Oral to nasal endotracheal tube exchange using both video and flexible laryngoscopes

This case describes the use of a video laryngoscope and flexible intubation scope to facilitate the exchange of an oral endotracheal tube for a nasal endotracheal tube in a patient with a potentially difficult airway

External patient temperature control in emergency centres, trauma centres, intensive care units and operating theatres: A multi-society literature review

Here we review the available literature supporting the routine and timely use of external patient warming devices of all possible types during emergency department and peri-operative situations, including the role of best ambient temperature, and provides a best-practice statement on the need for such devices. It aims to present a guideline document endorsed by the major South African professional societies in the field of emergency and peri-operative care

The Durban World Congress Ethics Round Table conference report: I. Differences between withholding and withdrawing life-sustaining treatments

Introduction: Withholding life-sustaining treatments (WHLST) and withdrawing life-sustaining treatments (WDLST) occur in most intensive care units (ICUs) around the world to varying degrees. Methods: Speakers from invited faculty of the World Federation of Societies of Intensive and Critical Care Medicine Congress in 2013 with an interest in ethics were approached to participate in an ethics round table. Participants were asked if they agreed with the statement "There is no moral difference between withholding and withdrawing a mechanical ventilator." Differences between WHLST and WDLST were discussed. Official statements relating to WHLST and WDLST from intensive care societies, professional bodies, and government statements were sourced, documented, and compared. Results: Sixteen respondents stated that there was no moral difference between withholding or withdrawing a mechanical ventilator, 2 were neutral, and 4 stated that there was a difference. Most ethicists and medical organizations state that there is no moral difference between WHLST and WDLST. A review of guidelines noted that all but 1 of 29 considered WHLST and WDLST as ethically or legally equivalent. Conclusions: Most respondents, practicing intensivists, stated that there is no difference between WHLST and WDLST, supporting most ethicists and professional organizations. A minority of physicians still do not accept their equivalency

Intermittent, ambulatory dobutamine infusions in patients with severe congestive heart failure

Thirteen ambulatory patients with severe congestive heart failure were treated with weekly outpatient 48-hour infusions of dobutamine. All 13 patients had at least a 25% increase in cardiac output during initial dobutamine titration, with a corresponding improvement in systemic vascular resistance. Improvement in functional class was achieved in only seven patients. Additionally, only three patients survived the 26-week study period. Although no change in ventricular ectopy was noted during the initial dobutamine infusions, six patients experienced sudden death; three other patients died of progressive heart failure and one died from pulmonary embolism. These data suggest that chronic intermittent ambulatory dobutamine infusions are only partly successful in improving symptoms and probably do not prolong survival in patients with severe congestive heart failure. Administration of this form of therapy on a clinical basis should be undertaken cautiously until safety and efficacy are demonstrated in prospective, controlled trials.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/26035/1/0000108.pd

The Durban World Congress Ethics Round Table Conference Report: III. Withdrawing Mechanical ventilation-the approach should be individualized

Purpose: The purpose of this study is to determine the approaches used in withdrawing mechanical ventilator support. Materials and methods: Speakers from the invited faculty of the World Federation of Societies of Intensive and Critical Care Medicine Congress in 2013 with an interest in ethics were asked to provide a detailed description of individual approaches to the process of withdrawal of mechanical ventilation. Results: Twenty-one participants originating from 13 countries, responded to the questionnaire. Four respondents indicated that they do not practice withdrawal of mechanical ventilation, and another 4 indicated that their approach is highly variable depending on the clinical scenario. Immediate withdrawal of ventilation was practiced by a large number of the respondents (7/16; 44%). A terminal wean was practiced by just more than a third of the respondents (6/16; 38%). Extubation was practiced in more than 70% of instances among most of the respondents (9/17; 53%). Two of the respondents (2/17; 12%) indicated that they would extubate all patients, whereas 14 respondents indicated that they would not extubate all their patients. The emphasis was on tailoring the approach used to suit individual case scenarios. Conclusions: Withdrawing of ventilator support is not universal. However, even when withdrawing mechanical ventilation is acceptable, the approach to achieve this end point is highly variable and individualized

Ernst Freund as Precursor of the Rational Study of Corporate Law

Gindis, David, Ernst Freund as Precursor of the Rational Study of Corporate Law (October 27, 2017). Journal of Institutional Economics, Forthcoming. Available at SSRN: https://ssrn.com/abstract=2905547, doi: https://dx.doi.org/10.2139/ssrn.2905547The rise of large business corporations in the late 19th century compelled many American observers to admit that the nature of the corporation had yet to be understood. Published in this context, Ernst Freund's little-known The Legal Nature of Corporations (1897) was an original attempt to come to terms with a new legal and economic reality. But it can also be described, to paraphrase Oliver Wendell Holmes, as the earliest example of the rational study of corporate law. The paper shows that Freund had the intuitions of an institutional economist, and engaged in what today would be called comparative institutional analysis. Remarkably, his argument that the corporate form secures property against insider defection and against outsiders anticipated recent work on entity shielding and capital lock-in, and can be read as an early contribution to what today would be called the theory of the firm.Peer reviewe

The cellular chloride channels CLIC1 and CLIC4 contribute to virus-mediated cell motility

