Strategic Idealizations of Science to Oppose Environmenal Regulation: A Case Study of Five TMDL Controversies

Proponents of environmental regulation have catalogued various strategies used by takeholders to delay or weaken regulatory efforts, including (1) manufacturing or magnifying uncertainty; (2) demanding “sound science” (and thereby imposing unreasonable standards of evidence); and (3) data quality initiatives that permit deconstruction of credible studies by highlighting inevitable assumptions, funding sources, and areas for further research. Such strategies can be termed “idealizations” of science insofar as they rely on an unrealistic image of good science as somehow capable of avoiding tentative conclusions, institutional interests, consensual assumptions, and the need for further research. The question remains, however, when does an argument based on scientific uncertainty reflect a valid concern, and when is such an argument merely strategic? This Article is based on a study that was structured to identify whether and how arguments and challenges based on idealizations of science were used in the initial (pre-litigation) stages of several Philadelphia-area water quality controversies. The purpose of this Article is to describe the results of our study, including our sense that idealized arguments, at least in the early stages of TMDL disputes, are not very effective

Strategic Idealizations of Science to Oppose Environmenal Regulation: A Case Study of Five TMDL Controversies

Proponents of environmental regulation have catalogued various strategies used by takeholders to delay or weaken regulatory efforts, including (1) manufacturing or magnifying uncertainty; (2) demanding “sound science” (and thereby imposing unreasonable standards of evidence); and (3) data quality initiatives that permit deconstruction of credible studies by highlighting inevitable assumptions, funding sources, and areas for further research. Such strategies can be termed “idealizations” of science insofar as they rely on an unrealistic image of good science as somehow capable of avoiding tentative conclusions, institutional interests, consensual assumptions, and the need for further research. The question remains, however, when does an argument based on scientific uncertainty reflect a valid concern, and when is such an argument merely strategic? This Article is based on a study that was structured to identify whether and how arguments and challenges based on idealizations of science were used in the initial (pre-litigation) stages of several Philadelphia-area water quality controversies. The purpose of this Article is to describe the results of our study, including our sense that idealized arguments, at least in the early stages of TMDL disputes, are not very effective

Strategic Idealizations of Science to Oppose Environmental Regulation: A Case Study of Five TMDL Controversies

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Pan-cancer Alterations of the MYC Oncogene and Its Proximal Network across the Cancer Genome Atlas

Although theMYConcogene has been implicated incancer, a systematic assessment of alterations ofMYC, related transcription factors, and co-regulatoryproteins, forming the proximal MYC network (PMN),across human cancers is lacking. Using computa-tional approaches, we define genomic and proteo-mic features associated with MYC and the PMNacross the 33 cancers of The Cancer Genome Atlas.Pan-cancer, 28% of all samples had at least one ofthe MYC paralogs amplified. In contrast, the MYCantagonists MGA and MNT were the most frequentlymutated or deleted members, proposing a roleas tumor suppressors.MYCalterations were mutu-ally exclusive withPIK3CA,PTEN,APC,orBRAFalterations, suggesting that MYC is a distinct onco-genic driver. Expression analysis revealed MYC-associated pathways in tumor subtypes, such asimmune response and growth factor signaling; chro-matin, translation, and DNA replication/repair wereconserved pan-cancer. This analysis reveals insightsinto MYC biology and is a reference for biomarkersand therapeutics for cancers with alterations ofMYC or the PMN

The Baltimore declaration toward the exploration of organoid intelligence

We, the participants of the First Organoid Intelligence Workshop - "Forming an OI Community" (22-24 February 2022), call on the international scientific community to explore the potential of human brain-based organoid cell cultures to advance our understanding of the brain and unleash new forms of biocomputing while recognizing and addressing the associated ethical implications. The term "organoid intelligence" (OI) has been coined to describe this research and development approach (1) in a manner consistent with the term "artificial intelligence" (AI) - used to describe the enablement of computers to perform tasks normally requiring human intelligence. OI has the potential for diverse and far-reaching applications that could benefit humankind and our planet, and which urge the strategic development of OI as a collaborative scientific discipline. OI holds promise to elucidate the physiology of human cognitive functions such as memory and learning. It presents game-changing opportunities in biological and hybrid computing that could overcome significant limitations in silicon-based computing. It offers the prospect of unparalleled advances in interfaces between brains and machines. Finally, OI could allow breakthroughs in modeling and treating dementias and other neurogenerative disorders that cause an immense and growing disease burden globally. Realizing the world-changing potential of OI will require scientific breakthroughs. We need advances in human stem cell technology and bioengineering to recreate brain architectures and to model their potential for pseudo-cognitive capabilities. We need interface breakthroughs to allow us to deliver input signals to organoids, measure output signals, and employ feedback mechanisms to model learning processes. We also need novel machine learning, big data, and AI technologies to allow us to understand brain organoids

Hyperoxemia and excess oxygen use in early acute respiratory distress syndrome : Insights from the LUNG SAFE study

