set); and (3) Brown Norway donors and Wistar Furth immunosuppressed receptors (cyclosporin A set). Cyclosporin A (10 mg/kg/d) treated rats had a transplantation survival rate of up to 30 days: 83.3% among isogenic animals and 60% among allogeneic. There was 100% rejection by the 9th day after the transplantation in allogeneic non-immunosuppressed rats. Biopsies embedded with historesin were taken from the flap and normal contralateral skin (used as control) on the 3rd, 7th, 15th, and 30th days after the surgery. A quantitative study of infiltrating lymphocytes in the flaps, with and without cyclosporin A, was done by evaluating the local inflammatory infiltrate. A significant increase in the number of lymphocytes among the rejection and immunosuppressed groups was seen, as compared to the isogenic set. Local lymphocytosis in allogeneic non-immunosuppressed transplantations reached its highest level on the 3rd day after surgery, before gross findings of rejection, which could only be seen by naked eye on the 5th or 6th day. Therefore, we conclude that cyclosporin A is effective in preserving allogenic transplantation in rats. Biopsies of transplanted areas may contribute to earlier diagnosis of the need for immunosuppressive therapy.

Use of tacrolimus in rescue therapy of acute and chronic rejection in liver transplantation

PURPOSE: To study the indications and results of tacrolimus as rescue therapy for acute cellular or chronic rejection in liver transplantation. PATIENTS AND METHODS: Eighteen liver transplant recipients who underwent rescue therapy with tacrolimus between March 1995 and August 1999 were retrospectively studied. The treatment indication, patients, and graft situation were recorded as of October 31st, 1999. The response to tacrolimus was defined as patient survival with a functional graft and histological reversal of acute cellular, or for chronic rejection, bilirubin serum levels decreasing to up to twice the upper normal limit. RESULTS: Fourteen cases (77.8%) presented a good response. The response rate for the different indications was: (1) acute cellular + sepsis - 0/1 case; (2) recurrent acute cellular - 1/1 case; (3) OKT3-resistant acute cellular - 2/2 cases; (4) steroid-resistant acute cellular + active viral infection - 3/3 cases; (5) chronic rejection - 8/11 cases (72.7% response rate). The 4 patients who did not respond died. CONCLUSION: Tacrolimus rescue therapy was successful in most cases of acute cellular and chronic rejection in liver transplantation.

Peer interaction and learning opportunities in cohesive and less cohesive L2 classrooms

The present study investigates peer to peer oral interaction in two task based language teaching classrooms, one of which was a self-declared cohesive group, and the other a self- declared less cohesive group, both at B1 level. It studies how learners talk cohesion into being and considers how this talk leads to learning opportunities in these groups. The study was classroom-based and was carried out over the period of an academic year. Research was conducted in the classrooms and the tasks were part of regular class work. The research was framed within a sociocognitive perspective of second language learning and data came from a number of sources, namely questionnaires, interviews and audio recorded talk of dyads, triads and groups of four students completing a total of eight oral tasks. These audio recordings were transcribed and analysed qualitatively for interactions which encouraged a positive social dimension and behaviours which led to learning opportunities, using conversation analysis. In addition, recordings were analysed quantitatively for learning opportunities and quantity and quality of language produced. Results show that learners in both classes exhibited multiple behaviours in interaction which could promote a positive social dimension, although behaviours which could discourage positive affect amongst group members were also found. Analysis of interactions also revealed the many ways in which learners in both the cohesive and less cohesive class created learning opportunities. Further qualitative analysis of these interactions showed that a number of factors including how learners approach a task, the decisions they make at zones of interactional transition and the affective relationship between participants influence the amount of learning opportunities created, as well as the quality and quantity of language produced. The main conclusion of the study is that it is not the cohesive nature of the group as a whole but the nature of the relationship between the individual members of the small group completing the task which influences the effectiveness of oral interaction for learning.This study contributes to our understanding of the way in which learners individualise the learning space and highlights the situated nature of language learning. It shows how individuals interact with each other and the task, and how talk in interaction changes moment-by-moment as learners react to the ‘here and now’ of the classroom environment.

Community indentification in peer-t-peer collaborative consumption services

Even though collaborative consumption (CC) is gaining economic importance, research in CC is still in its infancy. Consumers’ reasons for participating have already been investigated but little research on consequences of participation has been conducted. This article examines whether interactions between customers in peer-to-peer CC services influence the willingness to coproduce service outcomes. Drawing on social exchange theory, it is proposed that this effect is mediated by consumers’ identification with the brand community. Furthermore, continuance intention in CC is introduced as a second stage moderator. In a cross-sectional study, customers of peer-to-peer accommodation sharing are surveyed. While customer-to-customer interactions were found to have a positive effect on brand community identification, brand community identification did not positively affect co-production intention. Surprisingly, the effect of brand community identification on co-production intention was negative. Moreover, continuance intention of customers did not moderate this relationship. Bearing in mind current challenges for researchers and companies, theoretical and managerial implications are discussed.

