CHALLENGING POLITICAL SPECTACLE THROUGH GRASSROOTS POLICY DIALOGUES

Can simply talking about policy strengthen democracy? Drawing on data collected for case studies of one Canadian and two U.S. grassroots organizations, we demonstrate that taking part in policy dialogues hosted by grassroots organizations enables participants to gain greater clarity regarding policy issues, policy processes, and citizens’ perspectives and enhances some participants’ ability to take direct action in policy processes. These outcomes, and the opportunities for authentic engagement in policy processes offered by grassroots policy dialogues, can help challenge contemporary policy processes characterized as political spectacle, and, ultimately, enhance democracy in education. Implications of the findings for grassroots organizations and the field of community organizing are also discussed.

A mechanism for the Arctic sea ice spring predictability barrier

The decline of Arctic sea ice extent has created a pressing need for accurate seasonal predictions of regional summer sea ice. Recent work has shown evidence for an Arctic sea ice spring predictability barrier, which may impose a sharp limit on regional forecasts initialized prior to spring. However, the physical mechanism for this barrier has remained elusive. In this work, we perform a daily sea ice mass (SIM) budget analysis in large ensemble experiments from two global climate models to investigate the mechanisms that underpin the spring predictability barrier. We find that predictability is limited in winter months by synoptically driven SIM export and negative feedbacks from sea ice growth. The spring barrier results from a sharp increase in predictability at melt onset, when ice‐albedo feedbacks act to enhance and persist the preexisting export‐generated mass anomaly. These results imply that ice thickness observations collected after melt onset are particularly critical for summer Arctic sea ice predictions

A mechanism for the Arctic sea ice spring predictability barrier

The decline of Arctic sea ice extent has created a pressing need for accurate seasonal predictions of regional summer sea ice. Recent work has shown evidence for an Arctic sea ice spring predictability barrier, which may impose a sharp limit on regional forecasts initialized prior to spring. However, the physical mechanism for this barrier has remained elusive. In this work, we perform a daily sea ice mass (SIM) budget analysis in large ensemble experiments from two global climate models to investigate the mechanisms that underpin the spring predictability barrier. We find that predictability is limited in winter months by synoptically driven SIM export and negative feedbacks from sea ice growth. The spring barrier results from a sharp increase in predictability at melt onset, when ice‐albedo feedbacks act to enhance and persist the preexisting export‐generated mass anomaly. These results imply that ice thickness observations collected after melt onset are particularly critical for summer Arctic sea ice predictions

Preconditioning of the Weddell Sea Polynya by the Ocean Mesoscale and Dense Water Overflows

The Weddell Sea polynya is a large opening in the open-ocean sea ice cover associated with intense deep convection in the ocean. A necessary condition to form and maintain a polynya is the presence of a strong subsurface heat reservoir. This study investigates the processes that control the stratification and hence the buildup of the subsurface heat reservoir in the Weddell Sea. To do so, a climate model run for 200 years under preindustrial forcing with two eddying resolutions in the ocean (0.25° CM2.5 and 0.10° CM2.6) is investigated. Over the course of the simulation, CM2.6 develops two polynyas in the Weddell Sea, while CM2.5 exhibits quasi-continuous deep convection but no polynyas, exemplifying that deep convection is not a sufficient condition for a polynya to occur. CM2.5 features a weaker subsurface heat reservoir than CM2.6 owing to weak stratification associated with episodes of gravitational instability and enhanced vertical mixing of heat, resulting in an erosion of the reservoir. In contrast, in CM2.6, the water column is more stably stratified, allowing the subsurface heat reservoir to build up. The enhanced stratification in CM2.6 arises from its refined horizontal grid spacing and resolution of topography, which allows, in particular, a better representation of the restratifying effect by transient mesoscale eddies and of the overflows of dense waters along the continental slope

MARIA M4:clinical evaluation of a prototype ultrawideband radar scanner for breast cancer detection

A microwave imaging system has been developed as a clinical diagnostic tool operating in the 3- to 8-GHz region using multistatic data collection. A total of 86 patients recruited from a symptomatic breast care clinic were scanned with a prototype design. The resultant three-dimensional images have been compared “blind” with available ultrasound and mammogram images to determine the detection rate. Images show the location of the strongest signal, and this corresponded in both older and younger women, with sensitivity of [Formula: see text] , which was found to be maintained in dense breasts. The pathway from clinical prototype to clinical evaluation is outlined

Volcanic glass from the 1.8 ka Taupō eruption (New Zealand) detected in Antarctic ice at ~ 230 CE.

Chemical anomalies in polar ice core records are frequently linked to volcanism; however, without the presence of (crypto)tephra particles, links to specific eruptions remain speculative. Correlating tephras yields estimates of eruption timing and potential source volcano, offers refinement of ice core chronologies, and provides insights into volcanic impacts. Here, we report on sparse rhyolitic glass shards detected in the Roosevelt Island Climate Evolution (RICE) ice core (West Antarctica), attributed to the 1.8 ka Taupō eruption (New Zealand)-one of the largest and most energetic Holocene eruptions globally. Six shards of a distinctive geochemical composition, identical within analytical uncertainties to proximal Taupō glass, are accompanied by a single shard indistinguishable from glass of the ~25.5 ka Ōruanui supereruption, also from Taupō volcano. This double fingerprint uniquely identifies the source volcano and helps link the shards to the climactic phase of the Taupō eruption. The englacial Taupō-derived glass shards coincide with a particle spike and conductivity anomaly at 278.84 m core depth, along with trachytic glass from a local Antarctic eruption of Mt. Melbourne. The assessed age of the sampled ice is 230 ± 19 CE (95% confidence), confirming that the published radiocarbon wiggle-match date of 232 ± 10 CE (2 SD) for the Taupō eruption is robust

