A Tempestuous Translation: Aimé Césaire’s Une tempête

Cet article soutient qu’Une tempête par Aimé Césaire (adaptation anti-colonialiste de La Tempête), est l’illustration de la traduction en tant qu’interprétation et révision créatrice. Avec une fidélité surprenante envers la pièce de Shakespeare, Césaire s’intéresse aux conflits raciaux et de classe inhérents à La Tempête et donne voix aux opprimés, aux colonisés et aux victimes de la répression. Une tempête se distingue comme une traduction qui aurait traversé le temps (l’ère des droits civiques des Noirs et des mouvements de libération africains) et l’espace (une refonte créatrice des références shakespeariennes dans une localisation caribéenne francophone).This article contends that Aimé Césaire’s Une tempête (an anti-colonialist adaptation of The Tempest), epitomizes translation as interpretation and creative revision. With a striking fidelity to Shakespeare’s play, Césaire engages with the racial and class conflicts intrinsic to The Tempest and gives voice to the occluded colonized and oppressed. Une tempête stands out as a translation through time (the era of black civil rights and African liberation movements), and space (creatively refashioning Shakespearean references into a francophone Caribbean location)

Clinical and Laboratory Measurement to Improve Patient Blood Management: Foundations to the Three Pillar Framework

Transfusion may be a life-saving procedure. However, history shows that the risks of transfusion have been underestimated and transfusion overused. Blood has been considered dispensable and inadequate thought given to its management, not just to prevent transfusion, but to maximise patient outcomes. Voices heralding the need for blood optimisation and conservation throughout the twentieth century have combined to develop a field known as patient blood management. Patient blood management has been described in terms of three pillars, primarily from a perioperative perspective: optimising the blood pre-operatively; minimising blood loss intraoperatively; and understanding and improving tolerance of anaemia. In this thesis I explore each pillar and argue that improving the way we measure blood-related outcomes has the potential to enhance patient blood management and the approach to transfusion therapy. Iron deficiency is the most common cause for anaemia worldwide. It is particularly common in pregnancy where it can impact the mother's quality of life, the need for transfusion and potentially have far-reaching effects for children. Despite this, there is a lack of consensus on recognising and treating it during pregnancy. I have explored the use of novel red cell and reticulocyte indices, readily available from automated blood count analysers, as tools for detecting iron deficiency. While effective, these were no better than mean cell volume, although as a screening tool, a higher cut-off value is required. I also argue that there is value is screening with ferritin during pregnancy and show that this is best applied in first trimester. Red cell transfusion guidelines advocate transfusion based on individual patient needs rather than specific haemoglobin triggers. Measuring this is difficult and most randomised studies have transfused solely based on haemoglobin. I explored tolerance of anaemia in a different light - near infrared. Near infrared spectroscopy can measure tissue oxygenation and provides a potential transfusion trigger. A systematic literature review showed that tissue oxygenation is affected by anaemia and does respond to changes in haemoglobin. However, there was too much heterogeneity to recommend routine clinical use for transfusion decisions, perhaps as it was most frequently used in acute settings where reduced blood flow is a confounding factor. I therefore explored its utility in chronic anaemia setting and with exercise to see whether poor muscle oxygenation is a limiting factor for activity in anaemia. While there was a measurable impact, there remains too much heterogeneity to identify a transfusion trigger based on tissue oxygenation. Finally, I have explored alternative strategies for managing thrombocytopenia. Platelets for transfusion are often not kept in rural and regional areas. I have shown through in vitro and transfusion studies that cryoprecipitate improves whole blood haemostasis in thrombocytopenia and should be considered as an option in bleeding patients unable to access platelet transfusions. Cryoprecipitate may be more effective than cryopreserved platelets currently under investigation. These results highlight the continuing role for research into novel ways to monitor and appropriate target treatment for the blood. They support the concept of research being included amongst a revised model of patient blood management

Platelets and cancer the plot doesn't always thicken

Background Platelets have critical roles in preventing blood loss following injury, promoting wound healing, and in fighting infection through innate immune defense strategies. Key Results Deficiencies in platelet number or function either as a result of disease, as a consequence of therapy, or both can lead to dramatic and potentially fatal consequences. Conclusions and Inferences With the advent of new therapeutics targeting pathways within hematological malignant cells that are also important for platelet function, monitoring the state of a patient's haemostasis system is now an important clinical consideration.This work was supported in part by funding from the National Health and Medical Research Council of Australia and the Australian Research Council

