Dedicated anticoagulation management protocols in fragility femoral fracture care - a source of significant variance and limited effectiveness in improving time to surgery: The hip and femoral fracture anticoagulation surgical timing evaluation (HASTE) study.

INTRODUCTION: Approximately 20 % of femoral fragility fracture patients take anticoagulants, typically warfarin or Direct Oral AntiCoagulant (DOAC). These can impact timing of surgery affecting patient survival. Due to several possible approaches and numerous factors to consider in the preoperative workup of anticoagulated patients, potential for variations in clinical practice exist. Some hospitals employ dedicated anticoagulation management protocols to address this issue, and to improve time to surgery. This study aimed to determine the proportion of hospitals with such protocols, compare protocol guidance between hospitals, and evaluate the effectiveness of protocols in facilitating prompt surgery. METHODS: Data was prospectively collected through a collaborative, multicentre approach involving hospitals across the UK. Femoral fragility fracture patients aged ≥60 years and admitted to hospital between 1st May to 31st July 2023 were included. Information from dedicated anticoagulation management protocols were collated on several domains relating to perioperative care including administration of reversal agents and instructions on timing of surgery as well as others. Logistic regression was used to evaluate effects of dedicated protocols on time to surgery. RESULTS: Dedicated protocols for management of patients taking warfarin and DOACs were present at 41 (52.6 %) and 43 (55.1 %) hospitals respectively. For patients taking warfarin, 39/41 (95.1 %) protocols specified the dose of vitamin k and the most common was 5 milligrams intravenously (n=21). INR threshold values for proceeding to surgery varied between protocols; 1.5 (n=28), 1.8 (n=6), and 2 (n=6). For patients taking DOACs, 35/43 (81.4 %) and 8/43 (18.6 %) protocols advised timing of surgery based on renal function and absolute time from last dose respectively. Analysis of 10,197 patients from 78 hospitals showed fewer patients taking DOACs received surgery within 36 h of admission at hospitals with a dedicated protocol compared to those without (adjusted OR 0.73, 95% CI 0.54-0.99, p=0.040), while there were no differences among patients taking warfarin (adjusted OR 1.64, 95% CI 0.75-3.57, p=0.219). CONCLUSIONS: Around half of hospitals employed a dedicated anticoagulation management protocol for femoral fragility fracture patients, and substantial variation was observed in guidance between protocols. Dedicated protocols currently being used at hospitals were ineffective at improving the defined targets for time to surgery.

Factors affecting patient flow in a neurosurgery department.

INTRODUCTION: Patient flow is the process by which movement of patients and clinical productivity is achieved. The objectives of this study were to implement and evaluate the NHS Improvement SAFER patient flow bundle, evaluate the impact of the Red2Green initiative, and assess the impact of frailty on patient flow. MATERIALS AND METHODS: All patients admitted to a neurosurgery unit from 1 September to 30 November 2017 were included. Using guidance set out by NHS, data were prospectively collected from daily ward lists and patient notes, including demographics, admission and discharge details, length of stay, anticipated discharge date, red days with reasons and frailty (Rockwood Clinical Frailty Scale). NHS reference costs were used for cost analyses. RESULTS: A total of 420 patients (55% elective) were included, totalling 3909 bed days. All patients received daily senior reviews before midday, and anticipated discharge dates were set at daily multidisciplinary team meetings. Ten per cent of patients were discharged before midday. There were 21% (837) red days, significantly more (76%) for emergency patients (639 vs 198 elective; P < 0.001); 63% red days were attributed to awaiting a bed in a local hospital; 25% (106) patients were classed as frail (50 elective), which was associated with a significantly longer length of stay (17.3 vs 6; P < 0.01), and more red days (615 vs 222; p<0.01). Considering excess bed charges and lost revenue (with penalties), red days cost over £1 million per year. CONCLUSIONS: SAFER has identified areas for improvement in patient flow, with obvious cost implications. It has created a platform for discussion within the referral network and identified a role for a geriatric liaison service.

Data on dopant characteristics and band alignment of CdTe cells with and without a ZnO highly-resistive-transparent buffer layer.

