Nurse titrated analgesia and sedation in intensive care increases the frequency of comfort assessment and reduces midazolam use in paediatric patients following cardiac surgery

BACKGROUND Pain and sedation protocols are suggested to improve the outcomes of patients within paediatric intensive care. However, it is not clear how protocols will influence practice within individual units. OBJECTIVES Evaluate a nurse led pain and sedation protocols impact on pain scoring and analgesic and sedative administration for post-operative cardiac patients within a paediatric intensive care unit. METHODS A retrospective chart review was performed on 100 patients admitted to a tertiary paediatric intensive care unit pre and post introduction of an analgesic and sedative protocol. Stata12 was used to perform Chi-squared or Student's t-test to compare data between the groups. RESULTS Post protocol introduction documentation of pain assessments increased (pre protocol 3/24h vs post protocol 5/24h, p=0.006). Along with a reduction in administration of midazolam (57.6mcg/kg/min pre protocol vs 24.5mcg/kg/min post protocol, p=0.0001). Children's pain scores remained unchanged despite this change, with a trend towards more scores in the optimal range in the post protocol group (5 pre protocol vs 12 post protocol, p=0.06). CONCLUSIONS Introducing a pain and sedation protocol changed bedside nurse practice in pain and sedation management. The protocol has enabled nurses to provide pain and sedation management in a consistent and timely manner and reduced the dose of midazolam required to maintain comfort according to the patients COMFORT B scores. Individual evaluation of practice change is recommended to units who implement nurse led analgesic and sedative protocols to monitor changes in practice

Associations between COVID-19 therapies and inpatient gastrointestinal bleeding: A multisite retrospective study.

Little data is available regarding the incidence of gastrointestinal bleeding in adults hospitalized with COVID-19 infection and the influence of patient comorbidities and demographics, COVID-19 therapies, and typical medications used. In this retrospective study, we utilized the National COVID Cohort Collaborative to investigate the primary outcome of the development of gastrointestinal bleeding in 512 467 hospitalized US adults (age \u3e18 years) within 14 days of a COVID-19 infection and the influence of demographics, comorbidities, and selected medications. Gastrointestinal bleeding developed in 0.44% of patients hospitalized with COVID-19. Comorbidities associated with gastrointestinal bleeding include peptic ulcer disease (adjusted odds ratio [aOR] 10.2), obesity (aOR 1.27), chronic kidney disease (aOR 1.20), and tobacco use disorder (aOR 1.28). Lower risk of gastrointestinal bleeding was seen among women (aOR 0.76), Latinx (aOR 0.85), and vaccinated patients (aOR 0.74). Dexamethasone alone or with remdesivir was associated with lower risk of gastrointestinal bleeding (aOR 0.69 and aOR 0.83, respectively). Remdesivir monotherapy was associated with upper gastrointestinal bleeding (aOR 1.25). Proton pump inhibitors were more often prescribed in patients with gastrointestinal bleeding, likely representing treatment for gastrointestinal bleeding rather than a risk factor for its development. In adult patients hospitalized with COVID-19, the use of dexamethasone alone or in combination with remdesivir is negatively associated with gastrointestinal bleeding. Remdesivir monotherapy is associated with increased risk of upper gastrointestinal bleeding

Experimental study of the deformation and breakage of 3D printed agglomerates: Effects of packing density and inter-particle bond strength

Characterization of the mechanical properties of agglomerates is important in order to understand their deformation and breakage. However, research progress has been hampered by limitations in our ability to manufacture reproducible agglomerates with well-controlled and fully characterised mechanical properties. In this paper, we report on the preparation and testing of agglomerates with tuneable properties using 3D printing technology. Two typical agglomerate structures with different packing densities were designed and printed using a PolyJet 3D printer. Each agglomerate consisted of rigid primary particles connected by either rigid or rubber-like inter-particle cylindrical bonds. Compression tests (using speeds in the range 0.02–0.5 mm/s) and drop weight impact tests were carried out to investigate the effect of bond material and strain rate on mechanical properties of the agglomerates. The results show that strain rate affects their deformation and breakage significantly, and breakage patterns of the two structures are different under uniaxial compression and impact test conditions. These results demonstrate the broad utility of 3D printed agglomerates as ideal “test” agglomerates for a range of breakage studies, including validating computer simulations of DEM breakage

Clinical characteristics of ovarian cancer classified by BRCA1, BRCA2, and RAD51C status.

