Sub-picoliter Traceability of Microdroplet Gravimetry and Microscopy.

Gravimetry typically lacks the resolution to measure single microdroplets, whereas microscopy is often inaccurate beyond the resolution limit. To address these issues, we advance and integrate these complementary methods, introducing simultaneous measurements of the same microdroplets, comprehensive calibrations that are independently traceable to the International System of Units (SI), and Monte-Carlo evaluations of volumetric uncertainty. We achieve sub-picoliter agreement of measurements of microdroplets in flight with volumes of approximately 70 pL, with ensemble gravimetry and optical microscopy both yielding 95% coverage intervals of ±0.6 pL, or relative uncertainties of ±0.9%, and root-mean-square deviations of mean values between the two methods of 0.2 pL or 0.3%. These uncertainties match previous gravimetry results and improve upon previous microscopy results by an order of magnitude. Gravimetry precision depends on the continuity of droplet formation, whereas microscopy accuracy requires that optical diffraction from an edge reference matches that from a microdroplet. Applying our microscopy method, we jet and image water microdroplets suspending fluorescent nanoplastics, count nanoplastic particles after deposition and evaporation, and transfer volumetric traceability to the number concentrations of single microdroplets. We expect that our methods will impact diverse fields involving dimensional metrology and volumetric analysis of microdroplets, including inkjet microfabrication, disease transmission, and industrial sprays.

Inpatient Rehabilitation After Pediatric and Adolescent Trauma: Outcomes and Discharge Needs.

INTRODUCTION: Traumatic injury is the leading cause of pediatric mortality and morbidity in the United States. Pediatric trauma survivors requiring inpatient rehabilitation (IPR) require coordinated, multispecialty follow-up. Knowledge of the nature and level of disability is necessary for planning this continued care that is specific to the needs of pediatric trauma patients. This study aims to describe the outcomes of pediatric and adolescent trauma patients using measures of functional progression. MATERIALS AND METHODS: A retrospective review of trauma patients aged ≤18 y admitted to IPR between January 2018 and December 2020 at the only certified pediatric rehabilitation center in the region was performed. RESULTS: Ninety five children and adolescents were admitted to IPR after traumatic injury with diagnoses of multitrauma (MT, N = 18), traumatic brain injury (TBI, N = 59), and spinal cord injury (SCI, N = 18). School aged children returned to school at high rates for all injury types (MT: 86.7%, TBI: 97.4%, SCI: 93.8%, P = ns). All groups had similar hospital and rehabilitation length of stay, and most patients required a durable medical equipment at discharge (79%). Using pediatric functional independence measure scoring progression from admission to discharge from IPR, SCI patients made significant improvement in bladder function and the least improvement in stair function. Patients sustaining a TBI made significant improvement in memory and comprehension tasks. CONCLUSIONS: Pediatric and adolescent trauma patients admitted to IPR had a positive progression during their therapy but required variable ongoing care depending on the mechanism of injury. Excellent rates of returning to school were seen across the three injury types.

Quantification of Carbon Nanotubes in Environmental Matrices: Current Capabilities, Case Studies, and Future Prospects.

Carbon nanotubes (CNTs) have numerous exciting potential applications and some that have reached commercialization. As such, quantitative measurements of CNTs in key environmental matrices (water, soil, sediment, and biological tissues) are needed to address concerns about their potential environmental and human health risks and to inform application development. However, standard methods for CNT quantification are not yet available. We systematically and critically review each component of the current methods for CNT quantification including CNT extraction approaches, potential biases, limits of detection, and potential for standardization. This review reveals that many of the techniques with the lowest detection limits require uncommon equipment or expertise, and thus, they are not frequently accessible. Additionally, changes to the CNTs (e.g., agglomeration) after environmental release and matrix effects can cause biases for many of the techniques, and biasing factors vary among the techniques. Five case studies are provided to illustrate how to use this information to inform responses to real-world scenarios such as monitoring potential CNT discharge into a river or ecotoxicity testing by a testing laboratory. Overall, substantial progress has been made in improving CNT quantification during the past ten years, but additional work is needed for standardization, development of extraction techniques from complex matrices, and multimethod comparisons of standard samples to reveal the comparability of techniques.

Information-seeking among chronic disease prevention staff in state health departments: use of academic journals.

