Diagnosis, treatment, and prevention of vector-borne disease (VBD) in pets is one cornerstone of companion animal practices. Veterinarians are facing new challenges associated with the emergence, reemergence, and rising incidence of VBD, including heartworm disease, Lyme disease, anaplasmosis, and ehrlichiosis. Increases in the observed prevalence of these diseases have been attributed to a multitude of factors, including diagnostic tests with improved sensitivity, expanded annual testing practices, climatologic and ecological changes enhancing vector survival and expansion, emergence or recognition of novel pathogens, and increased movement of pets as travel companions. Veterinarians have the additional responsibility of providing information about zoonotic pathogen transmission from pets, especially to vulnerable human populations: the immunocompromised, children, and the elderly. Hindering efforts to protect pets and people is the dynamic and ever-changing nature of VBD prevalence and distribution. To address this deficit in understanding, the Companion Animal Parasite Council (CAPC) began efforts to annually forecast VBD prevalence in 2011. These forecasts provide veterinarians and pet owners with expected disease prevalence in advance of potential changes. This review summarizes the fidelity of VBD forecasts and illustrates the practical use of CAPC pathogen prevalence maps and forecast data in the practice of veterinary medicine and client education.

OBJECTIVES/SPECIFIC AIMS: Pancreatic ductal adenocarcinoma (PDA) has a dismal 5-year survival rate of 9%, making this disease one of the deadliest human malignancies (https://seer.cancer.gov/). Primary barriers to the treatment of pancreatic cancer include extensive stromal interactions and sustained immune suppression. Aberrant Hedgehog (HH) pathway activity is a hallmark of pancreatic tumorigenesis. Tumor-derived HH ligands signal in a paracrine fashion to the surrounding stroma to influence tumor growth. Expression of HH ligands increases during PDA progression, and previous work has shown that genetic deletion of Sonic HH (Shh) from the epithelium of mice with pancreatic tumors results in increased Indian HH (Ihh) expression. This research aims to investigate the translational impact of changes in immune infiltration following deletion of IHH in a preclinical mouse model of pancreatic cancer. METHODS/STUDY POPULATION: Ihh was deleted in tumor cells lines (IhhKO) derived from a genetically engineered mouse model of pancreatic cancer (LSL-KrasG12D/+;LSL-TrpR270H;P48-Cre), using CRISPR/Cas-9 gene editing to assess the role of Ihh in the tumor microenvironment. The level of HH signaling was determined using tumor cell co-cultures with Gli1lacZ fibroblasts (derived from mice with a lacZ reporter allele knocked into the Gli1 locus), in which Beta Galactosidase activity serves as a readout for HH signaling. WT and IhhKO tumor cells were orthotopically transplanted into the pancreas of syngeneic C57BL/6 mice. Human pancreas samples were obtained from surgical resection of pancreatic adenocarcinoma, or fine needle biopsy procedure (FNB). Immune profiling of mouse and human pancreatic tumors was performed using Cytometry Time-of-Flight analysis (CyTOF), and tumor composition was analyzed by single-cell RNA sequencing (scRNA seq). In vitro cultures with pancreatic fibroblasts treated with either WT or IhhKO tumor cell conditioned media (CM) were cultured with bone-marrow derived macrophages to assess tumor crosstalk. RESULTS/ANTICIPATED RESULTS: Tumor cells lacking Ihh were generated through CRISPR/Cas-9 deletion, and this was confirmed by qRT-PCR. Co-culture of IhhKO tumor cells with Gli1lacZ fibroblasts results in decreased Gli1 expression both in vitro and in vivo. Immune profiling revealed that tumors lacking Ihh have significantly fewer tumor associated macrophages (CD11b+/F4/80+/CD206+), resulting in decreased presence of immunosuppressive factors such as arginase 1 and PDL1. Immune phenotyping of human pancreatic tissues revealed similar populations of immunosuppressive myeloid cells present in tumors. In vitro co-cultures demonstrated that, in the presence of bone-marrow derived macrophages, immunosuppressive IL-6 production was reduced in pancreatic fibroblasts cultured with IhhKO-CM, as compared to fibroblasts cultured with WT-CM, providing mechanistic insight into the in vivo phenotype observed. Further, scRNA seq analysis suggests that modulation of HH signaling in the tumor microenvironment alters chemokine and immunomodulatory signaling pathways driven by fibroblasts in the pancreatic tumor microenvironment. DISCUSSION/SIGNIFICANCE OF IMPACT: HH signaling in pancreatic fibroblasts contributes to the establishment of an immune suppressive environment in pancreatic cancer. Combining methods to target HH signaling and immune checkpoint therapy has translational potential in treating pancreatic cancer patients.

