We investigated effects of sign language use and auditory deprivation from birth on the volumes of three cortical regions of the human brain: the visual cortex surrounding the calcarine sulcus in the occipital lobe; the language-related cortex in the inferior frontal gyrus (pars triangularis and pars opercularis); and the motor hand region in the precentral gyrus. The study included 25 congenitally deaf participants and 41 hearing participants (of which 16 were native sign language users); all were right-handed. Deaf participants exhibited a larger calcarine volume than hearing participants, which we interpret as the likely result of cross-modal compensation and/or dynamic interactions within sensory neural networks. Deaf participants also had increased volumes of the pars triangularis bilaterally compared to hearing signers and non-signers, which we interpret is related to the increased linguistic demands of speech processing and/or text reading for deaf individuals. Finally, although no statistically significant differences were found in the motor hand region for any of the groups, the deaf group was leftward asymmetric, the hearing signers essentially symmetric and the hearing non-signers were rightward asymmetric – results we interpret as the possible result of activity-dependent change due to life-long signing. The brain differences we observed in visual, motor, and language-related areas in adult deaf native signers provide evidence for the plasticity available for cognitive adaptation to varied environments during development. Across the lifespan, the structural and functional plasticity of the mammalian brain is expressed through a variety of mechanisms and pathways. Several factors influence the potential plastic response of the brain to environmental influences. The extreme and inherent plasticity of the brain in early development is “braked” by a variety of cellular processes that serve ultimately to demarcate a critical or sensitive learning period, during which highly stable functional pathways are trained and established . CorticaA potentially valuable source of insights into the structural and functional plasticity of the human brain is the neurocognitive study of deaf and hearing individuals who are native users of a sign language . CongeniDue to auditory deprivation during critical developmental periods, some neural changes should be evident in deaf compared to hearing individuals. Auditory regions of the brain are an obvious candidate for plastic changes, and we have shown that deaf people have decreased white matter in and around Heschl’s gyrus, the anatomical landmark for the primary auditory cortex ; this fiHere we investigate the effects of sensory deprivation and sign language expertise on plasticity in the human brain by comparing regional cortical volumes in adult, right-handed congenitally deaf signers, hearing signers who acquired American Sign Language (ASL) from birth from their deaf families, and hearing non-signers. We used high-resolution magnetic resonance imaging (MRI) and anatomical landmark-based morphometry to directly measure the cortical volumes of three important and informative regions incorporating visual, language, and motor areas: (1) a primary sensory cortical region – the cortex surrounding the calcarine sulcus in the medial occipital lobe, a proxy for the primary visual cortex or Brodmann area (BA) 17 ; (2) an Based on previous studies of enhanced visual ability in deaf individuals  study with 14 deaf native signers, N = 12) and reported increased gray matter density in the left motor hand area compared to hearing non-signers. The authors hypothesized that increased fine motor control of the dominant hand during signing contributed to volume increases in this area. If this hypothesis is correct, then we should observe differences in the size and/or asymmetry of the motor cortex in the hand region (the handknob) for the signing participants (both deaf and hearing) compared to the non-signers. However, changes in motor cortex may be even more pronounced for deaf signers because ASL is their dominant and most frequently used language compared to hearing signers , 25 hearing individuals with no knowledge of ASL , and 16 hearing individuals who acquired ASL as young children from their deaf parents . The hearing signers (who had no history of hearing loss) were born into deaf signing families and acquired expertise in ASL as children, concurrently with their acquisition of spoken language. The hearing non-signers were monolingual English speakers with no history of hearing loss. All subjects were right-handed, with scores on the Oldfield–Geschwind Handedness Inventory > +90 (maximum right-handed score +100). All subjects were healthy with no history of neurological or psychiatric illness. Twenty-one deaf subjects exhibited profound hearing loss (>90 dB in the better ear), three subjects had severe hearing loss (>75 dB in the better ear), and one subject had moderately severe hearing loss (>55 dB in the better ear). Data on early hearing aid use was available for 17 deaf subjects. None used a hearing aid consistently before the age of 2. Eleven were required to wear hearing aids at school, but only two also wore hearing aids at home, and six subjects did not wear hearing aids at home or at school. All deaf subjects were congenitally deaf and were born to deaf parents, and ASL was their primary and first language. All subjects gave informed consent in accordance with institutional and federal rules.post hoc using Automated Image Registration  were conducted using Brainvox , an inteRegions of interests were traced by hand in each hemisphere  on contiguous coronal or axial slices of the brain. The study focused on three cortical ROIs: the cortex surrounding the calcarine sulcus (corresponding to BA17), the pars triangularis and opercularis of the IFG , and the primary hand motor cortex (corresponding to a sector of BA4) and clearly visible on axial and parasagittal MRI slices . Total cFigure 1A). The ROI of the calcarine cortex included all side branches until its termination at the occipital pole. The surface cortex included was determined by extending a line from the cortical depth of the banks of the sulcus proper to the pial surface. It is important to note that while the calcarine sulcus is a strong anatomical landmark indicating the position of the primary visual cortex, the striate cortex itself extends variably onto the mesial surface of the occipital lobe surrounding the calcarine sulcus , both banks of the calcarine sulcus were traced posterior to the intersection with the parieto-occipital sulcus; anterior to this point, only the lower bank was traced  anteriorly, the ascending branch of the Sylvian fissure (AscSF); (2) posteriorly, the inferior precentral sulcus (PreCS); (3) superiorly, the inferior frontal sulcus (IFS); and (4) inferiorly, the Sylvian fissure (SF). The ascending branch of the SF does not typically reach the IFS, therefore a line connecting the superior end of the ascending branch of the SF to the IFS was drawn perpendicular to the AC–PC plane to close this boundary. When the IFS did not reach the inferior PreCS, a direct line, parallel to the AC–PC plane, from the posterior end of the IFS was used to close the superior boundary. The boundaries for the pars triangularis were: (1) posteriorly, the anterior boundary of pars opercularis formed predominantly by the ascending branch of the SF; (2) inferiorly, the horizontal branch of the SF (HzSF); and (3) antero-superiorly, the IFS, as it extends anteriorly and inferiorly toward the anterior end of the HzSF. A line was drawn from this point to the antero-inferior end of the IFS to close off the anterior boundary. If the IFS was broken into two or more segments, connecting lines were drawn to link the segments. The pars triangularis and opercularis ROIs included all of the cortex located within the boundaries. Gray matter volumes for Broca’s area and its right hemisphere homolog were determined by summing the volumes of the pars opercularis and triangularis.Tracing of Broca’s area and the homologous region in the right hemisphere (consisting of the pars triangularis and pars opercularis) was done following Figure 1C). It can be identified anatomically in MRI by a sector of the precentral gyrus projecting into the central sulcus (the handknob), which is clearly visible in the axial plane; its position can also be seen in both parasagittal and coronal slices . Hemispheric asymmetries were also examined with a conventional asymmetry index (AI) {(L - R)/[(L + R)/2]}.Statistical analyzes were performed using SPSS 19 for Windows . For each ROI, main effects of hemisphere  and group  were assessed using a 2 × 3 repeated measures analysis of variance (ANOVA) with total cerebral cortical (gray matter) volume as the covariable. F = 1.136; df = 2,63; p = 0.328); however, the average volume of the hearing signer group was somewhat smaller  than the deaf group  and the hearing non-signer group . Therefore, group differences for each of the target regions were assessed with total cortical hemisphere volume as a covariable.Volumes of major brain regions are often correlated for size , therefoTable 1 and Figure 2. The 2 × 3 repeated measures ANOVA showed a significant main effect for hemisphere . The volume of the calcarine cortex was strongly rightwardly asymmetric in all three groups. AI scores were -0.124 (SD = 0.120) for the hearing non-signers, -0.108 (SD = 0.166) for the deaf signers, and -0.161 (SD = 0.156) for the hearing signers. There were no significant differences among the groups for AI score. Within each group, pair-sampled t-tests showed that the right calcarine was significantly larger than the left . The interaction between hemisphere and participant group was not significant.The mean volumes of the left and right calcarine sulcus cortex are presented in F = 3.241; df = 2,62; p = 0.046). Post hoc group-wise comparisons showed that total calcarine volume was significantly larger in the deaf participants compared to hearing non-signing