Segmental Mobility Studies of Poly(N-isopropyl acrylamide) Interactions with Gold Nanoparticles and Its Use as a Thermally Driven Trapping System.

Thermal desolvation of poly(N-isopropylacrylamide) (PNIPAM) in the presence of a low concentration of gold nanoparticles incorporates the nanoparticles resulting in suspended aggregates. By covalently incorporating <1% acenaphthylene into the polymerization feed this copolymer is enabled to be used as a model to study the segmental mobility of the PNIPAM backbone in response to gold nanoparticles both below and above the desolvation temperature, showing that there is a physical conformational rearrangement of the soluble polymer at ultralow nanoparticle loadings, indicating low affinity interactions with the nanoparticles. Thermal desolvation is capable of extracting >99.9% of the nanoparticles from their solutions and hence demonstrates that poly(N-isopropylacrylamide) can act as an excellent scrubbing system to remove metallic nanomaterial pollutants from solution.

Binding of Bacteria to Poly(N-isopropylacrylamide) Modified with Vancomycin: Comparison of Behavior of Linear and Highly Branched Polymers.

The behavior of a linear copolymer of N-isopropylacrylamide with pendant vancomycin functionality was compared to an analogous highly branched copolymer with vancomycin functionality at the chain ends. Highly branched poly(N-isopropylacrylamide) modified with vancomycin (HB-PNIPAM-van) was synthesized by functionalization of the HB-PNIPAM, prepared using reversible addition-fragmentation chain transfer polymerization. Linear PNIPAM with pendant vancomycin functionality (L-PNIPAM-van) was synthesized by functionalization of poly(N-isopropylacrylamide-co-vinyl benzoic acid). HB-PNIPAM-van aggregated S. aureus effectively, whereas the L-PNIPAM-van polymer did not. It was found that when the HB-PNIPAM-van was incubated with S. aureus the resultant phase transition provided an increase in the intensity of fluorescence of a solvatochromic dye, nile red, added to the system. In contrast, a significantly lower increase in fluorescence intensity was obtained when L-PNIPAM-van was incubated with S. aureus. These data showed that the degree of desolvation of HB-PNIPAM-van was much greater than the desolvation of the linear version. Using microcalorimetry, it was shown that there were no significant differences in the affinities of the polymer ligands for d-Ala-d-Ala and therefore differences in the interactions with bacteria were associated with changes in the probability of access of the polymer bound ligands to the d-Ala-d-Ala dipeptide. The data support the hypothesis that generation of polymer systems that respond to cellular targets, for applications such as cell targeting, detection of pathogens etc., requires the use of branched polymers with ligands situated at the chain ends.

Digital ECMT Cancer Trial Matching Tool: an Open Source Research Application to Support Oncologists in the Identification of Precision Medicine Clinical Trials.

PURPOSE: Matching patients with cancer to precision medicine clinical trials on the basis of their tumor genotype has the potential to improve outcomes for patients who have exhausted standard-of-care treatment options. However, the matching process presents a substantial challenge because of the number of clinical trials available. We describe a free, open source research tool designed to extract relevant trial information to support oncologists in the matching process, and we illustrate its utility with recent case studies of patients who were matched to trials using this tool. METHODS: Trial records are sourced from ClinicalTrials.gov and indexed using natural language processing techniques, including named entity recognition, term normalization, and relationship extraction. Relationships between trials and genetic alterations are assigned scores on the basis of a rule-based system. All data are updated daily. A user interface is provided via R Shiny app. RESULTS: An instance of the trial match tool, configured for UK clinical trials, is hosted by the digital Experimental Cancer Medicine Team (see link in Data Sharing Statement). Users select the relevant cancer type and genetic alteration(s). Matching studies are ranked according to the score assigned for the selected genetic alterations. Results may be downloaded and attached to the patient's health record if desired. The tool is currently being used to support the ongoing TARGET National study, which aims to match up to 6,000 patients to early phase clinical trials. We present three case studies that exemplify relationships between genetic alterations and studies. CONCLUSION: With increasing numbers of precision medicine treatments and as comprehensive molecular profiling of tumor samples becomes more common, decision support tools are likely to become increasingly important. This work represents an important step toward the development and wider implementation of such systems.

Screening for influenza A(H1N1)pdm09, Auckland International Airport, New Zealand.

Entry screening for influenza A(H1N1)pdm09 at Auckland International Airport, New Zealand, detected 4 cases, which were later confirmed, among 456,518 passengers arriving April 27-June 22, 2009. On the basis of national influenza surveillance data, which suggest that ≈69 infected travelers passed through the airport, sensitivity for screening was only 5.8%.

