Validation of the DECAF score to predict hospital mortality in acute exacerbations of COPD

Background Hospitalisation due to acute exacerbations of COPD (AECOPD) is common, and subsequent mortality high. The DECAF score was derived for accurate prediction of mortality and risk strati fi cation to inform patient care. We aimed to validate the DECAF score, internally and externally, and to compare its performance to other predictive tools. Methods The study took place in the two hospitals within the derivation study (internal validation) and in four additional hospitals (external validation) between January 2012 and May 2014. Consecutive admissions were identi fi ed by screening admissions and searching coding records. Admission clinical data, including DECAF indices, and mortality were recorded. The prognostic value of DECAF and other scores were assessed by the area under the receiver operator characteristic (AUROC) curve. Results In the internal and external validation cohorts, 880 and 845 patients were recruited. Mean age was 73.1 (SD 10.3) years, 54.3% were female, and mean (SD) FEV 1 45.5 (18.3) per cent predicted. Overall mortality was 7.7%. The DECAF AUROC curve for inhospital mortality was 0.83 (95% CI 0.78 to 0.87) in the internal cohort and 0.82 (95% CI 0.77 to 0.87) in the external cohort, and was superior to other prognostic scores for inhospital or 30-day mortality. Conclusions DECAF is a robust predictor of mortality, using indices routinely available on admission. Its generalisability is supported by consistent strong performance; it can identify low-risk patients (DECAF 0 – 1) potentially suitable for Hospital at Home or early supported discharge services, and high-risk patients (DECAF 3 – 6) for escalation planning or appropriate early palliation. Trial registration number UKCRN ID 14214

The relationship between vertical leg stiffness and gross mechanical efficiency in cyclists

Background: Professional cyclists have been shown to have a mechanical efficiency that is 11% higher compared to amateur cyclists (Coyle et al. 1991: Med Sci Sports Exerc, 23 (1), 93-107). The variations in power between professional and amateur cyclists are associated with a greater torque development at the first phase of the pedal revolution (Coyle et al. 1991). It has also been shown in cyclists that a relationship exists between vertical leg stiffness and the peak power output (PPO) (r = 0.75, p < 0.01) achieved during a 30 s Wingate test (Pitchers et al. 2013: The relationship of vertical leg stiffness, peak power output and V̇O2max in recreationally active cyclists: identification of the interface between human and bike. 9th Annual Conference of the United Kingdom Strength & Conditioning Association, Nottingham, UK). Vertical leg stiffness may be important to cycling performance as the majority of the force produced is vertical and optimisation of the stretch shortening cycle may limit energy wastage during the propulsive phase (So et al. 2005: Phys Ther Sports, 6, 89-96; Fonda & Sarabon 2010: Sport Sci Rev, 19 (1), 187-210). The relationship between vertical leg stiffness and mechanical efficiency during cycling has yet to be examined. \ud Purpose: To assess the relationship between vertical leg stiffness and gross mechanical efficiency (GE) in cycling. \ud Methods: In a single group, within subjects design, 11 recreationally active male cyclists (age 34 ± 6 y, V̇O2max 57.4 ± 7.5 ml∙kg∙min-1, body mass 81 ± 1.2 kg, stature 1.81 ± 0.06 m) completed two testing sessions, with a minimum of 48 hr rest between each session. In the first testing session participants completed a stiffness familiarisation before an incremental cycle test to establish V̇O2max. At the second session participants completed 20 sub-maximal bilateral hops at a frequency of 2.3 Hz. This was followed by three 8 min sub-maximal cycling bouts at 50, 55 and 60 % of the participants’ individual maximal minute power (MMP) to establish GE (Table I). \ud Results: Mean values for GE and vertical leg stiffness were 19.0 ± 1.4 % and 34.1 ± 9.0 kN∙m-1, respectively. Pearson’s correlation coefficient revealed no relationship between vertical leg stiffness and GE (r = -0.07, p = 0.85). \ud Discussion: The main finding is that in recreationally active male cyclists there is no relationship between vertical leg stiffness and GE. In this group these findings indicate that GE is likely influenced more by other biological systems rather than the mechanical properties of the musculoskeletal system. However, these data may not be reflective of an elite sample where higher leg stiffness might be more likely to influence GE at higher power outputs.\ud Conclusion: Whilst vertical leg stiffness has been shown to have a strong relationship with PPO (Pitchers et al 2013) in recreational cyclists, this is not the case for GE. Further work is needed to establish if this is also the case in an elite population

