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    How long is enough? Identification of product dry-time as a primary driver of alcohol-based hand rub efficacy
    (2018-05) Suchomel, Miranda; Leslie, Rachel; Parker, Albert E.; Macinga, David R.
    Background The World Health Organization has called for the development of improved methodologies to evaluate alcohol-based handrub (ABHR) efficacy, including evaluation at “short application times and volumes that reflect actual use in healthcare facilities”. The objective of this study was to investigate variables influencing ABHR efficacy, under test conditions reflective of clinical use. Methods The test product (60% V/V 2-propanol) was evaluated according to a modified EN 1500 methodology, where application volumes of 1 mL, 2 mL, and 3 mL were rubbed until dry. Statistical analyses were performed to investigate the relative influences of product volume, hand size, and product dry-time on efficacy, and hand size and hand contamination on product dry-time. Results Mean log10 reduction factors (SD) were 1.99 (0.66), 2.96 (0.84) and 3.28 (0.96); and mean dry-times (SD) were 24 s (7 s), 50 s (14 s), and 67 s (20 s) at application volumes of 1 mL, 2 mL, and 3 mL, respectively (p ≤ 0.030). When data were examined at the individual volunteer level, there was a statistically significant correlation between dry-time and log reduction factor (p < 0.0001), independent of application volume. There was also a statistically significant correlation between hand surface area and dry-times (p = 0.047), but no correlation between hand surface area and efficacy (p = 0.698). Conclusions When keeping other variables such as alcohol type and concentration constant, product dry-time appears to be the primary driver of ABHR efficacy suggesting that dosing should be customized to each individual and focus on achieving a product dry-time delivering adequate efficacy.
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    Community Engaged Cumulative Risk Assessment of Exposure to Inorganic Well Water Contaminants, Crow Reservation, Montana
    (2018-01) Eggers, Margaret J.; Doyle, John T.; Lefthand, M. J.; Young, Sara L.; Moore-Nall, Anita L.; Kindness, L.; Medicine, R. O.; Ford, Tim E.; Dietrich, E.; Parker, Albert E.; Hoover, J. H.; Camper, Anne K.
    An estimated 11 million people in the US have home wells with unsafe levels of hazardous metals and nitrate. The national scope of the health risk from consuming this water has not been assessed as home wells are largely unregulated and data on well water treatment and consumption are lacking. Here, we assessed health risks from consumption of contaminated well water on the Crow Reservation by conducting a community-engaged, cumulative risk assessment. Well water testing, surveys and interviews were used to collect data on contaminant concentrations, water treatment methods, well water consumption, and well and septic system protection and maintenance practices. Additive Hazard Index calculations show that the water in more than 39% of wells is unsafe due to uranium, manganese, nitrate, zinc and/or arsenic. Most families’ financial resources are limited, and 95% of participants do not employ water treatment technologies. Despite widespread high total dissolved solids, poor taste and odor, 80% of families consume their well water. Lack of environmental health literacy about well water safety, pre-existing health conditions and limited environmental enforcement also contribute to vulnerability. Ensuring access to safe drinking water and providing accompanying education are urgent public health priorities for Crow and other rural US families with low environmental health literacy and limited financial resources.
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    Surface micropattern reduces colonization and medical device-associated infections
    (2017-11) Xu, Binjie; Wei, Qiuhua; Mettetal, M. Ryan; Han, Jie; Rau, Lindsey; Tie, Jinfeng; May, Rhea M.; Pathe, Eric T.; Reddy, Shravanthi T.; Sullivan, Lauren; Parker, Albert E.; Maul, Donald H.; Brennan, Anthony B.; Mann, Ethan E.