Publisher Copyright: © 2020 The Author(s). Copyright: Copyright 2020 Elsevier B.V., All rights reserved.Background: Concerns exist regarding the prevalence and impact of unnecessary oxygen use in patients with acute respiratory distress syndrome (ARDS). We examined this issue in patients with ARDS enrolled in the Large observational study to UNderstand the Global impact of Severe Acute respiratory FailurE (LUNG SAFE) study. Methods: In this secondary analysis of the LUNG SAFE study, we wished to determine the prevalence and the outcomes associated with hyperoxemia on day 1, sustained hyperoxemia, and excessive oxygen use in patients with early ARDS. Patients who fulfilled criteria of ARDS on day 1 and day 2 of acute hypoxemic respiratory failure were categorized based on the presence of hyperoxemia (PaO2 > 100 mmHg) on day 1, sustained (i.e., present on day 1 and day 2) hyperoxemia, or excessive oxygen use (FIO2 ≥ 0.60 during hyperoxemia). Results: Of 2005 patients that met the inclusion criteria, 131 (6.5%) were hypoxemic (PaO2 < 55 mmHg), 607 (30%) had hyperoxemia on day 1, and 250 (12%) had sustained hyperoxemia. Excess FIO2 use occurred in 400 (66%) out of 607 patients with hyperoxemia. Excess FIO2 use decreased from day 1 to day 2 of ARDS, with most hyperoxemic patients on day 2 receiving relatively low FIO2. Multivariate analyses found no independent relationship between day 1 hyperoxemia, sustained hyperoxemia, or excess FIO2 use and adverse clinical outcomes. Mortality was 42% in patients with excess FIO2 use, compared to 39% in a propensity-matched sample of normoxemic (PaO2 55-100 mmHg) patients (P = 0.47). Conclusions: Hyperoxemia and excess oxygen use are both prevalent in early ARDS but are most often non-sustained. No relationship was found between hyperoxemia or excessive oxygen use and patient outcome in this cohort. Trial registration: LUNG-SAFE is registered with ClinicalTrials.gov, NCT02010073publishersversionPeer reviewe

Analysis of Epithelial and Mesenchymal Markers in Ovarian Cancer Reveals Phenotypic Heterogeneity and Plasticity

Peer reviewe

Effect of angiotensin-converting enzyme inhibitor and angiotensin receptor blocker initiation on organ support-free days in patients hospitalized with COVID-19

IMPORTANCE Overactivation of the renin-angiotensin system (RAS) may contribute to poor clinical outcomes in patients with COVID-19. Objective To determine whether angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) initiation improves outcomes in patients hospitalized for COVID-19. DESIGN, SETTING, AND PARTICIPANTS In an ongoing, adaptive platform randomized clinical trial, 721 critically ill and 58 non–critically ill hospitalized adults were randomized to receive an RAS inhibitor or control between March 16, 2021, and February 25, 2022, at 69 sites in 7 countries (final follow-up on June 1, 2022). INTERVENTIONS Patients were randomized to receive open-label initiation of an ACE inhibitor (n = 257), ARB (n = 248), ARB in combination with DMX-200 (a chemokine receptor-2 inhibitor; n = 10), or no RAS inhibitor (control; n = 264) for up to 10 days. MAIN OUTCOMES AND MEASURES The primary outcome was organ support–free days, a composite of hospital survival and days alive without cardiovascular or respiratory organ support through 21 days. The primary analysis was a bayesian cumulative logistic model. Odds ratios (ORs) greater than 1 represent improved outcomes. RESULTS On February 25, 2022, enrollment was discontinued due to safety concerns. Among 679 critically ill patients with available primary outcome data, the median age was 56 years and 239 participants (35.2%) were women. Median (IQR) organ support–free days among critically ill patients was 10 (–1 to 16) in the ACE inhibitor group (n = 231), 8 (–1 to 17) in the ARB group (n = 217), and 12 (0 to 17) in the control group (n = 231) (median adjusted odds ratios of 0.77 [95% bayesian credible interval, 0.58-1.06] for improvement for ACE inhibitor and 0.76 [95% credible interval, 0.56-1.05] for ARB compared with control). The posterior probabilities that ACE inhibitors and ARBs worsened organ support–free days compared with control were 94.9% and 95.4%, respectively. Hospital survival occurred in 166 of 231 critically ill participants (71.9%) in the ACE inhibitor group, 152 of 217 (70.0%) in the ARB group, and 182 of 231 (78.8%) in the control group (posterior probabilities that ACE inhibitor and ARB worsened hospital survival compared with control were 95.3% and 98.1%, respectively). CONCLUSIONS AND RELEVANCE In this trial, among critically ill adults with COVID-19, initiation of an ACE inhibitor or ARB did not improve, and likely worsened, clinical outcomes. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT0273570

Preclinical modelling of militarily relevant traumatic brain injuries: Challenges and recommendations for future directions.

As a follow-up to the 2008 state-of-the-art (SOTA) conference on traumatic brain injuries (TBIs), the 2015 event organized by the United States Department of Veterans Affairs (VA) Office of Research and Development (ORD) analysed the knowledge gained over the last 7 years as it relates to basic scientific methods, experimental findings, diagnosis, therapy, and rehabilitation of TBIs and blast-induced neurotraumas (BINTs). The current article summarizes the discussions and recommendations of the scientific panel attending the Preclinical Modeling and Therapeutic Development Workshop of the conference, with special emphasis on factors slowing research progress and recommendations for ways of addressing the most significant pitfalls