Variation in care and outcome for fragile hip fracture patients: a European multicentre study benchmarking fulfilment of established quality indicators.

PURPOSE: Despite the availability of clinical guidelines for hip fracture patients, adherence to these guidelines is challenging, potentially resulting in suboptimal patient care. The goal of this study was (1) to evaluate and benchmark the adherence to recently established quality indicators (QIs), and (2) to study clinical outcomes, in fragile hip fracture patients from different European countries. METHODS: This observational, cross-sectional multicenter study was performed in 10 hospitals from 9 European countries including data of 298 consecutive patients. RESULTS: A large variation both within and between hospitals were seen regarding adherence to the individual QIs. QIs with the lowest overall adherence rates were the administration of systemic steroids (5.4%) and tranexamic acid (20.1%). Indicators with the highest adherence rates (above 95%) were pre-operative (99.3%) and post-operative haemoglobin level assessment (100%). The overall median time to surgery was 22.6 h (range 15.7-42.5 h). The median LOS was 9.0 days (range 5.0-19.0 days). The most common complications were delirium (23.2%) and postsurgical constipation (25.2%). CONCLUSION: The present study shows large variation in the care for fragile patients with hip fractures indicating room for improvement. Therefore, hospitals should invest in benchmarking and knowledge-sharing. Large quality improvement initiatives with longitudinal follow up of both process and outcome indicators should be initiated.

AKAP150-anchored PKA regulation of synaptic transmission and plasticity, neuronal excitability and CRF neuromodulation in the lateral habenula.

Numerous studies of hippocampal synaptic function in learning and memory have established the functional significance of the scaffolding A-kinase anchoring protein 150 (AKAP150) in kinase and phosphatase regulation of synaptic receptor and ion channel trafficking/function and hence synaptic transmission/plasticity, and neuronal excitability. Emerging evidence also suggests that AKAP150 signaling may play a critical role in brain's processing of rewarding/aversive experiences. Here we focused on an unexplored role of AKAP150 in the lateral habenula (LHb), a diencephalic brain region that integrates and relays negative reward signals from forebrain striatal and limbic structures to midbrain monoaminergic centers. LHb aberrant activity (specifically hyperactivity) is also linked to depression. Using whole cell patch clamp recordings in LHb of male wildtype (WT) and ΔPKA knockin mice (with deficiency in AKAP-anchoring of PKA), we found that the genetic disruption of PKA anchoring to AKAP150 significantly reduced AMPA receptor (AMPAR)-mediated glutamatergic transmission and prevented the induction of presynaptic endocannabinoid (eCB)-mediated long-term depression (LTD) in LHb neurons. Moreover, ΔPKA mutation potentiated GABAA receptor (GABAAR)-mediated inhibitory transmission postsynaptically while increasing LHb intrinsic neuronal excitability through suppression of medium afterhyperpolarizations (mAHPs). Given that LHb is a highly stress-responsive brain region, we further tested the effects of corticotropin releasing factor (CRF) stress neuromodulator on synaptic transmission and intrinsic excitability of LHb neurons in WT and ΔPKA mice. As in our earlier study in rat LHb, CRF significantly suppressed GABAergic transmission onto LHb neurons and increased intrinsic excitability by diminishing small-conductance potassium (SK) channel-mediated mAHPs. ΔPKA mutation-induced suppression of mAHPs also blunted the synaptic and neuroexcitatory actions of CRF in mouse LHb. Altogether, our data suggest that AKAP150 complex signaling plays a critical role in regulation of AMPAR and GABAAR synaptic strength, glutamatergic plasticity and CRF neuromodulation possibly through AMPAR and potassium channel trafficking and eCB signaling within the LHb.

A review of the microtremor horizontal-to-vertical spectral ratio (MHVSR) method.