    PURPOSE: Surface microtopography offers a promising approach for infection control. The goal of this study was to provide evidence that micropatterned surfaces significantly reduce the potential risk of medical device-associated infections. METHODOLOGY: Micropatterned and smooth surfaces were challenged in vitro against the colonization and transference of two representative bacterial pathogens - Staphylococcus aureus and Pseudomonas aeruginosa. A percutaneous rat model was used to assess the effectiveness of the micropattern against device-associated S. aureus infections. After the percutaneous insertion of silicone rods into (healthy or immunocompromised) rats, their backs were inoculated with S. aureus. The bacterial burdens were determined in tissues under the rods and in the spleens. RESULTS: The micropatterns reduced adherence by S. aureus (92.3 and 90.5 % reduction for flat and cylindrical surfaces, respectively), while P. aeruginosa colonization was limited by 99.9 % (flat) and 95.5 % (cylindrical). The micropatterned surfaces restricted transference by 95.1 % for S. aureus and 94.9 % for P. aeruginosa, compared to smooth surfaces. Rats with micropatterned devices had substantially fewer S. aureus in subcutaneous tissues (91 %) and spleens (88 %) compared to those with smooth ones. In a follow-up study, immunocompromised rats with micropatterned devices had significantly lower bacterial burdens on devices (99.5 and 99.9 % reduction on external and internal segments, respectively), as well as in subcutaneous tissues (97.8 %) and spleens (90.7 %) compared to those with smooth devices. CONCLUSION: Micropatterned surfaces exhibited significantly reduced colonization and transference in vitro, as well as lower bacterial burdens in animal models. These results indicate that introducing this micropattern onto surfaces has high potential to reduce medical device-associated infections. KEYWORDS: hospital-acquired infections; infections; medical devices; micropatterns
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    Who Goes in and Out of the Hospital Patient Room?
    (2017-06) Arbogast, James W.; Quinn, Jeff; Clark, Tracy; Moore, Lori; Thompson, Maria; Wagner, Pamela; Young, Elizabeth; Parker, Albert E.
    BACKGROUND: The objective of this study was to determine what percentage of entries and exits (E/E) in and out of the patient room should be attributed to healthcare workers (HCWs) in a wide variety of hospital units. This is a critical question for hospitals considering an automated monitoring system (AMS) to measure hand hygiene performance (HHP) as a complement to data from visual observation. HCWs often implicate others and do not perceive a need to change their HH behavior because they are convinced that visitors, patients, and others are responsible for very low HHP data. METHODS: Events (defined as patient room E/E) were observed and recorded by nurses not employed by the hospital. Observations were made in US and Canadian hospital units including emergency, ICU, medical surgical, oncology, and pediatrics. Observers classified events by: HCWs (e.g., nursing staff, aides, doctors, EVS, etc.), patients plus visitors, and other (e.g., clergy, hospice workers). Logistic regression was used to determine who was responsible for the most E/E events by category of individuals. RESULTS: Observers recorded a total of 14,876 E/E events in 29 units of 16 hospitals with units varying in size from 10 to 41 beds. 84.3% of all E/E were attributed to HCWs; 15.0% were from patients plus visitors and 0.7% from others. The odds are 6 to 1 that an E/E into a patient room is by a HCW (P < .0005). Pediatric units had the lowest percentage of HCWs E/E (76.7% total) CONCLUSIONS: This study demonstrates HCWs account for the greatest proportion of hospitalized patient room E/E. Further, the data show that others share a very small percentage of room E/E countering the argument that those individuals are responsible for the low unit HHP measured by AMS. This study demonstrates that other categories of individuals are not a deterrent to increasing unit-level HHP.
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    Type and amount of organic amendments affect enhanced biogenic methane production from coal and microbial community structure
    (2018-01) Davis, Katherine J.; Shipeng, Lu; Barnhart, Elliott P.; Parker, Albert E.; Fields, Matthew W.; Gerlach, Robin
    Slow rates of coal-to-methane conversion limit biogenic methane production from coalbeds. This study demonstrates that rates of coal-to-methane conversion can be increased by the addition of small amounts of organic amendments. Algae, cyanobacteria, yeast cells, and granulated yeast extract were tested at two concentrations (0.1 and 0.5 g/L), and similar increases in total methane produced and methane production rates were observed for all amendments at a given concentration. In 0.1 g/L amended systems, the amount of carbon converted to methane minus the amount produced in coal only systems exceeded the amount of carbon added in the form of amendment, suggesting enhanced coal-to-methane conversion through amendment addition. The amount of methane produced in the 0.5 g/L amended systems did not exceed the amount of carbon added. While the archaeal communities did not vary significantly, the bacterial populations appeared to be strongly influenced by the presence of coal when 0.1 g/L of amendment was added; at an amendment concentration of 0.5 g/L the bacterial community composition appeared to be affected most strongly by the amendment type. Overall, the results suggest that small amounts of amendment are not only sufficient but possibly advantageous if faster in situ coal-to-methane production is to be promoted.
