Lessons learned and recommendations in conducting solutions-driven environmental and public health research.

Solutions-driven research is a transdisciplinary approach that incorporates diverse forms of expertise to identify solutions to stakeholder-identified environmental problems. This qualitative evaluation of early solutions-driven research projects provides transferable recommendations to improve researcher and stakeholder experiences and outcomes in transdisciplinary environmental research projects. Researchers with the U.S. Environmental Protection Agency (EPA) Office of Research and Development recently piloted a solutions-driven research approach in two parallel projects; one addressing nutrient management related to coastal waters and another studying wildland fire smoke impacts on indoor air quality. Studying the experiences of those involved with these pilots can enhance the integration of researcher and experiential expertise, improving solutions-driven research outcomes. Data collection included semi-structured interviews with 17 EPA researchers and 12 other stakeholders and reflective case narratives from the authors. We used conventional content analysis to qualitatively analyze perspectives on implementing innovative engagement and research approaches in a solutions-driven process. Findings that reflect common perspectives include the importance of continuous engagement, the challenges of differing timelines and priorities for researchers and stakeholders, and the need to define consistent markers of success across researchers and stakeholders. Key lessons to improve transdisciplinary research identified from the analysis are (1) improving clarity of roles and responsibilities; (2) planning to provide sufficient, continuous project funding over multiple years; (3) expecting research needs and plans to adapt to evolving circumstances; and (4) clearly defining the end of the project.

Elbow luxation in a patient with congenital dislocation of the radial head.

Elbow dislocations are commonly seen and can occur after trauma or be congenital. The literature on congenital dislocations is scarce. No cases of an additional luxation of a pre-existing congenital radial head dislocation with a traumatic ulnohumeral dislocation have been described. This case involves a young man with no prior history who presented after trauma of the right elbow. He presented with pain, and his radial head was palpable behind the olecranon, and on imaging it appeared to be more proximal. After additional imaging, the dislocation of the radial head turned out to be congenital combined with an additional luxation of the ulna. This finding influenced our diagnostic approach and reposition method, which, instead of only traction-countertraction, also included pronation and supination.This case highlights the clinical importance of identifying and recognising a patient with a congenital dislocation of the radial head and an additional luxation of the elbow.

Influence of size, crosslinking degree and surface structure of poly(N-vinylcaprolactam)-based microgels on their penetration into multicellular tumor spheroids.

Current nanomedicine suffers from a big challenge due to the fact that most of the nanocarrier systems lack the desired tumor penetration depth, thereby limiting their clinical translation. Unlike the nanomaterials with a similar size or shape, microgels display excellent softness, fluidity and deformability, as well as stimuli-responsiveness in the tumor microenvironment. Herein, we report the synthesis of temperature-responsive poly(N-vinylcaprolactam)/oligo (ethylene glycol) acrylate/glycidyl methacrylate (PVCL/OEGA/GMA) microgels with different hydrodynamic radii (100-500 nm), crosslinking densities, 2-methoxyethyl acrylate (MEA) contents and OEGA chain lengths using a precipitation polymerization method and the investigation of the microgels in terms of their tumor penetration capability using a multicellular tumor spheroid (MCTS) model. The prepared microgels were well characterized with different techniques. We show that regardless of the size, crosslinking density, MEA content and OEGA chain length, all microgels display the desired cytocompatibility in the given concentration range. In vitro cellular uptake data reveal that similar to 2-dimensional (2-D) adherent cells, microgels with a smaller size display more enhanced cellular uptake than those having a larger size in the 3-D MCTS model. Likewise, 3-D MCTS penetration results indicate that the PVCL/OEGA/GMA microgels with the smallest radius of 100 nm exhibit the deepest penetration length. We then selected the microgels with a radius of 200 nm but with different physicochemical parameters to investigate their cellular uptake and tumor penetration behavior. Our data show that microgels with varying crosslinking densities, MEA contents and OEGA chain lengths do not have any appreciable changes in terms of their cellular uptake and penetration in the 3-D MCTS model. Our study provides new insights for the design of different microgel-based systems for further cancer theranostic applications.

Ultrafast carrier kinetics in exfoliated graphene and thin graphite films.