The single-station microtremor horizontal-to-vertical spectral ratio (MHVSR) method was initially proposed to retrieve the site amplification function and its resonance frequencies produced by unconsolidated sediments overlying high-velocity bedrock. Presently, MHVSR measurements are predominantly conducted to obtain an estimate of the fundamental site frequency at sites where a strong subsurface impedance contrast exists. Of the earthquake site characterization methods presented in this special issue, the MHVSR method is the furthest behind in terms of consensus towards standardized guidelines and commercial use. The greatest challenges to an international standardization of MHVSR acquisition and analysis are (1) the what - the underlying composition of the microtremor wavefield is site-dependent, and thus, the appropriate theoretical (forward) model for inversion is still debated; and (2) the how - many factors and options are involved in the data acquisition, processing, and interpretation stages. This paper reviews briefly a historical development of the MHVSR technique and the physical basis of an MHVSR (the what). We then summarize recommendations for MHVSR acquisition and analysis (the how). Specific sections address MHVSR interpretation and uncertainty assessment.

Longitudinal evaluation of laboratory-based serological assays for SARS-CoV-2 antibody detection.

Serological assays for SARS-CoV-2 infection are now widely available for use in diagnostic laboratories. Limited data are available on the performance characteristics in different settings, and at time periods remote from the initial infection. Validation of the Abbott (Architect SARS-CoV-2 IgG), DiaSorin (Liaison SARS-CoV-2 S1/S2 IgG) and Roche (Cobas Elecsys Anti-SARS-CoV-2) assays was undertaken utilising 217 serum samples from 131 participants up to 7 months following COVID-19 infection. The Abbott and DiaSorin assays were implemented into routine laboratory workflow, with outcomes reported for 2764 clinical specimens. Sensitivity and specificity were concordant with the range reported by the manufacturers for all assays. Sensitivity across the convalescent period was highest for the Roche at 95.2-100% (95% CI 81.0-100%), then the DiaSorin at 88.1-100% (95% CI 76.0-100%), followed by the Abbott 68.2-100% (95% CI 53.4-100%). Sensitivity of the Abbott assay fell from approximately 5 months; on this assay paired serum samples for 45 participants showed a significant drop in the signal-to-cut-off ratio and 10 sero-reversion events. When used in clinical practice, all samples testing positive by both DiaSorin and Abbott assays were confirmed as true positive results. In this low prevalence setting, despite high laboratory specificity, the positive predictive value of a single positive assay was low. Comprehensive validation of serological assays is necessary to determine the optimal assay for each diagnostic setting. In this low prevalence setting we found implementation of two assays with different antibody targets maximised sensitivity and specificity, with confirmatory testing necessary for any sample which was positive in only one assay.

Nonlinear ultrasound simulation in an axisymmetric coordinate system using a k-space pseudospectral method.

A full-wave model for nonlinear ultrasound propagation through a heterogeneous and absorbing medium in an axisymmetric coordinate system is developed. The model equations are solved using a nonstandard or k-space pseudospectral time domain method. Spatial gradients in the axial direction are calculated using the Fourier collocation spectral method, and spatial gradients in the radial direction are calculated using discrete trigonometric transforms. Time integration is performed using a k-space corrected finite difference scheme. This scheme is exact for plane waves propagating linearly in the axial direction in a homogeneous and lossless medium and significantly reduces numerical dispersion in the more general case. The implementation of the model is described, and performance benchmarks are given for a range of grid sizes. The model is validated by comparison with several analytical solutions. This includes one-dimensional absorption and nonlinearity, the pressure field generated by plane-piston and bowl transducers, and the scattering of a plane wave by a sphere. The general utility of the model is then demonstrated by simulating nonlinear transcranial ultrasound using a simplified head model.

Do low-fat foods alter risk of colorectal cancer from processed meat?