Photovoltaic enhancement of cadmium telluride (CdTe) thin film solar cells using a 50 nm thick, atomic-layer-deposited zinc oxide (ZnO) buffer film was reported in "Enhancement of the photocurrent and efficiency of CdTe solar cells suppressing the front contact reflection using a highly-resistive ZnO buffer layer" (Kartopu et al., 2019) [1]. Data presented here are the dopant profiles of two solar cells prepared side-by-side, one with and one without the ZnO highly resistive transparent (HRT) buffer, which displayed an open-circuit potential (Voc) difference of 25 mV (in favor of the no-buffer device), as well as their simulated device data. The concentration of absorber dopant atoms (arsenic) was measured using the secondary ion mass spectroscopy (SIMS) method, while the density of active dopants was calculated from the capacitance-voltage (CV) measurements. The solar cell simulation data was obtained using the SCAPS software, a one-dimensional solar cell simulation programme. The presented data indicates a small loss (around 20 mV) of Voc for the HRT buffered cells.

Paradoxical upgrading reaction in extra-pulmonary tuberculosis: association with vitamin D therapy.

SETTING: Glasgow, Scotland, UK. BACKGROUND: Paradoxical reactions in tuberculosis (TB) are a notable example of our incomplete understanding of host-pathogen interactions during anti-tuberculosis treatment. OBJECTIVES: To determine risk factors for a TB paradoxical reaction, and specifically to assess for an independent association with vitamin D use. DESIGN: Consecutive human immunodeficiency virus (HIV) negative adult patients treated for extra-pulmonary TB were identified from an Extended Surveillance of Mycobacterial Infections database. In our setting, vitamin D was variably prescribed for newly diagnosed TB patients. A previously published definition of paradoxical TB reaction was retrospectively applied to, and data on all previously described risk factors were extracted from, centralised electronic patient records. The association with vitamin D use was assessed using multivariate logistic regression. RESULTS: Of the 249 patients included, most had TB adenopathy; 222/249 had microbiologically and/or histologically confirmed TB. Vitamin D was prescribed for 57/249 (23%) patients; 37/249 (15%) were classified as having paradoxical reactions. Younger age, acid-fast bacilli-positive invasive samples, multiple disease sites, lower lymphocyte count and vitamin D use were found to be independent risk factors. CONCLUSION: We speculate that vitamin D-mediated signalling of pro-inflammatory innate immune cells, along with high antigenic load, may mediate paradoxical reactions in anti-tuberculosis treatment.

Restrictive antibiotic stewardship associated with reduced hospital mortality in gram-negative infection.

INTRODUCTION: : Antimicrobial stewardship has an important role in the control of Clostridium difficile infection (CDI) and antibiotic resistance. An important component of UK stewardship interventions is the restriction of broad-spectrum beta-lactam antibiotics and promotion of agents associated with a lower risk of CDI such as gentamicin. While the introduction of restrictive antibiotic guidance has been associated with improvements in CDI and antimicrobial resistance, evidence of the effect on outcome following severe infection is lacking. METHODS: : In 2008, Glasgow hospitals introduced a restrictive antibiotic guideline. A retrospective before/after study assessed outcome following Gram-negative bacteraemia in the 2-year period around implementation. RESULTS: : Introduction of restrictive antibiotic guidelines was associated with a reduction in utilization of ceftriaxone and co-amoxiclav and an increase in amoxicillin and gentamicin. Approximately 1593 episodes of bacteremia were included in the study. The mortality over 1-year following Gram-negative bacteraemia was lower in the period following guideline implementation (RR 0.852, P = 0.045). There was no evidence of a difference in secondary outcomes including ITU admission, length of stay, readmission, recurrence of bacteraemia and need for renal replacement therapy. There was a fall in CDI (RR 0.571, P = 0.014) and a reduction in bacterial resistance to ceftriaxone and co-amoxiclav but no evidence of an increase in gentamicin resistance after guideline implementation. CONCLUSION: : Restrictive antibiotic guidelines were associated with a reduction in CDI and bacterial resistance but no evidence of adverse outcomes following Gram-negative bacteraemia. There was a small reduction in one year mortality.

A murine model of early Pseudomonas aeruginosa lung disease with transition to chronic infection.

