36 research outputs found
Control of disseminated intravascular coagulation in Klippel-Trenaunay-Weber syndrome using enoxaparin and recombinant activated factor VIIa: a case report
<p>Abstract</p> <p>Introduction</p> <p>Vascular malformation is associated with coagulopathies, especially when hemostasis is challenged.</p> <p>Case presentation</p> <p>We present the case of an 11-year-old Hispanic girl with Klippel-Trenaunay-Weber syndrome that developed disseminated intravascular coagulation after minor surgery, which was controlled by blood product transfusions and enoxaparin to address an ongoing consumptive coagulopathy. The patient, however, developed bacteremia and liver trauma that resulted in severe bleeding. To the best of our knowledge, we report here the first known instance of administering recombinant coagulation factor VIIa to control acute bleeding in a patient with Klippel-Trenaunay-Weber syndrome.</p> <p>Conclusions</p> <p>This case illustrates the concept of enoxaparin maintenance to suppress an ongoing consumptive coagulopathy and the use of recombinant coagulation factor VIIa to control its potentially fatal severe bleeding episodes.</p
The conservation status of the world's freshwater molluscs
With the biodiversity crisis continuing unchecked, we need to establish levels and drivers of extinction risk, and reassessments over time, to effectively allocate conservation resources and track progress towards global conservation targets. Given that threat appears particularly high in freshwaters, we assessed the extinction risk of 1428 randomly selected freshwater molluscs using the IUCN Red List Categories and Criteria, as part of the Sampled Red List Index project. We show that close to one-third of species in our sample are estimated to be threatened with extinction, with highest levels of threat in the Nearctic, Palearctic and Australasia and among gastropods. Threat levels were higher in lotic than lentic systems. Pollution (chemical and physical) and the modification of natural systems (e.g. through damming and water abstraction) were the most frequently reported threats to freshwater molluscs, with some regional variation. Given that we found little spatial congruence between species richness patterns of freshwater molluscs and other freshwater taxa, apart from crayfish, new additional conservation priority areas emerged from our study. We discuss the implications of our findings for freshwater mollusc conservation, the adequacy of a sampled approach and important next steps to estimate trends in freshwater mollusc extinction risk over time
Country Concepts and the Rational Actor Trap: Limitations to Strategic Management of International NGOs
Growing criticism of inefficient development aid demanded new planning instruments of donors, including international NGOs (INGOs). A reorientation from isolated project-planning towards holistic country concepts and the increasing rationality of a result-orientated planning process were seen as answer. However, whether these country concepts - newly introduced by major INGOs too - have increased the efficiency of development cooperation is open to question. Firstly, there have been counteracting external factors, like the globalization of the aid business, that demanded structural changes in the composition of INGO portfolios towards growing short-term humanitarian aid; this was hardly compatible with the requirements of medium-term country planning. Secondly, the underlying vision of rationality as a remedy for the major ills of development aid was in itself a fallacy. A major change in the methodology of planning, closely connected with a shift of emphasis in the approach to development cooperation, away from project planning and service delivery, towards supporting the socio-cultural and political environment of the recipient communities, demands a reorientation of aid management: The most urgent change needed is by donors, away from the blinkers of result-orientated planning towards participative organizational cultures of learning.Des critiques croissantes de l'aide au développement inefficace exigent de nouveaux instruments de planification des bailleurs de fonds, y compris les ONG internationales (ONGI). Une réorientation de la planification des projets isolés vers des concepts holistiques de la planification de l’aide par pays ainsi que la rationalité croissante d'un processus de planification orientée vers les résultats ont été considérés comme réponse. Toutefois, si ces concepts de pays - nouvellement introduites par les grandes OING eux aussi - ont augmenté l'efficacité de la coopération au développement est ouvert à la question. Tout d'abord, il y a eu l’impact des facteurs externes, comme la mondialisation de l'entreprise de l'aide, qui a exigé des changements structurels dans la composition des portefeuilles des OING vers la croissance de l'aide humanitaire à court terme. Cela était difficilement compatible avec les exigences de l'aménagement du territoire à moyen terme. Deuxièmement, la vision sous-jacente de la rationalité accrue de la planification, concentré sur les resultats, comme un remède pour les grands maux de l'aide au développement était en soi une erreur. Un changement majeur dans la méthodologie de la planification, étroitement liée à un changement d'orientation dans l'approche de la coopération au développement, qui n’est pas concentrer sur planification du projet et la prestation de services, mais qui soutienne l'environnement socio-culturel et politique des communautés bénéficiaires, exige une réorientation de la gestion de l’aide: Le changement le plus urgent est un changement par les donateurs eux-mêmes, qui devrait implanter des cultures de collaboration étroit avec les partenaires et la population locale
Adverse Drug Reactions in Children—A Systematic Review
Adverse drug reactions in children are an important public health problem. We have undertaken a systematic review of observational studies in children in three settings: causing admission to hospital, occurring during hospital stay and occurring in the community. We were particularly interested in understanding how ADRs might be better detected, assessed and avoided
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
The Effect Of Olefinic Terminal Chains On The Mesomorphic Properties Of 4,4′-Disubstituted Diphenyldiacetylenes
New diphenyldiacetylenes of the type equation presented with A, B = H and/or F; m = 0, 1; n = 1-4; and X = CnH2n+1, F, CF3 or CN were synthesized and their mesomorphic properties determined by hot stage polarizing microscopy and DSC. When m = 0, all of these compounds showed only a nematic phase except when X = CF3 when both nematic and smectic A phases were seen. Both clearing and melting temperatures were higher than those reported for substitution with the corresponding alkyl chains but the much larger increase in clearing temperatures produced considerably wider nematic phases. Eutectic mixtures of a few of these olefins yielded nematic materials also having much wider temperature ranges and higher clearing temperatures than the eutectic mixtures of the alkyl compounds, while retaining their high birefringence and low viscosities. Such materials are of interest for beam-steering devices. Four of the diacetylenes with m = 1 (A, B = H) were also prepared (X = C6H13, F, n = 2, 3). When X was C6H13 (n = 2), the nematic range was smaller in the 2- than in the 1-olefin but wider than in the alkyl series. When X = F, either no nematic phase or a monotropic one was observed, whereas the 1-olefins gave a much wider nematic phase. Both transition temperatures were lower than those for the corresponding 1-olefin and alkyl analogues. The compound with X = C6H13 and n = 2 had a melting temperature below room temperature