Ergonomics in the anaesthetic workplace: Guideline from the Association of Anaesthetists.

Ergonomics in relation to anaesthesia is the scientific study of the interaction between anaesthetists and their workspace environment in order to promote safety, performance and well-being. The foundation for avoiding pain or discomfort at work is to adopt and maintain a good posture, whether sitting or standing. Anaesthetists should aim to keep their posture as natural and neutral as possible. The successful practice of anaesthesia relies on optimisation of ergonomics and lack of attention to detail in this area is associated with impaired performance. The anaesthetic team should wear comfortable clothing, including appropriately-sized personal protective equipment where necessary. Temperature, humidity and light should be adequate at all times. The team should comply with infection prevention and control guidelines and monitoring as recommended by the Association of Anaesthetists. Any equipment or machinery that is mobile should be positioned where it is easy to view or reach without having to change the body or head position significantly when interacting with it. Patients who are supine should, whenever possible, be raised upwards to limit the need to lean towards them. Any item required during a procedure should be positioned on trays or trolleys that are close to the dominant hand. Pregnancy affects the requirements for standing, manually handling, applying force when operating equipment or moving machines and the period over which the individual might have to work without a break. Employers have a duty to make reasonable adjustments to accommodate disability in the workplace. Any member of staff with a physical impairment needs to be accommodated and this includes making provision for a wheelchair user who needs to enter the operating theatre and perform their work.

An evaluation of a new practice-based small group learning (PBSGL) initiative in Wales.

In 2018, a new practice-based small group learning (PBSGL) pilot initiative was launched in Wales to promote interprofessional learning among different primary care professionals. The aim of this study was to evaluate the initiative in order to identify its strengths and areas for improvement. Data were collected through focus groups with PBSGL groups in Wales and analysed thematically. Participants generally held positive views of PBSGL and were impressed with the variety and overall relevance of the learning materials, although concern was raised about the relevance of all learning materials to the Welsh context. The interprofessional component was valued for reducing feelings of isolation and all participants were able to contribute to discussions, an outcome helped by existing relationships among group members. Many participants reflected on occasions where they had made changes to their practice as a result of PBSGL activity. Time and funding were cited as potential barriers to continuing participation in PBSGL and there is scope to tailor material more to the context of the healthcare system in Wales.

Introducing a novel respiratory function monitor for neonatal resuscitation training.

Background: A respiratory function monitor (RFM) gives immediate feedback, allowing clinicians to adjust face mask ventilation to correct leak or inappropriate tidal volumes. We audited the satisfaction of clinicians with a neonatal resuscitation training package, incorporating a novel RFM. Methods: This was a mixed-methods study conducted at The Royal Women's Hospital, Melbourne, Australia. Clinicians were approached to complete a neonatal resuscitation training session. Participants watched a training video, then provided ventilation to term and preterm manikins first without, and then with, the RFM. Clinicians completed a survey after the session and undertook a follow-up session three months later. The primary outcome was participant satisfaction with the RFM. Secondary outcomes included participants' self-assessment of face mask leak and tidal volumes when using the RFM. Results: Fifty clinicians completed both the initial and follow-up session. Participants reported high levels of satisfaction with the RFM for both term and preterm manikins: on a scale from 0, meaning "not at all", and 100, meaning "yes, for all resuscitations", the median response (interquartile range, IQR) was 82 (74-94) vs 81.5 (69-94.5). Levels of satisfaction were similar for less experienced and more experienced clinicians: median (IQR) 83 (77-93) vs 81 (71.5-95) respectively. When using the monitor, clinicians accurately self-assessed that they achieved leak below 30% and tidal volumes within the target range at least 80% of the time. Conclusion: Clinicians of all experience levels had a high level of satisfaction with a training package including a novel RFM.

LIII-Edge Anomalous X-ray Scattering by Cesium Measured with Synchrotron Radiation.

Diffraction of monochromatized synchrotron radiation by crystals of cesium hydrogen tartrate has been used to measure the magnitude and phase of x-ray scattering for cesium near the LIII absorption edge. In this wavelength region the scattering amplitude of cesium is reduced by as much as 25 electrons per atom, compared to scattering of copper Kalpha x-rays. This change, which varies as a function of wavelength, affects the diffraction intensities in a manner similar to isomorphous substitution, and it is large enough to have promise for phase determination in the study of macromolecular structures. This experiment also demonstrates that accurate diffractometer measurements are possible with synchrotron radiation produced by an electron storage ring.

