Recasting Economics as if the Climate and Global Ecology Really Mattered

Peer reviewedPublisher PD

Quantitative Electroencephalography in Guiding Treatment of Major Depression

This paper reviews significant contributions to the evidence for the use of quantitative electroencephalography features as biomarkers of depression treatment and examines the potential of such technology to guide pharmacotherapy. Frequency band abnormalities such as alpha and theta band abnormalities have shown promise as have combinatorial measures such as cordance (a measure combining alpha and theta power) and the Antidepressant Treatment Response Index in predicting medication treatment response. Nevertheless, studies have been hampered by methodological problems and inconsistencies, and these approaches have ultimately failed to elicit any significant interest in actual clinical practice. More recent machine learning approaches such as the Psychiatric Encephalography Evaluation Registry (PEER) technology and other efforts analyze large datasets to develop variables that may best predict response rather than test a priori hypotheses. PEER is a technology that may go beyond predicting response to a particular antidepressant and help to guide pharmacotherapy

Effective risk governance for environmental policy making: a knowledge management perspective

Effective risk management within environmental policy making requires knowledge on natural, economic and social systems to be integrated; knowledge characterised by complexity, uncertainty and ambiguity. We describe a case study in a (UK) central government department exploring how risk governance supports and hinders this challenging integration of knowledge. Forty-five semi-structured interviews were completed over a two year period. We found that lateral knowledge transfer between teams working on different policy areas was widely viewed as a key source of knowledge. However, the process of lateral knowledge transfer was predominantly informal and unsupported by risk governance structures. We argue this made decision quality vulnerable to a loss of knowledge through staff turnover, and time and resource pressures. Our conclusion is that the predominant form of risk governance framework, with its focus on centralised decision-making and vertical knowledge transfer is insufficient to support risk-based, environmental policy making. We discuss how risk governance can better support environmental policy makers through systematic knowledge management practices

Loss Factor Estimation Using the Impulse Response Decay Method on a Stiffened Structure

High-frequency vibroacoustic modeling is typically performed using energy-based techniques such as Statistical Energy Analysis (SEA). Energy models require an estimate of the internal damping loss factor. Unfortunately, the loss factor is difficult to estimate analytically, and experimental methods such as the power injection method can require extensive measurements over the structure of interest. This paper discusses the implications of estimating damping loss factors using the impulse response decay method (IRDM) from a limited set of response measurements. An automated procedure for implementing IRDM is described and then evaluated using data from a finite element model of a stiffened, curved panel. Estimated loss factors are compared with loss factors computed using a power injection method and a manual curve fit. The paper discusses the sensitivity of the IRDM loss factor estimates to damping of connected subsystems and the number and location of points in the measurement ensemble

Polypharmacy or medication washout: an old tool revisited

There has been a rapid increase in the use of polypharmacy in psychiatry possibly due to the introduction of newer drugs, greater availability of these newer drugs, excessive confidence in clinical trial results, widespread prescribing of psychotropic medications by primary care, and pressure to augment with additional medications for unresolved side effects or greater efficacy. Even the new generation of medications may not hold significant advantages over older drugs. In fact, there may be additional safety risks with polypharmacy being so widespread. Washout, as a clinical tool, is rarely done in medication management today. Studies have shown that augmenting therapy with additional medications resulted in 9.1%–34.1% dropouts due to intolerance of the augmentation, whereas studies of medication washout demonstrated only 5.9%–7.8% intolerance to the washout procedure. These perils justify reconsideration of medication washout before deciding on augmentation. There are unwarranted fears and resistance in the medical community toward medication washout, especially at the moment a physician is trying to decide whether to washout or add more medications to the treatment regimen. However, medication washout provides unique benefits to the physician: it establishes a new baseline of the disorder, helps identify medication efficacy from their adverse effects, and provides clarity of diagnosis and potential reduction of drug treatments, drug interactions, and costs. It may also reduce overall adverse events, not to mention a potential to reduce liability. After washout, physicians may be able to select the appropriate polypharmacy more effectively and safely, if necessary. Washout, while not for every patient, may be an effective tool for physicians who need to decide on whether to add potentially risky polypharmacy for a given patient. The risks of washout may, in some cases, be lower and the benefits may be clearly helpful for diagnosis, understanding medication effects, the doctor/patient relationship, and safer use of polypharmacy if indicated

Erroneously old radiocarbon ages from terrestrial pollen concentrates in Yellowstone Lake, Wyoming, USA