Time-resolved transmissivity and reflectivity of exfoliated graphene and thin graphite films on a 295 K SiO(2)/Si substrate are measured at 1300 nm following excitation by 150 fs, 800 nm pump pulses. From the extracted transient optical conductivity we identify a fast recovery time constant which increases from approximately 200 to 300 fs and a longer one which increases from 2.5 to 5 ps as the number of atomic layers increases from 1 to approximately 260. We attribute the temporal recovery to carrier cooling and recombination with the layer dependence related to substrate coupling. Results are compared with related measurements for epitaxial, multilayer graphene.

Angiotensin receptor blockade with candesartan attenuates atherosclerosis, plaque disruption, and macrophage accumulation within the plaque in a rabbit model.

BACKGROUND: Little is known about whether direct angiotensin receptor blockade can reduce atherosclerosis and plaque disruption. This study evaluated the effect of angiotensin receptor blockade on both the development of atherosclerosis and the disruption of plaque in a modified Constantinides animal model. METHODS AND RESULTS: Twenty-eight New Zealand White rabbits underwent aortic balloon injury followed by a 1% cholesterol diet for 8 weeks. Thirteen rabbits received candesartan at 0.5 mg x kg(-1) x d(-1) beginning 2 days before aortic balloon injury and continued for the total 8 weeks of the cholesterol diet. The rabbits were then pharmacologically triggered and humanely killed, and their aortas were analyzed. The degree of atherosclerosis was determined by intima-media ratio of the infrarenal portion of the aorta. The frequency of intra-aortic thrombosis, a measure of plaque disruption, and the percentages of macrophage area and collagen-staining area of the plaque were determined. Candesartan-treated rabbits had less atherosclerosis (intima-media infrarenal aorta ratio of 1.18+/-0.08 versus 1.57+/-0.08 [mean+/-SEM] for the placebo group, P<0.001); fewer thrombi (3 of 13 versus 11 of 15; P<0.05); lower percentage area of macrophages to total plaque (18.8+/-2.7% versus 27+/-2.5%, P<0.05); and higher collagen to total plaque area (45+/-3% versus 35+/-2%, P<0.01). CONCLUSIONS: These results demonstrate that angiotensin receptor blockade attenuates the degree of atherosclerosis and reduces both plaque disruption and macrophage accumulation while increasing collagen deposition in the aortas of this animal model.

Evaluation of electronic microarrays for genotyping factor V, factor II, and MTHFR.

BACKGROUND: Genetic risk factors associated with venous thrombosis include mutations in the factor V (Leiden), factor II (prothrombin), and methylenetetrahydrofolate reductase (MTHFR) genes. We evaluated a method using electronically addressable microarrays for the detection of mutations in these genes that have been associated with vascular disease. METHODS: The NanoChip Molecular Biology Workstation (Nanogen) uses electronic microarrays for mutation detection. Factor V, factor II, and MTHFR genotypes identified in the NanoChip system on 225 samples were compared with genotypes from LightCycler assays (Roche). We determined within- and between-cartridge signal and ratio variation and analyzed the effect of additional mutations at or near the detection area used for the NanoChip assays. RESULTS: Genotypes determined for all three mutations on the NanoChip platform were in complete concordance with LightCycler results. Within-cartridge signal variation as measured by the CV of fluorescence signals was <10% for each allele when present. The within-cartridge CV for heterozygous mutant/wild-type ratios was <8.5%, and between-cartridge CV was <18%. A dilution study showed that results could be obtained in this assay with 6 ng of nucleic acid per PCR, the lowest input tested. The presence of additional sequence variations near the expected mutations can produce equivocal or discrepant results. CONCLUSIONS: Mutation detection using the NanoChip Molecular Biology Workstation was accurate and reproducible for the three assays evaluated.

GCAP1 rescues rod photoreceptor response in GCAP1/GCAP2 knockout mice.

Visual transduction in retinal photoreceptors operates through a dynamic interplay of two second messengers, Ca(2+) and cGMP. Ca(2+) regulates the activity of guanylate cyclase (GC) and the synthesis of cGMP by acting on a GC-activating protein (GCAP). While this action is critical for rapid termination of the light response, the GCAP responsible has not been identified. To test if GCAP1, one of two GCAPs present in mouse rods, supports the generation of normal flash responses, transgenic mice were generated that express only GCAP1 under the control of the endogenous promoter. Paired flash responses revealed a correlation between the degree of recovery of the rod a-wave and expression levels of GCAP1. In single cell recordings, the majority of the rods generated flash responses that were indistinguishable from wild type. These results demonstrate that GCAP1 at near normal levels supports the generation of wild-type flash responses in the absence of GCAP2.