Determining information for inclusion in a decision-support intervention for clinical trial participation : A modified Delphi approach

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The acanthamoeba shikimate pathway has a unique molecular arrangement and is essential for aromatic amino acid biosynthesis

The shikimate pathway is the only known biosynthetic route for de novo synthesis of aromatic compounds. It is described as an ancient eukaryotic innovation that has been retained in a subset of eukaryotes, replaced in plants through the acquisition of the chloroplast, but lost in many including humans. Herein, we demonstrate that Acanthamoeba castellanii possesses the shikimate pathway by biochemical and a combination of bioinformatics and molecular biological methods. The growth of A. castellanii (Neff strain and a recently isolated clinical specimen, both T4 genotypes) is inhibited by glyphosate [N-(phosphonomethyl) glycine], an inhibitor of EPSP synthase and the addition of phenylalanine and tryptophan, which are dependent on the shikimate pathway, rescued A. castellanii from glyphosate indicating that glyphosate was specific in action. A. castellanii has a novel complement of shikimate pathway enzymes including unique gene fusions, two Type I and one Type II DAHP synthases (for which their likely sensitivities to feedback inhibition by phenylalanine, tyrosine and tryptophan has been modelled) and a canonical chorismate synthase. The shikimate pathway in A. castellanii therefore has a novel molecular arrangement, is required for amino acid biosynthesis and represents an attractive target for antimicrobials

A core outcome set for localised prostate cancer effectiveness trials : protocol for a systematic review of the literature and stakeholder involvement through interviews and a Delphi survey

Acknowledgements We would like to thank Professor Craig Ramsay, Professor Luke Vale, and Professor Vikki Entwistle for their comments on earlier drafts of the protocol. This study is funded by the Cancer Research Aberdeen and North East Scotland (CRANES) charity. Paula Williamson would like to acknowledge funding from the European Union Seventh Framework Programme (FP7/2007-2013, FP7/2007-2011) under grant agreement number 305081 for the COMET initiative, which provided support for this work.Peer reviewedPublisher PD

No effect of seed source on multiple aspects of ecosystem functioning during ecological restoration: cultivars compared to local ecotypes of dominant grasses

Genetic principles underlie recommendations to use local seed, but a paucity of information exists on the genetic distinction and ecological consequences of using different seed sources in restorations. We established a field experiment to test whether cultivars and local ecotypes of dominant prairie grasses were genetically distinct and differentially influenced ecosystem functioning. Whole plots were assigned to cultivar and local ecotype grass sources. Three subplots within each whole plot were seeded to unique pools of subordinate species. The cultivar of the increasingly dominant grass, Sorghastrum nutans, was genetically different than the local ecotype, but genetic diversity was similar between the two sources. There were no differences in aboveground net primary production, soil carbon accrual, and net nitrogen mineralization rate in soil between the grass sources. Comparable productivity of the grass sources among the species pools for four years shows functional equivalence in terms of biomass production. Subordinate species comprised over half the aboveground productivity, which may have diluted the potential for documented trait differences between the grass sources to influence ecosystem processes. Regionally developed cultivars may be a suitable alternative to local ecotypes for restoration in fragmented landscapes with limited gene flow between natural and restored prairie and negligible recruitment by seed

A randomized trial comparing treatments for varicose veins

Supported by a grant from the Health Technology Assessment Programme of the National Institute for Health Research (06/45/02). The Health Services Research Unit is funded by the Chief Scientist Office of the Scottish Government Health Directorate. We thank Janice Cruden for her secretarial support and data management; Gladys McPherson and the programming team at the Centre for Healthcare Randomised Trials; Tracey Davidson, Lynda Constable, Jackie Ellington, Laura Elliott, and Yvonne Fernie for help with scoring the Aberdeen Varicose Vein Questionnaire; Luke Vale and Laura Ternent, our original economists in the group; members of the Project Management Group for their ongoing advice and support of the trial; members of the study team (Graeme MacLennan, Maria Prior, and Denise Bolsover) who contributed to the behavioral recovery component of the trial; the independent members of the trial steering committee (Alun Davies [chair], Ian Loftus, and Jane Nixon) and the data and safety monitoring committee (Gerry Stansby [chair], Winston Banya, and Marcus Flather); and the staff members at recruitment sites (see the Supplementary Appendix) who facilitated recruitment, treatment, and follow-up of trial participants.Peer reviewedPublisher PD

Integrating larval connectivity into the marine conservation decision-making process across spatial scales.