OBJECTIVES: We investigated potential causes of the high incidence rate of colorectal cancer (CRC) in New Zealand. STUDY DESIGN: A national population-based case-control study of 806 cases and 1025 controls was conducted to determine the risk factors for CRC in this population. METHODS: Information about family history of CRC, ethnicity, diet, school milk consumption, exercise, and height and weight at age 20 years were collected by a self-administered questionnaire from cases and controls. RESULTS: Response rates were 84% for cases and 65% for controls. Increasing preference for low-fat food alternatives was associated with reducing odds ratios (OR) for CRC (Ptrend<0.001) with a considerably reduced OR of always versus never choosing low-fat food alternatives (OR = 0.39, 95% confidence interval = 0.26, 0.58). Increased consumption of dairy products or milk was associated with reduced risk of CRC. Belonging to the male gender, having a first degree relative with CRC, and increasing consumption of processed meat, lamb, pork, and bread were associated with elevated risks of CRC. The increased risk from consumption of processed meat was not evident in subjects who regularly or always preferred low-fat food. CONCLUSIONS: A preference for low-fat food may ameliorate an increased risk of CRC from the consumption of processed meat.

Breast cancer and cytomegalovirus.

PURPOSE: To determine whether cytomegalovirus is causally associated with breast cancer and whether cytomegalovirus should be categorised as an oncogenic virus. METHODS: We undertook a review of published epidemiological and laboratory studies, using established causal criteria: Bradford Hill criteria to determine whether cytomegalovirus is associated with breast cancer; and Evans/Mueller criteria to determine whether cytomegalovirus should be categorised as an oncogenic virus. RESULTS: Although there are inconsistencies in the findings of published epidemiological and laboratory studies, these may be explained by factors such as: differences in timing of blood samples, differences in selection of cases and controls, or high cytomegalovirus seroprevalence among participants in the epidemiological studies; and, in the laboratory studies, differences in sample preparations, age of sample, whether or not paired breast cancer and normal breast tissue samples were used, differences in the tests, primers and/or antibodies used, differences in histological types of breast cancer studied, and/or features of the virus. CONCLUSIONS: Overall, the results of published studies of cytomegalovirus and breast cancer suggest cytomegalovirus is a causal factor for at least some types of breast cancer. If the evidence for a link between cytomegalovirus and breast cancer continues to strengthen, further research could lead to: targeted screening; therapy using antiviral drugs; and, perhaps, primary prevention of a significant proportion of breast cancer. Vaccination against viruses has already been shown to be effective in preventing cervix and liver cancer; cytomegalovirus vaccines are already under development.

Enhancing bowel screening: Preventing colorectal cancer by flexible sigmoidoscopy in New Zealand.

OBJECTIVES: The prevention of colorectal cancer (CRC) attainable from introducing once-in-a-lifetime flexible sigmoidoscopy (FSIG) screening was assessed. STUDY DESIGN: This is a review of relevant available information for the assessment of the impact and resource demands of FSIG in New Zealand. METHODS: The reduction in bowel cancer incidence achievable by one-off FSIG screening from 50 to 59 years of age, an age group for which bowel screening is not currently offered, was reviewed. The prevention of CRC attainable from an offer of screening at 55 years of age in New Zealand was also estimated. The number and cost of the FSIG screening procedures required and referrals for colonoscopies and the savings in treatment were calculated. RESULTS: Annually, about 27,500 FSIG screening procedures would be required if 50% of those turning 55 years of age accepted an offer of once-in-a-lifetime FSIG screening. This would result in three-four-fold fewer people being referred for colonoscopy than in the national 2-yearly faecal immunochemical test (FIT) screening programme and subsequently reduce demand for colonoscopy from a false-positive FIT. The number of CRC cases prevented would increase over 17 years to more than 300 per year by 2033. After 10-15 years of screening, the annual savings in health service costs, primarily from CRC prevented, were sufficient to completely fund the FSIG screening. CONCLUSIONS: Inclusion of FSIG screening in the national bowel screening programme would significantly reduce both the incidence and mortality of CRC in New Zealand, reduce the colonoscopy demand of current bowel screening and reduce long-term health service costs.

Representing arbitrary acoustic source and sensor distributions in Fourier collocation methods.

