Validation of a mobile app for reducing errors of administration of medications in an emergency.

Medication errors occur frequently and are a risk to patient safety. To reduce mistakes in the medication process in emergencies, a mobile app has been developed supporting the calculation of doses and administration of drugs. A simulation study was performed to validate the app as a tool to reduce medication errors. This was a randomised crossover study conducted in the Academic Hospital. The participants included were residents and attendings in anaesthesiology. 74 Participants performed four simulation scenarios in which they had to calculate and administer drugs for emergencies. Two scenarios were performed with the app ("app scenarios") and the other two scenarios were performed without the use of the app ("control scenarios"). The order of drugs, simulation patients and usage of aid were randomized. The accuracy of administered drug doses were measured. Medications were categorised as either "accurate" ([Formula: see text]% of target dosage) or "wrong" (less than 50% or more than 200% of target dosage). The dosage calculated and the dosage administered were documented separately to differentiate between calculation and handling errors. During app scenarios, there were no "wrong" dosages, whereas 6.8 (95% CI 2.7-10.8%) of dosages in control scenarios were evaluated as "wrong". The probability of giving an "accurate" dosage was increased from 77.7 (70.9-84.5%) in control scenarios to 93.9 (90-97.8%) in app scenarios. Calculation errors were the main cause for wrong dosing. The app is an appropriate and feasible tool to reduce calculation and handling errors and may increase patient safety.

Detection of delayed cerebral ischemia (DCI) in subarachnoid haemorrhage applying near-infrared spectroscopy: elimination of the extracerebral signal by transcutaneous and intraparenchymatous measurements in parallel.

BACKGROUND: Detection of delayed cerebral ischemia (DCI) in high-grade subarachnoid haemorrhage (SAH) is an unsolved issue. Conventional near-infrared spectroscopy (NIRS) with optodes applied over the skin is controversial because the NIRS signal is contaminated by extracerebral tissue. The objective is to quantify and subtract the contribution from extracerebral tissue from the signal by using measurements in parallel with a NIRS brain tissue probe and conventional NIRS. METHODS: In a patient with high-grade SAH, two approaches for NIRS were applied. First, a conventional brain tissue probe for intracranial pressure (ICP) monitoring, supplied by optical fibres, was placed into the brain tissue 2 cm deep from the dura. Second, for conventional NIRS, a plaster-based patch carrying optodes (one emitter, two detectors) was attached to the skin. Central venous injections of 0.3 mg/kg body weight (bw) indocyanine green (ICG) were performed. ICG dye dilution curves obtained with the probe and patch were collected simultaneously and analysed for blood flow values. RESULTS: Twelve measurements in parallel with the probe and patch were performed. Mean cerebral blood flow (CBF) for the probe was higher (24.8 ± 9.1 ml/100 g/min) compared with the values obtained with the patch (for detector 1, extra-cerebral blood flow [ECBF] mean 5.1 ± 1.8 ml/100 g/min; p = 0.002; for detector 2, 6.6 ± 2.1 ml/100 g/min; p = 0.002). CBF values obtained with the probe correlated with blood flow values obtained with the patch (for CBF vs. ECBF detector 1, r = 0.72 [p = 0.008]; ECBF detector 2, r = 0.79 [p = 0.002]). CONCLUSIONS: Blood flow values obtained with conventional NIRS correlated significantly with absolute CBF values obtained directly within the brain tissue. Simultaneous measurements with the NeMo Probe and NeMo Patch allow quantification and subtraction of the contribution from extracerebral tissues from the signal obtained with conventional NIRS.

Association between cumulative surgeon experience and long-term outcomes in complex abdominal wall reconstruction.