Pseudomonas aeruginosa (PA) remains an important pathogen in patients with cystic fibrosis (CF) lung disease as well as non-CF bronchiectasis and chronic obstructive airways disease. Initial infections are cleared but chronic infection with mucoid strains ensues in the majority of CF patients and specific interventions to prevent this critical infection transition are lacking. The PA bead model has been widely used to study pulmonary P.aeruginosa infection but has limitations in animal husbandry and in accurately mimicking human disease. We have developed an adapted agar bead murine model using a clinical mucoid strain that demonstrates the key features of transition from transitory to chronic airways infection. Infected animals show very limited acute morbidity and mortality, but undergo infection-related weight loss and neutrophilic inflammation, development of anti-pseudomonal antibodies, variable bacterial clearance, endobronchial infection and microbial adaptation with PA small colony variants. We anticipate this model will allow research into the host and microbial factors governing this critical period in Pseudomonas aeruginosa pulmonary pathogenesis when transition to chronicity is occurring.

Simple merging technique for improving resolution in qualitative single image phase contrast tomography.

For dynamic samples and/or for simple ease-of-use experiments, single-image phase contrast tomography is a very effective method for the 3D visualization of materials which would otherwise be indiscernible in attenuation based x-ray imaging. With binary samples (e.g. air-material) and monochromatic wavefields a transport-of-intensity (TIE)-based phase retrieval algorithm is known to retrieve accurate quantitative maps of the phase distribution. For mixed material samples and/or white beam radiation the algorithm can still produce useful qualitative tomographic reconstructions with significantly improved area contrast. The stability of the algorithm comes with a recognized associated loss of spatial resolution due to its essential behaviour as a low-pass filter. One possible answer to this is an image fusion technique that merges the slices reconstructed from raw phase contrast images and those after phase retrieval, where the improved contrast may be acquired without the associated loss of high-frequency information. We present this technique as a simple few-parameter Fourier method, which is easily tunable and highly compatible with current reconstruction steps.

Unraveling wetting transition through surface textures with X-rays: liquid meniscus penetration phenomena.

In this report we show that synchrotron X-ray radiography is a powerful method to study liquid-air interface penetration through opaque microtextured surface roughness, leading to wetting transition. We investigate this wetting phenomenon in the context of sessile drop evaporation, and establish that liquid interface sinking into the surface texture is indeed dictated by the balance of capillary and Laplace pressures, where the intrinsically three-dimensional nature of the meniscus must be accounted for. Air bubble entrapment in the texture underneath impacting water drops is also visualized and the mechanisms of post-impact drop evaporation are discussed.

Risk of venous thromboembolism in patients treated for bacterial infection in the community with outpatient parenteral antimicrobial therapy.

BACKGROUND: It is recommended that venous thromboembolism (VTE) prophylaxis be considered for patients receiving outpatient parenteral antimicrobial therapy (OPAT), but there is no published data to quantify VTE risk in this patient group. AIM AND METHOD: The aim of this retrospective cohort study was to establish VTE incidence in patients managed through an OPAT service and assess utility of a common VTE prediction score normally used for inpatients. Consecutive episodes of OPAT between May 2009 and May 2012 were included. Patients on long-term anti-coagulants, those with an established indication for extended, outpatient VTE prophylaxis (i.e. patients referred to OPAT following hip or knee arthroplasty) were excluded. The Padua VTE Prediction Score was retrospectively applied to the cohort. The primary outcome was incidence of symptomatic VTE during or up to 90 days after completion of OPAT treatment. RESULTS: There were 780 included patient episodes; 105 (13.5%) patients had a Padua VTE risk score >3; no patients received pharmacological VTE prophylaxis during OPAT treatment. During or up to 90 days following OPAT, two proximal lower limb DVTs were diagnosed, giving VTE incidence of 2/780 (0.26%, 95% CI: 0.03-0.92%), and there were eight deaths of which none were suspected to be related to VTE. There was one intracranial haemorrhage associated death. CONCLUSION: This retrospective cohort study found a low incidence of VTE in OPAT patients, and does not support routine application of inpatient VTE prophylaxis algorithms to patients treated for infection in the community.