Incidence and predictors of immediate complications following perioperative non-obstetric epidural punctures

Background: Epidural Anesthesia (EA) is a well-established procedure. The aim of the present study was to evaluate the incidence of immediate complications following epidural puncture, such as sanguineous puncture, accidental dural perforation, unsuccessful catheter placement or insufficient analgesia and to identify patient and maneuver related risk factors. Methods: A total of 7958 non-obstetrical EA were analyzed. The risk of each complication was calculated according to the preconditions and the level of puncture. For probabilistic evaluation we used a logistic regression model with forward selection. Results: The risk of sanguineous puncture (n = 247, 3.1%) increases with both the patient's age (P = 0.013) and the more caudal the approach (P &lt; 0.01). Dural perforation (n = 123, 1.6%) was found to be influenced only by advanced age (P = 0.019). Unsuccessful catheter placement (n = 68, 0.94%) occurred more often in smaller individuals (P < 0.001) and at lower lumbar sites (P < 0.01). Amongst all cases with successful catheter placement a (partial) insufficient analgesia was found in 692 cases (8.8%). This risk of insufficient analgesia decreased with patient's age (P < 0.01), being least likely for punctures of the lower thoracic spine (P < 0.001). Conclusions: Compared to more cranial levels, EA of the lower spine is associated with an increased risk of sanguineous and unsuccessful puncture. Insufficient analgesia more often accompanies high thoracic and low lumbar approaches. The risk of a sanguineous puncture increases in elderly patients. Gender, weight and body mass index seem to have no influence on the investigated complications

Incidence and predictors of immediate complications following perioperative non-obstetric epidural punctures

Background: Epidural Anesthesia (EA) is a well-established procedure. The aim of the present study was to evaluate the incidence of immediate complications following epidural puncture, such as sanguineous puncture, accidental dural perforation, unsuccessful catheter placement or insufficient analgesia and to identify patient and maneuver related risk factors. Methods: A total of 7958 non-obstetrical EA were analyzed. The risk of each complication was calculated according to the preconditions and the level of puncture. For probabilistic evaluation we used a logistic regression model with forward selection. Results: The risk of sanguineous puncture (n = 247, 3.1%) increases with both the patient's age (P = 0.013) and the more caudal the approach (P &lt; 0.01). Dural perforation (n = 123, 1.6%) was found to be influenced only by advanced age (P = 0.019). Unsuccessful catheter placement (n = 68, 0.94%) occurred more often in smaller individuals (P < 0.001) and at lower lumbar sites (P < 0.01). Amongst all cases with successful catheter placement a (partial) insufficient analgesia was found in 692 cases (8.8%). This risk of insufficient analgesia decreased with patient's age (P < 0.01), being least likely for punctures of the lower thoracic spine (P < 0.001). Conclusions: Compared to more cranial levels, EA of the lower spine is associated with an increased risk of sanguineous and unsuccessful puncture. Insufficient analgesia more often accompanies high thoracic and low lumbar approaches. The risk of a sanguineous puncture increases in elderly patients. Gender, weight and body mass index seem to have no influence on the investigated complications

A conceptual framework for evaluating cooking systems

PUBLISHED 7 March 2022Tami C Bond, Christian L, Orange, Paul R Medwell, George Sizoomu, Samer Abdelnour, Verena Brinkmann, Philip Lloyd and Crispin Pemberton-Pigot

Integrative Genomics Identifies the Molecular Basis of Resistance to Azacitidine Therapy in Myelodysplastic Syndromes