PURPOSE: While many factors have been correlated with lesser outcomes in abdominal wall reconstruction (AWR), the impact of surgeon experience has yet to be elucidated. We sought to evaluate the effect of cumulative surgeon experience on long-term complex AWR outcomes. METHODS: We conducted a comprehensive review of all consecutive patients who underwent AWR using biologic mesh for the repair of ventral hernias or tumor resection defects from March 2005 to June 2019. The primary outcome measure was hernia recurrence (HR). Secondary outcomes were surgical site occurrences (SSOs) and surgical site infections (SSIs). Patients were a priori categorized into the following groups according to the cumulative number of hernia repairs performed by their surgeons: low (< 50), moderate experience (50-100), and high (> 100) experience. RESULTS: We identified 60 surgeons and 650 consecutive patients (62% women) who met our inclusion criteria. In adjusted models, AWR performed by surgeons with high experience was associated with a fourfold lower risk of HR (hazard ratio, 0.28; 95% confidence interval, 0.08 to 0.87), but the odds of surgical site occurrences (odds ratio, 0.72, 95% confidence interval, 0.34 to 1.52) and surgical site infections (odds ratio, 0.89, 95% confidence interval, 0.26 to 2.86) did not differ significantly in the high-experience group. CONCLUSIONS: High surgical experience, defined as > 100 cumulative hernia repairs, is predictive for markedly lower HR rates in complex AWR. These findings have potential implications for preoperative risk assessment, patient-centered surgeon selection, regulatory oversight, specific referral patterns, designations of centers of excellence, and individual provider or trainee quality improvement.

Substantia nigra echomorphology and motor cortex excitability.

The aim of our study was to investigate the relation between substantia nigra (SN) echomorphology and indices of motor cortex excitability. Nigral hyperechogenicity in healthy individuals is thought to represent an SN abnormality or predisposition to Parkinson's disease (PD) and its prevalence is greater in the very old. Our study involved 20 old healthy subjects (aged 72-84 years) known to have normal (n=10) or abnormal (n=10) SN echomorphology. All were in good health with no overt neurological signs. SN morphology was assessed with transcranial sonography through the pre-auricular bone window. Motor cortical excitability and intracortical inhibition were assessed with transcranial magnetic stimulation (TMS) over the first dorsal interosseus motor area. Single stimuli were delivered during relaxation and voluntary contraction and paired stimuli were delivered during relaxation. Each cortical hemisphere was analysed separately. The response to single-pulse TMS (in motor cortex ipsilateral to the target SN) did not differ between groups. However, a significant difference between groups was observed in the paired pulse paradigm (conditioning stimulus intensity: 70% resting motor threshold; interstimulus interval: 2 ms). The conditioned motor evoked potential amplitude was significantly larger ipsilateral to the hyperechogenic SN than in controls (P=0.014). Thus, healthy subjects with SN hyperechogenicity exhibit significantly less intracortical inhibition within the motor cortex than subjects with normal echomorphology. Decreased intracortical inhibition is also observed in PD patients. This study provides further evidence that SN hyperechogenicity in healthy individuals is associated with changes characteristic of PD supporting a role for this feature as a vulnerability marker or state marker for subtle nigral dopaminergic dysfunction.

Dissolution in nasal fluid, retention and anti-inflammatory activity of fluticasone furoate in human nasal tissue ex vivo.

BACKGROUND: Intranasal glucocorticoids represent the most effective pharmacologic treatment of allergic rhinitis. So far, no clinical data are available that compare fluticasone furoate (FF) with other intranasally applied glucocorticoids. OBJECTIVE: Because the pharmacokinetic behaviour of drugs governs their presence at the therapeutic target site we analysed selected in vitro properties of FF in comparison with triamcinolone acetonide (TCA), budesonide (Bud), fluticasone propionate (FP) and mometasone furoate (MF). Additionally, we determined the anti-inflammatory activity of the glucocorticoid fraction residing in human nasal tissue samples after washing. METHODS: We analysed the solubility of the compounds in artificial human nasal fluid and the retention in human nasal tissue as well as typical spray volumes of commercially available drug preparations. As an anti-inflammatory measure, we evaluated the inhibition of IL-8 release from epithelial cells. RESULTS: FF is delivered in the smallest application volume per spray. Despite the low aqueous solubility of glucocorticoids, a fraction of the compounds is already dissolved in the aqueous supernatants of drug preparations (Bud>TCA>FP>MF>FF). The dissolution of FP, MF and FF was significantly enhanced in artificial nasal fluid and FF displayed the most pronounced enhancement of solubility in the presence of proteins. Consistent with this result, the highest retention in nasal tissue was observed for FF, followed by FP>MF>Bud>TCA. After washing of the nasal tissue samples, all compounds inhibited IL-8 release, with FF displaying the highest activity. CONCLUSION: FF displayed beneficial properties for nasal application. Its low application volume per spray is a prerequisite for effective drug utilization by avoiding immediate loss by nose runoff or drip down the throat. Sustained dissolution and high tissue binding of FF should contribute towards an extended presence of compounds in nasal tissue as a basis for a prolonged pharmacologic activity.

