Comparison of the renal clearances of inulin and radioactive labelled hypaque as measures of the glomerular filtration rate in man

The standard method of estimating the rate of glomerular filtration (G.F.R.) in man has been by the renal clearance of inulin since it was demonstrated. that this plant polysaccharide is neither secreted nor reabsorbed by the renal tubules. The criteria which must be satisfied by a substance for its renal clearance to cive a valid measure of glomerular filtration rate have been discussed in detail by Smith (1951). Chemical methods for the determination of inulin in plasma and urine have been rather unsatisfactory (Smith 1951) and a variety of substances have been studied in an attempt to find a substitute for inulin. The endogenous creatinine clearance is widely used for clinical purposes but the creatinine/inulin clearance ratio exceeds unity in many human subjects indicating a variable deree of tubular secretion of creatinine (Smith 1 951 , Berlune et al 1 964) and this clearance is not a reliable measure of glomerular filtration in man.Recently a number of compounds labelled with radioisotopes have been studied and found to have clearances similar to'that of inulin. Allyl inulin labelled with ¹²⁵I has a clearance virtually identical to that of inulin in the dog (Concannon et al 1964) but is not readily available and is difficult to sterilise. Radioactive ⁵⁷Co-labelled cyanocobalamin gives a satisfactory measure of G.F.R. if only the free vitamin in the plasma is measured (Nelp et al 1964, Cutler and Glatte 1965). However, even after a large loading dose of unlabelled cyanocobalamin, plasma protein binding, of the labelled compound occurs and is variable in extent, nor is it easy to determine the proportion. of the labelled vitamin which is plasma bound in vivo (Skins and Sgherzi 1964, Donaldson and Doig unpublished observations). The most convenient inulin substitutes so far available are .the radiographic contrast media sodium diatrizoate ( Hypaque) and meglumin diatrizoate (Renografin) labelled with ¹³I or ¹²⁵I. In man Hypaque appears to fulfil many of Smith's criteria, it is not significantly bound to plasma proteins (Lasser et al 1962) nor does it readily penetrate red blood cells (Denneberg et al 1961), its renal excretion is complete and its extrarenal excretion negligible (Denneberg 1965). Hypac,ue and Renografin have been shown by various authors to have clearances very similar to the simultaneous inulin or thiosulphate clearance in man and the literature on these compounds has been well reviewed by Denneberg (1965). However some authors have not found the Hypaque and inulin or thiosulphate clearances to be identical (Bianchi and Zampieri 1961, Woodruff and Malvin 1560, Stokes et al 1 ;62, Denneberg 1565 and while some comparisons were carried out during continuous infusion of inulin and Hypaque (Burbank et al 1963), others were made on the basis of a single injection of Hypaque (Bianchi and Zampieri 1961). The latter are difficult to interpret physiologically; the difficulties inherent in all "single injection" clearances have been discussed by Smith (1951) and Robson et al (1949) .It has been variously suggested that Hypaque is neither reabsorbed nor secreted by the renal tubules in man (Burbank et al 1963), nor in the dog Woodruff and Malvin 1960), that it is reabsorbed in man (Bianchi and Zampieri 1961) and in dog (Stokes et al 1962) and that it is both secreted and reabsorbed in man (Denneberg 1965).Morris et al (1965) found that the clearance of ¹³¹I Renografin did not alter when the plasma level was raised by large doses of inactive Renografin, suggesting that this compound is not handled by the tubules. However they studied only two subjects in this way. Hypaque would be expected to behave in the renal tubules in the same way as Renografin as it is the diatrizoate ion which is estimated in both cases. However Denneberg (1965) found that the Hypaque /inulin clearance ratio fell, on average, after the administration of the tubular blocking agent probenecid and concluded that Hypaque is secreted and perhaps also reabsorbed by the renal tubules in man.Because of this confusion in the literature about tubular handling of Hypaque in man, the studies described in this paper were carried out in an attempt to resolve the Question of whether or not radioactive labelled Hypaque is handled by the renal tubules and to investigate its clearance as a measure of the rate of glomerular filtration in human subjects

A prospective development study investigating focal irreversible electroporation in men with localised prostate cancer: Nanoknife Electroporation Ablation Trial (NEAT).

