Clogging the machinery: the BBC's experiment in science coordination, 1949–1953

In 1949, physicist Mark Oliphant criticised the BBC’s handling of science in a letter to the Director General William Haley. It initiated a chain of events which led to the experimental appointment of a science adviser, Henry Dale, to improve the ‘coordination’ of science broadcasts. The experiment failed, but the episode revealed conflicting views of the BBC’s responsibility towards science held by scientists and BBC staff. For the scientists, science had a special status, both as knowledge and as an activity, which in their view obligated the BBC to make special arrangements for it. BBC staff, however, had their own professional procedures which they were unwilling to abandon. The events unfolded within a few years of the end of the Second World War, when social attitudes to science had been coloured by the recent conflict, and when the BBC itself was under scrutiny from the William Beveridge’s Committee. The BBC was also embarking on new initiatives, notably the revival of adult education. These contextual factors bear on the story, which is about the relationship between a public service broadcaster and the external constituencies it relies on, but must appear to remain independent from. The article therefore extends earlier studies showing how external bodies have attempted to manipulate the inner workings of the BBC to their own advantage (e.g. those by Doctor and Karpf) by looking at the little-researched area of science broadcasting. The article is largely based on unpublished archive documents

Office-based tracheoesophageal puncture: Updates in techniques and outcomes

PURPOSE: Tracheoesophageal Puncture (TEP) is an effective rehabilitation method for postlaryngectomy speech and has already been described as a procedure that is safely performed in the office. We review our long-term experience with office-based TEP over the past seven years in the largest cohort published to date. MATERIALS AND METHODS: A retrospective chart review was performed of all patients who underwent TEP by a single surgeon from 2005 through 2012, including office-based and operating room procedures. Indications for the chosen technique (office versus operating room) and surgical outcomes were evaluated. RESULTS: 59 patients underwent 72 TEP procedures, with 55 performed in the outpatient setting and 17 performed in the operating room, all without complication. The indications for performing TEP’s in the operating room included 2 primary TEP’s, 14 due to concomitant procedures requiring general anesthesia, and 1 due to failed attempt at office-based TEP. 19 patients with prior rotational or free flap reconstruction successfully underwent office-based TEP. CONCLUSIONS: TEP in an office-based setting with immediate voice prosthesis placement continues to be a safe method of voice rehabilitation for postlaryngectomy patients, including those who have previously undergone free flap or rotational flap reconstruction. Office-based TEP is now our primary approach for postlaryngectomy voice rehabilitation

Hematologic Dysfunction Criteria in Critically Ill Children: The PODIUM Consensus Conference

CONTEXT Studies of organ dysfunction in children are limited by a lack of consensus around organ dysfunction criteria. OBJECTIVES To derive evidence-informed, consensus-based criteria for hematologic dysfunction in critically ill children. DATA SOURCES Data sources included PubMed and Embase from January 1992 to January 2020. STUDY SELECTION Studies were included if they evaluated assessment/scoring tools to screen for hematologic dysfunction and assessed outcomes of mortality, functional status, organ-specific outcomes, or other patient-centered outcomes. Studies of adults or premature infants, animal studies, reviews/commentaries, small case series, and non-English language studies with inability to determine eligibility were excluded. DATA EXTRACTION Data were abstracted from each eligible study into a standard data extraction form along with risk of bias assessment. RESULTS Twenty-nine studies were included. The systematic review supports the following criteria for hematologic dysfunction: thrombocytopenia (platelet count <100000 cells/µL in patients without hematologic or oncologic diagnosis, platelet count <30000 cells/µL in patients with hematologic or oncologic diagnoses, or platelet count decreased ≥50% from baseline; or leukocyte count <3000 cells/µL; or hemoglobin concentration between 5 and 7 g/dL (nonsevere) or <5 g/dL (severe). LIMITATIONS Most studies evaluated pre-specified thresholds of cytopenias. No studies addressed associations between the etiology or progression of cytopenias overtime with outcomes, and no studies evaluated cellular function. CONCLUSIONS Hematologic dysfunction, as defined by cytopenia, is a risk factor for poor outcome in critically ill children, although specific threshold values associated with increased mortality are poorly defined by the current literature

The impact of restrictive transfusion practices on hemodynamically stable critically ill children without heart disease: a secondary analysis of the age of blood in children in the PICU trial∗

