Development of an antimicrobial blended white LED system containing pulsed 405-nm LEDs for decontamination applications

This study details the design, build and testing of a prototype antimicrobial blended white light unit containing pulsed red, yellow, green and 405nm LEDs. With a push for alternative methods of disinfection, optical methods have become a topic of interest. Ultra-violet (UV) light is widely known for its antimicrobial properties however; 405nm light has demonstrated significant antimicrobial properties against many common hospital acquired pathogens. In this study, a pulsed, blended, white-light prototype with a high content of 405 nm antimicrobial light, was designed, built and tested. Antimicrobial efficacy testing of the prototype was conducted using Staphylococcus aureus and Pseudomonas. aeruginosa, two bacteria which are common causes of hospital acquired infections. These were exposure to 3 different light outputs from the prototype and the surviving bacteria enumerated. Results showed that the mixed light output provided a much better CRI and light output under which to work. Also, the light output containing 405 nm light provided an antimicrobial effect, with decontamination of 103 CFUml-1 populations of both bacterial species. The other light content (red, yellow, green) had no beneficial or adverse effects on the antimicrobial properties of the 405nm light. The results suggest that with further development, it could be possible to produce an antimicrobial blended white light containing pulsed 405nm light that could supplement or even replace standard white lighting in certain environments

Pulsed ultraviolet light decontamination of artificially-generated microbiological aerosols

Airborne transmission of infectious organisms is a major public health concern, particularly within healthcare and communal public environments. Methods of environmental decontamination utilising pulsed ultraviolet (UV) light are currently available, however it is important that germicidal efficacy against airborne contamination is established. This study demonstrates evidence of the dose-response kinetics of airborne bacterial contamination when exposed to pulsed UV-rich (PUV) light. Bacterial aerosols (Staphylococcus epidermidis) were generated using a 6-Jet Collison nebuliser, and introduced into a custom-designed aerosol chamber which enabled prolonged airborne suspension and circulation. Bacterial aerosols were exposed to short duration pulses (~20 µs) of UV-rich light emitted from a xenon-filled flashlamp. The lamp was operated using a 1 kV solid–state pulsed power source, with a pulse frequency of 1 Hz, and output energy of 20 J/pulse. Post-treatment, air samples were extracted from the chamber using a BioSampler liquid impinger, and the surviving fraction was enumerated using standard microbiological culture methods. Results demonstrate successful aerosol inactivation, with a 66.4% reduction achieved with only 10 pulses of UV-rich light (P=<0.0002). Inactivation using continuous UV light was also investigated in order to quantify the comparative efficacy of these antimicrobial light regions. In addition to determining the inactivation kinetics, the spectral outputs of the pulsed and continuous UV sources were captured and compared in order to assess their comparative UV-C content, and subsequently assess how this UV content relates to their germicidal efficiency. Overall, results provide evidence of the dose-response kinetics of bacterial aerosols to PUV-rich light. As with continuous UV light, safety restrictions limit its application to unoccupied environments, or within sealed enclosures such as air handling units, however the reduced treatment times with PUV provides operational advantages over continuous light treatment

Coupling Control Variates for Markov Chain Monte Carlo

We show that Markov couplings can be used to improve the accuracy of Markov chain Monte Carlo calculations in some situations where the steady-state probability distribution is not explicitly known. The technique generalizes the notion of control variates from classical Monte Carlo integration. We illustrate it using two models of nonequilibrium transport

Efficacy of Pulsed 405-nm LEDs for antimicrobial photodynamic inactivation : effects of intensity, frequency, and duty cycle