Development of novel methods for non-canonical myeloma protein analysis with an innovative adaptation of immunofixation electrophoresis, native top-down mass spectrometry, and middle-down de novo sequencing

OBJECTIVES: Multiple myeloma (MM) is a malignant plasma cell neoplasm, requiring the integration of clinical examination, laboratory and radiological investigations for diagnosis. Detection and isotypic identification of the monoclonal protein(s) and measurement of other relevant biomarkers in serum and urine are pivotal analyses. However, occasionally this approach fails to characterize complex protein signatures. Here we describe the development and application of next generation mass spectrometry (MS) techniques, and a novel adaptation of immunofixation, to interrogate non-canonical monoclonal immunoproteins. METHODS: Immunoprecipitation immunofixation (IP-IFE) was performed on a Sebia Hydrasys Scan2. Middle-down de novo sequencing and native MS were performed with multiple instruments (21T FT-ICR, Q Exactive HF, Orbitrap Fusion Lumos, and Orbitrap Eclipse). Post-acquisition data analysis was performed using Xcalibur Qual Browser, ProSight Lite, and TDValidator. RESULTS: We adapted a novel variation of immunofixation electrophoresis (IFE) with an antibody-specific immunosubtraction step, providing insight into the clonal signature of gamma-zone monoclonal immunoglobulin (M-protein) species. We developed and applied advanced mass spectrometric techniques such as middle-down de novo sequencing to attain in-depth characterization of the primary sequence of an M-protein. Quaternary structures of M-proteins were elucidated by native MS, revealing a previously unprecedented non-covalently associated hetero-tetrameric immunoglobulin. CONCLUSIONS: Next generation proteomic solutions offer great potential for characterizing complex protein structures and may eventually replace current electrophoretic approaches for the identification and quantification of M-proteins. They can also contribute to greater understanding of MM pathogenesis, enabling classification of patients into new subtypes, improved risk stratification and the potential to inform decisions on future personalized treatment modalities

Parental energy-sensing pathways control intergenerational offspring sex determination in the nematode Auanema freiburgensis

Background: Environmental stimuli experienced by the parental generation influence the phenotype of subsequent generations (Demoinet et al., Proc Natl Acad Sci U S A 114:E2689-E2698, 2017; Burton et al., Nat Cell Biol 19:252–257, 2017; Agrawal et al., Nature 401:60-63, 1999). The effects of these stimuli on the parental generation may be passed through the germline, but the mechanisms at the basis of this non-Mendelian type of inheritance, their level of conservation, how they lead to adaptive vs non-adaptive, and intergenerational vs transgenerational inheritance are poorly understood. Here we show that modulation of nutrient-sensing pathways in the parental generation of the nematode Auanema freiburgensis regulates phenotypic plasticity of its offspring. Results: In response to con-specific pheromones indicative of stress, AMP-activated protein kinase (AMPK), mechanistic target of rapamycin complex 1 (mTORC1), and insulin signaling regulate stress resistance and sex determination across one generation, and these effects can be mimicked by pathway modulators. The effectors of these pathways are closely associated with the chromatin, and their regulation affects the chromatin acetylation status in the germline. Conclusion: These results suggest that highly conserved metabolic sensors regulate phenotypic plasticity through regulation of subcellular localization of their effectors, leading to changes in chromatin acetylation and epigenetic status of the germline

External influences and priority-setting for anti-cancer agents: a case study of media coverage in adjuvant trastuzumab for breast cancer

<p>Abstract</p> <p>Background</p> <p>Setting priorities for the funding of new anti-cancer agents is becoming increasingly complex. The funding of adjuvant trastuzumab for breast cancer has brought this dilemma to the fore. In this paper we review external factors that may influence decision-making bodies and present a case study of media response in Ontario, Canada to adjuvant trastuzumab for breast cancer.</p> <p>Methods</p> <p>A comprehensive search of the databases of Canadian national and local newspapers and television was performed. Articles pertaining to trastuzumab in adjuvant breast cancer as well as 17 other anti-cancer drugs and indications were retrieved. The search period was from the date when individual trial results were announced to the date funding was made available in Ontario.</p> <p>Results</p> <p>During the 2.6 months between the release of the trastuzumab results to funding approval in Ontario, we identified 51 episodes of media coverage. For the 17 other drugs/indications (7 breast and 10 non-breast), the median time to funding approval was 31 months (range 14–46). Other recent major advances in oncology such as adjuvant vinorelbine/cisplatin for resected NSCLC and docetaxel for advanced prostate cancer received considerably less media attention (17 media reports for each) than trastuzumab. The median number of media reports for breast cancer drugs was 4.5 compared to 2.5 for non-breast cancer drugs (p = 0.56).</p> <p>Conclusion</p> <p>Priority-setting for novel anti-cancer agents is a complex process that tries to ensure fair use of constrained resources to fund therapies with the best evidence of clinical benefit. However, this process is subject to external factors including the influence of media, patient advocates, politicians, and industry. The data in this case study serve to illustrate the significant involvement one (or all) of these external factors may play in the debate over priority-setting.</p