ALBERT

Description: While there is great potential in the chief values and prospects of a circular economy, this alone will not bring the circular economy to market or scale. In order for a circular economy to materialize, an integrated approach that focuses on a long-term system change or transition is required. To set the change process in motion, many (public and private) players (companies, authorities, citizens, and research institutions) need to be involved. Among the many stakeholders, a genuine enabler to implement a successful and sustainable circular strategy is the logistics industry. Given that The Netherlands is used as a case study, in this paper, we focus on the Dutch logistics industry and how this industry can contribute to the broader Dutch agenda to realize a more circular economy. It implies looking at the specific transition agenda for the logistics industry in relation to a circular economy, what barriers may exist that might hamper such a transition, and how public policy-makers are dealing with and can tackle these barriers.

Description: Payments for Environmental Services (PES) are praised as innovative policy instruments and they influence the governance of forest restoration efforts in two major ways. The first is the establishment of multi-stakeholder agencies as intermediary bodies between funders and planters to manage the funds and to distribute incentives to planters. The second implication is that specific contracts assign objectives to land users in the form of conditions for payments that are believed to increase the chances for sustained impacts on the ground. These implications are important in the assessment of the potential of PES to operate as new and effective funding schemes for forest restoration. They are analyzed by looking at two prominent payments for watershed service programs in Indonesia—Cidanau (Banten province in Java) and West Lombok (Eastern Indonesia)—with combined economic and political science approaches. We derive lessons for the governance of funding efforts (e.g., multi-stakeholder agencies are not a guarantee of success; mixed results are obtained from a reliance on mandatory funding with ad hoc regulations, as opposed to voluntary contributions by the service beneficiary) and for the governance of financial expenditure (e.g., absolute need for evaluation procedures for the internal governance of farmer groups). Furthermore, we observe that these governance features provide no guarantee that restoration plots with the highest relevance for ecosystem services are targeted by the PES.

Description: Water, Vol. 10, Pages 35: Spatiotemporal Characteristics of Extreme Precipitation Regimes in the Eastern Inland River Basin of Inner Mongolian Plateau, China Water doi: 10.3390/w10010035 Authors: Wei Li Limin Duan Yanyun Luo Tingxi Liu Buren Scharaw In this work, we use the gridded precipitation dataset (with a resolution of 0.5° × 0.5°) of the eastern part of inland river basin of Inner Mongolian Plateau from 1961–2015 as the basis and adopt the methods of climatic diagnosis (e.g., the Modified Mann-Kendall method, principal component analysis, and correlation analysis) to analyze the spatial and temporal variations of six extreme precipitation indices. Furthermore, we analyzed the relationship between El Niño–Southern Oscillation (ENSO) events and the observed extreme precipitation. The results indicated that the gridded dataset can be used to describe the precipitation distribution in our study area. In recent 55 years, the inter-annual variation trends of extreme precipitation indices are generally dominated by declination except for the maximum precipitation over five days (RX5DAY) and the heavy precipitation (R95P), in particular, the decreasing regions of consecutive dry days (CDD) accounts for 91% of the entire basin, 17.28% of which is showing the significant downward trend. Contrary to CDD, the spatial distribution of the other five indices is gradually decreasing from northeast to southwest, and the precipitation intensity (SDII) ranges from 3.8–5.3 mm·d−1, with relatively small spatial differences. To some extent, CDD and R95P can used to characterize the extreme precipitation regimes. Moreover, the number of days with heavy precipitation (RR10), SDII, and R95P are more susceptible to the ENSO events. In addition, the moderate El Niño event may increase the probability of CDD, while the La Niña events may increase the risk of the heavy rainfall regime in the study area.

Description: Two patients with leukemia experienced profound thrombocytopenia and refractoriness to platelet transfusion during vancomycin treatment. In one patient, withdrawal of drug and administration of platelet transfusions restored platelet counts to near normal levels (approximately 100 x 10(9)/L), however, subsequent challenge with vancomycin due to recurring infection again precipitated severe thrombocytopenia (platelets less than 10 x 10(9)/L) and life- threatening hemorrhagic symptoms. Potent vancomycin-dependent antiplatelet antibodies were detected in the serum of both patients during the refractory period using staphylococcal protein A rosette formation. Employing a monoclonal antibody-antigen capture enzyme- linked immunosorbent assay (ELISA), the patients were found to have vancomycin-dependent IgG antibodies that bound specifically to platelet glycoproteins (GP) IIb and/or IIIa. One of these antibodies failed to react with platelets deficient in GPIIb/IIIa obtained from an individual with Glanzmann's thrombasthenia. These findings provide the first major evidence for drug-dependent antibodies in association with severe thrombocytopenia and refractoriness to platelet transfusion in alloimmunized leukemia patients and, further, provide the first demonstration of vancomycin-dependent antibodies reactive with platelets.

Description: Two patients with leukemia experienced profound thrombocytopenia and refractoriness to platelet transfusion during vancomycin treatment. In one patient, withdrawal of drug and administration of platelet transfusions restored platelet counts to near normal levels (approximately 100 x 10(9)/L), however, subsequent challenge with vancomycin due to recurring infection again precipitated severe thrombocytopenia (platelets less than 10 x 10(9)/L) and life- threatening hemorrhagic symptoms. Potent vancomycin-dependent antiplatelet antibodies were detected in the serum of both patients during the refractory period using staphylococcal protein A rosette formation. Employing a monoclonal antibody-antigen capture enzyme- linked immunosorbent assay (ELISA), the patients were found to have vancomycin-dependent IgG antibodies that bound specifically to platelet glycoproteins (GP) IIb and/or IIIa. One of these antibodies failed to react with platelets deficient in GPIIb/IIIa obtained from an individual with Glanzmann's thrombasthenia. These findings provide the first major evidence for drug-dependent antibodies in association with severe thrombocytopenia and refractoriness to platelet transfusion in alloimmunized leukemia patients and, further, provide the first demonstration of vancomycin-dependent antibodies reactive with platelets.

