New EU Anti-Money Laundering Rules Adopted in 2024 Briefer

This briefer is a summary of a report drafted by the European Center for Not-for-Profit Law and Philanthropy Europe Association, with input from experts and practitioners who kindly shared their insights with us, particularly Civil Society Europe. In this briefer, we analyse the new set of rules aimed at fighting money laundering and terrorist financing that was adopted by the European Parliament and the Council of the European Union in May 2024

Unpacking the EU AML/CFT Package : Impacts on the Non-Profit Sector

Civil society organisations, be they associations, foundations or other public-benefitlegal arrangements, are increasingly affected by policies and security measuresadopted by global bodies, governments and private sector actors with the aim tocounter money-laundering and terrorism financing (AML/CFT). In May 2024, theEuropean Parliament and the Council of the European Union, adopted a new Anti-Money Laundering / Countering the Financing of Terrorism package (hereafter alsoreferred to as: "package"), which was published in the Official Journal on 19 June2024. This paper aims to give a simple overview over this new EU AML/CFT packageand its potential impact on the non-profit sector. This paper can be considered a'living document', which will be updated as our understanding of the packageevolves based on new developments or information

Evidence for diagnosis of early chronic pancreatitis after three episodes of acute pancreatitis : a cross-sectional multicentre international study with experimental animal model

Chronic pancreatitis (CP) is an end-stage disease with no specific therapy; therefore, an early diagnosis is of crucial importance. In this study, data from 1315 and 318 patients were analysed from acute pancreatitis (AP) and CP registries, respectively. The population from the AP registry was divided into AP (n=983), recurrent AP (RAP, n=270) and CP (n=62) groups. The prevalence of CP in combination with AP, RAP2, RAP3, RAP4 and RAP5+was 0%, 1%, 16%, 50% and 47%, respectively, suggesting that three or more episodes of AP is a strong risk factor for CP. Laboratory, imaging and clinical biomarkers highlighted that patients with RAP3+do not show a significant difference between RAPs and CP. Data from CP registries showed 98% of patients had at least one AP and the average number of episodes was four. We mimicked the human RAPs in a mouse model and found that three or more episodes of AP cause early chronic-like morphological changes in the pancreas. We concluded that three or more attacks of AP with no morphological changes to the pancreas could be considered as early CP (ECP).The new diagnostic criteria for ECP allow the majority of CP patients to be diagnosed earlier. They can be used in hospitals with no additional costs in healthcare.Peer reviewe

Endoscopic sphincterotomy for delaying choLecystectomy in mild acute biliarY pancreatitis (EMILY study): Protocol of a multicentre randomised clinical trial

Introduction: According to the literature, early cholecystectomy is necessary to avoid complications related to gallstones after an initial episode of acute biliary pancreatitis (ABP). A randomised, controlled multicentre trial (the PONCHO trial) revealed that in the case of gallstone-induced pancreatitis, early cholecystectomy was safe in patients with mild gallstone pancreatitis and reduced the risk of recurrent gallstone-related complications, as compared with interval cholecystectomy. We hypothesise that carrying out a sphincterotomy (ES) allows us to delay cholecystectomy, thus making it logistically easier to perform and potentially increasing the efficacy and safety of the procedure. Methods/Design: EMILY is a prospective, randomised, controlled multicentre trial. All patients with mild ABP, who underwent ES during the index admission or in the medical history will be informed to take part in EMILY study. The patients will be randomised into two groups: (1) early cholecystectomy (within 6 days after discharge) and (2) patients with delayed (interval) cholecystectomy (between 45 and 60 days after discharge). During a 12-month period, 93 patients will be enrolled from participating clinics. The primary endpoint is a composite endpoint of mortality and recurrent acute biliary events (that is, recurrent ABP, acute cholecystitis, uncomplicated biliary colic and cholangitis). The secondary endpoints are organ failure, biliary leakage, technical difficulty of the cholecystectomy, surgical and other complications

Operational Research: Methods and Applications

Throughout its history, Operational Research has evolved to include a variety of methods, models and algorithms that have been applied to a diverse and wide range of contexts. This encyclopedic article consists of two main sections: methods and applications. The first aims to summarise the up-to-date knowledge and provide an overview of the state-of-the-art methods and key developments in the various subdomains of the field. The second offers a wide-ranging list of areas where Operational Research has been applied. The article is meant to be read in a nonlinear fashion. It should be used as a point of reference or first-port-of-call for a diverse pool of readers: academics, researchers, students, and practitioners. The entries within the methods and applications sections are presented in alphabetical order

