Simple non-mydriatic retinal photography is feasible and demonstrates retinal microvascular dilation in Chronic Obstructive Pulmonary Disease (COPD).

BACKGROUND: Chronic Obstructive Pulmonary Disease (COPD) is associated with an increased risk of myocardial infarction and stroke but it remains unclear how to identify microvascular changes in this population. OBJECTIVES: We hypothesized that simple non-mydriatic retinal photography is feasible and can be used to assess microvascular damage in COPD. METHODS: Novel Vascular Manifestations of COPD was a prospective study comparing smokers with and without COPD, matched for age. Non-mydriatic, retinal fundus photographs were assessed using semi-automated software. RESULTS: Retinal images from 24 COPD and 22 control participants were compared. Cases were of similar age to controls (65.2 vs. 63.1 years, p = 0.38), had significantly lower Forced Expiratory Volume in one second (FEV1) (53.4 vs 100.1% predicted; p < 0.001) and smoked more than controls (41.7 vs. 29.6 pack years; p = 0.04). COPD participants had wider mean arteriolar (155.6 ±15 uM vs. controls [142.2 ± 12 uM]; p = 0.002) and venular diameters (216.8 ±20.7 uM vs. [201.3± 19.1 uM]; p = 0.012). Differences in retinal vessel caliber were independent of confounders, odds ratios (OR) = 1.08 (95% confidence intervals [CI] = 1.02, 1.13; p = 0.007) and OR = 1.05 (CI = 1.01, 1.09; p = 0.011) per uM increase in arteriolar and venular diameter respectively. FEV1 remained significantly associated with retinal vessel dilatation r = -0.39 (p = 0.02). CONCLUSIONS: Non-mydriatic retinal imaging is easily facilitated. We found significant arteriole and venous dilation in COPD compared to age-matched smokers without COPD associated with lung function independent of standard cardiovascular risk factors. Retinal microvascular changes are known to be strongly associated with future vascular events and retinal photography offers potential to identify this risk. TRIAL REGISTRATION: clinicaltrials.gov NCT02060292

Response to letter to editor: 'Comment on Arch et al., Trials. 2016;17:517'

In October 2015 we published the paper ‘Measurement of HbA1c in multicentre diabetes trials – should blood samples be tested locally or sent to a central laboratory: an agreement analysis’. Chatterjee and Pradhan have submitted a letter to the editor asking critical questions regarding the methods we used. We offer this letter in response

Studying Townsend and glow modes in an atmospheric-pressure DBD using mass spectrometry

Ambient molecular beam mass spectrometry has been employed to examine the effects of the mode of operation and the excitation waveform on the ionic content of a helium-based atmospheric-pressure parallel plate dielectric barrier discharge. By applying 10 kHz microsecond voltage pulses with a nanosecond rise times and 10 kHz sinusoidal voltage waveforms, distinctly different glow and Townsend modes were produced, respectively. Results showed a significant difference in the dominant ion species between the two modes. In the Townsend mode, molecular oxygen ions, atomic oxygen anions and nitric oxide anions are the most abundant species, however, in the glow mode water clusters ions and hydrated nitric oxygen anions dominate. Several hypotheses are put forward to explain these differences, including low electron densities and energies in the Townsend mode, more efficient ionization of water molecules through penning ionization and charge exchange with other species in glow mode, and large temperature gradients due to the pulsed nature of the glow mode, leading to more favorable conditions for cluster formation

Mass spectrometric investigation of the ionic species in a dielectric barrier discharge operating in helium-water vapour mixtures

Using advanced mass spectrometry the chemistry of ionic species present in an atmospheric-pressure parallel plate dielectric barrier discharge (DBD) with a single dielectric on the powered electrode have been identified. The discharge was driven in helium with controllable concentrations of water vapour using an excitation frequency of 10 kHz and an applied voltage of 1.2 kV. Both negative and positive ions were identified and their relative intensity determined with variation of water concentration in the discharge, inter-electrode spacing, gas residence time and nominal applied power. The most abundant negative ions were of the family , while the positive ions were dominated by those of the form , with n up to 9 in both cases. Negative and positive ions responded in a similar way to changes in the operating parameters, with the particular response depending on the ion mass. Increasing the inter-electrode spacing and the water concentration in the discharge led to an increase in the intensity of large mass ionic water clusters. However, increasing the residence time of the species in the plasma region and increasing the applied power resulted in fragmentation of large water clusters to produce smaller ions