Accurately representing acoustic source distributions is an important part of ultrasound simulation. This is challenging for grid-based collocation methods when such distributions do not coincide with the grid points, for instance when the source is a curved, two-dimensional surface embedded in a three-dimensional domain. Typically, grid points close to the source surface are defined as source points, but this can result in "staircasing" and substantial errors in the resulting acoustic fields. This paper describes a technique for accurately representing arbitrary source distributions within Fourier collocation methods. The method works by applying a discrete, band-limiting convolution operator to the continuous source distribution, after which source grid weights can be generated. This allows arbitrarily shaped sources, for example, focused bowls and circular pistons, to be defined on the grid without staircasing errors. The technique is examined through simulations of a range of ultrasound sources, and comparisons with analytical solutions show excellent accuracy and convergence rates. Extensions of the technique are also discussed, including application to initial value problems, distributed sensors, and moving sources.

Equivalent-Source Acoustic Holography for Projecting Measured Ultrasound Fields Through Complex Media.

Holographic projections of experimental ultrasound measurements generally use the angular spectrum method or Rayleigh integral, where the measured data are imposed as a Dirichlet boundary condition. In contrast, full-wave models, which can account for more complex wave behavior, often use interior mass or velocity sources to introduce acoustic energy into the simulation. Here, a method to generate an equivalent interior source that reproduces the measurement data is proposed based on gradient-based optimization. The equivalent-source can then be used with full-wave models (for example, the open-source k-Wave toolbox) to compute holographic projections through complex media including nonlinearity and heterogeneous material properties. Numerical and experimental results using both time-domain and continuous-wave sources are used to demonstrate the accuracy of the approach.

Metal concentrations in seagrass (Halophila ovalis) tissue and ambient sediment in a highly modified estuarine environment (Sydney estuary, Australia).

Research into sediment-seagrass tissue metal relationships has been undertaken in Sydney estuary due to the recognized role contamination plays in threats to seagrass health. Seagrass (Halophila ovalis) leaf tissue concentrations are elevated in Cu, Pb and Zn and contain the highest reported root Cr concentrations. Seagrass metal concentrations were significantly different between species H. ovalis and Zostera capricorni; between root and leaf tissue; and between sampling locations. Greatest tissue enrichment was for Pb, however metals were not enriched in seagrass relative to surficial sediment. Fine and total sediment metal concentrations were temporally consistent between collection years 2013/15, whereas root tissue metals changed between years and sites and leaf metal contents were temporally inconsistent. Extractable metal concentrations in fine sediment (<62.5 µm) showed moderate significant correlation with root tissue and a weak significant relationship with leaf tissue, whereas total sediment metal showed no such relationships. Management implications are provided.

The relationship between metal concentrations in seagrass (Zostera capricorni) tissue and ambient fine sediment in modified and near-pristine estuaries (Sydney estuaries, Australia).

Seagrass (Zostera capricorni) tissue metal concentrations in Sydney estuary are some of the highest reported for urban environments. A strong declining metal (As, Co, Cr, Cu, Mn, Pb and Zn) concentration gradient in fine sediment from highly modified to the near-pristine estuarine environments was matched by a concurrent and statistically significant, moderately strong, relationship with declining metal concentrations for leaf, rhizomes and root tissue types. Leaf tissue more consistently expressed metal concentration uptake from sediment. Rhizome tissue contained the highest concentrations for all metals, except Mn, while leaf concentrations were higher for Cr and Zn and roots were more elevated in Cr and Pb. Tissue Cr, Pb and Zn were close to background for reference sites for leaves. Maximum tissue enrichment over background was 25, 19, 47 and 8 times for Cr, Cu, Pb and Zn. Bio-sediment accumulation factors were generally <1 for all metals.

An open source, 3D printed preclinical MRI phantom for repeated measures of contrast agents and reference standards.

