Evaluating the test re-test reliability and inter-subject variability of health care provider manual fluid resuscitation performance

BACKGROUND: Health Care Providers (HCPs) report that manual techniques of intravascular fluid resuscitation are commonly used during pediatric shock management. The optimal pediatric fluid resuscitation technique is currently unknown. We sought to determine HCP test-retest reliability (repeatability) and inter-subject variability of fluid resuscitation performance outcomes to inform the design of future studies. METHODS: Fifteen consenting HCPs from McMaster Children’s Hospital, in Hamilton, Canada participated in this single-arm interventional trial. Participants were oriented to a non-clinical model representing a 15 kg toddler, which incorporated a 22-gauge IV catheter. Following a standardization procedure, participants administered 600 mL (40 mL/kg) of saline to the simulated child under emergency conditions using prefilled 60-mL syringes. Each participant completed 5 testing trials. All testing was video recorded, with fluid administration time outcome data (in seconds) extracted from trial videos by two blinded outcome assessors. Data describing catheter dislodgement events, volume of saline effectively delivered, and participant demographics were also collected. The primary outcome of fluid administration time test-retest reliability was analyzed by one-way analysis of variance (ANOVA) and intra-class correlation (ICC), with good reliability defined as ICC > 0.70. RESULTS: Differences in HCP fluid administration times are attributable to inter-subject variability rather than intra-subject variability based on one-way ANOVA analysis, F (14,60) = 43.125; p < 0.001. Test-retest reliability of subjects was excellent with ICC = 0.97 (95% CI: 0.95-0.99); p < 0.001. CONCLUSIONS: Findings demonstrate excellent test-retest reliability of HCP fluid resuscitation performance in a setting involving a non-clinical model. Investigators can justify a single evaluation of HCP performance in future studies. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/1756-0500-7-724) contains supplementary material, which is available to authorized users

A Case Report on Longitudinal Collection of Tumour Biopsies for Gene Expression-Based Tumour Microenvironment Analysis from Pancreatic Cancer Patients Treated with Endoscopic Ultrasound Guided Radiofrequency Ablation.

BACKGROUND: Most patients with pancreatic ductal adenocarcinoma (PDAC) are metastatic at presentation with dismal prognosis warranting improved systemic therapy options. Longitudinal sampling for the assessment of treatment response poses a challenge for validating novel therapies. In this case study, we evaluate the feasibility of collecting endoscopic ultrasound (EUS)-guided longitudinal fine-needle aspiration biopsies (FNABs) from two PDAC patients and conduct gene expression studies associated with tumour microenvironment changes associated with radiofrequency ablation (RFA). METHODS: EUS-guided serial/longitudinal FNABs of tumour were collected before and after treatment from two stage III inoperable gemcitabine-treated PDAC patients treated with targeted RFA three times. Biopsies were analysed using a custom NanoString panel (144 genes) consisting of cancer and cancer-associated fibroblast (CAFs) subtypes and immune changes. CAF culture was established from one FNAB and characterised by immunofluorescence and immunoblotting. RESULTS: Two-course RFA led to the upregulation of the CD1E gene (involved in antigen presentation) in both patients 1 and 2 (4.5 and 3.9-fold changes) compared to baseline. Patient 1 showed increased T cell genes (CD4-8.7-fold change, CD8-35.7-fold change), cytolytic function (6.4-fold change) and inflammatory response (8-fold change). A greater than 2-fold upregulation of immune checkpoint genes was observed post-second RFA in both patients. Further, two-course RFA led to increased PDGFRα (4.5-fold change) and CAF subtypes B and C genes in patient 1 and subtypes A, B and D genes in patient 2. Patient 2-derived CAFs post-first RFA showed expression of PDGFRα, POSTN and MYH11 proteins. Finally, RFA led to the downregulation of classical PDAC subtype-specific genes in both patients. CONCLUSIONS: This case study suggests longitudinal EUS-FNAB as a potential resource to study tumour and microenvironmental changes associated with RFA treatment. A large sample size is required in the future to assess the efficacy and safety of the treatment and perform comprehensive statistical analysis of EUS-RFA-based molecular changes in PDAC

Knot Theory: from Fox 3-colorings of links to Yang-Baxter homology and Khovanov homology

This paper is an extended account of my "Introductory Plenary talk at Knots in Hellas 2016" conference We start from the short introduction to Knot Theory from the historical perspective, starting from Heraclas text (the first century AD), mentioning R.Llull (1232-1315), A.Kircher (1602-1680), Leibniz idea of Geometria Situs (1679), and J.B.Listing (student of Gauss) work of 1847. We spend some space on Ralph H. Fox (1913-1973) elementary introduction to diagram colorings (1956). In the second section we describe how Fox work was generalized to distributive colorings (racks and quandles) and eventually in the work of Jones and Turaev to link invariants via Yang-Baxter operators, here the importance of statistical mechanics to topology will be mentioned. Finally we describe recent developments which started with Mikhail Khovanov work on categorification of the Jones polynomial. By analogy to Khovanov homology we build homology of distributive structures (including homology of Fox colorings) and generalize it to homology of Yang-Baxter operators. We speculate, with supporting evidence, on co-cycle invariants of knots coming from Yang-Baxter homology. Here the work of Fenn-Rourke-Sanderson (geometric realization of pre-cubic sets of link diagrams) and Carter-Kamada-Saito (co-cycle invariants of links) will be discussed and expanded. Dedicated to Lou Kauffman for his 70th birthday.Comment: 35 pages, 31 figures, for Knots in Hellas II Proceedings, Springer, part of the series Proceedings in Mathematics & Statistics (PROMS

Neural correlates of enhanced visual short-term memory for angry faces: An fMRI study

