Measurable residual mutated IDH1 before allogeneic transplant for acute myeloid leukemia.

Measurable residual disease (MRD) in adults with acute myeloid leukemia (AML) in complete remission is an important prognostic marker, but detection methodology requires optimization. Persistence of mutated NPM1 or FLT3-ITD in the blood of adult patients with AML in first complete remission (CR1) prior to allogeneic hematopoietic cell transplant (alloHCT) associates with increased relapse and death after transplant. The prognostic implications of persistence of other common AML-associated mutations, such as IDH1, at this treatment landmark however remain incompletely defined.

Measurable residual mutated IDH2 before allogeneic transplant for acute myeloid leukemia.

Routine genetic profiling of acute myeloid leukemia (AML) at initial diagnosis has allowed subgroup specific prognostication, drug development, and clinical management strategies. The optimal approach for treatment response assessment for AML subgroups has not yet however been determined. A nationwide cohort of 257 adult patients in first remission (CR1) from AML associated with an IDH2 mutation (IDH2m) undergoing allogeneic transplant during the period 2013-2019 in the United States had rates of relapse and survival three years after transplantation of 24% and 71%, respectively.

Persistent mutations are not associated with increased relapse or death in patients with -mutated acute myeloid leukemia undergoing allogeneic hematopoietic cell transplant with post-transplant cyclophosphamide.

The presence of measurable residual disease (MRD) prior to an allogeneic hematopoietic transplant (alloHCT) in Acute Myeloid Leukemia (AML) has been shown to be associated with an increased risk of post-transplant relapse. Since the Isocitrate Dehydrogenase genes (/) are mutated in a considerable proportion of patients with AML, we studied if these mutations would serve as useful targets for MRD. Fifty-five -mutated AML patients undergoing non-myeloablative alloHCT with post-transplant cyclophosphamide at a single center were sequenced at baseline using a multi-gene panel followed by targeted testing for persistent mutations at the pre- and post-alloHCT timepoints by digital droplet PCR or error-corrected next generation sequencing.

Measurable Residual before Allogeneic Transplant for Acute Myeloid Leukemia.

Measurable residual disease (MRD) in adults with acute myeloid leukemia (AML) in complete remission is an important prognostic marker, but detection methodology requires optimization. The persistence of mutated or -ITD in the blood of adult patients with AML in first complete remission (CR1) prior to allogeneic hematopoetic cell transplant (alloHCT) has been established as associated with increased relapse and death after transplant. The prognostic implications of persistence of other common AML-associated mutations, such as , at this treatment landmark however remains incompletely defined.

Contrived Materials and a Data Set for the Evaluation of Liquid Biopsy Tests: A Blood Profiling Atlas in Cancer (BLOODPAC) Community Study.

The Blood Profiling Atlas in Cancer (BLOODPAC) Consortium is a collaborative effort involving stakeholders from the public, industry, academia, and regulatory agencies focused on developing shared best practices on liquid biopsy. This report describes the results from the JFDI (Just Freaking Do It) study, a BLOODPAC initiative to develop standards on the use of contrived materials mimicking cell-free circulating tumor DNA, to comparatively evaluate clinical laboratory testing procedures. Nine independent laboratories tested the concordance, sensitivity, and specificity of commercially available contrived materials with known variant-allele frequencies (VAFs) ranging from 0.

Droplet digital PCR for the detection of second-generation tyrosine kinase inhibitor-resistant BCR::ABL1 kinase domain mutations in chronic myeloid leukemia.

One of the indications for BCR::ABL1 mutation testing in chronic myeloid leukemia (CML) is when tyrosine kinase inhibitor therapy (TKI) needs to be changed for unsatisfactory response. In this study, we evaluated a droplet digital PCR (ddPCR)-based multiplex strategy for the detection and quantitation of transcripts harbouring mutations conferring resistance to second-generation TKIs (2GTKIs). Parallel quantitation of e13a2, e14a2 and e1a2 BCR::ABL1 fusion transcripts enables to express results as percentage of mutation positive- over total BCR::ABL1 transcripts.

Between Laboratory Reproducibility of DNA Extraction from Human Blood and Fresh Frozen Tissue.

Standardization of molecular diagnostics is fundamental for effective application of genetic analyses in personalized medicine. The amount of DNA extracted from a specimen can have a significant impact on diagnostic accuracy, especially in cases where the diagnostic variant has a low concentration such as cancer. Blood and tissue samples were supplied to genetic laboratories to assess the reproducibility of extraction methodologies; DNA was extracted using participants' routine procedures and returned to the external quality assessment provider.

Building a Social Mandate for Climate Action: Lessons from COVID-19.