Treatment of persistent rejection with methotrexate in stable patients submitted to heart transplantation

OBJECTIVE:To evaluate the use of methotrexate for the treatment of recurrent rejection in heart transplant recipients. METHODS: We studied 6 patients submitted to heart transplantation that showed rejection grade > or = 3A (ISHLT) in two consecutives endomyocardial biopsy specimens. The dose was 11.26±3.75mg/week. The evaluated data were: ventricular function, endomyocardial biopsy, white cell count and number of rejection episodes before and after methotrexate administration. RESULTS: There was a reduction in the number of rejection episodes (5.17±1.47 before methotrexate; 2.33±1.75 after 6 months and 3.17±2.99 after 12 months of treatment, p=0.0193). The ventricular function was normal with ejection fraction of 76.5±4.80 before and 75.6±4.59 after methotrexate (p=0.4859). One patient did not finish the treatment because he showed signs of rejection associated with severe pericardial effusion. Five patients had a reduction in the white cell count (8,108±23.72 before and 5650±1350 after methotrexate, p=0.0961). One pulmonary infection with complete resolution after antibiotic treatment was observed. CONCLUSION: Methotrexate in low doses is an effective adjunct therapy in the treatment of recurrent rejection after heart transplantation.

Erkennung und Vermeidung von unkooperativem Verhalten in Peer-to-Peer-Datenstrukturen

Peer-to-Peer, reputation, trust

Diagnosis of Rejection by Analyzing Ventricular Late Potentials in Heart Transplant Patients

Background: Heart transplant rejection originates slow and fragmented conduction. Signal-averaged ECG (SAECG) is a stratification method in the risk of rejection. Objective: To develop a risk score for rejection, using SAECG variables. Methods: We studied 28 transplant patients. First, we divided the sample into two groups based on the occurrence of acute rejection (5 with rejection and 23 without). In a second phase, we divided the sample considering the existence or not of rejection in at least one biopsy performed on the follow-up period (rejection pm1: 18 with rejection and 10 without). Results: On conventional ECG, the presence of fibrosis was the only criterion associated with acute rejection (OR = 19; 95% CI = 1.65-218.47; p = 0.02). Considering the rejection pm1, an association was found with the SAECG variables, mainly with RMS40 (OR = 0.97; 95% CI = 0.87-0.99; p = 0.03) and LAS40 (OR = 1.06; 95% IC = 1.01-1.11; p = 0.03). We formulated a risk score including those variables, and evaluated its discriminative performance in our sample. The presence of fibrosis with increasing of LAS40 and decreasing of RMS40 showed a good ability to distinguish between patients with and without rejection (AUC = 0.82; p < 0.01), assuming a cutoff point of sensitivity = 83.3% and specificity = 60%. Conclusion: The SAECG distinguished between patients with and without rejection. The usefulness of the proposed risk score must be demonstrated in larger follow-up studies.

On the design of peer punishment experiments

We discuss how technologies of peer punishment might bias the results that are observed in experiments. A crucial parameter is the “fine-to-fee” ratio, which describes by how much the punished subjects income is reduced relatively to the fee the punishing subject has to pay to inflict punishment. We show that a punishment technology commonly used in experiments embeds a variable fine-to-fee ratio and show that it confounds the empirical findings about why, whom, and how much subjects punish.

Extracorporeal membrane oxygenation support after heart explantation: a proposal on how to deal with hyperacute rejection of heart transplant

Purpose: In extreme situations, such as hyperacute rejection of heart transplant or major bleeding per-operating complications, an urgent heart explantation might be the only means of survival. The aim of this experimental study was to improve the surgical technique and the hemodynamics of an Extracorporeal Membrane Oxygenation (ECMO) support through a peripheral vascular access in an acardia model. Methods: An ECMO support was established in 7 bovine experiments (59±6.1 kg) by the transjugular insertion to the caval axis of a self-expanded cannula, with return through a carotid artery. After baseline measurements of pump flow and arterial and central venous pressure, ventricular fibrillation was induced (B), the great arteries were clamped, the heart was excised and right and left atria remnants, containing the pulmonary veins, were sutured together leaving an atrial septal defect (ASD) over the cannula in the caval axis. Measurements were taken with the pulmonary artery (PA) clamped (C) and anastomosed with the caval axis (D). Regular arterial and central venous blood gases tests were performed. The ANOVA test for repeated measures was used to test the null hypothesis and a Bonferroni t method for assessing the significance in the between groups pairwise comparison of mean pump flow. Results: Initial pump flow (A) was 4.3±0.6 L/min dropping to 2.8±0.7 L/min (P B-A= 0.003) 10 minutes after induction of ventricular fibrillation (B). After cardiectomy, with the pulmonary artery clamped (C) it augmented not significantly to 3.5±0.8 L/min (P C-B= 0.33, P C-A= 0.029). Finally, PA anastomosis to the caval axis was followed by an almost to baseline pump flow augmentation (4.1±0.7 L/min, P D-B= 0.009, P D-C= 0.006, P D-A= 0.597), permitting a full ECMO support in acardia by a peripheral vascular access. Conclusions: ECMO support in acardia is feasible, providing new opportunities in situations where heart must urgently be explanted, as in hyperacute rejection of heart transplant. Adequate drainage of pulmonary circulation is pivotal in order to avoid pulmonary congestion and loss of volume from the normal right to left shunt of bronchial vessels. Furthermore, the PA anastomosis to the caval axis not only improves pump flow but it also permits an ECMO support by a peripheral vascular access and the closure of the chest.

