The improvement in tear film stability was thought to play an important role in making the patients feel more

comfortable. This is consistent with previous studies, which reported that the TBUT is related to the dry eye symptoms [60] and [61]. This study has several limitations. First, its limited duration did not allow us to predict how long the effects of KRG administration would persist. The duration of the effect and optimal administration schedule for KRG treatment requires further investigation in patients with glaucoma. Second, because this study was performed only with Korean participants, we could not exclude any possible ethnic-related differences. Third, we did not evaluate the systemic effects of KRG, although no adverse events were noted during the study period. Checking vital BEZ235 molecular weight signs, including systemic blood pressure, or CB-839 performing blood tests to evaluate the inflammatory state would have enhanced our study. Despite these limitations, this is the first placebo-controlled study reporting the effect of KRG supplementation on the ocular surface and dry eye symptoms. In conclusion, our results indicated that daily supplementation of 3 g of

KRG for 8 weeks significantly improved the TBUT score and subjective dry eye symptoms, as compared to placebo. This improvement in dry eye was presumed to be induced by the anti-inflammatory property of KRG. Although further studies are required to identify a detailed mechanism, the use of KRG as a nutritional supplement is expected to be a clinically valuable additional option for dry eye and patients with glaucoma using antiglaucoma eye drops. None of the authors have any conflicts of interest to declare. The authors are grateful to Hye Sun Lee (Department of Research Affairs, Biostatistics medroxyprogesterone Collaboration Unit, Yonsei University College of Medicine, Seoul, Korea) for her help with the statistics. This work was supported by the 2010 grant from the Korean Society of Ginseng funded, Seoul, Korea.

“
“Colorectal cancer is one of the most common malignancies worldwide [1] and [2], and the 5-year survival rate is < 10% in the advanced stages [3]. Numerous effective drugs, including those currently used for cancer treatment, have been developed from botanical sources [4] and [5]. Thus, there still is a significant unexploited resource in herbal medicines. In our previous studies, we assessed the colon cancer chemoprevention potential of American ginseng, a very commonly used herbal medicine in the USA. [6] and [7]. In an in vivo investigation, the tumor xenograft nude mice model was used and significant antitumor effects of ginseng compounds were observed [8]. However, the xenograft mice model was not a commonly appreciated model for colon cancer studies.

The increase in hepatic triglyceride accumulation after EtOH feeding was significantly inhibited by RGE treatment (Fig. 2A). Lipid accumulation was also assessed by Oil Red O staining. Control mice did not show steatosis, whereas EtOH-fed mice exhibited a substantial increase in lipid droplets, which was in line with the results of H&E microscopy (Fig. 2B). RGE completely inhibited lipid infiltration in the liver, confirming Selleckchem ATM inhibitor the ability of RGE to prevent hepatic fat accumulation. The expression of hepatic fat metabolism-related genes was also assessed by quantitative real-time PCR. As shown in Fig. 3A, hepatic expression of

several lipogenic gene, including SREBP-1, FAS, and ACC was INCB018424 upregulated by EtOH feeding. This enhancement was completely reversed by RGE treatment. As previously reported, chronic alcohol consumption decreased fat oxidation-related genes, such as

Sirt1 and PPARα. However, RGE prevented EtOH-mediated decreases in lipogenic gene expression (Fig. 3A). Furthermore, RGE abolished the EtOH-induced enhancement SREBP-1 and depletion of PPARα protein in the liver (Fig. 3B). These results demonstrate that RGE inhibits EtOH-induced lipogenesis and restores alcohol-mediated decreases in fatty acid oxidation. Sustained exposure to EtOH leads to prolonged oxidative stress, which promotes lipid peroxidation and generation of reactive aldehydes, such as 4-HNE [27]. Previously, 4-HNE-positive cells were markedly increased in mice fed alcohol. However, RGE treatment led to a significant, dose-dependent reduction in 4-HNE positive cells (Fig. 4A). These data provide direct evidence that RGE