31st Annual Meeting and Associated Programs of the Society for Immunotherapy of Cancer (SITC 2016) : part two

Background The immunological escape of tumors represents one of the main ob- stacles to the treatment of malignancies. The blockade of PD-1 or CTLA-4 receptors represented a milestone in the history of immunotherapy. However, immune checkpoint inhibitors seem to be effective in specific cohorts of patients. It has been proposed that their efficacy relies on the presence of an immunological response. Thus, we hypothesized that disruption of the PD-L1/PD-1 axis would synergize with our oncolytic vaccine platform PeptiCRAd. Methods We used murine B16OVA in vivo tumor models and flow cytometry analysis to investigate the immunological background. Results First, we found that high-burden B16OVA tumors were refractory to combination immunotherapy. However, with a more aggressive schedule, tumors with a lower burden were more susceptible to the combination of PeptiCRAd and PD-L1 blockade. The therapy signifi- cantly increased the median survival of mice (Fig. 7). Interestingly, the reduced growth of contralaterally injected B16F10 cells sug- gested the presence of a long lasting immunological memory also against non-targeted antigens. Concerning the functional state of tumor infiltrating lymphocytes (TILs), we found that all the immune therapies would enhance the percentage of activated (PD-1pos TIM- 3neg) T lymphocytes and reduce the amount of exhausted (PD-1pos TIM-3pos) cells compared to placebo. As expected, we found that PeptiCRAd monotherapy could increase the number of antigen spe- cific CD8+ T cells compared to other treatments. However, only the combination with PD-L1 blockade could significantly increase the ra- tio between activated and exhausted pentamer positive cells (p= 0.0058), suggesting that by disrupting the PD-1/PD-L1 axis we could decrease the amount of dysfunctional antigen specific T cells. We ob- served that the anatomical location deeply influenced the state of CD4+ and CD8+ T lymphocytes. In fact, TIM-3 expression was in- creased by 2 fold on TILs compared to splenic and lymphoid T cells. In the CD8+ compartment, the expression of PD-1 on the surface seemed to be restricted to the tumor micro-environment, while CD4 + T cells had a high expression of PD-1 also in lymphoid organs. Interestingly, we found that the levels of PD-1 were significantly higher on CD8+ T cells than on CD4+ T cells into the tumor micro- environment (p < 0.0001). Conclusions In conclusion, we demonstrated that the efficacy of immune check- point inhibitors might be strongly enhanced by their combination with cancer vaccines. PeptiCRAd was able to increase the number of antigen-specific T cells and PD-L1 blockade prevented their exhaus- tion, resulting in long-lasting immunological memory and increased median survival

Short-term Effects of Grazing Exclusion on Net Ecosystem CO2 Exchange and Net Primary Production in a Pannonian Sandy Grassland

Using portable, non-destructive own developed chambers (d=60 cm) and infrared gas analyses, the in situ field investigation was performed to study the seasonal and inter-annual dynamics of the stand level CO2-flux and production of sandy grassland that has been extensively grazed for decades. Furthermore, NEE measurements and biomass samples were used to identify the initial effects of grazing exclusion on CO2 exchange, aboveground phytomass and potential plant productivity in years of significantly different precipitation levels. A considerable inter-annual variation in all of the studied parameters was found both in the non-grazed and grazed stands. As a result of the grazing exclusion the CO2 uptake potential of the non-grazed stand increased by 13% compared to the grazed stand. It was more significant in the extreme dry year (220%), however, in wet year slightly lower average carbon sequestration was detected at the non-grazed stand (-13%), than that of the grazed area. Significant carbon sequestration potential was only detected during wet periods in both stands. The rate of CO2 uptake was found to be nearly six times higher in the non-grazed stand in the wet year than in the previous extremely dry year. The drought in 2003 significantly reduced the CO2 uptake of both stands, leading to lower annual net primary production and potential plant productivity. The annual net primary production dropped by almost 40% in the extremely dry year but then it rose by nearly two and a half times in the subsequent year with adequate rainfall

