Omobranchus sewalli is a native Indo-Pacific blenniid recently introduced and established along the Brazilian coast. The putative introduction was through ballast water and/or ship hull biofouling. Herein, we report the presence of the species for the first time inside of the Paranaguá Estuarine Complex (PEC) which is recognized as a RAMSAR site and listed as a Wetland of International Importance. The mature specimens of O. sewalli were found in intertidal and shallow subtidal waters in the mixture zone in the estuary, suggesting the establishment of the population. The presence of port terminals in this area indicates that O. sewalli colonize PEC using ship hull fouling or larval dispersal from the shallow inner shelf.

The purpose of the current study was to revisit a controversial topic: whether frequencies of phonological consonant and vowel classes differ in speech directed to children and to adults. In addition, the current study investigated whether the frequency of phonological consonant and vowel classes changes with children’s increasing chronological and/or developmental age. This study analyzed speech input from 44 adults to four different age groups of listeners (i.e., three groups of children at 6, 18, and 36 months of age and one group of adult listeners) in terms of frequency of occurrence of consonant and vowel classes. Results revealed that consonant stop, nasal, fricative and glide manner classes as well as all four consonant place classes were significantly different in speech directed to the four different age groups. A perspective is discussed to better understand the nature of frequency input of phonological sound classes.

The quenching of cluster satellite galaxies is inextricably linked to the suppression of their cold interstellar medium (ISM) by environmental mechanisms. While the removal of neutral atomic hydrogen (H i) at large radii is well studied, how the environment impacts the remaining gas in the centres of galaxies, which are dominated by molecular gas, is less clear. Using new observations from the Virgo Environment traced in CO survey (VERTICO) and archival H i data, we study the H i and molecular gas within the optical discs of Virgo cluster galaxies on 1.2-kpc scales with spatially resolved scaling relations between stellar ($\Sigma_{\star}$), H i ($\Sigma_{\text{H}\,{\small\text{I}}}$), and molecular gas ($\Sigma_{\text{mol}}$) surface densities. Adopting H i deficiency as a measure of environmental impact, we find evidence that, in addition to removing the H i at large radii, the cluster processes also lower the average $\Sigma_{\text{H}\,{\small\text{I}}}$ of the remaining gas even in the central $1.2\,$kpc. The impact on molecular gas is comparatively weaker than on the H i, and we show that the lower $\Sigma_{\text{mol}}$ gas is removed first. In the most H i-deficient galaxies, however, we find evidence that environmental processes reduce the typical $\Sigma_{\text{mol}}$ of the remaining gas by nearly a factor of 3. We find no evidence for environment-driven elevation of $\Sigma_{\text{H}\,{\small\text{I}}}$ or $\Sigma_{\text{mol}}$ in H i-deficient galaxies. Using the ratio of $\Sigma_{\text{mol}}$-to-$\Sigma_{\text{H}\,{\small\text{I}}}$ in individual regions, we show that changes in the ISM physical conditions, estimated using the total gas surface density and midplane hydrostatic pressure, cannot explain the observed reduction in molecular gas content. Instead, we suggest that direct stripping of the molecular gas is required to explain our results.

ABSTRACT IMPACT: Melanoma leptomeningeal disease (LMD) is a devastating subtype of central nervous system (CNS) metastatic disease that is associated with limited treatment options and an extremely poor prognosis, thus requiring the development of preclinical models of LMD for therapeutic development. OBJECTIVES/GOALS:

1. 1. Develop an immunocompetent murine model of melanoma LMD with tumors bearing genetic mutations commonly found in patients, specifically BRAF(V600E)/PTEN-/-

2. 2. Assess the safety of intrathecal (IT) immunotherapy, specifically anti-PD1 antibody (aPD1)

3. 3. Evaluate the therapeutic efficacy of IT aPD1 checkpoint blockade in murine melanoma LMD METHODS/STUDY POPULATION: To develop BRAF(V600E)/PTEN-/- LMD models, we acquired BP, D4M, and D4M-UV2 (irradiated) murine melanoma cell lines and luciferase-tagged them. 1.5x10^4 cells were suspended in 10 uL serum-free media and injected into the cisterna magna of female C57BL/6 mice. Brain and spinal cord were harvested for histologic assessment once mice were moribund. To assess safety of IT aPD1, we injected IT control IgG or IT aPD1 (13 ug, 26 ug, 39 ug) and monitored weights or harvested at days 7 or 14 for IHC staining of inflammation markers. To evaluate therapeutic efficacy of IT aPD1, BP cells were directly injected as above. After 3 days, mice underwent imaging to confirm tumor uptake and randomization to receive 13 ug IT control IgG or aPD1 once + 200 ug systemic (Sys) control IgG or aPD1 (days 0, 3, and 5), and then monitored for survival. RESULTS/ANTICIPATED RESULTS: For LMD development, all mice survived cisternal injection of BP, D4M, and D4M-UV2 cells and median survival was 17, 19, and 30 days, respectively. Presence of leptomeningeal deposits was confirmed for all tumor-bearing mice by IHC for MART1. For safety of IT aPD1, all mice survived the procedure and no mice displayed morbidity or >10% weight loss over 14 days of observation. IHC assessment of brain and spinal cord samples from mice treated with 13 ug aPD1 revealed focal ischemia related to injection site and no other signs of neurological damage or inflammation. IT aPD1 treatment of mice with BP leptomeningeal tumors demonstrated no significant survival advantage, although both IT aPD1 +/- Sys aPD1 had mice live up to days 29 and 26, respectively, compared to both IT control IgG +/- Sys aPD1, for which all mice died by day 22. DISCUSSION/SIGNIFICANCE OF FINDINGS: We demonstrate that cisternal injection of murine BRAF(V600E)/PTEN-/- melanoma cell lines yield LMD with reproducible survival and that treatment with IT aPD1 in this model is feasible and safe. Together these findings establish a new model to facilitate the development of more effective immunotherapy strategies for melanoma patients with LMD.