A modular implementation of dispersive materials for time-domain simulations with application to gold nanospheres at optical frequencies.

The development of photonic nano-structures can strongly benefit from full-field electromagnetic (EM) simulations. To this end, geometrical flexibility and accurate material modelling are crucial requirements set on the simulation method. This paper introduces a modular implementation of dispersive materials for time-domain EM simulations with focus on the Finite-Volume Time-Domain (FVTD) method. The proposed treatment can handle electric and magnetic dispersive materials exhibiting multi-pole Debye, Lorentz and Drude models, which can be mixed and combined without restrictions. The presented technique is verified in several illustrative examples, where the backscattering from dispersive spheres is calculated. The amount of flexibility and freedom gained from the proposed implementation will be demonstrated in the challenging simulation of the plasmonic resonance behavior of two gold nanospheres coupled in close proximity, where the dispersive characteristic of gold is approximated by realistic values in the optical frequency range.

Investigation of the exclusive 3He(e,e' pn)1H reaction.

Cross sections for the 3He(e,e' pn)1H reaction were measured for the first time at energy transfers of 220 and 270 MeV for several momentum transfers ranging from 300 to 450 MeV/c. Cross sections are presented as a function of the momentum of the recoil proton and the momentum transfer. Continuum Faddeev calculations using the Argonne V18 and Bonn-B nucleon-nucleon potentials overestimate the measured cross sections by a factor 5 at low recoil proton momentum with the discrepancy becoming smaller at higher recoil proton momentum.

A central role for the armadillo protein plakoglobin in the autoimmune disease pemphigus vulgaris.

In pemphigus vulgaris (PV), autoantibody binding to desmoglein (Dsg) 3 induces loss of intercellular adhesion in skin and mucous membranes. Two hypotheses are currently favored to explain the underlying molecular mechanisms: (a) disruption of adhesion through steric hindrance, and (b) interference of desmosomal cadherin-bound antibody with intracellular events, which we speculated to involve plakoglobin. To investigate the second hypothesis we established keratinocyte cultures from plakoglobin knockout (PG-/-) embryos and PG+/+ control mice. Although both cell types exhibited desmosomal cadherin-mediated adhesion during calcium-induced differentiation and bound PV immunoglobin (IgG) at their cell surface, only PG+/+ keratinocytes responded with keratin retraction and loss of adhesion. When full-length plakoglobin was reintroduced into PG-/- cells, responsiveness to PV IgG was restored. Moreover, in these cells like in PG+/+ keratinocytes, PV IgG binding severely affected the linear distribution of plakoglobin at the plasma membrane. Taken together, the establishment of an in vitro model using PG+/+ and PG-/- keratinocytes allowed us (a) to exclude the steric hindrance only hypothesis, and (b) to demonstrate for the first time that plakoglobin plays a central role in PV, a finding that will provide a novel direction for investigations of the molecular mechanisms leading to PV, and on the function of plakoglobin in differentiating keratinocytes.

A predicted operon map for Mycobacterium tuberculosis.

The prediction of operons in Mycobacterium tuberculosis (MTB) is a first step toward understanding the regulatory network of this pathogen. Here we apply a statistical model using logistic regression to predict operons in MTB. As predictors, our model incorporates intergenic distance and the correlation of gene expression calculated for adjacent gene pairs from over 474 microarray experiments with MTB RNA. We validate our findings with known examples from the literature and experimentation. From this model, we rank each potential operon pair by the strength of evidence for cotranscription, choose a classification threshold with a true positive rate of over 90% at a false positive rate of 9.1%, and use it to construct an operon map for the MTB genome.

An ultra-high vacuum scanning tunneling microscope operating at sub-Kelvin temperatures and high magnetic fields for spin-resolved measurements.