Establishment of CORONET, COVID-19 Risk in Oncology Evaluation Tool, to Identify Patients With Cancer at Low Versus High Risk of Severe Complications of COVID-19 Disease On Presentation to Hospital.

PURPOSE: Patients with cancer are at increased risk of severe COVID-19 disease, but have heterogeneous presentations and outcomes. Decision-making tools for hospital admission, severity prediction, and increased monitoring for early intervention are critical. We sought to identify features of COVID-19 disease in patients with cancer predicting severe disease and build a decision support online tool, COVID-19 Risk in Oncology Evaluation Tool (CORONET). METHODS: Patients with active cancer (stage I-IV) and laboratory-confirmed COVID-19 disease presenting to hospitals worldwide were included. Discharge (within 24 hours), admission (≥ 24 hours inpatient), oxygen (O2) requirement, and death were combined in a 0-3 point severity scale. Association of features with outcomes were investigated using Lasso regression and Random Forest combined with Shapley Additive Explanations. The CORONET model was then examined in the entire cohort to build an online CORONET decision support tool. Admission and severe disease thresholds were established through pragmatically defined cost functions. Finally, the CORONET model was validated on an external cohort. RESULTS: The model development data set comprised 920 patients, with median age 70 (range 5-99) years, 56% males, 44% females, and 81% solid versus 19% hematologic cancers. In derivation, Random Forest demonstrated superior performance over Lasso with lower mean squared error (0.801 v 0.807) and was selected for development. During validation (n = 282 patients), the performance of CORONET varied depending on the country cohort. CORONET cutoffs for admission and mortality of 1.0 and 2.3 were established. The CORONET decision support tool recommended admission for 95% of patients eventually requiring oxygen and 97% of those who died (94% and 98% in validation, respectively). The specificity for mortality prediction was 92% and 83% in derivation and validation, respectively. Shapley Additive Explanations revealed that National Early Warning Score 2, C-reactive protein, and albumin were the most important features contributing to COVID-19 severity prediction in patients with cancer at time of hospital presentation. CONCLUSION: CORONET, a decision support tool validated in health care systems worldwide, can aid admission decisions and predict COVID-19 severity in patients with cancer.

An International Comparison of Presentation, Outcomes and CORONET Predictive Score Performance in Patients with Cancer Presenting with COVID-19 across Different Pandemic Waves.

Patients with cancer have been shown to have increased risk of COVID-19 severity. We previously built and validated the COVID-19 Risk in Oncology Evaluation Tool (CORONET) to predict the likely severity of COVID-19 in patients with active cancer who present to hospital. We assessed the differences in presentation and outcomes of patients with cancer and COVID-19, depending on the wave of the pandemic. We examined differences in features at presentation and outcomes in patients worldwide, depending on the waves of the pandemic: wave 1 D614G (n = 1430), wave 2 Alpha (n = 475), and wave 4 Omicron variant (n = 63, UK and Spain only). The performance of CORONET was evaluated on 258, 48, and 54 patients for each wave, respectively. We found that mortality rates were reduced in subsequent waves. The majority of patients were vaccinated in wave 4, and 94% were treated with steroids if they required oxygen. The stages of cancer and the median ages of patients significantly differed, but features associated with worse COVID-19 outcomes remained predictive and did not differ between waves. The CORONET tool performed well in all waves, with scores in an area under the curve (AUC) of >0.72. We concluded that patients with cancer who present to hospital with COVID-19 have similar features of severity, which remain discriminatory despite differences in variants and vaccination status. Survival improved following the first wave of the pandemic, which may be associated with vaccination and the increased steroid use in those patients requiring oxygen. The CORONET model demonstrated good performance, independent of the SARS-CoV-2 variants.

Semi-interpenetrating Polyurethane Network Foams Containing Highly Branched Poly(N-isopropyl acrylamide) with Vancomycin Functionality.

Highly branched poly(N-isopropylacrylamide) (HB-PNIPAM), functionalized with vancomycin at the chain ends, acted as a bacterial adhesive and was incorporated into polyurethane foams to form semi-interpenetrating networks. PNIPAM was labeled with a solvatochromic dye, Nile red. It was found that the thermal response of the polymer was dependent on the architecture, and temperature-dependent color changes were observed within the foam. The foams had open pore structures, and the presence of HB-PNIPAM substantially reduced the shrinkage of the foam as the temperature was increased up to 20 °C. The foams were selectively adhesive for Staphylococcus aureus (Gram-positive bacteria) compared to Pseudomonas aeruginosa (Gram-negative bacteria), and the presence of S. aureus was indicated by increased fluorescence intensity (590-800 nm).