participants . There were no significant differences between the hearing signing and non-signing participants. Examining each hemisphere separately, we found that the deaf participants’ left calcarine volume was significantly larger than for both the hearing non-signers  and the hearing signers . The right calcarine was also larger in the deaf group compared to the other two groups, but the differences were not significant.The 2 × 3 ANOVA also showed a significant effect of group . There was no interaction between hemisphere and participant group.The volumetric results for the pars triangularis and pars opercularis for the left and right hemispheres are presented in F = 6.627; df = 2,62; p = 0.002). Post hoc tests showed the pars triangularis volumes were significantly larger for the deaf signers compared to the hearing non-signers for the combined volume , for the left hemisphere volume , and for the right hemisphere volume . A similar pattern was seen comparing the deaf signers to the hearing signers, with the combined volume (L + R) difference reaching statistical significance . There were no significant differences between the hearing non-signers and hearing signers in the pars triangularis volumes.For the pars triangularis, there was no significant main effect of hemisphere or interaction between participant group and hemisphere. However, there was a significant main effect of group . The hearing signers had essentially symmetrical handknobs. Comparing the deaf signers to the hearing non-signers (leaving the hearing signers out of the model), the AI score was significantly different between the two groups .Motor handknob cortical volume results by hemisphere are presented in The results presented here expand our perspective on the scope of structural cortical plasticity associated with congenital deafness and life-long signing. We found significant differences between the deaf and hearing groups in the cortex of the calcarine sulcus and the pars triangularis, while the handknob results suggested that this region may be lateralized differently in deaf signers compared to hearing non-signers. In general, the hearing signers were more similar to the hearing non-signers than to the deaf signers, suggesting a primary influence of auditory deprivation in shaping neuroanatomical plasticity. This is not to say that the differences observed between deaf and hearing individuals were solely due to lack of auditory experience, but that the combination of sign language usage and deafness may have had a large role in shaping the cortical differences we observed.t-tests. A rightward gray matter asymmetry in the cortex of the medial occipital lobe in the neighborhood of the calcarine sulcus has been observed in several studies using automated assessment methods . Given the positive correlation between intracalcarine striate cortex volume and total striate cortex volume  is known to be involved in a variety of linguistic and cognitive functions that may differ for deaf and hearing individuals . However, we speculate that the increased demands faced by congenitally deaf individuals for deciphering spoken language through both print and lip reading may underlie the increased cortical volumes observed here.Our results revealed that the pars triangularis  was significantly larger in the deaf group compared to either of the hearing groups. The pars opercularis showed no significant group differences, although there was a trend for larger volumes in the deaf group. These results partially replicate the findings of For deaf children, access to sound-based phonology is greatly reduced or absent, and many struggle to learn to read. Recent neuroimaging studies with deaf adults have reported that when the reading task requires phonological processing, deaf readers exhibit greater activation in the IFG (both pars triangularis and pars opercularis) compared to hearing readers . Less skIn addition, the demands of acquiring spoken language primarily from visual input may also lead to an increase in the volume of the pars triangularis. For deaf individuals, speech reading will have to rely, necessarily, on visual and articulatory rather than auditory cues. The increased volume of Broca’s area (mainly pars triangularis) shown here, and the increased volume of the left posterior insula described earlier , may repThe handknob is a reliable landmark for the position of the hand primary motor cortex in the precentral gyrus M1; . HoweverSurprisingly, an expected direct link between anatomy (the volume or gray matter density of the handknob) and handedness has not been definitively established. The strong expectation is that the handknob would be larger on the contralateral side to the dominant hand. Direct evidence to support or refute this expectation has been lacking, possibly because there have been very few direct volumetric studies of the human handknob, and various proxy or indirect measurements have produced equivocal results see . An autoOur results for right-handed non-signers, based on direct anatomical measurement of the volume of gray matter encompassed by the region corresponding to the hand, are consistent with those studies finding a rightward asymmetry in the handknob. Our AI indicated that the right hemisphere handknob was about 14% larger than the left, a magnitude of asymmetry that is generally considered to be noteworthy. It is interesting to note that neither of the two signing groups exhibited such a rightward asymmetry: the hearing signers were essentially symmetrical, while the deaf signers were actually 11% larger in the left hemisphere. The AI of the deaf individuals was significantly different from that of the hearing non-signers. This intriguing finding together with the finding of essential symmetry in the hearing signers suggests the possibility of activity-dependent plasticity resulting from sign language usage and deserves further investigation.Our results are also consistent with Penhune et al.’s (2003) hypothesis that the fine motor control of the hands required for signing leads to structural changes in the hand motor region. Furthermore, plastic gray matter changes in the hand region with motor training have been reported . There aCongenitally deaf individuals who are native users of sign language showed evidence of structural cortical changes in each of the three brain regions examined. Increased bilateral volumes of the calcarine cortex and the pars triangularis in deaf individuals relative to the volumes of both signing and non-signing hearing individuals provide evidence of likely developmental cortical plasticity in response to an environment of auditory deprivation. Differences in lateralization of the motor hand region observed for deaf and hearing signers may be related to early and prolonged use of sign language. Because of the variability seen in this region, this finding should be further pursued in larger samples. Overall, the study of structural and functional brain anatomy in congenitally deaf signers provides an insight into the variety of forces that influence cognitive and structural adaptation to specific environments.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.


The present study seeks to describe and analyze the syntactic features of children with severely hearing loss who had access to the hearing aids compared with children with normal hearing, assigning them to the same separate gender classes. In the present study, eight children with severe hearing impairment who used a hearing aid and eight hearing children matched for age and gender were selected using an available sampling method based on the principles of auditory-verbal approach. Hearing children had an average age of 5.45 ±1.9 years and subjects had a mean age of 5.43±2.17 years and their rehabilitation had begun before they were 18 months old. The assessment instrument of the study included the language development test, TOLDP-3. The syntactic skills of these children were analyzed and compared with the hearing children of the same age based on gender. There was a significant difference between the syntactic scores of the hearing-impaired children and the scores of the hearing children of the same age in the “sentence imitation”  and “grammatical completion”  subtests, with no significant difference in the “grammatical understanding” subtest . Moreover, there was no significant difference between male and female children with hearing impairment in terms of syntactic skills development.With early diagnosis and timely rehabilitating intervention, children with hearing loss can perform in a similar way to children of their age with normal hearing in some syntactical areas. Furthermore, the gender factor in the present study had no effect on the development of syntactical skills of children with hearing loss.  