System analysis of a Peer-to-Peer Video-on-Demand architecture: Kangaroo

Architectural design and deployment of Peer-to-Peer Video-on-Demand (P2PVoD) systems which support VCR functionalities is attracting the interest of an increasing number of research groups within the scientific community; especially due to the intrinsic characteristics of such systems and the benefits that peers could provide at reducing the server load. This work focuses on the performance analysis of a P2P-VoD system considering user behaviors obtained from real traces together with other synthetic user patterns. The experiments performed show that it is feasible to achieve a performance close to the best possible. Future work will consider monitoring the physical characteristics of the network in order to improve the design of different aspects of a VoD system.

Unionism and Peer-Referencing

This study assesses the 'fair-wage-effort' hypothesis, by examining (a) the relationship between relative wage comparisons and job satisfaction and quitting intensions, and (b) the relative ranking of stated effort inducing-incentives, in a novel dataset of unionised and non-unionised European employees. By distinguishing between downward and upward-looking wage comparisons, it is shown that wage comparisons to similar workers exert an asymmetric impact on the job satisfaction of union workers, a pattern consistent with inequity-aversion and conformism to the reference point. Moreover, union workers evaluate peer observation and good industrial relations more highly than payment and other incentives. In contrast, non-union workers are found to be more status-seeking in their satisfaction responses and less dependent on their peers in their effort choices The results are robust to endogenous union membership, considerations of generic loss aversion and across different tenure profiles. They are supportive of the individual egalitarian bias of collective wage determination and self-enforcing effort norms.

A web-based pilot study of inter-pathologist reproducibility using the ISHLT 2004 working formulation for biopsy diagnosis of cardiac allograft rejection: The European experience.

BACKGROUND: The aim of this study was to assess, at the European level and using digital technology, the inter-pathologist reproducibility of the ISHLT 2004 system and to compare it with the 1990 system We also assessed the reproducibility of the morphologic criteria for diagnosis of antibody-mediated rejection detailed in the 2004 grading system. METHODS: The hematoxylin-eosin-stained sections of 20 sets of endomyocardial biopsies were pre-selected and graded by two pathologists (A.A. and M.B.) and digitized using a telepathology digital pathology system (Aperio ImageScope System; for details refer to http://aperio.com/). Their diagnoses were considered the index diagnoses, which covered all grades of acute cellular rejection (ACR), early ischemic lesions, Quilty lesions, late ischemic lesions and (in the 2005 system) antibody-mediated rejection (AMR). Eighteen pathologists from 16 heart transplant centers in 7 European countries participated in the study. Inter-observer reproducibility was assessed using Fleiss's kappa and Krippendorff's alpha statistics. RESULTS: The combined kappa value of all grades diagnosed by all 18 pathologists was 0.31 for the 1990 grading system and 0.39 for the 2005 grading system, with alpha statistics at 0.57 and 0.55, respectively. Kappa values by grade for 1990/2005, respectively, were: 0 = 0.52/0.51; 1A/1R = 0.24/0.36; 1B = 0.15; 2 = 0.13; 3A/2R = 0.29/0.29; 3B/3R = 0.13/0.23; and 4 = 0.18. For the 2 cases of AMR, 6 of 18 pathologists correctly suspected AMR on the hematoxylin-eosin slides, whereas, in each of 17 of the 18 AMR-negative cases a small percentage of pathologists (range 5% to 33%) overinterpreted the findings as suggestive for AMR. CONCLUSIONS: Reproducibility studies of cardiac biopsies by pathologists in different centers at the international level were feasible using digitized slides rather than conventional histology glass slides. There was a small improvement in interobserver agreement between pathologists of different European centers when moving from the 1990 ISHLT classification to the "new" 2005 ISHLT classification. Morphologic suspicion of AMR in the 2004 system on hematoxylin-eosin-stained slides only was poor, highlighting the need for better standardization of morphologic criteria for AMR. Ongoing educational programs are needed to ensure standardization of diagnosis of both acute cellular and antibody-mediated rejection.