Larval dispersal connectivity is typically integrated into spatial conservation decisions at regional or national scales, but implementing agencies struggle with translating these methods to local scales. We used larval dispersal connectivity at regional (hundreds of kilometers) and local (tens of kilometers) scales to aid in design of networks of no-take reserves in Southeast Sulawesi, Indonesia. We used Marxan with Connectivity informed by biophysical larval dispersal models and remotely sensed coral reef habitat data to design marine reserve networks for 4 commercially important reef species across the region. We complemented regional spatial prioritization with decision trees that combined network-based connectivity metrics and habitat quality to design reserve boundaries locally. Decision trees were used in consensus-based workshops with stakeholders to qualitatively assess site desirability, and Marxan was used to identify areas for subsequent network expansion. Priority areas for protection and expected benefits differed among species, with little overlap in reserve network solutions. Because reef quality varied considerably across reefs, we suggest reef degradation must inform the interpretation of larval dispersal patterns and the conservation benefits achievable from protecting reefs. Our methods can be readily applied by conservation practitioners, in this region and elsewhere, to integrate connectivity data across multiple spatial scales

Narcissism and prosocial behavior

There are many motivations for prosocial behavior, some more altruistic and some more egoistic. We posit that more narcissistic people may perform prosocial acts strategically, for example, to improve their reputations or to receive something in return

Purkinje cell input to cerebellar nuclei in tottering: Ultrastructure and physiology

Homozygous tottering mice are spontaneous ataxic mutants, which carry a mutation in the gene encoding the ion pore of the P/Q-type voltage-gated calcium channels. P/Q-type calcium channels are prominently expressed in Purkinje cell terminals, but it is unknown to what extent these inhibitory terminals in tottering mice are affected at the morphological and electrophysiological level. Here, we investigated the distribution and ultrastructure of their Purkinje cell terminals in the cerebellar nuclei as well as the activities of their target neurons. The densities of Purkinje cell terminals and their synapses were not significantly affected in the mutants. However, the Purkinje cell terminals were enlarged and had an increased number of vacuoles, whorled bodies, and mitochondria. These differences started to occur between 3 and 5 weeks of age and persisted throughout adulthood. Stimulation of Purkinje cells in adult tottering mice resulted in inhibition at normal latencies, but the activities of their postsynaptic neurons in the cerebellar nuclei were abnormal in that the frequency and irregularity of their spiking patterns were enhanced. Thus, although the number of their terminals and their synaptic contacts appear quantitatively intact, Purkinje cells in tottering mice show several signs of axonal damage that may contribute to altered postsynaptic activities in the cerebellar nuclei

The Feasibility and Utility of Harnessing Digital Health to Understand Clinical Trajectories in Medication Treatment for Opioid Use Disorder: D-TECT Study Design and Methodological Considerations

Introduction: Across the U.S., the prevalence of opioid use disorder (OUD) and the rates of opioid overdoses have risen precipitously in recent years. Several effective medications for OUD (MOUD) exist and have been shown to be life-saving. A large volume of research has identified a confluence of factors that predict attrition and continued substance use during substance use disorder treatment. However, much of this literature has examined a small set of potential moderators or mediators of outcomes in MOUD treatment and may lead to over-simplified accounts of treatment non-adherence. Digital health methodologies offer great promise for capturing intensive, longitudinal ecologically-valid data from individuals in MOUD treatment to extend our understanding of factors that impact treatment engagement and outcomes. Methods: This paper describes the protocol (including the study design and methodological considerations) from a novel study supported by the National Drug Abuse Treatment Clinical Trials Network at the National Institute on Drug Abuse (NIDA). This study (D-TECT) primarily seeks to evaluate the feasibility of collecting ecological momentary assessment (EMA), smartphone and smartwatch sensor data, and social media data among patients in outpatient MOUD treatment. It secondarily seeks to examine the utility of EMA, digital sensing, and social media data (separately and compared to one another) in predicting MOUD treatment retention, opioid use events, and medication adherence [as captured in electronic health records (EHR) and EMA data]. To our knowledge, this is the first project to include all three sources of digitally derived data (EMA, digital sensing, and social media) in understanding the clinical trajectories of patients in MOUD treatment. These multiple data streams will allow us to understand the relative and combined utility of collecting digital data from these diverse data sources. The inclusion of EHR data allows us to focus on the utility of digital health data in predicting objectively measured clinical outcomes. Discussion: Results may be useful in elucidating novel relations between digital data sources and OUD treatment outcomes. It may also inform approaches to enhancing outcomes measurement in clinical trials by allowing for the assessment of dynamic interactions between individuals\u27 daily lives and their MOUD treatment response. Clinical Trial Registration: Identifier: NCT04535583