Measuring human-error probabilities in drug preparation: a pilot simulation study

Objectives: Designing a safe medication process requires the ability to model its reliability using methods such as probabilistic risk assessment (PRA). However, lack of data, especially on human-error probabilities (HEPs), limits its use. To assess whether small-scale simulations could help generate HEP data, a pilot study was conducted among nurses and anaesthetists. It focused on two core activities, namely, the manual preparation of medications and the arithmetic necessary to prepare drugs. Its specific objectives were to evaluate whether HEPs could be high enough to be measurable and to determine whether these HEPs could be sensitive to individuals and task details. These would give some insight into the level of detail required by PRA analysis. Methods: Thirty nurse and 28 anaesthetist volunteers were involved in the experiment. Nurses and anaesthetists had to prepare medications for 20 patients and 22 syringes of various drugs, respectively. Both groups had to perform 22 calculations relating to the preparation of drugs. HEPs, distribution of HEPs and dependency of HEPs on individuals and task details were assessed. Results: In the preparation tasks, overall HEP was 3.0% for nurses and 6.5% for anaesthetists. In the arithmetic tasks, overall HEP was 23.8% for nurses and 8.9% for anaesthetists. A statistically significant difference was noted between the two groups. In both preparation and arithmetic tasks, HEPs were dependent on individual nurses but not on individual anaesthetists. In every instance, HEPs were dependent on task details. Conclusion: Our study illustrates that small-scale simulations represent an interesting way of generating HEPs. HEPs are, indeed, in the range of 10−2 and 10−1. But in most cases, HEPs depend heavily on operators and task details. This dependency means that the influence of these parameters must be determined before advanced PRA analysis. There is therefore an urgent need to develop experimental research into assessing this influence by means of randomised controlled trial

Magnetic-Torque Enhanced by Tunable Dipolar interactions

We use tunable dipolar-interactions between the spins of nitrogen-vacancy (NV) centers in diamond to rotate a diamond crystal. Specifically, we employ cross-relaxation between the electronic spin of pairs of NV centers in a trapped diamond to enhance the anisotropic NV paramagnetism and thus to increase the associated spin torque. Our observations open a path towards the use of mechanical oscillators to detect paramagnetic defects that lack optical transitions, to investigation of angular momentum conservation in spin relaxation processes and to novel means of cooling the motion of mechanical oscillators.Comment: 15 page

Optical Detection of Paramagnetic Defects in a CVD-grown Diamond

The electronic spins of the nitrogen-vacancy centers (NV centers) in Chemical-Vapor-Deposition (CVD) grown diamonds form ideal probes of magnetic fields and temperature, as well as promising qu-bits for quantum information processing. Studying and controlling the magnetic environment of NV centers in such high purity crystals is thus essential for these applications. We demonstrate optical detection of paramagnetic species, such as hydrogen-related complexes, in a CVD-grown diamond. The resonant transfer of the NV centers' polarized electronic spins to the electronic spins of these species generates conspicuous features in the NV photoluminescence by employing magnetic field scans along the [100] crystal direction. Our results offer prospects for more detailed studies of CVD-grown processes as well as for coherent control of the spin of novel classes of hyper-polarized paramagnetic species.Comment: 8 pages including appendi

Warming permafrost and active layer variability at Cime Bianche, Western European Alps

The objective of this paper is to provide a first synthesis on the state and recent evolution of permafrost at the monitoring site of Cime Bianche (3100 m a.s.l.) on the Italian side of the Western Alps. The analysis is based on 7 years of ground temperature observations in two boreholes and seven surface points. The analysis aims to quantify the spatial and temporal variability of ground surface temperature in relation to snow cover, the small-scale spatial variability of the active layer thickness and current temperature trends in deep permafrost.Results show that the heterogeneity of snow cover thickness, both in space and time, is the main factor controlling ground surface temperatures and leads to a mean range of spatial variability (2.5 ± 0.1 °C) which far exceeds the mean range of observed inter-annual variability (1.6 ± 0.1 °C). The active layer thickness measured in two boreholes at a distance of 30 m shows a mean difference of 2.0 ± 0.1 m with the active layer of one borehole consistently deeper. As revealed by temperature analysis and geophysical soundings, such a difference is mainly driven by the ice/water content in the sub-surface and not by the snow cover regimes. The analysis of deep temperature time series reveals that permafrost is warming. The detected trends are statistically significant starting from a depth below 8 m with warming rates between 0.1 and 0.01 °C yr⁻¹