OBJECTIVES: Guidelines recommend against RBC transfusion in hemodynamically stable (HDS) children without cardiac disease, if hemoglobin is greater than or equal to 7 g/dL. We sought to assess the clinical and economic impact of compliance with RBC transfusion guidelines. DESIGN: A nonprespecified secondary analysis of noncardiac, HDS patients in the randomized trial Age of Blood in Children (NCT01977547) in PICUs. Costs analyzed included ICU stay and physician fees. Stabilized inverse propensity for treatment weighting was used to create a cohort balanced with respect to potential confounding variables. Weighted regression models were fit to evaluate outcomes based on guideline compliance. SETTING: Fifty international tertiary care centers. PATIENTS: Critically ill children 3 days to 16 years old transfused RBCs at less than or equal to 7 days of ICU admission. Six-hundred eighty-seven subjects who met eligibility criteria were included in the analysis. INTERVENTIONS: Initial RBC transfusions administered when hemoglobin was less than 7 g/dL were considered "compliant"or "non-compliant"if hemoglobin was greater than or equal to 7 g/dL. MEASUREMENTS AND MAIN RESULTS: Frequency of new or progressive multiple organ system dysfunction (NPMODS), ICU survival, and associated costs. The hypothesis was formulated after data collection but exposure groups were masked until completion of planned analyses. Forty-nine percent of patients (338/687) received a noncompliant initial transfusion. Weighted cohorts were balanced with respect to confounding variables (absolute standardized differences < 0.1). No differences were noted in NPMODS frequency (relative risk, 0.86; 95% CI, 0.61-1.22; p = 0.4). Patients receiving compliant transfusions had more ICU-free days (mean difference, 1.73; 95% CI, 0.57-2.88; p = 0.003). Compliance reduced mean costs in ICU by $38,845 U.S. dollars per patient (95$65,048-$12,641). CONCLUSIONS: Deferring transfusion until hemoglobin is less than 7 g/dL is not associated with increased organ dysfunction in this population but is independently associated with increased likelihood of live ICU discharge and lower ICU costs

Collaborative Design and Implementation of a Multisite Community Coalition Evaluation

Evaluation designs assessing community coalitions must balance measures of how coalitions do their work and evidence that the coalitions are making a difference. The Allies cross-site evaluation attempts to determine the combined effects of the seven coalitions’ work at the individual, organizational, and community levels. Principal components considered are (a) contextual factors of the coalition community, (b) coalition processes and structure, (c) planning and planning products, (d) implementation actions, (e) activities and collaborations, (f) anticipated intermediate outcomes, and (g) expected asthma related health outcomes. Measurements are quantitative and qualitative, and data generated by these methods are used as ends in themselves and as a way to confirm or inform other measures. Evaluation has been an integral part of the planning and implementation phases of the Allies coalition work, with a priority of involving all of the partners in conceiving of and deciding upon the elements of assessment.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/83257/1/08 Lachance et al. HPP 7.2 44S-55S.pd

Bacterial and enchytraeid abundance accelerate soil carbon turnover along a lowland vegetation gradient in interior Alaska

Boreal wetlands are characterized by a mosaic of plant communities, including forests, shrublands, grasslands, and fens, which are structured largely by changes in topography and water table position. The soil associated with these plant communities contain quantitatively and qualitatively different forms of soil organic matter (SOM) and nutrient availability that drive changes in biogeochemical cycling rates. Therefore different boreal plant communities likely contain different soil biotic communities which in turn affect rates of organic matter decomposition. We examined relationships between plant communities, microbial communities, enchytraeids, and soil C turnover in near-surface soils along a shallow topographic soil moisture and vegetation gradient in interior Alaska. We tested the hypothesis that as soil moisture increases along the gradient, surface soils would become increasingly dominated by bacteria and mesofauna and have more rapid rates of C turnover. We utilized bomb radiocarbon techniques to infer rates of C turnover and the 13C isotopic composition of SOM and respired CO 2 to infer the degree of soil humification. Soil phenol oxidase and peroxidase enzyme activities were generally higher in the rich fen compared with the forest and bog birch sites. Results indicated greater C fluxes and more rapid C turnover in the surface soils of the fen sites compared to the wetland forest and shrub sites. Quantitative PCR analyses of soil bacteria and archaea, combined with enchytraeid counts, indicated that surface soils from the lowland fen ecosystems had higher abundances of these microbial and mesofaunal groups. Fungal abundance was highly variable and not significantly different among sites. Microbial data was utilized in a food web model that confirmed that rapidly cycling systems are dominated by bacterial activity and enchytraeid grazing. However, our results also suggest that oxidative enzymes play an important role in the C mineralization process in saturated systems, which has been often ignored