In medical imaging, clinicians, researchers and technicians have begun to use 3D printing to create specialized phantoms to replace commercial ones due to their customizable and iterative nature. Presented here is the design of a 3D printed open source, reusable magnetic resonance imaging (MRI) phantom, capable of flood-filling, with removable samples for measurements of contrast agent solutions and reference standards, and for use in evaluating acquisition techniques and image reconstruction performance. The phantom was designed using SolidWorks, a computer-aided design software package. The phantom consists of custom and off-the-shelf parts and incorporates an air hole and Luer Lock system to aid in flood filling, a marker for orientation of samples in the filled mode and bolt and tube holes for assembly. The cost of construction for all materials is under $90. All design files are open-source and available for download. To demonstrate utility, B0 field mapping was performed using a series of gadolinium concentrations in both the unfilled and flood-filled mode. An excellent linear agreement (R2>0.998) was observed between measured relaxation rates (R1/R2) and gadolinium concentration. The phantom provides a reliable setup to test data acquisition and reconstruction methods and verify physical alignment in alternative nuclei MRI techniques (e.g. carbon-13 and fluorine-19 MRI). A cost-effective, open-source MRI phantom design for repeated quantitative measurement of contrast agents and reference standards in preclinical research is presented. Specifically, the work is an example of how the emerging technology of 3D printing improves flexibility and access for custom phantom design.

Rapid calculation of acoustic fields from arbitrary continuous-wave sources.

A Green's function solution is derived for calculating the acoustic field generated by phased array transducers of arbitrary shape when driven by a single frequency continuous wave excitation with spatially varying amplitude and phase. The solution is based on the Green's function for the homogeneous wave equation expressed in the spatial frequency domain or k-space. The temporal convolution integral is solved analytically, and the remaining integrals are expressed in the form of the spatial Fourier transform. This allows the acoustic pressure for all spatial positions to be calculated in a single step using two fast Fourier transforms. The model is demonstrated through several numerical examples, including single element rectangular and spherically focused bowl transducers, and multi-element linear and hemispherical arrays.

Treating a novel plasticity defect rescues episodic memory in Fragile X model mice.

Episodic memory, a fundamental component of human cognition, is significantly impaired in autism. We believe we report the first evidence for this problem in the Fmr1-knockout (KO) mouse model of Fragile X syndrome and describe potentially treatable underlying causes. The hippocampus is critical for the formation and use of episodes, with semantic (cue identity) information relayed to the structure via the lateral perforant path (LPP). The unusual form of synaptic plasticity expressed by the LPP (lppLTP) was profoundly impaired in Fmr1-KOs relative to wild-type mice. Two factors contributed to this defect: (i) reduced GluN1 subunit levels in synaptic NMDA receptors and related currents, and (ii) impaired retrograde synaptic signaling by the endocannabinoid 2-arachidonoylglycerol (2-AG). Studies using a novel serial cue paradigm showed that episodic encoding is dependent on both the LPP and the endocannabinoid receptor CB1, and is strikingly impaired in Fmr1-KOs. Enhancing 2-AG signaling rescued both lppLTP and learning in the mutants. Thus, two consequences of the Fragile-X mutation converge on plasticity at one site in hippocampus to prevent encoding of a basic element of cognitive memory. Collectively, the results suggest a clinically plausible approach to treatment.

Time domain reconstruction of sound speed and attenuation in ultrasound computed tomography using full wave inversion.

Ultrasound computed tomography (USCT) is a non-invasive imaging technique that provides information about the acoustic properties of soft tissues in the body, such as the speed of sound (SS) and acoustic attenuation (AA). Knowledge of these properties can improve the discrimination between benign and malignant masses, especially in breast cancer studies. Full wave inversion (FWI) methods for image reconstruction in USCT provide the best image quality compared to more approximate methods. Using FWI, the SS is usually recovered in the time domain, and the AA is usually recovered in the frequency domain. Nevertheless, as both properties can be obtained from the same data, it is desirable to have a common framework to reconstruct both distributions. In this work, an algorithm is proposed to reconstruct both the SS and AA distributions using a time domain FWI methodology based on the fractional Laplacian wave equation, an adjoint field formulation, and a gradient-descent method. The optimization code employs a Compute Unified Device Architecture version of the software k-Wave, which provides high computational efficiency. The performance of the method was evaluated using simulated noisy data from numerical breast phantoms. Errors were less than 0.5% in the recovered SS and 10% in the AA.

Characterisation of a phantom for multiwavelength quantitative photoacoustic imaging.