We present the construction and performance of an ultra-low-temperature scanning tunneling microscope (STM), working in ultra-high vacuum (UHV) conditions and in high magnetic fields up to 9 T. The cryogenic environment of the STM is generated by a single-shot 3He magnet cryostat in combination with a 4He dewar system. At a base temperature (300 mK), the cryostat has an operation time of approximately 80 h. The special design of the microscope allows the transfer of the STM head from the cryostat to a UHV chamber system, where samples and STM tips can be easily exchanged. The UHV chambers are equipped with specific surface science treatment tools for the functionalization of samples and tips, including high-temperature treatments and thin film deposition. This, in particular, enables spin-resolved tunneling measurements. We present test measurements using well-known samples and tips based on superconductors and metallic materials such as LiFeAs, Nb, Fe, and W. The measurements demonstrate the outstanding performance of the STM with high spatial and energy resolution as well as the spin-resolved capability.

LabDisk with complete reagent prestorage for sample-to-answer nucleic acid based detection of respiratory pathogens verified with influenza A H3N2 virus.

Portable point-of-care devices for pathogen detection require easy, minimal and user-friendly handling steps and need to have the same diagnostic performance compared to centralized laboratories. In this work we present a fully automated sample-to-answer detection of influenza A H3N2 virus in a centrifugal LabDisk with complete prestorage of reagents. Thus, the initial supply of the sample remains the only manual handling step. The self-contained LabDisk automates by centrifugal microfluidics all necessary process chains for PCR-based pathogen detection: pathogen lysis, magnetic bead based nucleic acid extraction, aliquoting of the eluate into 8 reaction cavities, and real-time reverse transcription polymerase chain reaction (RT-PCR). Prestored reagents comprise air dried specific primers and fluorescence probes, lyophilized RT-PCR mastermix and stick-packaged liquid reagents for nucleic acid extraction. Employing two different release frequencies for the stick-packaged liquid reagents enables on-demand release of highly wetting extraction buffers, such as sequential release of lysis and binding buffer. Microfluidic process-flow was successful in 54 out of 55 tested LabDisks. We demonstrate successful detection of the respiratory pathogen influenza A H3N2 virus in a total of 18 LabDisks with sample concentrations down to 2.39 × 10(4) viral RNA copies per ml, which is in the range of clinical relevance. Furthermore, we detected RNA bacteriophage MS2 acting as internal control in 3 LabDisks with a sample concentration down to 75 plaque forming units (pfu) per ml. All experiments were applied in a 2 kg portable, laptop controlled point-of-care device. The turnaround time of the complete analysis from sample-to-answer was less than 3.5 hours.

Two distinct superconducting phases in LiFeAs.

A non-trivial temperature evolution of superconductivity including a temperature-induced phase transition between two superconducting phases or even a time-reversal symmetry breaking order parameter is in principle expected in multiband superconductors such as iron-pnictides. Here we present scanning tunnelling spectroscopy data of LiFeAs which reveal two distinct superconducting phases: at = 18 K a partial superconducting gap opens, evidenced by subtle, yet clear features in the tunnelling spectra, i.e. particle-hole symmetric coherence peak and dip-hump structures. At Tc = 16 K, these features substantiate dramatically and become characteristic of full superconductivity. Remarkably, the distance between the dip-hump structures and the coherence peaks remains practically constant in the whole temperature regimeT ≤ . This rules out the connection of the dip-hump structures to an antiferromagnetic spin resonance.

Does crossing the legs decrease arterial pressure in diabetic patients with peripheral vascular disease?

OBJECTIVE: To evaluate the effect of crossing the legs at the knee and the ankle on peripheral arterial pressures. RESEARCH DESIGN AND METHODS: A prospective study of 6 diabetic patients with known peripheral vascular disease and 5 nondiabetic control subjects without peripheral vascular disease was conducted. Peripheral arterial pressures were taken at the ankle and at the great toe before and after crossing the legs at the knees and ankles. Comparisons were made of measurements obtained in the supine and sitting positions. All crossed leg measurements were taken in the sitting position. RESULTS: Ankle arm indexes and digital arm indexes pressures taken in the sitting position were equal to or higher than supine pressures, with the exception of one subject, GB. In this patient, ankle arm indexes and digital arm indexes on the right extremity were lower in the sitting position, but increased with the legs crossed at the knees and ankles compared with the uncrossed sitting position. In all patients, lower extremity pressures that decreased slightly with crossing the legs remained higher than pressures obtained in the supine position. Statistical analyses showed no significant differences. Wave forms did not change even when there was a slight decrease in ankle arm indexes or digital arm indexes. Control subjects without peripheral vascular disease showed no change in pressures with crossing the legs. CONCLUSIONS: Crossing the legs at the knees and ankles does not result in a significant decrease in peripheral arterial pressures in diabetic patients with peripheral vascular disease.