Use of scientific evidence aids in ensuring that public health interventions have the best possible health and economic return on investment. We describe use of academic journals by state health department chronic disease prevention staff to find public health evidence. We surveyed more than 900 state health department staff from all states and the District of Columbia. Participants identified top journals or barriers to journal use. We used descriptive statistics to examine individual and aggregate state health department responses. On average, 45.7% of staff per state health department use journals. Common barriers to use included lack of time, lack of access, and expense. Strategies for increasing journal use are provided.

Health care system collaboration to address chronic diseases: a nationwide snapshot from state public health practitioners.

INTRODUCTION: Until recently, health care systems in the United States often lacked a unified approach to prevent and manage chronic disease. Recent efforts have been made to close this gap through various calls for increased collaboration between public health and health care systems to better coordinate provision of services and programs. Currently, the extent to which the public health workforce has responded is relatively unknown. The objective of this study is to explore health care system collaboration efforts and activities among a population-based sample of state public health practitioners. METHODS: During spring 2013, a national survey was administered to state-level chronic disease public health practitioners. Respondents were asked to indicate whether or not they collaborate with health care systems. Those who reported "yes" were asked to indicate all topic areas in which they collaborate and provide qualitative examples of their collaborative work. RESULTS: A total of 759 respondents (84%) reported collaboration. Common topics of collaboration activities were tobacco, cardiovascular health, and cancer screening. More client-oriented interventions than system-wide interventions were found in the qualitative examples provided. Respondents who collaborated were also more likely to use the Community Guide, use evidence-based decision making, and work in program areas that involved secondary, rather than primary, prevention. CONCLUSION: The study findings indicate a need for greater guidance on collaboration efforts that involve system-wide and cross-system interventions. Tools such as the Community Guide and evidence-based training courses may be useful in providing such guidance.

Loading and distribution of a model small molecule drug in poly(N-isopropylacrylamide) brushes: a neutron reflectometry and AFM study.

The structure of a hydrated poly(N-isopropylacrylamide) brush loaded with 5 vol % Isoniazid is studied as a function of temperature using neutron reflectometry (NR) and atomic force microscopy (AFM). NR measurements show that Isoniazid increases the thickness of the brush before, during and after the polymer collapse, and it is retained inside the brush at all measured temperatures. The Isoniazid concentration in the expanded brush is ~14% higher than in the bulk solution, and the concentration nearly doubles in the collapsed polymer, suggesting stronger binding between Isoniazid and the polymer compared to water, even at temperatures below the lower critical solution temperature (LCST) where the polymer is hydrophilic. Typically, additives that bind strongly to the polymer backbone and increase the hydrophilicity of the polymer will delay the onset of the LCST, which is suggested by AFM and NR measurements. The extent of small-molecule loading and distribution throughout a thermo-responsive polymer brush, such as pNIPAAm, will have important consequences for applications such as drug delivery and gating.

Single molecule tracking studies of lower critical solution temperature transition behavior in poly(N-isopropylacrylamide).

Spatial and temporal heterogeneities in expanded and collapsed surface bound poly(N-isopropylacrylamide), pNIPAAm, films are studied by single molecule tracking (SMT) experiments. Tracking data are analyzed using both radius of gyration (R(g)) evolution and confinement level calculations to elucidate the range of behaviors displayed by single Rhodamine6G (R6G) molecules. Confined diffusion that is dictated by the free volume within surface tethered chains is observed with considerable dispersion among individual R6G molecules. Thus, the distribution of probe behavior reflects nanometer-scale information about the behavior of the probe-polymer system at temperatures above (T > T(LCST)) and below (T < T(LCST)) the lower critical solution temperature (LCST). In this context, confinement-level analysis and R(g) evolution both show a larger degree of confinement of the probe in pNIPAAm at T > T(LCST). Temperature-dependent changes in confinement are evidenced at T > T(LCST) by a higher percentage of confined steps, longer periods of confined events, and smaller area of confined zones, as well as a shift in the overall distribution of R(g) evolution paths and final R(g) distributions.

Trajectory analysis of single molecules exhibiting non-brownian motion.