INTRODUCTION: Focal therapy may reduce the toxicity of current radical treatments while maintaining the oncological benefit. Irreversible electroporation (IRE) has been proposed to be tissue selective and so might have favourable characteristics compared to the currently used prostate ablative technologies. The aim of this trial is to determine the adverse events, genito-urinary side effects and early histological outcomes of focal IRE in men with localised prostate cancer. METHODS: This is a single centre prospective development (stage 2a) study following the IDEAL recommendations for evaluating new surgical procedures. Twenty men who have MRI-visible disease localised in the anterior part of the prostate will be recruited. The sample size permits a precision estimate around key functional outcomes. Inclusion criteria include PSA ≤ 15 ng/ml, Gleason score ≤ 4 + 3, stage T2N0M0 and absence of clinically significant disease outside the treatment area. Treatment delivery will be changed in an adaptive iterative manner so as to allow optimisation of the IRE protocol. After focal IRE, men will be followed during 12 months using validated patient reported outcome measures (IPSS, IIEF-15, UCLA-EPIC, EQ-5D, FACT-P, MAX-PC). Early disease control will be evaluated by mpMRI and targeted transperineal biopsy of the treated area at 6 months. DISCUSSION: The NEAT trial will assess the early functional and disease control outcome of focal IRE using an adaptive design. Our protocol can provide guidance for designing an adaptive trial to assess new surgical technologies in the challenging landscape of health technology assessment in prostate cancer treatment

A practical laboratory method to determine ceftazidime-avibactam-aztreonam synergy in patients with New Delhi Metallo-beta-lactamase (NDM) producing Enterobacterales infection

Background: In response to infection with New Delhi Metallo-beta-lactamase (NDM) producing Enterobacterales, combination antimicrobial therapy with ceftazidime/avibactam (CAZ/AVI) plus aztreonam (ATM) has been explored. This study evaluated a practical laboratory method of testing for clinically significant synergy between CAZ/AVI+ATM in NDM producing Enterobacterales. Methods: Minimum inhibitory concentration (MIC) of clinical NDM producing isolates were determined for ATM alone and CAZ/AVI+ATM using broth dilution. Restoration of ATM breakpoint following the addition of CAZ/AVI was explored. A CAZ/AVI E-test/ATM disc method was compared to broth dilution. Results: Of 43 isolates, 33/43 (77%) isolates were ATM resistant (median [range] MIC=56 [16 – 512] mg/L). Addition of CAZ/AVI restored the ATM breakpoint (MIC <4mg/L) in 29/33 (89%) of resistant isolates. Overall, the E-test/disc method correlated with findings from broth dilution in 35/43 (81%) of cases. E-test/disc sensitivity was 77% and specificity 85%. Positive predictive value was 92% and negative predictive value 61%. Conclusion: CAZ/AVI+ATM demonstrated significant synergy in most ATM resistant NDM producing Enterobacterales. The E-test/disc method is a quick, reproducible, and reliable method of testing for clinically relevant synergy in the microbiology laboratory

Corporate Culture and Its Connection with External and Internal Public Relations

The main aim of this article is to present the influence of corporate culture on company's stakeholders. This paper signalises the tendency in corporate communication with its internal and external publics. It is focused on two issues: corporate social responsibility and employer branding. Those two categories are consequences of corporate culture model.Głównym celem artykułu jest zaprezentowanie wpływu jaki wywiera charakter kultury korporacyjnej na związanych z przedsiębiorstwem interesariuszy (stakeholders). W artykule zasygnalizowane zostały główne tendencje wyznaczające charakter komunikacji między organizacją a jej wewnętrznym i zewnętrznym otoczeniem. Tekst koncentruje się na dwóch kwestiach: społecznej odpowiedzialności przedsiębiorstwa (corporate social responsibilty) i budowanie wizerunku pracodawcy (employer branding), które zaprezentowane zostały jako efekty określonego modelu kultury organizacyjnej

Reducing vortex density in superconductors using the ratchet effect

A serious obstacle that impedes the application of low and high temperature superconductor (SC) devices is the presence of trapped flux. Flux lines or vortices are induced by fields as small as the Earth's magnetic field. Once present, vortices dissipate energy and generate internal noise, limiting the operation of numerous superconducting devices. Methods used to overcome this difficulty include the pinning of vortices by the incorporation of impurities and defects, the construction of flux dams, slots and holes and magnetic shields which block the penetration of new flux lines in the bulk of the SC or reduce the magnetic field in the immediate vicinity of the superconducting device. Naturally, the most desirable would be to remove the vortices from the bulk of the SC. There is no known phenomenon, however, that could form the basis for such a process. Here we show that the application of an ac current to a SC that is patterned with an asymmetric pinning potential can induce vortex motion whose direction is determined only by the asymmetry of the pattern. The mechanism responsible for this phenomenon is the so called ratchet effect, and its working principle applies to both low and high temperature SCs. As a first step here we demonstrate that with an appropriate choice of the pinning potential the ratchet effect can be used to remove vortices from low temperature SCs in the parameter range required for various applications.Comment: 7 pages, 4 figures, Nature (in press