We evaluated homologous recombination deficient (HRD) phenotypes in epithelial ovarian cancer (EOC) considering BRCA1, BRCA2, and RAD51C in a large well-annotated patient set. We evaluated EOC patients for germline deleterious mutations (n = 899), somatic mutations (n = 279) and epigenetic alterations (n = 482) in these genes using NGS and genome-wide methylation arrays. Deleterious germline mutations were identified in 32 (3.6%) patients for BRCA1, in 28 (3.1%) for BRCA2 and in 26 (2.9%) for RAD51C. Ten somatically sequenced patients had deleterious alterations, six (2.1%) in BRCA1 and four (1.4%) in BRCA2. Fifty two patients (10.8%) had methylated BRCA1 or RAD51C. HRD patients with germline or somatic alterations in any gene were more likely to be high grade serous, have an earlier diagnosis age and have ovarian and/or breast cancer family history. The HRD phenotype was most common in high grade serous EOC. Identification of EOC patients with an HRD phenotype may help tailor specific therapies.This work was supported by National Institutes of Health grants R01-CA122443, P50-CA136393, P30-CA15083, and the Fred C. and Katherine B. Andersen Foundation. We thank Gary Kenney, M.D. for pathology review of tumor tissue. We thank Craig Luccarini, Caroline Baynes from University of Cambridge for assisting our sample sequencing

Orientia tsutsugamushi ankyrin repeat-containing protein family members are Type 1 secretion system substrates that traffic to the host cell endoplasmic reticulum

Scrub typhus is an understudied, potentially fatal infection that threatens one billion persons in the Asia-Pacific region. How the causative obligate intracellular bacterium, Orientia tsutsugamushi, facilitates its intracellular survival and pathogenesis is poorly understood. Many intracellular bacterial pathogens utilize the Type 1 (T1SS) or Type 4 secretion system (T4SS) to translocate ankyrin repeat-containing proteins (Anks) that traffic to distinct subcellular locations and modulate host cell processes. The O. tsutsugamushi genome encodes one of the largest known bacterial Ank repertoires plus T1SS and T4SS components. Whether these potential virulence factors are expressed during infection, how the Anks are potentially secreted, and to where they localize in the host cell are not known. We determined that O. tsutsugamushi transcriptionally expresses 20 unique ank genes as well as genes for both T1SS and T4SS during infection of mammalian host cells. Examination of the Anks’ C-termini revealed that the majority of them resemble T1SS substrates. Escherichia coli expressing a functional T1SS was able to secrete chimeric hemolysin proteins bearing the C-termini of 19 of 20 O. tsutsugamushi Anks in an HlyBD-dependent manner. Thus, O. tsutsugamushi Anks C-termini are T1SS-compatible. Conversely, Coxiella burnetii could not secrete heterologously expressed Anks in a T4SS-dependent manner. Analysis of the subcellular distribution patterns of 20 ectopically expressed Anks revealed that, while 6 remained cytosolic or trafficked to the nucleus, 14 localized to, and in some cases, altered the morphology of the endoplasmic reticulum. This study identifies O. tsutsugamushi Anks as T1SS substrates and indicates that many display a tropism for the host cell secretory pathway

Deformation of 3D printed agglomerates: Multiscale experimental tests and DEM simulation

Agglomerates are widely used in industry, and their mechanical properties are of great interest. In this work, we propose a new concept of using a coordinated multiscale approach to match the physical and digital agglomerate structures and properties. By using a multi-material 3D printing technology, the inter-particle bond properties and agglomerate structures could be precisely controlled and replicated. Quasi-static compression tests have been carried out for the 3D printed samples at different scales. A Timoshenko Beam Bond Model (TBBM) with bond properties matching those of the 3D printed agglomerates is used to describe bond deformations. Discrete Element Method (DEM) is then employed to simulate the agglomerate crushing process. The results show that for both agglomerate structures, the DEM simulation and experimental results show good agreement at the initial elastic deformation stage. This work opens up the chance for significant advances in agglomerate deformation and breakage modelling in future

