Management of pneumonia in intensive care

Pneumonia, an inflammatory infiltrate of the alveolar airspace, is commonly triggered by bacterial infection of the lungs, or less commonly by viral or fungal infection. It remains the commonest infective reason for admission to Intensive Care as well as being the most common secondary infection acquired whilst in the Intensive Care Unit. It presents a significant global burden of disease and is especially prevalent in low- and middle-income countries. The major categories of pneumonia encountered by the Intensive Care clinician are community-acquired, ventilator-acquired, non-ventilator hospital-acquired and pneumonia in the immunocompromised patient. An appreciation of the type of pneumonia a patient has developed is critical to its effective treatment. Pneumonia is the commonest precipitant of acute respiratory distress syndrome (ARDS) and clinicians should be mindful that the evidence-base surrounding ARDS will, in large part, apply to severe pneumonia. The causative organisms which lead to pneumonia vary depending on the site of acquisition (community or hospital-acquired), the immune status of the patient and the presence of intercurrent medications including antibiotics. Current standard microbiological testing is seldom able to give a rapid answer as to which microorganisms are present and causing infection. Therefore, empirical therapy guided by a knowledge of local microbial flora and resistance patterns is the recommended course of action. This approach risks the over-treatment of pneumonia with unnecessarily broad-spectrum agents which bring with them the problems of antibiotic-associated harm. Novel rapid diagnostic tests aimed at both the pathogen and the host response hold promise in the rationalisation and appropriate targeting of antimicrobial therapy. At present neither scoring systems nor diagnostic tests are able to accurately risk stratify a patient’s need for intensive care admission. Beyond antibiotic therapy, a number of adjuvant therapies have been trialled in pneumonia although none have yet made it into widespread clinical use. Corticosteroids are recommended in some cases of community-acquired pneumonia, but their role in the patient with severe community-acquired pneumonia in ICU remains uncertain whilst they are a risk factor for the development of hospital and ventilator-acquired pneumonia. Immuno-stimulation has not yet translated from small scale clinical trials into clinical use. Supportive management includes lung protective ventilation, and those interventions proven to improve outcomes in ARDS. This review will give an overview of the epidemiology of severe pneumonia, the microbiological causes and diagnostic strategies. It will then turn to management, including antimicrobial therapy, role of adjuvant therapies, respiratory support and prevention of complications

TOp TEn resistant Microorganisms at intensive care unit: a 2018 global expert survey (TOTEM study protocol)

Background: This global survey will provide global expert ranking of the most urgent multidrug bacteria present at the intensive care units (ICU) that have become a threat in daily clinical practice. We believe efforts on education, investigation, funding and development of new antimicrobials or new antimicrobial approach should be directed in near future. The 2018 study protocol is reported here in. Methods: A global survey will be performed using an electronic platform (SurveyMonkey®). The survey will compile data on key aspects of the actual threat of antimicrobial-resistant bacteria globally in the ICU

Human Papilloma Virus (HPV) Oral Prevalence in Scotland (HOPSCOTCH):a feasibility study in dental settings

The purpose of this study was to test the feasibility of undertaking a full population investigation into the prevalence, incidence, and persistence of oral Human Papilloma Virus (HPV) in Scotland via dental settings. Male and female patients aged 16-69 years were recruited by Research Nurses in 3 primary care and dental outreach teaching centres and 2 General Dental Practices (GDPs), and by Dental Care Teams in 2 further GDPs. Participants completed a questionnaire (via an online tablet computer or paper) with socioeconomic, lifestyle, and sexual history items; and were followed up at 6-months for further questionnaire through appointment or post/online. Saline oral gargle/rinse samples, collected at baseline and follow-up, were subject to molecular HPV genotyping centrally. 1213 dental patients were approached and 402 individuals consented (participation rate 33.1%). 390 completed the baseline questionnaire and 380 provided a baseline oral specimen. Follow-up rate was 61.6% at 6 months. While recruitment was no different in Research Nurse vs Dental Care Team models the Nurse model ensured more rapid recruitment. There were relatively few missing responses in the questionnaire and high levels of disclosure of risk behaviours (99% answered some of the sexual history questions). Data linkage of participant data to routine health records including HPV vaccination data was successful with 99.1% matching. Oral rinse/gargle sample collection and subsequent HPV testing was feasible. Preliminary analyses found over 95% of samples to be valid for molecular HPV detection prevalence of oral HPV infection of 5.5% (95%CI 3.7, 8.3). It is feasible to recruit and follow-up dental patients largely representative / reflective of the wider population, suggesting it would be possible to undertake a study to investigate the prevalence, incidence, and determinants of oral HPV infection in dental settings

