The environmental stress sensitivities of pathogenic Candida species, including Candida auris, and implications for their spread in the hospital setting

We are grateful to Dr. David Stead, Evelyn Argo and Craig Pattison (Aberdeen Proteomics Core Facility) for their expert identification of Candida isolates by MALDI ToF MS, and to Dr Jill King and our colleagues in the Aberdeen Fungal Group for their helpful advice. AJPB and NARG were supported by a programme grant from the Medical Research Council [www.mrc.ac.uk] (grant number MR/M026663/1) and by the Medical Research Council Centre for Medical Mycology and the University of Aberdeen (grant number MR/N006364/1). AJPB was also supported by the UK Biotechnology and Biological Research Council [www.bbsrc.ac.uk] (grant numbers BB/F00513X/1, BB/P020119/1), and AWW by the Scottish Government’s Rural and Environment Science and Analytical Services (RESAS) division. NARG was also supported by grants from the Wellcome Trust [www.wellcome.ac.uk] (grant numbers 075470, 086827, 093378, 097377, 099197, 101873, 102705, 200208). DMM was supported by National Centre for the Replacement, Refinement and Reduction of Animals in Research (NC3Rs) [www.nc3rs.org.uk] (grant numbers NC/S001557/1 and NC/N002482/1) and the UK Biotechnology and Biological Research Council [www.bbsrc.ac.uk] (grant number BB/P02050X/1). HH was supported by the John Duthie Scholarship from the University of Aberdeen’s Development Trust. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.Peer reviewedPublisher PD

Life on Jackson Creek, Smith County, Texas: Archeological Investigations of a 14th Century Caddo Domicile at the Leaning Rock Site (41SM325)

The 14th century Caddo Leaning Rock site was initially discovered in the Fall of 2004. It was located during reconnaissance to search out a location for the survey portion of the Texas Archeologica! Society\u27s Academy IO I held in Tyler in February 2005. This was not a formal survey with transect lines. nor one using regularly spaced shovel tests. but was rather more of a windshield \u27 type survey, consisting of driving across pasture lands looking at gopher mounds and checking fore, evidence of archeological deposits on likely looking landforms. !n this area. landform and soil type seem to be the major determining factors in locating Caddo sites. The sandy soils in the scattered gopher mounds appeared almost white. especially in droughty conditions that prevailed at the time. causing an area with darker mounds of soil to catch my attention. Pocket gophers (G. breviceps) can play havoc with buried archeological deposits but can also be useful in bringing buried soils along with archeological materials to the surface from their underground tunnel system. While this dark area could have been the result of past historic land clearing and burning activities. a closer inspection revealed burned bone. mussel she!L and Caddo sherds mixed in the dark brown soils in the scattered gopher mounds. The next step was to record the site with the State of Texas, obtaining the trinomial 41SM325. It is common practice to also gin: sites informal names and after recording several hundred sites, selecting a name becomes a challenge. One large sandstone slab, pan of the R-horizon that is exposed around the margins of Leaning Rock. was unearthed during prior landclearing activities and pushed up against a lonely pine tree on the northern margins of the site: consequently the nom de plume Leaning Rock

Protocol of the adaptive study of IL-2 dose frequency on regulatory T cells in type 1 diabetes (DILfrequency): a mechanistic, non-randomised, repeat dose, open-label, response-adaptive study.

INTRODUCTION: Type 1 diabetes (T1D) is caused by autoimmune destruction of the insulin-producing β cells in the pancreatic islets, leading to insulinopenia and hyperglycaemia. Genetic analyses indicate that alterations of the interleukin-2 (IL-2) pathway mediating immune activation and tolerance predispose to T1D, specifically the polymorphic expression of the IL-2 receptor-α chain (CD25) on T lymphocytes. Replacement of physiological doses of IL-2 could restore self-tolerance and prevent further autoimmunity by enhancing the function of CD4(+) T regulatory cells (Tregs) to limit the activation of auto reactive T effector cells (Teffs). In this experimental medicine study, we use an adaptive trial design to determine the optimal dosing regimen for IL-2 to improve Treg function while limiting activation of Teffs in participants with T1D. METHODS AND ANALYSIS: The Adaptive study of IL-2 dose frequency on Tregs in type 1 diabetes(DILfrequency) is a mechanistic, non-randomised, repeat dose open-label, response-adaptive study of 36 participants with T1D. The objective is to establish the optimal dose and frequency of ultra-low dose IL-2: to increase Treg frequency within the physiological range, to increase CD25 expression on Tregs, without increasing CD4(+) Teffs. DILfrequency has an initial learning phase where 12 participants are allocated to six different doses and frequencies followed by an interim statistical analysis. After analysis of the learning phase, the Dose and Frequency Committee will select the optimal targets for Treg frequency, Treg CD25 expression and Teff frequency. Three groups of eight participants will be treated consecutively in the confirming phase. Each dose and frequency selected will be based on statistical analysis of all data collected from the previous groups. ETHICS: Ethical approval for DILfrequency was granted on 12 August 2014. RESULTS: The results of this study will be reported, through peer-reviewed journals, conference presentations and an internal organisational report. TRIAL REGISTRATION NUMBERS: NCT02265809, ISRCTN40319192, CRN17571.This work is funded by The Sir Jules Thorn Award for Biomedical Research 2013 (13/JTA), the JDRF (9-2011-253), the Wellcome Trust (091157) and the National Institute for Health Research Cambridge Biomedical Research Centre. The Cambridge Institute for Medical Research is in receipt of a Wellcome Trust Strategic Award (100140). AM was supported by the Medical Research Council [grant number G0800860] and the National Institute for Health Research Cambridge Biomedical Research Centre.This is the final version of the article. It was first available from BMJ via http://dx.doi.org/10.1136/bmjopen-2015-00979