A muscle mimetic polyelectrolyte-nanoclay organic-inorganic hybrid hydrogel: its self-healing, shape-memory and actuation properties.

In this investigation, we report a non-covalent (ionic interlocking and hydrogen bonding) strategy of self-healing in a covalently crosslinked organic-inorganic hybrid nanocomposite hydrogel, with specific emphasis on tuning its properties fitting into a muscle mimetic material. The hydrogel was prepared via an in situ free radical polymerization of sodium acrylate (SA) and successive crosslinking in the presence of starch grafted with poly(2-(methacryloyloxy)ethyl trimethyl ammonium chloride) (PMTAC) and montmorillonite modified with cetyl ammonium bromide (OMMT). This hydrogel shows stimuli triggered self-healing following damage in both neutral and acidic solutions (pH = 7.4 and pH = 1.2). This behavior was reported using stress-strain experiments and rheological analyses of the hydrogel segments joined at their fracture points. The hydrogel was also able to display shape memory properties in the presence of water as well as stimuli (salt, acid and electric impulse) driven actuation behavior. It was observed that the ultimate tensile strength (UTS) of the self-healed hydrogel at pH = 7.4 was comparable to the extensor digitorum longus (EDL) muscle of a New Zealand white rabbit and the as synthesized self-healable hydrogel was found to be non-cytotoxic against NIH 3T3 fibroblast cells.

Highly-branched poly(N-isopropyl acrylamide) functionalised with pendant Nile red and chain end vancomycin for the detection of Gram-positive bacteria.

This study shows how highly branched poly(N-isopropyl acrylamide) (HB-PNIPAM) with a chain pendant solvatochromic dye (Nile red) could provide a fluorescence signal, as end groups bind to bacteria and chain segments become desolvated, indicating the presence of bacteria. Vancomycin was attached to chain ends of HB-PNIPAM or as pendant groups on linear polymers each containing Nile red. Location of the dye was varied between placement in the core of the branched polymer coil or the outer domains. Both calorimetric and fluorescence data showed that branched polymers responded to binding of both the peptide target (D-Ala-D-Aa) and bacteria in a different manner than analogous linear polymers; binding and response was more extensive in the branched variant. The fluorescence data showed that only segments located in the outer domains of branched polymers responded to binding of Gram-positive bacteria with little response when linear analogous polymer or branched polymer with the dye in the inner core was exposed to Staphylococcus aureus.

Integrating open-source technologies to build low-cost information systems for improved access to public health data.

Effective public health practice relies on the availability of public health data sources and assessment tools to convey information to investigators, practitioners, policy makers, and the general public. Emerging communication technologies on the Internet can deliver all components of the "who, what, when, and where" quartet more quickly than ever with a potentially higher level of quality and assurance, using new analysis and visualization tools. Open-source software provides the opportunity to build low-cost information systems allowing health departments with modest resources access to modern data analysis and visualization tools. In this paper, we integrate open-source technologies and public health data to create a web information system which is accessible to a wide audience through the Internet. Our web application, "EpiVue," was tested using two public health datasets from the Washington State Cancer Registry and Washington State Center for Health Statistics. A third dataset shows the extensibility and scalability of EpiVue in displaying gender-based longevity statistics over a twenty-year interval for 3,143 United States counties. In addition to providing an integrated visualization framework, EpiVue's highly interactive web environment empowers users by allowing them to upload their own geospatial public health data in either comma-separated text files or MS Excel spreadsheet files and visualize the geospatial datasets with Google Maps.

Antibiotic functionalised polymers reduce bacterial biofilm and bioburden in a simulated infection of the cornea.

Microbial keratitis can arise from penetrating injuries to the cornea. Corneal trauma promotes bacterial attachment and biofilm growth, which decrease the effectiveness of antimicrobials against microbial keratitis. Improved therapeutic efficacy can be achieved by reducing microbial burden prior to antimicrobial therapy. This paper assesses a highly-branched poly(N-isopropyl acrylamide) with vancomycin end groups (HB-PNIPAM-van), for reducing bacterial attachment and biofilm formation. The polymer lacked antimicrobial activity against Staphylococcus aureus, but significantly inhibited biofilm formation (p = 0.0008) on plastic. Furthermore, pre-incubation of S. aureus cells with HB-PNIPAM-van reduced cell attachment by 50% and application of HB-PNIPAM-van to infected ex vivo rabbit corneas caused a 1-log reduction in bacterial recovery, compared to controls (p = 0.002). In conclusion, HB-PNIPAM-van may be a useful adjunct to antimicrobial therapy in the treatment of corneal infections.

