Background: Alzheimer’s disease, Parkinson’s disease, and Huntington’s disease are neurodegenerative disorders characterized by progressive structural and functional loss of specific neuronal populations, protein aggregation, insidious adult onset, and chronic progression. Modeling these diseases in animal models is useful for studying the relationship between neuronal dysfunction and abnormal behaviours and for screening therapies. Methods: We conducted a comprehensive descriptive review of the numerous animal models currently available to study these three diseases with a focus on their utilities and limitations. Results: A vast range of genetic and toxin-induced models have been generated. Our review outlines how these models differ with regards to the genetic manipulation or toxin used and the brain regions lesioned, describes the extent to which they mimic the neuropathological and behavioral deficits seen in the human conditions, and discusses the advantages and drawbacks of each model. Conclusions: We recommend the adoption of a conservative approach when extrapolating findings based on a single animal model and the validation of findings using multiple models. Investing in additional preclinical studies before embarking on more expensive human trials will improve our understanding of the neuropathology underlying neuronal demise and enhance the chances of identifying effective therapies.

Aiming to study the rough-wall turbulent boundary layer structure over differently arranged roughness elements, an experimental study was conducted on flows with regular and random roughness. Varying planform densities of truncated cone roughness elements in a square staggered pattern were investigated. The same planform densities were also investigated in random arrangements. Velocity statistics were measured via two-component laser Doppler velocimetry and stereoscopic particle image velocimetry. Friction velocity, thickness, roughness length and zero-plane displacement, determined from spatially averaged flow statistics, showed only minor differences between the regular and random arrangements at the same density. Recent a priori morphometric and statistical drag prediction methods were evaluated against experimentally determined roughness length. Observed differences between regular and random surface flow parameters were due to the presence of secondary flows which manifest as high-momentum pathways and low-momentum pathways in the streamwise velocity. Contrary to expectation, these secondary flows were present over the random surfaces and not discernible over the regular surfaces. Previously identified streamwise-coherent spanwise roughness heterogeneity does not seem to be present, suggesting that such roughness heterogeneity is not necessary to sustain secondary flows. Evidence suggests that the observed secondary flows were initiated at the front edge of the roughness and sustained over irregular roughness. Due to the secondary flows, local turbulent boundary layer profiles do not scale with local wall shear stress but appear to scale with local turbulent shear stress above the roughness canopy. Additionally, quadrant analysis shows distinct changes in the populations of ejection and sweep events.

OBJECTIVES/GOALS: The objectives of this presentation are to discuss 1) the implementation of Consent to Contact at an Academic Medical Center; 2) the access to lists of potential participants by study teams; and 3) the challenges and adjustments made to the initial conceptualized process. METHODS/STUDY POPULATION: Participant recruitment is critical to the success of all research studies. It is particularly challenging when investigators do not have a patient population from which to recruit. Thus, the University of Miami launched the CTC initiative in 2016 to facilitate study recruitment. Study investigators can request access to a registry of participants who agreed to be contacted and meet the initial study eligibility criteria. A multidisciplinary Operational Committee provides oversight and regulates access to the CTC registry. RESULTS/ANTICIPATED RESULTS: The registry has over 110K patients who have agreed to be contacted for eligible research studies. The demographic distribution of the patients in the registry mirrors the diversity of the UHealth population. As of January 2018, when the registry became available to the research community, 25 study teams from different departments, including the All of Us Research Program, have requested potential participant lists. The process of requesting access to patient lists is adapted to studies’ needs, with particular reference to sensitive populations, such as HIV/AIDS, substance abuse, etc. Results on utilization and satisfaction of the CTC initiative are being collected and will be presented. DISCUSSION/SIGNIFICANCE OF IMPACT: The CTC initiative allows UHealth patients to opt-in to the registry for research studies. The Operational Committee continues to monitor the successful consent of patients to participate in individual research studies and improving the request process.

Delivering high quality genomics-informed care to patients requires accurate test results whose clinical implications are understood. While other actors, including state agencies, professional organizations, and clinicians, are involved, this article focuses on the extent to which the federal agencies that play the most prominent roles — the Centers for Medicare and Medicaid Services enforcing CLIA and the FDA — effectively ensure that these elements are met and concludes by suggesting possible ways to improve their oversight of genomic testing.