Nitrosative stress and corneal transplant endothelial cell death during acute graft rejection.

BACKGROUND: Nitrosative stress takes place in endothelial cells (EC) during corneal acute graft rejection. The purpose of this study was to evaluate the potential role of peroxynitrite on corneal EC death. METHODS: The effect of peroxynitrite was evaluated in vivo. Fifty, 250, and 500 microM in 1.5 microL of the natural or denatured peroxynitrite in 50 microM NaOH, 50 microM NaOH alone, or balanced salt solution were injected into the anterior chamber of rat eyes (n=3/group). Corneal toxic signs after injection were assessed by slit-lamp, in vivo confocal imaging, pachymetry, and EC count. The effect of peroxynitrite was also evaluated on nitrotyrosine and leucocyte elastase inhibitor/LDNase II immunohistochemistry. Human corneas were incubated with peroxynitrite and the effect on EC viability was evaluated. A specific inducible nitric oxide synthase inhibitor (iNOS) was administered systemically in rats undergoing allogeneic corneal graft rejection and the effect on EC was evaluated by EC count. RESULTS: Rat eyes receiving as little as 50 microM peroxynitrite showed a specific dose-dependent toxicity on EC. We observed an intense nitrotyrosine staining of human and rat EC exposed to peroxynitrite associated with leucocyte elastase inhibitor nuclear translocation, a noncaspase dependent apoptosis reaction. Specific inhibition of iNOS generation prevented EC death and enhanced EC survival of the grafted corneas. However, inhibition of iNOS did not have a significant influence on the incidence of graft rejection. CONCLUSION: Nitrosative stress during acute corneal graft rejection in rat eyes induces a noncaspase dependent apoptotic death in EC. Inhibition of nitric oxide production during the corneal graft rejection has protective effects on the corneal EC survival.

Peer-Practual: una tutoria entre iguals interprofessional als estudis de magisteri i psicopedagogia

Es presenten els resultats d’un projecte d’innovació didàctica consistent en la realització conjunta de pràctiques professionals entre estudiants de Magisteri d’educació Infantil i Educació Primària, i estudiants de Psicopedagogia. Aquests estudiants van treballar en parelles i van realitzar un conjunt d’activitats, pròpies de les seves futures funcions professionals, amb el suport del company. Concretament la pràctica va consistir en la planificació, desenvolupament i avaluació d’una unitat didàctica sobre un tema curricular. Mentre l’estudiant de Magisteri preparava els materials i activitats corresponents, la seva parella, l’estudiant de Psicopedagogia, l’assessorava en cada una de les fases d’instauració. Per afavorir aquesta dinàmica, els estudiants van comptar en diferents suports i instruments: - Els tutors de la universitat, corresponents a cadascun dels estudis implicats, - Una plataforma Moodle específicament organitzada per tal que els estudiants poguessin analitzar tot el procés conjuntament. En aquest espai podien utilitzar des de recursos per a la programació de la unitat, eines per realitzar un diari personal, un calendari d’activitats conjuntes o esquemes gràfics, fins a altres per editar vídeos gravats de les sessions de classe i per afavorir la seva comunicació. El projecte pretenia contribuir a millorar, tant algunes competències professionals relatives ambdós tipus d’estudiants, com modificar determinades concepcions i actituds entre mestres i psicopedagogs. Els resultats mostren que ambdós objectius van esser assolits amb escreix i que, a més d’aprendre determinades competències professionals, certs prejudicis i actituds sobre les dificultats i interès de treballar am altre, es van eliminar de manera contundent.

Allogeneic beta-islet cells correct diabetes and resist immune rejection.

Allogeneic MHC-incompatible organ or cell grafts are usually promptly rejected by immunocompetent hosts. Here we tested allogeneic beta-islet cell graft acceptance by immune or naive C57BL/6 mice rendered diabetic with streptozotocin (STZ). Fully MHC-mismatched insulin-producing growth-regulated beta-islet cells were transplanted under the kidney capsule or s.c. Although previously or simultaneously primed mice rejected grafts, STZ-treated diabetic mice accepted islet cell grafts, and hyperglycemia was corrected within 2-4 weeks in absence of conventional immunosuppression. Allogeneic grafts that controlled hyperglycemia expressed MHC antigens, were not rejected for &gt;100 days, and resisted a challenge by allogeneic skin grafts or multiple injections of allogeneic cells. Importantly, the skin grafts were rejected in a primary fashion by the grafted and corrected host, indicating neither tolerization nor priming. Such strictly extralymphatic cell grafts that are immunologically largely ignored should be applicable clinically.