Ion channels regulate many aspects of cell physiology, including cell proliferation, motility, and migration, and aberrant expression and activity of ion channels is associated with various stages of tumor development, with K⁺ and Cl⁻ channels now being considered the most active during tumorigenesis. Accordingly, emerging in vitro and preclinical studies have revealed that pharmacological manipulation of ion channel activity offers protection against several cancers. Merkel cell polyomavirus (MCPyV) is a major cause of Merkel cell carcinoma (MCC), primarily because of the expression of two early regulatory proteins termed small and large tumor antigens (ST and LT, respectively). Several molecular mechanisms have been attributed to MCPyV-mediated cancer formation but, thus far, no studies have investigated any potential link to cellular ion channels. Here we demonstrate that Cl⁻ channel modulation can reduce MCPyV ST-induced cell motility and invasiveness. Proteomic analysis revealed that MCPyV ST up-regulates two Cl⁻ channels, CLIC1 and CLIC4, which when silenced, inhibit MCPyV ST-induced motility and invasiveness, implicating their function as critical to MCPyV-induced metastatic processes. Consistent with these data, we confirmed that CLIC1 and CLIC4 are up-regulated in primary MCPyV-positive MCC patient samples. We therefore, for the first time, implicate cellular ion channels as a key host cell factor contributing to virus-mediated cellular transformation. Given the intense interest in ion channel modulating drugs for human disease. This highlights CLIC1 and CLIC4 activity as potential targets for MCPyV-induced MCC

LSST: from Science Drivers to Reference Design and Anticipated Data Products

(Abridged) We describe here the most ambitious survey currently planned in the optical, the Large Synoptic Survey Telescope (LSST). A vast array of science will be enabled by a single wide-deep-fast sky survey, and LSST will have unique survey capability in the faint time domain. The LSST design is driven by four main science themes: probing dark energy and dark matter, taking an inventory of the Solar System, exploring the transient optical sky, and mapping the Milky Way. LSST will be a wide-field ground-based system sited at Cerro Pach\'{o}n in northern Chile. The telescope will have an 8.4 m (6.5 m effective) primary mirror, a 9.6 deg$^2$ field of view, and a 3.2 Gigapixel camera. The standard observing sequence will consist of pairs of 15-second exposures in a given field, with two such visits in each pointing in a given night. With these repeats, the LSST system is capable of imaging about 10,000 square degrees of sky in a single filter in three nights. The typical 5$\sigma$ point-source depth in a single visit in $r$ will be $\sim 24.5$ (AB). The project is in the construction phase and will begin regular survey operations by 2022. The survey area will be contained within 30,000 deg$^2$ with $\delta<+34.5^\circ$, and will be imaged multiple times in six bands, $ugrizy$, covering the wavelength range 320--1050 nm. About 90\% of the observing time will be devoted to a deep-wide-fast survey mode which will uniformly observe a 18,000 deg$^2$ region about 800 times (summed over all six bands) during the anticipated 10 years of operations, and yield a coadded map to $r\sim27.5$. The remaining 10\% of the observing time will be allocated to projects such as a Very Deep and Fast time domain survey. The goal is to make LSST data products, including a relational database of about 32 trillion observations of 40 billion objects, available to the public and scientists around the world.Comment: 57 pages, 32 color figures, version with high-resolution figures available from https://www.lsst.org/overvie

Evaluation of polygenic risk scores for breast and ovarian cancer risk prediction in BRCA1 and BRCA2 mutation carriers

Background: Genome-wide association studies (GWAS) have identified 94 common single-nucleotide polymorphisms (SNPs) associated with breast cancer (BC) risk and 18 associated with ovarian cancer (OC) risk. Several of these are also associated with risk of BC or OC for women who carry a pathogenic mutation in the high-risk BC and OC genes BRCA1 or BRCA2. The combined effects of these variants on BC or OC risk for BRCA1 and BRCA2 mutation carriers have not yet been assessed while their clinical management could benefit from improved personalized risk estimates. Methods: We constructed polygenic risk scores (PRS) using BC and OC susceptibility SNPs identified through population-based GWAS: for BC (overall, estrogen receptor [ER]-positive, and ER-negative) and for OC. Using data from 15 252 female BRCA1 and 8211 BRCA2 carriers, the association of each PRS with BC or OC risk was evaluated using a weighted cohort approach, with time to diagnosis as the outcome and estimation of the hazard ratios (HRs) per standard deviation increase in the PRS. Results: The PRS for ER-negative BC displayed the strongest association with BC risk in BRCA1 carriers (HR = 1.27, 95% confidence interval [CI] = 1.23 to 1.31, P = 8.2 x 10(53)). In BRCA2 carriers, the strongest association with BC risk was seen for the overall BC PRS (HR = 1.22, 95% CI = 1.17 to 1.28, P = 7.2 x 10(-20)). The OC PRS was strongly associated with OC risk for both BRCA1 and BRCA2 carriers. These translate to differences in absolute risks (more than 10% in each case) between the top and bottom deciles of the PRS distribution; for example, the OC risk was 6% by age 80 years for BRCA2 carriers at the 10th percentile of the OC PRS compared with 19% risk for those at the 90th percentile of PRS. Conclusions: BC and OC PRS are predictive of cancer risk in BRCA1 and BRCA2 carriers. Incorporation of the PRS into risk prediction models has promise to better inform decisions on cancer risk management