Intervening to alleviate word-finding difficulties in children: case series data and a computational modelling foundation

We evaluated a simple computational model of productive vocabulary acquisition, applied to simulating two case studies of 7-year-old children with developmental word-finding difficulties across four core behavioural tasks. Developmental models were created, which captured the deficits of each child. In order to predict the effects of intervention, we exposed the computational models to simulated behavioural interventions of two types, targeting the improvement of either phonological or semantic knowledge. The model was then evaluated by testing the predictions from the simulations against the actual results from an intervention study carried out with the two children. For one child it was predicted that the phonological intervention would be effective, and the semantic intervention would not. This was borne out in the behavioural study. For the second child, the predictions were less clear and depended on the nature of simulated damage to the model. The behavioural study found an effect of semantic but not phonological intervention. Through an explicit computational simulation, we therefore employed intervention data to evaluate our theoretical understanding of the processes underlying acquisition of lexical items for production and how they may vary in children with developmental language difficulties

The role of SP-B1-25 peptides in lung surfactant monolayers exposed to gold nanoparticles

YesLung surfactant (LS) monolayers that continuously expand and compress during breathing cycles, act as the first line barrier for inhaled nanoparticles. It is known that nanoparticles which adsorb to the surface of the surfactant layer facilitate the rearrangement of lipids and peptides at various stages of the breathing cycle. However, the structural mechanisms for this ability of the lipid rearrangement are not yet fully understood. Coarse-grained molecular dynamics simulations are performed to investigate the role of surfactant protein B (SP-B) segments (SP-B1–25) in modulating the biophysical properties of the surfactant monolayer in the presence of polydisperse gold nanoparticles (AuNPs) at different concentrations. Herein, we observe that the AuNPs significantly alter the inherent structural and dynamical properties of the monolayer and its components in three different breathing states. When adsorbed into the monolayer, the AuNPs inhibit the ability of the monolayer to recover its surface tension and other properties. The presence of SP-B1–25 in the monolayer accelerates the diffusion of the monolayer phospholipids, contrarily to the role of AuNPs on phospholipid diffusion. Also, the AuNPs and the peptides in the monolayer significantly increase their agglomeration in the presence of one another. Overall, the simulations predict that the presence of polydisperse AuNPs hampers the stability and biophysical functions of the LS in contrast to the role of the peptide. This study provides a clear view of the hydrophobic peptide role in the LS monolayer at the interface along with the interactions and the translocation of AuNPs that could have a significant impact to assess the NPs inhalation.This work was completed with the support of University of Technology Sydney (UTS) FEIT Research Scholarship, UTS IRS (S. I. H.)

Developing a Graphical Route Information Panel (GRIP) for use on the UK motorway network. The first steps

This paper describes the initial stages of research to develop design guidelines and draft designs for Graphical Route Information Panels to be used on the UK motorway network to display traffic congestion information. The studies utilised a funnelling approach to initially capture the broad design principles involving all stakeholders and then narrow down the design options using a range of validation and evaluation activities to achieve the desired design guidelines. Guidance for graphical road based display design is presented along with a methodological approach for the implementation of new designs

Magnetic Field Stimulated Transitions of Excited States in Fast Muonic Helium Ions

It is shown that one can stimulate, by using the present-day laboratory magnetic fields, transitions between the $lm$ sub-levels of fast $\mu He^+$ ions formating in muon catalyzed fusion. Strong fields also cause the self-ionization from highly excited states of such muonic ions. Both effects are the consequence of the interaction of the bound muon with the oscillating field of the Stark term coupling the center-of-mass and muon motions of the $\mu He^+$ ion due to the non-separability of the collective and internal variables in this system. The performed calculations show a possibility to drive the population of the $lm$ sub-levels by applying a field of a few $Tesla$, which affects the reactivation rate and is especially important to the $K\alpha$ $x$-ray production in muon catalyzed fusion. It is also shown that the $2s-2p$ splitting in $\mu He^+$ due to the vacuum polarization slightly decreases the stimulated transition rates.Comment: 5 figure

Levitation of quantum Hall critical states in a lattice model with spatially correlated disorder