We investigate the factors associated with the occurrence and abundance of external and blood parasites in African penguins (Spheniscus demersus), an endangered seabird that breeds exclusively on the coasts of Namibia and South Africa. External parasites were collected using the dust-ruffling method from 171 African Penguins admitted at a rehabilitation facility in the Western Cape, South Africa. Additionally, blood smears were obtained upon admission and weekly during rehabilitation and examined for blood parasites. Fleas Parapsyllus longicornis humboldti, ticks Ornithodoros capensis and lice Austrogoniodes demersus were recovered from 93, 63 and 40%, respectively, of the penguins upon admission to the centre. Rescue location and age group were identified as significant determinants of flea abundance, whereas month of admission was a significant determinant of tick abundance. Blood parasites were also common on admission, with Babesia being the most frequent (46% prevalence) whereas Borrelia was recorded sporadically (1.2%) and Plasmodium was recorded once. The prevalence and abundance of ticks on admission was positively associated with Babesia infection on admission. Our findings demonstrate the variability and contributing factor of parasite infections in an endangered species of penguin, and highlight the need for additional research on the parasite–host dynamics involving these potential disease vectors.

Eudialyte-group minerals (EGM) attract global interest as potential resources for high-field-strength elements (e.g. Zr, Nb, Ta, and rare-earth elements), i.e. critical materials for modern technologies. They are particularly valued for their relative enrichment in the most critical lanthanides, i.e. Nd and heavy rare earth elements (Gd–Lu). However, rare earth element (REE) substitution mechanisms into the EGM structure are still poorly understood. Light and heavy REE may occupy different sites and there may be ordering and/or defect clustering in the structure. This study uses X-ray absorption spectroscopy to determine the structural state of REE in EGM from prospective eudialyte-bearing complexes. Yttrium K-edge and Nd L3-edge spectra were collected as proxies for heavy and light REE, respectively, and compared to natural and synthetic REE-bearing standards. Extended X-ray absorption fine structure data yield best fits for Y in six-fold coordination with Y–O distances of 2.24–2.32 Å, and a second coordination sphere comprising Fe, Na, Ca, Si and O at radial distances of 3.6–3.8 Å. These findings are consistent with dominant Y3+ substitution for Ca2+ on the octahedral M1 site in all the samples studied, and exclude preferential substitution of Y3+ onto the smaller octahedral Z site or the large low-symmetry N4 site.

Using lattice strain theory, we constructed relative partitioning models to predict site preferences of lanthanides we have not measured directly. The models predict that all REE are favoured on the Ca-dominant M1 site and that preferential partitioning of heavy over light REE increases in EGM containing significant Mn in the M1-octahedral rings (oneillite subgroup). Thus, the flat REE profiles that make EGM such attractive exploration targets are not due to preferential partitioning of light and heavy REE onto different sites. Instead, local ordering of Mn- and Ca-occupied M1 sites may influence the capacity of EGM to accommodate heavy REE.

The importance of parasites as a selective force in host evolution is a topic of current interest. However, short-term ecological studies of host–parasite systems, on which such studies are usually based, provide only snap-shots of what may be dynamic systems. We report here on four surveys, carried out over a period of 12 years, of helminths of spiny mice (Acomys dimidiatus), the numerically dominant rodents inhabiting dry montane wadis in the Sinai Peninsula. With host age (age-dependent effects on prevalence and abundance were prominent) and sex (female bias in abundance in helminth diversity and in several taxa including Cestoda) taken into consideration, we focus on the relative importance of temporal and spatial effects on helminth infracommunities. We show that site of capture is the major determinant of prevalence and abundance of species (and higher taxa) contributing to helminth community structure, the only exceptions being Streptopharaus spp. and Dentostomella kuntzi. We provide evidence that most (notably the Spiruroidea, Protospirura muricola, Mastophorus muris and Gongylonema aegypti, but with exceptions among the Oxyuroidae, e.g. Syphacia minuta), show elements of temporal-site stability, with a rank order of measures among sites remaining similar over successive surveys. Hence, there are some elements of predictability in these systems.

