The Geopolitics of Climate Knowledge Mobilization:Transdisciplinary Research at the Science–Policy Interface(s) in the Americas

Climate change and sustainability science have become more international in scope and transdisciplinary in nature, in response to growing expectations that scientific knowledge directly informs collective action and transformation. In this article, we move past idealized models of the science–policy interface to examine the social processes and geopolitical dynamics of knowledge mobilization. We argue that sociotechnical imaginaries of transdisciplinary research, deployed in parallel to “universal” regimes of evidence-based decision-making from the global North, conceal how international collaborations of scientists and societal actors actually experience knowledge mobilization, its systemic barriers, and its paths to policy action. Through ethnographic study of a transdisciplinary research program in the Americas, coupled with in-depth analysis of Colombia, we reveal divergences in how participants envision and experience knowledge mobilization and identify persistent disparities that diminish the capacity of researchers to influence decision-making and fit climate knowledge within broader neoliberal development paradigms. Results of the study point to a plurality of science–policy interface(s), each shaped by national sociotechnical imaginaries, development priorities, and local social orders. We conclude that a geopolitical approach to transdisciplinary science is necessary to understand how climate and sustainability knowledge circulates unevenly in a world marked by persistent inequality and dominance. </jats:p

Combination of hydrogel nanoparticles and proteomics to reveal secreted proteins associated with decidualization of human uterine stromal cells

<p>Abstract</p> <p>Background</p> <p>Identification of secreted proteins of low abundance is often limited by abundant and high molecular weight (MW) proteins. We have optimised a procedure to overcome this limitation.</p> <p>Results</p> <p>Low MW proteins in the conditioned media of cultured cells were first captured using dual-size exclusion/affinity hydrogel nanoparticles and their identities were then revealed by proteomics.</p> <p>Conclusions</p> <p>This technique enables the analysis of secreted proteins of cultured cells low MW and low abundance.</p

Locally performed postoperative circulating tumour DNA testing performed during routine clinical care to predict recurrence of colorectal cancer

Background: Identifying patients at high risk for colorectal cancer recurrence is essential for improving prognosis. In the postoperative period, circulating tumour DNA (ctDNA) has been demonstrated as a significant prognostic indicator of recurrence. These results have been obtained under the strict rigours of clinical trials, but not validated in a real-world setting using in-house testing. We report the outcomes of locally performed postoperative ctDNA testing conducted during routine clinical care and the association with the recurrence of colorectal cancer. Methods: We recruited 36 consecutive patients with newly diagnosed colorectal cancer between 2018 and 2020. Postoperative plasma samples were collected at the first outpatient review following resection. Tumour-informed ctDNA analysis was performed using droplet digital polymerase chain reaction or targeted next-generation sequencing. Results: At the time of surgery, there were 24 patients (66.7%) with localized cancer, nine (25%) with nodal spread, and three (8.3%) with metastatic disease. The median time from surgery to plasma sample donation was 22 days (IQR 20–28 days). At least one somatic mutation was identified in primary tumour tissue for 28 (77.8%) patients. Postoperative ctDNA was detected in five patients (13.9%). The median duration of follow-up was 32.0 months (IQR 27.2–38.1 months). Two patients (5.56%) developed metastatic recurrence. However, neither had detectable postoperative ctDNA. There were no instances of loco-regional recurrence. Conclusion: Analysis of postoperative ctDNA testing can be performed locally, however this study did not reproduce the adverse association between detectable postoperative ctDNA and the development of colorectal cancer recurrence seen in clinical trials

Comparison of circulating tumour dna and extracellular vesicle dna by low-pass whole-genome sequencing reveals molecular drivers of disease in a breast cancer patient

© 2020 by the authors. Licensee MDPI, Basel, Switzerland. There is increasing recognition of circulating tumour DNA (ctDNA) as a non-invasive alternative to tumour tissue for the molecular characterisation and monitoring of disease. Recent evidence suggests that cancer-associated changes can also be detected in the DNA contained within extracellular vesicles (EVs). As yet, there has been limited investigation into the relationship between EV DNA and ctDNA, and no studies have examined the EV DNA of breast cancer patients. The aim of this study was to use low-pass whole-genome sequencing to identify copy number variants (CNVs) in serial samples of both ctDNA and EV DNA from a patient with breast cancer. Of the 52 CNVs identified in tumour DNA, 36 (69%) were detected in at least one ctDNA sample and 13 (25%) in at least one EV DNA sample. The number of detectable variants in ctDNA and EV DNA increased over the natural history of the patient’s disease, which was associated with progression to cerebral metastases. This case study demonstrates that, while CNVs are detectable in patient EV DNA, ctDNA has greater sensitivity than EV DNA for serial monitoring of breast cancer