The translation research in a dental setting (TRiaDS) programme protocol

Background: It is well documented that the translation of knowledge into clinical practice is a slow and haphazard process. This is no less true for dental healthcare than other types of healthcare. One common policy strategy to help promote knowledge translation is the production of clinical guidance, but it has been demonstrated that the simple publication of guidance is unlikely to optimise practice. Additional knowledge translation interventions have been shown to be effective, but effectiveness varies and much of this variation is unexplained. The need for researchers to move beyond single studies to develop a generalisable, theory based, knowledge translation framework has been identified.For dentistry in Scotland, the production of clinical guidance is the responsibility of the Scottish Dental Clinical Effectiveness Programme (SDCEP). TRiaDS (Translation Research in a Dental Setting) is a multidisciplinary research collaboration, embedded within the SDCEP guidance development process, which aims to establish a practical evaluative framework for the translation of guidance and to conduct and evaluate a programme of integrated, multi-disciplinary research to enhance the science of knowledge translation.Methods: Set in General Dental Practice the TRiaDS programmatic evaluation employs a standardised process using optimal methods and theory. For each SDCEP guidance document a diagnostic analysis is undertaken alongside the guidance development process. Information is gathered about current dental care activities. Key recommendations and their required behaviours are identified and prioritised. Stakeholder questionnaires and interviews are used to identify and elicit salient beliefs regarding potential barriers and enablers towards the key recommendations and behaviours. Where possible routinely collected data are used to measure compliance with the guidance and to inform decisions about whether a knowledge translation intervention is required. Interventions are theory based and informed by evidence gathered during the diagnostic phase and by prior published evidence. They are evaluated using a range of experimental and quasi-experimental study designs, and data collection continues beyond the end of the intervention to investigate the sustainability of an intervention effect.Discussion: The TRiaDS programmatic approach is a significant step forward towards the development of a practical, generalisable framework for knowledge translation research. The multidisciplinary composition of the TRiaDS team enables consideration of the individual, organisational and system determinants of professional behaviour change. In addition the embedding of TRiaDS within a national programme of guidance development offers a unique opportunity to inform and influence the guidance development process, and enables TRiaDS to inform dental services practitioners, policy makers and patients on how best to translate national recommendations into routine clinical activities

Comparative study of in situ N2 rotational Raman spectroscopy methods for probing energy thermalisation processes during spin-exchange optical pumping

Spin-exchange optical pumping (SEOP) has been widely used to produce enhancements in nuclear spin polarisation for hyperpolarised noble gases. However, some key fundamental physical processes underlying SEOP remain poorly understood, particularly in regards to how pump laser energy absorbed during SEOP is thermalised, distributed and dissipated. This study uses in situ ultra-low frequency Raman spectroscopy to probe rotational temperatures of nitrogen buffer gas during optical pumping under conditions of high resonant laser flux and binary Xe/N2 gas mixtures. We compare two methods of collecting the Raman scattering signal from the SEOP cell: a conventional orthogonal arrangement combining intrinsic spatial filtering with the utilisation of the internal baffles of the Raman spectrometer, eliminating probe laser light and Rayleigh scattering, versus a new in-line modular design that uses ultra-narrowband notch filters to remove such unwanted contributions. We report a ~23-fold improvement in detection sensitivity using the in-line module, which leads to faster data acquisition and more accurate real-time monitoring of energy transport processes during optical pumping. The utility of this approach is demonstrated via measurements of the local internal gas temperature (which can greatly exceed the externally measured temperature) as a function of incident laser power and position within the cell

Construction and analysis of tag single nucleotide polymorphism maps for six human-mouse orthologous candidate genes in type 1 diabetes.

