3,351 research outputs found

    Guiding Transformation: How Medical Practices Can Become Patient-Centered Medical Homes

    Get PDF
    Describes in detail eight change concepts as a guide to transforming a practice into a patient-centered medical home, including engaged leadership, quality improvement strategy, continuous and team-based healing relationships, and enhanced access

    An unusual 'shovel-billed' dinosaur with trophic specializations from the early Campanian of Trans-Pecos Texas, and the ancestral hadrosaurian crest

    Get PDF
    We describe a new genus and species of hadrosaurid dinosaur, Aquilarhinus palimentus, from the lower shale member of the Aguja Formation (lower Campanian) of Big Bend National Park, south-western Texas. This species is characterized by several autapomorphies of the facial skeleton and mandible, including a crest composed of broadly arched nasals. Notably, the symphyseal processes of the dentary are elongated and reflected dorsally, causing the dentaries to meet with a 'W'-shaped anterior profile. A hypothesized shovel-shaped 'bill', associated with widening of the skull, in A. palimentus might have been used in shovelling out and scooping up semiaquatic vegetation. This animal is otherwise superficially similar to kritosaurins like Gryposaurus but differs in the retention of key plesiomorphic character states in the maxilla and jugal. Phylogenetic analysis reveals Aquilarhinus to be a non-saurolophid hadrosaurid allied to Latirhinus from the late Campanian of Mexico, which bears a similar broadly arched nasal. The recognition of this lineage adds to the diversity of non-saurolophid hadrosaurids and points to the existence of a hitherto unknown diversity of 'duck-billed' dinosaurs outside of the saurolophine-lambeosaurine radiation. Cranial crests were ancestral for early hadrosaurids and evolved before the saurolophid radiation. Ancestrally, crests were 'solid', and consisted of arched nasals. These were retained among kritosaurins and subsequently modified into the diverse crest morphologies observed among derived saurolophines. Lambeosaurine 'hollow-crested' crest morphology departed from the ancestral, 'solid-crested' pre-saurolophid condition early following the origin of that clade

    Dysfunctional stem and progenitor cells impair fracture healing with age

    Get PDF
    Successful fracture healing requires the simultaneous regeneration of both the bone and vasculature; mesenchymal stem cells (MSCs) are directed to replace the bone tissue, while endothelial progenitor cells (EPCs) form the new vasculature that supplies blood to the fracture site. In the elderly, the healing process is slowed, partly due to decreased regenerative function of these stem and progenitor cells. MSCs from older individuals are impaired with regard to cell number, proliferative capacity, ability to migrate, and osteochondrogenic differentiation potential. The proliferation, migration and function of EPCs are also compromised with advanced age. Although the reasons for cellular dysfunction with age are complex and multidimensional, reduced expression of growth factors, accumulation of oxidative damage from reactive oxygen species, and altered signaling of the Sirtuin-1 pathway are contributing factors to aging at the cellular level of both MSCs and EPCs. Because of these geriatric-specific issues, effective treatment for fracture repair may require new therapeutic techniques to restore cellular function. Some suggested directions for potential treatments include cellular therapies, pharmacological agents, treatments targeting age-related molecular mechanisms, and physical therapeutics. Advanced age is the primary risk factor for a fracture, due to the low bone mass and inferior bone quality associated with aging; a better understanding of the dysfunctional behavior of the aging cell will provide a foundation for new treatments to decrease healing time and reduce the development of complications during the extended recovery from fracture healing in the elderly

    Proteomic and functional mapping of cardiac NaV1.5 channel phosphorylation sites

    Get PDF
    Phosphorylation of the voltage-gated Na+ (NaV) channel NaV1.5 regulates cardiac excitability, yet the phosphorylation sites regulating its function and the underlying mechanisms remain largely unknown. Using a systematic, quantitative phosphoproteomic approach, we analyzed NaV1.5 channel complexes purified from nonfailing and failing mouse left ventricles, and we identified 42 phosphorylation sites on NaV1.5. Most sites are clustered, and three of these clusters are highly phosphorylated. Analyses of phosphosilent and phosphomimetic NaV1.5 mutants revealed the roles of three phosphosites in regulating NaV1.5 channel expression and gating. The phosphorylated serines S664 and S667 regulate the voltage dependence of channel activation in a cumulative manner, whereas the nearby S671, the phosphorylation of which is increased in failing hearts, regulates cell surface NaV1.5 expression and peak Na+ current. No additional roles could be assigned to the other clusters of phosphosites. Taken together, our results demonstrate that ventricular NaV1.5 is highly phosphorylated and that the phosphorylation-dependent regulation of NaV1.5 channels is highly complex, site specific, and dynamic

    Prenatal Alcohol Exposure and Placental Insufficiency Results in Reduced Neuronal Complexity in the Rat Prefrontal Cortex