Myelodysplastic syndromes and chronic myelomonocytic leukemia are blood disorders characterized by ineffective hematopoiesis and progressive marrow failure that can transform into acute leukemia. The DNA methyltransferase inhibitor 5-azacytidine (AZA) is the most effective pharmacological option, but only ∼50% of patients respond. A response only manifests after many months of treatment and is transient. The reasons underlying AZA resistance are unknown, and few alternatives exist for non-responders. Here, we show that AZA responders have more hematopoietic progenitor cells (HPCs) in the cell cycle. Non-responder HPC quiescence is mediated by integrin α5 (ITGA5) signaling and their hematopoietic potential improved by combining AZA with an ITGA5 inhibitor. AZA response is associated with the induction of an inflammatory response in HPCs in vivo. By molecular bar coding and tracking individual clones, we found that, although AZA alters the sub-clonal contribution to different lineages, founder clones are not eliminated and continue to drive hematopoiesis even in complete responders.The authors acknowledge funding from the National Health and Medical Research Council (NHMRC), Leukaemia Foundation, Anthony Rothe Foundation, Cancer Institute for New South Wales, South Eastern Area Laboratory Services (SEALS), Wellcome Trust, Leukemia and Lymphoma Society, Medical Research Council (UK), Swedish Cancer Society, Cancer Society in Stockholm, Swedish Research Council, Bloodwise UK, and the NIHR Biomedical Research Centre, Oxford

Pulmonary venous circulating tumor cell dissemination before tumor resection and disease relapse

Approximately 50% of patients with early-stage non-small-cell lung cancer (NSCLC) who undergo surgery with curative intent will relapse within 5 years1,2. Detection of circulating tumor cells (CTCs) at the time of surgery may represent a tool to identify patients at higher risk of recurrence for whom more frequent monitoring is advised. Here we asked whether CellSearch-detected pulmonary venous CTCs (PV-CTCs) at surgical resection of early-stage NSCLC represent subclones responsible for subsequent disease relapse. PV-CTCs were detected in 48% of 100 patients enrolled into the TRACERx study3, were associated with lung-cancer-specific relapse and remained an independent predictor of relapse in multivariate analysis adjusted for tumor stage. In a case study, genomic profiling of single PV-CTCs collected at surgery revealed higher mutation overlap with metastasis detected 10 months later (91%) than with the primary tumor (79%), suggesting that early-disseminating PV-CTCs were responsible for disease relapse. Together, PV-CTC enumeration and genomic profiling highlight the potential of PV-CTCs as early predictors of NSCLC recurrence after surgery. However, the limited sensitivity of PV-CTCs in predicting relapse suggests that further studies using a larger, independent cohort are warranted to confirm and better define the potential clinical utility of PV-CTCs in early-stage NSCLC

GSTZ1 genotypes correlate with dichloroacetate pharmacokinetics and chronic side effects in multiple myeloma patients in a pilot phase 2 clinical trial

Dichloroacetate (DCA) is an investigational drug targeting the glycolytic hallmark of cancer by inhibiting pyruvate dehydrogenase kinases (PDK). It is metabolized by GSTZ1, which has common polymorphisms altering enzyme or promoter activity. GSTZ1 is also irreversibly inactivated by DCA. In the first clinical trial of DCA in a hematological malignancy, DiCAM (DiChloroAcetate in Myeloma), we have examined the relationship between DCA concentrations, GSTZ1 genotype, side effects, and patient response. DiCAM recruited seven myeloma patients in partial remission. DCA was administered orally for 3 months with a loading dose. Pharmacokinetics were performed on day 1 and 8. Trough and peak concentrations of DCA were measured monthly. GSTZ1 genotypes were correlated with drug concentrations, tolerability, and disease outcomes. One patient responded and two patients showed a partial response after one month of DCA treatment, which included the loading dose. The initial half‐life of DCA was shorter in two patients, correlating with heterozygosity for GSTZ1*A genotype, a high enzyme activity variant. Over 3 months, one patient maintained DCA trough concentrations approximately threefold higher than other patients, which correlated with a low activity promoter genotype (−1002A, rs7160195) for GSTZ1. This patient displayed the strongest response, but also the strongest neuropathy. Overall, serum concentrations of DCA were sufficient to inhibit the constitutive target PDK2, but unlikely to inhibit targets induced in cancer. Promoter GSTZ1 polymorphisms may be important determinants of DCA concentrations and neuropathy during chronic treatment. Novel dosing regimens may be necessary to achieve effective DCA concentrations in most cancer patients while avoiding neuropathy.This work was supported by The Canberra Hospital Private Practice Trust Fund, Cancer Council ACT Project Grant APP1103848, and the Monaro Committee for Cancer Researc