© The Author(s), 2021. This article is distributed under the terms of the Creative Commons Attribution License. The definitive version was published in [Schiller, C. M., Whitlock, C., Elder, K. L., Iverson, N. A., & Abbott, M. B. Erroneously old radiocarbon ages from terrestrial pollen concentrates in Yellowstone Lake, Wyoming, USA. Radiocarbon, 63(1), (2021): 321-342, https://doi.org/10.1017/RDC.2020.118.Accelerator mass spectrometry (AMS) dating of pollen concentrates is often used in lake sediment records where large, terrestrial plant remains are unavailable. Ages produced from chemically concentrated pollen as well as manually picked Pinaceae grains in Yellowstone Lake (Wyoming) sediments were consistently 1700–4300 cal years older than ages established by terrestrial plant remains, tephrochronology, and the age of the sediment-water interface. Previous studies have successfully utilized the same laboratory space and methods, suggesting the source of old-carbon contamination is specific to these samples. Manually picking pollen grains precludes admixture of non-pollen materials. Furthermore, no clear source of old pollen grains occurs on the deglaciated landscape, making reworking of old pollen grains unlikely. High volumes of CO2 are degassed in the Yellowstone Caldera, potentially introducing old carbon to pollen. While uptake of old CO2 through photosynthesis is minor (F14C approximately 0.99), old-carbon contamination may still take place in the water column or in surficial lake sediments. It remains unclear, however, what mechanism allows for the erroneous ages of highly refractory pollen grains while terrestrial plant remains were unaffected. In the absence of a satisfactory explanation for erroneously old radiocarbon ages from pollen concentrates, we propose steps for further study.This research was supported by NSF Grant No. 1515353 to C. Whitlock and sampling in Yellowstone National Park was conducted under permits YELL-SCI-0009 and YELL-SCI-5054

A proposed syntax for Minimotif Semantics, version 1

<p>Abstract</p> <p>Background</p> <p>One of the most important developments in bioinformatics over the past few decades has been the observation that short linear peptide sequences (minimotifs) mediate many classes of cellular functions such as protein-protein interactions, molecular trafficking and post-translational modifications. As both the creators and curators of a database which catalogues minimotifs, Minimotif Miner, the authors have a unique perspective on the commonalities of the many functional roles of minimotifs. There is an obvious usefulness in standardizing functional annotations both in allowing for the facile exchange of data between various bioinformatics resources, as well as the internal clustering of sets of related data elements. With these two purposes in mind, the authors provide a proposed syntax for minimotif semantics primarily useful for functional annotation.</p> <p>Results</p> <p>Herein, we present a structured syntax of minimotifs and their functional annotation. A syntax-based model of minimotif function with established minimotif sequence definitions was implemented using a relational database management system (RDBMS). To assess the usefulness of our standardized semantics, a series of database queries and stored procedures were used to classify SH3 domain binding minimotifs into 10 groups spanning 700 unique binding sequences.</p> <p>Conclusion</p> <p>Our derived minimotif syntax is currently being used to normalize minimotif covalent chemistry and functional definitions within the MnM database. Analysis of SH3 binding minimotif data spanning many different studies within our database reveals unique attributes and frequencies which can be used to classify different types of binding minimotifs. Implementation of the syntax in the relational database enables the application of many different analysis protocols of minimotif data and is an important tool that will help to better understand specificity of minimotif-driven molecular interactions with proteins.</p

A Phase 1 study of intravenous infusions of tigecycline in patients with acute myeloid leukemia.

Acute myeloid leukemia (AML) cells meet the higher energy, metabolic, and signaling demands of the cell by increasing mitochondrial biogenesis and mitochondrial protein translation. Blocking mitochondrial protein synthesis through genetic and chemical approaches kills human AML cells at all stages of development in vitro and in vivo. Tigecycline is an antimicrobial that we found inhibits mitochondrial protein synthesis in AML cells. Therefore, we conducted a phase 1 dose-escalation study of tigecycline administered intravenously daily 5 of 7 days for 2 weeks to patients with AML. A total of 27 adult patients with relapsed and refractory AML were enrolled in this study with 42 cycles being administered over seven dose levels (50-350 mg/day). Two patients experienced DLTs related to tigecycline at the 350 mg/day level resulting in a maximal tolerated dose of tigecycline of 300 mg as a once daily infusion. Pharmacokinetic experiments showed that tigecycline had a markedly shorter half-life in these patients than reported for noncancer patients. No significant pharmacodynamic changes or clinical responses were observed. Thus, we have defined the safety of once daily tigecycline in patients with refractory AML. Future studies should focus on schedules of the drug that permit more sustained target inhibition