The COVID-19 imposed lockdown has led to a number of temporary environmental side effects (reduced global emissions, cleaner air, less noise), that the climate community has aspired to achieve over a number of decades. However, these benefits have been achieved at a massive cost to welfare and the economy. This commentary draws lessons from the COVID-19 crisis for climate change.

A comparative study of digital PCR and real-time qPCR for the detection and quantification of HPV mRNA in sentinel lymph nodes of cervical cancer patients.

Background: Qualitative analyses showed that the presence of HPV mRNA in sentinel lymph nodes of cervical cancer patients with pN0 status is associated with significantly decreased recurrence free survival. To further address the clinical potential of the strategy and to define prognostic threshold levels it is necessary to use a quantitative assay. Here, we compare two methods of quantification: digital PCR and standard quantitative PCR.

'Green' on the ground but not in the air: Pro-environmental attitudes are related to household behaviours but not discretionary air travel.

The rise in greenhouse gas emissions from air travel could be reduced by individuals voluntarily abstaining from, or reducing, flights for leisure and recreational purposes. In theory, we might expect that people with pro-environmental value orientations and concerns about the risks of climate change, and those who engage in more pro-environmental household behaviours, would also be more likely to abstain from such voluntary air travel, or at least to fly less far. Analysis of two large datasets from the United Kingdom, weighted to be representative of the whole population, tested these associations.

Public Reception of Climate Science: Coherence, Reliability, and Independence.

Possible measures to mitigate climate change require global collective actions whose impacts will be felt by many, if not all. Implementing such actions requires successful communication of the reasons for them, and hence the underlying climate science, to a degree that far exceeds typical scientific issues which do not require large-scale societal response. Empirical studies have identified factors, such as the perceived level of consensus in scientific opinion and the perceived reliability of scientists, that can limit people's trust in science communicators and their subsequent acceptance of climate change claims.

Geoengineering, climate change scepticism and the 'moral hazard' argument: an experimental study of UK public perceptions.

Many commentators have expressed concerns that researching and/or developing geoengineering technologies may undermine support for existing climate policies-the so-called moral hazard argument. This argument plays a central role in policy debates about geoengineering. However, there has not yet been a systematic investigation of how members of the public view the moral hazard argument, or whether it impacts on people's beliefs about geoengineering and climate change.

Exploring early public responses to geoengineering.

Proposals for geoengineering the Earth's climate are prime examples of emerging or 'upstream' technologies, because many aspects of their effectiveness, cost and risks are yet to be researched, and in many cases are highly uncertain. This paper contributes to the emerging debate about the social acceptability of geoengineering technologies by presenting preliminary evidence on public responses to geoengineering from two of the very first UK studies of public perceptions and responses. The discussion draws upon two datasets: qualitative data (from an interview study conducted in 42 households in 2009), and quantitative data (from a subsequent nationwide survey (n=1822) of British public opinion).

Communicating environmental risks: Clarifying the severity effect in interpretations of verbal probability expressions.

Verbal probability expressions are frequently used to communicate risk and uncertainty. The Intergovernmental Panel on Climate Change (IPCC), for example, uses them to convey risks associated with climate change. Given the potential for human action to mitigate future environmental risks, it is important to understand how people respond to these expressions.

Integration of metabolomics and transcriptomics data to aid biomarker discovery in type 2 diabetes.

Type 2 diabetes (T2D), one of the most common diseases in the western world, is characterized by insulin resistance and impaired beta-cell function but currently it is difficult to determine the precise pathophysiology in individual T2D patients. Non-targeted metabolomics technologies have the potential for providing novel biomarkers of disease and drug efficacy, and are increasingly being incorporated into biomarker exploration studies. Contextualization of metabolomics results is enhanced by integration of study data from other platforms, such as transcriptomics, thus linking known metabolites and genes to relevant biochemical pathways.

Evaluating science arguments: evidence, uncertainty, and argument strength.

Public debates about socioscientific issues are increasingly prevalent, but the public response to messages about, for example, climate change, does not always seem to match the seriousness of the problem identified by scientists. Is there anything unique about appeals based on scientific evidence-do people evaluate science and nonscience arguments differently? In an attempt to apply a systematic framework to people's evaluation of science arguments, the authors draw on the Bayesian approach to informal argumentation. The Bayesian approach permits questions about how people evaluate science arguments to be posed and comparisons to be made between the evaluation of science and nonscience arguments.

Estimating the probability of negative events.

How well we are attuned to the statistics of our environment is a fundamental question in understanding human behaviour. It seems particularly important to be able to provide accurate assessments of the probability with which negative events occur so as to guide rational choice of preventative actions. One question that arises here is whether or not our probability estimates for negative events are systematically biased by their severity.