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    An ensemble Kalman filter using the conjugate gradient sampler
    (2013) Bardsley, Johnathan Matheas; Solonen, Antti; Parker, Albert E.; Haario, Heikki; Howard, Marylesa
    The ensemble Kalman filter (EnKF) is a technique for dynamic state estimation. EnKF approximates the standard extended Kalman filter (EKF) by creating an ensemble of model states whose mean and empirical covariance are then used within the EKF formulas. The technique has a number of advantages for large-scale, nonlinear problems. First, large-scale covariance matrices required within EKF are replaced by low-rank and low-storage approximations, making implementation of EnKF more efficient. Moreover, for a nonlinear state space model, implementation of EKF requires the associated tangent linear and adjoint codes, while implementation of EnKF does not. However, for EnKF to be effective, the choice of the ensemble members is extremely important. In this paper, we show how to use the conjugate gradient (CG) method, and the recently introduced CG sampler, to create the ensemble members at each filtering step. This requires the use of a variational formulation of EKF. The effectiveness of the method is demonstrated on both a large-scale linear, and a small-scale, nonlinear, chaotic problem. In our examples, the CG-EnKF performs better than the standard EnKF, especially when the ensemble size is small.
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    Physiology of Pseudomonas aeruginosa in biofilms as revealed by transcriptome analysis
    (2010) Folsom, James P.; Richards, Lee A.; Roe, Frank L.; Ehrlich, Garth D.; Parker, Albert E.; Mazurie, Aurélien J.; Stewart, Philip S.
    BACKGROUND: Transcriptome analysis was applied to characterize the physiological activities of Pseudomonas aeruginosa grown for three days in drip-flow biofilm reactors. Conventional applications of transcriptional profiling often compare two paired data sets that differ in a single experimentally controlled variable. In contrast this study obtained the transcriptome of a single biofilm state, ranked transcript signals to make the priorities of the population manifest, and compared rankings for a priori identified physiological marker genes between the biofilm and published data sets.RESULTS: Biofilms tolerated exposure to antibiotics, harbored steep oxygen concentration gradients, and exhibited stratified and heterogeneous spatial patterns of protein synthetic activity. Transcriptional profiling was performed and the signal intensity of each transcript was ranked to gain insight into the physiological state of the biofilm population. Similar rankings were obtained from data sets published in the GEO database (www.ncbi.nlm.nih.gov/geo). By comparing the rank of genes selected as markers for particular physiological activities between the biofilm and comparator data sets, it was possible to infer qualitative features of the physiological state of the biofilm bacteria. These biofilms appeared, from their transcriptome, to be glucose nourished, iron replete, oxygen limited, and growing slowly or exhibiting stationary phase character. Genes associated with elaboration of type IV pili were strongly expressed in the biofilm. The biofilm population did not indicate oxidative stress, homoserine lactone mediated quorum sensing, or activation of efflux pumps. Using correlations with transcript ranks, the average specific growth rate of biofilm cells was estimated to be 0.08 h-1.CONCLUSIONS: Collectively these data underscore the oxygen-limited, slow-growing nature of the biofilm population and are consistent with antimicrobial tolerance due to low metabolic activity.