Language is such a complex system that only humans have the capacity to learn it. Furthermore, language skills are acquired gradually and in specific steps. At the age of 5, a child’s linguistic system is almost identical to that of an adult to the extent that he/she can meditate and express thoughts accurately via language . The first 36 months of a child's life are critical for language learning, and are incomparable with any other periods of life in terms of language acquisition. Therefore, age is a crucial factor in the emergence and development of language . AccordiThe speech of children with hearing impairment, especially those with severe hearing loss (71– 90dB threshold), is barely comprehensible; an issue that can expose these children to a plethora of social, emotional, educational, and perceptive problems . The resLinguists define syntax as the organization or arrangement of the words in a sentence. In syntactic relations, two types of relations are usually mentioned: syntagmatic relations as well as hierarchical and paradigmatic relations. In a linear organization of the speech, we deal with the syntagmatic elements in a specific order, while in the hierarchical (syntagmatic) organization, the internalized structures are addressed. Both cases require grammatical knowledge, which, as pointed out by Chomsky, is innate and internalized in the human being, waiting to be recalled and utilized when the situation arises .Grammatical and syntactic problems are among the linguistic issues that children with hearing loss encounter. Studies have shown that children with hearing loss pass the growth stage of language development at a slower pace compared with their peers; a subject that has been investigated in different linguistic areas including syntax, semantics, pragmatics and even writing . The devBamford and Saunders also showed that the hearing impaired are more likely to use content words, nouns, and verbs in their speech while grammatical words such as prepositions, pronouns, auxiliary verbs and conjunctions are rarely used . Gray clIn this study, hearing-aid users were compared with hearing children matched in ability on one aspect of language; general syntactic ability. Unlike most studies which focus on the rate of language learning or extent of delay, this study compares the syntactic profile of hearing-aid users with that of hearing children. It is known that hearing-impaired children often demon- strate delays relative to their hearing peers; this study will allow us to compare the extent of those delays across different areas of syntax acquisition. Given the importance of hearing sense, as discussed earlier, this study defines the importance of syntax and identifies strategies to promote the development of syntax in spoken language through listening. Further, the current research seeks to examine the syntactic skills and the role of gender in children with hearing loss under training by adopting a descriptive-analytic perspective, and compares it with the normal children in order to identify the difference between these two groups and offer effective clinical strategies for the early rehabilitative intervention by speech and language pathologists, audiologist, and linguists. The present research is a cross-sectional descriptive-analytical study that draws on an available sampling method. The population included eight hearing children with an average age of 5.45 years and eight hearing-impaired children with a mean age of 5.43 years  with bilateral sensory-neural hearing loss who had been exposed to rehabilitative programs with an auditory-verbal approach. Subjects were selected for the study after completing a questionnaire to collect personal information and recording scores, including information about personal and family status as well as auditory and training state. For children with congenital hearing loss, the information was collected from the rehabilitation file. Monolingual and Persian-speaking children with normal hearing from the same class, who were the same age as the children with hearing loss and had no precedent of hearing problems, were also included in the study. Hearing-impaired children, with normal visual and hearing parents, whose mean hearing loss was between 71 and 90 dB (severe) were included in the study. Aside from hearing impairment, exclusion criteria included history of mental disability, cerebral palsy, and a background of any other related diseases. These children were examined by a psychologist through an IQ test by Wechsler Nonverbal and Good-Enough Scales and an occupational therapist using Infant Sensorimotor Development, infant sensorimotor development and the prediction of childhood IQ developed by Hogarty S and co-workers in 1972 , that diThe language development test, TOLDP-3, which includes syntactic subtests such as "grammatical understanding", "sentence imitation", and "grammatical completion", was used in this study. TOLDP-3 was introduced by Newcomer and Hammill in 1997 as a language development test. TOLDP-3 was developed for children aged 0–4 to 8–11 years. The test was normalized for the Iranian context by Saeid Hassan- zadeh and Asghar Minaee in 2001  ,20.Statistical analysisData obtained from syntactic subtests in the two classes of children with hearing loss and children with normal hearing as well as gender-segregated classes of male and female children with hearing impairment were analyzed by SPSS software based on Version 19. The mean and standard deviation were used for descriptive analysis, while the t-test was used for independent groups in the above classes because the distribution of data was normal according to the Kolmogrov-Smirnov test. P<0.05 was statistically considered significant. All children in the learning center have been taught by routine rehabilitation without any intervention. However, signed informed consent was provided by parents of all the children. According to As it can be seen, there was no notable difference between the two groups in the grammatical understanding subtest, while in the two other subtests  a considerable difference between the standard scores of the two groups was observed.A parametric test (t-independent) was used due to the normal distribution of the data to compare the syntactic skills of both male and female children with hearing impairment. In order to compare the syntactic skills between children with hearing loss and children with normal hearing, a parametric test (t-independent) was used due to the normal distribution of the data.The results of this study show that the performance of children with hearing loss and children with normal hearing in the two subtests of sentence imitation and sentence completion, which required proper use of vocabularies and sentences, were in line with the finding of Peters  and BamfConsidering that gender is one of the factors influencing the language of the children; the studies suggest that this effect is only significant in the early language learning stages. According to the present study, there was no significant difference between male and female children with hearing impairment in syntactic aspects in all three subtests, and they had almost similar standard scores and syntactic gains. This finding is in keeping with the studies of Clark and Stewart (1973), Roberts and Block (1972), Arshi (2000) on the difference between male and female children with hearing impairment in terms of linguistic capacities, which did not report any difference in this regard . The studies of Mofidi et al show that normal students who attended preschool language learning courses had a superior performance in syntactic skills such as grammatical understanding, sentence imitation, and grammatical completion compared with students who failed to attend these classes . This isOur study also had some limitations. Apart from limited sampling, the results were based on cross-sectional data instead of a longitudinal study. Another limitation was the range of our subjects with hearing loss, since all subjects had severe hearing loss. To investigate the hearing loss effect it also could be appropriate to evaluate cochlear implant. Syntax is one of the skills that is learned during growth, particularly the critical period. The development of language skills is influenced by the manner of speech of the people around the child, especially the mother, as well as sentence complexity, repetition and practice, and proper communicative events. Thus, the comparison of the syntactic skills of children with hearing loss and children with normal hearing in this paper shows that the earlier exposure of children with hearing loss to natural and appropriate environment as well as timely and proper rehabilitative education with emphasis on auditory sense can improve the performance of these children to the level of normal children in some syntactic areas, and minimize the delay in other areas through persistency and proper planning. We recommend that, in the future, studies include a large sample and a specific intervention. After a period of time, studies should also investigate children with a hearing aid with respect to other aspects of language skills such as speech production and speech perception.


ApcMin/+ mice will be described. Finally, chemoprevention of inflammation-associated colon carcinogenesis will be mentioned.Chronic inflammation is a well-recognized risk factor for development of human cancer in several tissues, including large bowel. Inflammatory bowel disease, including ulcerative colitis and Crohn's disease, is a longstanding inflammatory disease of intestine with increased risk for colorectal cancer development. Several molecular events involved in chronic inflammatory process may contribute to multistep carcinogenesis of human colorectal cancer in the inflamed colon. They include overproduction of reactive oxygen and nitrogen species, overproduction and upregulation of productions and enzymes of arachidonic acid biosynthesis pathway and cytokines, and intestinal immune system dysfunction. In this paper, I will describe several methods to induce colorectal neoplasm in the inflamed colon. First, I will introduce a protocol of a novel inflammation-associated colon carcinogenesis in mice. In addition, powerful tumor-promotion/progression activity of dextran sodium sulfate in the large bowel of  Helicobacter pylori and reported its infection closely associated with gastric cancer development, won the Nobel Prize in Physiology or Medicine in 2005, there have been an increasing number of reports on PubMed as to the relationship between inflammation and carcinogenesis in a variety of tissues  in inflammatory bowl diseases (IBDs) such as ulcerative colitis (UC) and Crohn's disease (CD)  [3]. I hPatients with UC as well as those with colorectal cancer have been increasing in Asian countries including Japan, similarly to Western countries  5]. The. The5]. de novo type, and colitic cancer type)  2, iNOS, and several cytokines produced in the infiltrated inflammatory cells and accumulation of genetic abnormality, such as a loss of the DCC gene, leads to invasive colorectal cancer. Unlike common colorectal cancer (adenoma-carcinoma sequence type), it has been thought that the APC  and K-ras genes and microsatellite instability (MSI) are hardly involved in this type, but there remains to