Submillimeter Studies of Prestellar Cores and Protostars: Probing the Initial Conditions for Protostellar Collapse

Improving our understanding of the initial conditions and earliest stages of protostellar collapse is crucial to gain insight into the origin of stellar masses, multiple systems, and protoplanetary disks. Observationally, there are two complementary approaches to this problem: (1) studying the structure and kinematics of prestellar cores observed prior to protostar formation, and (2) studying the structure of young (e.g. Class 0) accreting protostars observed soon after point mass formation. We discuss recent advances made in this area thanks to (sub)millimeter mapping observations with large single-dish telescopes and interferometers. In particular, we argue that the beginning of protostellar collapse is much more violent in cluster-forming clouds than in regions of distributed star formation. Major breakthroughs are expected in this field from future large submillimeter instruments such as Herschel and ALMA.Comment: 12 pages, 9 figures, to appear in the proceedings of the conference "Chemistry as a Diagnostic of Star Formation" (C.L. Curry & M. Fich eds.

Theory of Star Formation

We review current understanding of star formation, outlining an overall theoretical framework and the observations that motivate it. A conception of star formation has emerged in which turbulence plays a dual role, both creating overdensities to initiate gravitational contraction or collapse, and countering the effects of gravity in these overdense regions. The key dynamical processes involved in star formation -- turbulence, magnetic fields, and self-gravity -- are highly nonlinear and multidimensional. Physical arguments are used to identify and explain the features and scalings involved in star formation, and results from numerical simulations are used to quantify these effects. We divide star formation into large-scale and small-scale regimes and review each in turn. Large scales range from galaxies to giant molecular clouds (GMCs) and their substructures. Important problems include how GMCs form and evolve, what determines the star formation rate (SFR), and what determines the initial mass function (IMF). Small scales range from dense cores to the protostellar systems they beget. We discuss formation of both low- and high-mass stars, including ongoing accretion. The development of winds and outflows is increasingly well understood, as are the mechanisms governing angular momentum transport in disks. Although outstanding questions remain, the framework is now in place to build a comprehensive theory of star formation that will be tested by the next generation of telescopes.Comment: 120 pages, to appear in ARAA. No changes from v1 text; permission statement adde

High temperature superconductivity (Tc onset at 34K) in the high pressure orthorhombic phase of FeSe

We have studied the structural and superconducting properties of tetragonal FeSe under pressures up to 26GPa using synchrotron radiation and diamond anvil cells. The bulk modulus of the tetragonal phase is 28.5(3)GPa, much smaller than the rest of Fe based superconductors. At 12GPa we observe a phase transition from the tetragonal to an orthorhombic symmetry. The high pressure orthorhombic phase has a higher Tc reaching 34K at 22GPa.Comment: 15 pages, 4 figure

Circulating microRNAs Reveal Time Course of Organ Injury in a Porcine Model of Acetaminophen-Induced Acute Liver Failure

Acute liver failure is a rare but catastrophic condition which can progress rapidly to multi-organ failure. Studies investigating the onset of individual organ injury such as the liver, kidneys and brain during the evolution of acute liver failure, are lacking. MicroRNAs are short, non-coding strands of RNA that are released into the circulation following tissue injury. In this study, we have characterised the release of both global microRNA and specific microRNA species into the plasma using a porcine model of acetaminophen-induced acute liver failure. Pigs were induced to acute liver failure with oral acetaminophen over 19h±2h and death occurred 13h±3h thereafter. Global microRNA concentrations increased 4h prior to acute liver failure in plasma (P<0.0001) but not in isolated exosomes, and were associated with increasing plasma levels of the damage-associated molecular pattern molecule, genomic DNA (P<0.0001). MiR122 increased around the time of onset of acute liver failure (P<0.0001) and was associated with increasing international normalised ratio (P<0.0001). MiR192 increased 8h after acute liver failure (P<0.0001) and was associated with increasing creatinine (P<0.0001). The increase in miR124-1 occurred concurrent with the pre-terminal increase in intracranial pressure (P<0.0001) and was associated with decreasing cerebral perfusion pressure (P<0.002)