The Grid that Binds: The Renewable Energy Transition in Germany, France, and Italy

The current energy crisis and climate change are just some of the challenges that the European Union and its member states are forced to reckon with. The loss of fossil fuel supplies from Russia in the wake of the invasion of Ukraine forced the acceleration of the renewable energy transition and created a new set of problems to be addressed, namely the effectiveness of climate work that had already begun, and what the roadmap for the future would look like. Examining the history and infrastructure of Germany, France, and Italy presents insights into how this challenge can be met, and why countries take the paths they do when responding to such crises. Additionally, it demonstrates the most effective role of the European Union at this time. When the European Union does not enforce a single agenda on member states, and instead acts as a support structure that supports trans-European projects and partnerships, it more effectively maintains European unity and integration, allowing each member state to draw on its own resources most efficiently, while providing the financial and structural means to accelerate the renewable energy transition, improving Europe’s energy security as a whole, and working towards the climate goals established in the European Green Deal

How Do You Build a "Culture of Health"? A Critical Analysis of Challenges and Opportunities from Medical Anthropology.

The Robert Wood Johnson Foundation's Culture of Health Action Framework aims to "make health a shared value" and improve population health equity through widespread culture change. The authors draw upon their expertise as anthropologists to identify 3 challenges that they believe must be addressed in order to effectively achieve the health equity and population health improvement goals of the Culture of Health initiative: clarifying and demystifying the concept of "culture," contextualizing "community" within networks of power and inequality, and confronting the crises of trust and solidarity in the contemporary United States. The authors suggest that those who seek to build a "Culture of Health" refine their understanding of how "culture" is experienced, advocate for policies and practices that break down unhealthy consolidations of power, and innovate solutions to building consensus in a divided nation

2013 Colorado forest insect and disease update

The reports describes "an annual investigation of critical forest health issues, including the identification of priority areas across the state where current forest conditions demand timely action." They are intended to "expand Coloradans' knowledge of and interest in our state's forest resources.".Reports produced by the Colorado State Forest Service in conjunction with Colorado Department of Natural Resources, Division of Forestry.Includes bibliographical references.January 2014.Includes the 2013 Colorado forest insect and disease update supplement.The theme of the 2013 report is Caring for Colorado's Forests: Today's Challenges, Tomorrow's Opportunities. How best to care for this vital resource has been a major topic of discussion. This year's report focuses on the values our forests provide and includes several examples of the successful collaborative forest management programs that were created to address the impacts of mountain pine beetle, threats associated with wildfire, and protection of critical watersheds and other values at risk. Hopefully theseexamples will lead to the identification of other potential solutions to the challenges our forests are facing. One thing is clear: forest stewardship is best achieved through the collective efforts of private landowners, public land managers, non-governmentalconservation organizations, elected officials and other interested stakeholders. The mission of the Colorado State Forest Service is to "achieve stewardship of Colorado's diverse forest environments for the benefit of present and future generations." At no time in Colorado's history has the CSFS mission been so relevant - and working with stakeholders to identify and implement innovative programs will help us further our mission

Tips for Junior Doctors and Medical Students: Writing and Publishing Undergraduate Textbooks

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The induction of macrophage gene expression by LPS predominantly utilizes Myd88-independent signaling cascades

Myeloid differentiation protein-88 (MyD88) is a signal adaptor protein required for cytokine production following engagement of Toll-like receptors (TLRs) by their cognate ligands. Activation of both TLR-3 and TLR-4, however, can engage signaling events independent of MyD88 expression. The relative importance of these MyD88-dependent and -independent signaling pathways in the macrophage response to lipopolysaccharide (LPS) is unknown. Here we define these events using microarray expression profiling of LPS-stimulated macrophages taken from MyD88-null and wild-type mice. Of the 1,055 genes found to be LPS responsive, only 21.5% were dependent on MyD88 expression, with MyD88-independent genes constituting 74.7% of the genetic response. This MyD88-independent gene expression was predominantly transcriptionally regulated, as it was unaffected by cycloheximide blockade of new protein synthesis. A previously undescribed group of LPS-regulated genes (3.8%), whose induction or repression was significantly greater in the absence of MyD88, was also identified by these studies. The regulation of these genes suggested that MyD88 could serve as a molecular brake, constraining gene activity in a subset of LPS-responsive genes. The findings generated with LPS stimulation were recapitulated by exposure of macrophages to live Escherichia coli. These expression-profiling studies redefine the current dogma of TLR-4 signaling and establish that MyD88, although essential for some of the best-characterized macrophage responses to LPS, is not required for the regulation of the majority of genes engaged by macrophage exposure to endotoxin or live bacteria

A Comprehensive Study to Delineate the Role of an Extracellular Vesicle-Associated MicroRNA-29a in Chronic Methamphetamine Use Disorder