Objective: This study investigates possible advantages in pulsed over continuous 405-nm LED-light for bacterial inactivation and energy efficiency. Background: Alternative non-antibiotic methods of disinfection and infection control have become of significant interest. Recent studies have demonstrated the application of systems using 405-nm light-emitting diodes for continuous disinfection of the clinical environment, and also for potential treatment of contaminated wounds. Methods: Liquid suspensions of 103 CFU/ml populations of Staphylococcus aureus were subject to pulsed 405-nm light of different frequencies, duty cycles and intensities, and for different lengths of time. Results: Pulsed exposures with the same average irradiance of 16 mWcm2 and varying duty cycle (25%, 50%, 75%), showed very similar performance compared with continuous exposures, with 95-98% reduction of S. aureus achieved for all duty cycles. The pulsing frequency was varied in intervals from 100 Hz - 10 kHz and appeared to have little effect on antimicrobial efficacy. However, when comparing pulsed with continuous exposure, an improvement in inactivation per unit optical energy was achieved, with results showing an increase of approximately 83% in optical efficiency. Conclusions: These results suggest that under pulsed conditions a lower energy consumption and lower perceived brightness could be achieved, thus potentially providing improved operating conditions for medical/infection-control applications without compromising antimicrobial efficacy

Stochastic modelling of reaction-diffusion processes: algorithms for bimolecular reactions

Several stochastic simulation algorithms (SSAs) have been recently proposed for modelling reaction-diffusion processes in cellular and molecular biology. In this paper, two commonly used SSAs are studied. The first SSA is an on-lattice model described by the reaction-diffusion master equation. The second SSA is an off-lattice model based on the simulation of Brownian motion of individual molecules and their reactive collisions. In both cases, it is shown that the commonly used implementation of bimolecular reactions (i.e. the reactions of the form A + B -> C, or A + A -> C) might lead to incorrect results. Improvements of both SSAs are suggested which overcome the difficulties highlighted. In particular, a formula is presented for the smallest possible compartment size (lattice spacing) which can be correctly implemented in the first model. This implementation uses a new formula for the rate of bimolecular reactions per compartment (lattice site).Comment: 33 pages, submitted to Physical Biolog

Finite-size and correlation-induced effects in Mean-field Dynamics

The brain's activity is characterized by the interaction of a very large number of neurons that are strongly affected by noise. However, signals often arise at macroscopic scales integrating the effect of many neurons into a reliable pattern of activity. In order to study such large neuronal assemblies, one is often led to derive mean-field limits summarizing the effect of the interaction of a large number of neurons into an effective signal. Classical mean-field approaches consider the evolution of a deterministic variable, the mean activity, thus neglecting the stochastic nature of neural behavior. In this article, we build upon two recent approaches that include correlations and higher order moments in mean-field equations, and study how these stochastic effects influence the solutions of the mean-field equations, both in the limit of an infinite number of neurons and for large yet finite networks. We introduce a new model, the infinite model, which arises from both equations by a rescaling of the variables and, which is invertible for finite-size networks, and hence, provides equivalent equations to those previously derived models. The study of this model allows us to understand qualitative behavior of such large-scale networks. We show that, though the solutions of the deterministic mean-field equation constitute uncorrelated solutions of the new mean-field equations, the stability properties of limit cycles are modified by the presence of correlations, and additional non-trivial behaviors including periodic orbits appear when there were none in the mean field. The origin of all these behaviors is then explored in finite-size networks where interesting mesoscopic scale effects appear. This study leads us to show that the infinite-size system appears as a singular limit of the network equations, and for any finite network, the system will differ from the infinite system

The Application of Digital Pathology to Improve Accuracy in Glomerular Enumeration in Renal Biopsies.

BACKGROUND: In renal biopsy reporting, quantitative measurements, such as glomerular number and percentage of globally sclerotic glomeruli, is central to diagnostic accuracy and prognosis. The aim of this study is to determine the number of glomeruli and percent globally sclerotic in renal biopsies by means of registration of serial tissue sections and manual enumeration, compared to the numbers in pathology reports from routine light microscopic assessment. DESIGN: We reviewed 277 biopsies from the Nephrotic Syndrome Study Network (NEPTUNE) digital pathology repository, enumerating 9,379 glomeruli by means of whole slide imaging. Glomerular number and the percentage of globally sclerotic glomeruli are values routinely recorded in the official renal biopsy pathology report from the 25 participating centers. Two general trends in reporting were noted: total number per biopsy or average number per level/section. Both of these approaches were assessed for their accuracy in comparison to the analogous numbers of annotated glomeruli on WSI. RESULTS: The number of glomeruli annotated was consistently higher than those reported (p CONCLUSIONS: Although glass slides were not available for direct comparison to whole slide image annotation, this study indicates that routine manual light microscopy assessment of number of glomeruli is inaccurate, and the magnitude of this error is proportional to the total number of glomeruli