Quantitative photoacoustic imaging (qPAI) has the potential to provide high- resolution in vivo images of chromophore concentration, which may be indicative of tissue function and pathology. Many strategies have been proposed recently for extracting quantitative information, but many have not been experimentally verified. Experimental phantom-based validation studies can be used to test the robustness and accuracy of such algorithms in order to ensure reliable in vivo application is possible. The phantoms used in such studies must have well-characterised optical and acoustic properties similar to tissue, and be versatile and stable. Polyvinyl chloride plastisol (PVCP) has been suggested as a phantom for quality control and system evaluation. By characterising its multiwavelength optical properties, broadband acoustic properties and thermoelastic behaviour, this paper examines its potential as a phantom for qPAI studies too. PVCP's acoustic properties were assessed for various formulations, as well as its intrinsic optical absorption, and scattering with added TiO2, over a range of wavelengths from 400-2000 nm. To change the absorption coefficient, pigment-based chromophores that are stable during the phantom fabrication process, were used. These yielded unique spectra analogous to tissue chromophores and linear with concentration. At the high peak powers typically used in photoacoustic imaging, nonlinear optical absorption was observed. The Grüneisen parameter was measured to be [Formula: see text] = 1.01 ± 0.05, larger than typically found in tissue, though useful for increased PA signal. Single and multiwavelength 3D PA imaging of various fabricated PVCP phantoms were demonstrated.

Enhanced Recovery After Surgery (ERAS) for gastrointestinal surgery, part 2: consensus statement for anaesthesia practice.

BACKGROUND: The present interdisciplinary consensus review proposes clinical considerations and recommendations for anaesthetic practice in patients undergoing gastrointestinal surgery with an Enhanced Recovery after Surgery (ERAS) programme. METHODS: Studies were selected with particular attention being paid to meta-analyses, randomized controlled trials and large prospective cohort studies. For each item of the perioperative treatment pathway, available English-language literature was examined and reviewed. The group reached a consensus recommendation after critical appraisal of the literature. RESULTS: This consensus statement demonstrates that anaesthesiologists control several preoperative, intraoperative and postoperative ERAS elements. Further research is needed to verify the strength of these recommendations. CONCLUSIONS: Based on the evidence available for each element of perioperative care pathways, the Enhanced Recovery After Surgery (ERAS®) Society presents a comprehensive consensus review, clinical considerations and recommendations for anaesthesia care in patients undergoing gastrointestinal surgery within an ERAS programme. This unified protocol facilitates involvement of anaesthesiologists in the implementation of the ERAS programmes and allows for comparison between centres and it eventually might facilitate the design of multi-institutional prospective and adequately powered randomized trials.

Azithromycin and the treatment of lymphocytic airway inflammation after lung transplantation.

Lymphocytic airway inflammation is a major risk factor for chronic lung allograft dysfunction, for which there is no established treatment. We investigated whether azithromycin could control lymphocytic airway inflammation and improve allograft function. Fifteen lung transplant recipients demonstrating acute allograft dysfunction due to isolated lymphocytic airway inflammation were prospectively treated with azithromycin for at least 6 months (NCT01109160). Spirometry (FVC, FEV1 , FEF25-75 , Tiffeneau index) and FeNO were assessed before and up to 12 months after initiation of azithromycin. Radiologic features, local inflammation assessed on airway biopsy (rejection score, IL-17(+) cells/mm(2) lamina propria) and broncho-alveolar lavage fluid (total and differential cell counts, chemokine and cytokine levels); as well as systemic C-reactive protein levels were compared between baseline and after 3 months of treatment. Airflow improved and FeNO decreased to baseline levels after 1 month of azithromycin and were sustained thereafter. After 3 months of treatment, radiologic abnormalities, submucosal cellular inflammation, lavage protein levels of IL-1ß, IL-8/CXCL-8, IP-10/CXCL-10, RANTES/CCL5, MIP1-α/CCL3, MIP-1ß/CCL4, Eotaxin, PDGF-BB, total cell count, neutrophils and eosinophils, as well as plasma C-reactive protein levels all significantly decreased compared to baseline (p < 0.05). Administration of azithromycin was associated with suppression of posttransplant lymphocytic airway inflammation and clinical improvement in lung allograft function.