be further discussed . Of . Of de nNat Med since 1998 . Ab. Ab10]. nce 1998 –15, we cnce 1998 –18, had β-catenin in the nuclei of colorectal adenocarcinoma cells was observed.Since DSS is a nongenotoxic carcinogen , male ICDose dependence of tumor-promotion activity of DSS after a single intraperitoneal administration of AOM (10 mg/kg body weight) was subsequently examined at five doses  of DSS  21]. Th. Th21]. γ expression in the colonic mucosa at five and 10 weeks after the AOM administration  [β-catenin   as an in-catenin . Mutatio2 and 34 . HoweverThere was a report of a difference in sensitivity of DSS-induced colitis among the species of mice . To inveMin/+  Apcmice, known as an animal model for familial adenomatous polyposis (FAP), multiple tumors (tubular adenomas) develop in the small intestine, instead of the large intestine in human FAP, and markedly few tumors develop in the large bowel. However, dysplastic crypts are observed in the colonic mucosa of Min/+  Apcmice (Min/+Apc mice were given drinking water containing 2% DSS for one week without the initiation (carcinogen) treatment [β-catenin, COX-2, iNOS, and p53 antibodies  rats in Kyoto University will give new insight in the pathogenesis of colorectal cancer development in the inflamed coon [Taken together, development of a mouse inflammation-associated colorectal carcinogenesis model was briefly described here, and the model was named as the TANAKA model. This model was possible to induce colorectal tumors in a short-term period in rats as well by similar treatment regimens (AOM/DSS and DMH/DSS) , 31. It med coon .β-cyclodextrin inclusion compounds of auraptene and 4′-geranyloxyferulic acid [Studies on chemoprevention of inflammation-associated colorectal carcinogenesis by several natural and synthetic compounds against have been reported using the AOM/DSS-induced mouse and rat colorectal carcinogenesis models. Several are promising compounds and their clinical application is expected. Representative compounds are auraptene and nobiletin from citrus fruits , collinilic acid , tricin lic acid , melatonlic acid , ursodeolic acid , COX-2 slic acid , iNOS selic acid , PPAR lilic acid , and a llic acid . All theγ by comprehensive gene expression analysis in the colonic mucosa of mice that received AOM and DSS [κB and Nrf2 were expressed in not only inflammatory cells but also cancer cells in the TANAKA (AOM/DSS) model [Animal colorectal carcinogenesis models of our own making with the background of colitis mimicking human UC are introduced, and the exploration of chemopreventive compounds using these animal models is described. In addition, we confirmed upregulation of Wif1, Plat, Myc, and Plscr2 and downregulation of Pparbp, Tgfb3, and PPAR and DSS . Moreove and DSS . SignifiS) model , these mS) model  and tumoS) model  for the


Zea mays) red aleurone1 (pr1) encodes a CYP450-dependent flavonoid 3’-hydroxylase (ZmF3’H1) required for the biosynthesis of purple and red anthocyanin pigments. We previously showed that Zmf3’h1 is regulated by C1 (Colorless1) and R1 (Red1) transcription factors. The current study demonstrates that, in addition to its role in anthocyanin biosynthesis, the Zmf3’h1 gene also participates in the biosynthesis of 3-deoxyflavonoids and phlobaphenes that accumulate in maize pericarps, cob glumes, and silks. Biosynthesis of 3-deoxyflavonoids is regulated by P1 (Pericarp color1) and is independent from the action of C1 and R1 transcription factors.The maize  accumulate luteoforol, while null pr1 lines with a functional or non-functional p1 allele  accumulate apiforol. Apiforol lacks a hydroxyl group at the 3’-position of the flavylium B-ring, while luteoforol has this hydroxyl group. Our biochemical analysis of accumulated compounds in different pr1 genotypes showed that the pr1 encoded ZmF3’H1 has a role in the conversion of mono-hydroxylated to bi-hydroxylated compounds in the B-ring. Steady state RNA analyses demonstrated that Zmf3’h1 mRNA accumulation requires a functional p1 allele. Using a combination of EMSA and ChIP experiments, we established that the Zmf3’h1 gene is a direct target of P1. Highlighting the significance of the Zmf3’h1 gene for resistance against biotic stress, we also show here that the p1 controlled 3-deoxyanthocyanidin and C-glycosyl flavone (maysin) defence compounds accumulate at significantly higher levels in Pr1 silks as compared to pr1 silks. By virtue of increased maysin synthesis in Pr1 plants, corn ear worm larvae fed on Pr1; P1 silks showed slower growth as compared to pr1; P1 silks.In maize, apiforol and luteoforol are the precursors of condensed phlobaphenes. Maize lines with functional alleles of Zmf3’h1 gene participates in the biosynthesis of phlobaphenes and agronomically important 3-deoxyflavonoid compounds under the regulatory control of P1.Our results show that the  Zea mays) flavonoid biosynthesis provides an excellent system to study gene interaction in plants because of its extensive characterization at genetic, biochemical, and molecular levels  inbred line was obtained from the National Seed Storage Laboratory , while P1rr 4B2, P1ww1112 and pdel2 genetic stocks were obtained from Dr. Thomas Peterson, Iowa State University, Ames, IA -60Zea maAmes, IA ,62. The  P1ww 4Co inbred lr region .Pr1 and pr1 alleles in the genetic background of different p alleles, methanol extract were treated with aqueous HCl. This converts flavan 4-ols such as apiforol and luteoforol to their corresponding 3-deoxyanthocyanidins (i.e. apigeninidin and luteolinidin). The treated Pr1 extracts had λ max of 498 nm that shifted in alcoholic AlCl3 to a shoulder at 546 nm. The addition of HCl restored its absorption to 498 nm. The results of our samples were verified using commercial standards for apigeninidin and luteolinidin . The commercial sample of apigeninidin had a λ max of 475 nm and did not respond to AlCl3, whereas luteolinidin had a λ max of 495 nm that shifted in AlCl3 to 546 nm and reverted to 498 nm upon re-addition of HCl.To detect the presence of flavan 4-ols, 500 mg of cob-glumes were macerated with a plastic grinder in an Eppendorf tube containing 1 mL of 30% HCl/70% butanol (v/v) and incubated for 60 min at 37°C . Samplesc2 cDNA ATP by using T4-polynucleotide kinase. The radioactively labeled DNA fragments were purified by PAGE and quantified by scintillation counter. Ten ng of purified P1MYB was incubated with an equal molar amount of probes (with radioactivity ~105 CPM) for 30 min and the P1MYB-probe complex was separated by PAGE. After PAGE, the gel was dried onto Whatman paper and then subjected to autoradiography at -70°C.EMSA was performed as previously described . The twoP1rr pericarps, equal amounts of the pPHP611 plasmid [r in the plasmid. The primer sets used for ChIP-qPCR were the following: qChIP-ZmCopia-F, 5′-CGATGTGAAGACAGCATTCCT-3′, qChIP-ZmCopia-R, 5′-CTCAAGTGACATCCCATGTGT-3′, qChIP-ZmAct1-5UTR-F, 5′-TTTAAGGCTGCTGTACTGCTGTAGA-3′, qChIP-ZmAct1-5UTR-R, 5′-CACTTTCTGCTCATGGTTTAAGG-3′, qrt Zmf3′h1Prom-A1, 5′-AGATCGCGGGTAGGTAGGAG-3′, and qrt Zmf3’h1Prom-B1, 5′-ACTGGTGGCGAGGGTGTAGT-3′. The following primer sets were used to detect Ampr gene: ChIP-Amp-F, 5′-GTAGTTATCTACACGACGGGGAGT-3′, and ChIP-Amp-R, 5′-ATCAGTGAGGCACCTATCTCAGC-3′.ChIP experiments using pericarps were performed as previously described . Real-ti plasmid  were spi plasmid  in each Primary ear shoots were covered prior to silk emergence to prevent random pollination. Silks were collected on ice 2 d after emergence from the ear and subsequently freeze dried. Silk samples were then shipped on dry ice to the Richard B. Russell Research Centre  for biochemical analysis. Flavones were extracted with 125 mL methanol at -20°C for 14 d. Concentration of flavones were determined by reversed-phase HPLC ,74 and eHelicoverpa zea Boddie) eggs were obtained from Benzon Research Company, Carlisle, PA. Eggs were incubated at 28°C. They hatched after 48 h to produce neonate larvae. Maize lines with Pr1 or pr1 alleles in genetic backgrounds of four different p1 alleles; P1wr, P1rr, P1ww, and pdel2 were grown during the summer of 2007. Silks collected 2 to 3 d after emergence were pooled from 20 field grown plants per genotype. The experiment was conducted as a randomized complete block design with 30 replications and two cups per replicate. Freshly collected silks were filled into 1 oz. plastic diet cups containing 10 mL of 2.5% (w/v) agar to prevent silk drying. Instead of adding silk extracts to the artificial insect diet, fresh silk tissues were used to maximize the resemblance to natural larval feeding conditions. One neonate larvae was introduced into each cup and larvae were allowed to feed in a controlled environment maintained at 28°C, 75% RH, and a photoperiod of 14/10 h (light/dark). Larval weights were recorded after eight days of feeding and larvae were subsequently transferred to artificial diet [Corn earworm , Pr1/P1-wr (middle), Pr1/p-del2 (bottom) plants.Click here for file