effectively inhibits lipid peroxidation and the formation of 4-HNE to protect hepatocytes from necrotic changes caused by EtOH. It is well known that prolonged reactive oxygen species (ROS) exposure leads to increased nitrotyrosine levels [28]. Nitrotyrosine immunoreactive cells were increased in the chronic EtOH-administration group as compared with the Immune system control. However, RGE treatment dramatically reduced the number of nitrotyrosine positive cells (Fig. 4B). We next assessed whether RGE treatment inhibited the induction of CYP2E1 caused by chronic alcohol intake. As anticipated, RGE significantly repressed the induction of CYP2E1 by EtOH (Fig. 4C). Our present data suggest that RGE protects against chronic alcohol-induced oxidative stress and hepatic injury. Next, we examined whether the effect of RGE on hepatic steatosis is associated with AMPK activation. Immunoblot analysis showed that the level of phosphorylated AMPKα in liver homogenates notably decreased after 4 weeks of alcohol administration as previously reported (Fig. 5) [24]. Treatment of alcohol-fed mice with RGE resulted in a complete recovery of AMPKα phosphorylation levels. We further measured the levels of phosphorylated ACC, a direct downstream substrate of AMPK.

Experimental and clinical studies increasingly show that alcohol-induced oxidative

stress is considered to be an early and indispensable step in the development of ALD [3]. Several pathways contribute to alcohol-induced oxidative stress. One of the central pathways is through the induction of cytochrome P450 2E1 (CYP2E1) by alcohol, leading to the induction of lipid peroxidation in hepatocytes [4]. Indeed, transgenic mice overexpressing CYP2E1 showed significantly increased liver damage following alcohol administration when compared with wild type mice [5]. By contrast, CYP2E1 knockout mice [6], and pharmacological inhibitors of CYP2E1 such as diallyl sulfide [7] and [8], phenethyl isothiocyanate [7] and [8], and chlormethiazole [9] decreased ethanol (EtOH)-induced lipid peroxidation and pathologic alterations. Chronic alcohol ingestion has been shown to increase levels of sterol regulatory element-binding protein-1 BGB324 (SREBP-1), a master transcription factor that regulates lipogenic enzyme expression, including fatty acid synthase (FAS), acetyl-CoA carboxylase (ACC), and stearoyl-CoA

desaturase-1 [10] and [11]. Alcohol intake also lowered levels of peroxisome proliferator-activated receptor-α (PPARα), a key transcriptional regulator of lipolytic enzymes, such as carnitinepalmitoyl-transferase-1 and uncoupling proteins [12]. In addition to regulating transcription factors associated with fat metabolism, alcohol affects the activities of enzymes involved in energy metabolism, including Epigenetic inhibitor in vivo adenosine monophosphate-activated protein kinase (AMPK) and sirtuin 1 (Sirt1). AMPK, a conserved cellular energy status sensor, is a serine–threonine kinase that can phosphorylate and subsequently

inactivate SREBP-1 in hepatocytes, thereby attenuating steatosis [13]. Expression of the Sirt1, nicotinamide adenine dinucleotide-dependent class III histone deacetylase, is decreased in mice fed with alcohol, resulting in increased levels of SREBP-1 acetylation [14]. In addition, hepatocyte-specific knockout of Sirt1 impaired PPARα signaling and β-oxidation, Etomidate whereas overexpression of Sirt1 elevated the PPARα target gene expression [15]. Hence, the AMPK/Sirt1 signaling axis is a promising therapeutic target to attenuate lipogenesis and increase lipolysis in ALD. Korean ginseng (Panax ginseng Meyer) is one of the oldest and most commonly used botanicals in the history of traditional Oriental medicine. It has a variety of pharmacological activities, including anti-inflammatory, -tumor, and -aging [16]. The ginseng saponins, ginsenosides, play a key role in most physiological and pharmacological actions of ginseng [17]. Korean Red Ginseng (KRG) is heat- and steam-processed to enhance biological and pharmacological activities [18]. Red ginseng contains higher amounts of ginsenosides, and some ginsenosides are only found in red ginseng [19].

05, a standard deviation (SD) in percent change from baseline in fasting serum triglycerides of 25%, and 80% power, it was estimated that 60 subjects would be required per group, and 300 subjects would be required, in

total. However, a large degree of intra-individual selleck screening library variation was observed in the TG measurements, which were not accounted for in the power calculation. Thus, in addition to present the TG level changes after 6 and 12 weeks, the mean changes from baseline at 6 and 12 weeks in fasting TG in the four krill oil groups were pooled in a time- and dose-independent manner for comparison to the placebo group. By doing so, the statistical power was increased and the relative (%) changes from baseline in fasting TGs were compared using a Student’s t-test. However, the pooling approach can only be seen as explorative data analysis. The other lipid parameters (total cholesterol, LDL-C and HDL-C) were not associated with large intra-individual signaling pathway variability and were therefore compared to the