Four techniques for analyzing single molecule tracking data--confinement level analysis, time series analysis and statistical analysis of lateral diffusion, multistate kinetics, and a newly developed method, radius of gyration evolution analysis--are compared using a set of sample fluorophore trajectories obtained from the lipophilic carbocyanine dye 1,1'-dioctadecyl-3,3,3'3'-tetramethylindocarbocyanine, DiIC(18), partitioned into surface tethered poly(n-isopropylacrylamide). The purpose here is two-fold: first to test that these techniques can be applied to single molecules trajectories, which typically contain a smaller total number of frames than those obtained from other particles, e.g. quantum dots or gold nanoparticles; and second to critically compare the information obtained from each method against the others. A set of five SMT trajectories, ranging in length from 41 to 273 steps with a 30 ms frame transfer exposure, were all successfully analyzed by all four techniques, provided two important criteria were met: enough steps to define the motion were acquired in the trajectory, generally on the order of 50 steps, and the fast and slow diffusion coefficients differ by at least a factor of 5. Beyond that the four trajectory analysis methods studied provide partially confirmatory and partially complementary information. SMT data resulting from more complex physical behavior may well benefit from using these techniques in succession to identify and sort populations.

HSD10 disease in a female: A case report and review of literature.

HSD10 disease is a rare X-linked mitochondrial disorder caused by pathogenic variants in the HSD17B10 gene. The phenotype results from impaired 17ß-hydroxysteroid dehydrogenase 10 (17ß-HSD10) protein structure and function. HSD10 is a multifunctional protein involved in enzymatic degradation of isoleucine and branched-chain fatty acids, the metabolism of sex hormones and neurosteroids, as well as in regulating mitochondrial RNA maturation. HSD10 disease is characterised by progressive neurologic impairment. Disease onset is varied and includes neonatal-onset, infantile-onset and late-onset in males. Females can also be affected. Our index case is a 45-month-old female, who initially presented at 11 months of age with global developmental delay. She subsequently began to lose previously acquired cognitive and motor skills starting around 29 months of age. Brain MRI showed abnormalities in the basal ganglia indicative of possible mitochondrial disease. Urine organic acid analysis revealed elevations of 2-methyl-3-hydroxybutyric acid and tiglyglycine. HSD17B10 gene sequencing revealed a likely pathogenic variant, NM_001037811.2:c.439C>T (p.Arg147Cys) inherited from her mother, expected to be causative of HSD10 disease. Her X-chromosome inactivation study is consistent with a skewed X-inactivation pattern. We report a female patient with HSD10 disease caused by a missense pathogenic variant, Arg147Cys in the HSD17B10 gene. The patient is the fifth severely affected female with this disease. This case adds to the small number of known affected families with this highly variable disease in the literature. These findings support the possibility of X-inactivation patterns influencing the penetrance of HSD10 disease in females.

Clinical impact of pharmacogenetic profiling with a clinical decision support tool in polypharmacy home health patients: A prospective pilot randomized controlled trial.

BACKGROUND: In polypharmacy patients under home health management, pharmacogenetic testing coupled with guidance from a clinical decision support tool (CDST) on reducing drug, gene, and cumulative interaction risk may provide valuable insights in prescription drug treatment, reducing re-hospitalization and emergency department (ED) visits. We assessed the clinical impact of pharmacogenetic profiling integrating binary and cumulative drug and gene interaction warnings on home health polypharmacy patients. METHODS AND FINDINGS: This prospective, open-label, randomized controlled trial was conducted at one hospital-based home health agency between February 2015 and February 2016. Recruitment came from patient referrals to home health at hospital discharge. Eligible patients were aged 50 years and older and taking or initiating treatment with medications with potential or significant drug-gene-based interactions. Subjects (n = 110) were randomized to pharmacogenetic profiling (n = 57). The study pharmacist reviewed drug-drug, drug-gene, and cumulative drug and/or gene interactions using the YouScript® CDST to provide drug therapy recommendations to clinicians. The control group (n = 53) received treatment as usual including pharmacist guided medication management using a standard drug information resource. The primary outcome measure was the number of re-hospitalizations and ED visits at 30 and 60 days after discharge from the hospital. The mean number of re-hospitalizations per patient in the tested vs. untested group was 0.25 vs. 0.38 at 30 days (relative risk (RR), 0.65; 95% confidence interval (CI), 0.32-1.28; P = 0.21) and 0.33 vs. 0.70 at 60 days following enrollment (RR, 0.48; 95% CI, 0.27-0.82; P = 0.007). The mean number of ED visits per patient in the tested vs. untested group was 0.25 vs. 0.40 at 30 days (RR, 0.62; 95% CI, 0.31-1.21; P = 0.16) and 0.39 vs. 0.66 at 60 days (RR, 0.58; 95% CI, 0.34-0.99; P = 0.045). Differences in composite outcomes at 60 days (exploratory endpoints) were also found. Of the total 124 drug therapy recommendations passed on to clinicians, 96 (77%) were followed. These findings should be verified with additional prospective confirmatory studies involving real-world applications in larger populations to broaden acceptance in routine clinical practice. CONCLUSIONS: Pharmacogenetic testing of polypharmacy patients aged 50 and older, supported by an appropriate CDST, considerably reduced re-hospitalizations and ED visits at 60 days following enrollment resulting in potential health resource utilization savings and improved healthcare. TRIAL REGISTRATION: ClinicalTrials.gov NCT02378220.