Catalytic galactose oxidase models: biomimetic Cu(II)-phenoxyl-radical reactivity.

Biomimetic functional models of the mononuclear copper enzyme galactose oxidase are presented that catalytically oxidize benzylic and allylic alcohols to aldehydes with O2 under mild conditions. The mechanistic fidelity between the models and the natural system is pronounced. Modest structural mimicry proves sufficient to transfer an unusual ligand-based radical mechanism, previously unprecedented outside the protein matrix, to a simple chemical system.

In Situ X-ray Absorption Study of Surface Complexes: Selenium Oxyanions on agr-FeOOH.

A novel application of x-ray absorption spectroscopy has provided structural information for ions sorbed at oxide-water interfaces. As an example, in situ extended x-ray absorption fine structure (EXAFS) measurements of adsorbed selenate and selenite ions at ah alpha-FeOOH(goethite)-water interface have been performed; these measurements show that selenate forms a weakly bonded, outer-sphere complex and that selenite forms a strongly bonded, inner-sphere complex. The selenite ion is bonded directly to the goethite surface in a bidentate fashion with two iron atoms 3.38 angstroms from the selenium atom. Adsorbed selenate has no iron atom in the second coordination shell of selenium, which indicates retention of its hydration sphere upon sorption. This method provides direct structural information for adsorbed species at solid-liquid interfaces.

Phase determination by multiple-wavelength x-ray diffraction: crystal structure of a basic "blue" copper protein from cucumbers.

A novel x-ray diffraction technique, multiple-wavelength anomalous dispersion (MAD) phasing, has been applied to the de novo determination of an unknown protein structure, that of the "blue" copper protein isolated from cucumber seedlings. This method makes use of crystallographic phases determined from measurements made at several wavelengths and has recently been made technically feasible through the use of intense, polychromatic synchrotron radiation together with accurate data collection from multiwire electronic area detectors. In contrast with all of the conventional methods of solving protein structures, which require either multiple isomorphous derivatives or coordinates of a similar structure for molecular replacement, this technique allows direct solution of the classical "phase problem" in x-ray crystallography. MAD phase assignment should be particularly useful for determining structures of small to medium-sized metalloproteins for which isomorphous derivatives are difficult or impossible to make. The structure of this particular protein provides new insights into the spectroscopic and redox properties of blue copper proteins, an important class of metalloproteins widely distributed in nature.

Enhanced anxiety-like behavior emerges with weight gain in male and female obesity-susceptible rats.

Epidemiological data suggest that body mass index and obesity are strong risk factors for depression and anxiety. However, it is difficult to separate cause from effect, as predisposition to obesity may enhance susceptibility to anxiety, or vice versa. Here, we examined the effect of diet and obesity on anxiety-like behaviors in male and female selectively bred obesity-prone and obesity-resistant rats, and outbred Sprague-Dawley rats. We found that when obesity-prone and obesity-resistant rats do not differ in weight or fat mass, measures of anxiety-like behavior in the elevated plus maze and open field are similar between the two groups. However, once weight and fat mass diverge, group differences emerge, with greater anxiety in obesity-prone relative to obesity-resistant rats. This same pattern was observed for males and females. Interestingly, even when obesity-resistant rats were "forced" to gain fat mass comparable to obesity-prone rats (via prolonged access to 60% high-fat diet), anxiety-like behaviors did not differ from lean chow fed controls. In addition, a positive correlation between anxiety-like behaviors and adiposity were observed in male but not in female obesity-prone rats. Finally, diet-induced weight gain in and of itself was not sufficient to increase measures of anxiety in outbred male rats. Together, these data suggest that interactions between susceptibility to obesity and physiological alterations accompanying weight gain may contribute to the development of enhanced anxiety.

Vertebral fractures assessment in children: Evaluation of DXA imaging versus conventional spine radiography.