    Get PDF
    Prenatal Alcohol Exposure (PAE) can produce long-term neurodevelopmental deficits and impaired executive function. Alcohol exposure during gestation is associated with impaired fetal development caused by placental insufficiency. The impact following PAE and placental insufficiency (PI) remains unknown. Utilizing a three-dimensional (3D) Sholl analysis, we hypothesized that PAE+PI will result in decreased neuronal complexity within the frontal cortex, a region critical to executive functioning. Pregnant Long-Evans rats voluntarily drank 5% ethanol or saccharin water until embryonic day 18 (E18) to mimic moderate PAE. On E19, a laparotomy was performed to occlude the uterine artery for 60 minutes to induce PI. The pups delivered normally. At postnatal day 100 (P100), brains were extracted and Golgi-Cox stained. Coronal sections were imaged utilizing a Leica TCS SP8 Confocal microscope with z-stacking capabilities. A 3D Sholl analysis was conducted within Imaris software to assess variance in neural complexity between treatment groups. Analysis was completed with a 2-way ANOVA and t-test. Five PAE+PI and 5 control brains were collected. In the medial frontal cortex, 3 neurons were analyzed from each hemisphere. No statistical difference was noted between the two hemispheres, so the data was combined for each animal resulting in 6 neurons being analyzed. The proximal dendritic complexity was similar between groups. PAE+PI resulted in significantly diminished complexity more distal from the soma; at 80 mm the PAE+PI group had an average of 2.4 intersections while the control group had an average of 3.3 (p\u3c0.05). At 90 mm, the PAE+PI group continued to have fewer intersections compared to controls (1.8 vs. 2.6). This is the first study to investigate the dendritic complexity following PAE combined with PI within the frontal cortex. Given the importance of this region to executive function, this may provide insight into the long-term deficits that are observed and provide support for interventions

    Double Averaging Analysis Applied to a Large Eddy Simulation of Coupled Turbulent Overlying and Porewater Flow

    Get PDF
    Freestream turbulence in rivers is a key contributor to the flux of dissolved nutrients, carbon, and other ecologically important solutes into porewater. To advance understanding of turbulent hyporheic exchange and porewater transport, we investigate flow over and through a rough bed of spheres using large eddy simulation (LES). We apply double averaging (combined space and time averaging) to the LES results to determine the mean velocity distribution, momentum balance, and drag forces. Our simulations show large-scale freestream structures interacting strongly with vortices generated at the surfaces of individual spheres to control turbulent momentum fluxes into the bed. The transition between turbulent flow and Darcy flow occurs over the first row of spheres, where turbulence decays rapidly and turbulent kinetic energy, Reynolds stress, and drag forces peak. Below this region, turbulence is only present in the high-velocity flow in open pore throats. Experimental observations suggest that minimum mean porewater velocity occurs in the first open pore space below the transition region, but our results show that the minimum occurs between the first and second pore spaces. The simulation mean porewater velocities are approximately half those captured in measurements because the model resolves the entire flow continuum while measurements can access high-velocity fluid in open pores. The high-resolution dual time-space averaging of the LES resolves both turbulent and mean flow features that are important to interfacial solute and particle fluxes, providing a means to include turbulent hyporheic exchange in upscaled river models, which has not been achieved to date

    Prospective surveillance of invasive group a streptococcal disease, Fiji, 2005-2007.

    Get PDF
    We undertook a prospective active surveillance study of invasive group A streptococcal (GAS) disease in Fiji over a 23-month period, 2005-2007. We identified 64 cases of invasive GAS disease, which represents an average annualized all-ages incidence of 9.9 cases/100,000 population per year (95% confidence interval [CI] 7.6-12.6). Rates were highest in those >65 years of age and in those <5 years, particularly in infants, for whom the incidence was 44.9/100,000 (95% CI 18.1-92.5). The case-fatality rate was 32% and was associated with increasing age and underlying coexisting disease, including diabetes and renal disease. Fifty-five of the GAS isolates underwent emm sequence typing; the types were highly diverse, with 38 different emm subtypes and no particular dominant type. Our data support the view that invasive GAS disease is common in developing countries and deserves increased public health attention

    New Insights from Seafloor Mapping of a Hawaiian Marine Monument

    Get PDF
    On 15 June 2006, when U.S. President George W. Bush signed the proclamation creating the Papahānaumokuākea Marine National Monument (PMNM), he probably wasn’t thinking about underwater morphology. To fully understand the coral reefs and marine ecosystems that the monument was created to protect, however, scientists need to have a detailed picture of the seafloor features, home to corals and other species, as well as the geologic history of the area. Thanks to a recent, multi-institution expedition, such a seafloor features that will not only inform conservation efforts but also enable geologists and geophysicists to revise their understanding of Hawaii’s complex geologic past. Specifically, data should help scientists answer fundamental questions about the area’s regional geology. For instance, which seamounts were truly formed because of Hawaiian hotspot volcanism, and which seamounts were not
    corecore