Association of the built environment with physical activity and obesity in older persons.

OBJECTIVE: We examined whether older persons who live in areas that are conducive to walking are more active or less obese than those living in areas where walking is more difficult. METHODS: We used data from the Adult Changes in Thought cohort study for a cross-sectional analysis of 936 participants aged 65 to 97 years. The Walkable and Bikable Communities Project previously formulated a walkability score to predict the probability of walking in King County, Washington. Data from the cohort study were linked to the walkability score at the participant level using a geographic information system. Analyses tested for associations between walkability score and activity and body mass index. RESULTS: Higher walkability scores were associated with significantly more walking for exercise across buffers (circular zones around each respondent's home) of varying radii (for men, odds ratio [OR]=5.86; 95% confidence interval [CI]=1.01, 34.17 to OR=9.14; CI=1.23, 68.11; for women, OR=1.63; CI=0.94, 2.83 to OR=1.77; CI=1.03, 3.04). A trend toward lower body mass index in men living in more walkable neighborhoods did not reach statistical significance. CONCLUSIONS: Findings suggest that neighborhood characteristics are associated with the frequency of walking for physical activity in older people. Whether frequency of walking reduces obesity prevalence is less clear.

Comparing a single-stage geocoding method to a multi-stage geocoding method: how much and where do they disagree?

BACKGROUND: Geocoding methods vary among spatial epidemiology studies. Errors in the geocoding process and differential match rates may reduce study validity. We compared two geocoding methods using 8,157 Washington State addresses. The multi-stage geocoding method implemented by the state health department used a sequence of local and national reference files. The single-stage method used a single national reference file. For each address geocoded by both methods, we measured the distance between the locations assigned by each method. Area-level characteristics were collected from census data, and modeled as predictors of the discordance between geocoded address coordinates. RESULTS: The multi-stage method had a higher match rate than the single-stage method: 99% versus 95%. Of 7,686 addresses were geocoded by both methods, 96% were geocoded to the same census tract by both methods and 98% were geocoded to locations within 1 km of each other by the two methods. The distance between geocoded coordinates for the same address was higher in sparsely populated and low poverty areas, and counties with local reference files. CONCLUSION: The multi-stage geocoding method had a higher match rate than the single-stage method. An examination of differences in the location assigned to the same address suggested that study results may be most sensitive to the choice of geocoding method in sparsely populated or low-poverty areas.

Core (Polystyrene)-Shell [Poly(glycerol monomethacrylate)] Particles.

A set of water-swollen core-shell particles was synthesized by emulsion polymerization of a 1,3-dioxolane functional monomer in water. After removal of the 1,3-dioxolane group, the particles' shells were shown to swell in aqueous media. Upon hydrolysis, the particles increased in size from around 70 to 100-130 nm. A bicinchoninic acid assay and ζ-potential measurements were used to investigate the adsorption of lysozyme, albumin, or fibrinogen. Each of the core-shell particles adsorbed significantly less protein than the noncoated core (polystyrene) particles. Differences were observed as both the amount of difunctional, cross-linking monomer and the amount of shell monomer in the feed were changed. The core-shell particles were shown to be resistant to protein adsorption, and the degree to which the three proteins adsorbed was dependent on the formulation of the shell.

Analysis using size exclusion chromatography of poly(N-isopropyl acrylamide) using methanol as an eluent.

Size Exclusion Chromatography is traditionally carried out in either aqueous or non-polar solvents. A system to present molar mass distributions of polymers using methanol as a mobile phase is presented. This is shown to be a suitable system for determining the molar mass distributions poly(N-isopropylacrylamide)s (PNIPAM); a polymer class that is often difficult to analyze by size exclusion chromatography. DOSY NMR was used to provide intrinsic viscosity data that was used in conjunction with a viscometric detector to provide absolute calibration. Then the utility of the system was shown by providing the absolute molar mass distributions of dispersed highly branched PNIPAM with biologically functional end groups.

Current practices in spatial analysis of cancer data: mapping health statistics to inform policymakers and the public.