BACKGROUND: One strategy to help identify susceptibility genes for complex, multifactorial diseases is to map disease loci in a representative animal model of the disorder. The nonobese diabetic (NOD) mouse is a model for human type 1 diabetes. Linkage and congenic strain analyses have identified several NOD mouse Idd (insulin dependent diabetes) loci, which have been mapped to small chromosome intervals, for which the orthologous regions in the human genome can be identified. Here, we have conducted re-sequencing and association analysis of six orthologous genes identified in NOD Idd loci: NRAMP1/SLC11A1 (orthologous to Nramp1/Slc11a1 in Idd5.2), FRAP1 (orthologous to Frap1 in Idd9.2), 4-1BB/CD137/TNFRSF9 (orthologous to 4-1bb/Cd137/Tnrfrsf9 in Idd9.3), CD101/IGSF2 (orthologous to Cd101/Igsf2 in Idd10), B2M (orthologous to B2m in Idd13) and VAV3 (orthologous to Vav3 in Idd18). RESULTS: Re-sequencing of a total of 110 kb of DNA from 32 or 96 type 1 diabetes cases yielded 220 single nucleotide polymorphisms (SNPs). Sixty-five SNPs, including 54 informative tag SNPs, and a microsatellite were selected and genotyped in up to 1,632 type 1 diabetes families and 1,709 cases and 1,829 controls. CONCLUSION: None of the candidate regions showed evidence of association with type 1 diabetes (P values > 0.2), indicating that common variation in these key candidate genes does not play a major role in type 1 diabetes susceptibility in the European ancestry populations studied.RIGHTS : This article is licensed under the BioMed Central licence at http://www.biomedcentral.com/about/license which is similar to the 'Creative Commons Attribution Licence'. In brief you may : copy, distribute, and display the work; make derivative works; or make commercial use of the work - under the following conditions: the original author must be given credit; for any reuse or distribution, it must be made clear to others what the license terms of this work are

Expertise in research integration and implementation for tackling complex problems: when is it needed, where can it be found and how can it be strengthened?

© 2020, The Author(s). Expertise in research integration and implementation is an essential but often overlooked component of tackling complex societal and environmental problems. We focus on expertise relevant to any complex problem, especially contributory expertise, divided into ‘knowing-that’ and ‘knowing-how.’ We also deal with interactional expertise and the fact that much expertise is tacit. We explore three questions. First, in examining ‘when is expertise in research integration and implementation required?,’ we review tasks essential (a) to developing more comprehensive understandings of complex problems, plus possible ways to address them, and (b) for supporting implementation of those understandings into government policy, community practice, business and social innovation, or other initiatives. Second, in considering ‘where can expertise in research integration and implementation currently be found?,’ we describe three realms: (a) specific approaches, including interdisciplinarity, transdisciplinarity, systems thinking and sustainability science; (b) case-based experience that is independent of these specific approaches; and (c) research examining elements of integration and implementation, specifically considering unknowns and fostering innovation. We highlight examples of expertise in each realm and demonstrate how fragmentation currently precludes clear identification of research integration and implementation expertise. Third, in exploring ‘what is required to strengthen expertise in research integration and implementation?,’ we propose building a knowledge bank. We delve into three key challenges: compiling existing expertise, indexing and organising the expertise to make it widely accessible, and understanding and overcoming the core reasons for the existing fragmentation. A growing knowledge bank of expertise in research integration and implementation on the one hand, and accumulating success in addressing complex societal and environmental problems on the other, will form a virtuous cycle so that each strengthens the other. Building a coalition of researchers and institutions will ensure this expertise and its application are valued and sustained

Chorioamnionitis: Case definition & guidelines for data collection, analysis, and presentation of immunization safety data

Chorioamnionitis is a term encompassing a broad spectrum of disease during pregnancy that is characterized by inflammation and/or infection of intrauterine structures such as the placenta, the chorion and amnion. The clinical presentation of chorioamnionitis can vary based on clinical, microbiologic, and histologic factors which interact and overlap to varying degrees

Are Adolescents with ADHD Interested in Genetic Testing for Nicotine Addiction Susceptibility?

It has been well-established that some adolescents diagnosed with attention-deficit/hyperactivity disorder (ADHD) are at increased risk for cigarette smoking. Current research on the genetic basis of this association could ultimately translate into genetic tests capable of identifying smoking-prone adolescents with ADHD. In this study we examined 81 ADHD affected adolescents’ (age 13–21) interest in genetic testing for nicotine addiction susceptibility. Fifty-seven percent of adolescents indicated a fair amount of interest or more in testing. Most adolescents indicated that the personal information revealed from testing would be either useful (29%) or interesting (37%). Implications for genetically-informed smoking prevention and cessation interventions in high risk adolescents with ADHD are discussed