Short-term Effects of Grazing Exclusion on Net Ecosystem CO2 Exchange and Net Primary Production in a Pannonian Sandy Grassland

Using portable, non-destructive own developed chambers (d=60 cm) and infrared gas analyses, the in situ field investigation was performed to study the seasonal and inter-annual dynamics of the stand level CO2-flux and production of sandy grassland that has been extensively grazed for decades. Furthermore, NEE measurements and biomass samples were used to identify the initial effects of grazing exclusion on CO2 exchange, aboveground phytomass and potential plant productivity in years of significantly different precipitation levels. A considerable inter-annual variation in all of the studied parameters was found both in the non-grazed and grazed stands. As a result of the grazing exclusion the CO2 uptake potential of the non-grazed stand increased by 13% compared to the grazed stand. It was more significant in the extreme dry year (220%), however, in wet year slightly lower average carbon sequestration was detected at the non-grazed stand (-13%), than that of the grazed area. Significant carbon sequestration potential was only detected during wet periods in both stands. The rate of CO2 uptake was found to be nearly six times higher in the non-grazed stand in the wet year than in the previous extremely dry year. The drought in 2003 significantly reduced the CO2 uptake of both stands, leading to lower annual net primary production and potential plant productivity. The annual net primary production dropped by almost 40% in the extremely dry year but then it rose by nearly two and a half times in the subsequent year with adequate rainfall

MO1019: Sigma-1 Receptor Agonists are Protective in a Rat Model of Kidney Transplantation

Abstract BACKGROUND AND AIMS End-stage renal disease affects nearly 2 million people worldwide. The disease is associated with an irreversible deterioration in renal function and can only be treated by dialysis or kidney transplantation (KTx). KTx is associated with better long-term outcomes and quality of life compared with dialysis, but the shortage of donor organs is a serious and unsolved problem. Graft survival is highly dependent on the extent of cold and warm ischemic injury during Tx. We recently described the renoprotective effects of Sigma-1 receptor (S1R) agonist treatment in IRI. Thus, our aim was to develop a novel preservation solution that, with the addition of S1R agonist compounds, minimizes ischemic damage in order to improve the condition of grafts and so increase the number of organs suitable for Tx. METHOD Kidneys of male Wistar rats were perfused and placed in ice cold (i) custodiol preservation solution; custodiol containing S1R agonists, (ii) fluvoxamine or (iii) SA-4503 for 2 h, then autotransplanted and sacrificed 24 h after reperfusion. Sham-operated rats served as controls. In a second experiment, kidneys of wild-type and S1R knockout mice were perfused and placed in an ice-cold preservation solution containing an original, selective S1R agonist compound (VCC) for 24 h of cold ischemia and tissue samples were collected. Renal function parameters were determined. Renal expression of tubular injury markers (Kim-1, Ngal) and inflammatory cytokines (Il-1α, Il-6, Tnf-α, Mcp-1) were measured. Periodic acid-Schiff staining was performed on kidney tissue sections to evaluate structural changes. CD45 immunostaining was performed on kidney sections to determine the extent of leukocyte infiltration. DNA fragmentation resulted by apoptotic events in the kidney was evaluated by TUNEL-assay. RESULTS S1R agonists mitigated renal functional impairment and tubular dilatation following Tx. Expression of early and sensitive tubular injury markers was markedly less elevated in S1R agonist-treated kidneys. S1R agonists alleviated renal apoptosis as shown on TUNEL-stained kidney sections. Decreased numbers of CD45 + leukocytes and decreased inflammatory cytokine expressions confirmed the anti-inflammatory effect of S1R agonists. The S1R agonist VCC compound mitigated cold ischemic structural kidney damage in wild-type but not in S1R KO mice, which confirms the protective role of the receptor. CONCLUSION The addition of S1R agonists to the preservation solution during Tx improves graft function and alleviates structural damage, thus improving long-term outcomes. S1R agonists reduce graft injury during cold storage, therefore the number of transplantable donor organs can be increased. FUNDING OTKA PD-131 637; FK-124 491; 2020–4.1.1.-TKP2020-6 183 069 269; 2020–4.1.1.-TKP2020-6 183 169 273; KDP-2020/1 019 145. </jats:sec