Hearing is essential for humans to communicate with one another. Early diagnosis of hearing loss and intervention in neonates and infants can reduce developmental problems. The aim of the present study was to assess the prevalence of hearing impairment in newborns admitted to a neonatal intensive care unit (NICU) and analyze the associated risk factors.This cross-sectional study was conducted to assess the prevalence of hearing loss in neonates who were admitted to the NICU at Nemazee Hospital, Shiraz University of Medical Sciences between January 2006 and January 2007. Auditory function was examined using otoacoustic emission (OAE) followed by auditory brainstem response (ABR) tests. Relevant potential risk factors were considered and neonates with a family history of hearing loss and craniofacial abnormality were excluded. For statistical analysis logistic regression, the chi-squared test, and Fisher’s exact test were used. Among the 124 neonates included in the study, 17 (13.7%) showed hearing loss in the short term. There was a significant statistical relationship between gestational age of less than 36 weeks (P=0.013), antibiotic therapy (P= 0.033), oxygen therapy (P=0.04), and hearing loss. On the contrary, there was no significant relationship between hearing loss and use of a ventilator, or the presence of sepsis, hyperbilirubinemia, congenial heart disease, transient tachypnea of newborn, congenital pneumonia, or respiratory distress syndrome.Auditory function in neonates who are admitted to a NICU, especially those treated with oxygen or antibiotics and those born prematurely, should be assessed during their stay in hospital. The importance of early diagnosis of hearing loss and intervention in these neonates and avoidance of any unnecessary oxygen or antibiotic therapy needs to be further promoted.  Recent advances in neonatal medicine have increased the survival rate of newborns, especially those admitted to neonatal intensive care units (NICUs). Due to problems such as prematurity, low Apqar scores, infection, and hyperbilirubinemia, and the risks associated with treatment strategies including mechanical ventilation, oxygen therapy, administration of antibiotics and other medications, infants in NICUs face various problems including hearing impairment. Significant hearing loss is the most common disorder at birth, occurring in 1 to 2 newborns per 1000 in the general population and 24% to 46% . Many factors might play a role in placing these NICU babies at an increased risk of hearing loss, including underlying disease processes as well as the treatment they receive ,5. In adScreening procedures to detect hearing impairment may be divided into two categories: behavioral and electrophysiological. Behavioral techniques produce a high number of false-negative results due to the relative subjectivity of the assessment and difficulty in detecting mild or unilateral hearing loss. Electrophysiological procedures have greater sensitivity and specificity and include measuring the following: auditory brainstem responses (ABR), automated auditory brainstem responses (AABR), and evoked otoacoustic emissions (EOAE) . Various An observational cross-sectional study was conducted between January 2006 and January 2007. All the newborns admitted to the NICU at Nemazee Hospital, which is affiliated to Shiraz University of Medical Sciences, were included in the study. Information about the condition of each neonate was collected in the form of a questionnaire and included: gestational age ; family history of congenital hearing loss and consanguinity; presence of conditions including asphyxia (Apqar score < 4), sepsis, respiratory distress syndrome, transient tachypnea of newborn (TTN), congenital pneumonia, congenial heart disease (CHD), or hyperbilirubinemia (20 mg/d1); and treatments used including phototherapy (>2 days), mechanical ventilation (>5 days), antibiotic therapy including aminoglycosides (>5 days), or oxygen therapy (>1 week and > 40% FIO2). Babies who had craniofacial malformation and those with a family history of deafness were excluded from the study. The presence of unilateral or bilateral hearing loss was considered as deafness in this study. At the time of discharge from the hospital, infants were tested using OAE and ABR screening. Infants were screened by using distortion-product OAEs (DPOAEs), set at a 2 to 5 kHz screen with 3 of 4 frequency bands being required to be present for a pass. The intensity was calibrated at a 65 dB sound pressure level for band 1 and 55 dB sound pressure level for band 2. Parameters for the ABR included a 100 μs click stimulus, alternating polarity, a click rate of 37.1 clicks per second, and an intensity of 35 dB. The low-pass filter was set at 1500 Hz, and the high pass filter was set to 100 Hz; a minimum of 1536 sweeps up to a maximum of 2 trials of 6144 sweeps were obtained.A patented signal-detection algorithm, the point-optimized variance ratio, determined the presence of an ABR and assigned a pass or fail result. A point-optimized variance ratio score of 3.50 was necessary for a pass. The specificity of the screening ABR test is in excess of 98.5%. The verified theoretical sensitivity for the ABR test is 99.96% . The result was considered normal when the newborn responded to a 35 dB signal in both ears separately and impaired when a response to 35 dB was not detected in at least one ear. The data were analyzed by an ENT specialist. In this study logistic regression, the chi-squared test and Fisher’s exact test were used and P-values of less than 0.05 were accepted as significant. The protocol was assessed and approved by the Research Ethics Committee of the Medical Council of I.R.I. and informed consent was obtained from the parents. A total of 124 neonates were included in this cross-sectional study and 17 of these had hearing loss. Statistical analyses in the form of logistic regression were performed to assess the risk factors associated with hearing loss. The relationship of oxygen therapy with hearing loss was analyzed using the chi-squared test and in some cases Fisher’s exact test was used due to low sample numbers. Out of the total study group, 11 (13.6%) of the 73 boys and 6 (11.7%) of the 51 girls showed evidence of hearing loss. Statistical analysis indicated that hearing loss was not related to gender (P=0.95). Of the 69 neonates who were born at a gestational age of greater than 36 weeks, 4 (2.42%) had sensorineural hearing loss. In contrast, 10 (8.06%) of the 55 preterm neonates (less than 36 weeks) had hearing loss and there was a statistically significant relationship between gestational age and hearing loss (P=0.013). A total of 7 (14.8%) of the 47 neonates with hyperbilirubinemia had bilirubin levels of greater than 20 mg/dl and required exchange transfusion but only 2 (28.5%) of them had hearing loss. There was no statistically significant relationship between hearing loss and bilirubin levels of greater than 20 mg/dl. In terms of medical treatments, of the 105 cases who were administered antibiotics (aminoglycoside) 19 (14.8%) had hearing loss, which was a significantly greater number than that observed in the babies who did not receive antibiotics P=0.00; . For oxygen therapy, 21 (17.0%) of the 103 babies who received the therapy (>1 week and >40% FIO2) also had hearing loss, which was a statistically significant result  = 4.16, P=0.041; There was no statistically significant relationship between hearing loss and the other risk factors identifed including respiratory distress syndrome (28%), TTN (4.8%), congenital pneumonia (6.4%), CHD (3.2%), mechanical ventilation for longer than 5 days (8.8%), hyperbilirubinemia of less than or equal to 20 mg/dl (5.6%), phototherapy for more than 2 days (20%), asphyxia (Apqar score < 4 [6.4%]), and sepsis (32%). The average duration of hospitalization was 21 days (range: 12–36 days).It is generally accepted that screening for hearing loss in neonates is crucial, and it has been reported that the use of a universal newborn hearing screening is more valuable than screening just those who have been admitted to a NICU . RecogniIn this study on 124 neonates admitted to the NICU of Nemazee Hospital, Shiraz University of Medical Sciences, hearing loss was confirmed in 17 cases indicating the importance of screening for hearing loss in this category of neonates. In order to determine the relative risk factors associated with hearing loss in neonates we considered only those who had be admitted to the NICU as the incidence of hearing impairment is 24% to 46% in this group. Infants were tested using OAE and ABR, which has been suggested by previous reports to be a successful two-step screening protocol for at risk babies ,14.Our results indicate that as the prevalence of hearing loss in newborns with a gestational age of less than 36 weeks was clearly higher, prematurity should be considered as a risk factor for hearing loss in the NICU population. These babies face problems due to the underdevelopment of their respiratory system, which requires more and longer oxygen therapy, and as a consequence of their weakened immune system they are also exposed to various infections and thus the chance of sepsis and the use of antibiotic therapy will be higher. Both of these variables are significantly associated with hearing loss in our study.It has been reported in literature that adequate oxygenation and perfusion are essential for cochlear function and that hypoxia can lead to hearing loss . Our anaThe literature considers the use of ototoxic medication to be an important risk factor for deafness in the neonatal period ,17 and iWith regards to mechanical ventilation for more than five days, the data in the literature point to the procedure as an important cause of deafness. In the present study, mechanical ventilation was not identified to be significantly associated with hearing loss, perhaps due to the short duration of ventilation that was used in most cases. The use of phototherapy has also been studied in the literature and we included it as a variable in this analysis because it is a very common procedure in our unit and it involves a high noise level  . The number of children submitted to phototherapy was higher than the number considered as having hyperbilirubinemia, since the indication for phototherapy includes other children in addition to those with total bilirubin levels of greater than 20 mg/dl. We did not observe an association between the use of phototherapy and hearing impairment. In addition, although severe hyperbilirubinemia is a neonatal risk factor that has been proven to be associated with hearing loss, no significant relationship was observed in the present study. This may be because most of the newborns in the NICU has undergone exchange transfusion before the fatal complications of high bilirubin could occur.In conclusion we would like to stress the importance of identifying infants with hearing disorders, administering early treatment, and performing appropriate tests in infants at high risk of hearing impairment. When dealing with these babies treatments such as unnecessary oxygen or antibiotic therapy should be refused.