Separation, Sizing, and Quantitation of Engineered Nanoparticles in an Organism Model Using Inductively Coupled Plasma Mass Spectrometry and Image Analysis.

For environmental studies assessing uptake of orally ingested engineered nanoparticles (ENPs), a key step in ensuring accurate quantification of ingested ENPs is efficient separation of the organism from ENPs that are either nonspecifically adsorbed to the organism and/or suspended in the dispersion following exposure. Here, we measure the uptake of 30 and 60 nm gold nanoparticles (AuNPs) by the nematode, Caenorhabditis elegans, using a sucrose density gradient centrifugation protocol to remove noningested AuNPs. Both conventional inductively coupled plasma mass spectrometry (ICP-MS) and single particle (sp)ICP-MS are utilized to measure the total mass and size distribution, respectively, of ingested AuNPs. Scanning electron microscopy/energy-dispersive X-ray spectroscopy (SEM/EDS) imaging confirmed that traditional nematode washing procedures were ineffective at removing excess suspended and/or adsorbed AuNPs after exposure. Water rinsing procedures had AuNP removal efficiencies ranging from 57 to 97% and 22 to 83%, while the sucrose density gradient procedure had removal efficiencies of 100 and 93 to 98%, respectively, for the 30 and 60 nm AuNP exposure conditions. Quantification of total Au uptake was performed following acidic digestion of nonexposed and Au-exposed nematodes, whereas an alkaline digestion procedure was optimized for the liberation of ingested AuNPs for spICP-MS characterization. Size distributions and particle number concentrations were determined for AuNPs ingested by nematodes with corresponding confirmation of nematode uptake via high-pressure freezing/freeze substitution resin preparation and large-area SEM imaging. Methods for the separation and in vivo quantification of ENPs in multicellular organisms will facilitate robust studies of ENP uptake, biotransformation, and hazard assessment in the environment.

Evidence-Based Diabetes Prevention and Control Programs and Policies in Local Health Departments.

PURPOSE: The purpose of this study is to: (1) assess implementation of evidence-based programs and policies (EBPPs) related to diabetes prevention and control in local health departments, (2) assess feasibility of non-implemented diabetes prevention and control EBPPs, and (3) examine individual- and organizational-level factors associated with implementation of diabetes prevention and control EBPPs. METHODS: An online survey was administered in January 2015 to key representatives of all local health departments in Missouri. Descriptive statistics were used to describe implementation and perceived feasibility of 20 diabetes prevention and control EBPPs. Logistic regression was used to examine the association between individual and organizational factors and diabetes prevention and control EBPP implementation. RESULTS: One hundred local health departments participated (89% response rate) in the online survey. Most frequently implemented diabetes-related EBPPs in local health departments included: nutrition education for agency or community members, increased fruit and vegetable access in community settings, and community-wide campaigns to promote physical activity. Increased encouragement to others in the department to use evidence-based decision making and agency incentives to help employees use evidence-based decision making were positively associated with implementation of diabetes prevention and control EBPPs. CONCLUSIONS: Local health departments are on the "front line" of public health, and this study demonstrates the important role these organizations play in implementing diabetes prevention and control EBPPs. Potential leverage points for more widespread adoption of diabetes-related EBPPs in local health departments include education about and encouragement of evidence-based decision making and organizational incentives for employees to integrate evidence-based decision making into their diabetes prevention and control activities.