The fate of the current carrying states of a quantum Hall system is considered in the situation when the disorder strength is increased and the transition from the quantum Hall liquid to the Hall insulator takes place. We investigate a two-dimensional lattice model with spatially correlated disorder potentials and calculate the density of states and the localization length either by using a recursive Green function method or by direct diagonalization in connection with the procedure of level statistics. From the knowledge of the energy and disorder dependence of the localization length and the density of states (DOS) of the corresponding Landau bands, the movement of the current carrying states in the disorder--energy and disorder--filling-factor plane can be traced by tuning the disorder strength. We show results for all sub-bands, particularly the traces of the Chern and anti-Chern states as well as the peak positions of the DOS. For small disorder strength $W$ we recover the well known weak levitation of the critical states, but we also reveal, for larger $W$, the strong levitation of these states across the Landau gaps without merging. We find the behavior to be similar for exponentially, Gaussian, and Lorentzian correlated disorder potentials. Our study resolves the discrepancies of previously published work in demonstrating the conflicting results to be only special cases of a general lattice model with spatially correlated disorder potentials. To test whether the mixing between consecutive Landau bands is the origin of the observed floating, we truncate the Hilbert space of our model Hamiltonian and calculate the behavior of the current carrying states under these restricted conditions.Comment: 10 pages, incl. 13 figures, accepted for publication in PR

Anterior thalamic nuclei neurons sustain memory

A hippocampal-diencephalic-cortical network supports memory function. The anterior thalamic nuclei (ATN) form a key anatomical hub within this system. Consistent with this, injury to the mammillary body-ATN axis is associated with examples of clinical amnesia. However, there is only limited and indirect support that the output of ATN neurons actively enhances memory. Here, in rats, we first showed that mammillothalamic tract (MTT) lesions caused a persistent impairment in spatial working memory. MTT lesions also reduced rhythmic electrical activity across the memory system. Next, we introduced 8.5 Hz optogenetic theta-burst stimulation of the ATN glutamatergic neurons. The exogenously-triggered, regular pattern of stimulation produced an acute and substantial improvement of spatial working memory in rats with MTT lesions and enhanced rhythmic electrical activity. Neither behaviour nor rhythmic activity was affected by endogenous stimulation derived from the dorsal hippocampus. Analysis of immediate early gene activity, after the rats foraged for food in an open field, showed that exogenously-triggered ATN stimulation also increased Zif268 expression across memory-related structures. These findings provide clear evidence that increased ATN neuronal activity supports memory. They suggest that ATN-focused gene therapy may be feasible to counter clinical amnesia associated with dysfunction in the mammillary body-ATN axis

Effect of denosumab on osteolytic lesion activity after total hip arthroplasty: a single-centre, randomised, double-blind, placebo-controlled, proof of concept trial

Background Osteolysis causes recurrent pain and disability after total hip arthroplasty. We investigated the effect of the human monoclonal antibody denosumab on osteolytic lesion activity in patients undergoing revision total hip arthroplasty surgery to show the biological proof of concept for a non-surgical treatment for the disease. Methods We did a phase 2, randomised, double-blind, placebo-controlled, proof of concept superiority trial at Sheffield Teaching Hospitals, Sheffield, UK. Eligible patients aged 30 years or older and scheduled for revision surgery for symptomatic, radiographically confirmed osteolysis were randomly allocated (1:1) to subcutaneous denosumab (60 mg single-dose) or placebo by an independent pharmacist using a random number table. The primary outcome was the between-group difference in osteoclast number per mm of bone surface of biopsies taken from the osteolytic membrane–bone interface at surgery 8 weeks later, measured by quantitative histomorphometry in all patients who underwent revision surgery. Adverse events were analysed in all randomly assigned participants. This trial is registered with the EU Clinical Trials Register (EudraCT 2011-000541-20). Findings Between Dec 12, 2012, and June 24, 2018, 51 patients were assessed for eligibility, of whom 24 were randomly assigned to study treatment. Two patients had their revision surgery cancelled for unrelated reasons, leaving 22 patients (ten in the denosumab group) for analysis of the primary outcome. There were 83% fewer osteoclasts at the osteolysis membrane–bone interface in the denosumab versus the placebo group (median 0·05 per mm [IQR 0·11] vs 0·30 mm [0·40], p=0·011). No deaths or treatment-related serious adverse events occurred. Seven adverse events, including one severe adverse event, occurred in four (36%) of 11 patients in the denosumab group. In the placebo group ten adverse events, including three severe adverse events, occurred in five (38%) of 13 patients. Interpretation To our knowledge, this is the first clinical trial of an investigational drug for osteolysis that shows tissue-specific biological efficacy. These results justify the need for future trials that target earlier-stage disease to test for clinical efficacy in reducing the need for revision surgery. Funding Amgen