corresponding measures in the placebo group using an analysis of variance (ANOVA), without pooling the data points across the krill oil groups. The TG data presented in Table 4 was analyzed using ANOVA. The statistical analyses were performed in JMP 10.0.2 (SAS Institute, Cary, NC). Changes were considered statistically significant at p < 0.05. All data are presented as means ± SD, unless otherwise specified. A total of 300 subjects were randomized into five groups and were supplemented with either placebo (olive oil) or one of four krill oil doses (0.5, 1, 2 or 4 g/day) (Fig. 1). Altogether, data for 33 subjects were not included in the efficacy analysis. The average of the Screening and Day 0 TG values was used as baseline TG values. However,

twenty-four subjects had a fasting TG level within the range required for inclusion at screening (i.e., between 150 and 499 mg/dL, find more inclusive); and not at baseline, where the fasting TG levels were normal (i.e., <150 mg/dL). Data for these 24 subjects were excluded from the analysis. Of the other 9 subjects whose data were not included in the efficacy analysis, 1 subject was determined from the dietary records to consume fatty fish more than twice per month, 1 subject had adverse events (hypertension; not related to study product intake), 3 subjects withdrew from the study (two because of scheduling conflicts and one for personal reasons) and 4 subjects had major protocol deviations (all four were not fasted at blood sampling). Daily EPA and DHA doses are depicted in Table 2, as are the numbers of subjects that could be used for the efficacy assessments. More males (69%) than females participated in the study. Most subject characteristics at baseline were not significantly different between the groups. In particular mean fasting serum TG values at baseline, which were approximately 232 mg/dL, were similar between the groups.

In between each injection, regeneration of the BSA sensor was performed using a low-pH buffer [48]. Selectivity of the developed BSA-imprinted electrode was tested together with other proteins (HSA, IgG) and selectivity as a result of imprinting efficiency was indicated with the comparison of the results obtained from NIP (non-imprinted) electrode. Bovine serum albumin (BSA), tyramine (99%, HOC6H4CH2CH2NH2) and human serum albumin (HSA) were obtained from Sigma (Steinheim, Germany). Acryloyl chloride

and 1-dodecanethiol were obtained from Aldrich (Deisenhofen, Germany). Glutaraldehyde 50% (w/v), triethylamine, 3-amino-propyl-triethoxysilane (APTES) and α-α’-azoisobutyronitrile (AIBN) were purchased from Fluka (Buchs, Switzerland). Human gamma globulin (human IgG) was purchased from Octapharma AB (Stockholm, Sweden). Glass microscope Cytoskeletal Signaling inhibitor cover slips (24 × 40 mm) (Menzel-Glaser) were selleck chemicals llc used as the base for protein stamp in microcontact imprinting. All other chemicals used were of analytical grade. All buffers were prepared with water processed using a reverse osmosis step with a Milli-Q system from Millipore (Bedford, MA, USA). Prior to use, all buffers were filtered through a Millipore filter (pore size 0.22 μm) and degassed for 1 h. The microcontact-BSA imprinted capacitive electrodes were prepared in three steps:

(a) Preparation of the glass cover slips (protein stamps): Glass cover slips (24 × 40 mm) were used for the preparation of protein stamps in this procedure. In the first step, cover slips were cleaned in 10 mL of 1 M HCl, de-ionized water, 1 M NaOH, de-ionized water and ethanol, respectively in ultrasonic cleaner for 10 min in each step. After cleaning, the cover slips were dried with nitrogen gas. The cleaned cover slips were immersed in 10% (v/v) APTES (3-amino-propyl-triethoxysilane) in ethanol

at room temperature for 1 h to introduce amino groups on the surface. Subsequently, the electrodes were rinsed with ethanol to remove any unbound APTES molecules. For the activation of the amino groups on the APTES modified cover slip surface, they were immersed in 5% (v/v) glutaraldehyde (GA) solution in 10 mM phosphate buffer (pH 7.4) at room temperature for 2 h. Then, the cover slips were rinsed with phosphate buffer to remove excess GA and dried with nitrogen triclocarban gas. In the last step, the cover slips were immersed in 0.1 mg/mL BSA solution (in phosphate buffer, 10 mM, pH 7.4) at 4 °C for 24 h for the immobilization of BSA onto the surface. Finally, the cover slips were washed with phosphate buffer and then, dried with nitrogen gas. They were kept at 4 °C in a closed Petri dish until use. (b) Preparation of the capacitive gold electrodes: In the first step, gold electrodes were washed with ethanol, de-ionized water, acetone, de-ionized water and piranha solution (3:1, H2SO4:H2O2, v/v), respectively for 10 min in each step in ultrasonic cleaner.