Inhibition of neointimal hyperplasia in a rabbit vein graft model following non-viral transfection with human iNOS cDNA.

Vein graft failure caused by neointimal hyperplasia (IH) after coronary artery bypass grafting with saphenous veins is a major clinical problem. The lack of safe and efficient vectors for vascular gene transfer has significantly hindered progress in this field. We have developed a Receptor-Targeted Nanocomplex (RTN) vector system for this purpose and assessed its therapeutic efficacy in a rabbit vein graft model of bypass grafting. Adventitial delivery of ß-Galactosidase showed widespread transfection throughout the vein wall on day 7, estimated at about 10% of cells in the adventitia and media. Vein grafts were then transfected with a plasmid encoding inducible nitric oxide synthase (iNOS) and engrafted into the carotid artery. Fluorescent immunohistochemistry analysis of samples from rabbits killed at 7 days after surgery showed that mostly endothelial cells and macrophages were transfected. Morphometric analysis of vein graft samples from the 28-day groups showed approximately a 50% reduction of neointimal thickness and 64% reduction of neointimal area in the iNOS-treated group compared with the surgery control groups. This study demonstrates efficacy of iNOS gene delivery by the RTN formulation in reducing IH in the rabbit model of vein graft disease.

Biological vulnerability of two exploited sharks of the genus Deania (Centrophoridae).

Life-history parameters of Deania calcea and Deania quadrispinosa suggested that their productivity was very low. Maturity (L(T50) ) occurs at c. 80% of maximum observed total lengths (L(T) ) for both species and sexes. A large proportion of mature females were neither pre-ovulatory nor pregnant, and the reproductive cycle included a distinct resting phase after pregnancy. For D. calcea, mean ovarian fecundity was 12 and maximum observed litter size was 10 (average of six); D. quadrispinosa averaged 17 pups per litter. Birth L(T) was 28-33 cm for D. calcea and 23-25 cm for D. quadrispinosa. The male and female reproductive cycles were aseasonal, and consequently, the length of the reproductive cycle could not be determined. Preliminary ageing data from dorsal-spine growth bands suggested that female D. calcea lived to 31-36 years and males to 24-32 years. The L(T) -at-age data using external bands on the spines showed maturity occurring at 15·5 years (males) and 21·5 years (females), whereas banding on the internal dentine indicated maturity at 10·5 and 17·5 years for males and females. Thus, a female lifetime of 31-36 years allowed for a maximum of 7 litters if a 2 year cycle is assumed or only five litters with a 3 year cycle, resulting in a lifetime fecundity of only 42 pups (2 year cycle) or even lower (3 year cycle).

X-ray mosaic nanotomography of large microorganisms.

Full-field X-ray microscopy is a valuable tool for 3D observation of biological systems. In the soft X-ray domain organelles can be visualized in individual cells while hard X-ray microscopes excel in imaging of larger complex biological tissue. The field of view of these instruments is typically 10(3) times the spatial resolution. We exploit the assets of the hard X-ray sub-micrometer imaging and extend the standard approach by widening the effective field of view to match the size of the sample. We show that global tomography of biological systems exceeding several times the field of view is feasible also at the nanoscale with moderate radiation dose. We address the performance issues and limitations of the TOMCAT full-field microscope and more generally for Zernike phase contrast imaging. Two biologically relevant systems were investigated. The first being the largest known bacteria (Thiomargarita namibiensis), the second is a small myriapod species (Pauropoda sp.). Both examples illustrate the capacity of the unique, structured condenser based broad-band full-field microscope to access the 3D structural details of biological systems at the nanoscale while avoiding complicated sample preparation, or even keeping the sample environment close to the natural state.

Observation of few-cycle, strong-field phenomena in surface plasmon fields.

We present experimental evidence of the generation of few-cycle propagating surface plasmon polariton wavepackets. These ultrashort plasmonic pulses comprised of only 2-3 field oscillations were characterized by an autocorrelation measurement based on electron photoemission. By exploiting plasmonic field enhancement, we achieved plasmon-induced tunnelling emission from the metal surface at low laser intensity, opening perspectives for strong-field experiments with low pulse energies. All-optical electron acceleration up to keV kinetic energy is also demonstrated in these surface-confined, few-cycle fields with only 1.35×10(12) W/cm2 focused laser intensity. The experimental results are found to be in excellent agreement with the model.