Methods developed for real-time time scale modification (TSM) of speech signal are presented. They are based on the non-uniform, speech rate depended SOLA algorithm (Synchronous Overlap and Add). Influence of the proposed method on the intelligibility of speech was investigated for two separate groups of listeners, i.e. hearing impaired children and elderly listeners. It was shown that for the speech with average rate equal to or higher than 6.48 vowels/s, all of the proposed methods have statistically significant impact on the improvement of speech intelligibility for hearing impaired children with reduced hearing resolution and one of the proposed methods significantly improves comprehension of speech in the group of elderly listeners with reduced hearing resolution.http://www.diagnosticpathology.diagnomx.eu/vs/2065486371761991 Time scale modification algorithms have been widely used for supporting various types of speech perception disorders. The main fields of TSM application are: Language Learning Impairment (LLI) -3, SeconIn this work, three methods for real-time TSM, dedicated for listeners with hearing resolution deficit are presented. Effectiveness of these methods was examined for two different age groups of listeners: the hearing impaired children and the elderly persons with presbycusis. The latter group was chosen based on the assumption that main difficulties in speech comprehension in elderly people are associated with central auditory processing aspects of hearing ,13. The The proposed TSM methods were designed in such a way that they could work in real-time on mobile devices. Applications of these methods may be the same as those proposed by Nakamura  . Three different TSM methods for the real-time speech stretching are proposed: an uniform real-time TSM  described by authors in an earlier paper , and twoAll the proposed TSM methods are based on the assumption that the input signal contains redundant information, i.e. silence passages  and prolonged vowels. These parts of the signal may be removed or at least they should not be stretched. This approach allows saving extra time in which the stretched speech could be presented.In addition, as it was postulated by Coyle , Chu 1717 and Deα(t). It is defined by the equation (1):All of the algorithms used in the content analysis block were described in details in earlier papers -16, thusSa is the time shift of the frame used during the analysis step, Ss is the time shift of the frame used during the synthesis step. If the value of α(t) is greater than 1, the input signal will be stretched, if α(t) is lower than 1, the signal will be shortened; for α(t) equal to 1, the time scale modification will not be performed. Since the TSM will be performed only in order to expand the time of the input signal, α(t) will take values equal or higher than 1.where d parameter . The value of αd should be specified . Additionally, elimination of redundancy in the input signal is performed by replacing intervals of silence longer than 200 ms with the time-expanded speech.In this method, a speech signal is stretched using constant values of the scaling factor. Input signal is time-extended only when the voice is detected by the VAD and vowel prolongation was not observed by the vowels detector. Despite the fact that the input signal is non-uniformly time scaled , the speech signal is modified uniformly . The stretching procedure is controlled by the αα(t) used in this method are presented in Table d stands for the value of the scaling factor specified by the user. The rate of speech is estimated based on the analysis of vowels positions. Speech with the rate higher than or equal to 5.16 vowels/s is marked as fast. Selection of this threshold was based on the manually labeled utterance rates , where the average value and standard deviation of ROS obtained from all the recordings in the database, were calculated [α(t) are used, and for speech with a normal rate, these values are reduced. Two additional restrictions were added to ensure that vowels will be stretched using values of α(t) not lower than for consonants: for slow speech, if the calculated value of α(t) is lower than 1, it is set to 1, and for fast speech, if the calculated value of α(t) is lower than 1.1, it is set to 1.1. The important is also fact that only not for all silence passages α(t) is defined because some of them are removed to ensure the synchronization between the input and output signal.The second method of time-expansion of speech signals is performed using the same principles as in the method A, but additionally, the scaling factor values may vary depending on the input signal content and the ROS. Values of lculated . Wheneved value is used. The value of the ROSd is specified by the user. As a result of speech modification, stretched speech has the rate close to the ROSd value. The signal processing procedure applied to this method is the same as in the algorithm B, but the current value of scaling factor is calculated for every signal frame separately, according to equations (2)(3)(4):Two methods presented above use the scaling factor as the control value of the output speech rate. This is not a natural way of specifying the speech rate, since for the same values of the scaling factor, the stretched speech will have different rates depending on the rate of the input speech. Therefore, authors of this paper have proposed the method in which, as the control value of time-expansion, a desired ROScons(t) is the value of scaling factor for the current frame (provided a consonant was detected), αvowel(t) is the value of scaling factor for the current frame (provided a vowel was detected) , Δt is the time interval used for the ROS estimation , Δtvowel is the duration of the vowel in the estimation interval, η is the ratio between the scaling factor used for the vowels and the scaling factor used for consonants .where αd was set to 1.5 (for method A and B) and ROSd was equal to 3 vowels/s. These values of the scaling factor were also used during speech intelligibility tests described in Section 3. The choice of αd value was based on the results presented by Nejime et al.[d equal to 1.5, the highest improvement in speech comprehension could be achieved. The chosen value of ROSd ensures the same ROS expansion as for the methods A and B.Examples of speech stretching obtained using the proposed methods are shown in Figure me et al.. He had off, and the unmodified speech is send to the output. This threshold is exceeded much often for the method A than for methods B and C and its value can be defined by the user. During the experiments, Δtoff was set to 3 seconds.An analysis of Figure Evaluation of the proposed methods of TSM was performed employing the sentence intelligibility test (SIT). A word recognition test was not performed, because as it was shown by the Nejime , time exmean1 = 7.58 vowels/s, ROSmean2 = 6.43 vowels/s) and PMT  were used as the input signal during the experiment. In case of SIT, sentences were divided into two separate sets. The first set contained 40 sentences spoken with the highest speech rate , and the second set included 40 sentences with the second highest speech rate. During the test, each listener had to repeat words constituting the sentences. The word error rate (WER), as well as average improvement in speech intelligibility were measured. For WER calculation, the percentage of words repeated incorrectly was used, while the improvement of speech intelligibility, obtained for the proposed methods, was calculated as a difference between the WERs for the original and for the time-expanded speech.In case of SIT, 4 different types of speech were examined, i.e. the original speech and the speech stretched using three proposed TSM methods. As the speech material, Polish matrix test (PMT)  for elde50) defined by Versfeld [50 (Speech Reception Threshold) [50 value represented a threshold, defined in syllables/s, for which 50% of the sentences in the test were correctly recognized by the listener. In our research, we have used a speech rate expressed as number of vowels/s. Thus, the speech rate defined by us is the derivation of the number of syllables/s.Additionally, each listener performed a time-compressed speech test (TCST) in order to obtain their individual 50% time-compressed speech threshold  . Speech The main difference between the test proposed by Versfeld  and a st• each listener has to repeat 13 sentences• the scaling factor is modified for each sentence according to the rules:• if all words in the last sentence were repeated correctly, the value of scaling factor increases,• otherwise the value of scaling factor decreases.50 is calculated as a geometric average of the last 10 average rates of the sentences.• TCTFor the elderly listeners, a tonal audiometry was performed in order to obtain their hearing level threshold. Listeners were using binaural headphones during the TCST and SIT and the signal level was set to a comfortable value. Each listener was asked at the beginning of test if the speech level is appropriate for them and if not, the level was adjusted. All listeners with hearing aids (HA) and cochlear implants (CI) were using their devices during the experiment.mean1 (this part lasted about 20 minutes); and part two: SIT performed for the input speech with the average ROS equal to ROSmean2 (this part lasted about 12 minutes). The hearing thresholds were provided by the audiologist who performed this examination earlier.The group of elderly people was examined during one session which lasted about 40 minutes. Tests for children were conducted in two separate sessions, because it was difficult for them to concentrate on the test for so long. Examination of children was divided into part one: TCST and SIT performed for the input speech with the average ROS equal to ROSIn both groups of listeners, 17 volunteers were investigated. The average age of hearing impaired children was 9.35 years , whereas the average age of elderly listeners was 80.76 years .50, time expansion of speech significantly improves the speech perception. At the beginning, the results of TCST were analyzed in order to divide listeners  into subgroups containing listeners with the normal and the reduced hearing resolution. In Table 50 (4.81 vowels/s) is lower than for the hearing impaired children. The difference is mainly related to the differences occurring in the input speech material. For the children, three-word sentences were used during the experiment (PPMT) while for the adults, five-words sentences were used (PMT). Longer sentences are more difficult to remember and repeat. Therefore, authors have assumed that the reason of the differences is associated with the length of sentences.The results obtained for both groups of listeners were analyzed in order to verify a hypothesis that for listeners with a low value of TCT50 value lower than the 95% confidence interval value, then his hearing resolution is reduced. Two TCT50 thresholds were used. For the group of hearing impaired children, TCT50 threshold was equal to 5.71 vowels/s and for the elderly listeners it was 3.99 vowels/s. In Figure 50 calculated for all subgroups of listeners are presented. The subgroups of hearing impaired children and elderly people with the reduced hearing resolution contained 6 listeners and in the subgroups of listeners with the normal hearing resolution, 11 hearing impaired children and 11 elderly people were included.Both groups of listeners were divided into subgroups based on Versfeld’s assumptions , i.e. ifAnalysis of the SIT was performed separately for the group of the hearing impaired children and the elderly listeners. Statistical importance of the differences between mean values of the WER obtained for the original speech and the modified one was examined using an one-way repeated measures ANOVA (RM ANOVA) test and the Friedman’s test. For all analyses, a normal distribution of