Linker-free covalent immobilization of nisin using atmospheric pressure plasma induced grafting

The linker-free covalent immobilization of polymers on surfaces has the potential to impart new properties and functions to surfaces for a wide range of applications. However, most current methods for the production of these surfaces involve multiple chemical steps and do not have a high degree of control over the chemical functionalities at the surface. A comprehensive study detailing the facile two-step covalent grafting of the antimicrobial peptide nisin onto polystyrene surfaces is reported. Functionalization is achieved using an atmospheric pressure plasma jet, and the reaction is monitored and compared with a standard wet chemical functionalization approach using a variety of analytical techniques. The reactive species produced by the atmospheric pressure plasma jet were analyzed by mass spectrometry and optical emission spectroscopy. The surface chemistry and topography of the functionalized surfaces were determined using contact angle measurements, Fourier infrared spectroscopy (FTIR), X-ray photoelectron spectroscopy and atomic force microscopy respectively. Following surface analysis, the antimicrobial efficacy of the covalently grafted nisin against two major food borne pathogens (Staphylococcus aureus and Listeria monocytogenes) was assessed at two different pHs. The results demonstrated that a post-plasma treatment step after nisin deposition is required to covalently graft the peptide onto the surface. The covalent immobilization of nisin resulted in a significant reduction in bacterial counts within a short 30 minutes contact time. These surfaces were also significantly more antimicrobial compared to those prepared via a more traditional wet chemical approach indicating that the reported method could be a less expensive and less time consuming alternative

The impact of the COVID-19 pandemic upon pancreatic cancer treatment (CONTACT Study): a UK national observational cohort study.

INTRODUCTION: CONTACT is a national multidisciplinary study assessing the impact of the COVID-19 pandemic upon diagnostic and treatment pathways among patients with pancreatic ductal adenocarcinoma (PDAC). METHODS: The treatment of consecutive patients with newly diagnosed PDAC from a pre-COVID-19 pandemic cohort (07/01/2019-03/03/2019) were compared to a cohort diagnosed during the first wave of the UK pandemic ('COVID' cohort, 16/03/2020-10/05/2020), with 12-month follow-up. RESULTS: Among 984 patients (pre-COVID: n = 483, COVID: n = 501), the COVID cohort was less likely to receive staging investigations other than CT scanning (29.5% vs. 37.2%, p = 0.010). Among patients treated with curative intent, there was a reduction in the proportion of patients recommended surgery (54.5% vs. 76.6%, p = 0.001) and increase in the proportion recommended upfront chemotherapy (45.5% vs. 23.4%, p = 0.002). Among patients on a non-curative pathway, fewer patients were recommended (47.4% vs. 57.3%, p = 0.004) or received palliative anti-cancer therapy (20.5% vs. 26.5%, p = 0.045). Ultimately, fewer patients in the COVID cohort underwent surgical resection (6.4% vs. 9.3%, p = 0.036), whilst more patients received no anti-cancer treatment (69.3% vs. 59.2% p = 0.009). Despite these differences, there was no difference in median overall survival between the COVID and pre-COVID cohorts, (3.5 (IQR 2.8-4.1) vs. 4.4 (IQR 3.6-5.2) months, p = 0.093). CONCLUSION: Pathways for patients with PDAC were significantly disrupted during the first wave of the COVID-19 pandemic, with fewer patients receiving standard treatments. However, no significant impact on survival was discerned

Optimality Driven Nearest Centroid Classification from Genomic Data

Nearest-centroid classifiers have recently been successfully employed in high-dimensional applications, such as in genomics. A necessary step when building a classifier for high-dimensional data is feature selection. Feature selection is frequently carried out by computing univariate scores for each feature individually, without consideration for how a subset of features performs as a whole. We introduce a new feature selection approach for high-dimensional nearest centroid classifiers that instead is based on the theoretically optimal choice of a given number of features, which we determine directly here. This allows us to develop a new greedy algorithm to estimate this optimal nearest-centroid classifier with a given number of features. In addition, whereas the centroids are usually formed from maximum likelihood estimates, we investigate the applicability of high-dimensional shrinkage estimates of centroids. We apply the proposed method to clinical classification based on gene-expression microarrays, demonstrating that the proposed method can outperform existing nearest centroid classifiers