Experiments on the National Ignition Facility show that multi-dimensional effects currently dominate the implosion performance. Low mode implosion symmetry and hydrodynamic instabilities seeded by capsule mounting features appear to be two key limiting factors for implosion performance. One reason these factors have a large impact on the performance of inertial confinement fusion implosions is the high convergence required to achieve high fusion gains. To tackle these problems, a predictable implosion platform is needed meaning experiments must trade-off high gain for performance. LANL has adopted three main approaches to develop a one-dimensional (1D) implosion platform where 1D means measured yield over the 1D clean calculation. A high adiabat, low convergence platform is being developed using beryllium capsules enabling larger case-to-capsule ratios to improve symmetry. The second approach is liquid fuel layers using wetted foam targets. With liquid fuel layers, the implosion convergence can be controlled via the initial vapor pressure set by the target fielding temperature. The last method is double shell targets. For double shells, the smaller inner shell houses the DT fuel and the convergence of this cavity is relatively small compared to hot spot ignition. However, double shell targets have a different set of trade-off versus advantages. Details for each of these approaches are described.

Mental health research funding priorities in high-income countries must balance longer-term investment in identifying neurobiological mechanisms of disease with shorter-term funding of novel prevention and treatment strategies to alleviate the current burden of mental illness. Prioritising one area of science over others risks reduced returns on the entire scientific portfolio.

Defensive chemicals in anuran skin secretions function in protection against potential predators. Although studies have demonstrated that particular chemicals are effective against certain predators, very little is known about how different chemicals from different species function against the same predators. Understanding how different chemicals function as a defence against similar predators is fundamental to the ecology and evolution of chemical defences in frogs. In the present study, the defensive function of bufadienolide-based defences in adult Rhaebo haematiticus (Bufonidae) were compared with alkaloid-based defences in adult and juvenile Dendrobates auratus (Dendrobatidae) against the same predators. Most bufonids contain synthesized bufadienolides, whereas dendrobatids contain dietary-derived alkaloids. Predation trials were performed with two potential invertebrate predators, Paraponera clavata (bullet ant) and Cupiennius coccineus (ctenid spider), to determine how these predators respond to two different types of frog chemical defence. The non-chemically defended frog Craugastor fitzingeri served as a control in all predation trials. Our results suggest that bufadienolide defences of R. haematiticus and alkaloid defences of D. auratus are equally effective towards bullet ant and ctenid spider predators. The similar avoidance and cleaning behaviours exhibited by these ants and spiders after contact with bufadienolides and alkaloids suggest that both types of defence are unpalatable to these arthropod predators.

The monthly intracisternal inoculation of young adult New Zealand white rabbits with low-dose (100 Μg) aluminum chloride induces aggregates of phosphorylated neurofilament that mimics the intraneuronal inclusions of amyotrophic lateral sclerosis. The chronic progressive myelopathy and topographically-specific motor neuron degeneration that occurs in the absence of suppressions of neurofilament messenger RNA levels in this model contrasts with the acute fulminant encephalomyelopathy and nonspecific gene suppressions that occur subsequent to high-dose (1000 Μg) aluminum chloride inoculations. Further analysis of this unique model of chronic motor system degeneration can be expected to provide additional insights into the pathogenesis of amyotrophic lateral sclerosis.

Because of its central role in the global carbon cycle, quantifying the biomass of photosynthetic microalgae in the oceans is crucial to our ability to estimate the oceans’ carbon drawdown. Many traditional methods of primary production assessment have proven to be extremely time consuming and, consequently, have handled only very small sample sizes. The recent advent of in situ bio-optical sensors, such as the water quality monitor (WQM), is now providing lower cost and higher throughput data on these crucial biological communities. These WQMs, however, only quantify the total fluorescence of all individual cells within their optical sample windows, irrespective of size. In this paper, we further develop an established model, based on Pareto random variables, of the size structure of the microalgae community to understand the effect of the WQMs’ sampling and data pooling on their estimates of algal biomass. Unfortunately, evaluating sums of Pareto variables is a notoriously difficult problem. Here, we utilize an approximation for the right-tail of the resulting distribution to derive parameter estimates for the underlying size structure of the microalgae community.

The forest and agriculture sectors are linked by having a portion of their land bases suitable for use in either sector. A substantial part of the southern land base is suitable for either forestry or agriculture use, with most of forestation on U.S. agriculture land in the South. We examine how land exchanges between forestry and agriculture are influenced by specific federal conservation and farm support policies, including changes in the Conservation Reserve Program. Reallocation of land is a significant part of the sectors' responses to the policies, along with intensification of timber management on existing southern forests.