Homelessness and water insecurity in the Global North: Trapped in the dwelling paradox

In this article, we introduce the “dwelling paradox” to explore how the state actively produces water insecurity for people experiencing homelessness in the Global North. We explain that the dwelling paradox is (1) produced by a modernist ideology of public service delivery that privileges water provision through private infrastructural connections in the home; (2) is reproduced by the welfare-warfare state, which has increasingly weaponized public water facilities and criminalized body functions in public space; and (3) is actively contested by some houseless communities, who challenge hegemonic ideals of the “home”—and its water infrastructure—as a private, atomized space. In advancing a relational and spatial understanding of water insecurity, we use the dwelling paradox to illustrate how unhoused people are caught in a space of institutional entrapment that is forged by state power and amplified by anti-homeless legislation. Such spaces of entrapment make it extremely difficult for unhoused people to achieve a safe, healthy, and thriving life—the basis of the human rights to water and sanitation. This article is categorized under: Human Water \u3e Water Governance

Low-coverage whole-genome sequencing of extracellular vesicle-associated DNA in patients with metastatic cancer

© 2021, The Author(s). Low-coverage whole-genome sequencing (LC-WGS) can provide insight into oncogenic molecular changes. Serum extracellular vesicles (EV) represent a novel liquid biopsy source of tumoral DNA. This study compared copy number alteration (CNA) profiles generated from LC-WGS of formalin-fixed paraffin-embedded (FFPE) tumoral DNA and EV-DNA obtained from cancer patients. Patients with squamous cell carcinoma of the base of tongue (n = 3) and cutaneous squamous cell carcinoma (n = 2) were included. LC-WGS (0.5-1X coverage) was performed on FFPE-DNA and serum EV-DNA. Similarity between CNA profiles was analysed using QDNAseq. FFPE samples had a mean CNA of 31 (range 17–50) over 1.9 × 109 (range 1.0–2.6 × 109) bp in length, and EV samples had a mean CNA value of 17 (range 7–19) over 7.6 × 108 (range 2.9–15 × 108) bp in length. A mean of 8 (range 0–21) CNA over 5.9 × 108 (range 1.6–14 × 108) bp in length was found to overlap between EV and FFPE-derived samples per patient. Although the mean correlation efficient between samples was r = 0.34 (range − .08 to 0.99), this was not statistically significant (p \u3e 0.05). Regions of highest deletion and duplication in FFPE samples were not well reflected in the EV-DNA. Selected CNA regions in EV-associated DNA were reflective of the primary tumor, however appreciation of global CNA and areas of most significant change was lost. The utility of LC-WGS of EV-derived DNA is likely limited to molecular alterations of known interest

The Extracellular Vesicle Citrullinome and Signature in a Piglet Model of Neonatal Seizures

Neonatal seizures are commonly associated with acute perinatal brain injury, while understanding regarding the downstream molecular pathways related to seizures remains unclear. Furthermore, effective treatment and reliable biomarkers are still lacking. Post-translational modifications can contribute to changes in protein function, and post-translational citrullination, which is caused by modification of arginine to citrulline via the calcium-mediated activation of the peptidylarginine deiminase (PAD) enzyme family, is being increasingly linked to neurological injury. Extracellular vesicles (EVs) are lipid-bilayer structures released from cells; they can be isolated from most body fluids and act as potential liquid biomarkers for disease conditions and response to treatment. As EVs carry a range of genetic and protein cargo that can be characteristic of pathological processes, the current study assessed modified citrullinated protein cargo in EVs isolated from plasma and CSF in a piglet neonatal seizure model, also following phenobarbitone treatment. Our findings provide novel insights into roles for PAD-mediated changes on EV signatures in neonatal seizures and highlight the potential of plasma- and CSF-EVs to monitor responses to treatment

A comparative study of extracellular vesicle-associated and cell-free DNA and RNA for HPV detection in oropharyngeal squamous cell carcinoma