Planetary Nebulae Kinematics in M31

We present kinematics of 135 planetary nebulae in M31 from a survey covering 3.9 square degrees and extending out to 15 kpc from the southwest major axis and more than 20 kpc along the minor axis. The majority of our sample, even well outside the disk, shows significant rotational support (mean line-of-sight velocity 116 km/s). We argue that these PN belong to the outer part of M31's large de Vaucouleurs bulge. Only five PN have velocities clearly inconsistent with this fast rotating bulge. All five may belong to tidal streams in M31's outer halo. One is projected on the Northern Spur, and is counter-rotating with respect to the disk there. Two are projected along the major axis at X=-10 kpc and have M32-like velocities; they could be debris from that galaxy. The remaining two halo PN are located near the center of the galaxy and their velocities follow the gradient found by Ibata et al. (2004), implying that these PN could belong to the Southern Stream. If M31 has a non-rotating, pressure-supported halo, we have yet to find it, and it must be a very minor component of the galaxy.Comment: accepted to ApJ; main body of paper is 36 pages, including 14 figure

The Stellar Population of the M31 Spiral Arm Around OB Association A24

A study of the stellar population of the M31 spiral arm around OB association A24 was carried out based on the photometric data obtained from deep V and JHK imaging. The luminosity function was obtained for -7 <~ Mbol <~ -3.5 by applying the extinction correction corresponding to Av=1 and the bolometric correction BC(K) as an empirical function of (J-K)o. In comparing the observed color-luminosity diagrams with semitheoretical isochrones modified for the dust-shell effects, we found the young population of t <~ 30 Myr with supergiants of Mbol <~ -5, the bulk of the intermediate-age population of t ~ 0.2 - 2.5 Gyr with bright asymptotic giant branch (AGB) stars of -5 <~ Mbol <~ -4, and old populations of t ~> 3 Gyr with AGB and red giant branch (RGB) stars of Mbol ~> -4. The average star formation rate was estimated to be ~1.8x10^4 M_o/Myr and ~0.7x10^4 M_o/Myr per deprojected disk area of 1 kpc^2 from the number density of B0 V stars around Mv=-4.0 (age ~10 Myr) and the number density of bright AGB stars around Mbol = -4.3 (age ~1 Gyr), respectively. A study of the local variation in the V and the J and H luminosity functions revealed a kind of anticorrelation between the population of the young component and that of the intermediate-age component when subdomains of ~100 pc scales were concerned. This finding suggests that the disk domain around the A24 area experienced a series of star formation episodes alternatively among different subdomains with a timescale of a few spiral passage periods. Brief discussions are given about the interstellar extinction and about the lifetimes of bright AGB stars and the highly red objects (HROs) in the same area.Comment: 27 pages, 11 figures, accepted: ApJ, July 1, 199

Smooth muscle cell-specific knockout of neuropilin-1 impairs postnatal lung development and pathological vascular smooth muscle cell accumulation

Neuropilin 1 (NRP1) is important for neuronal and cardiovascular development due to its role in conveying class 3 semaphorin and vascular endothelial growth factor signaling, respectively. NRP1 is expressed in smooth muscle cells (SMCs) and mediates their migration and proliferation in cell culture and is implicated in pathological SMC remodeling in vivo. To address the importance of Nrp1 for SMC function during development, we generated conditional inducible Nrp1 SMC-specific knockout mice. Induction of early postnatal SMC-specific Nrp1 knockout led to pulmonary hemorrhage associated with defects in alveogenesis and revealed a specific requirement for Nrp1 in myofibroblast recruitment to the alveolar septae and PDGF-AA-induced migration in vitro. Furthermore, SMC-specific Nrp1 knockout inhibited PDGF-BB-stimulated SMC outgrowth ex vivo in aortic ring assays and reduced pathological arterial neointima formation in vivo. In contrast, we observed little significant effect of SMC-specific Nrp1 knockout on neonatal retinal vascularization. Our results point to a requirement of Nrp1 in vascular smooth muscle and myofibroblast function in vivo, which may have relevance for postnatal lung development and for pathologies characterized by excessive SMC and/or myofibroblast proliferation