Description: Abstract 3960 Multiple myeloma (MM) is a B cell neoplasm characterized by clonal expansion of malignant plasma cells in the bone marrow. Despite the use of new drugs such as lenalidomide and bortezomib, MM remains an incurable disease. Successful treatment of MM with allogeneic stem cell transplantation suggests that MM is susceptible to immunologic approaches. NK cells are the primary effectors of the innate immune response against infectious pathogens and malignant transformation. Unlike T and B cells, NK cells do not recognize antigens in the context of classical major histocompatibility complex (MHC) but lyse target cells without specific antigen recognition. Nevertheless, MM cells have developed mechanisms to evade innate immune surveillance and the molecular basis for target resistance to NK cell-mediated lysis is not well understood. To identify novel pathways that modulate MM cell resistance to the immune system, we previously developed a genetic screen to detect cell-cell interactions using a large lentiviral shRNA library containing a total of 6,144 shRNAs targeting more than 1,000 human genes. Using this approach we found that silencing JAK1 and JAK2 results in significantly increased MM cell susceptibility to NK cell lysis. This effect was not noted when JAK3 and TYK2 were targeted. JAK1, JAK2 JAK3 and TYK2 are members of a family of tyrosine kinases that are constitutively associated with many membrane cytokine receptors. After activation, JAK proteins regulate phosphorylation/activation of STAT proteins, which subsequently initiate gene transcription. To understand JAK1 and JAK2 involvement in MM resistance to NK cells, we undertook a series of experiments to analyze the JAK signaling pathway in MM cells. We first analyzed the activation status of STAT proteins in a series of MM cell lines (IM-9, KM12BM, RPMI 8226, U266) in which JAK1 and JAK2 expression was reduced by specific shRNAs. Constitutive activation of STAT proteins was not affected by JAK1 or JAK2 gene silencing suggesting that these kinases were not activated in the absence of cytokine receptor-mediated signaling. Since JAK1 and JAK2 are associated with the IFN-γ receptor and we previously showed that JAK1 and JAK2 silencing induces increased secretion of IFN-γ from NK cells, we pre incubated MM cell lines with NK activated supernatant or recombinant IFN-γ and tested them for STAT activation. 15 min incubation was sufficient to initiate phosphorylation of STAT1 but no other STATs were activated. Silencing of JAK1 or JAK2 with specific shRNAs prevented STAT1 activation. To validate this finding, we tested primary MM cells treated with different concentrations of Jak inhibitor 1 (0 nM, 10 nM, 30 nM and 40 nM). These cells had a similar STAT profile at their basal level when compared with the previously tested MM cell lines. Pre-incubation with NK activated supernatant or IFN-γ also induced rapid activation of STAT1, which was completely inhibited when cells were pre-treated with Jak inhibitor 1. Treatment of MM cells with 10, 30 and 40 nM of Jak inhibitor enhanced killing by NK cells by 46.6%, 51% and 53%, compared to untreated cells (p=0.0036, p=0.0011 and p=0.0010 respectively). These findings demonstrate that IFN-γ signals rapidly enhance resistance of MM cells to NK cells but inhibition of this pathway at the level of JAK1 and JAK2 reverses this effect and induces susceptibility to NK cell mediated lysis. Disclosures: No relevant conflicts of interest to declare.

Description: A 27 year old male with end-stage renal failure secondary to IgA nephropathy received a living related renal transplant in 10/2002, complicated by severe cellular and humoral rejection. Immunosuppression included steroids, OKT3, cyclosporine A, rapamycin, thymoglobulin, antithymocyte globulin, and plasmapheresis. He developed multiple complications including severe pancytopenia, pleural effusions, Pseudomonas sepsis, and Vancomycin resistant enterococcus cystitis. Transplant nephrectomy was required 2/2003 for intractable rejection with blood clots in the urine, revealing large nodules of monomorphous B-cell PTLD throughout the renal parenchyma, along with type 2 acute cellular rejection. The B-cells were CD20 positive, and in situ hybridization for EBER was positive in the majority of the cells. PTLD staging was negative in other sites including brain and bone marrow. All immunosuppression was discontinued shortly following the nephrectomy, and he was placed on acyclovir for 3 months until he developed progressive cytopenias. In 8/2003 he underwent open brain biopsy following 2 grand mal seizures and an MRI showing multiple bilateral nonenhancing cortical and subcortical lesions up to several centimeters, with enhancing right temporal and parietal lesions with surrounding vasogenic edema and regional mass effect. Right temporal lobe biospy showed extensive high grade monomorphous B-cell PTLD with necrosis and vascular involvement. Lymphoma staging including lumbar puncture was otherwise negative and LDH was normal. He received a brief course of steroids and valacyclovir in the perioperative period. His performance status remained extremely poor, on hemodialysis, and thus he was not considered a good candidate for systemic chemotherapy, brain radiotherapy, or intrathecal chemotherapy. We elected to give a total of 8 courses of rituximab at 375 mg/m2 intravenously weekly. Although systemic rituximab does not generally penetrate the central nervous system very well, it was presumed that the blood brain barrier in this patient was broken down due to extensive lymphomatous cerebral disease. By 9/2003 there was improvement in the brain parenchymal lesions, and since 11/2003 there has been complete stabilization of residual involuted nonenhancing lesions. He remains in complete clinical remission, off rituximab for 22 months. This excellent response suggests that systemic rituximab can be an effective treatment in selected cases of PTLD in which extensive brain disease is present.