Understanding and managing uncertainty and variability for wastewater monitoring beyond the pandemic : lessons learned from the United Kingdom national COVID-19 surveillance programmes

The COVID-19 pandemic has put unprecedented pressure on public health resources around the world. From adversity, opportunities have arisen to measure the state and dynamics of human disease at a scale not seen before. In the United Kingdom, the evidence that wastewater could be used to monitor the SARS-CoV-2 virus prompted the development of National wastewater surveillance programmes. The scale and pace of this work has proven to be unique in monitoring of virus dynamics at a national level, demonstrating the importance of wastewater-based epidemiology (WBE) for public health protection. Beyond COVID-19, it can provide additional value for monitoring and informing on a range of biological and chemical markers of human health. A discussion of measurement uncertainty associated with surveillance of wastewater, focusing on lessons-learned from the UK programmes monitoring COVID-19 is presented, showing that sources of uncertainty impacting measurement quality and interpretation of data for public health decision-making, are varied and complex. While some factors remain poorly understood, we present approaches taken by the UK programmes to manage and mitigate the more tractable sources of uncertainty. This work provides a platform to integrate uncertainty management into WBE activities as part of global One Health initiatives beyond the pandemic

The experience of the International Consortium on Acute Promyelocytic Leukemia in monitoring minimal residual disease in acute promyelocytic leukaemia

Fundacao de Amparo a Pesquisa do Estado de Sao Paulo (FAPESP)Univ Sao Paulo, Dept Internal Med, Div Haematol, Ribeirao Preto, BrazilUniv Sao Paulo, Dept Internal Med, Div Clin Oncol, Ribeirao Preto, BrazilUniv Sao Paulo, Med Sch Ribeirao Preto, Ctr Cell Based Therapy, Ribeirao Preto, BrazilUniv Fed Pernambuco, Dept Genet, Recife, PE, BrazilSabin Clin Lab, Brasilia, DF, BrazilFdn Hematol & Hemoterapia Pernambuco HEMOPE, Recife, PE, BrazilUniv Fed Rio Grande do Sul, Haematol Serv, Univ Hosp, Porto Alegre, RS, BrazilUniv Fed Parana, Bone Marrow Transplantat Unit, Univ Hosp, Curitiba, Parana, BrazilUniv Estadual Campinas, Hemoctr, Campinas, SP, BrazilUniv Fed Minas Gerais, Haematol Serv, Univ Hosp, Belo Horizonte, MG, BrazilUniv Fed Sao Paulo, Div Haematol, Sao Paulo, BrazilSanta Casa Med Sch, Haematol Serv, Sao Paulo, BrazilUniv Valencia, Hosp Univ & Politecn La Fe, Dept Haematol, Valencia, BrazilUniv Valencia, Dept Med, Valencia, BrazilUniv Tor Vergata, Dept Biomed & Prevent, Rome, ItalySanta Lucia Fdn, Rome, ItalyKings Coll London, Fac Life Sci & Med, Dept Med & Mol Genet, London, EnglandUniv Fed Sao Paulo, Div Haematol, Sao Paulo, BrazilFAPESP: 2013/08135-2FAPESP: 2011/17111-4Web of Scienc

The experience of the International Consortium on Acute Promyelocytic Leukemia in monitoring minimal residual disease in acute promyelocytic leukaemia

Fundacao de Amparo a Pesquisa do Estado de Sao Paulo (FAPESP)Univ Sao Paulo, Dept Internal Med, Div Haematol, Ribeirao Preto, BrazilUniv Sao Paulo, Dept Internal Med, Div Clin Oncol, Ribeirao Preto, BrazilUniv Sao Paulo, Med Sch Ribeirao Preto, Ctr Cell Based Therapy, Ribeirao Preto, BrazilUniv Fed Pernambuco, Dept Genet, Recife, PE, BrazilSabin Clin Lab, Brasilia, DF, BrazilFdn Hematol & Hemoterapia Pernambuco HEMOPE, Recife, PE, BrazilUniv Fed Rio Grande do Sul, Haematol Serv, Univ Hosp, Porto Alegre, RS, BrazilUniv Fed Parana, Bone Marrow Transplantat Unit, Univ Hosp, Curitiba, Parana, BrazilUniv Estadual Campinas, Hemoctr, Campinas, SP, BrazilUniv Fed Minas Gerais, Haematol Serv, Univ Hosp, Belo Horizonte, MG, BrazilUniv Fed Sao Paulo, Div Haematol, Sao Paulo, BrazilSanta Casa Med Sch, Haematol Serv, Sao Paulo, BrazilUniv Valencia, Hosp Univ & Politecn La Fe, Dept Haematol, Valencia, BrazilUniv Valencia, Dept Med, Valencia, BrazilUniv Tor Vergata, Dept Biomed & Prevent, Rome, ItalySanta Lucia Fdn, Rome, ItalyKings Coll London, Fac Life Sci & Med, Dept Med & Mol Genet, London, EnglandUniv Fed Sao Paulo, Div Haematol, Sao Paulo, BrazilFAPESP: 2013/08135-2FAPESP: 2011/17111-4Web of Scienc