OBJECTIVES/SPECIFIC AIMS: To examine rural-urban disparities in prevalence of diagnosed diabetes in veterans receiving care at the VA and to determine the extent to which demographic factors and obesity levels contribute to identified disparities. METHODS/STUDY POPULATION: A retrospective serial cross-sectional analysis was employed. A stratified weighted random sample of veterans who received care at a VA facility was selected each year for 2007 through 2012. Rural Urban Commuting Area (RUCA) codes were based on resident zip code. Diabetes was defined by two or more primary or secondary ICD-9 codes for diabetes (250.xx) within a 12 month period. Data were analyzed using complex survey-specific procedures. RESULTS/ANTICIPATED RESULTS: Diabetes prevalence 2007-2012 was lowest in urban (20.5%-21.0%), followed by highly rural (21.1%-22.1%) and rural (22.3%-23.0%) areas with the prevalence being significantly higher on the insular islands (31.0%-32.4%). In 2012, 41% of urban, 43% of rural and highly rural and 30% of insular island veterans were obese. Relative to urban areas, the odds ratio for prevalent diabetes was 1.10 (95% CI: 1.08, 1.12) for rural veterans, 1.19 (95% CI: 1.16, 1.23) for insular island veterans, and 1.00 (95% CI: 0.98, 1.02) for highly rural veterans. DISCUSSION/SIGNIFICANCE OF IMPACT: Prevalence of diagnosed diabetes is high in veterans residing in rural, highly rural and urban areas, but markedly higher on the insular islands. Understanding the burden of disease and factors driving disparities provides information required to develop targeted interventions.

Some researchers have suggested that young children choose to say mainly words containing sounds they can produce and avoid words with sounds they find difficult to produce. This proposed pattern of ‘selection’ supports a hypothesis of dominance of phonological factors in words children choose to say. Based on longitudinal spontaneous data samples during their first 50 word period, word-based tokens produced by two English and two French monolingual children were analyzed. Token frequencies in spontaneously produced word targets (SW-T) were compared to children's actual productions (SW-A) of those target words to understand relationships between targets children choose to say and their patterns in actual productions, (i.e., to evaluate the presence of ‘selection’). Place of articulation (i.e., labial, coronal and dorsal) in initial word position within CV, CVC, and CVCV word forms was compared. Analysis of spontaneous output in daily interactions in children learning two languages with differing phonological systems enables a more general evaluation of issues related to the interface of phonological and lexical aspects during the earliest period of language acquisition.

This study investigates whether the earliest words children choose to say are mainly words containing sounds they can produce (cf. ‘phonological dominance’ hypotheses), or whether children choose words without regard to their phonological characteristics (cf. ‘lexical dominance’ hypotheses). Phonological properties of words in spontaneous speech from six children age 0;8 to 2;11 were analyzed by comparing sound distributions of consonant place and manner. Word-initial and word-final consonant patterns in children's Word Targets versus Actual Word Forms were analyzed as a function of vocabulary size. Word-initial results showed more overall evidence for phonological dominance. In word-final position, at lower vocabulary sizes, results showed several differences between Word Targets and Actual Word Forms, consistent with lexical dominance. These findings challenge an ‘either–or’ phonological versus lexical dominance approach, and support consideration of a multifactorial set of influences, including different phonological dimensions and word positions, on the words that young children choose to say.

Analyses of two infilled lakes in Blekinge, southeast Sweden, indicate the presence of at least three tephra horizons of Termination 1 and early Holocene age. Geochemical analyses confirm the presence of the Borrobol Tephra, the Askja Tephra (10,000 14C yr B.P.), and one previously unreported tephra of Icelandic origin. Extending the limits of the Borrobol Tephra to Scandinavia illustrates that this ash is far more widespread than previously realized and is therefore, an important marker horizon for determining the rate and timing of the initial warming at the start of Greenland Interstade 1 (GI-1) within Europe. The relatively unknown Askja Tephra and the newly discovered Hässeldalen Tephra are stratigraphically placed at the Younger Dryas/Preboreal transition. This paper demonstrates the suitability and success associated with the extraction techniques for tracing microtephra horizons in areas distal to volcanic sources.

The goal of this study was to investigate non-adjacent consonant sequence patterns in target words during the first-word period in infants learning American English. In the spontaneous speech of eighteen participants, target words with a Consonant–Vowel–Consonant (C1VC2) shape were analyzed. Target words were grouped into nine types, categorized by place of articulation (labial, coronal, dorsal) of initial and final consonants (e.g. mom, labial–labial; mat, labial–coronal; dog, coronal–dorsal). The results indicated that some consonant sequences occurred much more frequently than others in early target words. The two most frequent types were coronal–coronal (e.g. dad) and labial–coronal (e.g. mat). The least frequent type was dorsal–dorsal (e.g. cake). These patterns are consistent with phonotactic characteristics of English and infants' production capacities reported in previous studies. This study demonstrates that infants' expressive vocabularies reflect both ambient language characteristics and their own production capacities, at least for consonant sequences in C1VC2 word forms.