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    Symmetry breaking clusters in soft clustering decoding of neural codes
    (2010-02) Parker, Albert E.; Dimitrov, Alexander G.; Gedeon, Tomas
    Information-based distortion methods have been used successfully in the analysis of neural coding problems. These approaches allow the discovery of neural symbols and the corresponding stimulus space of a neuron or neural ensemble quantitatively, while making few assumptions about the nature of either the code or of relevant stimulus features. The neural codebook is derived by quantizing sensory stimuli and neural responses into a small set of clusters, and optimizing the quantization to minimize an information distortion function. The method of annealing has been used to solve the corresponding high-dimensional nonlinear optimization problem. The annealing solutions undergo a series of bifurcations, which we study using bifurcation theory in the presence of symmetries. In this contribution we describe these symmetry breaking bifurcations in detail, and indicate some of the consequences of the form of the bifurcations. In particular, we show that the annealing solutions break symmetry at pitchfork bifurcations, and that subcritical branches can exist. Thus, at a subcritical bifurcation, there are local information distortion solutions which are not found by the method of annealing. Since the annealing procedure is guaranteed to converge to a local solution eventually, the subcritical branch must turn and become optimal at some later saddle-node bifurcation, which we have shown occur generically for this class of problems. This implies that the rate distortion curve, while convex for noninformation-based distortion measures, is not convex for information-based distortion methods.
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    An in vitro model for the growth and analysis of chronic wound MRSA biofilms
    (2011-09) Agostinho, Alessandra; Hartman, A.; Lipp, C.; Parker, Albert E.; Stewart, Philip S.; James, Garth A.
    Aims: To develop an in vitro model (Colony/drip-flow reactor – C/DFR) for the growth and analysis of methicillin-resistant Staphylococcus aureus (MRSA) biofilms. Methods and Results: Using the C/DFR model, biofilms were grown on the top of polycarbonate filter membranes inoculated with a clinical isolate of MRSA, placed on absorbent pads in the DFR and harvested after 72 h. The biofilms varied from 256 to 308 µm in thickness with a repeatability standard deviation of 0·22. Testing of antimicrobial agents was also performed where C/DFR biofilms were grown in parallel with conventional colony biofilms. A saline solution (control), 1% silver sulfadiazine solution, and 0·25% Dakin’s solution were used to treat the biofilms for 15 min. Microscopic evaluation of biofilm morphology and thickness was conducted. The Dakins solution in both models produced statistically significantly higher log reductions than silver sulfadiazine treatment. Conclusions: The C/DFR biofilms were thick and repeatable and exhibited higher resistance to Dakins solution than the treated colony biofilms. Significance and Impact of the Study: The C/DFR can be used as a tool for examining complex biofilm physiology as well as for performing comparative experiments that test wound care products and novel antimicrobials.
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    Comparing the chlorine disinfection of detached biofilm clusters with those of sessile biofilms and planktonic cells in single-and dual-species cultures
    (2011-10) Behnke, S.; Parker, Albert E.; Woodall, Dawn; Camper, Anne K.
    Although the detachment of cells from biofilms is of fundamental importance to the dissemination of organisms in both public health and clinical settings, the disinfection efficacies of commonly used biocides on detached biofilm particles have not been investigated. Therefore, the question arises whether cells in detached aggregates can be killed with disinfectant concentrations sufficient to inactivate planktonic cells. Burkholderia cepacia and Pseudomonas aeruginosa were grown in standardized laboratory reactors as single species and in coculture. Cluster size distributions in chemostats and biofilm reactor effluent were measured. Chlorine susceptibility was assessed for planktonic cultures, attached biofilm, and particles and cells detached from the biofilm. Disinfection tolerance generally increased with a higher percentage of larger cell clusters in the chemostat and detached biofilm. Samples with a lower percentage of large clusters were more easily disinfected. Thus, disinfection tolerance depended on the cluster size distribution rather than sample type for chemostat and detached biofilm. Intact biofilms were more tolerant to chlorine independent of species. Homogenization of samples led to significantly increased susceptibility in all biofilm samples as well as detached clusters for single-species B. cepacia, B. cepacia in coculture, and P. aeruginosa in coculture. The disinfection efficacy was also dependent on species composition; coculture was advantageous to the survival of both species when grown as a biofilm or as clusters detached from biofilm but, surprisingly, resulted in a lower disinfection tolerance when they were grown as a mixed planktonic culture.
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