Opportunities to optimise colistin stewardship in hospitalised patients in South Africa: Results of a multisite utilisation audit

Background. Colistin is an old antibiotic that has been reintroduced as salvage therapy in hospitalised patients because it is frequently the only agent active against Gram-negative bacteria. Various guidelines for colistin administration have led to confusion in establishing the appropriate dose, which has potential for adverse consequences including treatment failure or toxicity. The emergence and spread of colistin resistance has been documented in South Africa (SA), but no local information exists on how and why colistin is used in  hospitals, and similarly, compliance with current dosing guidelines is unknown.Objectives. To evaluate the current utilisation of colistin in SA hospitals, in order to identify stewardship opportunities that could enhance the appropriate use of this antibiotic.Methods. Electronic patient records of adult patients on intravenous (IV) colistin therapy for >72 hours in four private hospitals were retrospectively audited over a 10-month period (1 September 2015 - 30 June 2016). The following data were recorded: patient demographics, culture and susceptibility profiles, diagnosis, and indication for use. Compliance with six colistin process measures was audited: obtaining a culture prior to initiation, administration of a loading dose, administration of the correct loading dose, adjustments to maintenance dose according to renal function, whether colistin was administered in combination with another antibiotic, and whether de-escalation following culture and sensitivity results  occurred. Outcome measures included effects on renal function, overall hospital mortality, intensive care unit length of stay (LoS), and hospital LoS.Results. Records of 199 patients on IV colistin were reviewed. There was 99.0% compliance with obtaining a culture prior to antibiotic therapy, 93.5% compliance with prescription of a loading dose, and 98.5% compliance regarding prescription of colistin in combination with another agent. However, overall composite compliance with the six colistin stewardship process measures was 82.0%. Non-compliance related to inappropriate loading and  maintenance doses, lack of adjustment according to renal function and lack of de-escalation following culture sensitivity was evident. Significantly shorter durations of treatment were noted in patients who received higher loading doses (p=0.040) and in those who received maintenance doses of 4.5 MU twice daily v. 3 MU three times daily (p=0.0027). In addition, compared with patients who survived, more patients who died received the 3 MU three times daily maintenance dose (p=0.0037; phi coefficient 0.26).Conclusions. The study identified multiple stewardship opportunities to optimise colistin therapy in hospitalised patients. Urgent implementation of a stewardship bundle to improve colistin utilisation is warranted.

Aversive Counterconditioning Attenuates Reward Signaling in the Ventral Striatum

Appetitive conditioning refers to the process of learning cue-reward associations and is mediated by the mesocorticolimbic system. Appetitive conditioned responses are difficult to extinguish, especially for highly salient reward such as food and drugs. We investigate whether aversive counterconditioning can alter reward reinstatement in the ventral striatum in healthy volunteers using functional magnetic resonance imaging (fMRI). In the initial conditioning phase, two different stimuli were reinforced with a monetary reward. In the subsequent counterconditioning phase, one of these stimuli was paired with an aversive shock to the wrist. In the following extinction phase, none of the stimuli were reinforced. In the final reinstatement phase, reward was reinstated by informing the participants that the monetary gain could be doubled. Our fMRI data revealed that reward signaling in the ventral striatum and ventral tegmental area following reinstatement was smaller for the stimulus that was counterconditioned with an electrical shock, compared to the non-counterconditioned stimulus. A functional connectivity analysis showed that aversive counterconditioning strengthened striatal connectivity with the hippocampus and insula. These results suggest that reward signaling in the ventral striatum can be attenuated through aversive counterconditioning, possibly by concurrent retrieval of the aversive association through enhanced connectivity with hippocampus and insula

Enhanced T-odd P-odd Electromagnetic Moments in Reflection Asymmetric Nuclei

Collective P- and T- odd moments produced by parity and time invariance violating forces in reflection asymmetric nuclei are considered. The enhanced collective Schiff, electric dipole and octupole moments appear due to the mixing of rotational levels of opposite parity. These moments can exceed single-particle moments by more than two orders of magnitude. The enhancement is due to the collective nature of the intrinsic moments and the small energy separation between members of parity doublets. In turn these nuclear moments induce enhanced T- and P- odd effects in atoms and molecules. First a simple estimate is given and then a detailed theoretical treatment of the collective T-, P- odd electric moments in reflection asymmetric, odd-mass nuclei is presented and various corrections evaluated. Calculations are performed for octupole deformed long-lived odd-mass isotopes of Rn, Fr, Ra, Ac and Pa and the corresponding atoms. Experiments with such atoms may improve substantially the limits on time reversal violation.Comment: 28 pages, Revte

Nuclear Octupole Correlations and the Enhancement of Atomic Time-Reversal Violation