Purpose: This study compares the detection sensitivity of two separate liquid biopsy sources, cell-free (cf) DNA/RNA and extracellular vesicle (EV)-associated DNA/RNA (EV-DNA/RNA), to identify circulating Human Papilloma Virus (HPV) DNA/RNA in plasma obtained from patients with oropharyngeal squamous cell carcinoma (OPCSCC). We also report on the longitudinal changes observed in HPV-DNA levels in response to treatment. Experimental design: A prospective study was conducted that included 22 patients with locally advanced disease and six patients with metastatic OPCSCC. Twenty-three patients had HPV-related OPCSCC defined by p16 immunohistochemistry. Levels of circulating HPV-DNA and HPV-RNA from plasma-derived cf-DNA/RNA and EV-DNA/RNA were quantified using digital droplet PCR. Results: Circulating HPV-DNA was detected with higher sensitivity in cf-DNA compared to EV-DNA at 91% vs. 42% (p = \u3c 0.001). Similarly, circulating tumoral HPV-RNA was detected at a higher sensitivity in cf-RNA compared to EV-RNA, at 83% vs. 50% (p = 0.0019). In the locally advanced cohort, 100% (n = 16) of HPV-OPCSCC patients demonstrated a reduction in circulating HPV-DNA levels in cf-DNA following curative treatment, with 81% of patients demonstrating complete clearance to undetectable levels. However, in metastatic HPV-OPCSCC patients (n = 4), HPV-DNA levels did not correlate with treatment response. Conclusion: Our study demonstrates that although HPV-DNA/RNA can be detected in EV associated DNA/RNA, cf-DNA/RNA is the more sensitive liquid biopsy medium. As circulating HPV-DNA levels were found to only correlate with treatment response in the locally advanced but not metastatic setting in our small cohort of patients, the use of HPV-DNA as a dynamic biomarker to monitor treatment response requires further evaluation. © 2020, The Author(s)

A comparative study of extracellular vesicle-associated and cell-free DNA and RNA for HPV detection in oropharyngeal squamous cell carcinoma

Purpose: This study compares the detection sensitivity of two separate liquid biopsy sources, cell-free (cf) DNA/RNA and extracellular vesicle (EV)-associated DNA/RNA (EV-DNA/RNA), to identify circulating Human Papilloma Virus (HPV) DNA/RNA in plasma obtained from patients with oropharyngeal squamous cell carcinoma (OPCSCC). We also report on the longitudinal changes observed in HPV-DNA levels in response to treatment. Experimental design: A prospective study was conducted that included 22 patients with locally advanced disease and six patients with metastatic OPCSCC. Twenty-three patients had HPV-related OPCSCC defined by p16 immunohistochemistry. Levels of circulating HPV-DNA and HPV-RNA from plasma-derived cf-DNA/RNA and EV-DNA/RNA were quantified using digital droplet PCR. Results: Circulating HPV-DNA was detected with higher sensitivity in cf-DNA compared to EV-DNA at 91% vs. 42% (p = \u3c 0.001). Similarly, circulating tumoral HPV-RNA was detected at a higher sensitivity in cf-RNA compared to EV-RNA, at 83% vs. 50% (p = 0.0019). In the locally advanced cohort, 100% (n = 16) of HPV-OPCSCC patients demonstrated a reduction in circulating HPV-DNA levels in cf-DNA following curative treatment, with 81% of patients demonstrating complete clearance to undetectable levels. However, in metastatic HPV-OPCSCC patients (n = 4), HPV-DNA levels did not correlate with treatment response. Conclusion: Our study demonstrates that although HPV-DNA/RNA can be detected in EV associated DNA/RNA, cf-DNA/RNA is the more sensitive liquid biopsy medium. As circulating HPV-DNA levels were found to only correlate with treatment response in the locally advanced but not metastatic setting in our small cohort of patients, the use of HPV-DNA as a dynamic biomarker to monitor treatment response requires further evaluation. © 2020, The Author(s)

Exposing the myths of household water insecurity in the global north: A critical review

Safe and secure water is a cornerstone of modern life in the global North. This article critically examines a set of prevalent myths about household water in high-income countries, with a focus on Canada and the United States. Taking a relational approach, we argue that household water insecurity is a product of institutionalized structures and power, manifests unevenly through space and time, and is reproduced in places we tend to assume are the most water-secure in the world. We first briefly introduce “modern water” and the modern infrastructural ideal, a highly influential set of ideas that have shaped household water provision and infrastructure development over the past two centuries. Against this backdrop, we consolidate evidence to disrupt a set of narratives about water in high-income countries: the notion that water access is universal, clean, affordable, trustworthy, and uniformly or equitably governed. We identify five thematic areas of future research to delineate an agenda for advancing scholarship and action—including challenges of legal and regulatory regimes, the housing-water nexus, water affordability, and water quality and contamination. Data gaps underpin the experiences of household water insecurity. Taken together, our review of water security for households in high-income countries provides a conceptual map to direct critical research in this area for the coming years