The Application of Digital Pathology to Improve Accuracy in Glomerular Enumeration in Renal Biopsies

In renal biopsy reporting, quantitative measurements, such as glomerular number and percentage of globally sclerotic glomeruli, is central to diagnostic accuracy and prognosis. The aim of this study is to determine the number of glomeruli and percent globally sclerotic in renal biopsies by means of registration of serial tissue sections and manual enumeration, compared to the numbers in pathology reports from routine light microscopic assessment

Food for contagion : synthesis and future directions for studying host-parasite responses to resource shifts in anthropogenic environments

Human-provided resource subsidies for wildlife are diverse, common and have profound consequences for wildlife-pathogen interactions, as demonstrated by papers in this themed issue spanning empirical, theoretical and management perspectives from a range of study systems. Contributions cut across scales of organization, from the within-host dynamics of immune function, to population-level impacts on parasite transmission, to landscape-and regional-scale patterns of infection. In this concluding paper, we identify common threads and key findings from author contributions, including the consequences of resource subsidies for (i) host immunity; (ii) animal aggregation and contact rates; (iii) host movement and landscape-level infection patterns; and (iv) interspecific contacts and cross-species transmission. Exciting avenues for future work include studies that integrate mechanistic modelling and empirical approaches to better explore cross-scale processes, and experimental manipulations of food resources to quantify host and pathogen responses. Work is also needed to examine evolutionary responses to provisioning, and ask how diet-altered changes to the host microbiome influence infection processes. Given the massive public health and conservation implications of anthropogenic resource shifts, we end by underscoring the need for practical recommendations to manage supplemental feeding practices, limit human-wildlife conflicts over shared food resources and reduce cross-species transmission risks, including to humans. This article is part of the theme issue 'Anthropogenic resource subsidies and host-parasite dynamics in wildlife'.Peer reviewe

Obstructive pulmonary disease in patients with previous tuberculosis: Pathophysiology of a community-based cohort

Background. An association between chronic airflow limitation (CAL) and a history of pulmonary tuberculosis (PTB) has been confirmed in epidemiological studies, but the mechanisms responsible for this association are unclear. It is debated whether CAL in this context should be viewed as chronic obstructive pulmonary disease (COPD) or a separate phenotype. Objective. To compare lung physiology and high-resolution computed tomography (HRCT) findings in subjects with CAL and evidence of previous (healed) PTB with those in subjects with smoking-related COPD without evidence of previous PTB. Methods. Subjects with CAL identified during a Burden of Obstructive Lung Disease (BOLD) study performed in South Africa were studied. Investigations included questionnaires, lung physiology (spirometry, body plethysmography and diffusing capacity) and quantitative HRCT scans to assess bronchial anatomy and the presence of emphysema (–200 HU). Findings in subjects with a past history and/or HRCT evidence of PTB were compared with those in subjects without these features. Results. One hundred and seven of 196 eligible subjects (54.6%) were enrolled, 104 performed physiology tests and 94 had an HRCT scan. Based on history and HRCT findings, subjects were categorised as no previous PTB (NPTB, n=31), probable previous PTB (n=33) or definite previous PTB (DPTB, n=39). Subjects with DPTB had a lower diffusing capacity (Δ=–17.7%; p=0.001) and inspiratory capacity (Δ=–21.5%; p=0.001) than NPTB subjects, and higher gas-trapping and fibrosis but not emphysema scores (Δ=+6.2% (p=0.021), +0.36% (p=0.017) and +3.5% (p=0.098), respectively). Conclusions. The mechanisms of CAL associated with previous PTB appear to differ from those in the more common smoking-related COPD and warrant further study..info:eu-repo/semantics/publishedVersio