Vertebral fracture assessment (VFA) by DXA is an accepted tool in adults. However, its use in children has not been assessed. The aim of this study was to evaluate DXA VFA and morphometric analysis (MXA) using a GE Lunar iDXA bone densitometer against spinal radiographic assessment (RA) for the identification of vertebral fractures in children. Spine RA and VFA (T3-L5) were acquired on the same day in 80 children. Forty children considered high risk for fracture by their metabolic bone specialist were referred for spinal RA. Another 40 children were recruited as part of a prospective fracture study and were considered low risk for vertebral fracture. Agreement between RA and VFA was assessed by an expert paediatric radiologist and two paediatricians with expertise in bone pathology. Agreement between RA and MXA was assessed by an expert paediatric radiologist, two clinical scientists and an experienced paediatric radiographer. Vertebrae were ranked as normal, mild, moderate or severe if they had <10%, 11-25%, 26-50% and >50% deformity, respectively. Levels of agreement were calculated using the Cohen kappa score. Evaluating the data from all readable vertebrae, 121 mild, 44 moderate and 16 severe vertebral fractures were identified; with 26, 8, and 5 subjects having at least one mild, moderate or severe fracture, respectively. Depending on rater, 92.8-94.8% of the vertebrae were evaluable by RA. In contrast, 98.4% were evaluable by VFA and only 83.6% were evaluable by MXA. Moderate agreement was found between raters for RA [kappa 0.526-0.592], and VFA [kappa 0.601-0.658] and between RA and VFA [kappa 0.630-0.687]. In contrast, only slight agreement was noted between raters for MXA [kappa 0.361-0.406] and between VFA and MXA [kappa 0.137-0.325]. Agreement substantially improved if the deformities were dichotomised as normal or mild versus moderate or severe [kappa 0.826-0.834]. For the detection of moderate and/or severe fractures the sensitivities & specificities were 81.3% & 99.3%, and 62.5% & 99.2% for VFA and MXA, respectively. This study demonstrates that VFA is as good as RA for detecting moderate and severe vertebral fractures. Given the significant radiation dose saving of VFA compared with RA, VFA is recommended as a diagnostic tool for the assessment of moderate or severe vertebral fracture in children.

Genome-wide significant loci for addiction and anxiety.

BACKGROUND: Psychiatric comorbidity is common among individuals with addictive disorders, with patients frequently suffering from anxiety disorders. While the genetic architecture of comorbid addictive and anxiety disorders remains unclear, elucidating the genes involved could provide important insights into the underlying etiology. METHODS: Here we examine a sample of 1284 Mexican-Americans from randomly selected extended pedigrees. Variance decomposition methods were used to examine the role of genetics in addiction phenotypes (lifetime history of alcohol dependence, drug dependence or chronic smoking) and various forms of clinically relevant anxiety. Genome-wide univariate and bivariate linkage scans were conducted to localize the chromosomal regions influencing these traits. RESULTS: Addiction phenotypes and anxiety were shown to be heritable and univariate genome-wide linkage scans revealed significant quantitative trait loci for drug dependence (14q13.2-q21.2, LOD=3.322) and a broad anxiety phenotype (12q24.32-q24.33, LOD=2.918). Significant positive genetic correlations were observed between anxiety and each of the addiction subtypes (ρg=0.550-0.655) and further investigation with bivariate linkage analyses identified significant pleiotropic signals for alcohol dependence-anxiety (9q33.1-q33.2, LOD=3.054) and drug dependence-anxiety (18p11.23-p11.22, LOD=3.425). CONCLUSIONS: This study confirms the shared genetic underpinnings of addiction and anxiety and identifies genomic loci involved in the etiology of these comorbid disorders. The linkage signal for anxiety on 12q24 spans the location of TMEM132D, an emerging gene of interest from previous GWAS of anxiety traits, whilst the bivariate linkage signal identified for anxiety-alcohol on 9q33 peak coincides with a region where rare CNVs have been associated with psychiatric disorders. Other signals identified implicate novel regions of the genome in addiction genetics.

Blue form of bacteriorhodopsin and its order-disorder transition during dehydration.

Freshly-prepared blue membranes from Halobacterium halobium, previously reported to be disordered, are shown to have a distinct crystal lattice structure, slightly different from the native form. The lattice of the blue form is disrupted irreversibly when dehydrated. The disorder process was observed using time-resolved small-angle X-ray diffraction and analyzed by radial autocorrelation functions. The diffraction peaks of the in-plane lattice first sharpen and increase due to improved membrane orientation, then the trimer lattice becomes disordered and the unit cell dimension decreases by 1.8 A. In contrast, dehydration of purple membranes does not disorder the lattice, and the unit cell dimension shrinks by only 1.0 A. Comparisons of radial autocorrelation functions for the blue membrane during drying show drastic loss of inter-trimer, long-range correlation while the intra-trimer, short-range correlations remain more or less unchanged. This suggests that the deionized protein trimers can maintain their overall structure during the dehydration, even though the lattice dimension decreases appreciably and the two-dimensional crystallinity is disrupted.

A lysozyme folding intermediate revealed by solution X-ray scattering.