Longitudinal Fibular Deficiency: A Cross-Sectional Study Comparing Lower Limb Function of Children and Young People with That of Unaffected Peers

Longitudinal fibular deficiency (LFD), or fibular hemimelia, is congenital partial or complete absence of the fibula. We aimed to compare the lower limb function of children and young people with LFD to that of unaffected peers. A cross-sectional study of Australian children and young people with LFD, and of unaffected peers, was undertaken. Twenty-three (12 males) children and young people with LFD (74% of those eligible) and 213 unaffected peers, all aged 7&ndash;21 years were subject to the Knee Osteoarthritis Outcome Score (KOOS/KOOS-Child) and the Cumberland Ankle Instability Tool (CAIT/CAIT-Youth). Linear regression models compared affected children and young people to unaffected peers. Participants with LFD scored lower in both outcomes (adjusted p &lt; 0.05). The difference between participants with LFD and unaffected peers was significantly greater among younger participants than older participants for KOOS activities and sports domain scores (adjusted p &le; 0.01). Differences in the other KOOS domains (pain/symptoms/quality of life) and ankle function (CAIT scores) were not affected by age (adjusted p &ge; 0.08). Children and young people with LFD on average report reduced lower limb function compared to unaffected peers. Knee-related activities and sports domains appear to be worse in younger children with LFD, and scores in these domains become closer to those of unaffected peers as they become older

Force plate monitoring of human hemodynamics

which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Background: Noninvasive recording of movements caused by the heartbeat and the blood circulation is known as ballistocardiography. Several studies have shown the capability of a force plate to detect cardiac activity in the human body. The aim of this paper is to present a new method based on differential geometry of curves to handle multivariate time series obtained by ballistocardiographic force plate measurements. Results: We show that the recoils of the body caused by cardiac motion and blood circulation provide a noninvasive method of displaying the motions of the heart muscle and the propagation of the pulse wave along the aorta and its branches. The results are compared with the data obtained invasively during a cardiac catheterization. We show that the described noninvasive method is able to determine the moment of a particular heart movement or the time when the pulse wave reaches certain morphological structure. Conclusions: Monitoring of heart movements and pulse wave propagation may be used e.g. to estimate the aortic pulse wave velocity, which is widely accepted as an index of aortic stiffness wit

Integrated Polygenic Tool Substantially Enhances Coronary Artery Disease Prediction

BACKGROUND: There is considerable interest in whether genetic data can be used to improve standard cardiovascular disease risk calculators, as the latter are routinely used in clinical practice to manage preventative treatment. METHODS: Using the UK Biobank resource, we developed our own polygenic risk score for coronary artery disease (CAD). We used an additional 60 000 UK Biobank individuals to develop an integrated risk tool (IRT) that combined our polygenic risk score with established risk tools (either the American Heart Association/American College of Cardiology pooled cohort equations [PCE] or UK QRISK3), and we tested our IRT in an additional, independent set of 186 451 UK Biobank individuals. RESULTS: The novel CAD polygenic risk score shows superior predictive power for CAD events, compared with other published polygenic risk scores, and is largely uncorrelated with PCE and QRISK3. When combined with PCE into an IRT, it has superior predictive accuracy. Overall, 10.4% of incident CAD cases were misclassified as low risk by PCE and correctly classified as high risk by the IRT, compared with 4.4% misclassified by the IRT and correctly classified by PCE. The overall net reclassification improvement for the IRT was 5.9% (95% CI, 4.7–7.0). When individuals were stratified into age-by-sex subgroups, the improvement was larger for all subgroups (range, 8.3%–15.4%), with the best performance in 40- to 54-year-old men (15.4% [95% CI, 11.6–19.3]). Comparable results were found using a different risk tool (QRISK3) and also a broader definition of cardiovascular disease. Use of the IRT is estimated to avoid up to 12 000 deaths in the United States over a 5-year period. CONCLUSIONS: An IRT that includes polygenic risk outperforms current risk stratification tools and offers greater opportunity for early interventions. Given the plummeting costs of genetic tests, future iterations of CAD risk tools would be enhanced with the addition of a person’s polygenic risk