A New Catalog of HII Regions in M31

We present a new catalog of HII regions in M31. The full disk of the galaxy is covered in a 2.2 deg^2 mosaic of 10 fields observed with the Mosaic Camera as part of the Local Group Galaxies survey. We used HIIphot, a code for automated photometry of HII regions, to identify the regions and measure their fluxes and sizes. A 10 {\sigma} detection level was used to exclude diffuse gas fluctuations and star residuals after continuum subtraction. That selection limit may result in missing some faint HII regions, but our catalog of 3691 HII regions is still complete to a luminosity of LH{\alpha} = 10^34 erg/s. This is five times fainter than the only previous CCD-based study which contained 967 objects in the NE half of M31. We determined the H{\alpha} luminosity function (LF) by fitting a power law to luminosities larger than LH{\alpha} = 10^36.7 and determined a slope of 2.52\pm0.07. The in-arm and inter-arm LFs peak at different luminosities but they have similar bright-end slopes. The inter- arm regions are less populated (40% of total detected regions) and constitute only 14% of the total luminosity of LH{\alpha} = 5.6 /times 10^40 erg/s (after extinction correction and considering 65% contribution from diffused ionized gas). A star formation rate of 0.44 M\odot/yr was estimated from the H{\alpha} total luminosity; this value is consistent with the determination from the Spitzer 8 {\mu}m image. We removed all known and potential planetary nebulae, yet we found a double peaked luminosity function. The inter-arm older population suggests a starburst between 15 and 20 million years ago. This result is in agreement with UV studies of the star formation history in M31 which found a star formation rate decrease in the recent past. We found a fair spatial correlation between the HII regions and stellar clusters in selected star forming regions. Most of the matched regions lie within the arm regions.Comment: accepted to be published at A

Luminous AGB stars in nearby galaxies. A study using Virtual Observatory tools

Aims. This study focuses on very luminous Mbol<-6.0 mag AGB stars with J-Ks>1.5 mag and H-Ks>0.4 mag in the LMC, SMC, M31, and M33 from 2MASS data. Methods.The data were taken from the 2MASS All-Sky Point Source catalogue archive. We used Virtual Observatory tools and took advantage of its capabilities at various stages in the analysis. Results. It is well known that stars with the colors we selected correspond mainly to carbon stars. Although the most luminous AGBs detected here contain a large number of carbon stars,they are not included in existing catalogues produced from data in the optical domain, where they are not visible since they are dust-enshrouded. A comparison of the AGB stars detected with combined near and mid-infrared data from MSX and 2MASS in the LMC shows that 10% of the bright AGB stars are bright carbon stars never detected before and that the other 50% are OH/IR oxygen rich stars, whereas the 40% that remain were not cross-matched. Conclusions. The catalogues of the most luminous AGB stars compiled here are an important complement to existing data. In the LMC, these bright AGB stars are centrally located, whereas they are concentrated in an active star-formation ring in M31. In the SMC and M33, there are not enough of them to draw definite conclusions, although they tend to be centrally located. Their luminosity functions are similar for the four galaxies we studied.Comment: 16 pages, 12 figures, 4 tables (Appendix A), accepted in A&

Efficacy of secukinumab and adalimumab in psoriatic arthritis patients with concomitant moderate to severe plaque psoriasis: results from the EXCEED, a randomised, double‐blind head‐to‐head monotherapy study

Background: Secukinumab [an interleukin (IL)‐17A inhibitor] has demonstrated significantly higher efficacy vs. etanercept (a tumour necrosis factor inhibitor) and ustekinumab (an IL‐12/23 inhibitor) in patients with moderate‐to‐severe plaque psoriasis. Objectives: To report 52‐week results from a prespecified analysis of patients with active psoriatic arthritis (PsA) having concomitant moderate‐to‐severe plaque psoriasis from the head‐to‐head EXCEED monotherapy study comparing secukinumab with adalimumab. Methods: Patients were randomized to receive secukinumab 300 mg via subcutaneous injection at baseline, week 1–4, and then every 4 weeks until week 48 or adalimumab 40 mg via subcutaneous injection every 2 weeks from baseline until week 50. Assessments in patients with concomitant moderate‐to‐severe psoriasis, defined as having affected body surface area &gt; 10% or Psoriasis Area and Severity Index (PASI) ≥ 10 at baseline, included musculoskeletal, skin and quality‐of‐life outcomes. Missing data were handled using multiple imputation. Results: Of the 853 patients [secukinumab (N = 426), adalimumab (N = 427)], 211 (24·7%) had concomitant moderate‐to‐severe psoriasis [secukinumab (N = 110, 25·8%), adalimumab (N = 101, 23·7%)]. Up to week 50, 5·5% of patients discontinued secukinumab vs.17·8% in the adalimumab group. The proportion of patients who achieved American College of Rheumatology (ACR) 20 response was 76·4% with secukinumab vs. 68·3% with adalimumab (P = 0·175), PASI 100 response was 39·1% vs. 23·8% (P = 0·013), and simultaneous improvement in ACR 50 and PASI 100 response at week 52 was 28·2% vs. 17·7%, respectively (P = 0·06). Secukinumab demonstrated consistently higher responses vs. adalimumab across skin endpoints. Conclusions: This prespecified analysis in PsA patients with concomitant moderate‐to‐severe plaque psoriasis in the EXCEED study provides further evidence that IL‐17 inhibitors offer a comprehensive biological treatment to manage the concomitant features of psoriasis and PsA