data was checked using the Shapiro-Wilk test and the hypothesis of the sphericity was verified using the Mauchly's test. The RM ANOVA test was performed only when both assumptions  were met, otherwise the non-parametric Friedman test was used. For all tests, the significance level equal to 0.05 was assumed.The hearing impaired children group contained 9 children with CI and 8 children with HA. The results of hearing tests obtained for this group of listeners were presented in Table mean2 is much lower than for the average ROSmean1. This relation is valid for both subgroups of the hearing impaired children . It may be related to the fact that the ROSmean2 value (6.43 vowels/s) is close to the average values of the TCT50 obtained for both subgroups of the hearing impaired children (the subgroup with reduced hearing resolution μ(TCT50) = 5.16 vowels/s and the subgroup with normal μ(TCT50) = 6.98 vowels/s). Furthermore, the ROSmean1 value (7.48 vowels/s) is higher than the average values of the TCT50 achieved in both subgroups of children. It should be also pointed out that the average WER obtained in two subgroups for the speech spoken with the ROS equal to ROSmean1 is similarly high  and for the ROS equal to ROSmean2, it is comparatively small . Based on these observations, the following conclusion can be made: the hearing impaired children in both subgroups had comparable problems with comprehension of the unmodified speech.It can be seen that WER obtained for the speech spoken with the average ROS equal to ROS50 and WER, a relationship between values of these measures are presented in Figure 50 and WER calculated for the subgroups of normal/reduced hearing resolution and for the whole group of hearing impaired children were: -0.09, -0.62, and −0.41, respectively. It can be seen that only for the subgroup of hearing impaired children with reduced hearing resolution, linear correlation is noticeable. Negative correlation value reflects the reverse relation. Therefore, the following conclusion can be made: the lower TCT50 was achieved in TCST, the higher WER value will be obtained in the SIT test for the high rate unmodified speech.In order to verify if there is a correlation between the TCTmean1) and in Figure mean2).The influence of the proposed TSM methods on speech intelligibility was analyzed separately for two subgroups. The average values of intelligibility improvements are presented in Figure mean1 . For the input ROS equal to ROSmean1, the results of SIT obtained by the subgroup of children with TCT50 < 5.71 vowels/s did not show the normal distribution. Therefore, for these data, Friedman’s non-parametric test was applied. The statistic value of the test was equal to χ2(3) = 113.5. Since the number of listeners in this subgroup was low (6 persons), in order to increase the reliability of the result, the p-value was not calculated but the test statistic value was compared with the suitable critical value read from the tables (χ2(3)cv = 76). Hence, the critical test value is lower than the obtained Friedman’s statistic value, the differences between the WERs obtained for the unmodified speech and the speech modified using algorithm A-C are statistically important. In order to check which algorithm causes this situation, a post hoc non-parametric test equivalent to the Least Significant Difference Fisher’s test was performed. For the pairs of unmodified speech and speech modified using algorithms from A to C, the following statistical values were obtained: 12.5 (A), 13.5 (B), and 8.0 (C). These results were compared with the critical value equal to 6.2. Since all the statistics values were higher than the critical value for all the proposed algorithms, differences between the WER obtained for the unmodified and modified speech are statistically important.To verify if the differences of the average WER values are statistically important, appropriate analyses were performed  and the assumption of sphericity was met. For these reasons, RM ANOVA was calculated for these data. The following results were obtained: F = 3.44 and p = 0.03. Since the achieved p value is lower than the assumed significance level in at least one pair, the differences between average values of WER are statistically important. Additionally, the post hoc LSD test shows that only differences in average WER between the pairs ‘original-method A’ (t(10) = −2.83; p = 0.02) and ‘method A- method B’ (t(10) = 2.54); p = 0.03) are statistically important. This results shows that for the subgroup of hearing impaired children with the normal hearing resolution, method A gives statistically important improvement of in speech intelligibility.For the same speech rate and the subgroup of children with TCT50 for the subgroup of hearing impaired children with the reduced hearing resolutions and the improvement in speech ineligibility for the time-expanded speech while using methods A-C, as well as for the subgroup of hearing impaired children with normal hearing resolution and the improvement in speech ineligibility for the time-expanded speech while using method A. The correlation coefficient obtained for the first subgroup for methods A-C were equal to −0.59 (A), -0.16(B), and 0.08 (C). Only for the method A there is a significant linear correlation between these values. For the second subgroup and the method A, the correlation coefficient was equal to 0.07. Therefore, there is no linear correlation between these values. In Figure Additionally, the correlation coefficient was calculated to validate if there is a linear relationship between the TCTmean2, improvement in speech ineligibility was observed only for the subgroup of children with reduced hearing resolution and methods A-B  and for the subgroup of children with normal hearing resolution and method C (3.94%). In other cases, a slight decrease in WER was observed (from −5.55% to −0.3%). For the subgroup of children with reduced hearing resolution, RM ANOVA was calculated . The results of the test show that there are no statistically important differences in WER between the analysed methods  = 1.51; p = 0.25). For the subgroup of children with normal hearing resolution, the Friedman’s test was performed  and there was no statistically important difference in WER between the methods (χ2(3) = 0.30; p = 0.82). Therefore, none of the proposed methods affect the intelligibility of speech spoken with ROS equal to ROSmean2.In case of the speech spoken with ROSmean3 = 6.48 vowels/s) is higher than for the speech spoken with the lower rate (ROSmean4 = 4.88 vowels/s). However, for this group of listeners, the differences in WER between the subgroups of listeners with normal and reduced hearing resolution are significant .The results of hearing tests performed for the group of elderly listeners are presented in Table 50 and WER. In Figure 50 and WER was presented. The triangles represent the results obtained by the subgroup of elderly listeners with normal hearing resolution and the squares – the results achieved by the subgroup of subjects with reduced hearing resolution. The solid line shows the linear regression calculated for all elderly listeners. The Pearson correlation coefficients calculated for both subgroups  and for all elderly subjects were equal to: -0.71, 0.12 and −0.58, respectively. Only for the subgroup of subjects with normal hearing resolution, the linear correlation could be found.Based on the obtained results, it was investigated if there is a linear correlation between the TCTmean3 and ROSmean4) and for two subgroups . In Figure mean3: improvement from 14.66% to 20% and for ROSmean4: from 6% to 11.66%). For the subgroups of listeners with reduced hearing resolution, a small improvement was observed only for speech spoken with the ROS equal to ROSmean3 (from 2.18% to 5.09%) and for the subgroup of subjects with normal hearing resolution, the improvement is negligible . For the speech spoken with the ROS equal to ROSmean3 in the subgroup of listeners with the reduced hearing resolution, both conditions of the RM ANOVA test were met. The test results prove that there are statistically important differences in WER between the proposed methods  = 4.36, p = 0.021). The post hoc LSD test indicates that these differences are significant only for the method B (t(5) = −2.68, p = 0.043). For the subgroup of listeners with normal hearing resolution, the RM ANOVA test did not confirm that the differences between WER values are statistically important  = 1.25, p = 0.3). For the speech spoken with ROS equal to ROSmean4, and for both subgroups of elderly listeners, the RM ANOVA test shows that the differences between the obtained WER values are not statistically important  = 2.62, p = 0.089; F = 0.48, p = 0.69).Influence of the proposed time-expansion method was analysed separately for two different input speech rates . For the hearing impaired children with reduced hearing resolution, all the proposed methods gave statistically important improvement. For the group of elderly listeners, only the method B produces statistically important improvement of speech comprehension. The importance of this improvement was proved in the group of listeners with very low hearing resolution (TCT50 < 3.99 vowels/s). These results are similar to those presented by Nejime et al. [50 and WER was observed. Second, a not so high but significant correlation was found for the relation between TCT50 and the improvement (in subgroups with deficit in hearing resolution) of intelligibility of speech stretched using the method B for elderly listeners and the method A for the hearing impaired children.The speech intelligibility test performed in two groups of listeners (the hearing impaired children and the elderly listeners) have shown that there are differences in speech comprehension in case of time scale modified speech in comparison to the original one. These differences are significant only if a very fast speech is used as the input signal for the test , the obtained results are consistent with those presented by Uchanski et al. [For the speech spoken with lower rates (ROSi et al. . There a50, but also for children with normal hearing resolution. The presented results are in a good accordance with the state-of-the-art results and extend them with the introduction of analysis of the impact of the input speech rate on the relation between the TSM and speech intelligibility. Another novelty is the usage of TCT50 as a measure of the hearing resolution deficit. It was shown that this parameter correlates with the improvement achieved by employing time-expanded speech.Three methods for real-time speech stretching were proposed and verified experimentally. It was proved that the method B significantly improves speech comprehension in hearing impaired children, as well as in elderly people with deficit in the hearing resolution. In turn, the proposed non-uniform real-time speech stretching method A brings satisfying results not only for the hearing impaired children with low value of TCTmean1 and ROSmean2 was shown.In Figures mean3 and ROSmean4 was shown.In Figure 50: Speech Reception Threshold; TCT50: 50% time-compressed speech threshold; ANOVA: Analysis Of Variance; RM: ANOVA: Repeated Measures ANOVA; CI: Cochlear Implant; HA: hearing aid; LSD: Least Significant Difference; RGDT: Random Gap Detection Test.TSM: Time Scale Modification; LLI: Language Learning Impaired; CAPD: Central Auditory Processing Disorders; VAD: Voice Activity Detection; SOLA: Synchronous Overlap and Add; ROS: Rate of Speech; SIR: Sentence Intelligibility Test; PMT: Polish Matrix Test; PPMT: Pediatric Polish Matrix Test; WER: Word Error Rate; TCST: Time-Compressed Speech Test; SRTThe authors declare that they have no competing interests.Conceived and designed the experiments: AK, AC. Performed the experiments: AK. Analyzed the data: AK. Wrote the paper: AK, AC. Revised the paper: AK, AC. All authors read and approved the final manuscript.