, 2008). Test chemicals are dissolved or uniformly distributed in either physiological saline, 5% dimethyl sulfoxide (DMSO) in physiological saline, or mineral oils as test solvents, as opposed to culture medium which is often used in cytotoxic tests. This allows for water insoluble materials, acids and amides to be evaluated

(Takahashi et al., 2008), which would otherwise have weakened effects when media is used as a solvent, due to the buffering effect that the media may have. As the name suggests, the exposure time to a given chemical is very short, it is only 5 min, compared to longer exposure times used in the FL assay (15 min) and the neutral red assay (1, 5 or 30 min) (Takahashi et al., 2008) for example. It is believed that that the short exposure is more similar to actual exposure conditions to a consumer Bioactive Compound Library concentration product, whilst also providing fast results (Kojima et al., 2013 and Takahashi et al., 2011). This C59 wnt cell line also allows the STE to be used for high-throughput screening to evaluate many chemicals. Two different concentrations of the test material are evaluated, 5 and 0.5%, respectively. Post exposure cell viability is compared to a solvent control (relative viability) (OECD, 2014a and Takahashi et al., 2011). If the cell viability is ≤70% at both 0.5 and 5% concentration, then the chemical is classified as GHS Category 1. If cell viability if ≥70% at

both concentrations then the chemical is classified as GHS No Category (OECD, 2014a). The STE was submitted to the OECD in 2011 as a method of high-throughput screening (Kojima et al., 2013) to evaluate minimal, moderate and severe eye irritation. The STE is currently under investigation via the OECD for regulatory acceptance as part of a tiered-testing strategy for either top–down or bottom–up approaches. It is recommended that STE is used for the identification of GHS Category 1, severe irritants and GHS No Category, non-irritants, although in both instances further testing is required to establish a definitive

classification ( OECD, 2014a). It is not recommended for the identification of GHS Category 2 (A or B) chemicals. Penetration of a dye or reagent through a barrier of cells is another approach to assess cytotoxicity FER (Fig. 6). The FL assay (TG 460, (OECD, 2012c) can reveal the toxic effects of chemicals following a short exposure. A monolayer of Madin–Darby canine kidney (MDCK) cells are grown on permeable cell inserts. The test works by measuring the amount of fluorescein leakage through the cell monolayer which can be used to determine the integrity of the barrier formed by the cells. Cytotoxicity would result in an increase in the penetration of fluorescein through the monolayer. Increased in vivo permeability of the corneal epithelium correlates with the degree of inflammation and surface damage as eye irritation occurs.

Among patients with advanced disease (stage IIIB/IV), prognosis remains poor, with 5-year survival estimated at 15.9% [3]. For patients with advanced (stage IIIB/IV) NSCLC, clinical guidelines recommend the use of 2-drug combination regimens as first-line

therapy [4] and [5]. First-line treatment is often a combination therapy using platinum plus taxane-based chemotherapeutic agents with or without biologics or platinum plus targeted small-molecule therapy. Recent evidence from various phase III clinical trials has demonstrated the efficacy of specific combination treatments like pemetrexed/cisplatin (Pem/Cis) and paclitaxel/carboplatin/bevacizumab (Pac/Carbo/Bev) in the first-line setting for patients with advanced nonsquamous NSCLC [6] and [7]. Despite lack of data from phase III trials directly comparing clinical outcomes selleck compound associated with Pem/Cis with Pac/Carbo and Pac/Carbo/Bev, these three regimens are frequently used in clinical practice as first-line treatment. Additionally, to our knowledge, few studies have used real-world data to compare the clinical and economic outcomes associated with these treatment strategies. The primary objective of this retrospective observational study was Selleckchem Galunisertib to examine the real-world incremental