Copyright: © 2008 Jackson et al.Background: Fluid and effective social communication requires that both face identity and emotional expression information are encoded and maintained in visual short-term memory (VSTM) to enable a coherent, ongoing picture of the world and its players. This appears to be of particular evolutionary importance when confronted with potentially threatening displays of emotion - previous research has shown better VSTM for angry versus happy or neutral face identities.Methodology/Principal Findings: Using functional magnetic resonance imaging, here we investigated the neural correlates of this angry face benefit in VSTM. Participants were shown between one and four to-be-remembered angry, happy, or neutral faces, and after a short retention delay they stated whether a single probe face had been present or not in the previous display. All faces in any one display expressed the same emotion, and the task required memory for face identity. We find enhanced VSTM for angry face identities and describe the right hemisphere brain network underpinning this effect, which involves the globus pallidus, superior temporal sulcus, and frontal lobe. Increased activity in the globus pallidus was significantly correlated with the angry benefit in VSTM. Areas modulated by emotion were distinct from those modulated by memory load.Conclusions/Significance: Our results provide evidence for a key role of the basal ganglia as an interface between emotion and cognition, supported by a frontal, temporal, and occipital network.The authors were supported by a Wellcome Trust grant (grant number 077185/Z/05/Z) and by BBSRC (UK) grant BBS/B/16178

Laser Cooling of Optically Trapped Molecules

Calcium monofluoride (CaF) molecules are loaded into an optical dipole trap (ODT) and subsequently laser cooled within the trap. Starting with magneto-optical trapping, we sub-Doppler cool CaF and then load $150(30)$ CaF molecules into an ODT. Enhanced loading by a factor of five is obtained when sub-Doppler cooling light and trapping light are on simultaneously. For trapped molecules, we directly observe efficient sub-Doppler cooling to a temperature of $60(5)$ $\mu\text{K}$. The trapped molecular density of $8(2)\times10^7$ cm$^{-3}$ is an order of magnitude greater than in the initial sub-Doppler cooled sample. The trap lifetime of 750(40) ms is dominated by background gas collisions.Comment: 5 pages, 5 figure

Simultaneous chronic rupture of quadriceps tendon and contra-lateral patellar tendon in a patient affected by tertiary hyperparatiroidism

Spontaneous ruptures of the extensor mechanism of the knee are very rare. They tend to increase considerably in patients with metabolic diseases such as chronic renal failure, hyperparathyroidism, diabetes, gout, and systemic lupus erythematosus. The reported case regards a 48-year-old man with chronic, spontaneous and simultaneous quadriceps, and contra-lateral patellar tendon rupture. The patient suffered from chronic renal failure and for the past year from tertiary hyperparathyroidism. Ruptured tendons were repaired and both knee were evaluated monthly for the next 12 months. Good functional recovery was achieved on both knees without relapse. This case emphasizes the importance of long-term high parathyroid hormone level in the etiology of tendons ruptures

High Energy Neutrinos from Quasars

We review and clarify the assumptions of our basic model for neutrino production in the cores of quasars, as well as those modifications to the model subsequently made by other workers. We also present a revised estimate of the neutrino background flux and spectrum obtained using more recent empirical studies of quasars and their evolution. We compare our results with other thoeretical calculations and experimental upper limits on the AGN neutrino background flux. We also estimate possible neutrino fluxes from the jets of blazars detected recently by the EGRET experiment on the Compton Gamma Ray Observatory. We discuss the theoretical implications of these estimates.Comment: 14 pg., ps file (includes figures), To be published in Space Science Review

Host-Associated Bacteriophage Isolation and Preparation for Viral Metagenomics.

Prokaryotic viruses, or bacteriophages, are viruses that infect bacteria and archaea. These viruses have been known to associate with host systems for decades, yet only recently have their influence on the regulation of host-associated bacteria been appreciated. These studies have been conducted in many host systems, from the base of animal life in the Cnidarian phylum to mammals. These prokaryotic viruses are useful for regulating the number of bacteria in a host ecosystem and for regulating the strains of bacteria useful for the microbiome. These viruses are likely selected by the host to maintain bacterial populations. Viral metagenomics allows researchers to profile the communities of viruses associating with animal hosts, and importantly helps to determine the functional role these viruses play. Further, viral metagenomics show the sphere of viral involvement in gene flow and gene shuffling in an ever-changing host environment. The influence of prokaryotic viruses could, therefore, have a clear impact on host health

Developmental Neurotoxicity of Pyrethroid Insecticides: Critical Review and Future Research Needs

Pyrethroid insecticides have been used for more than 40 years and account for 25% of the worldwide insecticide market. Although their acute neurotoxicity to adults has been well characterized, information regarding the potential developmental neurotoxicity of this class of compounds is limited. There is a large age dependence to the acute toxicity of pyrethroids in which neonatal rats are at least an order of magnitude more sensitive than adults to two pyrethroids. There is no information on age-dependent toxicity for most pyrethroids. In the present review we examine the scientific data related to potential for age-dependent and developmental neurotoxicity of pyrethroids. As a basis for understanding this neurotoxicity, we discuss the heterogeneity and ontogeny of voltage-sensitive sodium channels, a primary neuronal target of pyrethroids. We also summarize 22 studies of the developmental neurotoxicity of pyrethroids and review the strengths and limitations of these studies. These studies examined numerous end points, with changes in motor activity and muscarinic acetylcholine receptor density the most common. Many of the developmental neurotoxicity studies suffer from inadequate study design, problematic statistical analyses, use of formulated products, and/or inadequate controls. These factors confound interpretation of results. To better understand the potential for developmental exposure to pyrethroids to cause neurotoxicity, additional, well-designed and well-executed developmental neurotoxicity studies are needed. These studies should employ state-of-the-science methods to promote a greater understanding of the mode of action of pyrethroids in the developing nervous system