Intelligent problem-solvers externalize cognitive operations

The use of forward models (mechanisms that predict the future state of a system) is well established in cognitive and computational neuroscience. We compare and contrast two recent, but interestingly divergent, accounts of the place of forward models in the human cognitive architecture. On the Auxiliary Forward Model (AFM) account, forward models are special-purpose prediction mechanisms implemented by additional circuitry distinct from core mechanisms of perception and action. On the Integral Forward Model (IFM) account, forward models lie at the heart of all forms of perception and action. We compare these neighbouring but importantly different visions and consider their implications for the cognitive sciences. We end by asking what kinds of empirical research might offer evidence favouring one or the other of these approaches

Digital transformations and the archival nature of surrogates

Large-scale digitization is generating extraordinary collections of visual and textual surrogates, potentially endowed with transcendent long-term cultural and research values. Understanding the nature of digital surrogacy is a substantial intellectual opportunity for archival science and the digital humanities, because of the increasing independence of surrogate collections from their archival sources. The paper presents an argument that one of the most significant requirements for the long-term access to collections of digital surrogates is to treat digital surrogates as archival records that embody traces of their fluid lifecycles and therefore are worthy of management and preservation as archives. It advances a theory of the archival nature of surrogacy founded on longstanding notions of archival quality, the traces of their source and the conditions of their creation, and the functional ‘‘work of the archive.’’ The paper presents evidence supporting a ‘‘secondary provenance’’ derived from re-digitization, re-ingestion of multiple versions, and de facto replacement of the original sources. The design of the underlying research that motivates the paper and summary findings are reported separately. The research has been supported generously by the US Institute of Museum and Library Services.Institute for Museum and Library ServicesPeer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/111825/1/J26 Conway Digital Transformations 2014-pers.pdfDescription of J26 Conway Digital Transformations 2014-pers.pdf : Main articl

Mirroring Intentional Forgetting in a Shared-Goal Learning Situation

Background: Intentional forgetting refers to the surprising phenomenon that we can forget previously successfully encoded memories if we are instructed to do so. Here, we show that participants cannot only intentionally forget episodic memories but they can also mirror the ‘‘forgetting performance’ ’ of an observed model. Methodology/Principal Findings: In four experiments a participant observed a model who took part in a memory experiment. In Experiment 1 and 2 observers saw a movie about the experiment, whereas in Experiment 3 and 4 the observers and the models took part together in a real laboratory experiment. The observed memory experiment was a directed forgetting experiment where the models learned two lists of items and were instructed either to forget or to remember the first list. In Experiment 1 and 3 observers were instructed to simply observe the experiment (‘‘simple observation’ ’ instruction). In Experiment 2 and 4, observers received instructions aimed to induce the same learning goal for the observers and the models (‘‘observation with goal-sharing’ ’ instruction). A directed forgetting effect (the reliably lower recall of to-be-forgotten items) emerged only when models received the ‘‘observation with goal-sharing’ ’ instruction (P,.001 in Experiment 2, and P,.05 in Experiment 4), and it was absent when observers received the ‘‘simple observation’’ instruction (P..1 in Experiment 1 and 3). Conclusion: If people observe another person with the same intention to learn, and see that this person is instructed t

A Dopaminergic Gene Cluster in the Prefrontal Cortex Predicts Performance Indicative of General Intelligence in Genetically Heterogeneous Mice