The Ethics of Corporate Governance

How should corporate directors determine what is the right decision? For at least the past 30 years the debate has raged as to whether shareholder value should take precedence over corporate social responsibility when crucial decisions arise. Directors face pressure, not least from ethical investors, to do the good thing when they seek to make the right choice. Corporate governance theory has tended to look to agency theory and the need of boards to curb excessive executive power to guide directors' decisions. While useful for those purposes, agency theory provides only limited guidance. Supplementing it with the alternatives - stakeholder theory and stewardship theory - tends to put directors in conflict with their legal obligations to work in the interests of shareholders. This paper seeks to reframe the discussion about corporate governance in terms of the ethical debate between consequential, teleological approaches to ethics and idealist, deontological ones, suggesting that directors are - for good reason - more inclined toward utilitarian judgments like those underpinning shareholder value. But the problems with shareholder value have become so great that a different framework is needed: strategic value, with an emphasis on long-term value creation judged from a decidedly utilitarian standpoint

Technical Note: Error metrics for estimating the accuracy of needle/instrument placement during transperineal MR/US-guided prostate interventions

Purpose: Image-guided systems that fuse magnetic resonance imaging (MRI) with three-dimensional (3D) ultrasound (US) images for performing targeted prostate needle biopsy and minimally-invasive treatments for prostate cancer are of increasing clinical interest. To date, a wide range of different accuracy estimation procedures and error metrics have been reported, which makes comparing the performance of different systems difficult. Methods: A set of 9 measures are presented to assess the accuracy of MRI-US image registration, needle positioning, needle guidance, and overall system error, with the aim of providing a methodology for estimating the accuracy of instrument placement using a MR/US-guided transperineal approach. Results: Using the SmartTarget fusion system, an MRI-US image alignment error was determined to be 2.0±1.0 mm (mean ± SD), and an overall system instrument targeting error of 3.0±1.2 mm. Three needle deployments for each target phantom lesion was found to result in a 100% lesion hit rate and a median predicted cancer core length of 5.2 mm. Conclusions: The application of a comprehensive, unbiased validation assessment for MR/TRUS guided systems can provide useful information on system performance for quality assurance and system comparison. Furthermore, such an analysis can be helpful in identifying relationships between these errors, providing insight into the technical behaviour of these systems

Chirality Change in String Theory

It is known that string theory compactifications leading to low energy effective theories with different chiral matter content ({\it e.g.} different numbers of standard model generations) are connected through phase transitions, described by non-trivial quantum fixed point theories. We point out that such compactifications are also connected on a purely classical level, through transitions that can be described using standard effective field theory. We illustrate this with examples, including some in which the transition proceeds entirely through supersymmetric configurations.Comment: 50 pages, 2 figure

Measures on Banach Manifolds and Supersymmetric Quantum Field Theory

We show how to construct measures on Banach manifolds associated to supersymmetric quantum field theories. These measures are mathematically well-defined objects inspired by the formal path integrals appearing in the physics literature on quantum field theory. We give three concrete examples of our construction. The first example is a family $\mu_P^{s,t}$ of measures on a space of functions on the two-torus, parametrized by a polynomial $P$ (the Wess-Zumino-Landau-Ginzburg model). The second is a family \mu_\cG^{s,t} of measures on a space \cG of maps from $\P^1$ to a Lie group (the Wess-Zumino-Novikov-Witten model). Finally we study a family $\mu_{M,G}^{s,t}$ of measures on the product of a space of connection s on the trivial principal bundle with structure group $G$ on a three-dimensional manifold $M$ with a space of \fg-valued three-forms on $M.$ We show that these measures are positive, and that the measures \mu_\cG^{s,t} are Borel probability measures. As an application we show that formulas arising from expectations in the measures \mu_\cG^{s,1} reproduce formulas discovered by Frenkel and Zhu in the theory of vertex operator algebras. We conjecture that a similar computation for the measures $\mu_{M,SU(2)}^{s,t},$ where $M$ is a homology three-sphere, will yield the Casson invariant of $M.$Comment: Minor correction