We examine the time-reversal-violating nuclear ``Schiff moment'' that induces electric dipole moments in atoms. After presenting a self-contained derivation of the form of the Schiff operator, we show that the distribution of Schiff strength, an important ingredient in the ground-state Schiff moment, is very different from the electric-dipole-strength distribution, with the Schiff moment receiving no strength from the giant dipole resonance in the Goldhaber-Teller model. We then present shell-model calculations in light nuclei that confirm the negligible role of the dipole resonance and show the Schiff strength to be strongly correlated with low-lying octupole strength. Next, we turn to heavy nuclei, examining recent arguments for the strong enhancement of Schiff moments in octupole-deformed nuclei over that of 199Hg, for example. We concur that there is a significant enhancement while pointing to effects neglected in previous work (both in the octupole-deformed nuclides and 199Hg) that may reduce it somewhat, and emphasizing the need for microscopic calculations to resolve the issue. Finally, we show that static octupole deformation is not essential for the development of collective Schiff moments; nuclei with strong octupole vibrations have them as well, and some could be exploited by experiment.Comment: 25 pages, 4 figures embedded in tex

Systematic study of the effect of short range correlations on the form factors and densities of s-p and s-d shell nuclei

Analytical expressions of the one- and two-body terms in the cluster expansion of the charge form factors and densities of the s-p and s-d shell nuclei with N=Z are derived. They depend on the harmonic oscillator parameter b and the parameter $\beta$ which originates from the Jastrow correlation function. These expressions are used for the systematic study of the effect of short range correlations on the form factors and densities and of the mass dependence of the parameters b and $\beta$. These parameters have been determined by fit to the experimental charge form factors. The inclusion of the correlations reproduces the experimental charge form factors at the high momentum transfers ($q\geq 2 1/fm$). It is found that while the parameter $\beta$ is almost constant for the closed shell nuclei, $^4$He, $^{16}$O and $^{40}$Ca, its values are larger (less correlated systems) for the open shell nuclei, indicating a shell effect in the closed shell nuclei.Comment: Latex, 21 pages, 6 figures, 1 tabl

Crystal chemistry search of multiferroics with the stereochemically active lone pair

On the basis of our previous studies of magnetoelectric ordering of BiFeO3, TbMnO3, TbMn2O5 and BiMn2O5 we formulate the crystal chemistry criteria for the search of multiferroics and reveal potential multiferroics Pb2Cu(OH)4Cl2, Pb5Cr3F19, Mn(SeO3){\dot}H2O and BiPbSr2MnO6 each containing the ion with a lone pair.Comment: 4 pages, 8 figures,submitted to J Supercond Nov Mag

Strange particle production in 158 and 40 AA GeV/cc Pb-Pb and p-Be collisions

Results on strange particle production in Pb-Pb collisions at 158 and 40 $A$ GeV/$c$ beam momentum from the NA57 experiment at CERN SPS are presented. Particle yields and ratios are compared with those measured at RHIC. Strangeness enhancements with respect to p-Be reactions at the same beam momenta have been also measured: results about their dependence on centrality and collision energy are reported and discussed.Comment: Contribution to the proceedings of the "Hot Quarks 2004" Conference, July 18-24 2004, New Mexico, USA, submitted to Journal of Physics G 7 pages, 5 figure

Lichenometric dating (lichenometry) and the biology of the lichen genus rhizocarpon:challenges and future directions

Lichenometric dating (lichenometry) involves the use of lichen measurements to estimate the age of exposure of various substrata. Because of low radial growth rates and considerable longevity, species of the crustose lichen genus Rhizocarpon have been the most useful in lichenometry. The primary assumption of lichenometry is that colonization, growth and mortality of Rhizocarpon are similar on surfaces of known and unknown age so that the largest thalli present on the respective faces are of comparable age. This review describes the current state of knowledge regarding the biology of Rhizocarpon and considers two main questions: (1) to what extent does existing knowledge support this assumption; and (2) what further biological observations would be useful both to test its validity and to improve the accuracy of lichenometric dates? A review of the Rhizocarpon literature identified gaps in knowledge regarding early development, the growth rate/size curve, mortality, regeneration, competitive effects, colonization, and succession on rock surfaces. The data suggest that these processes may not be comparable on different rock surfaces, especially in regions where growth rates and thallus turnover are high. In addition, several variables could differ between rock surfaces and influence maximum thallus size, including rate and timing of colonization, radial growth rates, environmental differences, thallus fusion, allelopathy, thallus mortality, colonization and competition. Comparative measurements of these variables on surfaces of known and unknown age may help to determine whether the basic assumptions of lichenometry are valid. Ultimately, it may be possible to take these differences into account when interpreting estimated dates

Results on cascade production in lead-lead interactions from the NA57 experiment

The NA57 experiment has been designed to study the production of strange and multi-strange particles in Pb-Pb and p-Be collisions at the CERN SPS. The predecessor experiment WA97 has measured an enhanced abundance of strange particles in Pb-Pb collisions relative to p-A reactions at 160 GeV/c per nucleon beam momentum. NA57 has extended the WA97 measurements to investigate the evolution of the strangeness enhancement pattern as a function of the beam energy and over a wider centrality range. In this paper, we report results on cascade production for about the 60% most central collisions at 160 GeV/c per nucleon