Equilibrium unfolding of hen egg lysozyme as a function of urea concentration at pH 2.9 has been studied by solution X-ray scattering. Differences in the unfolding transition are observed as monitored by the radius of gyration Rg, and by far and near UV CD (circular dichroism) at 222 nm and 298 nm, respectively. This suggests the existence of a third unfolding species, in addition to the native and the unfolded states. A singular value decomposition (SVD) analysis was made of the scattering curves at different urea concentrations. This analysis shows clear evidence of a third basis component in the X-ray scattering curves, thus supporting the results of the Rg and CD measurements. The denaturant binding model was employed to estimate the thermodynamic parameters of denaturation for the intermediate and unfolded states. Use of these parameters to refine the SVD analysis allows us to reconstruct a scattering profile for the pure intermediate state. Simplified partially folded models, based on the crystal structure of hen lysozyme, support a working model for the intermediate, whose structure may be correlated with that of the kinetic intermediate found in the refolding pathway studied by Dobson and coworkers.

Kinetics of lysozyme refolding: structural characterization of a non-specifically collapsed state using time-resolved X-ray scattering.

We report time-resolved small angle X-ray scattering (SAXS) studies of the structural characteristics of the collapsed state of lysozyme from henegg white (HEL) obtained on initiating refolding by rapidly changing solvent conditions from 8 M to 1.1 M urea at pH 2.9. At this reduced pH the lifetime, of about one second, of the non-specifically collapsed ensemble is considerably prolonged relative to its value at pH 5.2. The SAXS studies are combined with time resolved measurements of tryptophan fluorescence and of the rate of formation of native molecules using interrupted refolding experiments. We observe large burst phase changes in intrinsic tryptophan fluorescence and in the radius of gyration (Rg) which is reduced from 22 A in the fully unfolded state to approximately 19 to 20 A. Subsequent decrease of the Rg to the value for native lysozyme (15 A) follows the time course of formation of native molecules. Single exponential fits to the singular value decomposition (SVD) components of the SAXS data allow reconstruction of the SAXS profile at early time points of refolding. The results of this analysis suggest a globular shape of the collapsed state. A similar fit to the forward scattering amplitude, I(0), suggests that the collapsed state has a solvent accessible surface area which is considerably increased relative to that of the native protein. These results show directly that the non-specifically collapsed state formed during the burst phase in lysozyme refolding indeed represents a molecular compaction and a change in shape from a fully denatured random coil state (albeit restricted by disulfide bonds) to an ensemble of globular conformations which, however, have not yet formed a solvent-protected hydrophobic core.

Location of terbium binding sites on acetylcholine receptor-enriched membranes.

Acetylcholine receptor-enriched membranes bind 45 terbium cations per receptor. The Tb(III) X-ray scattering factor changes by as much as 30% over a 50 eV range about the L3 absorption edge. We exploit these changes to modulate the contribution of these ions to the X-ray diffraction pattern of oriented receptor-enriched membranes by varying the incident X-ray energy. Difference Fourier analysis of the meridional diffraction amplitudes at two X-ray energies revealed six localized regions of Tb(III) density across the membrane. Most significant is the finding of 18 Tb(III) ions near the entrance and 11 ions near the exit of the ion channel as well as 4 or 5 Tb(III) ions localized in the channel itself. This evidence strongly suggests the presence of anionic carboxylate side-chains on the channel lining.

Characterization of transient intermediates in lysozyme folding with time-resolved small-angle X-ray scattering.

We have used synchrotron radiation, together with stopped-flow and continuous-flow mixing techniques to monitor refolding of lysozyme at pH 5.2. From data measured at times which range from 14 ms to two seconds, we can monitor changes in the size, the shape and the pair distribution function of the polypeptide chain during the folding process. Comparison of the results with the properties of native and GdmCl-unfolded lysozyme shows that a major chain collapse occurs in the dead-time of mixing. During this process about 50 % of the change in radius of gyration between the unfolded protein and the native state occurs and the polypeptide chain adopts a globular shape. Time-resolved fluorescence spectra of this collapsed state suggest that the hydrophobic side-chains are still highly solvent accessible. A subsequently formed intermediate with helical structure in the alpha-domain is nearly identical in size and shape with native lysozyme and has a solvent-inaccessible hydrophobic core. Despite its native-like properties, this intermediate is only slightly more stable (DeltaG0=-4 kJ/mol) than the collapsed state and still much less stable than native lysozyme (DeltaDeltaG0=36 kJ/mol) at 20 degrees C.