Extracellular vesicles (EVs), which express a repertoire of cargo molecules (cf. proteins, microRNA, lipids, etc.), have been garnering a prominent role in the modulation of several cellular processes. Here, using both non-human primate and rodent model systems, we provide evidence that brain-derived EV (BDE) miRNA, miR-29a-3p (mir-29a), is significantly increased during chronic methamphetamine (MA) exposure. Further, miR-29a levels show significant increase both with drug-seeking and reinstatement in a rat MA self-administration model. We also show that EV-associated miR-29a is enriched in EV pool comprising of small EVs and exomeres and further plays a critical role in MA-induced inflammation and synaptodendritic damage. Furthermore, treatment with the anti-inflammatory drug ibudilast (AV411), which is known to reduce MA relapse, decreased the expression of miR-29a and subsequently attenuated inflammation and rescued synaptodendritic injury. Finally, using plasma from MUD subjects, we provide translational evidence that EV-miR29a could potentially serve as a biomarker to detect neuronal damage in humans diagnosed with MA use disorder (MUD). In summary, our work suggests that EV-associated miR-29a-3p plays a crucial role in MUD and might be used as a potential blood-based biomarker for detecting chronic inflammation and synaptic damage

A comprehensive study to delineate the role of an extracellular vesicle-associated microRNA-29a in chronic methamphetamine use disorder

Extracellular vesicles (EVs), which express a repertoire of cargo molecules (cf. proteins, microRNA, lipids, etc.), have been garnering a prominent role in the modulation of several cellular processes. Here, using both non-human primate and rodent model systems, we provide evidence that brain-derived EV (BDE) miRNA, miR- 29a-3p (mir-29a), is significantly increased during chronic methamphetamine (MA) exposure. Further, miR-29a levels show significant increase both with drug-seeking and reinstatement in a rat MA self-administration model. We also show that EVassociated miR-29a is enriched in EV pool comprising of small EVs and exomeres and further plays a critical role in MA-induced inflammation and synaptodendritic damage. Furthermore, treatment with the anti-inflammatory drug ibudilast (AV411), which is known to reduce MA relapse, decreased the expression of miR-29a and subsequently attenuated inflammation and rescued synaptodendritic injury. Finally, using plasma fromMUDsubjects, we provide translational evidence that EV-miR29a could potentially serve as a biomarker to detect neuronal damage in humans diagnosed with MA use disorder (MUD). In summary, our work suggests that EVassociated miR-29a-3p plays a crucial role in MUD and might be used as a potential blood-based biomarker for detecting chronic inflammation and synaptic damage

Cost and feasibility: an exploratory case study comparing use of a literature review method with questionnaires, interviews and focus groups to identify barriers for a behaviour-change intervention

Background: It is often recommended that behaviour-change interventions be tailored to barriers. There is a scarcity of research into the best method of barrier identification, although combining methods has been suggested to be beneficial. This paper compares the feasibility and costs of three different methods of barrier identification used in three implementation projects conducted in primary care. Methods: Underpinned by a theory-base, project one used a questionnaire and interviews; project two used a single focus group and questionnaire, and project three used a literature review of published barriers. The feasibility of each project, as experienced by the research team, and labour costs are summarised. Results: The literature review of published barriers was the least costly and most feasible method, being quick to conduct and avoiding the challenges of recruitment experienced when using interviews or a questionnaire. The feasibility of using questionnaires was further reduced by the time taken develop the instruments. Conducting a single focus group was also found to be a more feasible method, taking less time than interviews to collect and analyse the barriers. Conclusions: Considering the ease of recruitment, time required and cost of the different methods to collect barriers is crucial at the start of implementation studies. The literature review method is the least costly and most feasible method. Use of a single focus group was found to be more feasible than conducting individual interviews or administering a questionnaire, with less recruitment challenges experienced, and quicker data collection. Future research would benefit from comparing the robustness of the methods in terms of the comprehensiveness of barriers identified

Using Real-World Data to Guide Ustekinumab Dosing Strategies for Psoriasis: A Prospective Pharmacokinetic-Pharmacodynamic Study.

Variation in response to biologic therapy for inflammatory diseases, such as psoriasis, is partly driven by variation in drug exposure. Real-world psoriasis data were used to develop a pharmacokinetic/pharmacodynamic (PK/PD) model for the first-line therapeutic antibody ustekinumab. The impact of differing dosing strategies on response was explored. Data were collected from a UK prospective multicenter observational cohort (491 patients on ustekinumab monotherapy, drug levels, and anti-drug antibody measurements on 797 serum samples, 1,590 measurements of Psoriasis Area Severity Index (PASI)). Ustekinumab PKs were described with a linear one-compartment model. A maximum effect (Emax ) model inhibited progression of psoriatic skin lesions in the turnover PD mechanism describing PASI evolution while on treatment. A mixture model on half-maximal effective concentration identified a potential nonresponder group, with simulations suggesting that, in future, the model could be incorporated into a Bayesian therapeutic drug monitoring "dashboard" to individualize dosing and improve treatment outcomes

Bringing numerous methods for expression and promoter analysis to a public cloud computing service

Every year, a large number of novel algorithms are introduced to the scientific community for a myriad of applications, but using these across different research groups is often troublesome, due to suboptimal implementations and specific dependency requirements. This does not have to be the case, as public cloud computing services can easily house tractable implementations within self-contained dependency environments, making the methods easily accessible to a wider public. We have taken 14 popular methods, the majority related to expression data or promoter analysis, developed these up to a good implementation standard and housed the tools in isolated Docker containers which we integrated into the CyVerse Discovery Environment, making these easily usable for a wide community as part of the CyVerse UK project