Focal lesions in the rat central nervous system induced by endothelin-1.

Axon injury following cerebral ischemia has received little scientific attention compared to the abundance of information dealing with the pathophysiology of grey matter ischemia. There are differences in the initial response of grey and white matter to ischemia in vitro. In this study we investigate whether the vasoactive peptide, endothelin-1, can generate a focal ischemic lesion in the white matter and compare the findings with endothelin-1-induced lesions in the grey matter. Using a minimally invasive technique to microinject endothelin-1 into selected brain regions, we observed an acute reduction in local MRI perfusion in the injected hemisphere after 1 hour. Twenty-four hours after microinjection of 10 pmoles of endothelin-1, we observed a loss of neurons in the grey matter. At 72 hours, neutrophils were absent and a macrophage/microglia response and astrocyte gliosis were detected. No breakdown in the blood-brain barrier was detected. After injection of 10 pmoles endothelin-1 into the cortical white matter, we observed prolific amyloid precursor protein-positive immunostaining (indicative of axonal disruption) and an increase in tau-1 immunostaining in oligodendrocytes at 6 hours. Similar to the grey matter lesions, no neutrophils were present, a macrophage/microglia response did not occur until 72 hours and there was no disruption in the blood-brain barrier. Focal injections of endothelin-1 into specific areas of the rat CNS represent a model to investigate therapeutic approaches to white matter ischemia.

A canine model of paired graft thrombosis.

A novel canine model for reliably producing graft thrombosis is described. Two unilateral aortoiliac bypasses are performed while preserving the integrity of the native vascular tree. These grafts are briefly mechanically occluded at the time of the initial operation, and they remain occluded postoperatively because flow is preferentially directed through the larger-caliber, thrombo-resistant native circulation. Percutaneous temporary intra-arterial balloon occlusion of the native vessels redirects flow into the occluded graft segments, which can be used in experimental protocols. This new model for studying graft thrombosis requires only a single, simple operative procedure, and easily allows secondary percutaneous graft manipulation.

First determination of generalized polarizabilities of the proton by a virtual compton scattering experiment

Absolute differential cross sections for the reaction ep-->epgamma have been measured at a four-momentum transfer with virtuality Q2 = 0.33 GeV2 and polarization epsilon = 0.62 in the range 33.6 to 111.5 MeV/c for the momentum of the outgoing photon in the photon-proton center of mass frame. The experiment has been performed with the high-resolution spectrometers at the Mainz Microtron MAMI. From the photon angular distributions, two structure functions which are a linear combination of the generalized polarizabilities have been determined for the first time.

Parathyroid autotransplantation.

It has been clearly shown clinically that parathyroid tissue can be successfully autotransplanted and even allotransplanted if the host is immunosuppressed. Engraftment is almost always successful; however, if abnormal tissue has been transplanted, its function will continue to be abnormal if the same intrinsic (e.g., primary parathyroid hyperplasia) or extrinsic (renal osteodystrophy) stimulation existing before grafting continues in the postoperative period. In these patients the secretion of parathyroid hormone from the grafted parathyroid tissue can be shown to progressively increase with time. Although parathyroid autotransplantation is most frequently performed clinically for renal osteodystrophy, there is controversy about the operation, and some surgeons prefer the technique of 3 1/2 gland parathyroidectomy. Because of the generally good results with total parathyroidectomy and autotransplantation in patients with primary parathyroid hyperplasia, this procedure seems to be the operation of choice in this clinical setting. The clearest indication for parathyroid autotransplantation is in patients with radical operations on the thyroid gland or other head and neck organs where the parathyroids have been damaged or their viability is questioned.