High-resolution XANES studies on vanadium-containing haloperoxidase: pH-dependence and substrate binding.

High-resolution X-ray absorption vanadium K-edge spectra were recorded for samples of vanadium-containing bromoperoxidase from the brown alga, Ascophyllum nodosum, at pH 9, 7, 5 and 4, as well as for enzyme samples containing the substrates, hydrogen peroxide and bromide. The well-resolved features of the XANES spectra are discussed. The pH-dependence of the structure of the active site has been studied revealing no significant change of the absorption features. We were able to detect an interaction of H2O2 with the vanadium site of the bromoperoxidase using XAS spectroscopy, whereas addition of bromide causes no energy shift of the XANES spectrum. The possible role of vanadium during the enzymatic reaction is discussed on the basis of our results.

Internal carotid artery occlusion: operative risks and long-term stroke rates after contralateral carotid endarterectomy.

BACKGROUND: To determine the short- and long-term benefits of carotid endarterectomy (CEA) contralateral to an occluded internal carotid (ICA), we reviewed our experience since 1976. METHODS: In 66 (13.8%) of 478 patients undergoing 544 CEAs, the contralateral ICA was occluded. Mean follow-up was 50.1 months (range, 1 to 165 months). Complete follow-up was available in 83.0% of patients. RESULTS: Operative death occurred in one (1.5%) of 66 patients with contralateral occlusion and six (1.3%) of 478 patients without contralateral occlusion (p = 0.99). Operative strokes occurred in two (3.0%) of 66 patients with contralateral occlusion and 14 (2.9%) of 478 without contralateral occlusion (p = 0.99). Life-table stroke-free rates at 1, 3, 5, and 8 years were 96.8%, 93.0%, and 93.0% in patients with contralateral occlusion and 95.9%, 94.2%, 91.1%, and 88.0% in patients without contralateral occlusion (p = 0.36). Five- and 8-year stroke-free rates were 100% and 100% in the asymptomatic subgroup with occlusion, 95.9% and 92.2% in the asymptomatic subgroup without occlusion (p = 0.45), 91.2% and 91.2% in the symptomatic subgroup with occlusion, and 89.7% and 86.8% in the symptomatic subgroup without occlusion (p = 0.47). Life-table survival rates at 5 and 8 years were 72.5% and 56.0% in patients with contralateral occlusion and 81.8% and 69.0% in patients without contralateral occlusion (p = 0.15). CONCLUSIONS: CEA performed in patients with and without symptoms with a contralateral ICA occlusion produces short- and long-term mortality and stroke morbidity rates comparable to those of similar patients without contralateral ICA occlusion. The indications for CEA in patients with contralateral ICA occlusion should not differ from those applied to patients without contralateral occlusion.

Carotid endarterectomy without angiography: is color-flow duplex scanning sufficient?

BACKGROUND: This study was designed to determine whether clinical evaluation and color-flow duplex scanning (CFS) alone provide enough information for patients to undergo carotid endarterectomy (CEA) safely without preoperative cerebral angiography and to assess the appropriate role of CFS in the evaluation of extracranial carotid artery disease. METHODS: During a 31-month period 167 patients (114 symptomatic and 53 asymptomatic) underwent CFS and angiography during evaluation for CEA. One hundred fifty-three patients were studied retrospectively, and 14 were studied prospectively. Data were reviewed to determine whether cerebral angiography added information not provided by duplex findings and, if so, did the results alter clinical management. RESULTS: Of the 167 patients studied, 149 underwent CEA and 18 were treated medically. Results of the two diagnostic modalities agreed perfectly in 82% of the patients, with 99% of the stenoses estimated by CFS being classified within one category of those measured with angiography. The sensitivity of CFS for detecting greater than 50% diameter-reducing stenoses of the internal carotid artery was 98%, and the positive predictive value was 99%. For detecting greater than 80% stenoses, CFS had a sensitivity of 84% and a positive predictive value of 95%. Clinical management was altered by angiographic findings in only seven patients (4%). False-positive results (n = 5) were due to poor scanning technique or interpreter error (n = 2), anatomic variations (n = 2), and unknown cause (n = 1). All false-negative results (n = 2) were due to poor scanning technique. CONCLUSIONS: Ninety-six percent of the patients in this study would have received appropriate clinical management based on neurologic history and the results of CFS alone. Our results indicate that CFS is sufficient for determining the need for surgery in patients being considered for CEA and can supplant cerebral angiography in nearly all clinical circumstances.