The members of IAU Commission 29 Stellar Spectra are actively engaged in the quantitative analysis of spectra of various types of stars. With large and medium size telescopes equipped with high resolution spectrographs LTE and Non-LTE analysis of spectra of all types stars are being carried out. Spectra of stars in our Galaxy, in globular and open clusters, stars in LMC and SMC and in nearby galaxies are being studied. Accurate chemical composition analysis of various types of stars has been carried out during the past three years. Now the analysis of stellar spectra covers the wavelength range from X-ray region to IR and sub-millimeter range. Recently stellar spectra are being analysed using time-dependent, 3D, hydrodynamical model atmospheres to derive accurate stellar abundances.

A study is carried out of the linear global behaviour corresponding to the absolute instability of the rotating-disc boundary layer. It is based on direct numerical simulations of the complete linearized Navier–Stokes equations obtained with the novel velocity–vorticity method described in Davies & Carpenter (2001). As the equations are linear, they become separable with respect to the azimuthal coordinate, $\theta$. This permits us to simulate a single azimuthal mode. Impulse-like excitation is used throughout. This creates disturbances that take the form of wavepackets, initially containing a wide range of frequencies. When the real spatially inhomogeneous flow is approximated by a spatially homogeneous flow (the so-called parallel-flow approximation) the results ofthe simulations are fully in accordance with the theory of Lingwood (1995). If the flow parameters are such that her theory indicates convective behaviour the simulations clearly exhibit the same behaviour. And behaviour fully consistent with absolute instability is always found when the flow parameters lie within the theoretical absolutely unstable region. The numerical simulations of the actual inhomogeneous flow reproduce the behaviour seen in the experimental study of Lingwood (1996). In particular, there is close agreement between simulation and experiment for the ray paths traced out by the leading and trailing edges of the wavepackets. In absolutely unstable regions the short-term behaviour of the simulated disturbances exhibits strong temporal growth and upstream propagation. This is not sustained for longer times, however. The study suggests that convective behaviour eventually dominates at all the Reynolds numbers investigated, even for strongly absolutely unstable regions. Thus the absolute instability of the rotating-disc boundary layer does not produce a linear amplified global mode as observed in many other flows. Instead the absolute instability seems to be associated with transient temporal growth, much like an algebraically growing disturbance. There is no evidence of the absolute instability giving rise to a global oscillator. The maximum growth rates found for the simulated disturbances in the spatially inhomogeneous flow are determined by the convective components and are little different in the absolutely unstable cases from the purely convectively unstable ones. In addition to the study of the global behaviour for the usual rigid-walled rotating disc, we also investigated the effect of replacing an annular region of the disc surface with a compliant wall. It was found that the compliant annulus had the effect of suppressing the transient temporal growth in the inboard (i.e. upstream) absolutely unstable region. As time progressed the upstream influence of the compliant region became more extensive.

An energetic material has been routinely manufactured from nano-metric powders of aluminum (Al) and molybdenum trioxide (MoO3). When optimized, the burn-rate of these materials (∼400 m/s) exceeds that of conventional thermites (based on micron-sized powders), but is less than that of conventional explosives. Similar burn-rates around 350 m/s are measured for these “super-thermites” using n-Al powder in the size range between 30 and 90 nm in diameter (20–60 m2/g, 60–80 wt%Al) and an oxygen to fuel (O/F) mass ratio of 1.4. The burn-rate decreases when the surface area of the MoO3 is decreased from 64 to 40 m2/g, or when O/F is changed from 1.2. Thus, for each average particle diameter, there is an optimum burn-rate at an O/F ratio that depends on the wt%Al present in the material and the particle size distribution of the powder. The burn-rate is dependent on several materials and processing factors such as the quality of the nano-metric ingredients, the processing method, and exposure to air and light, so the effect of aging and environmental exposure on the individual ingredients has been investigated. The results of this powder aging study suggests that the surface area of n-MoO3 can decrease two-fold within 10–12 days, and the Al-metal content in n-Al can decrease as much as 50% over two years. Adequate handling and storage procedures must therefore be followed for the effective use of nano-metric powders and their super-thermite mixes.

Several lines of evidence suggest that the neuropeptide oxytocin (OT) may be involved in the pathophysiology of obsessive-compulsive behavior in humans and repetitive grooming behavior in animals. Trichotillomania (TTM), which is characterized by chronic hair pulling, may be conceptualized as a disorder of pathologic grooming. To investigate the role of OT in TTM, the cerebrospinal fluid (CSF) levels of OT in nine women with TTM and nine healthy female controls were measured. Early findings from this ongoing study fail to demonstrate a significant difference in CSF OT levels between women with TTM and healthy female controls.