cost effectiveness of a first-line chemotherapy regimen with pemetrexed plus platinum (Pem/Plat therapy) combination relative to the Pac/Carbo combination (doublet) and the Pac/Carbo/Bev combination (triplet) in patients with advanced nonsquamous NSCLC in the US outpatient medical oncology setting. This retrospective cohort study used data captured within the International Oncology Network (ION) clinical oncology database from January 2006 through December 2010. This electronic medical records (EMR) database captures outpatient-practice encounter history for

patients under very care of 175 geographically dispersed providers, representing 20 large, community-based practices across 13 states. The database includes laboratory results, diagnosis, disease profile, anthropomorphic measures, vital signs, treatment plan, specific therapy administrations associated with treatment plans, other medications such as supportive care agents, and performance status. The data elements described above are typically captured through either standardized fields or electronic progress notes. For purposes of this study, electronic progress notes were reviewed to abstract and/or verify information on necessary clinical and demographic characteristics, including advanced disease status, histology, and other inclusion criteria. In addition to clinical EMR data, practice management system (PMS) data are incorporated within the EMR database; these data include patient demographics, treatment given, diagnosis information, dates, and billed transactions from the outpatient medical oncology setting. Utilization outside of this setting (e.g.

Recent advances in genetic and imaging techniques have established the zebrafish as an excellent model to study behaviour. Their short development time, compact size and ease of imaging deep within the brain have allowed the neural circuits that control behaviour to be mapped. Increasingly sophisticated optogenetic tools and virtual world setups allow larval fish to be manipulated and monitored in real time 1, 2••, 3, 4 and 5]. Adult zebrafish are also emerging as a powerful model for behaviours including aggression, anxiety, learning, memory and shoaling 6, 7, 8•• and 9•] (Table 1). In this review we will highlight recent studies in which zebrafish have contributed to our understanding

of behavioural genetics. Zebrafish larvae start to hunt

prey such as paramecia from around 5-days post fertilisation. Prey capture is achieved through a series of stereotyped manoeuvres which are Sirolimus solubility dmso triggered when prey enters the field of view. The first movement is eye convergence followed by a calibrated series of J-turns — flexions of the caudal tail that orientate the fish towards its target. The sequence is completed by a capture swim [4]. Hunting behaviour can be measured by placing larvae in a virtual environment where films Alisertib are used to trigger tail and eye responses [4]. Small moving objects such as paramecia are detected by the optic tectum which responds visuotopically to moving (but not static) stimuli [10], as has been demonstrated using the genetically encoded calcium indicator

GCaMP7a [11•]. GCaMP is a modified version of GFP that increases in brightness upon entry of Ca2+ into the cell [12]. The genetic basis of GCaMP7a enables it to be restricted to specific populations of cells. The optic tectum projects to a pair of neurons in the lateral part of the nucleus of the medial longitudinal fasciculus (MLF) called MeLr and MeLc [13]. Laser ablation of the MeLr or MeLc reduces the ability of larvae to capture prey suggesting this behaviour is largely driven by MLF activation [13]. The combination of fixed-loop virtual environments and genetically based calcium indicators permits the investigation of how objects in the visual field are processed at all levels of the central ifoxetine nervous system. This setup could now be used to screen for novel mutants that show aberrant hunting behaviour. Lateralisation, asymmetries of body viscera, brain areas and behaviour is a widespread property of many vertebrates including fish. In the brain, lateralisation has the potential to specialise neural circuit function which may give rise to new behavioural phenotypes [14]. In zebrafish the left and right habenulae (Hb) of the epithalamus exhibit prominent asymmetries that are established by left-sided expression of Nodal pathway genes during development [15]. The Hb receives inputs from the olfactory bulb and retina and projects to the periaqueductal grey matter via the interpeduncular nucleus (IPN) [14].

Therefore, the equation of the ship’s motion in the body-fixed coordinate system adopted in the MMG is written as: equation(4) {(m+mx)u−(m+my)vr=X(m+my)v+(m+mx)ur=Y(Izz+Jzz)r=Nwhere m is the mass, mx and my are added mass, and u and v are components of velocity in the directions of the x-axis and the y-axis, respectively, and r is the angular acceleration. Izz and Jzz are the moment of