Comparison Between RT-PCR and RQ-PCR for Minimal Residual Disease Detection in Acute Promyelocytic Leukemia: The International Consortium on Acute Promyelocytic Leukemia (IC-APL) Experience

Univ Sao Paulo, Ribeirao Preto Med Sch, BR-14049 Ribeirao Preto, BrazilUniv Brasilia, Sch Med, Brasilia, DF, BrazilHEMOPE, Recife, PE, BrazilUniv Fed Rio Grande do Sul, Porto Alegre, RS, BrazilUniv Fed Parana, Hosp Clin, BR-80060000 Curitiba, PR, BrazilUniv Estadual Campinas, Natl Inst Sci & Technol Blood, Hematol & Hemotherapy Ctr, Campinas, SP, BrazilUniv Fed Minas Gerais, Clin Hosp, Belo Horizonte, MG, BrazilUNIFESP EPM, Sect Hematol & Blood Transfus, Dept Clin & Expt Oncol, Sao Paulo, BrazilSanta Casa Med Sch, Sao Paulo, BrazilAlbert Einstein Coll Med, Bronx, NY 10467 USAErasmus MC, Dept Hematol, Rotterdam, NetherlandsSt Jude Childrens Hosp, Memphis, TN 38105 USAUniv Roma Tor Vergata, Rome, ItalyKings Coll London, Sch Med, Dept Med & Mol Genet, London WC2R 2LS, EnglandUniv Hosp La Fe, Dept Hematol, Valencia, SpainUNIFESP EPM, Sect Hematol & Blood Transfus, Dept Clin & Expt Oncol, Sao Paulo, BrazilWeb of Scienc

Prognostic impact of KMT2E transcript levels on outcome of patients with acute promyelocytic leukaemia treated with all-trans retinoic acid and anthracycline-based chemotherapy: An International Consortium on Acute Promyelocytic Leukaemia study

The KMT2E (MLL5) gene encodes a histone methyltransferase implicated in the positive control of genes related to haematopoiesis. Its close relationship with retinoic acid-induced granulopoiesis suggests that the deregulated expression of KMT2E might lead acute promyelocytic leukaemia (APL) blasts to become less susceptible to the conventional treatment protocols. Here, we assessed the impact of KMT2E expression on the prognosis of 121 APL patients treated with ATRA and anthracycline-based chemotherapy. Univariate analysis showed that complete remission (P = 0·006), 2-year overall survival (OS) (P = 0·005) and 2-year disease-free survival (DFS) rates (P = 0·037) were significantly lower in patients with low KMT2E expression; additionally, the 2-year cumulative incidence of relapse was higher in patients with low KMT2E expression (P = 0·04). Multivariate analysis revealed that low KMT2E expression was independently associated with lower remission rate (odds ratio [OR]: 7·18, 95% confidence interval [CI]: 1·71-30·1; P = 0·007) and shorter OS (hazard ratio [HR]: 0·27, 95% CI: 0·08-0·87; P = 0·029). Evaluated as a continuous variable, KMT2E expression retained association with poor remission rate (OR: 10·3, 95% CI: 2·49-43·2; P = 0·001) and shorter survival (HR: 0·17, 95% IC: 0·05-0·53; P = 0·002), while the association with DFS was of marginal significance (HR: 1·01; 95% CI: 0·99-1·02; P = 0·06). In summary, low KMT2E expression may predict poor outcome in APL patients

High Δnp73/TAp73 ratio is associated with poor prognosis in acute promyelocytic leukemia

The TP73 gene transcript is alternatively spliced and translated into the transcriptionally active (TAp73) or inactive (ΔNp73) isoforms, with opposite effects on the expression of p53 target genes and on apoptosis induction. The imbalance between ΔNp73 and TAp73 may contribute to tumorigenesis and resistance to chemotherapy in human cancers, including hematologic malignancies. In acute promyelocytic leukemia (APL), both isoforms are expressed, but their relevance in determining response to therapy and contribution to leukemogenesis remains unknown. Here, we provide the first evidence that a higher ΔNp73/TAp73 RNA expression ratio is associated with lower survival, lower disease-free survival, and higher risk of relapse in patients with APL homogeneously treated with all-trans retinoic acid and anthracycline-based chemotherapy, according to the International Consortium on Acute Promyelocytic Leukemia (IC-APL) study. Cox proportional hazards modeling showed that a high ΔNp73/TAp73 ratio was independently associated with shorter overall survival (hazard ratio, 4.47; 95% confidence interval, 1.64-12.2; P = .0035). Our data support the hypothesis that the ΔNp73/TAp73 ratio is an important determinant of clinical response in APL and may offer a therapeutic target for enhancing chemosensitivity in blast cells