Cebus have found conflicting results, showing considerable variability across groups and species. In this study, we investigated the pattern of grooming in wild tufted capuchin females (Cebus apella nigritus) in Iguazú National Park, Argentina by testing both the assumption  and predictions  of Seyfarth's model. Study subjects were 9 adult females belonging to a single group. Results showed that grooming was given in return for tolerance during naturally occurring feeding, a benefit that higher-ranking females can more easily grant. Female grooming was directed up the hierarchy and was given more often to partners with similar rank. These findings provide supporting evidence for both the assumption and predictions of Seyfarth's model and represent, more generally, the first evidence of reciprocal behavioural interchanges driven by rank-related benefits in New World female primates.Seyfarth's model assumes that female primates derive rank-related benefits from higher-ranking females in exchange for grooming. As a consequence, the model predicts females prefer high-ranking females as grooming partners and compete for the opportunity to groom them. Therefore, allogrooming is expected to be directed up the dominance hierarchy and to occur more often between females with adjacent ranks. Although data from Old World primates generally support the model, studies on the relation between grooming and dominance rank in the New World genus  The distribution of grooming among group members is a fundamental aspect of primate sociality with direct implications for social bonding. In addition to its hygienic function Grooming is considered to be a low-cost service that individuals can exchange for other kinds of benefits Macaca fuscata) Papio hamadryas ursinus) Studies of Old World primates have provided consistent evidence that females direct their grooming up the dominance hierarchy Criticism of Seyfarth's Cebus apella nigritus, taxonomically synonymous with Sapajus nigritus) with the aim of testing Seyfarth's model. In particular, this study represents the first attempt in wild New World primates generally, and in the genus Cebus specifically, to analyse grooming distribution in relation to multiple rank-related benefits, namely agonistic support, reduced aggression, and tolerance during feeding. Previous investigations testing the predictions of Seyfarth's model Cebus have yielded conflicting results. Perry C. capucinus females groom up the hierarchy following the predictions of Seyfarth's model, whereas the opposite was found in C. olivaceusC. apellaThis study investigated the female-female grooming patterns in a large group of wild tufted capuchin monkeys  the increased likelihood of receiving agonistic support ; b) the reduced likelihood of receiving aggression ; c) the increased likelihood of receiving tolerance at food sources . Among the predictions of Seyfarth's model, we tested whether tufted capuchin females directed grooming up the dominance hierarchy, that is whether females gave more grooming to higher- rather than lower-ranking females (Prediction 1); and higher-ranking females received overall more grooming than lower-ranking females (Prediction 2). Then, we tested if competition for preferred grooming partners occurs by examining whether tufted capuchin females directed the majority of their grooming to females of adjacent ranks (Prediction 3); whether higher-ranking females were better able than lower-ranking females to allocate their grooming according to the rank of the recipient (Prediction 4); and whether higher-ranking females performed overall more grooming than lower-ranking females  (Prediction 5).This study was conducted in accordance with the Animal Behaviour Society's guidelines for the treatment of animals in behavioural research and teaching. In addition, permission to conduct research was provided by the Administración de Parques Nacionales in Argentina (no permission ID was given). Data collection was entirely based on observations of fully-habituated, wild groups and did not affect the monkeys' welfare. Because the study was only observational and approved by the local authorities, our institutions did not require an application to the ethics committee.Data were collected between June 2006 and March 2007 in Iguazú National Park, Argentina . The park is located in the northwestern side of the waterfalls of the Iguazú River and is characterized by semi-deciduous forest with a humid sub-tropical climate and marked seasonality in daylight duration and temperature Tufted capuchin monkeys are highly arboreal, medium-sized . For each polyadic aggressive interaction, only the initial aggressor, the initial receiver and the initial supporter were considered, as it is often impossible to determine the beneficiary of support when many individuals are involved. Agonistic support was considered only if it occurred within 30 seconds from the initial aggressive interaction. The supporter could intervene in the ongoing aggressive interaction aiding either the recipient  or the initiator of the original aggression .The study group was followed for at least 8 hours per day for up to 25 days per month. Data collection on adult females was based on focal animal sampling, Dominance ranks and calculation of dyadic scores: Females in the study group were placed in a linear dominance hierarchy based on the direction of dyadic aggressive and approach-avoidance interactions using MatMan 1.1  or only dominant-subordinate dyads . Such a distinction was needed because of the obvious influence of female-female dominance relationships on the distribution of tolerance and aggression .Considering a generic dyad A–B, directional dyadic grooming scores of A to B were the total number of grooming episodes given by A to B. Directional dyadic agonistic support scores of A to B were calculated as the number of support cases by A to B divided by the number of opportunities for support, which in turn was the number of aggressive interactions involving B, either as aggressor or as receiver, excluding aggressive interactions between A and B. These scores of agonistic support included all observed episodes of support between two female subjects against any other group member.Feeding within 3 m from a lower-ranking female was considered as a measure of tolerance by the higher-ranking partner. Therefore, only dominant-subordinate (but not subordinate-dominant) dyads were considered for calculations of directional dyadic scores of tolerance during feeding. If A was dominant over B, dyadic scores of tolerance provided during feeding were calculated as the number of times A was observed feeding within 3 m from B during 1-minute instantaneous samples in focal samples of A and B, divided by the total number of instantaneous samples collected during focal samples of A and B. This value was subsequently divided by an estimate of the proportion of time individual A spent feeding , allowing for an estimate of the probability of tolerance corrected for the opportunities A had of tolerating B . Similarly, directional dyadic scores of aggression were calculated considering dominant-subordinate dyads. If A was dominant over B, directional dyadic aggression scores were the total number of aggressive interactions initiated by A against B.Finally, time spent in proximity by the dyad A–B was calculated as the number of instances A and B were scored in 3 m proximity during 1-minute instantaneous samples divided by the total number of instantaneous samples collected in focal samples of A and B.Data points included in the analyses were either all female-female directional dyadic scores (N = 72), or the dominant-subordinate dyadic scores (N = 36) when analyses included tolerance and aggression.Testing the assumption of Seyfarth's model: In order to test whether the likelihood of giving support, tolerance during feeding and reduced aggression were associated with grooming received across female-female dyads, three within-subject linear regressions with robust standard errors “r”) as independent fixed effect variables. In order to test the effect of grooming on the three rank-related benefits simultaneously, we also ran a multivariate analysis of covariance (MANCOVA) in which dyadic scores of support, tolerance and aggression given were the dependent variables and dyadic scores of grooming received and kinship were the relevant independent variables. Subject identity was also added as an independent variable in order to obtain a within-subject analysis. Tests of significance were based on Wilk's lambda.Testing predictions of Seyfarth's model: A within-subject linear regression with robust standard errors To test whether higher-ranking females were better able to allocate their grooming in relation to the rank of the recipient (Prediction 4), for each female a Kendall correlation test between the dyadic grooming score and the rank of the grooming recipient was run. The resulting correlation coefficient for each female was then used as a measure of her distribution of grooming in relation to the rank of the recipient; we then tested the relation between these coefficients and the females' own rank with a Kendall correlation test.ad libitum and focal sampling, we assessed the potential occurrence of systematic biases by running a linear regression with grooming data recorded ad libitum as dependent variable and grooming data recorded using focal sampling as independent variable. The two variables were strongly correlated  confirming that ad libitum data provided an unbiased estimate of focal data. All statistical analyses were two-tailed and were run using Stata 10.1 (Stata Corp. 2007).As our statistical analyses on grooming combined data collected via β = −0.0002, t = −0.11, df = 61, p = 0.911), but females preferentially supported their kin . Thus, females did not preferentially support those females that groomed them most. Likewise, aggression given was not associated with grooming received , nor did kinship have a significant relationship with aggression given . Adding time spent in proximity as a further independent variable in this analysis (to control for the opportunities dominants had to behave aggressively) did not change the results . Therefore, dominant females did not refrain from aggressing those subordinate females that groomed them most. By contrast, tolerance given during feeding was positively associated with the amount of grooming received , and kinship had no significant effect . Dominant tufted capuchin females thus more often tolerated those subordinate females that groomed them most.Agonistic support given was not associated with the amount of grooming received  and to kinship .When the three rank-related benefits were analysed simultaneously in a MANCOVA, they resulted to be significantly related both to grooming received . The reasons for these inconsistencies are unclear, but several explanations are possible. First, in most studies of capuchin monkeys, kinship was unknown and it was thus impossible to control for such a factor. The results of this study show that kinship exerted a profound influence on behaviour: significant effects of kinship were observed on the distribution of agonistic support and grooming. Similarly, Perry et al. The published reports of female grooming patterns in the genus The present study provides the first clear evidence for the interchange of grooming for rank-related benefits  in wild New World monkeys. Thus far, analyses of the interchange of grooming for rank-related benefits in primates have focused mostly on agonistic support. In this study, we tested the assumption of Seyfarth's model by examining the relation between grooming and multiple forms of rank-related benefits. Our findings suggest that investigating other forms of rank-related benefits may prove fruitful because it is only when the assumption of the model are met that its predictions are expected to hold In conclusion, even though the relationship between grooming distribution and the acquisition of rank-related benefits warrants further consideration, results from our study highlight two important aspects. First, when testing the social function of grooming, different forms of return benefits should be considered