inertia and the added moment of inertia around G, respectively. X and Y are hydrodynamic forces, and N is the moment around the z-axis. According to the MMG model, the hydrodynamic forces and the moment Depsipeptide in the above equation can be written as: equation(5) {X=XH+XP+XR+XT+XA+XW+XEY=YH+YP+YR+YT+YA+YW+YEN=NH+NP+NR+NT+NA+NW+NEwhere the subscripts H, P, R, T, A, W, and E denote the hydrodynamic force or moment induced by the hull, propeller, rudder, thruster, air, wave, and external forces, respectively. Hydrodynamic forces caused by wind, waves, and currents are defined in (6), (7) and (8), PD0332991 respectively. equation(6) {XA=ρA2VA2ATCXA(θA)YA=ρA2VA2ALCYA(θA)NA=ρA2VA2LALCNA(θA)where ρ  A is the density of air, θ  A is the

relative wind direction, V  A is the relative wind velocity, and A  L and A  T are the frontal projected area and lateral projected area,

respectively. C  XA, C  YA, and C  NA are the coefficients. In this paper, these coefficients were estimated by the method of Fujiwara et al. (1998). equation(7) {XW=ρgh2B2/LCXW¯(U,TV,ℵ−φ0)YW=ρgh2B2/LCYW¯(ω0,ℵ−φ0)NW=ρgh2B2/LCNW¯(ω0,ℵ−φ0)where ρ   is the density of seawater, g   is the acceleration of gravity, h   is the amplitude of significant wave height, B   is the ship’s breadth, and L   is the length of the ship CXW¯., CYW¯ and CNW¯ are averages of short-term estimated coefficients calculated by the Research Initiative on Oceangoing Ships (RIOS) at the Institute GBA3 of Naval Architecture, Osaka University. It was established for the purpose of improving the performance of ships in wind and waves by calculating the hydrodynamic force on the hull surface, including the added resistance, wave-induced steady lateral force, and yaw moment. By using the principal properties, arrangement plan, and body plan of a certain ship, the frequency-domain response characteristics of wave-induced ship motions with six degrees of freedom can be computed utilizing the EUT (Enhanced Unified Theory) ( Kashiwagi et al., 1999). In the RIOS system, the wind wave is represented by the ITTC spectrum, and the swell is represented by the JONSWAP spectrum).

, 2011), a phenomenon referred to as sound symbolism. It has also been reported that toddlers

are not only sensitive to sound symbolism (Maurer et al., 2006) but also make selleck screening library use of sound symbolism in verb learning (Imai et al., 2008 and Kantartzis et al., 2011). The results from preverbal infants (Ozturk et al., 2013 and Peña et al., 2011) and those from toddlers (Imai et al., 2008, Kantartzis et al., 2011 and Maurer et al., 2006) support the idea that sound symbolism plays an important role in the ontogenesis of language (Imai and Kita, 2014, Imai et al., 2008 and Maurer et al., 2006). It is generally agreed that infants start to associate speech sounds and visual referents at around 12–14 months. At this age, however, the process is effortful because infants have limited information processing capacities and little experience in mapping words to the world (Fennell and Werker, 2003 and Werker et al., 1998). They may rely more on perceptually based cues that are available without prior word learning experiences, such as cross-modal correspondences between speech and visual input in their word learning. Indeed, previous research suggests that 14-month-old infants use sound-symbolic correspondences between speech sounds and object properties as a cue in their effort to establish word (speech sounds) – referent associations (Imai

et al., under review and Miyazaki et al., learn more 2013). Thus, there is some evidence that sound symbolism helps young infants at the initial stage of word learning. However, how sound symbolism is processed in the infants’ brain has not yet been addressed in the literature. It is not conceivable that four-month-old infants are actively engaged in semantic processing when they hear speech sounds together with a visually presented referent (Stager & Werker, 1997). Thus, infants at this age are likely to process

sound symbolism perceptually, Bay 11-7085 possibly on the basis of cross-modal binding mechanisms. However, at later times, the influence of sound symbolism is likely to transpire in temporal windows compatible with higher-level information processing, i.e., the semantic level. In this study, we investigated how 11-month-old infants respond to sound symbolism. If perceptual cross-modal mapping ability scaffolds the establishment of word-referent associations, we might see the effect of sound symbolism in two time-windows: (a) in an early time window coinciding with the time period of perceptual processing, and (b) in a time window coinciding with higher-level cognition and/or semantic processing. We chose to study 11-month-olds because they are just about to say their first words but there is little or no evidence to date for the successful establishment of novel word-referent associations in experimental settings at this age. To examine this possibility, we recorded EEG from nineteen children during the presentation of novel word – visual shape pairs that were either sound-symbolically congruent or incongruent (Fig.