Background: Genetically heterogeneous mice express a trait that is qualitatively and psychometrically analogous to general intelligence in humans, and as in humans, this trait co-varies with the processing efficacy of working memory (including its dependence on selective attention). Dopamine signaling in the prefrontal cortex (PFC) has been established to play a critical role in animals ’ performance in both working memory and selective attention tasks. Owing to this role of the PFC in the regulation of working memory, here we compared PFC gene expression profiles of 60 genetically diverse CD-1 mice that exhibited a wide range of general learning abilities (i.e., aggregate performance across five diverse learning tasks). Methodology/Principal Findings: Animals ’ general cognitive abilities were first determined based on their aggregate performance across a battery of five diverse learning tasks. With a procedure designed to minimize false positive identifications, analysis of gene expression microarrays (comprised of <25,000 genes) identified a small number (,20) of genes that were differentially expressed across animals that exhibited fast and slow aggregate learning abilities. Of these genes, one functional cluster was identified, and this cluster (Darpp-32, Drd1a, and Rgs9) is an established modulator of dopamine signaling. Subsequent quantitative PCR found that expression of these dopaminegic genes plus one vascular gene (Nudt6) were significantly correlated with individual animal’s general cognitive performance. Conclusions/Significance: These results indicate that D1-mediated dopamine signaling in the PFC, possibly through it

High-density functional-RNA arrays as a versatile platform for studying RNA-based interactions

We are just beginning to unravel the myriad of interactions in which non-coding RNAs participate. The intricate RNA interactome is the foundation of many biological processes, including bacterial virulence and human disease, and represents unexploited resources for the development of potential therapeutic interventions. However, identifying specific associations of a given RNA from the multitude of possible binding partners within the cell requires robust high-throughput systems for their rapid screening. Here, we present the first demonstration of functional-RNA arrays as a novel platform technology designed for the study of such interactions using immobilized, active RNAs. We have generated high-density RNA arrays by an innovative method involving surface-capture of in vitro transcribed RNAs. This approach has significant advantages over existing technologies, particularly in its versatility in regards to binding partner character. Indeed, proof-of-principle application of RNA arrays to both RNA–small molecule and RNA–RNA pairings is demonstrated, highlighting their potential as a platform technology for mapping RNA-based networks and for pharmaceutical screening. Furthermore, the simplicity of the method supports greater user-accessibility over currently available technologies. We anticipate that functional-RNA arrays will find broad utility in the expanding field of RNA characterization

Protecting eyewitness evidence: Examining the efficacy of a self-administered interview tool

Given the crucial role of eyewitness evidence, statements should be obtained as soon as possible after an incident. This is not always achieved due to demands on police resources. Two studies trace the development of a new tool, the Self-Administered Interview (SAI), designed to elicit a comprehensive initial statement. In Study 1, SAI participants reported more correct details than participants who provided a free recall account, and performed at the same level as participants given a Cognitive Interview. In Study 2, participants viewed a simulated crime and half recorded their statement using the SAI. After a delay of 1 week, all participants completed a free recall test. SAI participants recalled more correct details in the delayed recall task than control participants

Astrobiological Complexity with Probabilistic Cellular Automata

Search for extraterrestrial life and intelligence constitutes one of the major endeavors in science, but has yet been quantitatively modeled only rarely and in a cursory and superficial fashion. We argue that probabilistic cellular automata (PCA) represent the best quantitative framework for modeling astrobiological history of the Milky Way and its Galactic Habitable Zone. The relevant astrobiological parameters are to be modeled as the elements of the input probability matrix for the PCA kernel. With the underlying simplicity of the cellular automata constructs, this approach enables a quick analysis of large and ambiguous input parameters' space. We perform a simple clustering analysis of typical astrobiological histories and discuss the relevant boundary conditions of practical importance for planning and guiding actual empirical astrobiological and SETI projects. In addition to showing how the present framework is adaptable to more complex situations and updated observational databases from current and near-future space missions, we demonstrate how numerical results could offer a cautious rationale for continuation of practical SETI searches.Comment: 37 pages, 11 figures, 2 tables; added journal reference belo