BACKGROUND: To communicate population-based cancer statistics, cancer researchers have a long tradition of presenting data in a spatial representation, or map. Historically, health data were presented in printed atlases in which the map producer selected the content and format. The availability of geographic information systems (GIS) with comprehensive mapping and spatial analysis capability for desktop and Internet mapping has greatly expanded the number of producers and consumers of health maps, including policymakers and the public.Because health maps, particularly ones that show elevated cancer rates, historically have raised public concerns, it is essential that these maps be designed to be accurate, clear, and interpretable for the broad range of users who may view them. This article focuses on designing maps to communicate effectively. It is based on years of research into the use of health maps for communicating among public health researchers. RESULTS: The basics for designing maps that communicate effectively are similar to the basics for any mode of communication. Tasks include deciding on the purpose, knowing the audience and its characteristics, choosing a media suitable for both the purpose and the audience, and finally testing the map design to ensure that it suits the purpose with the intended audience, and communicates accurately and effectively. Special considerations for health maps include ensuring confidentiality and reflecting the uncertainty of small area statistics. Statistical maps need to be based on sound practices and principles developed by the statistical and cartographic communities. CONCLUSION: The biggest challenge is to ensure that maps of health statistics inform without misinforming. Advances in the sciences of cartography, statistics, and visualization of spatial data are constantly expanding the toolkit available to mapmakers to meet this challenge. Asking potential users to answer questions or to talk about what they see is still the best way to evaluate the effectiveness of a specific map design.

Analysis of the Auckland 2014 measles outbreak indicates that adolescents and young adults could benefit from catch-up vaccination.

AIM: To analyse the epidemiology, serology and vaccine effectiveness in a recent New Zealand measles outbreak that started in Auckland, from December, 2013 to June, 2014, to guide further preventive measures. METHOD: Cases had a clinically compatible illness, which was either confirmed by PCR or serology, or were linked to a laboratory confirmed case. RESULTS: A total of 113 cases with 3,113 contacts were traced and managed in the Auckland region. Thirteen overseas acquired cases, produced a total of 98 locally acquired secondary cases, (plus two cases with unknown travel history). The majority of cases occurred in adolescents and young adults; 68/113 cases (60.1%) were aged 10 to 19 years. Among cases, 38.9% (44/113) were unimmunised, and 31.8% (36/113) had unknown immunisation status. A further 15.0% (17/113) of cases had received one or two doses of measles, mumps, rubella (MMR) vaccine. Of the contacts who underwent serological testing for immunity (n=735), the lowest levels of serological immunity were observed in people aged 10 to 24 years. Vaccine effectiveness was calculated for the 15-24 year age cohort at 92% (95%CI; 82-97). CONCLUSION: Results suggest that an adolescent catch-up immunisation programme would prevent further outbreaks of imported measles.

Distance from home when death occurs: a population-based study of Washington State, 1989-2002.

OBJECTIVE: For patients who die in hospitals, the regionalization of tertiary health care services may be increasing the home-to-hospital distance, particularly for younger patients whose care is especially regionalized and for whom access to and use of home hospice services remains limited. The objective of this study was to test the hypotheses that the distance from home at the time of death in a hospital has increased over time and is inversely related to the age of the dying patient. METHODS: A population-based case series was conducted in Washington State of all deaths of state residents from 1989 to 2002. The main outcome measure was driving distance between home residence and location at the time of death. RESULTS: The overall mean distance from home to the hospital where death occurred has increased by 1% annually. Children who died in hospitals were much farther from home than their adult counterparts: the mean distance was 37.4 km for neonates and 50.9 km for children who were aged 1 to 9 years, compared with 19.9 km for adults who were aged 60 to 79 years and 14.0 km for patients who were older than 79 years. Disparities of distance were even greater among patients who were at the 90th percentile for distance (85.6 km for neonates compared with 30.8 for patient who were older than 79 years). CONCLUSIONS: The distance between home residence and the hospital where death occurs is greatest for children and has increased over time. Both of these findings have implications for the design of local and regional pediatric end-of-life supportive care services.

EpiQMS: an Internet application for access to public health data for citizens, providers, and public health investigators.

Access to epidemiologic data is critical to public health practice. Unfortunately, most published data are out of date and live databases are inaccessible because of issues of confidentiality, varying user needs, cost, security concerns, and other reasons. EpiQMS is a Web-based application that allows exploratory, statistical, and geographic analysis of public health data. Tables, graphs, and maps with adjustments for small areas are available at three levels: (1) the general public, (2) public health and medical practitioners, and (3) epidemiologists and health officers. The difference in each level is with respect to the presentation of small cell sizes and small geographies as set by the data set custodians.