Assessment of the use of a diffuser in propagation-based x-ray phase contrast imaging.

A rotating random-phase-screen diffuser is sometimes employed on synchrotron x-ray imaging beamlines to ameliorate field-of-view inhomogeneities due to electron-beam instabilities and beamline optics phase artifacts. The ideal result is a broader, more uniformly illuminated beam intensity for cleaner coherent x-ray images. The spinning diffuser may be modeled as an ensemble of transversely random thin phase screens, with the resulting set of intensity maps over the detector plane being incoherently averaged over the ensemble. Whilst the coherence width associated with the source is unaffected by the diffuser, the magnitude of the complex degree of second-order coherence may be significantly reduced [K. S. Morgan, S. C. Irvine, Y. Suzuki, K. Uesugi, A. Takeuchi, D. M. Paganin, and K. K. W. Siu, Opt. Commun. 283, 216 (2010)]. Through use of a computational model and experimental data obtained on x-ray beamline BL20XU at SPring-8, Japan, we investigate the effects of such a diffuser on the quality of Fresnel diffraction fringes in propagation-based x-ray phase contrast imaging. We show that careful choice of diffuser characteristics such as thickness and fiber size, together with appropriate placement of the diffuser, can result in the ideal scenario of negligible reduction in fringe contrast whilst the desired diffusing properties are retained.

Influence of the carrier-envelope phase of few-cycle pulses on ponderomotive surface-plasmon electron acceleration.

Control over basic processes through the electric field of a light wave can lead to new knowledge of fundamental light-matter interaction phenomena. We demonstrate, for the first time, that surface-plasmon (SP) electron acceleration can be coherently controlled through the carrier-envelope phase (CEP) of an excitation optical pulse. Analysis indicates that the physical origin of the CEP sensitivity arises from the electron's ponderomotive interaction with the oscillating electromagnetic field of the SP wave. The ponderomotive electron acceleration mechanism provides sensitive (nJ energies), high-contrast, single-shot CEP measurement capability of few-cycle laser pulses.

Transforming growth factor-beta-regulated expression of genes in macrophages implicated in the control of cholesterol homoeostasis.

The regulation of macrophage cholesterol homoeostasis is of crucial importance in the pathogenesis of atherosclerosis, an underlying cause of heart attack and stroke. Several recent studies have revealed a critical role for the cytokine TGF-beta (transforming growth factor-beta), a key regulator of the immune and inflammatory responses, in atherogenesis. We discuss here the TGF-beta signalling pathway and its role in this disease along with the outcome of our recent studies on the action of the cytokine on the expression of key genes implicated in the uptake or efflux of cholesterol by macrophages and the molecular mechanisms underlying such regulation.

Femtosecond electron pulse gating using surface plasmons.

We present a theoretical investigation of a novel all-optical method for electron beam gating via ponderomotive surface plasmon (SP) interaction. Using femtosecond optical pulses, large electric field gradient SP waves are launched on the surface of a metal film and selectively gate an external electron beam. It is shown that this method can generate electron pulses having similar durations as the laser pulse. The ultrashort electron packets are highly directional and examination of their spatial distribution reveals a large degree of spatial microbunching. Angle-resolved energy spectra of the electrons reveal that their final velocities are highly correlated with exit angle. Furthermore, it is demonstrated that the SP gating technique can be utilized for temporal characterization of ultrashort electron pulses with durations <100 fs.

Generation of 0.4-keV femtosecond electron pulses using impulsively excited surface plasmons.

We demonstrate the generation of 0.4-keV, sub-27 fs electron pulses using low-intensity laser pulses from a Ti:sapphire oscillator through the excitation of surface plasmon waves on a time scale within the plasmon lifetime. Modeling of the ponderomotive electron pulse acceleration yields electron energy spectra that are in excellent agreement with the observed ones. Our work opens a doorway for time-resolved experimentation using low-power, high-repetition rate laser pulses.