Promoting state health department evidence-based cancer and chronic disease prevention: a multi-phase dissemination study with a cluster randomized trial component.

BACKGROUND: Cancer and other chronic diseases reduce quality and length of life and productivity, and represent a significant financial burden to society. Evidence-based public health approaches to prevent cancer and other chronic diseases have been identified in recent decades and have the potential for high impact. Yet, barriers to implement prevention approaches persist as a result of multiple factors including lack of organizational support, limited resources, competing emerging priorities and crises, and limited skill among the public health workforce. The purpose of this study is to learn how best to promote the adoption of evidence based public health practice related to chronic disease prevention. METHODS/DESIGN: This paper describes the methods for a multi-phase dissemination study with a cluster randomized trial component that will evaluate the dissemination of public health knowledge about evidence-based prevention of cancer and other chronic diseases. Phase one involves development of measures of practitioner views on and organizational supports for evidence-based public health and data collection using a national online survey involving state health department chronic disease practitioners. In phase two, a cluster randomized trial design will be conducted to test receptivity and usefulness of dissemination strategies directed toward state health department chronic disease practitioners to enhance capacity and organizational support for evidence-based chronic disease prevention. Twelve state health department chronic disease units will be randomly selected and assigned to intervention or control. State health department staff and the university-based study team will jointly identify, refine, and select dissemination strategies within intervention units. Intervention (dissemination) strategies may include multi-day in-person training workshops, electronic information exchange modalities, and remote technical assistance. Evaluation methods include pre-post surveys, structured qualitative phone interviews, and abstraction of state-level chronic disease prevention program plans and progress reports. TRIAL REGISTRATION: clinicaltrials.gov: NCT01978054.

Beardia vancouverensis gen. et sp. nov. (Juglandaceae): permineralized fruits from the Eocene of British Columbia.

Large numbers of permineralized juglandaceous fruits were identified in calcareous nodules from the Eocene Appian Way locality on Vancouver Island, British Columbia, Canada. The fruits, small dorsiventrally flattened nutlets, 4.5-7.0 mm long and 5.5-9.0 × 3-5 mm in diameter, were studied using cellulose acetate peels. They are wingless, ribbed, and have a lobed epicarp that surrounds the nutlet. Cells of the inner epicarp are thin-walled and traversed by a system of branching vascular strands. The stony nutlet wall is composed of fibers, with an outer layer of distinctive idioblasts. The fruits have a symmetry like that in Juglandaceae, subfamily Juglandoideae, tribe Platycaryeae, while the fibrous nut walls are like those of subfamily Engelhardioideae. This unique combination of characters indicates that these fruits represent a new genus and species of Juglandaceae: Beardia vancouverensis gen. et sp. nov. The excellent preservation of the Appian Way specimens has allowed a unique view of the internal fruit anatomy and external morphology. As the only wingless, flattened nuts known in the family, they further extend the range of morphological variation in fruits in the family. These fossils further support the hypothesis that North America was an important center of generic diversity for Juglandaceae during the early Tertiary.

Microfluidic devices for energy conversion: planar integration and performance of a passive, fully immersed H2-O2 fuel cell.

We describe the fabrication and performance of a passive, microfluidics-based H2-O2 microfluidic fuel cell using thin film Pt electrodes embedded in a poly(dimethylsiloxane) (PDMS) device. The electrode array is fully immersed in a liquid electrolyte confined inside the microchannel network, which serves also as a thin gas-permeable membrane through which the reactants are fed to the electrodes. The cell operates at room temperature with a maximum power density of around 700 microW/cm(2), while its performance, as recorded by monitoring the corresponding polarization curves and the power density plots, is affected by the pH of the electrolyte, its concentration, the surface area of the Pt electrodes, and the thickness of the PDMS membrane. The best results were obtained in basic solutions using electrochemically roughened Pt electrodes, the roughness factor, R(f), of which was around 90 relative to a smooth Pt film. In addition, the operating lifetime of the fuel cell was found to be longer for the one using higher surface area electrodes.