Transfusion-related immunomodulation: review of the literature and implications for pediatric critical illness

Transfusion-related immunomodulation (TRIM) in the intensive care unit (ICU) is difficult to define and likely represents a complicated set of physiologic responses to transfusion, including both proinflammatory and immunosuppressive effects. Similarly, the immunologic response to critical illness in both adults and children is highly complex and is characterized by both acute inflammation and acquired immune suppression. How transfusion may contribute to or perpetuate these phenotypes in the ICU is poorly understood, despite the fact that transfusion is common in critically ill patients. Both hyperinflammation and severe immune suppression are associated with poor outcomes from critical illness, underscoring the need to understand potential immunologic consequences of blood product transfusion. In this review we outline the dynamic immunologic response to critical illness, provide clinical evidence in support of immunomodulatory effects of blood product transfusion, review preclinical and translational studies to date of TRIM, and provide insight into future research direction

Quantitative Analysis of Human Pluripotency and Neural Specification by In-Depth (Phospho)Proteomic Profiling

Controlled differentiation of human embryonic stem cells (hESCs) can be utilized for precise analysis of cell type identities during early development. We established a highly efficient neural induction strategy and an improved analytical platform, and determined proteomic and phosphoproteomic profiles of hESCs and their specified multipotent neural stem cell derivatives (hNSCs). This quantitative dataset (nearly 13,000 proteins and 60,000 phosphorylation sites) provides unique molecular insights into pluripotency and neural lineage entry. Systems-level comparative analysis of proteins (e.g., transcription factors, epigenetic regulators, kinase families), phosphorylation sites, and numerous biological pathways allowed the identification of distinct signatures in pluripotent and multipotent cells. Furthermore, as predicted by the dataset, we functionally validated an autocrine/paracrine mechanism by demonstrating that the secreted protein midkine is a regulator of neural specification. This resource is freely available to the scientific community, including a searchable website, PluriProt

Pharmacological perturbation of CDK9 using selective CDK9 inhibition or degradation

Cyclin-dependent kinase 9 (CDK9), an important regulator of transcriptional elongation, is a promising target for cancer therapy, particularly for cancers driven by transcriptional dysregulation. We characterized NVP-2, a selective ATP-competitive CDK9 inhibitor, and THAL-SNS-032, a selective CDK9 degrader consisting of a CDK-binding SNS-032 ligand linked to a thalidomide derivative that binds the E3 ubiquitin ligase Cereblon (CRBN). To our surprise, THAL-SNS-032 induced rapid degradation of CDK9 without affecting the levels of other SNS-032 targets. Moreover, the transcriptional changes elicited by THAL-SNS-032 were more like those caused by NVP-2 than those induced by SNS-032. Notably, compound washout did not significantly reduce levels of THAL-SNS-032-induced apoptosis, suggesting that CDK9 degradation had prolonged cytotoxic effects compared with CDK9 inhibition. Thus, our findings suggest that thalidomide conjugation represents a promising strategy for converting multi-targeted inhibitors into selective degraders and reveal that kinase degradation can induce distinct pharmacological effects compared with inhibition

Quantitative Analysis of Human Pluripotency and Neural Specification by In-Depth (Phospho)Proteomic Profiling

Controlled differentiation of human embryonic stem cells (hESCs) can be utilized for precise analysis of cell type identities during early development. We established a highly efficient neural induction strategy and an improved analytical platform, and determined proteomic and phosphoproteomic profiles of hESCs and their specified multipotent neural stem cell derivatives (hNSCs). This quantitative dataset (nearly 13,000 proteins and 60,000 phosphorylation sites) provides unique molecular insights into pluripotency and neural lineage entry. Systems-level comparative analysis of proteins (e.g., transcription factors, epigenetic regulators, kinase families), phosphorylation sites, and numerous biological pathways allowed the identification of distinct signatures in pluripotent and multipotent cells. Furthermore, as predicted by the dataset, we functionally validated an autocrine/paracrine mechanism by demonstrating that the secreted protein midkine is a regulator of neural specification. This resource is freely available to the scientific community, including a searchable website, PluriProt